pulmicort and Lung-Diseases

Chronic lung disease (CLD) remains an important cause of mortality and morbidity in preterm infants and inflammation plays an important role in its pathogenesis. The use of inhaled corticosteroids may modulate the inflammatory process without concomitant high systemic steroid concentrations and less risk of adverse effects.. To determine the effect of inhaled versus systemic corticosteroids started within the first two weeks of life on preventing CLD in ventilated very low birth weight (VLBW) infants.. Randomised and quasi-randomised trials were identified by searching The Cochrane Library, MEDLINE , EMBASE , CINAHL, reference lists of published trials and abstracts published in Pediatric Research or electronically on the Pediatric Academic Societies web site in June 2007.This search was updated in June 2011 and included additional searches of Clinicaltrials.gov, Controlled-trials.com and Web of Science.. Randomised or quasi-randomised clinical trials comparing inhaled versus systemic corticosteroid therapy (regardless of the dose and duration of therapy) started in the first two weeks of life in VLBW infants receiving assisted ventilation.. Outcomes including CLD at 28 days or 36 weeks postmenstrual age (PMA), mortality, the combined outcome of death or CLD at 28 days or 36 weeks PMA, other pulmonary outcomes and adverse effects were evaluated. All data were analysed using RevMan 5.1. Meta-analyses were performed using relative risk (RR), risk difference (RD), and mean difference (MD) with their 95% confidence intervals (CI). If RD was significant, the numbers needed to benefit (NNTB) or to harm (NNTH) were calculated.. No new trials were identified in this update. Two trials qualified for inclusion in this review. The incidence of CLD at 36 weeks PMA was increased (of borderline statistical significance) in the inhaled steroid group [RR 1.45 (95% CI 0.99 to 2.11); RD 0.11 (95% CI 0.00 to 0.21), p = 0.05, one trial, n = 278]. The incidence of CLD at 36 weeks PMA among all survivors [RR 1.34 (95% CI 0.94 to 1.90); RD 0.11 (95% CI -0.02 to 0.24), one trial, n = 206], oxygen dependency at 28 days (two trials, n = 294), death by 28 days (two trials, n = 294) or 36 weeks PMA (two trials, n = 294) and the combined outcome of death or CLD by 28 days (two trials, n = 294) or 36 weeks PMA (one trial, n = 278) did not differ significantly between the groups. The duration of mechanical ventilation was significantly longer in the inhaled steroid group as compared to the systemic steroid group [typical MD 4 days (95% CI 0.2 to 8); two trials, n = 294] as was the duration of supplemental oxygen [typical MD 11 days (95% CI 2 to 20); two trials, n = 294]. The incidence of hyperglycaemia was significantly lower in the group receiving inhaled steroids [RR 0.52 (95% CI 0.39 to 0.71); RD -0.25 (95% CI -0.37 to -0.14); one trial, n = 278; NNTB 4 (95% CI 3 to 7) to avoid one infant experiencing hyperglycaemia]. The rate of patent ductus arteriosus was increased in the group receiving inhaled steroids [RR 1.64 (95% CI 1.23 to 2.17); RD 0.21 (95% CI 0.10 to 0.33); one trial, n = 278; NNTH 5 (95% CI 3 to 10)]. No information was available on long-term neurodevelopmental outcomes.. This review found no evidence that early inhaled steroids confer important advantages over systemic steroids in the management of ventilator dependent preterm infants. Neither inhaled steroids nor systemic steroids can be recommended as a part of standard practice for ventilated preterm infants. Because they might have fewer adverse effects than systemic steroids, further randomised controlled trials of inhaled steroids are needed that address risk/benefit ratio of different delivery techniques, dosing schedules and long-term effects, with particular attention to neurodevelopmental outcome.

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Beclomethasone; Budesonide; Chronic Disease; Dexamethasone; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Lung Diseases; Randomized Controlled Trials as Topic; Respiration, Artificial; Respiratory System Agents; Steroids

A wide range of topics can be covered when considering a review of respiratory therapeutics. This review focuses on advances and controversies in the therapy of asthma, including issues regarding medications such as inhaled beta 2-agonists, inhaled corticosteroids, cromolyn sodium, and theophylline. Bronchodilator therapy for acute viral bronchiolitis remains a controversial issue and is discussed in light of recent published manuscripts. Issues regarding surfactant therapy for respiratory distress syndrome remain prominent in the neonatal respiratory therapeutics literature and recent findings in this area are reported. Advances in the treatment of cystic fibrosis, as well as a review concerning the pulmonary toxicity of various medications used in the treatment of pediatric illness are discussed.

