Combination Of Budesonide Research Articles

Endotracheal Surfactant and Budesonide Combination Therapy in Neonatal Acute Respiratory Distress Syndrome due to Late-Onset Sepsis.

Neonatal acute respiratory distress syndrome (NARDS) is an important cause of hypoxemic respiratory failure. This study aimed to investigate the short-term effects of endotracheal surfactant and budesonide combination therapy on NARDS secondary to late-onset neonatal sepsis (LONS). This was a retrospective, cross-sectional, and observational study. Newborns with NARDS due to LONS who received endotracheal surfactant and budesonide combination therapy between August 2022 and September 2023 were included in this study. Oxygenation status before endotracheal surfactant and budesonide treatment were compared with the values obtained two hours after treatment. Among 20 neonates, 10 (50%) were diagnosed with severe NARDS, and 10 (50%) were diagnosed with moderate NARDS. The mean corrected gestational age was 33.3±2.9 w when endotracheal surfactant and budesonide were administered to the neonates. The need for the fraction of inspired oxygen (0.75 [0.57-1.00]% vs. 0.55 [0.44-0.80]%; mean difference [MD]: 17.50%, 95% confidence interval [CI]: 14.99 to 22.50) and oxygen saturation index (OSI; 8.03 [4.98-13.94] vs. 4.71 [4.11-8.93]; MD: 2.23, 95% CI: 1.22 to 3.24) decreased (P=0.001 and P<0.001, respectively) after endotracheal surfactant and budesonide treatment. However, preductal oxygen saturation (SpO2 ; 93 [91-94]% vs. 95 [94-96]%; MD: -3.50%, 95% CI: -5.00 to -2.00) increased significantly after endotracheal surfactant and budesonide treatment when compared to pre-treatment values (P<0.001). The reduction in oxygen demand and OSI, along with an increase in SpO2 after treatment compared to pre-treatment values, suggests that endotracheal surfactant and budesonide combination therapy could be an effective option to improve oxygenation in NARDS secondary to LONS.

Budesonide and N-acetylcysteine inhibit activation of the NLRP3 inflammasome by regulating miR-381 to alleviate acute lung injury caused by the pyroptosis-mediated inflammatory response.

The anti-inflammatory effects of budesonide (BUN) and N-acetylcysteine (NAC) attenuate acute lung injury (ALI). The aim of this study was to investigate the effects of combination therapy consisting of BUN and NAC on ALI and the underlying mechanisms. In vitro and in vivo models of ALI were generated by LPS induction. Western blotting was used to detect the expression levels of pyroptosis-related proteins and inflammation-related factors, and RT-qPCR was used to detect the expression of miR-381. Cell proliferation and apoptosis were detected by CCK-8 and flow cytometry, respectively. ELISA was used to detect the levels of inflammation-related factors. HE staining was used to detect lung injury. The results showed that LPS effectively induced pyroptosis in cells and promoted the expression of pyroptosis-related proteins (Caspase1, Gasdermin D and NLRP3) and inflammatory cytokines (TNF-α, IL-6 and IL-1β). The combination of BUN and NAC significantly alleviated LPS-induced pyroptosis and inflammation. In addition, the combination of BUN and NAC effectively promoted miR-381 expression. Transfection of miR-381 mimics effectively alleviated LPS-induced pyroptosis and inflammation, while transfection of miR-381 inhibitors had the opposite effect. miR-381 negatively regulates NLRP3 expression. Treatment with a miR-381 inhibitor or pc-NLRP3 reversed the effects of the combination of BUN and NAC. In a mouse model of ALI, the combination of BUN and NAC effectively improved lung injury, while treatment with a miR-381 inhibitor or pc-NLRP3 effectively reversed this effect. Overall, this study revealed that BUN+NAC inhibits the activation of NLRP3 by regulating miR-381, thereby alleviating ALI caused by pyroptosis-mediated inflammation.

Meta-analysis of combined azithromycin and inhaled budesonide treatment for Chinese pediatric patients with mycoplasma pneumonia.

