Oral Budesonide and low serum albumin levels at surgery are associated with a higher risk of postoperative intra-abdominal septic complications after primary ileocaecal resection for Crohn's disease: A retrospective analysis of 853 consecutive patients.

BACKGROUND AND AIMS: The terminal ileum is the most frequent site of Crohn's Disease (CD) that necessitates surgery. Of the postoperative complications (POCs) associated with ileocaecal resection for CD, intra-abdominal septic complications (IASCs) include anastomotic leak, abscesses, and entero-cutaneous fistula. We aimed to identify predictors of IASCs and severe POCs (Clavien-Dindo ≥3) after primary ileocaecal resection for CD. METHODS: This is a retrospective single-centre cohort study including all consecutive primary ileocaecal resection for CD in a tertiary IBD centre between 2004 and 2021. RESULTS: A total of 853 patients underwent primary ileocaecal resection for CD. 307 (36.6 %) patients were receiving antibiotics, 253 (29.8 %), systemic steroids, and 178 (21.0 %) oral budesonide at surgery. At 90 days, 260 (30.8 %) patients developed POCs, 62 (7.3 %) severe POCs, and 56 (6.6 %) IASCs. At multivariate analysis, severe POCs were associated with lower preoperative albumin levels (OR1.58, 95 %CI 1.02-2.50, p = 0.040) and a history of cardiovascular diseases (OR2.36, 95 %CI 1.08-7.84, p = 0.030). IASCs were associated with lower preoperative albumin levels (OR1.81, 95 %CI 1.15-2.94, p = 0.011) and oral budesonide (OR2.07, 95 %CI 1.12-3.83, p = 0.021) with a dose-dependent effect. CONCLUSIONS: The independent association, dose-dependent effect, and biological plausibility of budesonide and IASCs suggest a robust causal effect. Oral budesonide should be carefully assessed before primary ileocaecal resection for CD.

[IgA nephropathy]. / IgA-Nephropathie.

IgA nephropathy (IgAN) is the most frequent primary form of glomerulonephritis. The origin of IgAN is only partially understood and appears to involve the occurrence of IgA1, which is normally secreted by mucous membranes, in the circulation followed by its glomerular deposition and inflammatory changes. Clinically, IgAN mostly follows an inapparent course and the disease is often only first diagnosed by kidney biopsy when kidney function disorders are already manifested. Key prognostic indicators include the extent of proteinuria and the already manifested evidence of irreversible kidney damage. Treatment includes supportive measures. The effectiveness of high-dose systemic corticosteroid treatment in European patients is uncertain and controversial due to the adverse side effects. Nefecon (encapsulated budesonide) is the first specific drug licensed for treatment of high risk IgAN patients. A number of further approaches are currently in clinical trials.

The role of budesonide intrapolyp injection in the management of type 2 chronic rhinosinusitis with nasal polyps: a randomised clinical trial.

PROBLEM: To assess the efficacy of budesonide intrapolyp injection in chronic rhinosinusitis with nasal polyps. METHOD: Ninety patients were divided into three groups; group A was given oral prednisolone, group B was given budesonide intrapolyp injection weekly for five consecutive weeks and group C was given budesonide as nasal irrigation for one month. Patients were assessed using Sino-Nasal Outcome Test 22 score, total nasal polyp score, serum immunoglobulin E, absolute eosinophilic count, and morning cortisol level before treatment, one week and three months after completing their treatment. RESULTS: Total nasal polyp score decreased significantly in all groups compared to those at baseline. Reduction in the oral and injection groups was greater than the wash group (p2 = 0.004), (p3 < 0.001), and the same trend concerning Sino-Nasal Outcome Test 22 score (p2 < 0.001), (p3 < 0.001). CONCLUSION: Budesonide is an effective agent used in intrapolyp injection with no documented systemic or visual side effects that has comparable results with oral steroids.

Incidence of hypocortisolism with long-term budesonide irrigation for chronic rhinosinusitis.

