Inhaled Budesonide Therapy Research Articles

Effect of inhaled budesonide therapy in term newborns with meconium aspiration syndrome

Background: Meconium aspiration syndrome is a common cause of respiratory distress in neonates. This study explores the possibility of altering the course of the disease by using anti-inflammatory agents to counter the chemical and inflammatory pneumonitis caused by meconium. The objective is to determine if inhaled budesonide therapy can alter the clinical course of the disease and improve outcome without causing any serious adverse effects. Methods: A comparative study was conducted in NICU of Cheluvamba hospital, Mysore over 12 months. Neonates with MAS were divided into interventional and control groups. Interventional group received budesonide nebulization 12th hourly starting after 6 hours of life, while control group received saline nebulization 12 hourly. Data was analysed by SPSS 20 software and student t test and chi square test were used to assess statistical significance. Results: The patient profile of the two groups was similar, with the interventional group showing early normalization of Downes score compared to controls. The duration of respiratory distress, oxygen dependency, and duration of hospital stay was significantly less in the steroid treated group compared to controls. There was no significant difference in the incidence of sepsis between the two groups, and three patients died during hospital stay due to pneumothorax with overwhelming sepsis with DIC. Conclusions: Nebulized budesonide improves clinical outcome in terms of morbidity and is relatively safe, however long term follow up required to recommend inhalational steroids as safe and effective.

Correlation of induced sputum eosinophil levels with clinical parameters in mild and moderate persistent asthma in children aged 7–18 years

ABSTRACTBackground: Treatment decisions in asthma are currently based on clinical assessment and spirometry. Sputum eosinophil, being a marker of airway inflammation, can serve as a tool for assessing severity and response to treatment in asthma patients. Objectives: To measure eosinophil percentage in induced sputum in children with asthma and correlate it with clinical asthma parameters. Methods: A prospective observational study was performed at tertiary care hospital on 91 children aged 7–18 years with newly diagnosed mild or moderate persistent asthma. Theinduced sputum eosinophil percentage was obtained at the time of enrollment and three months after treatment with inhaled budesonide. Patients were specifically evaluated for five clinical parameters of asthma, i.e., days of acute exacerbations, use of salbutamol as rescue medication, emergency visits, nighttime cough and days of school absence. Results: Sputum eosinophil percentage was high (3.1 ± 0.515%) at the time of enrollment which reduced significantly after three months of inhaled budesonide therapy [0.06 ± 0.164% (p < 0.0005)]. Children with moderate persistent asthma had significantly higher values of sputum eosinophil levels than children with mild persistent asthma at the time of enrollment (3.38 ± 0.64% vs. 2.99 ± 0.42%, p = 0.001) but the difference was not significant after three months of inhaled steroid therapy (0.07 ± 0.18 vs. 0.04 ± 0.12, p = 0.5104). A significant negative correlation was found between reduction in sputum eosinophil levels and improvement in FEV1 (r = −0.400, p = 0.0001). All the clinical asthma parameters also correlated significantly with the reduction in sputum eosinophil levels after three months of inhaled steroid therapy. Conclusion: Eosinophil levels in induced sputum correlate well with clinical asthma parameters and asthma severity in children. It is a simple, noninvasive and cheap method which can be used for the monitoring of asthma in a resource-limited setting.

Induced Sputum Nitrite Levels Correlate with Clinical Asthma Parameters in Children Aged 7-18 Years with Mild to Moderate Persistent Asthma.

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.

The role of early inhaled budesonide therapy in meconium aspiration in term newborns: a randomized control study

Objective: To study the clinical spectrum of Meconium aspiration syndrome babies and to find out the efficacy of early nebulized steroids (Budesonide) in the clinical course and outcome (morbidity and mortality) of neonates with meconium aspiration: randomized controlled trial.Method and material: A total of 78 neonates were included in the study. After randomization, intervention group received nebulization with Budesonide (0.5 mg dissolved in 2.5-ml sterile normal saline within 2 h of birth and second dose was given at 12 h of birth) whereas controls were nebulized with normal saline. All neonates were accessed for serial respiratory distress score (Downe's score), requirement (dependence) of oxygen (in days), duration of neonatal intensive-care unit (NICU) stay, any complication and their final outcome.Results: The mean days of oxygen requirement for the cases and controls were 1.79 and 3.46, respectively (p < 0.001). The mean respiratory rate in intervention group up to the age of 5 d was significantly less (p value < 0.01). There was significant difference in mean Downe’s score and mean duration of NICU stay in intervention group.Conclusion: Budesonide nebulization in meconium aspiration results in significant early improvement in general condition (early improvement in respiratory distress and early normalization of Downe’s score) of the newborn with lesser oxygen requirement, thus early discharge from NICU but has no impact on final outcome.