Budesonide, capable of reducing vascular permeability, suppressing mucus secretion, and alleviating edema and spasms, is widely used in China for combined infectious disease treatment. This study assesses budesonide's efficacy and safety as an adjunct to azithromycin in pediatric Mycoplasma pneumonia management in China, aiming to establish a strong theoretical foundation for its clinical application. We conducted a comprehensive search for qualifying studies across 5 English databases and 4 Chinese databases, covering publications until October 31, 2023. Endpoint analyses were performed using standard software (Stata Corporation, College Station, TX). This study was conducted in compliance with the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A total of 24 randomized controlled trials were involved in the current study, including 2034 patients. Our findings indicate that the combination of budesonide with azithromycin for the treatment of pediatric Mycoplasma pneumonia delivers superior therapeutic efficacy (Intravenous: odds ratio [OR], 0.156, P < .001; Sequential: OR, 0.163, P = .001; Oral: OR, 0.139, P < .001), improved pulmonary function (Forced expiratory volume in 1 second: weighted mean differences [WMD], -0.28, P = .001; Peak expiratory flow: WMD, -0.554, P = .002; Forced vital capacity: WMD, -0.321, P < .001), diminished lung inflammation (IL-6: WMD, 4.760, P = .002; c-reactive protein: WMD, 5.520, P < .001; TNF-α: WMD, 9.124, P < .001), reduced duration of fever, faster resolution of cough and rales, all without increasing the occurrence of adverse events. The combination of budesonide and azithromycin demonstrates enhanced therapeutic effectiveness, promotes improved pulmonary function, shortens the duration of symptoms, and effectively mitigates the overexpression of inflammatory factors like c-reactive protein, TNF-α, and IL-6, all without an associated increase in adverse reactions in pediatric mycoplasma pneumonia.

180 Navigating Uncharted Waters: Management of IgA Nephropathy with combined Budesonide and Sparsentan

180 Navigating Uncharted Waters: Management of IgA Nephropathy with combined Budesonide and Sparsentan

Postnatal budesonide improved lung function in preterm lambs exposed to antenatal steroids and chorioamnionitis.

A combination of budesonide and surfactant decreases the rates of BPD in infants and lung injury in preterm sheep. Whether this combination will show benefit in the setting of chorioamnionitis and antenatal steroids is not known. Ewes at 123 ± 1 day gestational age received intra-amniotic (IA) injections of 10 mg LPS before being randomized to receive either 0.25 mg/kg maternal betamethasone phosphate and acetate or saline by intramuscular (IM) injection at 48 and 24 h prior to delivery at 125 ± 1 day. Lambs (N = 6-9/group) underwent intentionally injurious ventilation for 15 min, then lambs received surfactant mixed with either: (1) saline; or (2) Budesonide 0.25 mg/kg and were ventilated for 4 h. Compared with LPS-exposed animals that received no IM steroid treatment, betamethasone exposed fetuses had improved hemodynamic stability, lung compliance, and ventilation efficiency. The addition of budesonide to surfactant further improved markers of injury and pro-inflammatory cytokine mRNA in both betamethasone IM or no IM lambs exposed to LPS IA. Antenatal betamethasone and IA LPS exposures decreased budesonide levels in the fetal lung and plasma. Antenatal betamethasone stabilizes physiologic parameters in LPS treated lambs. Budesonide mixed with surfactant further decreases injury and improves respiratory physiology in betamethasone treated animals. Antenatal betamethasone improved lung and systemic physiology in the setting of intra-amniotic LPS. The addition of budesonide to the surfactant further improved lung function. Budesonide levels in the plasma and lung were lower in lambs exposed to either LPS or LPS and Betamethasone animals, and these findings were not explained by increased esterification in the lungs. The combination of antenatal steroids and budesonide with surfactant had the lowest markers of pro-inflammatory cytokines in the lung of LPS exposed animals.

The effect of budesonide combined with bifidobacteria and lactobacilli on lung function and gut microbiota of patients with chronic obstructive pulmonary disease.

