Administration Of Budesonide Research Articles

Airway inflammation and remodeling of cigarette smoking exposure ovalbumin-induced asthma is alleviated by CpG oligodeoxynucleotides via affecting dendritic cell-mediated Th17 polarization

Cigarette smoking (CS) is common in asthma, aggravating inflammatory reactions. However, the current treatment strategies for asthma are still not effective enough, and novel therapeutic approaches are required for CS-induced asthmatic disorders. We here investigated the ability of CpG oligodeoxynucleotides (CpG-ODNs) to inhibit airway inflammation and remodeling in ovalbumin (OVA)-associated asthma in mice exposed to chronic CS, revealing potential mechanistic insights. Lung tissue specimens were histologically analyzed. Th1/Th2/Th17 associated cytokines in serum, bronchoalveolar lavage fluid (BALF), and lung specimens were quantitated by ELISA, qRT-PCR and immunoblot. Parameters of bone marrow-derived dendritic cells (BMDCs) functions were evaluated as well. The results showed that BALB/c mice after CS and OVA treatments developed an asthmatic phenotype with airway inflammation involving both eosinophils and neutrophils, goblet cell metaplasia, airway remodeling, and elevated OVA-specific serum IgE, serum IL-17A, and BALF Th17/Th2 associated cytokines. CpG-ODNs and budesonide were found to synergistically inhibit inflammatory cell recruitment in the lung, airway remodeling, IgE synthesis, and Th17/Th2 associated cytokines. Mechanistically, CpG-ODNs and budesonide acted synergistically on BMDCs via downregulation of TSLP receptor (TSLPR) and IL-23 production, and subsequently contributed to dampen Th17/Th2 polarization in CS-associated asthma. In conclusion, combined administration of CpG-ODNs and budesonide, in a synergistic manner, inhibits airway inflammation, and tissue remodeling mediated by BMDCs by regulating IL-23 secretion and blocking TSLP signaling, which subsequently contribute to alleviate Th17/Th2 imbalance in CS-associated asthma.

Intratracheal administration of budesonide with surfactant in very low birth weight infants to prevent bronchopulmonary dysplasia.

Respiratory distress syndrome (RDS) is a major cause of early postnatal death in preterm infants. Bronchopulmonary dysplasia (BPD) is one of the most fatal chronic respiratory complications of preterm infants after management of RDS. Anti-inflammatory therapy with corticosteroid is one of the effective treatments to prevent BPD. However, systemic administration of corticosteroid is not recommended because of long-term adverse effects. We studied the effect of early intratracheal instillation of budesonide with surfactant in preterm infants with severe RDS. Very low birth weight infants (VLBWIs) weighing less than 1,500 g who were admitted to the neonatal intensive care unit (NICU) of Busan Paik Hospital between January 2018 and December 2018 and diagnosed with severe RDS were enrolled. The treatment group was given a mixture of budesonide and surfactant (calfactant) while the control group was given surfactant (calfactant) only. Surfactant re-dosing, duration of mechanical ventilation, BPD, mortality, and retinopathy of prematurity (≥ stage 2) were not different between the two groups though there were decreasing trends in the treatment group compared to those in the control group. The duration of hospital stay was longer in the control group with statistical significance. Early intratracheal administration of budesonide with surfactant in preterm infants with severe RDS might decrease BPD and mortality without disturbing surfactant function. Further studies with different preparations of surfactants with a large number of preterm infants are required.

Оптимизация терапии у детей с бронхиальной астмой легкого течения с целью улучшения контроля в период эпидемического подъема острых респираторных инфекций