Topics: Adrenal Cortex Hormones; Adrenergic beta-Agonists; Anti-Inflammatory Agents; Asthma; Bronchiolitis, Viral; Bronchodilator Agents; Budesonide; Child; Cystic Fibrosis; Hemosiderosis; Humans; Infant, Newborn; Lung Diseases; Methotrexate; Pregnenediones; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn; Theophylline

We hypothesized that the use of inhaled budesonide (BUD) would alter somatic growth by increasing energy expenditure (EE) in premature infants with chronic lung disease (CLD).. A prospective study was conducted of the effect of BUD on EE, growth and salivary cortisol excretion in infants with CLD who required supplemental oxygen and were treated with inhaled BUD for 4 weeks according the severity of their CLD, or without BUD treatment. Infants were compared with a healthy control group matched for gestational age. EE, anthropometric measures and salivary cortisol levels were examined before, during and after BUD treatment.. A total of 30 spontaneously breathing premature infants were enrolled in the study. EE in CLD (BUD) and CLD (no BUD) patients were greater than EE in healthy preterm infants (p < 0.01) at the study time points. Growth did not differ between the groups. Salivary cortisol levels of treated infants were significantly lower when compared with the levels of nontreated infants.. The administration of inhaled BUD in preterm infants with CLD was associated with an increase in EE, a suppression of endogenous cortisol production and with no effect on duration of supplemental oxygen, but did not compromise their somatic growth.

Topics: Administration, Inhalation; Budesonide; Energy Metabolism; Growth; Humans; Hydrocortisone; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Lung Diseases

Budesonide is an inhaled steroid with a strong topical effect but with minimal systemic effects; it has been effectively delivered to animal lungs using surfactant as a vehicle. The purposes of this study were to determine whether early intratracheal instillation of budesonide using surfactant as a vehicle would improve pulmonary status, reduce mortality, and reduce chronic lung disease morbidity.. We conducted a prospective, randomized blind trial in 116 very low birth weight infants (< 1500 g) who had severe radiographic respiratory distress syndrome and required mechanical ventilation with fraction of inspired oxygen > or = 0.6 shortly after birth: 60 were in the treated group (intratracheal instillation of a mixture of 0.25 mg/kg of budesonide and 100.00 mg/kg of survanta, every 8 hours) and 56 were in the control group (100 mg/kg of survanta only, every 8 hours). The end point assessment was the number of infants who would die or develop chronic lung disease at 36 weeks' postconceptional age.. Infants in the treatment group required significantly lower mean airway pressure on day 1 and day 3 and had significantly lower oxygen index and PCO(2) during the first 3 days than infants in the control group. More infants were extubated in the treatment group than controls at 1 and 2 weeks. The combined outcome of deaths or chronic lung disease was significantly lower in the treatment group than in the control group (19 of 60 vs 34 of 56). No clinically significant adverse effects were observed during the study.. This pilot study indicated that early postnatal intratracheal instillation of budesonide using surfactant as vehicle significantly improved the combined outcome of death or chronic lung disease in small premature infants without causing immediate adverse effects. The results are encouraging, and a large sample multicenter trial is warranted.

Topics: Biological Products; Budesonide; Chronic Disease; Double-Blind Method; Female; Glucocorticoids; Humans; Infant, Newborn; Infant, Very Low Birth Weight; Instillation, Drug; Lung Diseases; Male; Pharmaceutical Vehicles; Prednisolone; Pulmonary Surfactants; Respiration, Artificial; Respiratory Distress Syndrome, Newborn; Survival Rate

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.. 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).. 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.. Although postnatal steroid therapy has been associated with poor long-term outcomes, this study failed to show significant differences in cognitive function between dexamethasone- and budesonide-allocated groups. There may be increased systolic blood pressure and a greater likelihood of developing asthma in childhood after postnatal dexamethasone treatment.