To explore the effects of budesonide combined with Bifidobacteria and Lactobacilli on the lung function and intestinal microbiota of patients with chronic obstructive pulmonary disease (COPD). Clinical data of 124 COPD patients admitted to Fengcheng Hospital, Fengxian District, Shanghai from February 2021 to February 2023 were retrospectively analyzed. Patients either received budesonide treatment alone (n=59, control group) or budesonide combined with Bifidobacteria and Lactobacilli (n=65, observation group). Levels of lung function indicators, symptom relief time, gut microbiota levels, and quality of life were compared between the two groups before and after the treatment. After two weeks of treatment, the improvement of lung function in the observation group was better than that in the control group (P<0.05). Compared to budesonide treatment alone, combined budesonide, Bifidobacteria, and Lactobacilli treatment were associated with shorter symptom relief time (P<0.05), and with more significant improvement of intestinal microbiota level (P<0.05) and the quality of life (P<0.05). Budesonide combined with Bifidobacteria and Lactobacilli can effectively alleviate clinical symptoms, regulate intestinal microbiota, improve lung function and the quality of life of COPD patients.

Сравнение эффективности будесонида ММХ в монотерапии и в комбинации с месалазином у больных язвенным колитом

The purpose — to study the treatment of ulcerative colitis (UC) as monotherapy with budesonide MMX and combined therapy with budesonide MMX with mesalazine by comparing the dose-response relationship. Materials and methods. The study included 41 patients with moderately active UC. The patients were divided into 2 groups: the first group (20 patients) was prescribed monotherapy with budesonide MMX at a standard dose of 9 mg per day; the second group (21 patients) received budesonide MMX at a dose of 9 mg with mesalazine at a dose of 3 g orally. The duration of treatment in both groups was 8 weeks. The UC severity at the beginning and after treatment was assessed using the full Mayo activity index. The construction of the dose-effect relationship (efficiency function) was carried out using the original technology developed by S.V. Krishtopenko et al. calculating the dose of budesonide in mg per 1 kg of body weight. Results. The difference in achieving clinical and endoscopic remission between the two groups of patients at the end of therapy was 17.1%, which did not reach statistical significance (p &gt; 0.05). The construction and analysis of efficiency functions in both groups made it possible to establish that the combination of budesonide with mesalazine was 19.1% (p &lt; 0.05) more effective only in patients weighing more than 82 kg. Conclusion. The analysis of dose-effect dependencies revealed the greater effectiveness of combination therapy of budesonide MMX with mesalazine, which significantly increased in patients weighing more than 82 kg.

Comparison of the efficacy of combined budesonide and fexofenadine versus combined fluticasone propionate and fexofenadine on the expression of class-4 semaphorins and their receptors in the peripheral blood cells of patients with allergic rhinitis

BackgroundAllergic rhinitis (AR) is a common immunoglobulin (Ig) E-mediated disease. This study aimed to evaluate the gene expression levels of class 4 semaphorins and their receptors in AR patients before and after treatment with budesonide and fexofenadine (B/F) compared to fluticasone propionate and fexofenadine (FP/F). MethodsIn this study, 29 AR patients (age 34.4 ± 1.2 years, 18 men and 11 women) were treated with B/F, and 24 AR patients (age 32.8 ± 1.9 years, 15 men and 9 women) were treated with FP/F for one month. Before and after treatment, peripheral blood samples were taken from patients. The expression levels of SEMA4A, SEMA4C, SEMA4D, Plexin-B2, and Plexin-D1 genes were measured using the qPCR method. In addition, the serum levels of IgE were measured using an enzyme-linked immunosorbent assay (ELISA). ResultsThe expression levels of SEMA4A (P = 0.011), 4C (P = 0.017), Plexin-B2 (P = 0.0005), and Plexin-D1 (P = 0.008) remarkably increased in AR patients treated with B/F. Our results show a significant reduction in the gene expression levels of SEMA4A (P = 0.002), 4C (P = 0.014), 4D (P = 0.003), Plexin-B2 (P = 0.033), and Plexin-D1 (P = 0.035) after treatment with FP/F. The serum levels of IgE increased in FP/F treated group (P = 0.017) and conversely decreased in the treated group with B/F (P = 0.019). Moreover, the percentages of eosinophils were reduced in both FP/F and B/F groups (P = 0.015 and P = 0.0001, respectively). ConclusionIn conclusion, concomitant use of fexofenadine and fluticasone propionate reduced SEMA4A, 4C, 4D, Plexin-B2, and Plexin-D1, while the SEMA4A, 4C, Plexin-B2, and Plexin-D1 gene expression levels were increased in the patient group treated with B/F.