BACKGROUND: Budesonide irrigations (BIs) are commonly used to control inflammation in chronic rhinosinusitis (CRS). In 2016 we reported an analysis of long-term BI with regard to hypothalamic-pituitary-adrenal axis function. We present a follow-up analysis in a larger cohort of patients with longer follow-up. METHODS: Patients were candidates for stimulated cortisol testing after regularly performing BI for CRS at least daily for ≥6 months. We retrospectively evaluated all patients who received stimulated cortisol testing at our center between 2012 and 2022. We correlated cortisol levels with the use of BI and other forms of corticosteroids. RESULTS: We analyzed 401 cortisol test results in 285 patients. The mean duration of use was 34 months. Overall, 21.8% of patients were hypocortisolemic (<18 ug/dL) at first test. In patients who used only BI, the rate of hypocortisolemia was 7.5%, whereas in patients who also used concurrent oral and inhaled corticosteroids, the rate was 40% to 50%. Lower cortisol levels were associated with male sex (p < 0.0001) and concomitant use of oral and inhaled steroids (p < 0.0001). Duration of BI use was not significantly associated with lower cortisol levels (p = 0.701), nor was greater dosing frequency (p = 0.289). CONCLUSION: Prolonged use of BI alone is not likely to cause hypocortisolemia in the majority of patients. However, concomitant use of inhaled and oral steroids and male sex may be associated with hypocortisolemia. Surveillance of cortisol levels may be considered in vulnerable populations who use BI regularly, particularly in patients using other forms of corticosteroids with known systemic absorption.

Adverse events associated with budesonide nasal irrigation reported to the US Food and Drug Administration: 2007 to 2022.

KEYPOINTS: Between 2007 and 2022, the FDA received 119 US-based reports mentioning budesonide nasal irrigation. Most reports were submitted by patients and alerted FDA to off-label usage of budesonide. Notable adverse events reported to the FDA included headache, dyspnea, and blurred vision.

An open-label study evaluating the safety and efficacy of budesonide in patients with IgA nephropathy at high risk of progression.

We sought to evaluate the efficacy and safety of budesonide (Budenofalk) in the treatment of patients with IgA Nephropathy. We conducted a prospective, interventional, open-label, single-arm, non-randomized study that enrolled 32 patients with IgAN at high risk of progression (BUDIGAN study, ISRCTN47722295, date of registration 14/02/2020). Patients were treated with Budesonide at a dose of 9 mg/day for 12 months, subsequently tapered to 3 mg/day for another 12 months. The primary endpoints were change of eGFR and proteinuria at 12, 24 and 36 months. The study cohort had a mean eGFR and 24-h proteinuria of 59 ± 24 ml/min/1.73m2 and 1.89 ± 1.5 g/day, respectively. Treatment with budesonide determined a reduction in proteinuria at 12-, 24- and 36-months by -32.9% (95% CI - 53.6 to - 12.2), - 49.7% (95% CI - 70.1 to - 29.4) and - 68.1% (95% CI - 80.6 to - 55.7). Budesonide determined an eGFR preservation corresponding to a 12-, 24- and 36-months change of + 7.68% (95% CI - 4.7 to 20.1), + 7.42% (95% CI - 7.23 to 22.1) and + 4.74% (95%CI - 13.5 to 23), respectively. The overall eGFR change/year was + 0.83 ml/min/y (95% CI - 0.54 to 4.46). Budesonide was well-tolerated, and treatment emergent adverse events were mostly mild in severity and reversible. Budesonide was effective in the treatment of patients with IgAN at high-risk of progression in terms of reducing proteinuria and preserving renal function over 36 months of therapy.

Pooled Phase 2 and 3 Efficacy and Safety Data on Budesonide Oral Suspension in Adolescents with Eosinophilic Esophagitis.