Background. Children with mild bronchial asthma (BA) are prone to poor control of symptoms during seasonal acute respiratory infections (ARIs). Objective. To optimize therapy in children with mild BA to improve disease control during seasonal ARIs. Patients and methods. This single-blind placebo-controlled prospective single-center trial evaluating the efficacy of ammonium glycyrrhizinate (Reglisam, ‘VIFITECH,’ Russia) and lasting 4 months included 63 children with mild BA (21 in the placebo group) aged 5 to 10 years with a disease duration of at least 3 months. We assessed respiratory function, FeNO level, results of the asthma control test, characteristics of BA exacerbations, and the need for betamimetics and budesonide via a nebulizer. We used the Student's t-test and Wilcoxon test to evaluate the differences in mean and median values; the differences were considered significant at р < 0.05. Results. The frequency and mean duration of ARIs were lower in the group of active therapy (1.06 ± 0.35 episodes and 6.52 ± 2.19 days) than in the placebo group (1.77 ± 0.26 episodes and 10.83 ± 3.07 days). The differences were statistically significant (р = 0.036 and р = 0.019, respectively). Patients receiving placebo required longer budesonide administration per one BA exacerbation: 11.72 ± 1.98 days vs 8.65 ± 2.17 days in patients receiving active therapy (р = 0.026). Significant differences in the respiratory function and FeNO level were observed only in the subgroup of patients who had incomplete asthma control upon enrollment. We observed no new adverse events that had not been reported earlier. Conclusion. Our findings suggest high efficacy of ammonium glycyrrhizinate used to enhance basic therapy for mild BA in children, in whom respiratory infections are the most common triggers of BA exacerbations. Key words: ammonium glycyrrhizinate, basic therapy, children, mild bronchial asthma, acute respiratory infections (ARIs)

Budesonide Foam for Ulcerative Colitis Patients Experiencing Inadequate Response to Biological Therapy.

BackgroundIn recent years, a plethora of therapeutic agents for ulcerative colitis (UC), especially novel biologics (Bio), have become available. Although it is now possible to use biological drugs, there should be no need for frequently changing medications. To avoid first-pass metabolism in the liver, thus reducing systemic bioavailability, budesonide foam has been applied as a topical steroid. We therefore evaluated whether budesonide foam has therapeutic value in UC patients who responded inadequately to Bio or to tacrolimus.Material/MethodsWe enrolled 10 patients who were experiencing an inadequate response to Bio (n=7) or to tacrolimus (n=3) at Juntendo University. We used Lichtiger’s index to assess UC activity and clinical response.ResultsOf the study patients, 4 were receiving adalimumab, 3 golimumab, and 3 tacrolimus. The average Lichtiger’s index before budesonide administration was 7.1 (range 13–3), which improved to 3.4 (range 7–0) after budesonide therapy (p=0.01). Notably, 4 of the 6 cases with a Lichtiger’s index >4 before budesonide administration achieved improvement of ≥3 points or remission.ConclusionsAlthough the number of patients was small, budesonide foam had significant efficacy when added to the treatment of patients having an inadequate response to Bio or to tacrolimus. These results suggest that in cases responding poorly to Bio, adding budesonide foam as combination therapy can achieve a clinical remission.

Budesonide enhances agonist-induced bronchodilation in human small airways by increasing cAMP production in airway smooth muscle.

The nongenomic mechanisms by which glucocorticoids modulate β2 agonist-induced-bronchodilation remain elusive. Our studies aimed to elucidate mechanisms mediating the beneficial effects of glucocorticoids on agonist-induced bronchodilation. Utilizing human precision-cut lung slices (hPCLS), we measured bronchodilation to formoterol, prostaglandin E2 (PGE2), cholera toxin (CTX), or forskolin in the presence and absence of budesonide. Using cultured human airway smooth muscle (HASM), intracellular cAMP was measured in live cells following exposure to formoterol, PGE2, or forskolin in the presence or absence of budesonide. We showed that simultaneous budesonide administration amplified formoterol-induced bronchodilation and attenuated agonist-induced phosphorylation of myosin light chain, a necessary signaling event mediating force generation. In parallel studies, cAMP levels were augmented by simultaneous exposure of HASM cells to formoterol and budesonide. Budesonide, fluticasone, and prednisone alone rapidly increased cAMP levels, but steroids alone had little effect on bronchodilation in hPCLS. Bronchodilation induced by PGE2, CTX, or forskolin was also augmented by simultaneous exposure to budesonide in hPCLS. Furthermore, HASM cells expressed membrane-bound glucocorticoid receptors that failed to translocate with glucocorticoid stimulation and that potentially mediated the rapid effects of steroids on β2 agonist-induced bronchodilation. Knockdown of glucocorticoid receptor-α had little effect on budesonide-induced and steroid-dependent augmentation of formoterol-induced cAMP generation in HASM. Collectively, these studies suggest that glucocorticoids amplify cAMP-dependent bronchodilation by directly increasing cAMP levels. These studies identify a molecular mechanism by which the combination of glucocorticoids and β2 agonists may augment bronchodilation in diseases such as asthma or chronic obstructive pulmonary disease.