Clinical efficacy of a triple combination of budesonide/ glycopyrronium bromide/formoterol in the treatment of chronic obstructive pulmonary disease

Chronic Obstructive Pulmonary Disease (COPD) is a chronic condition characterized by persistent airflow limitation, caused by chronic inflammation in response to exposure to inhaled damaging particles or gases. Exacerbations of COPD lead to the progression of symptoms, worsening lung function, reduced physical tolerance, and, as a result, contribute to an increase mortality. Therefore, the prevention of exacerbations is a primary objective in the management of COPD. The foundation of COPD therapy involves prescribing long-acting bronchodilators, and for some patients, the use of anti-inflammatory agents, such as inhaled corticosteroids (ICS). ICS are used in combination with long-acting beta2-agonists (LABA) or as part of triple therapy (ICS/LABA/ LAMA). The choice of triple therapy depends on the patient’s exacerbation history, severity of symptom, level of peripheral blood eosinophilia, risk of infectious complications, and the presence of a concomitant diagnosis of bronchial asthma. Triple therapy offers advantages in terms of improving lung function, disease symptoms, reducing exacerbation frequency, and significantly decreasing mortality compared to other inhaled therapy options for COPD. A significant advantage of this therapy has been shown in patients with eosinophilic COPD. Currently, three combined inhalation medications containing ICS/LABA/LAMA are available for COPD treatment in our country. This review provides basic information on the clinical efficacy and safety profile of one of them, budesonide/glycopyrronium bromide/formoterol, in patients with various COPD phenotypes.

The Efficacy of Combination Therapy with Ustekinumab and Budesonide for Crohn’s Disease: A Randomized Controlled Trial

Introduction: Limited data exist on the efficacy of combination therapy with ustekinumab and budesonide in patients with Crohn’s disease. Our objective was to compare the clinical outcomes of ustekinumab and budesonide combination therapy with those of ustekinumab monotherapy. Methods: In this phase 2 single-center, double-blind, randomized controlled trial, we assigned 19 patients with Crohn’s disease with a Crohn’s disease activity index (CDAI) equal to or greater than 220 and less than 450 in a 1:1 ratio to receive ustekinumab and budesonide or ustekinumab for 32 weeks. The primary endpoint was the clinical remission rate at 8 weeks. The secondary endpoints were the clinical remission rate at 32 weeks and mucosal healing rates at 8 and 32 weeks. Results: Of 19 patients, the mean age was 37.8 years, and 42.1% were women (CDAI ≥220 and <450). There was no difference between combination therapy and ustekinumab monotherapy in terms of clinical remission rates (50.0% vs. 30.0%, p = 0.39 at 8 weeks and 37.5% vs. 20.0%, p = 0.41) and mucosal healing rates (75.0% vs. 90.0%, p = 0.40 and 37.5% vs. 60.0%, p = 0.34 at 8 and 32 weeks, respectively). The most common adverse event was an exacerbation of Crohn’s. There were no differences in safety profiles between the two groups. Conclusions: Our study showed no difference between ustekinumab monotherapy and ustekinumab and budesonide combination therapy in terms of the induction and maintenance of remission (trial registration number: jRCTs021200013).