Topics: Administration, Inhalation; Age Factors; Budesonide; Child; Child Development; Dexamethasone; Female; Follow-Up Studies; Glucocorticoids; Humans; Ireland; Lung Diseases; Male; Nervous System; United Kingdom

To compare the effects of inhaled and systemic steroids on growth in very low birthweight (VLBW) infants with chronic lung disease (CLD).. Sixteen babies with CLD randomly received inhaled budesonide (100 microg four times daily for 10 days via Aerochamber) or systemic steroids (dexamethasone 0.5 mg/kg/day, reducing over nine days). Linear growth (lower leg length, LLL) was measured by knemometry twice weekly.. The gestational age, birth weight, postnatal age, and LLL velocity (LLLvel) were similar between the two groups at the start of treatment. At the end of the treatment period, LLLvel was reduced in the dexamethasone group (mean -0.01 mm/day) but had increased in the budesonide group (mean 0.48 mm/day). Mean weight gain was non-significantly lower in the dexamethasone group (5.8 g/kg/day) compared to the budesonide group (mean 12.7 g/kg/day).. Inhaled budesonide has less short term effects on growth than systemically administered dexamethasone.

Topics: Administration, Inhalation; Bronchodilator Agents; Budesonide; Chronic Disease; Dexamethasone; Glucocorticoids; Growth Disorders; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Lung Diseases; Weight Gain

We investigated the effect of an aerosolized corticosteroid (budesonide) on the oxygen requirement of infants at high risk for developing chronic lung disease (CLD) in a randomized, double-blind study. The study objective was to attain a 30% decrease in FiO2 levels in the budesonide treatment group after 14 d of therapy. Thirty very low birthweight (VLBW) infants (median (range)) gestational age 26 wk (23-29) and birthweight 805 g (525-1227) were randomized. Inclusion criteria were mechanical ventilation on day 6 of life, or if extubated on nasal continuous positive airway pressure with FiO2 > or = 0.3. The budesonide (Pulmicort) dose was 500 microg bid, or placebo. The aerosol was delivered with a dosimetric jet nebulizer, with variable inspiratory time and breath sensitivity. Inhalations were started on day 7 of life. Twenty-seven patients completed the study. A significant lowering of the FiO2 levels at 21 d of life was not detected. Infants who received budesonide were more often extubated during the study period (7/8 vs 2/9) and had a greater relative change from baseline in their oxygenation index (budesonide decreased 26% vs placebo increased 60%). Subsequent use of intravenous dexamethasone or inhaled budesonide in the treatment group was significantly less. All patients required O2 supplementation on day 28 of life. At 36 wk postconceptual age, 61% of infants in the budesonide group needed supplemental O2 as opposed to 79% in the placebo group. No side effects on growth or adrenal function were observed.. We conclude that inhaled budesonide aerosol via dosimetric jet nebulizer started on day 7 of life for infants at high risk for developing CLD decreases the need for mechanical ventilation similar to intravenous dexamethasone, but without significant side effects.

Topics: Aerosols; Birth Weight; Bronchodilator Agents; Budesonide; Chronic Disease; Double-Blind Method; Female; Gestational Age; Humans; Hydrocortisone; Infant; Infant, Newborn; Infant, Very Low Birth Weight; Lung Diseases; Male; Respiration, Artificial; Respiratory Distress Syndrome, Newborn; Weight Gain

Allergen inhalation by sensitized subjects results in acute bronchoconstriction, which can be followed by a later bronchoconstrictor response, allergen-induced airway hyperresponsiveness, and increases in airway inflammatory cells. Treatment with inhaled glucocorticosteroids attenuates allergen-induced asthmatic airway responses. The purpose of this study was to determine whether a 1-wk pretreatment with inhaled budesonide influences allergen-induced changes in inflammatory cells in blood and induced sputum. Seven subjects with mild atopic asthma were treated in a double-blind, placebo-controlled, randomized, crossover fashion with either inhaled budesonide 400 microg/d, or placebo for 7 d. Allergen challenges were carried out the morning after treatment was discontinued and sputum samples were obtained 7 h after allergen inhalation. Methacholine airway responsiveness was measured, and blood and sputum samples were obtained 24 h post-allergen. Budesonide treatment attenuated the magnitude of both the early and the late asthmatic response, reduced allergen-induced methacholine airway hyperresponsiveness, and attenuated allergen-induced increases in total eosinophils and activated eosinophils. These results suggest that the effects of inhaled glucocorticosteroids on allergen-induced airway responses may be mediated through their inhibition of allergen-induced eosinophil migration and activation.