Dry Powder and Budesonide Inhalation Suspension Deposition Rates in Asthmatic Airway-Obstruction Regions.

Steroid inhalation is the standard bronchial asthma therapy and it includes powdered metered doses, dry powder, and nebulizer suspension. However, particle sizes vary widely. The research goal was to demonstrate that different budesonide administration forms and devices have various deposition rates in the airway obstruction region. Here, we compared relative inhalation therapy efficacies and identified therapies that delivered the highest drug doses to the airway obstruction region. Weibel's anatomy data were used to identify the airway obstruction region in asthma. Based on European Standardization Committee data, we investigated the diameters of the drug particles being deposited there and evaluated the average particle size and distribution of the budesonide dosage forms and application devices. Drug dose depositions were measured by HPLC at each stage of a Cascade Impactor. Weibel's anatomy data indicated that the 1st–4th bronchial generations comprised the airway obstruction region and corresponded to the tracheobronchial area. According to the European Standardization, particles 2–6 µm in diameter were readily deposited there. The proportions of particles in this size range were 33.0%, 32.0%, 59.0%, and 78.0% for Turbuhaler, Symbicort, mesh-type NE-U22 suspension, and jet-type NE-C28 suspension, respectively. We localized the airway obstruction regions of bronchial asthma and identified the optimal inhalation therapy particle size. An electric nebulizer was more efficacious for budesonide administration than dry powder delivery. The NE-C28 treatment deposited 2.36x more budesonide in the airway obstruction region than dry powder delivery systems.

Chronic asthma-induced behavioral and hippocampal neuronal morphological changes are concurrent with BDNF, cofilin1 and Cdc42/RhoA alterations in immature mice

IntroductionRecent studies have found that persistent hypoxia caused by chronic asthma, especially during childhood, affects the development and function of the brain, but the mechanism is unclear. In the present study, BDNF and its signal pathway was investigated in mediating chronic asthma induced-neuronal changes that lead to behavior alterations. MethodsThe chronic asthma model was induced by sensitization with ovalbumin for more than 9 weeks in immature mice. Morris water maze test (MWMT), open field test (OFT) and elevated plus maze test (EPMT) were used to conduct behavioral evaluation. Neuronal morphology in hippocampal CA1, CA3 and DG was assessed using ImageJ's Sholl plugin and RESCONSTRUCT software. BDNF signaling pathway related molecules was determined by Western blotting. ResultsChronic asthma does affect the behavioral performances of immature mice evaluated in MWMT, OFT, and EPMT. The analysis by three-dimensional reconstruction software found that following the behavioral alteration of asthmatic mice, dendritic changes also occurred in hippocampal neurons, including shortened dendrite length, significantly reduced number of dendritic branches, decreased density of dendritic spines, and reduced percentage of functional dendritic spine types. At the same time, by immunofluorescence and western blotting, we also found that alterations in dendritic morphology were consistent with activation of cofilin1 and changes in BDNF-Cdc42/RhoA levels. Some of the changes mentioned above can be alleviated by intranasal administration of budesonide. ConclusionOur data suggest that response similar to nicotine withdrawal or/and hypoxia induced by childhood chronic asthma enhances the BDNF-Cdc42/RhoA signaling pathway and activates cofilin1, leading to the remodeling of actin, causing the loss of dendritic spines and atrophy of dendrites, eventually resulting in behavioral alterations.

Antiviral and anti-inflammatory activity of budesonide against human rhinovirus infection mediated via autophagy activation

Human rhinovirus (HRV) infection causes more than 80% of all common colds and is associated with severe complications in patients with asthma and chronic obstructive pulmonary disease. To identify antiviral drug against HRV infection, we screened 800 FDA-approved drugs and found budesonide as one of the possible drug candidates. Budesonide is a corticosteroid, which is commonly used to prevent exacerbation of asthma and symptoms of common cold. Budesonide specifically protects host cells from cytotoxicity following HRV infection, which depend on the expression of glucocorticoid receptor. Intranasal administration of budesonide lowered the pulmonary HRV load and the levels of IL-1β cytokine leading to decreased lung inflammation. Budesonide regulates IL-1β production following HRV infection independent of inflammasome activation. Instead, budesonide induces mitochondrial reactive oxygen species followed by activation of autophagy. Further, the inhibition of autophagy following chloroquine or bafilomycin A1 treatment reduced the anti-viral effect of budesonide against HRV, suggesting that the antiviral activity of budesonide was mediated via autophagy. The results suggest that budesonide represents a promising antiviral and anti-inflammatory drug candidate for the treatment of human rhinovirus infection.