Inhaled budesonide therapy in cats with naturally occurring chronic bronchial disease (feline asthma and chronic bronchitis)

To describe the long term use of inhaled budesonide in cats with naturally occurring asthma and chronic bronchitis and to measure its effects. Owners of 43 cats diagnosed with asthma or chronic bronchitis, which had been prescribed 400 µg of inhaled budesonide twice daily, were contacted and information was retrieved by a questionnaire. Nineteen cats still receiving inhaled budesonide after more than 2 months were re-evaluated clinically and underwent barometric whole body plethysmography and adrenocorticotropic hormone-stimulation testing. In 20 of the cats, therapy had been withdrawn by the owners. Cats (n=23) still receiving inhaled budesonide improved clinically and 19 cats that were reevaluated had significantly lower basal PENH (P=0·048) and higher PCPenh300 (P=0·049) values than before treatment. Corticosteroid-induced side effects were not observed in any cats but hypothalamic-pituitary-adrenal axis suppression was detected in 3 of 15 cases. Treatment with inhaled budesonide was well tolerated, resulting in improvement of clinical signs and barometric whole body plethysmography parameters. Although inhaled budesonide therapy was found to cause suppression of the hypothalamic-pituitary-adrenal axis in some cats, no cats showed clinical signs attributable to corticosteroid side effects.

Surfactant Protein D and Bronchial Dysplasia in Smokers at High Risk of Lung Cancer

Surfactant dysfunction has been implicated in both lung cancer and COPD. This study evaluated the relationship between surfactant protein D (SP-D) and the progression of bronchial dysplasia in heavy smokers. SP-D and oxidized glutathione levels were determined in samples of BAL fluid from 71 ex-smokers and current heavy smokers who participated in a lung cancer chemoprevention study with inhaled budesonide therapy. Bronchoscopy with biopsies was performed at baseline and was repeated at 6 months. The primary end point was the progression of bronchial dysplasia over 6 months. Log-normalized SP-D levels in BAL fluid were significantly associated with the progression of bronchial dysplasia. A 1-U decrease in log-normalized SP-D levels at baseline was associated with a 3.2-fold increase (95% confidence interval, 1.24 to 8.26) in the risk for progression. Reduced FEV(1) also predicted the progression of bronchial dysplasia (p < 0.05). Additional reductions in BAL fluid SP-D levels over the 6 months further increased the risk of progression (odds ratio, 1.76 for a 1-U decrease in log-normalized SP-D levels in BAL fluid; p = 0.023). Thirty-seven percent of the variation in SP-D levels in BAL fluid was related positively to the subject's FEV(1)/FVC ratio, and inversely to their plasma C-reactive protein levels and number of pack-years of smoking. Reduced SP-D expression in BAL fluid was associated with the progression of bronchial dysplasia. SP-D levels in BAL fluid may serve as a potential biomarker to identify smokers who are at risk of early lung cancer.

