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We performed a systematic review to investigate the definition of mild to moderate active ulcerative colitis (UC), and to describe predictors of good response to treatment in clinical trials assessing 5-ASA and/or budesonide. Thirty-nine randomized controlled trials were included. The UC Disease Activity Index (UCDAI) was the most frequent score used for defining mild to moderate active UC (16 studies, 41%), followed by Clinical Activity Index in 11 studies (28.2%). Four different cut-offs were used to define mild to moderate active UC using the UCDAI. The most frequently reported predictors of good response to treatment was a mild and moderate disease activity. There is heterogeneity in the definition of mild to moderate active UC in randomized clinical trials. A standardized definition of mild to moderate active UC used for inclusion of patients in clinical trials is needed.

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Azithromycin (AZI) is increasingly used for childhood asthma despite limited and inconsistent data. We aimed to evaluate the efficacy and safety of AZI in childhood asthma.We searched seven databases to include randomized controlled trials (RCTs) of AZI in the treatment of childhood asthma. Four reviewers independently screened the records. Risk of Bias 2 was used to assess the quality of RCTs. Risk ratios with 95% confidence interval (CI) from dichotomous outcomes, and mean difference (MD) with 95% CI from continuous outcomes were pooled.We included 19 eligible reports from 17 studies. The prevalence of exacerbations in AZI + budesonide (BUD) + βAZI may be beneficial in improving some clinical symptoms and lung functions in older asthma children (over 6 years old) with persistent asthma. But it still requires further research.

The aim of this study was to evaluate the pharmacokinetic bioequivalence of a generic budesonide nasal spray and a branded product in healthy Chinese subjects under fasting condition. A single-center, single-dose, randomized, open-label, crossover study was conducted in 32 healthy Chinese subjects under fasting condition. The subjects were administered 256 μg of generic budesonide nasal spray (test drug) or branded budesonide nasal spray (RHINOCORT AQUA, reference drug), respectively. For each period, the subjects were administered with 64 μg of budesonide per spray and 2 sprays for each nostril followed by a washout period of 7 days. Plasma concentration of budesonide was determined by a validated high-performance liquid chromatography-tandem mass spectrometry method. The pharmacokinetic (PK) parameters were calculated, and the bioequivalence was compared using the noncompartment model with the Phoenix WinNonlin 7.0 program. Results show that the 90% confidence intervals of the test/reference ratios of maximum concentration, area under the plasma concentration-time curve from time 0 to the last measurable concentration, and area under the plasma concentration-time curve from time 0 to infinity for the budesonide concentration were 84.8% to 102.7%, 84.6% to 94.4%, and 85.4% to 95.2%, respectively, all fall within the bioequivalent range of 80% to 125%. The test and reference budesonide nasal sprays were PK bioequivalents in healthy Chinese subjects with comparable PK parameters. No serious adverse events were reported, and the 2 products have a good and similar safety profile.

Background: Increase in lipid levels associated with the treatment of inflammatory bowel disease (IBD) has previously been reported. However, it is unknown if this effect is similar for all IBD drug classes.Aim: To precisely assess the effect of different IBD drug classes on lipid profilesMethods: We performed a systematic literature search of randomised controlled trials and observational cohort studies that assessed lipid levels before and after induction (10 weeks) of IBD treatment. Data of 11 studies (1663 patients) were pooled using random effects models. The influence of patient and disease characteristics on treatment effects on total cholesterol levels was analysed in 6 studies (1211 patients) for which individual data were available, using linear mixed models.Results: A statistically significant increase in total cholesterol was observed after induction treatment with corticosteroids (+1.19 mmol/L, 95% confidence interval [CI95] +0.52 to +2.59), and tofacitinib (+0.66 mmol/L, CI95 +0.42 to +0.79), but not after anti-TNF alpha treatment (-0.11 mmol/L, CI95 -0.26 to +0.36 mmol/L). Similar differences were observed after maintenance treatment. Treatment effects were significantly related to age, but not with other factors. Lipid changes were inversely correlated with but not modified by CRP changes.Conclusions: Increase in total cholesterol levels was strongest for corticosteroids followed by tofacitinib but was not observed for anti-TNF alpha agents. Whether total cholesterol change associated with IBD treatment has an effect on cardiovascular risk requires further study.

Background Medically refractory chronic rhinosinusitis (CRS) is often treated with functional endoscopic sinus surgery (FESS) and high-volume steroid nasal irrigation. While budesonide is the most common steroid irrigation for this indication, mometasone has a superior pharmacokinetic profile, which may allow dose escalation. The safety and efficacy of mometasone at higher concentrations than previously used in treating CRS have not been explored. Methods Patients were recruited from a tertiary level clinic between June 2018 and December 2019. Inclusion criteria included adults (>18 years); CRS diagnosis; previous FESS; pre-treatment morning cortisol within normal range; minimum of twice daily high-volume sinonasal mometasone irrigations (total dose of 4 mg) for 12 weeks; and post-treatment morning cortisol measured within 2 weeks following the study period. Patients with potential for endogenous or exogenous disruption of the HPA axis were excluded. Results 14 patients were enrolled in this prospective cohort study. In all but one patient, pre- and post-treatment morning cortisol levels were not significantly different and were within normal limits (6.7-25.4 μg/dL). Following an uninterrupted 12-week treatment course, no evidence of HPA axis suppression was found (P = 0.915). The single patient who was found to have a low (1.3 μg/dL) post-treatment morning serum cortisol level reportedly received an intraarticular steroid shot several days prior to the blood draw. She remained asymptomatic and her rechecked serum cortisol was within normal limits at 12.3 μg/dL. Conclusions High-volume 2 mg twice daily sinonasal mometasone irrigations did not cause HPA axis suppression in a representative sample of patients with refractory CRS post-FESS with normal baseline cortisol levels.