Shaken or Stirred? Evaluating the combination of budesonide-surfactant for survival free of bronchopulmonary dysplasia.

Commentary on: Yeh TF, Chen CM, Wu SY, Husan Z, Li TC, Hsieh WS, Tsai CH, Lin HC. Intratracheal Administration of Budesonide/Surfactant to Prevent Bronchopulmonary Dysplasia. Am J Respir Crit Care Med. 2016;193(1):86-95. PMID: 26351971. The magic bullet that prevents bronchopulmonary dysplasia (BPD) in very low-birthweight infants without increasing long-term side effects remains elusive. Because pulmonary inflammation is likely critical to the pathogenesis of BPD, numerous investigators have attempted to prevent the development of BPD with a wide variety of postnatal corticosteroid regimens 1. Unfortunately, systemic corticosteroids have been linked to increase risk of adverse neurodevelopmental outcomes 2. Inhaled corticosteroids combine more direct action on lung tissue with less systemic effect, but inhaled corticosteroids have also failed to reduce BPD 3, 4. Adding budesonide to surfactant potentiates the delivery of corticosteroid to the peripheral lung tissue 5. The authors posit that delivering this combination therapy early in the course of illness may unlock the minimum required anti-inflammatory stimuli necessary to prevent BPD while avoiding adverse outcomes. A paucity of data makes assessing the impact of the specific surfactant preparation used in this study difficult. This would likely be worthwhile to explore in future research. Yeh et al. found a significant reduction in the incidence of BPD or death after administration of budesonide–surfactant as compared to surfactant alone. The effect can be attributed to a reduction in BPD alone without a significant effect on mortality. While not powered to examine neurodevelopmental outcomes, it is encouraging that the surviving infants exhibited no trend towards adverse outcome at two to three years old. Both findings were confirmed by meta-analysis 6 with the group's prior pilot study 7. The major limitation of this study is the high incidence of BPD in the control group (50%). In a population with a lower prevalence of BPD, the relative risk reduction and number needed to treat are likely to be many fold different. Many infants experienced significant intervention prior to randomisation that could alter the magnitude of the treatment effect and thus the number needed to treat, such as mechanical ventilation and oxygen administration. While randomisation prevents the introduction of significant bias in this study, earlier surfactant administration may potentiate the budesonide effect when compared to other strategies shown to reduce BPD 8. The role of budesonide–surfactant administration should be re-evaluated in conjunction with other current treatment strategies known to prevent BPD. This would reassure clinicians that budesonide–surfactant therapy continues to offer benefit in the context of current clinical practice. In the end, Yeh et al. represent a potentially powerful intervention to reduce the risk of BPD. Considering the less than satisfactory results achieved by previous corticosteroid delivery methods, this is a significant achievement. However, the previous failure of postnatal corticosteroid administration has created a paradox, that is difficult to overcome. Clinicians continue to use corticosteroids in infants with moderate-to-severe BPD despite known risks, while at the same time demanding a high bar of evidence be achieved before altering current management. Before budesonide–surfactant can become the standard of care, further large trials are required in populations with a lower prevalence of BPD. We advocate for a multicentre trial in conjunction with noninvasive respiratory management that is powered to evaluate neurodevelopmental outcomes. None. https://ebneo.org/2017/11/shaken-or-stirred-evaluating-the-combination-of-budesonide-surfactant-for-survival-free-of-bronchopulmonary-dysplasia/ None.

In vitro and in vivo characterization of poractant alfa supplemented with budesonide for safe and effective intratracheal administration.

BackgroundThe intratracheal (IT) administration of budesonide using surfactant as a vehicle has been shown to reduce the incidence of bronchopulmonary dysplasia (BPD) in preterm infants. The objective of this study was to characterize the in vitro characteristics and in vivo safety and efficacy of the extemporaneous combination of budesonide and poractant alfa.MethodsThe stability, minimum surface tension, and viscosity of the preparation were evaluated by means of high-performance liquid chromatography (HPLC), Wilhelmy balance, and Rheometer, respectively. The safety and efficacy of the IT administration of the mixture were tested in two respiratory distress syndrome (RDS) animal models: twenty-seventh day gestational age premature rabbits and surfactant-depleted adult rabbits.ResultsA pre-formulation trial identified a suitable procedure to ensure the homogeneity and stability of the formulation. Wilhelmy Balance tests clarified that budesonide supplementation has no detrimental effect on poractant alfa surface tension activity. The addition of budesonide to poractant alfa did not affect the physiological response to surfactant treatment in both RDS animal models, and was associated to a significant reduction of lung inflammation in surfactant-depleted rabbits.ConclusionOur in vitro and in vivo analysis suggests that the IT administration of a characterized extemporaneous combination of poractant alfa and budesonide is a safe and efficacious procedure in the context of RDS.

