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Abstract Background Acute Mountain Sickness (AMS) is a pathophysiologic process that occurs in non-acclimated susceptible individuals rapidly ascending to high-altitude. Barometric pressure falls at high altitude and it translates to a decreased partial pressure of alveolar oxygen (PAO2) and arterial oxygen (PaO2). A gradual staged ascent with sufficient acclimatization can prevent AMS but emergent circumstances requiring exposure to rapid atmospheric pressure changes – such as for climbers, disaster or rescue team procedures, and military operations – establishes a need for effective prophylactic medications. This systematic review and meta-analysis aim to analyze the incidence of AMS during emergent ascent of non-acclimatized individuals receiving inhaled budesonide compared to placebo. Methods This current meta-analysis was conducted according to the guidance of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. We searched PubMed, Google Scholar and Embase for relevant studies. The efficacy of budesonide in reducing incidence of AMS was evaluated by calculating the pooled ORs and 95% CIs. The efficacy of budesonide in maintaining hemoglobin-oxygen saturation was evaluated by calculating standard mean difference (SMD) and 95% confidence intervals. Results We found that at high altitude, inhaled budesonide was effective in reducing the incidence of mild AMS [OR: 0.37; 95% CI, 0.14 to 0.9, p = 0.042] but was ineffective in reducing the incidence of severe AMS [OR: 0.46; 95% CI, 0.14 to 1.41, p = 0.17]. Inhaled budesonide was also effective in maintaining SpO2 (SMD: 0.47; 95% CI, 0.09 to 0.84, p = 0.014) at high altitude. However, it was not effective in maintaining or improving pulmonary function at high altitude. Systematic-review found no adverse effects of budesoide in the dose used for prophylaxis of AMS. Conclusions Our systematic review showed that prophylactic inhaled budesonide is effective in preventing mild AMS during emergency ascent but not effective in preventing severe AMS. Though statistically significant, authors recommend caution in interpretation of data and questions for further well designed randomized studies to evaluate the role of budesonide in prophylaxis of AMS during an emergent ascent.

Background: Acute Mountain Sickness (AMS) is a pathophysiologic process that occurs in non-acclimated susceptible individuals rapidly ascending to high-altitude. Barometric pressure falls at high altitude and it translates to a decreased partial pressure of alveolar oxygen (PAO2) and arterial oxygen (PaO2). A gradual staged ascent with sufficient acclimatization can prevent AMS but emergent circumstances requiring exposure to rapid atmospheric pressure changes - such as for climbers, disaster or rescue team procedures, and military operations - establishes a need for effective prophylactic medications. This systematic review and meta-analysis aim to analyze the incidence of AMS during emergent ascent of non-acclimatized individuals receiving inhaled budesonide compared to placebo.Methods: This current meta-analysis was conducted according to the guidance of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. We searched PubMed, Google Scholar and Embase for relevant studies. The efficacy of budesonide in reducing incidence of AMS was evaluated by calculating the pooled ORs and 95% CIs. The efficacy of budesonide in maintaining hemoglobin-oxygen saturation was evaluated by calculating standard mean difference (SMD) and 95% confidence intervals.Results: We found that at high altitude, inhaled budesonide was effective in reducing the incidence of mild AMS [OR: 0.37; 95% CI, 0.14 to 0.9, p = 0.042] but was ineffective in reducing the incidence of severe AMS [OR: 0.46; 95% CI, 0.14 to 1.41, p = 0.17]. Inhaled budesonide was also effective in maintaining SpO2 (SMD: 0.47; 95% CI, 0.09 to 0.84, p = 0.014) at high altitude. However, it was not effective in maintaining or improving pulmonary function at high altitude. Systematic-review found no adverse effects of budesoide in the dose used for prophylaxis of AMS.Conclusions: Our systematic review showed that prophylactic inhaled budesonide is effective in preventing mild AMS during emergency ascent but not effective in preventing severe AMS. Though statistically significant, authors recommend caution in interpretation of data and questions for further well designed randomized studies to evaluate the role of budesonide in prophylaxis of AMS during an emergent ascent. [ABSTRACT FROM AUTHOR]