Background Previously evidence has demonstrated that as-needed combination low-dose budesonide-formoterol reduced the risk of severe exacerbations compared with short-acting β2-agonist (SABA) reliever therapy in an adolescent with mild asthma. Concerns as if the extra benefit offered by this drug outweighs the additional cost. This study aimed to evaluate the cost-effectiveness of as-needed combination low-dose budesonide-formoterol compared with short-acting β2-agonist (SABA) reliever therapy in adolescents with mild asthma in Colombia. Methods A probabilistic Markov model was created to estimate the cost and quality-adjusted life-years (QALYs) of patients with mild asthma in Colombia. Total costs and QALYs of low-dose budesonide-formoterol compared with short-acting β2-agonist (SABA) were calculated over a lifetime horizon. Multiple sensitivity analyses were conducted. Cost-effectiveness was evaluated at a willingness-to-pay value of $19,000. Results The model suggests a potential gain of 0.03 QALYs and per patient per year on low-dose budesonide-formoterol. The cost difference per person was US$-4 per patient per year in favor of budesonide- formoterol. The position of dominance negates the need to calculate an incremental cost-effectiveness ratio. In the one-way and probabilistic sensitivity analyses, our base-case results were robust to variations of all assumptions and parameters. Conclusion In conclusion, low-dose budesonide-formoterol as a reliever was found to be cost-effective when added to usual care in adolescents with mild asthma. This evidence should promote economic evaluations in developed and developing countries for the inclusion of new drugs in health insurance plans.

Background Interleukin (IL)-10 is a key anti-inflammatory cytokine that may be reduced in asthma but is enhanced by corticosteroids, especially when combined with a statin, although the mechanisms of these effects are uncertain. Objective To study the role of autophagy in macrophages in promoting inflammation in asthma through reducing IL-10 secretion and how corticosteroids and statins may reverse this process. Methods We conducted a randomised double-blind placebo-controlled study in moderate to severe asthmatic patients (n = 44) to investigate the effect of an inhaled corticosteroid (budesonide 400 μg/day) and the combination of budesonide with an oral statin (simvastatin 10 mg/day) given for 8 weeks on autophagy protein expression in sputum cells by using immunocytochemistry and measurement of IL-10 release. In in vitro experiments, we studied cross-regulation between autophagy and IL-10 release by measuring the expression of autophagy proteins in M2-like macrophages and the effects of budesonide and simvastatin on these mechanisms. Results In asthmatic patients, inhaled budesonide inhibited airway macrophage autophagy (beclin-1, LC3) as well as autophagic flux (p62), which was enhanced by simvastatin and was correlated with increased sputum IL-10 and reduced IL-4 concentrations. In macrophages in vitro, budesonide and simvastatin inhibited rapamycin-induced autophagy as well as autophagic flux, with reduced expression of beclin-1 and LC3, but enhanced the accumulation of p62 and increased expression of IL-10, which itself further inhibited autophagy in macrophages. With siRNA-mediated silencing, LC3-deficient macrophages also showed a maximal induction of IL-10 transcription. Neutralisation of IL-10 with recombinant specific blocking antibody and silencing IL-10 transcription reversed the inhibitory effects of budesonide and simvastatin on macrophage autophagy. Conclusion and clinical relevance Inhibition by corticosteroids and a statin of macrophage autophagy enhances IL-10 production, resulting in the control of asthmatic inflammation.

Background Our institution tests the European Baseline Series (EBS) and a steroid series sequentially in all patients presenting for patch testing. The rate of steroid sensitization in New Zealand has not previously been documented. Objectives To investigate the rate of corticosteroid sensitization and assess additional benefit of testing the full steroid series over the steroid allergy markers in the EBS. Methods/patients Retrospective analysis of all patient demographics and patch test results over a 5-year period (2014 to 2019) was performed at a tertiary patch test clinic in Auckland, New Zealand. Results A total of 319 patients completed patch testing, and 4.4% were sensitized to one or more corticosteroids. As much as 79% of positive reactions were of current relevance; 11/14 reactions were to tixocortol pivalate or budesonide. The "number needed to test" to detect one additional case of corticosteroid sensitization by using the full corticosteroid series over the EBS alone was 107. Conclusions Although corticosteroid sensitization was not uncommon in our population, the results suggest that sequential testing with the corticosteroid markers (budesonide and tixocortol) in the standard series alone is adequate. The additional corticosteroid series should be added if the markers are positive or where there is a clinical suspicion of corticosteroid allergy.

OBJECTIVE To evaluate the efficacy of absorbable steroid-impregnated nasal packing on postoperative outcomes following functional endoscopic sinus surgery (FESS) for chronic rhinosinusitis (CRS). METHODS A systematic review of the literature was conducted as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Twelve databases (including Journals@Ovid, Embase®, Medline®, EBM Reviews and Joanna Briggs Institute EBP Database) were searched using relevant keywords and expanded with corresponding MeSH/Emtree terms. Results were narrowed to English articles assessing the efficacy of absorbable packing impregnated with steroids post-production placed at time of surgery under general anesthetic, with hollow-lumen devices and devices inserted in-office excluded. RESULTS Eight studies met criteria and were included in this review. Five evaluated the efficacy of the intervention in only CRS with nasal polyposis (CRSwNP) patients, two included all subtypes of CRS, and one included only CRS without nasal polyposis (CRSsNP). Of the eight studies, four studied the efficacy of Nasopore®, three studied bioabsorbable gels, and one studied bioabsorbable calcium alginate. Four studies applied triamcinolone as the operative steroid, with the other studies utilizing betamethasone, budesonide, mometasone, and dexamethasone. Seven studies demonstrated statistically significant improvements in endoscopic outcomes using validated scoring scales, albeit at differing timepoints. The one study which included only CRSsNP patients failed to find a significant difference. CONCLUSION Steroid-impregnated nasal packing appears to have positive effects on postoperative endoscopic outcomes in CRSwNP patients undergoing FESS. Additional research is needed to evaluate the efficacy of these interventions in more recently defined subtypes of CRS, and whether these interventions differ in their efficacy in eosinophilic and non-eosinophilic CRS. Laryngoscope, 131:1704-1714, 2021.