Safety of Inhaled Budesonide

Inhaled corticosteroid (ICS) therapy is central to the long-term management of asthma and is extensively used in the management of chronic obstructive pulmonary disease (COPD). While administration via inhalation limits systemic exposure compared with oral or injected corticosteroids and, therefore, the risk of systemic corticosteroid-related adverse effects, concerns over the long-term safety of ICS persist. The assessment of the long-term effects of ICS therapy requires considerable research effort over years or even decades. Surrogate markers/predictors for clinical endpoints such as adrenal crisis, reduced final height and fractures have been identified for use in relatively short-term studies. However, the predictive value of such markers remains questionable.Inhaled budesonide has been available since the early 1980s and there is a considerable evidence base investigating the safety of this agent. To assess the long-term safety of inhaled budesonide therapy in terms of the actual incidence of the clinical endpoints adrenal crisis/insufficiency, reduced final height, fractures and pregnancy complications, we undertook a review of the scientific literature. The external databases BIOSIS, Cochrane Central Register of Controlled Trials, Current Contents, EMBASE, International Pharmaceutical Abstracts and MEDLINE were searched, in addition to AstraZeneca's internal product literature database Planet, up to 29 February 2008. Only original articles of epidemiological studies, national surveys, clinical trials and case reports concerning inhaled budesonide were included.Eight surveys of adrenal crisis were found. The only survey with specified criteria for diagnosis involved 2912 paediatricians and endocrinologists and revealed 33 patients with adrenal crisis associated with ICS therapy; only one patient used budesonide (in co-treatment with fluticasone propionate). In addition, 14 case reports of adrenal crisis in budesonide-treated patients were found. In only two of these, budesonide was used at recommended doses and in the absence of interacting medication.Three retrospective studies and one prospective study assessing final height were found. None of them showed any reduced final height in patients receiving inhaled budesonide during childhood or adolescence.Seventeen epidemiological studies investigating the risk of fractures were found. When adjusting for confounding factors, they did not provide any unequivocal data for an increased fracture risk with budesonide. Four prospective placebo-controlled clinical trials of 2-6 years duration with inhaled budesonide in patients with asthma or COPD were found. None of the studies identified any association between inhaled budesonide and increased risk for fractures.Four studies using data from the Swedish birth and health registries showed there was no increased risk for congenital malformations, cardiovascular defects, decreased gestational age, birth weight or birth length among infants born to women using inhaled budesonide during pregnancy compared with the general population. This was confirmed by five observational studies in Australia, Canada, Hungary, Japan and the US. Similarly, one randomized clinical trial comparing pregnancy outcomes among asthma patients receiving inhaled budesonide or placebo did not demonstrate any difference in outcome of pregnancy.In summary, based on 25 years of experience with different doses and in different populations, inhaled budesonide therapy only in very rare cases appears to be associated with an increased risk of adrenal crisis, reduction in final height, increases in the number of fractures or complications during pregnancy.

The Effectiveness of High-Dose Inhaled Budesonide Therapy in the Treatment of Acute Asthma Exacerbations in Children

Purpose of the Study. The purpose of this study was to evaluate the efficacy of high-dose inhaled budesonide, in comparison to oral methylprednisolone, in the treatment of acute asthma exacerbations in children. Study Population. Sixty children, ages 4 to 17 years, who had experienced an acute asthma exacerbation over a period of 6 months. All patients met the American Thoracic Society criteria for asthma. Methods. Children who experienced an acute asthma attack unresponsive to home management, yet not severe enough to be hospitalized, were randomized into 2 groups. Group 1 received high-dose inhaled budesonide (1600 μg daily) plus dry powder terbutaline (2000 μg daily). Group 2 received oral methylprednisolone (1 mg/kg/day) plus …

Efficacy of budesonide in moderate to severe asthma

Background: The worldwide prevalence of asthma is increasing by ∼50% per decade. Budesonide is one of several inhaled corticosteroids available for the treatment of asthma and has been extensively evaluated in clinical trials.Objective: This article reviews the published literature on the efficacy of budesonide in the management of adult and pediatric patients with moderate to severe asthma and compares budesonide with other inhaled corticosteroids and nonsteroidal treatment options.Methods: All controlled, randomized studies in patients with moderate or severe asthma were considered for inclusion. Relevant studies were identified through a MEDLINE search of the period from 1980 to 2000 using the terms budesonide plus efficacy, with or without the terms fluticasone, mometasone, and beclomethasone. The manufacturer's reference database was used to identify additional publications.Results: Budesonide is associated with a dose-response effect in adults and children with moderate to severe asthma. The data on budesonide are in line with the current recommendation for a high starting dose of inhaled corticosteroid (800 μg/d), followed by downward titration to the minimal effective dose. Budesonide administered by Turbuhaler™ (AstraZeneca Pharmaceuticals LP, Wilmington, Del) dry-powder inhaler (DPI) was effective at a significantly lower dose than beclomethasone dipropionate (BDP) administered by pressurized metered-dose inhaler (pMDI) (P = 0.009), whereas its efficacy was similar to that of BDP delivered by hydrofluoroalkane pMDI and that of fluticasone propionate administered by DPI. Inhaled budesonide therapy was shown to be oral corticosteroid sparing in patients with severe asthma, thus reducing the total corticosteroid dose and the risk of systemic side effects. Pulmicort Respules® (AstraZeneca), a nebulized formulation, was effective in the treatment of moderate to severe asthma in patients aged ≥12 months.Conclusions: Once- or twice-daily administration of budesonide delivered via the Turbuhaler and Pulmicort Respules systems has been shown to be well tolerated and efficacious in populations with moderate to severe asthma.