OBJECTIVES: The objective of this study was to evaluate the efficacy and safety of budesonide oral suspension (BOS) in adolescents with eosinophilic esophagitis (EoE). METHODS: This post hoc analysis pooled data from two 12-week, randomized, double-blind, placebo-controlled studies of BOS 2.0 mg twice daily (b.i.d.) (phase 2, NCT01642212; phase 3, NCT02605837) in patients aged 11-17 years with EoE and dysphagia. Efficacy endpoints included histologic (≤6, ≤1, and <15 eosinophils per high-power field [eos/hpf]), dysphagia symptom (≥30% reduction in Dysphagia Symptom Questionnaire [DSQ] scores from baseline), and clinicopathologic (≤6 eos/hpf and ≥30% reduction in DSQ scores from baseline) responses at week 12. Change from baseline to week 12 in peak eosinophil counts, DSQ scores, EoE Histology Scoring System (EoEHSS) grade (severity) and stage (extent) total score ratios (TSRs), and total EoE Endoscopic Reference Scores (EREFS) were assessed. Safety outcomes were also examined. RESULTS: Overall, 76 adolescents were included (BOS, n = 45; placebo, n = 31). Significantly more patients who received BOS than placebo achieved histologic responses (≤6 eos/hpf: 46.7% vs 6.5%; ≤1 eos/hpf: 42.2% vs 0.0%; <15 eos/hpf: 53.3% vs 9.7%; P < 0.001) and a clinicopathologic response (31.1% vs 3.2%; P = 0.003) at week 12. More BOS-treated than placebo-treated patients achieved a dysphagia symptom response at week 12 (68.9% vs 58.1%; not statistically significant P = 0.314). BOS-treated patients had significantly greater reductions in EoEHSS grade and stage TSRs ( P < 0.001) and total EREFS ( P = 0.021) from baseline to week 12 than placebo-treated patients. BOS was well tolerated, with no clinically meaningful differences in adverse events versus placebo. CONCLUSIONS: BOS 2.0 mg b.i.d. significantly improved most efficacy outcomes in adolescents with EoE versus placebo.

Outcomes of Holmium Laser, Cryoablation, and Budesonide Inhalation for Treating Severe Central Airway Stenosis in Infants.

BACKGROUND: Central airway stenosis (CAS) in infants is characterized by dysphonia, dyspnea, cyanosis, repeated apnea, and infection. This case series study aimed to evaluate the safety and efficacy of holmium laser, cryoablation and budesonide inhalation in treating infants with severe CAS. METHODS: This retrospective study reviewed medical records data of 28 infants with severe CAS who underwent holmium laser treatment with cryoablation and/or balloon dilatation and budesonide inhalation therapy at Shanghai Children's Medical Center between June 2014 and May 2020. Outcomes were defined as treatment success when the stenotic area was <25% for the normal age group with stable reopening diameter at one-year follow-up. RESULTS: Patients' mean age was 12.8 ± 8.8 months and 17 (60%) were male. Sixteen cases had web-like stenosis and 12 had scar contracture stenosis. Among 16 patients with web-like stenosis, 8 (50%) underwent balloon dilation with cryotherapy and 8 (50%) underwent balloon dilation only; treatment success was achieved in 10 (62.5%) cases and after revised treatments in 5 (31.25%) cases. Among 12 patients with scar contracture stenosis, 6 (50%) underwent balloon dilation with cryotherapy, 4 (33.3%) underwent cryotherapy and 2 (16.7%) underwent balloon dilation only; treatment success was achieved in 3 (23.1%) cases and after 1-4 revised treatments in 8 (61.5%) cases. Symptoms of the 2 unsuccessful (7.1%) cases were relieved after tracheal stent insertion. Neither severe adverse events nor complications were observed during follow-up. CONCLUSION: Holmium laser with cryoablation followed by budesonide inhalation therapy safely and effectively cleans stenotic tissues and maintains airway reopening. Balloon dilation after holmium laser is recommended for treating web-like stenosis.

Formulation and Evaluation of the Anti-inflammatory, Anti-oxidative, and Anti-remodelling Effects of the Niosomal Myrtenol on the Lungs of Asthmatic Rats.

Asthma is a common chronic allergic disease that affects a significant percentage of the world's population. Niosomes are nanoparticles consisting of non-ionic surfactants that can be used for drug delivery. This research was designed to investigate the impacts of inhalation of simple and niosomal forms of myrtenol against adverse consequences of asthma in rats. Asthma induction was performed via injection of ovalbumin, followed by its inhalation. Niosomes were created by a heating protocol, and their physicochemical features were evaluated. Forty-nine male Wistar rats were allotted into 7 groups (n=7 each): Control (CTL), vacant niosome (VN), Asthma, Asthma+VN, Asthma+SM (simple myrtenol), Asthma+NM (niosomal myrtenol), and Asthma+B (budesonide). Lung remodeling, serum immunoglobulin E (IgE), inflammatory  and cytokines, and antioxidant factors in the lung tissue and bronchoalveolar fluid (BALF), as well as), were evaluated. The results showed that myrtenol-loaded niosomes had appropriate encapsulation efficiency, kinetic release, size, and zeta potential. The thickness of the epithelial cell layer in the lungs, as well as cell infiltration, fibrosis, IgE, reactive oxygen species, interleukin (IL)-6, and tumor nuclear factor alpha (TNF-α) levels, decreased significantly. In contrast, superoxide dismutase and glutathione peroxide activity increased significantly in the serum and BALF of the treated groups. The niosomal form of myrtenol revealed a higher efficacy than simple myrtenol and was similar to budesonide in ameliorating asthma indices.  Inhalation of simple and niosomal forms of myrtenol improved the detrimental changes in the asthmatic lung. The niosomal form induced more prominent anti-asthmatic effects comparable to those of budesonide.