• Measurement of pulmonary MRP1 activity with PET. • Intratracheal aerosolization of budesonide in rats. • Assessment of the effect of budesonide on pulmonary MRP1 activity. • Use of MK571 as a control inhibitor. • Transporter-mediated DDI at the pulmonary epithelium. Multidrug resistance-associated protein 1 (MRP1/ABCC1) is a highly abundant efflux transporter in the lungs, which protects cells from toxins and oxidative stress and has been implicated in the pathophysiology of chronic obstructive pulmonary disease and cystic fibrosis. There is evidence from in vitro studies that the inhaled glucocorticoid budesonide can inhibit MRP1 activity. We used positron emission tomography (PET) imaging with 6-bromo-7-[11C]methylpurine ([11C]BMP), which is transformed in vivo into a radiolabeled MRP1 substrate, to assess whether intratracheally (i.t.) aerosolized budesonide affects pulmonary MRP1 activity in rats. Three groups of rats (n = 5–6 each) underwent dynamic PET scans of the lungs after i.t. aerosolization of either [11C]BMP alone, or [11C]BMP mixed with either budesonide (0.04 mg, corresponding to the maximum soluble dose) or the model MRP1 inhibitor MK571 (2 mg). From PET-measured radioactivity concentration-time curves, the rate constant describing radioactivity elimination from the right lung (k E,lung) and the area under the curve (AUC lung) were calculated from 0 to 5 min after start of the PET scan as measures of pulmonary MRP1 activity. Co-administration of MK571 resulted in a pronounced decrease in k E,lung (25-fold, p < 0.0001) and an increase in AUC lung (5.3-fold, p < 0.0001) when compared with vehicle-treated animals. In contrast, in budesonide-treated animals k E,lung and AUC lung were not significantly different from the vehicle group. Our results show that i.t. aerosolized budesonide at an approximately 5 times higher dose than the maximum clinical dose leads to no change in pulmonary MRP1 activity, suggesting a lack of an effect of inhaled budesonide treatment on the MRP1-mediated cellular detoxifying capacity of the lungs. However, the strong effect observed for MK571 raises the possibility for the occurrence of transporter-mediated drug-drug interactions at the pulmonary epithelium with inhaled medicines. [Display omitted] [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study is to measure levels of nitrites in induced sputum in children with asthma and correlate it with clinical asthma parameters. Method: This prospective observational study was done in PGIMER, Dr. Ram Manohar Lohia Hospital, New Delhi, on 91 children aged 7-18 years with mild and moderate persistent asthma. Patients were specifically evaluated for five clinical parameters of asthma (i.e. Days of acute exacerbations, use of salbutamol as rescue medication, emergency visits, nights with cough, days of school absence) and induced sputum nitrite levels was done at the time of enrollment and 3 months after treatment with inhaled budesonide. Results: The mean age of subjects was 10.79 ± 2.563yrs. Six (6.59%) patients were not able to perform induced sputum, eighty five (93.41%) patients were suitable for data analysis. There was significant reduction in sputum nitrite levels from 33.42 ± 22.04nmol/ml at enrollment to 11.72 ± 5.61 nmol/ml (P < 0.0005) after 3 months of inhaled budesonide therapy. Significant positive correlation was found between reduction in sputum nitrite level and control of asthma symptoms: Days of acute exacerbations(r value = 0.548, P value = 0.0001), Days of salbutamol use as rescue medication (r value = 0.431, P value =< 0.0001), Number of emergency visits(r value = 0.414, P value = 0.0001), Nights with cough (r value = 0.259, P value = 0.0169), Days of school absence(r value = 0.411, P value = 0.0001). Sputum nitrite levels were significantly higher in moderate persistent asthmatics as compared to mild at the time of enrollment (P < 0.0005), which shows that induced sputum nitrite levels correlate with asthma severity. Conclusions: This study confirms that nitrites in induced sputum correlate well with clinical asthma parameters and asthma severity in children and is a simple, non invasive, and cheap method which can be used as a parameter for monitoring of asthma. [ABSTRACT FROM AUTHOR]

