Efficacy of Colchicine and Budesonide in Improvement Outcomes of Patients with Coronavirus Infection 2019 in Damascus, Syria: A Randomized Control Trial

COVID-19 was reported in China in 2019 and has spread worldwide. Transmission occurs through respiratory secretions and, less commonly, through contaminated surfaces. The severity of the disease can range from asymptomatic to acute respiratory distress syndrome (ARDS). In this study, we aim to investigate the efficacy of two agents (oral colchicine and budesonide inhaler) in COVID-19 infection management, compared with supportive care alone. 77 patients were admitted to the isolation section of Al Assad University Hospital, between the 1st of August and the 30th of August. A total of 49 patients were included in this randomized control trial, after excluding ineligible patients. The random sample was divided into three groups; the first group was supportive care plus colchicine, the second group was supportive care plus budesonide inhaler, and the control group was supportive care alone. PaO2/FiO2 was improved in the budesonide group, higher than the supportive and colchicine groups. The median hospitalization days were shorter when using colchicine or budesonide, opposed to supportive care alone (8 vs 10 days, respectively). 34 patients (69.3%) were discharged, and 27 patients (55.1%) were followed up until they were weaned from oxygen and made a complete recovery. There was a significant decrease in mortality with colchicine (3 patients; 21.4%) compared with supportive care (7 patients; 33.3%) and the budesonide group (5 patients; 35.7%).

A comparative study on the effectiveness of budesonide nasal irrigation versus normal saline nasal irrigation in post endoscopic sinus surgery patients

: Comparative studies evaluating budesonide and saline nasal irrigations for patients with polyposis/ rhinosinusitis are deficient in the current literature. This study aimed to evaluate the effectiveness of budesonide nasal irrigations compared with saline irrigations during postoperative care of patients with rhinosinusitis.: A total of 100 patients who underwent functional Endoscopic Sinus SurgeryESS) were randomly divided into two groups (A and B) of 50 participants each (normal saline [NS] + budesonide irrigation and NS irrigation alone, respectively). Pre- and post operative evaluation was done with a 22-item sinonasal outcomes test (SNOT-22), and Lund Kennedy endoscopic (LKE scores) in second and sixth week. : The condition of the patients significantly improved in both intervention arms related to SNOT-22 and LKE score at each postoperative visit (Group A: p<0.001, Group B: p<0.001). The reduction of SNOT 22 score was higher in budesonide group by 10% (mean SNOT 22 score from 33.31 to 15.84) compared to normal saline group (mean SNOT 22 score from 37.49 to 22.24). The reduction of LKEscore was higher in budesonide group by 18.69% (mean LKE score from 4.49 to 2.71) compared to normal saline group (mean LKE score from 5.02 to 4). : Steroid nasal irrigation is a good option in postoperative EES patients. The difference of reduction of both SNOT 22 score and LKEscore was statistically significant (p <0.05 and p<0.01 respectively) by repeated contrast test. This study is one of the few comparative studies evaluating budesonide and saline nasal irrigations in post-ESS patients.

A Randomized Clinical Trial of Intratracheal Administration of Surfactant and Budesonide Combination in Comparison to Surfactant for Prevention of Bronchopulmonary Dysplasia

Objectives: Bronchopulmonary dysplasia (BPD) remains a major problem in preterm infants occurring in up to 50% of infants born at < 28 weeks gestational age. Inflammation plays an important role in the pathogenesis of BPD. This study was conducted to evaluate the efficacy of intratracheal budesonide administration in combination with a surfactant in preventing BPD in preterm infants. Methods: In a randomized clinical trial, 128 preterm infants at < 30 weeks gestational age and weighing < 1500 g at birth were studied. All had respiratory distress syndrome (RDS) and needed surfactant replacement therapy. They were randomly allocated into two groups; surfactant group (n = 64) and surfactant + budesonide group (n = 64). Neonates in the surfactant group received intratracheal Curosurf 200 mg/ kg/dose. Patients in the surfactant + budesonide group were treated with intratracheal instillation of a mixed suspension of budesonide 0.25 mg/kg and Curosurf 200 mg/kg/ dose. Neonates were followed untill discharge for the primary outcome which was BPD and secondary outcomes including sepsis, patent ductus arteriosus (PDA), retinopathy of prematurity (ROP), and necrotizing enterocolitis (NEC). Results: The mean gestational age and birth weight of the studied neonates were 28.3±1.6 weeks and 1072.0±180.0 g, respectively. The demographic characteristics and RDS score were similar in the two groups. BPD occurred in 24 (37.5%) neonates in the surfactant + budesonide group and 38 (59.4%) neonates in surfactant group, p = 0.040. Hospital stay was 29.7±19.2 days (median = 30 days) in the surfactant group and 23.3±18.1 days (median = 20 days) in the surfactant + budesonide group, p = 0.050. The rates of sepsis, PDA, ROP, and NEC were not significantly different in the two groups. Conclusions: The use of budesonide in addition to surfactant for rescue therapy of RDS in preterm infants decreases the incidence of BPD and duration of respiratory support significantly. Large adequately powered clinical trials with long-term safety assessments are needed to confirm our findings before its routine use can be recommended.