Effect of Huangqi Granules Combined with Budesonide on Clinical Indexes, Clinical Efficacy, and Safety in Children with Bronchial Asthma

We have investigated the effect of a combination of Budesonide and Huangqi granules on pulmonary function in children with bronchial asthma. To this end, children diagnosed with bronchial asthma were divided into two treatment groups, one receiving Budesonide alone (the control group) and the other receiving additional Huangqi granules (the study group). The syndrome score, pulmonary and immune function indices, clinical efficacy, and adverse reactions were observed and compared between the two groups. Before treatment, there was no significant difference in any of the measures between the two groups. However, after treatment, all measures were significantly improved in both groups, with a greater improvement in the study group. Also, the difference in the adverse reaction rate between the two groups was insignificant. In conclusion, Huangqi granules combined with Budesonide can effectively improve the clinical symptoms and repair pulmonary function in children with bronchial asthma.

Insights of different analytical approaches for estimation of budesonide as COVID-19 replication inhibitor in its novel combinations: green assessment with AGREE and GAPI approaches

Simple, direct, rapid, and sensitive HPLC and spectrophotometric methods were established for simultaneous estimation of a novel combination of budesonide and azelastine (BUD/AZL) in their laboratory-prepared mixture and dosage form according to the medicinally recommended ratio 1:4.28. Budesonide is an important inhalation corticosteroid that plays a vital role in the inhibition of COVID-19 replication and cytokine production. The first chromatographic method was created for the simultaneous estimation of BUD epimers in the presence of AZL with excellent efficiency in a relatively short chromatographic run (< 9 min). The separation of BUD epimers with AZL was carried out on a C18 column using acetonitrile: phosphate buffer of pH 3.5 adjusted by 0.2 M orthophosphoric acid (40:60, v/v) as a mobile phase, UV detection at 230 nm and a flow rate of regulated at 2 mL/min. Besides, three spectrophotometric methods were applied for the simultaneous determination of the provided mixture adopting zero order, first order derivative, and ratio first derivative approaches. The Zero-order spectrophotometry was used for the determination of AZL in presence of BUD, where BUD shows no absorbance at 290 nm. The first derivative amplitude at 265 nm (1D265) (zero-crossing of AZL) and the ratio of first derivative amplitudes at 270 nm (1DD270) using 10.0 µg mL−1 AZL as divisor was chosen for the simultaneous determination of BUD in the presence of AZL in the binary mixture. The proposed methods were found to be rectilinear in the concentration range of (0.4–40.0 µg mL−1) and (0.05–40.0 µg mL−1) for BUD and AZL, respectively in the HPLC method. Whereas the concentration range for AZL in the zero-order method was (1.0–35.0 µg mL−1) and for BUD in the first derivative and ratio derivative method was (6.0–20.0 µg mL−1). Validation of the suggested approaches according to the ICH criteria was performed. Furthermore, to ensure the proposed approaches' greenness, The AGREE and GAPI metrics were utilized, and the afforded results revealed an excellent greenness of the proposed approaches.

Effect of budesonide and azithromycin on the chemotaxis of blood monocytes and lymphocytes in patients with chronic obstructive pulmonary disease

Objective. To evaluate the ability of a combination of budesonide and azithromycin to influence the migration of blood monocytes and lymphocytes in patients with chronic obstructive pulmonary disease (COPD).Materials and methods. Peripheral blood mononuclear cells from patients with COPD (n=8) were incubated with glucocorticoid budesonide (10 nM), macrolide antibiotic azithromycin (10 µg/mL), or their combination, and then transferred to chemotaxis chambers containing chemokines RANTES (CCL5, 10 nM) or IP-10 (CXCL10, 10 nM). Cells migrated to the lower compartment of the chamber were collected, stained with monoclonal antibodies to CD3, CD14, CD19, CD45 and counted on a flow cytometer.Results. Azithromycin alone and in combination with budesonide inhibited the migration of blood T-lymphocytes and B-cells and enhanced the migration of blood monocytes to RANTES and IP-10. The combination of azithromycin and budesonide had a more suppressive effect on the chemotaxis of blood T- and B-lymphocytes to RANTES and IP-10 than budesonide alone. The combination of azithromycin and budesonide had an effect similar to azithromycin alone on the migration of blood T- and B-lymphocytes, as well as monocytes in patients with COPD.Conclusion. The results of the study demonstrate the ability of azithromycin alone to modulate the chemotaxis of peripheral blood monocytes and lymphocytes in patients with COPD and the lack of advantages of its combination with budesonide.