Topics: Administration, Inhalation; Adult; Allergens; Bronchoconstriction; Bronchoconstrictor Agents; Bronchodilator Agents; Budesonide; Double-Blind Method; Eosinophils; Female; Humans; Lung Diseases; Male; Methacholine Chloride; Pregnenediones

The aim of this randomized, double-blind, placebo-controlled trial was to assess the short-term effect of a topical glucocorticoid (budesonide 600 mu g twice daily) vs. placebo administered by metered dose inhaler (MDL) and spacer (Aerochamber MV15) directly into endotracheal tube of intubated infants for 7 days. Twenty preterm infants (mean birthweight, 1,030 g; mean gestational age, 27.3 weeks)who still needed assisted ventilation at 14 days of age were randomly assigned to receive budesonide (n=9) or placebo (n=11) and completed the study. The primary outcome was the need for mechanical ventilation after 7 days of treatment. Other outcome variables included ventilator settings, blood gases, serum cortisol levels, and bronchoalveolar lavage inflammatory cell counts. No ventilated infant was extubated during the study period. The treatment group showed significant improvements in mean peak inspiratory pressure, ventilator efficiency index, and (A-a) oxygen difference. There were no changes in the placebo group. Serum cortisol levels and bronchoalveolar lavage cell counts did not change significantly during study period. There was no difference in side effects between the groups. This trial demonstrates that topical budesonide administered by MDL and Aerochamber produces clinical improvement in ventilated preterm infants, without glucocorticoid side effects.

Topics: Administration, Inhalation; Administration, Topical; Aerosols; Anti-Inflammatory Agents; Bronchoalveolar Lavage Fluid; Budesonide; Double-Blind Method; Female; Humans; Hydrocortisone; Infant, Newborn; Infant, Premature, Diseases; Lung Diseases; Male; Nebulizers and Vaporizers; Pilot Projects; Pregnenediones; Respiration, Artificial; Time Factors; Treatment Outcome

The aim of this investigation was to compare inhaled budesonide vs oral prednisone in the maintenance phase treatment of pulmonary sarcoidosis. Double-blind controlled study was performed in 40 patients with stage II or III pulmonary sarcoidosis. After initial systemic 6 weeks treatment with prednisone (40 reduced to 20 mg daily) patients were allocated either to systematically (P) or topically (B) treated group. P patients continued with 10 mg prednisone daily, B patients were given inhaled budesonide 1.6 mg daily. The progress of treatment was assessed by serial radiography, spirometry, serum ACE activity and plasma cortisol levels. All patients completed the 12 months treatment. Using a numerical score to assess changes on the chest radiograms P patients improved by 1.7 +/- 0.66 points; B patients improved by 1.15 +/- 0.81 points. Spirometric changes were insignificant. Serum ACE fell from 107 +/- 51 U/L in the P group and 92 +/- 40 U/L in the B group to 46 +/- 11 U/L and 38 +/- 21 U/L respectively during the initial phase of treatment. In the maintenance phase ACE levels remained lower than initial ones in both groups. Morning cortisol plasma levels studied in 10 patients (5 in each group) decreased significantly during the initial phase. Thereafter cortisol levels remained low in the P patients returning to the lower limit of normal values in the B patients. We conclude that inhaled budesonide may be a safe and effective alternative to oral steroids in the maintenance treatment of pulmonary sarcoidosis especially in the early, stage II, disease.

Topics: Administration, Inhalation; Administration, Oral; Adult; Aged; Bronchodilator Agents; Budesonide; Double-Blind Method; Female; Humans; Lung Diseases; Male; Middle Aged; Placebos; Prednisone; Pregnenediones; Respiration; Sarcoidosis; Time Factors

We investigated the effect of inhaled corticosteroids on the phenotypes and functional capacity of macrophages obtained by bronchoalveolar lavage from patients with pulmonary sarcoidosis. The results were correlated with clinical status and therapeutic efficacy. Ten symptomatic sarcoid patients (previously untreated) with radiological parenchymal shadowing and abnormal pulmonary function received inhaled budesonide, 800 micrograms m twice daily via a Nebuhaler for 16 weeks. A placebo group included ten healthy volunteers and five sarcoid patients with similar features to the treated group. Drug distribution studies showed that 10% of the inhaled drug was deposited in the alveolar region. All ten treated sarcoid patients had symptomatic relief with no adverse effects. Three of these ten patients had significant resolution of their radiological shadowing. No significant difference in pulmonary function was observed. At the cellular level, a significant decrease in lavage lymphocytosis was seen after 16 weeks, during which time there was a concomitant change in the phenotype and functional characteristics of the alveolar macrophage population. No similar changes were observed in the placebo group. Our results suggest that inhaled budesonide can modulate the aberrant immunological reactions existent in the lung in pulmonary sarcoidosis, and produce concomitant symptomatic relief with no side effects. It is postulated that this effect may occur through action on the local alveolar macrophage population.