Intratracheal budesonide mixed with surfactant to increase survival free of bronchopulmonary dysplasia in extremely preterm infants: study protocol for the international, multicenter, randomized PLUSS trial.

BACKGROUND: Bronchopulmonary dysplasia (BPD), an inflammatory-mediated chronic lung disease, is common in extremely preterm infants born before 28 weeks' gestation and is associated with an increased risk of adverse neurodevelopmental and respiratory outcomes in childhood. Effective and safe prophylactic therapies for BPD are urgently required. Systemic corticosteroids reduce rates of BPD in the short-term but are associated with poorer neurodevelopmental outcomes if given to ventilated infants in the first week after birth. Intratracheal administration of corticosteroid admixed with exogenous surfactant could overcome these concerns by minimizing systemic sequelae. Several small, randomized trials have found intratracheal budesonide in a surfactant vehicle to be a promising therapy to increase survival free of BPD. METHODS: An international, multicenter, double-blinded, randomized trial of intratracheal budesonide (a corticosteroid) mixed with surfactant for extremely preterm infants to increase survival free of BPD at 36 weeks' postmenstrual age (PMA; primary outcome). Extremely preterm infants aged < 48 h after birth are eligible if: (1) they are mechanically ventilated, or (2) they are receiving non-invasive respiratory support and there is a clinical decision to treat with surfactant. The intervention is budesonide (0.25 mg/kg) mixed with poractant alfa (200 mg/kg first intervention, 100 mg/kg if second intervention), administered intratracheally via an endotracheal tube or thin catheter. The comparator is poractant alfa alone (at the same doses). Secondary outcomes include the components of the primary outcome (death, BPD prior to or at 36 weeks' PMA), potential systemic side effects of corticosteroids, cost-effectiveness, early childhood health until 2 years of age, and neurodevelopmental outcomes at 2 years of age (corrected for prematurity). DISCUSSION: Combining budesonide with surfactant for intratracheal administration is a simple intervention that may reduce BPD in extremely preterm infants and translate into health benefits in later childhood. The PLUSS trial is powered for the primary outcome and will address gaps in the evidence due to its pragmatic and inclusive design, targeting all extremely preterm infants regardless of their initial mode of respiratory support. Should intratracheal budesonide mixed with surfactant increase survival free of BPD, without severe adverse effects, this readily available intervention could be introduced immediately into clinical practice. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ( https://www.anzctr.org.au ), ACTRN12617000322336. First registered on 28th February 2017.

A 60-Year-Old Woman with Primary Biliary Cholangitis and Crohn's Ileitis Following the Suspension of Ursodeoxycholic Acid.

BACKGROUND There is a recognized association between inflammatory bowel disease (IBD) and hepatobiliary autoimmune disease, particularly primary sclerosing cholangitis (PSC). There have been fewer reported cases of IBD and primary biliary cholangitis (PBC), which is treated with ursodeoxycholic acid (UDCA). This report presents the case of a 60-year-old woman with PBC who was diagnosed with Crohn's ileitis after suspension of UDCA treatment. CASE REPORT A 66-year-old female patient with PBC was admitted to our department for irrepressible chronic diarrhea and recurrent abdominal pain. PBC was diagnosed on the basis of serological data: chronic (>6 months) increase in alkaline phosphatase (ALP) associated with positivity for specific anti-nuclear antibodies (sp100 and gp210), without requiring a liver biopsy and a magnetic resonance cholangiopancreatography to rule out PSC. Given the intolerance and non-responsiveness according to the Toronto criteria (ALP <1.67 times the normal limit after 2 years) to UDCA at 15 mg/kg/day, an oral monotherapy treatment using obeticholic acid at 5 mg/day was prescribed. The patient complained of abdominal pain and upper gastrointestinal symptoms. The endoscopic/histologic and radiologic examinations supported the diagnosis of Crohn's ileitis. Given the potential benefits to PBC patients of what is described as off-label therapy, budesonide at a dosage of 9 mg/day p.o. was also administered. One month after discharge, an improvement was observed both in the cholestasis indices and in gastrointestinal symptoms. CONCLUSIONS This report presents a case of PBC in which the patient was diagnosed with Crohn's ileitis after cessation of treatment with UDCA, and highlights the importance of recognizing the association between autoimmune hepatobiliary disease and IBD.