The effect of orally administered Budesonide on the hypothalamic-pituitary-adrenal axis in dogs with inflammatory bowel disease

The aim of this study was to evaluate the effect of Budesonide on the hypothalamic-pituitary-adrenal (HPA) axis in dogs with inflammatory bowel disease. The effect of orally administered Budesonide (Entocort) on the HPA axis was analysed in 21 dogs with inflammatory bowel disease. Biochemical analyses were carried out to evaluate the activity levels of alanine aminotransferase, asparagine aminotransferase, alkaline phosphatase, cortisol and endogenous adrenocorticotropic hormone. Urine samples were collected from each patient before the study and after 30 days of the experiment to determine the composition and the physical and chemical properties of urine sediments. Considerably lower serum concentrations of cortisol and endogenous adrenocorticotropic hormone were observed after 30 days of treatment. A significant increase in alkaline phosphatase levels was noted on Day 30. In the studied dogs, the drop in HPA axis activity was correlated with side effects associated with the administered glucocorticosteroid (polyuria, polydipsia). In conclusion, we have shown that oral administration of Budesonide to dogs diagnosed with inflammatory bowel disease significantly suppressed the activity of the HPA axis.

P1.01-011 Roflumilast Attenuates Benzo(a)Pyrene-Induced Lung Cancer via Suppression of Airway Inflammation in Murine Model

Chronic airway inflammation has been emerging targets for lung cancer chemoprevention as well as treatment of COPD. The aim of the present study was to determine the role of roflumilast and aerosolized budesonide in benzo(a)pyrene-induced lung cancer in mice and to elucidate the possible their mechanisms. Female A/J mice were given a single dose of benzo(a)pyrene. Intraperitoneal administration of roflumilast (1mg/kg, 5mg/kg) began 2 weeks post-carcinogen treatment and continued tri-weekly for 28 weeks. Aerosolized budesonide was administered by aerosol delivery for 2 min/day and 5 days/week. Tumor load was determined by averaging the total tumor volume in each group. Benzo(a)pyrene induced an average tumor size of 9.4 ± 1.8 tumors per mouse, with an average tumor load of 19.5 ± 3.8mm3. Roflumilast treatment at 1 and 5 mg/kg did not inhibit tumor number, however, reduced tumor load, an average of 8.8 ± 2.0 mm3 at 5mg/kg treatment, significantly. Aerosolized budesonide administration did not show reductions of tumor number or load. The decreased expressions of cyclic AMP and protein kinase A caused by benzo(a)pyrene were increased by roflumilast treatment. NF-κB expression in tumor tissues was lower in the roflumilast group than the place group. In vivo experiments in the benzo(a)pyrene-induced model of lung cancer show that roflumilast significant inhibits tumorigenicity via suppression of inflammation. Possible mechanisms between cAMP pathway and lung cancer development will needed to be determined.

The effect of budesonide administration for serum IL-18 level in asthma children

目的 观察支气管哮喘儿童血清白细胞介素18(IL-18)的变化以及吸入布地奈德对其的影响。 方法 选取2014年5月至2015年5月本院诊断为支气管哮喘的患儿68例作为研究对象，其中40例患儿接受布地奈德雾化吸入治疗3个月为治疗组，其余28例未予以激素治疗患儿为常规治疗组。同时选取同时期同年龄组健康体检儿童60例为空白对照组，治疗组以布地奈德雾化吸入治疗3个月，分别测定各组患儿血清IL-18水平并比较其变化。 结果 哮喘患儿外周血血清IL-18水平显著高于健康对照组患儿(P<0.05)，治疗组患儿经过3个月的布地奈德雾化吸入治疗，其外周血IL-18水平较常规治疗组显著降低，但是仍显著高于对照组(P<0.05)。 结论 哮喘患儿血清IL-18水平升高，吸入布地奈德可降低IL-18水平。提示IL-18是哮喘临床疗效的有效评价指标。