Summary Introduction Inhaled steroids are widely used for persistent cough treatment. Although the side effects of long-term inhaled steroids have been well described in the literature, their laryngeal side effects after short-term use have not yet been defined. The aim of this study was to evaluate the effect of 1 month application of inhaled steroid treatment on voice parameters in patients with subacute or chronic cough. Furthermore, the efficacy of inhaled steroids on cough was investigated, as well. Material and Methods This study included 46 patients (27 females and 19 males) with a persistent cough lasting at least 3 weeks and treated with inhaled steroids. All patients were examined by a pulmonologist and lung auscultation where a posteroanterior chest X-ray and spirometry were performed. The patients were also examined by an otolaryngologist. Anterior rhinoscopy, flexible fiberoptic nasopharyngoscopy, and laryngostroboscopy were performed. Also, the patients' acoustic voice analyses were performed and recorded using a multidimensional voice program. Cough symptom index (CSI) scores were used to evaluate the response to treatment. Patients with an underlying disease that was unresponsive to inhaled steroids were excluded from study. The 46 patients were administered inhaled budesonide 400 mcg twice a day, for 1 month, and their acoustic voice analyses were performed again at the end of the treatment. In addition, CSI scores were determined after stopping medication. Results When pretreatment and posttreatment acoustic voice analysis parameters (Fo, Jita, Jitt, Shim, APQ, vAm, and NHR) were compared, statistically significant differences were detected for vAm ( P = 0.001) and F 0 ( P 0.003). After treatment with inhaled steroids, the CSI score reduced from 3 to 1 (median), and the difference was statistically significant. Conclusions Inhaled budesonide treatment in the proper dose seems to be an effective treatment for persistent cough, in the selected patient group. In addition, short-term budesonide application did not cause any negative effects on the voice parameters in these patients. These findings may be related to the steroid formulation used, the application method, and the duration of treatment. Further studies are needed on a larger group of patients with different formulations of inhaled steroids to clarify aforementioned issues. [ABSTRACT FROM AUTHOR]

Background: Asthma exacerbations lead to frequent emergency visits and hospitalizations, and are associated with high morbidity and occasionally mortality. New therapeutic strategies are needed. We sought to investigate whether the addition of high-dose inhaled budesonide to standard therapy would shorten the length of stay (LOS) in hospital of children admitted for asthma exacerbations. Methods: The study was designed as a single-center, double-blind, placebo-controlled and parallel-group trial. Children aged 7-72 months and admitted with an asthma exacerbation clinical asthma score (CAS) of between 3 and 9 were allocated to either the budesonide (n = 50) or the placebo (n = 50) group. Hospital LOS was compared between children who received 2 mg/day of budesonide versus placebo in addition to standard management of asthma exacerbation involving oxygen inhalation and β2-agonist, anticholinergic and oral corticosteroid therapy. All patients were assessed every 4 h. Children with a CAS <3, a peripheral oxygen saturation >95% and normal pulmonary function, and those with a symptom-free period of at least 4 h after salbutamol treatment were discharged. Results: Total hospital LOS was significantly shorter in the budesonide group than in the placebo group (median: 44 vs. 80 h, respectively; p = 0.01). When compared with placebo, the number of inpatients was significantly less in the budesonide group at all the assessed end points (Kaplan-Meier; p = 0.022). Additionally, nebulized budesonide was found to reduce the overall cost of treatment. Conclusion: We demonstrated that, for children hospitalized for asthma exacerbations, an additional 2 mg/day of nebulized budesonide significantly reduced hospital LOS as well as the overall cost of treatment. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Here we describe a patient who developed lung abscess caused by Candida albicans. There was no evidence of disseminated/ extrapulmonary candidiasis or any immunodeficiency. However, he was taking high doses of inhaled corticosteroid for chronic airflow obstruction. CT guided percutaneous needle aspiration provided the specimen which confirmed the diagnosis of pulmonary candidiasis. His sputum culture was also positive for Candida albicans. The patient achieved favourable out-come with a 4 weeks treatment with fluconazole. The case is presented here due to unique possible association of pulmonary candidiasis with intake of high doses of inhaled corticosteroids.

Theoretically, administration of inhaled corticosteroids may allow for beneficial effects on the pulmonary system of infants with evolving or established bronchopulmonary dysplasia (BPD) with a lower risk of undesirable side effects compared to systemic corticosteroids. However, before deciding whether to use inhaled corticosteroids for BPD in routine clinical practice, the available randomized study data need to be considered. Currently published systematic reviews from the Cochrane Collaboration conclude that there is no role for inhaled corticosteroids in neither prevention nor treatment of BPD outside clinical trials. In contrast multiple observational studies indicate that a large number of preterm infants in Europe, North America and East Asia receive inhaled corticosteroids for this indication in routine clinical care. This discrepancy between evidence and practice prompted a large randomized controlled trial (RCT) investigating the role of inhaled budesonide for the prevention of BPD which was recently published and showed a significant reduction in the incidence of BPD. However, the primary outcome (a composite of death or BPD at 36 weeks postmenstrual age) was only of borderline significance as a result of a non-significant trend to increased mortality in the budesonide group. Results of the long-term follow up from this study should be considered when defining the future role of inhaled corticosteroids for BPD. Additionally, updated systematic reviews will help to determine whether the observed mortality difference between the two comparison groups represents truth or artifact. [ABSTRACT FROM PUBLISHER]