Is It Really Feasible to Use Budesonide–Formoterol as Needed for Mild Persistent Asthma? A Systematic Review and Meta-Analysis

Background: Previous studies suggest that inhaled budesonide-formoterol used as needed could effectively reduce the severe exacerbation of mild persistent asthma. However, there are some differences between these studies, so we conducted a meta-analysis.Methods: We searched PubMed, Ovid MEDLINE, Cochrane Library and several web search engines to screen the literature until March 25, 2020 and used risk ratios (RR), odds ratios, hazard ratios (HR) and weighted mean differences with 95% confidence intervals (CI) to evaluate the pooled effects. Adolescent/adult patients with mild persistent asthma who used budesonide–formoterol as needed were included in this study. The primary outcome was to investigate the superiority of budesonide–formoterol as needed in reducing severe exacerbations in patients with mild persistent asthma. STATA 12.0 software was used for statistical analysis.Results: Across all 4 articles, 4,023 patients used budesonide–formoterol as needed (budesonide–formoterol group), 4,042 patients used budesonide maintenance plus short-acting β2-agonist (SABA) as needed (budesonide group), and 1,500 patients used SABA as needed (SABA group). The results showed that the incidence of severe exacerbations and the time to first severe exacerbation in the budesonide–formoterol group were significantly different from those for the SABA group (RR = 0.46, 95% CI = 0.36–0.59, p &lt; 0.001; HR = 0.43, 95% CI = 0.33–0.56, p &lt; 0.001; respectively), but there was no difference between the budesonide–formoterol group and budesonide group (RR = 0.86, 95% CI = 0.62–1.04, p = 0.093; HR = 0.77, 95% CI = 0.57–1.03, p = 0.079; respectively). There were statistically significant differences in the forced expiratory volume in 1 second and in the responses to the Asthma Control Questionnaire-5 between the budesonide-formoterol group and the SABA group, but the differences were not clinically significant. In addition, the daily dose of budesonide in the budesonide–formoterol group was significantly lower than that in the budesonide group, and there was no difference in the incidence of adverse events among the three groups.Conclusion: In summary, budesonide–formoterol used as needed may reduce severe exacerbation in adolescent/adult patients with mild persistent asthma.

Inhaled budesonide for COVID-19 in people at higher risk of adverse outcomes in the community: interim analyses from the PRINCIPLE trial

BACKGROUND Inhaled budesonide has shown efficacy for treating COVID-19 in the community but has not yet been tested in effectiveness trials. METHODS We performed a multicenter, open-label, multi-arm, adaptive platform randomized controlled trial involving people aged ≥65 years, or ≥50 years with comorbidities, and unwell ≤14 days with suspected COVID-19 in the community (PRINCIPLE). Participants were randomized to usual care, usual care plus inhaled budesonide (800μg twice daily for 14 days), or usual care plus other interventions. The co-primary endpoints are time to first self-reported recovery, and hospitalization/death related to COVID-19, both measured over 28 days from randomisation and analysed using Bayesian models. RESULTS The trial opened on April 2, 2020. Randomization to inhaled budesonide began on November 27, 2020 and was stopped on March 31, 2021 based on an interim analysis using data from March 4, 2021. Here, we report updated interim analysis data from March 25, 2021, at which point the trial had randomized 4663 participants with suspected COVID-19. Of these, 2617 (56.1%) tested SARS-CoV-2 positive and contributed data to this interim budesonide primary analysis; 751 budesonide, 1028 usual care and 643 to other interventions. Time to first self-reported recovery was shorter in the budesonide group compared to usual care (hazard ratio 1.208 [95% BCI 1.076 - 1.356], probability of superiority 0.999, estimated benefit [95% BCI] of 3.011 [1.134 - 5.41] days). Among those in the interim budesonide primary analysis who had the opportunity to contribute data for 28 days follow up, there were 59/692 (8.5%) COVID-19 related hospitalizations/deaths in the budesonide group vs 100/968 (10.3%) in the usual care group (estimated percentage benefit, 2.1% [95% BCI -0.7% - 4.8%], probability of superiority 0.928). CONCLUSIONS In this updated interim analysis, inhaled budesonide reduced time to recovery by a median of 3 days in people with COVID-19 with risk factors for adverse outcomes. Once 28 day follow up is complete for all participants randomized to budesonide, final analyses of time to recovery and hospitalization/death will be published. (Funded by the National Institute of Health Research/ United Kingdom Research Innovation [MC_PC_19079]; PRINCIPLE ISRCTN number, ISRCTN86534580.)