Combination therapy with budesonide and N-acetylcysteine ameliorates LPS-induced ALI by attenuating neutrophil recruitment through the miR-196b-5p/Socs3 molecular axis

BackgroundNeutrophil infiltration accelerates the inflammatory response and is highly correlated to the development of acute lung injury (ALI). Budesonide (BUD) and N-acetylcysteine (NAC) both inhibit the inflammatory response to alleviate ALI, so we further investigated whether their combination is better for ALI.MethodsIn this study, we investigated the effect and mechanism of Combined BUD and NAC therapy on LPS-induced ALI. Rat ALI model and neutrophil abnormal activation model were established by lipopolysaccharide (LPS). BUD and NAC were treated alone or in combination, or cells were transfected with miR-196b-5p mimic or si-Socs3 to evaluate the efficacy and mechanism of BUD and NAC alone or in combination. Histopathological observation of lungs was performed by Hematoxylin Eosin (HE) staining. The quantity of neutrophils and inflammatory factors level in bronchoalveolar lavage fluid (BALF) were determined by Richter-Gimza complex stain and Enzyme-Linked Immunosorbnent Assay (ELISA), respectively. ReverseTranscription-PolymeraseChainReaction (RT–qPCR) was utilized to assess miR-196b-5p and inflammatory factor mRNA levels. The expression level of Socs3 was detected by immunohistochemistry or Western Blot.ResultsBUD and NAC combined treatment had a better effect on neutrophil recruitment and inflammatory response in LPS-induced ALI than did BUD and NAC alone. Transfection of the miR-196b-5p mimic reversed the effect of combined BUD and NAC. In conclusion, the combination of BUD and NAC is a better treatment for ALI.ConclusionsCombination therapy with BUD and NAC ameliorates LPS-induced ALI by attenuating neutrophil recruitment through the miR-196b-5p/Socs3 molecular axis.

A “hydroxyl radicals standard” for evaluating the efficacy of anti-asthma drugs by using a two-photon NIR optical sensor

Asthma is a common chronic inflammatory disease of the airways and a condition closely associated with oxidative stress. However, the lack of effective biomarkers and non-invasive real-time monitoring tools remains a great challenge for the early diagnosis and therapy of asthma. Hydroxyl radicals represent a key reactive oxygen species in biological systems, and therefore the change of hydroxyl radical level may be observed to be elevated in asthmatic mice. To verify this conjecture, in this paper, we designed the first two-photon (TP) near-infrared (NIR) fluorescent probe to be used with high selectivity for monitoring the fluctuating changes of hydroxyl radicals. More importantly, using this new probe, we have successfully observed the changes of hydroxyl radicals during asthma by visualization means for the first time. Immediately following the imaging experiments on mice, we also found that the therapeutic effect of using the combination of budesonide and terbutaline administration in asthmatic mice was effective than what was achieved by the administration of budesonide or terbutaline alone. These findings suggest that this probe has the potential to be a powerful tool for future asthma diagnosis and assessment of the therapeutic effect of asthma co-administration. Notably, it is expected to establish a “hydroxyl radicals standard” for evaluating the efficacy of anti-asthma drug therapy by using fluorescence imaging techniques.

Curcumin-Loaded mPEG-PLGA Nanoparticles Attenuates the Apoptosis and Corticosteroid Resistance Induced by Cigarette Smoke Extract.