Changes in absorptive capacity and first‐pass metabolism in the small intestine affect oral drug bioavailability. Characterization of such changes as a consequence of inflammation is important for developing physiologically‐based pharmacokinetic (PBPK) models for inflammatory bowel disease. We sought to elucidate the impact of small intestinal Crohn’s disease (CD) on villous length and CYP3A4 expression in children. Freshly frozen duodenal and terminal ileum (TI) biopsies from 107 children (1–19 years) with and without CD were evaluated for active inflammation. Villous length and CYP3A4 mRNA/protein expression were compared among regions of active and inactive inflammation in CD and controls. A twofold reduction in villous length was observed in inflamed duodena and ilia of children with CD, but in the absence of regional inflammation, villi in CD were comparable in length to controls. Expression of CYP3A4 mRNA correlated significantly with villous length in the TI (P = 0.0003), with a trend observed in the duodenum that did not reach statistical significance. In the presence of active inflammation, a significant decrease in CYP3A protein expression was confirmed in the duodenum, where protein expression also correlated significantly with villous length across diagnoses (P

BACKGROUND Refractory chronic rhinosinusitis (CRS) remains a significant burden for patients, often leaving them with few therapeutic options that provide low-morbidity, long-term, and meaningful symptomatologic and endoscopic disease improvement. Macrolides have long been thought to offer both an immunomodulatory and antimicrobial effect. Our objective was to evaluate the efficacy of low-dose, long-term azithromycin in a carefully selected high-risk population failing appropriate medical therapy of budesonide nasal irrigations (BNIs) and endoscopic sinus surgery (ESS). METHODS A double-blind, randomized, placebo-controlled trial was completed in a single tertiary-care center assessing the addition of 250 mg azithromycin, 3 times per week for 16 weeks, in adults failing ESS and high-volume BNIs. Associated comorbidities, as well as symptomatologic, microbiologic, and serologic values, were systematically collected. RESULTS A total of 128 patients were enrolled and underwent ESS followed by BNI. At the 4-month post-ESS visit, 48 patients showed disease persistence and were randomized to azithromycin or placebo. Overall, azithromycin, when compared with placebo, did not show a statistically significant difference in disease clearance (54% vs 33%, respectively; p = 0.146), although patients with disease clearance who were on azithromycin showed significantly better 22-item Sino-Nasal Outcome Test score improvements than patients on placebo (18 vs -0.9, respectively; p = 0.046). In a subgroup analysis excluding aspirin-exacerbated respiratory disease (AERD) patients, azithromycin significantly improved disease clearance when compared with placebo (71% vs 35%, respectively; p = 0.031), with a number needed to treat of 3 (2.8). CONCLUSION Low-dose azithromycin is a therapeutic option with few side effects. Its use can show favorable clinical outcomes in this difficult-to-treat population, especially if patients are AERD-negative.

BACKGROUND The sinonasal microbiome is believed to play an important role in the pathophysiology of refractory chronic rhinosinusitis (CRS). We evaluated changes in the microbiome following a 4-month course of low-dose azithromycin. Assessing microbiome alterations following such a treatment may help identify underlying mechanisms of this drug. METHODS A total of 48 adults with refractory CRS were enrolled in a double-blind, randomized, placebo-controlled trial. Patients were randomized to 250 mg of azithromycin or placebo 3 times weekly for 4 months. During this time, daily budesonide saline irrigations were continued. Sinonasal swabs were collected by endoscopically-assisted method prior to treatment initiation and at the end of it, and sent for 16S ribosomal RNA gene sequencing. High-resolution ANCHOR pipeline was used to infer and annotate putative species. The 2 patient groups were compared using DESeq2 differential abundance analysis. RESULTS From initiation to the end of azithromycin treatment, patients showed a significant difference in beta diversity analysis (p = 0.0004) along with a significant decrease in 71 different operational taxonomic units (OTUs) of Staphylococcus aureus (false discovery rate [FDR] < 0.05) obtained from the differential abundance analysis. This was not observed in placebo-treated patients. By the end of treatments, azithromycin-treated patients had a significant decrease in 29 different OTUs of S. aureus (FDR < 0.05) when compared to placebo. CONCLUSION A 4-month course of 250 mg of azithromycin 3 times weekly in patients with refractory CRS significantly decreases S. aureus abundance in the sinonasal microbiome. Considering the pathogenic role of S. aureus in the refractory CRS population, azithromycin may constitute an additional therapeutic option to help control this disease.

Background There is no strict correlation between early bronchopulmonary dysplasia and long-term respiratory disease. Early inhaled corticosteroids seem to reduce the incidence of bronchopulmonary dysplasia, but the long-term outcome remains unknown. Research question The aim of this study was to evaluate the effect of early inhaled corticosteroids on chronic respiratory morbidity. Methods Fifty-nine survivors from the Prague cohort included in Neonatal European Study of Inhaled Steroids underwent further follow-up comprising of respiratory morbidity monitoring during the first 2 years of life followed by objective lung function testing performed at the age of 5.9 years (range 5-7 years). Both outcomes were pursued and finalized before the unblinding of budesonide subgroups. Results Fifty randomized (budesonide vs placebo group, 56% vs 44%) survivors were included in the study. Spirometry was successfully performed in 48 children. No statistically significant differences were found in the lung function test (forced expiratory flow [FEF] - FEF75 , FEF50, FEF25 , and FEF25-75; FEV1 , forced vital capacity [FVC], FEV1 /FVC) although mild trend to the improvement of expiratory flow pattern was observed in the budesonide group (median z-score of FEV1 /FVC -0.376 vs -0.983, P = .13; median z-score of FEF25-75 -1.004 vs -1.458, P = .13; median z-score of FEF75 -0.527 vs -0.996, P = .17). Children assigned to budesonide had a significantly lower rate of symptoms of chronic lung disease (34.6% vs 68.2%; P = .04) than children assigned to placebo. Interpretation Our study suggests that early inhaled budesonide was associated with the trend to the improvement of functional lung parameters and with a lower rate of symptoms of chronic lung disease within the first 2 years of life.

The main objectives in Crohn's disease are to avoid disease complications and preserve the patient's quality of life. Early disease control and close monitoring with specific targets to reach might be the only way to change the disease course. In two decades, we have moved from clinical response to full remission (clinical and endoscopic remission) requiring a tight monitoring of both symptoms and objective signs of inflammation. This review summarizes the concepts of tight control and treat-to-target and their potential for disease modification.