Immune-checkpoint inhibitor-associated grade 3 hepatotoxicity managed with enteric-coated budesonide monotherapy: A case report.

RATIONALE: The introduction of immune-checkpoint inhibitors (ICPI) in recent years has changed the natural course of many neoplasms. However, patients receiving these medications may present immune-mediated adverse events; management includes temporary or permanent cessation of treatment and corticosteroids, occasionally combined with other immunomodulators. Such immunosuppression, however, also has numerous adverse events and even if it is effective in controlling toxicity, it delays immunotherapy reinitiation, as current evidence requires dose tapering to ≤10 mg prednisolone equivalent before rechallenge. Enteric-coated budesonide is a corticosteroid formulation acting primarily to the intestine and liver, as a result of its extensive first-pass hepatic metabolism. PATIENT CONCERNS: A 76-year-old woman treated with ipilimumab for metastatic melanoma presented with abdominal pain, vomiting, and diarrhea for at least the previous 4 days. Laboratory tests, among others, revealed elevated aminotransferases and C-reactive protein. During hospitalization, the patient also developed fever. DIAGNOSIS: The patient, after excluding alternative causes of aminotransferase elevation, was diagnosed with grade 3 ipilimumab-associated hepatotoxicity. INTERVENTIONS: Budesonide monotherapy was administered; initial daily dose was 12 mg. OUTCOMES: Fever subsided after the first dose of budesonide. Aminotransferases returned to normal-near normal approximately 1 month after the first dose of budesonide. After this point, daily dose was reduced by 3 mg every 2 weeks, with no clinical or biochemical relapse. CONCLUSIONS: This case of ICPI hepatitis is, to our knowledge, the first in the literature managed with budesonide monotherapy. Therefore, budesonide may be a potentially attractive option for the management of ICPI-associated liver injury in cases where corticosteroid treatment is necessary due to its safety profile and the potential advantage of faster immunotherapy rechallenge in selected patients without requiring dose tapering, in contrast to systemically acting corticosteroids. Clinical trials should be conducted in the future in order to validate or refute these findings.

Finding Predictors of Azathioprine-Induced Pancreatitis in Patients With Inflammatory Bowel Disease.

OBJECTIVES: Azathioprine (AZA)-induced pancreatitis (AIP) is a common, idiosyncratic adverse effect whose incidence and risk factors data in inflammatory bowel disease (IBD) patients are not fully clarified. We aimed to establish the incidence, clinical course and identify risk factors for AIP. METHODS: A retrospective study including all IBD patients on AZA between January 2013 and July 2020 was conducted. Patients with AIP were considered. RESULTS: Azathioprine-induced pancreatitis occurred in 33 patients (7.5%; 442 patients on AZA). The mean time receiving AZA until AIP was 25 days, with a mean dose of 88 mg. All patients had a mild course of disease, which resolved with suspension of AZA and with no complications. Smoking (P = 0.02), single daily dose of AZA (P < 0.001), and concomitant budesonide (P = 0.001) were risk factors for AIP. In multivariate analysis, concomitant treatment with budesonide (odds ratio, 5.3; P = 0.002) and single daily dose of AZA (odds ratio, 3.8; P = 0.002) were the only predictors of AIP. CONCLUSIONS: Although AIP was a relatively common adverse effect, it presented a mild course in all patients. Smoking, concomitant use of budesonide, and single-dose regimen of AZA should be avoided in IBD patients treated with AZA.

Early Physiological and Adrenal Effects of Budesonide Mixed with Surfactant in Large Observational Preterm Cohort Study.