The present study was aim to prepare curcumin-loaded methoxypolyethylene-glycols-poly (lactic-co-glycolic acid) nanoparticles (Cur-mPEG-PLGA-NPs) and investigate curcumin’s effect on reversing corticosteroid resistance induced by cigarette smoke extract (CSE) in rat tracheal epithelial (RTE) cells. The Cur-mPEG-PLGA-NPs were spherical, regular in shape with smooth surfaces, and well distributed and Cur-mPEG-PLGA-NP suspensions had good water solubility and presented prolonged release. Furthermore, we found that Cur-mPEG-PLGA-NPs were internalized more than curcumin into the cells and significantly alleviated apoptosis in RTE cells. In addition, 10% CSE reduced the maximal inhibition percentage and increased the half-inhibitory concentration of budesonide (BUD) on IL-8 secretion, and curcumin restored the efficacy of BUD inhibition. BUD in combination with Cur-mPEG-PLGA-NPs showed higher inhibitory rates for LPS- and CSE-induced IL-8 secretion than that in combination with curcumin. Moverover, the relative expression levels of HDAC2 was reduced after CSE exposure and curcumin could improve HDAC2 expression and reverse CSE-induced corticosteroid resistance. Curcumin in high concentration and Cur-mPEG-PLGA-NPs restored HDAC2 levels in RTE cells and thus Cur-mPEG-PCL-NPs have higher biological activity than curcumin.

VEDOLIZUMAB FOR REFRACTORY MICROSCOPIC COLITIS: A CASE SERIES

Abstract INTRODUCTION Microscopic colitis (MC) is a chronic inflammatory disease of the colon that causes non-bloody, watery diarrhea occurs up to 15 times daily in the presence of normal-appearing mucosa in the colon. There are two main subtypes of MC based on histopathologic features, collagenous colitis (CC) and lymphocytic colitis (LC)1. Treatment of each subtype is similar and should be determined by the severity of symptoms. Some patients suffer severe symptoms despite maximum dosage of budesonide, in these cases biologic therapies should be considered. Vedolizumab, a monoclonal antibody that targets α4β7-integrin, is a gut-specific biologic with an exceptional safety profile. Here, we report our experience with vedolizumab for severe, refractory MC. METHODS Eleven patients presenting to the University of Kentucky with severe microscopic colitis refractory to maximum budesonide and Imodium therapy were treated with vedolizumab. Vedolizumab was given at standard induction dosing (300mg IV at week 0, 2 and 6, and then every 8 weeks). RESULTS Of the eleven patients included in this study, seven reported subjective symptomatic improvement on vedolizumab monotherapy, with four patients attaining less than 3 stools per day. Of the remaining four patients, one continues to do well on vedolizumab and budesonide combination therapy while another developed a rash after vedolizumab induction and treatment was stopped. The third patient was transitioned from vedolizumab to adalimumab and is now well controlled symptomatically and the final patient has not reached symptomatic remission of her disease. Interestingly, of the seven patients who displayed symptomatic improvement with vedolizumab monotherapy, 5/7 patients also showed improvement in albumin levels. DISCUSSION Vedolizumab use in refractory microscopic colitis is increasingly recognized as a conceivable therapy for symptomatic improvement and disease remission. Our case series corroborates these findings, as the majority of our patients reported overall improved quality of life. Vedolizumab binds to the α4β7-integrin and prevent adhesion to its ligand, MAdCAM-1, which causes downstream prevention of T-cell adhesion. Although the exact pathophysiology of microscopic colitis remains largely unidentified, it has been postulated that exposure to a luminal antigen may trigger an inflammatory cascade, leading to activation of CD8 T suppressor cells that attack and cause luminal damage to enterocytes2. This hypothesis is supported by vedolizumab’s mechanism of action and proposed efficacy in MC. Due to low volume studies, the data supporting vedolizumab use in refractory microscopic colitis remains limited, and further studies are needed to elucidate the its potential as a first-line therapy. However, based on our experience, we recommend considering vedolizumab for patients suffering from refractory MC.