Author(s): Yan, Carol H; Mundy, David C; Patel, Zara M | Abstract: BackgroundOlfactory dysfunction is a prevalent problem with a significant impact on quality of life and increased mortality. Limited effective therapies exist. Platelet-rich plasma (PRP) is an autologous biologic product with anti-inflammatory and neuroprotective effects. This novel pilot study evaluated the role of PRP on olfactory neuroregeneration in patients with hyposmia.MethodsSeven patients who had olfactory loss greater than 6 months in duration, no evidence of sinonasal inflammatory disease, and no improvement with olfactory training and budesonide topical rinses were enrolled in this preliminary study. Patients received a single intranasal injection of PRP into the mucosa of the olfactory cleft. The Sniffin' Sticks olfactory test consisting of threshold, discrimination, and identification measurements (TDI) was administered at the beginning of the study and at 1 and 3 months.ResultsAll patients reported a subjective improvement of their smell shortly after injection but then stabilized. At 3-month post-treatment, two patients with functional anosmia (TDI l 16) did not improve significantly. Five patients with hyposmia (TDI g 16 but l30) showed an improvement with 60% achieving normosmia (TDI g 30) at 3-month follow-up. On average, patients with baseline TDI g 16 improved by 5.85 points with the most significant improvement in the threshold subcomponent. There were no adverse outcomes from intranasal PRP injections.ConclusionPRP appears safe for use in the treatment of olfactory loss, and preliminary data suggest possible efficacy, especially for those with moderate yet persistent loss. Further studies will help determine optimal frequency and duration of use.Level of evidence 2b

BACKGROUND Chronic rhinosinusitis (CRS) is a local inflammatory process driven by eosinophils. Mucosal eosinophil count (MEC) has previously been demonstrated to be a reliable indicator of disease severity. We aim to evaluate use of MEC in guiding medical management of CRS after functional endoscopic sinus surgery (FESS). METHODS We retrospectively reviewed patients with CRS who underwent FESS from 2004 to 2017. Tissue MEC per high-power field (HPF) was determined by pathologic examination. MECs were compared by polyp status, postoperative medication requirements, and revision surgery. Patients received normal saline (NS) nasal irrigations with additional treatment as needed for disease control: 1-drug therapy (1-DT) intranasal steroid spray (ISS), 2-drug therapy (2-DT) ISS plus budesonide nasal irrigations (BNI) or leukotriene receptor antagonist (LRA), or 3-drug therapy (3-DT) ISS plus BNI and LRA. Correlations between MEC and 22-item Sino-Nasal Outcome Test (SNOT-22), preoperative computed tomography (CT), and nasal endoscopy scores were evaluated. RESULTS A total of 156 patients were included. Fifty-seven were managed with 1-DT, 35 with 2-DT, and 62 with 3-DT. Across all patients, mean postoperative 6-month and 1-year SNOT-22 (18.1 ± 17.0, 18.1 ± 20.2, respectively) and nasal endoscopy (3.6 ± 3.8, 3.6 ± 4.1, respectively) scores were significantly lower than preoperative scores (37.4 ± 22.8, 6.5 ± 4, respectively). With increasing MEC, odds of requiring 2-DT (odds ratio [OR] = 1.1, p = 0.0002), 3-DT (OR = 1.12, p < 0.0001), and revision surgery (OR = 1.11, p < 0.0001) were significantly increased. Preoperative endoscopy (ρ = 0.44, p < 0.0001) and CT scores (ρ = 0.51, p < 0.0001) and postoperative 6-month (ρ = 0.55, p < 0.0001) and 1-year (ρ = 0.4, p < 0.0001) endoscopy scores demonstrated good correlation with MEC. CONCLUSION MEC correlates with objective clinical disease severity and may guide aggressiveness of management for the individual patient.

Background Eosinophilic chronic rhinitis with nasal polyps (eos‐CRSwNP) is a subtype of nasal polyps (NPs) characterized by severe type‐2 inflammation and defective epithelial barrier function. The epithelial barrier plays important roles in the pathogenesis of NPs and type‐2 inflammation. Particular matter 2.5 (PM2.5) are fine particles with a diameter less than 2.5 μm, containing a mixture of different components. Here, we investigated the impact of PM2.5 on the barrier function of the eos‐CRSwNP epithelium and explored the reparative function of budesonide. Methods Samples from noninflammatory nasal mucosa and eos‐CRSwNP were collected to establish an in vitro air–liquid interface cultured model. The cells were exposed to PM2.5 at 50 or 100 µg/ml intermittently for 72 h, with or without budesonide pretreatment. Barrier function and tight junction (TJ) expression were reflected by measuring transepithelial resistance (TER), paracellular flux permeability of fluorescein isothiocyanate‐labeled 4‐kDa dextran, quantitative real‐time polymerase chain reaction (qPCR), and immunofluorescence staining of TJ proteins. Cytokine expression was measured by qPCR and enzyme‐linked immunosorbent assay or Luminex. Results PM2.5 increased paracellular flux and downregulated TJ protein expression (zona occuldens‐1, occludin, and claudin‐1), but did not change TER. These changes could be partially restored by budesonide treatment. Interleukin (IL)‐8, IL‐10, IL‐1α, and tissue inhibitor of metalloproteinase (TIMP)‐1 concentrations were significantly increased in the culture medium of cells exposed to PM2.5, and budesonide significantly reduced the changes in IL‐8, IL‐1α, and TIMP‐1. Conclusion PM2.5 impaired the barrier function of eos‐CRSwNP epithelial cells and increased the permeability of large molecules. PM2.5 also increased the secretion of pro‐inflammatory cytokines by nasal epithelial cells. Budesonide could partially repair the damage, suggesting potential applications in clinical practice.