Which Factors Predict Success After Discontinuation of Inhaled Budesonide Therapy in Children with Asthma?

Urinary eosinophil protein X (UEPX) concentration, lung function, and nonspecific bronchial hyperreactivity were determined in 40 asthmatic children (asymptomatic for 6.4 ± 3.0 months) (mean age 9.8 ± 2.9 years) receiving inhaled budesonide, in order to establish whether measurement of these parameters is useful in determining discontinuation of inhaled corticosteroid therapy. After the discontinuation of therapy, patients were asked to come to the Outpatient Clinic if symptoms recurred and did not respond to β2 mimetic usage in 24 hr. Otherwise they were to be seen 2–3 months later for a follow-up visit. UEPX concentration was determined and spirometry was performed on this visit. While UEPX concentrations had increased (p < 0.000l), FEV1, FEF 25–75 and PEF had decreased significantly 2.3 ± 0.53 months after the cessation of inhaled budesonide therapy in all children (p = 0.004, p = 0.02, p = 0.02, respectively). Due to clinical deterioration, inhaled corticosteroid therapy had to be restarted in 19 (48%) of the children (Group I), while the remaining 21 (52%) (Group II) continued to be asymptomatic during the 2.3 ± 0.5 months follow-up period. Although the initial UEPX concentrations, spirometer variables, and methacholine PC20 values of these two groups were not statistically different, the duration of clinical remission before discontinuation of budesonide prophylaxis was significantly longer in group II (p = 0.0037). We concluded that, in determining discontinuation of inhaled corticosteroid prophylaxis, duration of clinical remission seems to be a more useful criterion than measurement of UEPX levels, lung function test, and assessment of bronchial hyperreactivity.

Effect of inhaled budesonide therapy on lung function in schoolchildren born preterm

We investigated the effect of inhaled glucocorticoid (GC) on bronchial obstruction and on bronchial lability in schoolchildren born preterm. Twenty-one children with bronchial obstruction, increased responsiveness to a β 2 -agonist, and/or increased diurnal variation in peak expiratory flow (PEF) were selected for an open longitudinal study of the value of inhaled GC. None of these children had an earlier diagnosis of asthma or current GC treatment. Eighteen children with median (range) birth weight 1025 (640–1600) g and gestational age 28 (24–35) weeks, age at study 10·1 (7·7–13) years, were treated with inhaled budesonide in initially high (0·8 mg m −2day −1for 1 month) and subsequently lower dose (0·4 mg m −2day −1for 3 months). Daily symptom scores were recorded. Spirometric values were measured in the clinic at the beginning and end of each treatment period. At home, children used a data storage spirometer. After treatment with budesonide for 4 months, spirometric values in the clinic did not significantly change. The median forced expiratory volume in 1 sec (FEV 1) was 74% of predicted both at entry and after budesonide treatment. However, the median number of ≥20% diurnal change in PEF values at home decreased during treatment. According to the present study, inhaled budesonide for 4 months had no significant effect on basic lung function but may decrease bronchial lability in schoolchildren born preterm.

The effectiveness of high-dose inhaled budesonide therapy in the treatment of acute asthma exacerbations in children

International guidelines recommend the use of systemic steroids for the treatment of acute asthma attack if it has not been resolved within 24 to 36 hours of home management with regular beta2 mimetic inhalation. Such therapy for infrequent exacerbations is unlikely to have serious systemic effects. Unfortunately, many patients receiving frequent courses are potentially at risk for corticosteroid-induced side effects such as adrenal suppression, depression of linear growth, and osteoporosis. To decrease the use of frequent oral corticosteroid courses in children, this study was designed to evaluate the efficacy of high-dose inhaled steroids in comparison with oral steroids, in the therapy of acute asthma exacerbations in children. Sixty children who have experienced an acute exacerbation of asthma unresponsive to home management with regular use of inhaled beta2 mimetics, yet not severe enough to hospitalize, were randomized to be treated with either high-dose inhaled budesonide (1,600 microg daily) or oral methylprednisolone (1 mg/kg daily) plus medium-dose inhaled budesonide (800 microg daily, both in addition to inhaled terbutaline, 2,000 microg daily). Pre- and posttreatment pulmonary index scores, forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC and forced expiratory flow 25% to 75% (FEF25%-75%) were evaluated. The mean number of decrease in pulmonary index score was 2.61 +/- 1.12 in the high-dose budesonide-receiving group (group I) and 1.90 +/- 1.08 in the oral steroid-receiving group (group II). There was a statistically significant difference between the two groups, in favor of group I (P = .038). No statistically significant difference was detected between the two groups with respect to the increase in lung function test measurements (FEV1, FEV1/FVC, FEF25%-75%; P = .790, .959, .819, respectively). Short-term high-dose budesonide therapy can be considered an alternative for children who are experiencing an acute asthma attack that is unresponsive to home management with regular use of an inhaled beta2 mimetic, yet who are not severe enough to hospitalize.