VEDOLIZUMAB FOR REFRACTORY MICROSCOPIC COLITIS: A CASE SERIES

Microscopic colitis (MC) is a chronic inflammatory disease of the colon that causes non-bloody, watery diarrhea occurs up to 15 times daily in the presence of normal-appearing mucosa in the colon. There are two main subtypes of MC based on histopathologic features, collagenous colitis (CC) and lymphocytic colitis (LC)1. Treatment of each subtype is similar and should be determined by the severity of symptoms. Some patients suffer severe symptoms despite maximum dosage of budesonide, in these cases biologic therapies should be considered. Vedolizumab, a monoclonal antibody that targets α4β7-integrin, is a gut-specific biologic with an exceptional safety profile. Here, we report our experience with vedolizumab for severe, refractory MC. Eleven patients presenting to the University of Kentucky with severe microscopic colitis refractory to maximum budesonide and Imodium therapy were treated with vedolizumab. Vedolizumab was given at standard induction dosing (300mg IV at week 0, 2 and 6, and then every 8 weeks). Of the eleven patients included in this study, seven reported subjective symptomatic improvement on vedolizumab monotherapy, with four patients attaining less than 3 stools per day. Of the remaining four patients, one continues to do well on vedolizumab and budesonide combination therapy while another developed a rash after vedolizumab induction and treatment was stopped. The third patient was transitioned from vedolizumab to adalimumab and is now well controlled symptomatically and the final patient has not reached symptomatic remission of her disease. Interestingly, of the seven patients who displayed symptomatic improvement with vedolizumab monotherapy, 5/7 patients also showed improvement in albumin levels. Vedolizumab use in refractory microscopic colitis is increasingly recognized as a conceivable therapy for symptomatic improvement and disease remission. Our case series corroborates these findings, as the majority of our patients reported overall improved quality of life. Vedolizumab binds to the α4β7-integrin and prevent adhesion to its ligand, MAdCAM-1, which causes downstream prevention of T-cell adhesion. Although the exact pathophysiology of microscopic colitis remains largely unidentified, it has been postulated that exposure to a luminal antigen may trigger an inflammatory cascade, leading to activation of CD8 T suppressor cells that attack and cause luminal damage to enterocytes2. This hypothesis is supported by vedolizumab’s mechanism of action and proposed efficacy in MC. Due to low volume studies, the data supporting vedolizumab use in refractory microscopic colitis remains limited, and further studies are needed to elucidate the its potential as a first-line therapy. However, based on our experience, we recommend considering vedolizumab for patients suffering from refractory MC.

Effect of the combination of theophylline and budesonide on production of proinflammatory cytokines by blood cells of patients with chronic obstructive pulmonary disease

The objective: to evaluate the ability of the combination of theophylline and budesonide to suppress proinflammatory cytokine production byblood cells in patients with chronic obstructive pulmonary disease (COPD).Subjects and Methods. Peripheral blood mononuclear cells (PBMCs) or whole blood cells of COPD patients (n = 27) were incubated with budesonide (10 nM), theophylline (1 μM), or the combination thereof and stimulated with phytohemagglutinin (PHA) or phorbol myristate acetate (PMA) and ionomycin. The enzyme immunoassay was used to evaluate the secretion of thymic stromal lymphopoietin (TSLP), macrophage migration inhibitory factor (MIF), interleukin 17A (IL-17A), IL-33, and other mediators of PBMC cells, and induced PHA. The flow cytometry was used to analyze intracellular production of proinflammatory cytokines stimulated by PMA/ionomycin in T-helpers (CD4+) and cytotoxic T-lymphocytes (CD8+).Results. Theophylline reduced the secretion of IL-4 and IL-17A by PBMC cells. The combination of budesonide with theophylline inhibited the synthesis of IL-4, IL-5, IL-8, IL-13, IL-17A, IL-33, TSLP, MIF by PBMC cells as well as the production of IL-4, IL-8, tumor necrosis factor-α, and interferon-γ by cytotoxic T-lymphocytes and T-helpers. The combination of theophylline and budesonide had a more pronounced inhibitory effect on the production of IL-4 and IL-8 by PBMC cells as well as the synthesis of IL-4 by CD4+ T-cells and IL8 by CD8+ T-lymphocytes versus the effect of monotherapy with budesonide.

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

To determine if extremely preterm (EPT) neonates receiving dexamethasone for the prevention of BPD have a higher incidence of presumed adrenal insufficiency (PAI). Retrospective cohort study of neonates <28 weeks gestation examining PAI after dexamethasone use and PAI after intratracheal budesonide with surfactant administration. 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). 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.