BACKGROUND: Budesonide has been proven to be an effective treatment for microscopic colitis (MC). However, the two current commercially available preparations are released in the ileum. Beclomethasone dipropionate (Clipper®) is a synthetic corticosteroid with topical colonic release. OBJECTIVE: This study aimed to explore whether an open-label treatment with beclomethasone dipropionate is an effective treatment for MC. METHODS: Prospectively collected data of 30 patients from six centres were retrospectively analysed. All patients had a confirmed diagnosis of idiopathic MC (lymphocytic and collagenous colitis) and were symptomatic (i.e. ≥ 21 loose stools over a seven-day period). Treatment consisted of 10 mg beclomethasone daily for four weeks, followed by 5 mg daily for another four weeks. The primary end point was the proportion of patients in remission (i.e. a mean of

Background: Cortiment®MMX® (budesonide MMX®) is currently approved for the induction of remission in mild-to-moderate ulcerative colitis (UC) patients when 5-ASA treatment is not sufficient. Data in real-life settings are lacking. Methods: This was a multicentre observational prospective cohort study conducted in Europe and Canada. Effectiveness, safety, and tolerability of Cortiment®MMX® in a real-life setting of patients treated for mild-to-moderate UC was investigated. Patients were prescribed Cortiment®MMX® in accordance with the Summary of the Product Characteristics (SmPC). The primary endpoint was the clinical benefit of Cortiment® MMX® in routine practice (improvement ≥ 3 points in the clinical sub-scores of the Ulcerative Colitis Disease Activity Index, UCDAI). Results: Data from 326 patients with mild-to-moderate UC were analysed for the primary endpoint. Clinical benefit was achieved in 60.1% (196/326) of patients at the end of Cortiment®MMX® treatment. Clinical remission (UCDAI clinical sub-score ≤ 1), full symptoms resolution (rectal bleeding (RB) = 0 and stool frequency (SF) = 0) and symptoms resolution (RB = 0 + SF ≤ 1) at the end of the Cortiment®MMX® treatment were achieved in 51.8%, 45.1% and 63.2% of patients, respectively. The median time to symptoms resolution was 30 days (range 29.0–36.0 days). Fifty patients (14.3%) had to discontinue Cortiment®MMX® due to adverse events; 17.5% of patients (n = 61) reported at least one adverse event related to the study drug. Conclusions: This was the first time that a large cohort study was conducted with Cortiment®MMX® in a real-life setting. It demonstrated that Cortiment®MMX® is effective, safe and well tolerated in about 60% of UC patients.

BACKGROUND A short-course oral corticosteroid taper and topical intranasal corticosteroids may be used to maximize the success of medical management for chronic rhinosinusitis with nasal polyps (CRSwNP). In this study, we sought to identify characteristics that would be predictive of efficacy for this combination regimen. METHODS Sixty-four patients with CRS, bilateral polyps, a polyp score of at least 3, and a 22-item Sino-Nasal Outcome Test (SNOT-22) score ≥20 were prospectively enrolled and uniformly treated with a 15-day prednisone taper and twice daily dilute budesonide irrigations. Participants were assessed at enrollment and at follow up, 2 to 5 months later. Clinical and demographic characteristics were assessed at enrollment. At both time points, CRS symptoms were assessed with SNOT-22, and polyp score (range, 0 to 6) was assessed endoscopically. Associations were determined with regression. RESULTS Pretreatment SNOT-22 score (adjusted β = -0.83; 95% CI, -1.08 to -0.58; p < 0.001) and comorbid asthma (adjusted β = 15.75; 95% CI, 4.74 to 26.75; p = 0.007) were associated with a change in SNOT-22 experienced over the study period. Achieving a greater-than-1 minimal clinically important difference (MCID) improvement in SNOT-22 score was also associated with pretreatment SNOT-22 score (adjusted OR = 1.09; 95% CI, 1.04 to 1.14; p < 0.001) and comorbid asthma (adjusted OR = 0.13; 95% CI, 0.03 to 0.72; p = 0.019). SNOT-22 score ≥47 had 81.5% sensitivity and 78.4% specificity to detect patients experiencing 1 MCID improvement. Pretreatment polyp score was not associated with any outcome metric. CONCLUSION In treatment of CRSwNP with prednisone and budesonide irrigations, pretreatment endoscopy was not informative of treatment response. Pretreatment SNOT-22 and comorbid asthma may be more predictive.

The aim of the present study was to investigate if hyperhydration could influence the excretion and subsequent detection of budesonide (BDS) and its main metabolites (6β-hydroxy-budesonide and 16α-hydroxy-prednisolone) during doping control analysis by leading to concentrations below the WADA reporting level (30 ng/mL). The influence of hyperhydration on the plasma and urinary pharmacokinetic (PK) profiles of BDS and metabolites was also examined. Seven healthy physically active non-smoking Caucasian males participated in a 15-day clinical study. BDS was administered orally at a single dose of 9 mg on Days 1, 7, and 13. Hyperhydration was applied in the morning on two consecutive days, that is, 0 and 24 hours after first fluid ingestion. Water and a commercial sports drink were used as hyperhydration agents (20 mL/kg body weight). Results showed no significant difference (P > 0.05, 95% CI) on plasma or urinary PK parameters under hyperhydration conditions for all the analytes. However, significant differences (P

Objectives Current medications for allergic rhinitis (AR) may have undesirable side effects that could affect quality of life (QoL). Probiotics could be an alternative in these patients. The aim of this study was to assess the impact of add-on probiotics on symptoms and QoL of patients. Methods In this randomized crossover clinical trial, patients with persistent AR were included. Each subject received budesonide with probiotic supplements (BP) or budesonide with placebo for 8 weeks (B), then vice versa for a further 8 weeks. There was an 8-week washout. The primary outcome was the change of the Short Form 36-Item Health Survey (SF-36) score. The secondary outcomes were assessed by the Sinonasal Outcome Test-22 (SNOT-22) and the Control of Allergic Rhinitis and Asthma Test (CARAT) questionnaires. Results A total of 152 subjects (30.1 ± 7.6 years) completed the study. The SF-36 score in both groups showed improvement compared with baseline values. Treatment BP was more effective than that of B. The Cohen's d and the number needed to treat for Physical Component Scales of SF-36 were 0.40 and 10.77, respectively. These values for Mental Component Scales were 0.33 and 12.61, respectively. Also, treatment BP showed more reduction in the score of SNOT-22 and CARAT. Conclusion This study showed that the addition of probiotics to budesonide significantly improved QoL in persistent AR patients. However, the clinical situation of these patients may be not very representative of AR patients in general population. Further studies are recommended. Level of evidence 1b Laryngoscope, 129:1744-1750, 2019.

BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSION 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.