Glucocorticoids decrease the production of glucagon-like peptide-1 at the transcriptional level in intestinal L-cells

Glucocorticoids are widely used as anti-inflammatory or immunosuppressive drugs, but often induce hyperglycemia as a side effect. Glucagon-like peptide-1 (GLP-1) is secreted from intestinal L cells and plays crucial roles in maintaining glucose homeostasis. However, the direct effects of glucocorticoids on the GLP-1 production pathway in L cells remain unclear. We investigated the effects of glucocorticoids on GLP-1 production in vitro and in vivo. In L cell lines, glucocorticoids decreased GLP-1 release and expression of the precursor, proglucagon, at protein and mRNA levels, which were inhibited by mifepristone. The administration of dexamethasone or budesonide to mice significantly decreased the mRNA expression of proglucagon in the ileum and partially decreased glucose-stimulated GLP-1 secretion. Compound A, a dissociated glucocorticoid receptor modulator, did not affect the expression of proglucagon in vitro. These results suggested that glucocorticoids directly reduced GLP-1 production at the transcriptional level in L cells through a glucocorticoid receptor dimerization-dependent mechanism.

Effect of Surfactant and Budesonide on the Pulmonary Distribution of Fluorescent Dye in Mice

Surfactant is a useful vehicle for the intratracheal delivery of medicine to the distal lung. The aim of this study was to analyze the effect of intratracheal surfactant and budesonide instillation on the pulmonary distribution of fluorescent dye in mice. Male athymic nude mice were assigned randomly as controls, fluorescent dye, fluorescent dye+surfactant (50mg/kg), fluorescent dye+budesonide (0.25mg/kg), and fluorescent dye+surfactant+budesonide groups. A total volume of 60μL fluorescent solutions was intratracheally injected and followed by 60μL of air. We photographed and measured fluorescence in the lungs, from the back, 15 minutes after intratracheal administration using an IVIS Xenogen imaging instrument. The fluorescent dye (1,1'-dioctadecyltetramethyl indotricarbocyanine iodide) was most strongly detected near the trachea and weakly detected in the lungs in mice administered with fluorescent solutions. Almost no fluorescence was seen in the lung region of control mice. Intratracheal administration of surfactant or budesonide increased fluorescent intensity compared with control mice. Combined administration of surfactant and budesonide further increased fluorescent intensity compared with mice given surfactant or budesonide alone. Surfactant and budesonide enhance the pulmonary distribution of fluorescent dye in mice.

Hyaluronidase modulates bleomycin‐induced lung injury detected noninvasively in small rodents by radial proton MRI

To assess whether hyaluronic acid, a building block of proteoglycans and extracellular matrix with hydrophilic characteristics, might contribute to magnetic resonance imaging (MRI)-detected proton signals elicited by bleomycin in the lung. To this end, hyaluronidase, which degrades hyaluronic acid, was administered to bleomycin-challenged animals. Fibrosis was induced by oropharyngeal aspiration (OA) of bleomycin. Mice received bleomycin once daily (0.1 mg/kg) on 6 consecutive days, while rats were given a single dose (2 or 4 mg/kg). Hyaluronidase, budesonide, and the respective vehicles were also administered via OA. Animals were examined using a radial ultrashort echo time sequence. Histology of picrosirius reflecting collagen and tissue gene analysis were performed postmortem. In mice, hyaluronidase induced an increase of high intensity signals by 34 ± 12 μL (means ± SD, P = 0.007), consistent with the ability of the degradation products of hyaluronic acid to provoke acute inflammation. Budesonide was able to resolve hyaluronidase-induced signals or to prevent their formation. Combined administration of budesonide and hyaluronidase to bleomycin-treated rats resulted in an overall decrease (-17.1 ± 7%, P = 0.02) of the MRI-detected bleomycin-induced signals. Moreover, the relative gene expression of hyaluronidase was reduced (-61.8 ± 10.2%, P < 0.001) in fibrotic lungs. The present data indicate that hyaluronic acid contributes to the bleomycin-induced responses detected by MRI in the lung.