Calcitriol Combined With Budesonide Inhibits the Secretion and Expression of IL-33 in Mouse Airway Smooth Muscle Cells

BackgroundBronchial asthma (asthma) is a chronic respiratory inflammatory disease characterized by reversible airflow limitation and high airway reactivity. Current studies generally show that airway remodeling is the pathologic structural basis for the occurrence of reversible airflow restriction and airway hyper reactivity[1] [2].In the above process, airway smooth muscle cell (ASMC) hyperplasia and hypertrophy are considered to be the main mechanisms of airway remodeling[3]. Calcitriol can be combined with budesonide to more effectively inhibit airway inflammation and airway remodeling and play its role in the treatment of asthma[4, 5]. MethodsThe mouse airway smooth muscle cells were divided into blank group, TGF-β1 group, SIS3 group, budesonide group,calcitriol group and drug co-treatment group[6]. The IL-33 concentration in supernatant of each group was detected by ELISA method, and the expression of Smad3, pSmad3 and IL-33 protein in each group was detected by Western blotting method[7].ResultsELISA showed that the concentration of IL-33 in the supernatant of cell culture in budesonide group was lower than that in the calcitriolgroup, and the concentration of IL-33 in the drugco-treatment group was lower than that in any single drugtreatment group.The expression level of Smad3 protein, pSmad3 protein and IL-33 protein of western blot in the drug co-treatment group were significantly decreased[8, 9].ConclusionsCalcitriol combined with budesonide can effectively decrease the expression and secretion of IL-33 in mouseairway smooth muscle cells byactivatingTGF-β1/Smad3 signaling pathway [10].

Effect of Xiaoning Liquid on Gut Microbiota in Asthmatic Mice by 16s RDNA High - Throughput Sequencing

Background: To investigate the effects of Xiaoning liquid on gut microbiota in mouse during asthma.Methods: A total of 60 mice were randomly and averagely assigned to healthy control group, control group, budesonide group, and Xiaoning liquid group. The later three groups were used to establish an Ovalbumin (OVA) asthma model. The intestinal bacterial communities were compared among groups using 16S rRNA gene amplification. Analyzing the structure of gut microbiota with OTU analysis, Shannon–Wiener, PCA, PCOA, etc. 16s rDNA high- throughput sequencing. Results: The abundance and diversity of the gut microbiota in asthmatic mice increased, most obviously in the control group. The Bacteroidetes and Firmicutes levels increased in all asthmatic mice. The level of Bacteroides increased most obviously, making Bacteroides a useful marker of gut microbiota changes in asthmatic mice. The levels of Proteobacterium, Deferribacteraceae and Mucispirillum dropped significantly in the Xiaoning liquid group. Conclusions: Xiaoning liquid can reduce the species and numbers of pathogenic bacteria and restored the intestinal microecology of asthmatic mice. Xiaoning liquid has a positive effect on the function of gut microbiota.