Background This study aimed to identify factors that affect the prognosis of budesonide therapy for Crohn's disease patients. Method Change in Crohn's disease activity index (CDAI) scores at latest follow-up after budesonide therapy reported by individual studies were pooled to gain overall effect size under random effects model and then metaregression analyses were performed to identify factors affecting the change in CDAI scores after budesonide treatment. Results Fifteen studies (1875 patients; age, 35.6 years [95% confidence interval (CI): 34.1, 37.0]; 41.66% [95% CI: 37.44, 45.88] males; 33.3% [95% CI: 24.3, 42.3] smokers; weight, 64.7 kg [95% CI: 62.71 66.6] and height, 168 cm [95% CI: 165, 171]) were included. Disease duration was 7.0 years [95% CI: 5.7, 8.2] and duration of the current episode was 3.1 months [95% CI: 1.7, 4.4]. Proportion of patients with prior resection was 42% [95% CI: 34%, 50%]. The disease was 21% in the ileum, 61% in ileocecum, and 18% in the colon. Budesonide dose was 8.83 mg/d [95% CI: 7.52, 10.14]. In a follow-up duration of 21.0 weeks [95% CI: 15.2, 26.8], budesonide treatment was associated with improvement in CDAI score of -117.8 [95% CI: -134.0, -102.0]. The magnitude of the change in CDAI score at the latest follow-up was significantly inversely associated with the percentage of smokers, but positively associated with the baseline CDAI score and duration of the current episode. Conclusion Budesonide therapy to Crohn's disease patients appears to be more effective in patients with the more serious condition. Smoking may also affect the prognosis.

Background Asthma affects 350 million people worldwide including 45% to 70% with mild disease. Treatment is mainly with inhalers containing beta₂‐agonists, typically taken as required to relieve bronchospasm, and inhaled corticosteroids (ICS) as regular preventive therapy. Poor adherence to regular therapy is common and increases the risk of exacerbations, morbidity and mortality. Fixed‐dose combination inhalers containing both a steroid and a fast‐acting beta₂‐agonist (FABA) in the same device simplify inhalers regimens and ensure symptomatic relief is accompanied by preventative therapy. Their use is established in moderate asthma, but they may also have potential utility in mild asthma. Objectives To evaluate the efficacy and safety of single combined (fast‐onset beta₂‐agonist plus an inhaled corticosteroid (ICS)) inhaler only used as needed in people with mild asthma. Search methods We searched the Cochrane Airways Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase, ClinicalTrials.gov and the World Health Organization (WHO) trials portal. We contacted trial authors for further information and requested details regarding the possibility of unpublished trials. The most recent search was conducted on 19 March 2021. Selection criteria We included randomised controlled trials (RCTs) and cross‐over trials with at least one week washout period. We included studies of a single fixed‐dose FABA/ICS inhaler used as required compared with no treatment, placebo, short‐acting beta agonist (SABA) as required, regular ICS with SABA as required, regular fixed‐dose combination ICS/long‐acting beta agonist (LABA), or regular fixed‐dose combination ICS/FABA with as required ICS/FABA. We planned to include cluster‐randomised trials if the data had been or could be adjusted for clustering. We excluded trials shorter than 12 weeks. We included full texts, abstracts and unpublished data. Data collection and analysis Two review authors independently extracted data. We analysed dichotomous data as odds ratios (OR) or rate ratios (RR) and continuous data as mean difference (MD). We reported 95% confidence intervals (CIs). We used Cochrane's standard methodological procedures of meta‐analysis. We applied the GRADE approach to summarise results and to assess the overall certainty of evidence. Primary outcomes were exacerbations requiring systemic steroids, hospital admissions/emergency department or urgent care visits for asthma, and measures of asthma control. Main results We included six studies of which five contributed results to the meta‐analyses. All five used budesonide 200 μg and formoterol 6 μg in a dry powder formulation as the combination inhaler. Comparator fast‐acting bronchodilators included terbutaline and formoterol. Two studies included children aged 12+ and adults; two studies were open‐label. A total of 9657 participants were included, with a mean age of 36 to 43 years. 2.3% to 11% were current smokers. FABA / ICS as required versus FABA as required Compared with as‐required FABA alone, as‐required FABA/ICS reduced exacerbations requiring systemic steroids (OR 0.45, 95% CI 0.34 to 0.60, 2 RCTs, 2997 participants, high‐certainty evidence), equivalent to 109 people out of 1000 in the FABA alone group experiencing an exacerbation requiring systemic steroids, compared to 52 (95% CI 40 to 68) out of 1000 in the FABA/ICS as‐required group. FABA/ICS as required may also reduce the odds of an asthma‐related hospital admission or emergency department or urgent care visit (OR 0.35, 95% CI 0.20 to 0.60, 2 RCTs, 2997 participants, low‐certainty evidence). Compared with as‐required FABA alone, any changes in asthma control or spirometry, though favouring as‐required FABA/ICS, were small and less than the minimal clinically‐important differences. We did not find evidence of differences in asthma‐associated quality of life or mortality. For other secondary outcomes FABA/ICS as required was associated with reductions in fractional exhaled nitric oxide, probably reduces the odds of an adverse event (OR 0.82, 95% CI 0.71 to 0.95, 2 RCTs, 3002 participants, moderate‐certainty evidence) and may reduce total systemic steroid dose (MD ‐9.90, 95% CI ‐19.38 to ‐0.42, 1 RCT, 443 participants, low‐certainty evidence), and with an increase in the daily inhaled steroid dose (MD 77 μg beclomethasone equiv./day, 95% CI 69 to 84, 2 RCTs, 2554 participants, moderate‐certainty evidence). FABA/ICS as required versus regular ICS plus FABA as required There may be little or no difference in the number of people with asthma exacerbations requiring systemic steroid with FABA/ICS as required compared with regular ICS (OR 0.79, 95% CI 0.59 to 1.07, 4 RCTs, 8065 participants, low‐certainty evidence), equivalent to 81 people out of 1000 in the regular ICS plus FABA group experiencing an exacerbation requiring systemic steroids, compared to 65 (95% CI 49 to 86) out of 1000 FABA/ICS as required group. The odds of an asthma‐related hospital admission or emergency department or urgent care visit may be reduced in those taking FABA/ICS as required (OR 0.63, 95% CI 0.44 to 0.91, 4 RCTs, 8065 participants, low‐certainty evidence). Compared with regular ICS, any changes in asthma control, spirometry, peak flow rates (PFR), or asthma‐associated quality of life, though favouring regular ICS, were small and less than the minimal clinically important differences (MCID). Adverse events, serious adverse events, total systemic corticosteroid dose and mortality were similar between groups, although deaths were rare, so confidence intervals for this analysis were wide. We found moderate‐certainty evidence from four trials involving 7180 participants that FABA/ICS as required was likely associated with less average daily exposure to inhaled corticosteroids than those on regular ICS (MD ‐154.51 μg/day, 95% CI ‐207.94 to ‐101.09). Authors' conclusions We found FABA/ICS as required is clinically effective in adults and adolescents with mild asthma. Their use instead of FABA as required alone reduced exacerbations, hospital admissions or unscheduled healthcare visits and exposure to systemic corticosteroids and probably reduces adverse events. FABA/ICS as required is as effective as regular ICS and reduced asthma‐related hospital admissions or unscheduled healthcare visits, and average exposure to ICS, and is unlikely to be associated with an increase in adverse events. Further research is needed to explore use of FABA/ICS as required in children under 12 years of age, use of other FABA/ICS preparations, and long‐term outcomes beyond 52 weeks.