Acute asthma is the third commonest cause of pediatric emergency visits at PGIMER. Typically, it presents with acute onset respiratory distress and wheeze in a patient with past or family history of similar episodes. The severity of the acute episode of asthma is judged clinically and categorized as mild, moderate and severe. The initial therapy consists of oxygen, inhaled beta-2 agonists (salbutamol or terbutaline), inhaled budesonide (three doses over 1 h, at 20 min interval) in all and ipratropium bromide and systemic steroids (hydrocortisone or methylprednisolone) in acute severe asthma. Other causes of acute onset wheeze and breathing difficulty such as pneumonia, foreign body, cardiac failure etc. should be ruled out with help of chest radiography and appropriate laboratory investigations in first time wheezers and those not responding to 1 h of inhaled therapy. In case of inadequate response or worsening, intravenous infusion of magnesium sulphate, terbutaline or aminophylline may be used. Magnesium sulphate is the safest and most effective alternative among these. Severe cases may need ICU care and rarely, ventilatory support. [ABSTRACT FROM AUTHOR]

OBJECTIVES. The goals were to compare early school-age neurodevelopmental and respiratory outcomes for children who were treated with either early (<3 days) or delayed selective (>15 days) postnatal corticosteroid therapy and to compare systemic dexamethasone treatment with inhaled budesonide treatment. METHODS. One hundred twenty-seven (84%) of 152 survivors from the United Kingdom and Ireland who were recruited to the Open Study of Early Corticosteroid Treatment, a randomized trial of inhaled and systemic corticosteroid therapy to prevent chronic lung disease, were traced and assessed at a median age of 7 years. Outcome measures were level of disability, presence of cerebral palsy, cognitive ability, behavioral difficulties and competencies, growth, and respiratory symptoms. Results were adjusted for potential confounding variables (gestational age, birth weight, gender, prenatal steroid therapy, method of delivery, Apgar score at 5 minutes, and Clinical Risk Index for Babies score). RESULTS. There were no significant differences among the treatment groups in cognitive ability, behavioral competencies or difficulties, overall disability rates, cerebral palsy, combined outcomes of death or cerebral palsy and death or moderate/severe disability, growth, respiratory morbidity, or diastolic blood pressure. Those assigned to dexamethasone were more likely to have high systolic blood pressure and to have a diagnosis of asthma than were those assigned to budesonide. [ABSTRACT FROM AUTHOR]

Background/Aims: Asthmatic children on long-term treatment with inhaled corticosteroids (ICS) may exhibit mild adrenal suppression. We aimed to test the hypothesis that baseline adrenal function of some asthmatic children might be lower than that of others and that this difference might be accentuated by ICS therapy. Methods: A low-dose Synacthen test was performed in 41 prepubertal asthmatic children placed on long-term inhaled budesonide (400 μg/day) prior to the onset of ICS treatment, 6 and 12 months later. Five children withdrew before the 6- and another 2 before the 12-month follow-up. Results: Low adrenal function was demonstrated in 4 children (9.8%) upon recruitment and in another 8 at the 6-month evaluation (22.2%). Adrenal function normalized in the aforementioned 4 children at the 6-month evaluation, while 6 (17.6%) exhibited suppressed adrenal function at the 12-month evaluation. Three of these patients had also exhibited adrenal suppression at the 6-month visit. A significant improvement in peak cortisol values from baseline to the 6- and 12-month evaluation (95% confidence intervals: –283.9 to –69.0 and –239.8 to –50.8, respectively) was evident when children with suppressed adrenal response at the second or third evaluation were excluded. Conclusions: In many asthmatic children, adrenal response improves on long-term ICS. The expected adrenal suppression of certain patients on maintenance ICS appears to constitute a separate phenomenon. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