BACKGROUND: The combination of surfactant and budesonide has been shown to decrease BPD rates and severity. Budesonide may be released systemically from lungs, and the effects on the immature adrenal glands are not known. OBJECTIVE: The aim of this study was to determine if adrenal suppression rates are higher in preterm infants receiving budesonide with surfactant compared to surfactant alone. METHODS: A retrospective chart review of 608 infants ≤1,250 g received intubation for surfactant therapy from 2013 through 2020. In August 2016, budesonide was added to surfactant for these infants. Indicators of adrenal suppression, including mean blood pressures, plasma electrolyte levels, hydrocortisone use, and the use of vasoactive medications, were analyzed for the first 14 days after birth. Respiratory variables, biochemical signs of adrenal insufficiency, and neonatal morbidities were analyzed. RESULTS: There was no difference in hydrocortisone administration in the first 14 days between infants receiving budesonide with surfactant (n = 314) or surfactant alone (n = 294) (23% vs. 19%, p = 0.38). Budesonide exposed infants received hydrocortisone 3 days later than surfactant only infants (median DOL 5 vs. 2, p < 0.001). Infants receiving budesonide had higher blood pressures, required less dopamine (19% vs. 39%, p < 0.001) and dobutamine (2% vs. 6%, p = 0.02). Budesonide exposed infants were discharged home after a shorter NICU stay (85 days vs. 94 days, p = 0.02) and at a younger gestational age (39 vs. 40 weeks, p = 0.001). CONCLUSIONS: The use of surfactant and budesonide does not alter the rate of hydrocortisone use, but does delay the timing of treatment initiation and decreases the use of vasoactive medications.

Clinical Response to Intestine-targeted Steroid Therapy in Biopsy-proven Immunoglobulin A Nephropathy.

Primary immunoglobulin A (IgA) nephropathy is associated with a dysfunctional mucosal immune system, leading to renal deposition of IgA and injury. Fifty patients with biopsy-proven IgA nephropathy were included. All patients were initiated on renin-angiotensin-aldosterone system (RAAS) inhibitors, polyunsaturated fatty acids, and a controlled release formulation (CRF) of budesonide. All drugs were started together, as isolated RAAS inhibitors will not prevent the immunological damage caused by the ongoing deposition of IgA. Depending on the histology (mesangial hypercellularity, endocapillary proliferation, segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis, and crescents score), the patients received 9 mg or 12 mg of budesonide. All patients were followed up every 4 weeks to monitor renal function, 24-h urinary protein, and adverse effects. Our primary outcome was a mean change in the estimated glomerular filtration rate (eGFR) and 24-h urinary protein from the baseline to the end of 6 months. The percentage of decline in mean 24-h protein at 6 months from the baseline was 33%. The mean decrease in serum creatinine from the baseline was 0.73 mg/dL. The mean gain in eGFR from the baseline was an increase of 9 mL/min/1.73 m2. Of 50 patients, 11 (22%) achieved complete remission, 20 (40%) achieved partial remission, and 16 (32%) were non-responders. Three patients (6%) were lost to follow-up. The early initiation of CRF budesonide with optimized supportive care led to reductions in proteinuria and improvements in eGFR at 6 months in patients with IgA nephropathy. Early lesions with minimal chronicity showed an excellent response to budesonide.

Presumed adrenal insufficiency in neonates treated with corticosteroids for the prevention of bronchopulmonary dysplasia.

OBJECTIVE: To determine if extremely preterm (EPT) neonates receiving dexamethasone for the prevention of BPD have a higher incidence of presumed adrenal insufficiency (PAI). STUDY DESIGN: Retrospective cohort study of neonates <28 weeks gestation examining PAI after dexamethasone use and PAI after intratracheal budesonide with surfactant administration. RESULT: Of 332 neonates, 38% received dexamethasone. The incidence of PAI was higher in neonates who had received dexamethasone (20.8% vs 2.9%, p < 0.001). However, for intubated babies receiving surfactant, dexamethasone was not independently associated with increased PAI after adjusting for gestational age, birthweight, and race (aOR 2.92, 95% CI: 0.79-10.85). Dexamethasone was independently associated with increased PAI in infants previously receiving budesonide/surfactant treatment (aOR 5.38, 95% CI: 1.38-20.90). CONCLUSION: The use of dexamethasone alone was not associated with increased PAI, when adjusted for prematurity-related factors. The combination of budesonide with dexamethasone was significantly associated with increased PAI.

Chronic Rhinosinusitis Outcomes of Patients With Aspirin-Exacerbated Respiratory Disease Treated With Budesonide Irrigations: A Case Series.