BACKGROUND: Transient tachypnoea of the newborn (TTN) is characterized by tachypnoea and signs of respiratory distress. Transient tachypnoea typically appears within the first two hours of life in term and late preterm newborns. The administration of corticosteroids might compensate for the impaired hormonal changes which occur when infants are delivered late preterm, or at term but before the onset of spontaneous labour (elective caesarean section). Corticosteroids might improve the clearance of liquid from the lungs, thus reducing the effort required to breathe and improving respiratory distress. OBJECTIVES: The objective of this review is to assess whether postnatal corticosteroids — compared to placebo, no treatment or any other drugs administered to treat TTN — are effective and safe in the treatment of TTN in infants born at 34 weeks' gestational age or more. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 2), MEDLINE (1996 to 19 February 2019), Embase (1980 to 19 February 2019) and CINAHL (1982 to 19 February 2019). We applied no language restrictions. We searched clinical trial registries for ongoing studies. SELECTION CRITERIA: We included randomized controlled trials, quasi‐randomized controlled trials and cluster‐randomized trials comparing postnatal corticosteroids versus placebo or no treatment or any other drugs administered to infants born at 34 weeks' gestational age or more and less than three days of age with TTN. DATA COLLECTION AND ANALYSIS: For each of the included trials, two review authors independently extracted data (e.g. number of participants, birth weight, gestational age, duration of oxygen therapy, need for continuous positive airway pressure, need for mechanical ventilation, duration of mechanical ventilation, etc.) and assessed the risk of bias (e.g. adequacy of randomization and blinding, completeness of follow‐up). The primary outcomes considered in this review were need for nasal continuous positive airway pressure and need for mechanical ventilation. We used the GRADE approach to assess the certainty of the evidence. MAIN RESULTS: One trial, which included 49 infants, met the inclusion criteria. The trial compared the use of inhaled corticosteroids (budesonide) with placebo. We found no differences between groups in terms of need for nasal continuous positive airway pressure (risk ratio (RR) 1.27, 95% confidence interval (CI) 0.65 to 2.51; 1 study, 49 participants) and need for mechanical ventilation (RR 0.52, 95% CI 0.05 to 5.38; 1 study, 49 participants). The type of mechanical ventilation used in the included study was high‐frequency oscillation. Tests for heterogeneity were not applicable for any of the analyses as only one study was included. Out of the secondary outcomes we deemed to be of greatest importance to patients, the study only reported on duration of hospital stay, which was no different between groups. The quality of the evidence is very low, due to the imprecision of the estimates and indirectness. We identified no ongoing trials. AUTHORS' CONCLUSIONS: Given the paucity and very low quality of the available evidence, we are unable to determine the benefits and harms of postnatal administration of either inhaled or systemic corticosteroids for the management of TTN.

Introduction Microscopic colitis is a chronic inflammatory bowel disease characterised by normal or almost normal endoscopic appearance of the colon, chronic watery, non-bloody diarrhoea and distinct histological abnormalities, which identify three histological subtypes, the collagenous colitis, the lymphocytic colitis and the incomplete microscopic colitis. With ongoing uncertainties and new developments in the clinical management of microscopic colitis, there is a need for evidence-based guidelines to improve the medical care of patients suffering from this disorder. Methods Guidelines were developed by members from the European Microscopic Colitis Group and United European Gastroenterology in accordance with the Appraisal of Guidelines for Research and Evaluation II instrument. Following a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the certainty of the evidence. Statements and recommendations were developed by working groups consisting of gastroenterologists, pathologists and basic scientists, and voted upon using the Delphi method. Results These guidelines provide information on epidemiology and risk factors of microscopic colitis, as well as evidence-based statements and recommendations on diagnostic criteria and treatment options, including oral budesonide, bile acid binders, immunomodulators and biologics. Recommendations on the clinical management of microscopic colitis are provided based on evidence, expert opinion and best clinical practice. Conclusion These guidelines may support clinicians worldwide to improve the clinical management of patients with microscopic colitis. Funding Agencies|UEG Activity Grant

Hypoxia challenges left ventricular (LV) function due to reduced energy supply. Conflicting results exist whether high‐altitude exposure impairs LV diastolic function and thus contributes to the high altitude‐induced increase in systolic pulmonary artery pressure (sPAP) and reduction in stroke volume (SV). This study aimed to assess LV diastolic function, LV end‐diastolic pressure (LVEDP), and LA mechanics using comprehensive echocardiographic imaging in healthy volunteers at 4559 m. Fifty subjects performed rapid (

Chronic kidney disease has become a worldwide problem. Among chronic kidney disease patients, IgA nephropathy is common in the world. Serum levels of galactose deficient (Gd)-IgA1 and Gd-IgA1-specific antibodies are elevated in most IgA nephropathy patients. Glomerular Gd-IgA1 deposition has been observed by immunofluorescence. There are many reports that the anti-proteinuric effect is significantly greater in groups who receive tonsillectomy with steroid pulse therapy in IgA nephropathy patients. Furthermore, patients with tonsillectomy with steroid pulse therapy have shown a strong down-regulation of delta serum IgA/C3 per year and have conserved their renal function. New treatments, that is, Atacicept and glucocorticoid budesonide, have been developed for this disease.