We investigated the changes in renal excretion of calcium, sodium, and potassium in asthmatic children treated with inhaled budesonide, an inhaled glucocorticoid. Twenty-two asthmatic patients (7 female, 15 male, mean age 10.1±4.3 years) treated with 400-600 μg/day inhaled budesonide and 23 healthy children (6 female, 17 male, mean age 10.2±2.8 years) were enrolled in the study. The parameters recorded were serum sodium, potassium, calcium, phosphorus, alkaline phosphatase (ALP), type I collagen carboxyterminal telopeptide (ICTP), osteocalcin, intact parathyroid hormone (PTH) levels, first spot morning urine calcium/creatinine ratio, sodium/potassium ratio, and daily renal calcium excretion rate (UCa-ER). These parameters were measured in the control group and pre- and post-budesonide treatment in asthmatic children. Serum electrolytes, ALP, PTH, ICTP, and UCa-ER were in the normal ranges and were not significantly different between controls and asthmatic children. Serum levels of ICTP increased, while levels of osteocalcin decreased after budesonide therapy in the asthmatic group (P=0.001, P=0.005). UCa-ER was decreased after budesonide therapy in asthmatics (P=0.000). In conclusion, moderate doses of inhaled budesonide cause hypocalciuria and decreased bone turnover. These results may be attributed to a mechanism compensating for decreased absorption of calcium in the gut due to the topical effect of swallowed budesonide rather than the systemic effects of the drug. Increased bone metabolism and decreased turnover may have an important role in this compensatory mechanism. [ABSTRACT FROM AUTHOR]

The aim of present study was to evaluate clinical, functional, and antiinflammatory effects of inhaled budesonide and oral theophylline treatments in patients with mild to moderate asthma. The study included 38 patients. After a 10-day run-in period, the patients were randomly assigned into two groups. Group 1 received inhaled budesonide (Pulmicort Turbuhaler) 800 µg/day for 4 weeks. Group 2 received oral theophylline (Talotren tablets, 200 mg twice daily) for 4 weeks. Inhaled budesonide therapy was accompanied by a significant decrease in serum interleukin (IL)-5 levels (p < 0.0005) and blood, sputum, and nasal eosinophil counts (p < 0.005). It produced a significant reduction in daytime (p < 0.01) and nighttime (p < 0.005) symptom scores and an increase in morning (p < 0.005) and evening (p < 0.05) peak expiratory flow (PEF) and forced expiratory volume in 1 sec (FEV[sub 1]) values (p < 0.01). Theophylline therapy was associated with a significant decrease in blood (p < 0.02) and nasal (p < 0.01) eosinophil counts and serum IL-5 levels (p < 0.01). It resulted in significant improvements in daytime and nighttime symptom scores (p < 0.05), and morning PEF and FEV[sub 1] values (p < 0.05). These changes were more significant in group 1 than in group 2. There was no statistically significant difference between the two groups with respect to post-treatment values. Our results confirm the role of inhaled corticosteroids in the treatment of asthma and are consistent with the recommendation that theophylline exerts an anti-inflammatory effect. Further studies should be conducted to determine long-term benefits of theophylline. [ABSTRACT FROM AUTHOR]

In recent years, measurement of serum osteocalcin has been introduced for assessment of bone turnover in patients treated with exogeneous glucocorticoids. Studies in children with asthma on inhaled glucocorticoids, however, have shown inconsistent results. The aim of the present study is to assess bone turnover in prepubertal children and in adolescents with asthma treated with inhaled budesonide using three different osteocalcin assays: the Pharmacia Osteocalcin CAP FEIA, the CIS OSTK-PR and CIS IRMA ELSA-OSTEO assays. Two studies were conducted: 1) a randomised double blind two-period crossover study of 22 prepubertal children aged 5-12 years. In one period 800 ;g budesonide was given once in the moming, in the other 400 ;g was given twice daily; 2) a randomised double blind placebo controlled two period crossover study of inhaled budesonide 400 ;g twice daily in fourteen 13-16 year old adolescents with pubertal stages IIV, In both studies, treatment periods were of four weeks duration, and blood samples were collected at the last day of each period. In the prepubertal children none of the osteocalcin assays detected any statistically significant differences between any of the periods. In the adolescent group reduced levels of osteocalcin were seen during budesonide treatment. The suppression reached statistical significance with the CAP FEIA (P = 0,03) and the OSTK-PR (P = 0,01) assays, but not with the ELSA-OSTEO assay (P = 0,06), Correlation analyses showed statistically significant correlation coefficients varying between 0,58 and 0,91 (P = 0,03 and P < 0.0001, respectively). The effect of inhaled glucocorticoids on serum osteocalcin may depend on the assay applied, and inhaled glucocorticoids have differential effects in children and adolescents. [ABSTRACT FROM AUTHOR]