Role of Erythromycin-Regulated Histone Deacetylase-2 in Benign Tracheal Stenosis

Objective. This study aims to explore the role of erythromycin-regulated histone deacetylase-2 in benign tracheal stenosis. Methods. The rabbit model of tracheal stenosis was established. The rabbits were randomly divided into 8 groups. Histone deacetylase-2 (HDAC2) expression was detected by immunofluorescence. The expression of type I collagen and type III collagen was detected by immunohistochemical method. The expression of TGF-β1, VEGF and IL-8 in serum and alveolar lavage fluid was detected by ELISA. The expression of HDAC2, TGF-β1, VEGF and IL-8 in bronchi of each group was detected by Western blotting method. Results. In Erythromycin (ERY) group, ERY + Budesonide group, ERY + Vorinostat group and ERY + Budesonide + Vorinostat group, the degree of bronchial stenosis was alleviated, and the mucosal epithelium was still slightly proliferated. The effect of ERY combined with other drugs was more obvious. The HDAC2 protein expression increased significantly in ERY group, ERY + Budesonide group and ERY + Budesonide + Vorinostat group and decreased significantly in Vorinostat group, the expression of collagen I and III decreased significantly in ERY group, ERY + Budesonide group and ERY + Budesonide + Vorinostat group (P<0.05). The TGF-β1, IL-8 and VEGF levels decreased significantly in ERY group, ERY + Budesonide group, ERY + Vorinostat group and ERY + Budesonide + Vorinostat group (P<0.05). Conclusions. Erythromycin inhibited inflammation and excessive proliferation of granulation tissue after tracheobronchial mucosal injury by up-regulating the expression of HDAC2, it promoted wound healing and alleviated tracheobronchial stenosis. When combined with budesonide, penicillin and other glucocorticoids and antibiotics, it had a good synergistic effect. However, vorinostat could attenuate erythromycin’s effect by down-regulating the expression of HDAC2. It may have good clinical application prospects in the treatment of tracheal stenosis.

The role of budesonide and mometasone furoate on the nasal and sinus symptoms in allergic rhinosinuitis: a randomized study

<p class="abstract"><strong>Background:</strong> Allergic rhinosinuitis is one of the common clinical problems that otorhinolaryngologist faces daily. Sinusitis symptoms like headache, facial pain and eyelid oedema are frequent in patients with allergic rhinitis, which in turn will affect the cognitive function, productivity and quality of life which impair the efficiency of the individual work performance. It may result in a prescription for antibiotics but the role of antibiotics is debated. Anti-inflammatory drugs such as intranasal steroids play a major role in reducing the symptoms of allergic rhinitis. We plan to compare the efficacy of budesonide nasal spray with mometasone furoate nasal spray in reducing the nasal and sinus symptoms of allergic rhinosinusitis.</p><p class="abstract"><strong>Methods:</strong> 146 patients of allergic rhinitis with sinusitis symptoms were randomly divided into 2 groups as Group A (n=70) received 256 μg budesonide nasal spray of once daily and Group B (n=76) received 200 μg of mometasone furoate nasal spray daily. The patients were assessed by sino-nasal outcome test (SNOT) score and total nasal symptom score (TNSS) at 2, 6 and 12 weeks interval. </p><p class="abstract"><strong>Results:</strong> There is significant reduction in both the groups, in respect to the SNOT and TNSS scores. We also observed significant improvement in the SNOT score in the budesonide group when compared with the mometasone furoate group by 6weeks which continued till the 12 weeks (p=0.001).</p><p class="abstract"><strong>Conclusions:</strong> Budesonide nasal spray is more effective than mometasone furoate spray in managing both sinus and nasal symptoms in allergic rhinitis.</p>

To evaluate the efficacy of nebulized budesonide compared to oral prednisolone in the management of moderate exacerbation of acute asthma

Background: Corticosteroids are extremely effective drugs and are used extensively in the management of asthma. Inhaled corticosteroids may offer some benefit in patients with mild to moderate obstruction in acute exacerbation and also offer the advantage of administration directly to the lungs. Hence this study was done to evaluate the efficacy of nebulized budesonide as compared to oral prednisolone in the management of moderate exacerbation of acute asthma.Methods: A total of 80 children attending pediatric emergency of SMGS Hospital Jammu aged 1 to 18 years with a moderate exacerbation of asthma despite three salbutamol nebulizations were enrolled and randomized into two groups. First group recieved nebulized budesonide (800 mcg) at hourly intervals for three doses followed by twice a day (n=37) while second group recieved oral prednisolone 2 mg/kg/day in two divided doses (n=43). Both groups continued to receive oxygen inhalation and nebulized salbutamol (0.15 mg/kg/dose) initially at hourly intervals for 3 doses followed by 6 hourly. The pattern of response as observed by the pulmonary scores in the two groups was compared.Results: The pulmonary scores were significantly improved at 1, 2 and 6 hours after starting treatment in the budesonide group as compared to prednisolone group (p < 0.01) although the difference was not significant after 12 hours. Oxygen saturation also showed a significant early improvement.Conclusions: This early demonstrable significant improvement in the clinical parameters of the inhaled budesonide group apparently suggests that inhaled budesonide may be efficacious in treating moderate exacerbations of asthma.