Background Corticosteroids are the most potent drugs for the control of severe equine asthma, but adverse effects limit their chronic systemic administration. Inhaled medications allow for drug delivery directly into the airways, reducing the harmful effects of these drugs. Objectives To evaluate the efficacy of inhaled budesonide specifically formulated for the equine use and administered by a novel inhalation device in horses with severe asthma. Study design Experimental studies in horses with naturally occurring asthma with cross-over, randomised, blinded experimental designs. Methods In Study 1, budesonide (1800 μg twice daily) administered using a novel Respimat® based inhaler was compared to i.v. dexamethasone (0.04 mg/kg). In Study 2, 3 doses of budesonide (450, 900, and 1800 μg) were compared to oral dexamethasone (0.066 mg/kg). Lung function, bronchoalveolar fluid cytology (Study 1), CBC, serum chemistry, and serum cortisol and adrenocorticotropic hormone (ACTH) values were evaluated. Results In Study 1, there was a marked and significant improvement in the lung function of all horses treated with budesonide and dexamethasone. Neutrophil percentages in bronchoalveolar fluid decreased in all horses treated with dexamethasone and in four of six horses treated with budesonide. Serum cortisol and blood ACTH concentrations decreased with both treatments. In Study 2, there was a significant improvement in the lung function with all dosages of budesonide, and the effects of higher dosages were comparable to those of dexamethasone. Dexamethasone and budesonide at the two higher dosages induced a significant decrease of cortisol concentrations. Main limitations The Respimat® based inhaler is not currently commercially available. Conclusions Administration of budesonide with the Respimat® based inhaler provided dose-dependent relief of airway obstruction in horses with severe asthma, but also a suppression of serum cortisol.

Background Although intranasal steroids and anti-cysteinyl-leukotriene-receptor antagonists are efficacious in the treatment of seasonal allergic rhinitis (SAR), combinations of these agents have not unequivocally been demonstrated to be superior to the individual drugs. We aimed to compare the efficacy and potential mechanisms of budesonide nasal spray (BD), oral montelukast (MNT), and combination therapy comprising a half-dose of budesonide plus montelukast (hBD+MNT) in SAR patients. Methods We performed a single-center, randomized, open-label study in SAR subjects (n = 100). Participants were randomized to receive BD (256 μg), MNT (10 mg), or hBD (128 μg)+MNT for 14 days. Symptom severity scores, nasal cavity volume (NCV), fraction of exhaled nitric oxide (FeNO), eosinophil cationic protein (ECP), histamine and cysteinyl-leukotrienes (CysLTs), and T-cell subsets were assessed before and after treatment. Results All treatments significantly improved symptoms from baseline; however, hBD+MNT produced significantly greater improvements in nasal congestion compared with BD or MNT alone. The BD and hBD+MNT groups had fewer patients with uncontrolled symptoms and improved NCV to a greater level than the MNT group. FeNO was decreased to a significantly greater extent from baseline after hBD+MNT treatment than after BD and MNT treatments. ECP, histamine, and CysLTs showed significantly greater decreases after BD and hBD+MNT treatments than after MNT treatment. BD decreased T-helper 1 (Th1) and Th2 cells and increased T-regulatory (Treg) cells in nasal mucosa and MNT decreased Th1 cells and increased Treg cells in peripheral blood, and this trend was reflected with hBD+MNT. Conclusion The hBD+MNT combination may have an overall better efficacy profile than BD and MNT monotherapy for treatment of SAR.

This randomized, phase 1, single‐dose, crossover study (NCT02189304) compared the 12‐hour pharmacokinetic (PK) and safety profiles of budesonide/glycopyrronium/formoterol fumarate dihydrate metered dose inhaler (BGF MDI) 320/14.4/10 μg and budesonide/formoterol fumarate dihydrate (BFF) MDI 320/10 μg (both formulated using innovative co‐suspension delivery technology) to an active comparator (budesonide/formoterol fumarate dihydrate dry powder inhaler [BUD/FORM DPI] 320/9‐μg delivered dose) in healthy adults. The potential for PK interaction between glycopyrronium and budesonide/formoterol within BGF MDI was assessed. Of 72 subjects randomized, 59 completed treatment. Systemic budesonide exposure (primary objective) based on area under the plasma drug concentration‐time curve 0‐12 hours (AUC0‐12; % coefficient of variation) was 1598.38 (49.7), 1657.09 (50.4), and 1276.75 (70.4) pg·h/mL for BGF MDI, BFF MDI, and BUD/FORM DPI, respectively; and formoterol exposure (AUC0‐12 [% coefficient of variation]) was 39.16 (45.9), 39.53 (40.5), and 23.24 (59.2) pg·h/mL, respectively. BGF MDI and BFF MDI were bioequivalent for budesonide and formoterol. All treatments were well tolerated. While systemic exposure to budesonide and formoterol was higher for BGF MDI and BFF MDI than for BUD/FORM DPI, there were no appreciable differences in the incidence of pharmacologically predictable adverse events. This, coupled with the absence of PK interactions, suggests the BGF MDI safety profile will be comparable to BUD/FORM DPI.

Background Olfactory training (OT) helps many patients with olfactory loss, but unfortunately it is ineffective for a significant number of patients. Budesonide irrigations are widely used to help patients with paranasal sinus inflammation, but have never been tested as a treatment for olfactory loss. We sought to examine the effect of adding budesonide irrigation to olfactory training on patients with olfactory loss without any visible sign of sinonasal inflammation. Methods In this randomized, controlled trial, 138 patients with olfactory loss and without any visible sign of sinonasal inflammation were randomized to either OT with saline irrigations or OT with budesonide irrigations. The University of Pennsylvania Smell Identification Test (UPSIT) was administered at the beginning of the study and at 6 months. Results A total of 133 patients completed the study. Forty-seven patients (35.3%) had a clinically significant change in UPSIT score. Among those in the budesonide irrigation + olfactory therapy group, 43.9% improved, compared with 26.9% in the saline irrigation + olfactory therapy group (p = 0.039); this corresponds to an odds ratio of 3.93 (95% confidence interval, 1.20-12.88) in a fully adjusted model (p = 0.024). Younger age and shorter duration of olfactory loss were also significant predictors of improvement. Conclusion Adding budesonide irrigation to olfactory training significantly improved olfactory ability compared with olfactory training plus saline irrigation.