Single inhaler strategy in stepwise therapy of bronchial asthma: GINA 2014 update

Major advances of GINA (Global Initiative for Asthma) 2014 pertinent to definition, phenotypes and stepwise approach for adjusting treatment of asthma have been viewed in the article. The attention was focused on combinations of low - dose inhaled steroid (ICS) / formoterol (FOR) both as maintenance and reliever therapy (single inhaler strategy) or ICS / long - acting β 2 - agonist (LABA) as maintenance therapy plus short - acting β 2 - agonist (SABA) as - needed that are preferred options for treatment steps 3–4 in adults and adolescents. GINA experts emphasize that the single inhaler strategy is the treatment of choice for asthma patients with steps 3–4 experienced ≥ 1 exacerbation during the previous year. Administration of budesonide (BUD) / FOR as a single inhaler is recommended for patients > 18 years old with insufficient asthma control and frequent need in SABA. BUD / FOR as a single maintenance and reliever inhaler could reduce frequency of severe asthma exacerbations requiring hospitalizations and use of systemic steroids, improve asthma symptoms and lung function when compared to other treatment regimens. Preventive effects of BUD / FOR combination are provided by anti - inflammatory effect which is timely amplified by additional inhalations of the drug.

Comparison of the efficacy of nebulized budesonide and intravenous dexamethasone administration before extubation in prevention of post-extubation complications among patients admitted in the ICU

Background: Narrowing of the airway caused by tracheolaryngeal edema is one of the most common complications of endotracheal intubation particularly among patients requiring mechanical ventilation longer than 36 h that can cause other complications and increase mortality rate. The aim of this study was to investigate the efficacy of nebulized budesonide in comparison with intravenous (IV) dexamethasone administration before extubation in prevention of post­extubation complications. Materials and Methods: This double­blind clinical trial was carried out at the intensive care unit (ICU) of a tertiary care center (Alzahra Hospital in Isfahan). The study's population was comprised of 90 patients who had been admitted in the ICU and required intubation at least for 48 h. All patients were between 18 and 65 years of age. Having randomly divided the patients into two equal groups, the first group received nebulized budesonide while the second group was treated by IV dexamethasone 1 h before extubation. The treatment continued up to 48 h after extubation. The collected data from both groups was then subjected to statistical analyses to come to results. Results: There was no significant difference between the two groups; hence, both drugs were found to be effective in prophylaxis of the complications due to tracheal extubation. According to the findings of the current study, since nebulized budesonide has no systemic complications of IV corticosteroid, it can be used as the first choice in reducing the complications attributed to extubation.

Administration of budesonide in children with graft-versus-host disease

Administration of budesonide in children with graft-versus-host disease

Experimental research The effects of budesonide on angiogenesis in a murine asthma model

IntroductionThe aim of this study is to determine the effects and mechanisms of budesonide on angiogenesis in a murine asthma model.Material and methodsMurine asthma models were established and mice were divided into three groups: the model group (OVA-sensitized and challenged mice), the BUD group (budesonide-treated mice) and the PBS group (normal control mice). Mice in the BUD group were administered with inhaled budesonide (100 µg/kg) daily. The effects on airway inflammation, angiogenesis, expression of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) were examined.ResultsAdministration of budesonide ameliorated allergic airway inflammation (2.90 ±0.18 vs. 4.80 ±0.20, p < 0.01) and significantly reduced the percentage vascularity (0.78 ±0.14 vs. 2.83 ±0.90, p < 0.01) compared with those in the asthmatic model mice. It also reduced the expression of HIF-1α (immunohistochemistry results: 71.70 ±1.40 vs. 89.60 ±0.79, p < 0.001; western blotting results: 0.88 ±0.41 vs. 0.97 ±0.47, p < 0.05), as well as that of VEGF (immunohistochemistry results: 26.30 ±1.03 vs. 93.30 ±1.54, p < 0.001; western blotting results: 1.12 ±0.22 vs. 2.08 ±0.30, p < 0.01). Percentage vascularity had positive correlation with both HIF-1α (r = 0.785, p < 0.01) and VEGF (r = 0.693, p < 0.01) expression. Furthermore, there is positive relationship between HIF-1α and VEGF expression (r = 0.641, p < 0.05).ConclusionsThe results demonstrate that budesonide has an important inhibitory effect on angiogenesis in asthma. Inhaled administration of budesonide achieved anti-angiogenic activity through inhibition of HIF-1α and VEGF expression. The results support a potential anti-remodeling role for budesonide in the treatment of human asthma.