BACKGROUND: Pathophysiology-targeting treatments exist for aspirin-exacerbated respiratory disease (AERD) through aspirin desensitization and biologics, such as dupilumab. With increasing attention paid to these treatments, which may be associated with significant side effects and/or cost, there is little description of chronic rhinosinusitis with nasal polyps (CRSwNP) response to treatment with intranasal corticosteroids and saline irrigations in AERD. OBJECTIVE: To determine the effect of intranasal budesonide irrigations for the treatment of CRSwNP in AERD. METHODS: This is an observational study of 14 AERD patients presenting to a rhinology clinic for CRS who were treated with twice daily high volume, low pressure irrigations with 240 mL of saline to which a 0.5 mg/2 mL respule of budesonide was added. All participants completed a 22-item Sinonasal Outcome Test (SNOT-22) at enrollment and at follow up 1 to 6 months later. Polyp scores were also calculated at each time point. RESULTS: SNOT-22 scores ranged from 26 to 98 (median: 40.5) at enrollment and 3 to 85 (median: 38.5) at follow-up. Polyp scores ranged from 2 to 6 (median: 4) at enrollment at 0 to 6 (median: 2) at follow-up. Over the treatment period, change in SNOT-22 score ranged from -38 to 16 (median: -18) and change in polyp score ranged from -2 to 0 (median: -0.5). Approximately 57% of participants experienced at least 1 minimal clinically important difference in SNOT-22 score and 21% of participants had a SNOT-22 score <20 at follow-up. CONCLUSION: Medical management with intranasal corticosteroids and saline irrigations alone leads to significant improvement in sinonasal symptomatology in a subset of AERD.

Randomised clinical trial: adjunctive induction therapy with oral effervescent budesonide in newly diagnosed coeliac disease.

BACKGROUND: The healing of the mucosal lesion in patients with coeliac disease is slow. AIM: To determine whether concurrent budesonide and gluten-free diet hasten small bowel healing and symptomatic improvement in patients with newly diagnosed coeliac disease. METHODS: In a pilot, randomised, double-blind trial, effects on Marsh grading and quantitative duodenal morphometry of 10 weeks' effervescent budesonide (initially 9 mg/day) or placebo were assessed after 8 and 52 weeks. Multiple clinical measures and adverse events were assessed. RESULTS: Nineteen patients were randomised to budesonide and 18 to placebo. No differences (all P > 0.32) were observed for the week-8 mucosal response (Marsh 0 or 1) (budesonide: 37% vs placebo: 28%), week-8 remission (Marsh 0) (32% vs 17%), week-52 response (63% vs 44%) and week-52 remission (42% vs 33%). Likewise, the improvement from baseline in villous-height : crypt-depth ratio was not different for the treatment groups. There were no statistically significant differences in clinical measures or adverse events between the treatment groups. No corticosteroid adverse effects were observed. In a post hoc analysis of all patients, Marsh 3C was present at the diagnostic biopsy in 1/9 achieving mucosal remission at 8 weeks versus 18/23 not (P < 0.001) and mean villous-height : crypt-depth ratio was 1.06 (SD: 0.73) versus 0.46 (0.38) (P = 0.005). CONCLUSIONS: In this pilot trial, induction therapy with budesonide had no significant effect on mucosal healing in patients with coeliac disease concurrently initiated on a gluten-free diet. Mucosal remission at 8 weeks occurred in approximately one in four patients and was associated with less severe histological lesions at diagnosis.

Budesonide mixed with surfactant did not affect neurodevelopmental outcomes at 6 or 18 months corrected age in observational cohorts.

BACKGROUND: The addition of budesonide to surfactant in very-low-birth-weight infants with less severe RDS decreased bronchopulmonary dysplasia (BPD) severity. Long-term neurodevelopmental follow-up was needed to monitor for systemic effects of budesonide. METHODS: Infants ≤1250 g who received intratracheal budesonide (0.25 mg/kg) with surfactant (n = 173) were compared to a historical cohort who received surfactant alone (n = 294). Peabody Developmental Motor Scales II at 4-6 months corrected age and Bayley Scales of Infant & Toddler Development III at 18-22 months corrected age were compared. RESULTS: There were no differences in muscle tone or motor skills by Peabody exam. There were no differences in the cognitive, language, or motor domains between cohorts on Bayley III. CONCLUSIONS: In a cohort of infants treated with budesonide mixed with surfactant, there were no differences in developmental outcomes at 4-6 months or 18-22 months corrected age.