Efficacy of Inhaled Budesonide and Oral Theophylline in Asthmatic Subjects

The aim of present study was to evaluate clinical, functional, and anti-inflammatory 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 (FEV1) 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 FEV1 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.

Inhaled corticosteroid therapy is safe in tuberculin-positive asthmatic children.

Although treatment with oral corticosteroids can cause reactivation of latent Mycobacterium tuberculosis (TB) infection in purified protein derivative (PPD)-positive individuals with no evidence of clinical disease, little is known about the effects of inhaled corticosteroids in this respect. This study was undertaken to assess whether inhaled corticosteroid (CS) therapy reactivates latent TB infection in PPD-positive asthmatic children. We studied 32 PPD skin test-positive (> or =10 mm) children [age (mean +/- SD), 7.9 +/- 4.1 years] with no family history and no evidence of TB infection on chest radiograms who were receiving inhaled budesonide for the treatment of asthma. They were further evaluated with thorax computed tomography (CT) and erythrocyte sedimentation rate and closely observed for an additional 9 months. At enrollment the mean diameter of PPD reaction was 12.8 +/- 2.7 mm. The mean duration of inhaled CS treatment and the mean cumulative CS dose were 9.8 +/- 7.6 months and 275 +/-199 mg, respectively. Thorax CT studies revealed mediastinal lymph nodes in 7 of the 32 patients. There was no significant difference between children with and without mediastinal lymph nodes according to age, gender, size of PPD skin testing, erythrocyte sedimentation rate and duration and cumulative CS dose of inhaled budesonide therapy before study. A second thorax CT was obtained 9 months later in those 7 patients with lymphadenopathy (additional mean cumulative CS dose, 222.57 mg). There was no change in the size of their lymph nodes. Long term inhaled budesonide therapy appears to be safe in PPD-positive asthmatic children.

25 The effectiveness of high dose inhaled budesonide therapy in the treatment of acute asthma exacerbations in children

25 The effectiveness of high dose inhaled budesonide therapy in the treatment of acute asthma exacerbations in children

Changes in asthmatic patients' symptoms and lifestyles on institution of inhaled budesonide therapy

An open, multi-centre, general practice study was carried out in 1661 asthmatic patients to assess the efficacy, in terms of symptom relief and changes in lifestyle, of budesonide and to record objective lung function changes and any adverse events. After a 1-week run-in period on any pre-trial anti-asthma medication, patients received either 200 micrograms or 400 micrograms budesonide twice daily by metered dose inhaler for 4 weeks. Peak expiratory flow rate (PEFR) was measured by the doctor on entry, after the run-in, and at the end of the study and patients were asked to complete diary cards on a daily basis to record compliance, bronchodilator usage and the severity of cough, wheeze and sleep disturbance, and weekly to record 5 lifestyle assessments, e.g. physical activity. Analysis of data from the clinic visits and 1375 completed diary cards showed that PEFR increased significantly from 321 +/- 3 l/min at the end of the run-in to 368 +/- 3 l/min at the end of the trial; 77% of patients had an improved PEFR. Bronchodilator use decreased significantly from 4.2 +/- 0.1 times/day during the run-in period to 3.0 +/- 0.1 times/day at the end of the study; 65% of patients used less bronchodilator. Significant improvements were recorded in all the symptoms and lifestyle indices monitored; 76% of patients improved in at least 5 of the 11 assessments. Treatment-emergent adverse events occurred in 103 (6%) of patients: none was classified as serious or unexpected. No sub-group of patients was identified in which the results were at variance from the full sample. It is concluded that budesonide improves patients' lifestyle and ability to carry out normal activities, as well as improving PEFR and reducing bronchodilator use, in mild to moderately severe asthmatics treated in general practice.