Topics: Administration, Inhalation; Adult; Anti-Inflammatory Agents; Bronchoalveolar Lavage Fluid; Budesonide; Female; Humans; Lung Diseases; Lymphocyte Culture Test, Mixed; Macrophages; Male; Phenotype; Pregnenediones; Sarcoidosis

In a randomized, double-blind study 19 patients with newly-detected pulmonary sarcoidosis were treated with either inhaled budesonide, 800 micrograms twice daily (n = 9), or placebo (n = 10) for 8-10 weeks. Before and after treatment, chest roentgenograms, lung function tests, bronchoalveolar lavage (BAL) and biochemical tests were performed. Angiotensin converting enzyme (ACE) activity and beta2-microglobulin (beta 2M) concentrations were measured in serum. The same tests, as well as albumin and hyaluronan were measured in the BAL-fluid. The total cell number in BAL-fluid, differential counts and lymphocyte subpopulations were determined (total T- and B-lymphocytes, T-helper/inducer (OKT-4) and T-suppressor/cytotoxic (OKT-8) lymphocytes). No significant changes in chest roentgenograms or lung function tests were observed during the short study time. However, a decrease in serum ACE (p less than 0.1) and beta 2 M (p less than 0.05) as well as in BAL-hyaluronan (p less than 0.01) was found in the budesonide-treated patients as well as a decrease in the percentage of BAL T-lymphocytes (p less than 0.05) and the T4/T8 ratio (p less than 0.1). No significant changes were seen in the placebo group. The findings suggest that treatment with inhaled budesonide influences biochemical and cellular findings in patients with early sarcoidosis in the same way as treatment with systemic corticosteroids. The results may also explain clinical effects seen in sarcoidosis patients treated with inhaled corticosteroids. However, further studies are required to determine the long-term clinical benefits of inhaled steroids in pulmonary sarcoidosis.

Topics: Administration, Inhalation; Adult; beta 2-Microglobulin; Bronchoalveolar Lavage Fluid; Budesonide; Clinical Trials as Topic; Double-Blind Method; Female; Glucocorticoids; Humans; Hyaluronic Acid; Lung; Lung Diseases; Male; Middle Aged; Peptidyl-Dipeptidase A; Pregnenediones; Radiography; Random Allocation; Sarcoidosis

We combined high-energy wet media milling and spray drying to engineer dry powders for inhalation consisting of geometrically large, low-density particles with superior aerodynamic properties and fast dissolution. Peclet number proved to be a useful instrument to guide choice of the additives and process conditions for generating low-density powders by spray drying. Composite dry powders consisted of milled and stabilized budesonide nanoparticles, leucine or albumin as matrix formers, and ammonium carbonate as a pore former. Powders of different composition showed fairly large and comparable geometric particle sizes (d

Topics: Administration, Inhalation; Aerosols; Budesonide; Chemistry, Pharmaceutical; Desiccation; Drug Compounding; Drug Liberation; Excipients; Humans; Lung; Lung Diseases; Models, Biological; Nanoparticles; Particle Size; Powders; Surface Properties

Topics: Administration, Inhalation; Budesonide; Child; Glucocorticoids; Hemosiderosis; Hemosiderosis, Pulmonary; Humans; Hydroxychloroquine; Lung Diseases; Male; Prednisone

Our discovery that the perinatal period involves nucleotide modifications and gene overexpression in mouse lung prompted us to evaluate whether mice may become more susceptible to cigarette smoke when exposure starts immediately after birth. We previously showed that mainstream cigarette smoke is a quite potent carcinogen in neonatal mice. Further on, we showed that exposure of mice to environmental cigarette smoke (ECS), starting at birth, results in alterations of a variety of intermediate biomarkers. However, after 4 months of exposure to ECS followed by 7 months of recovery in filtered air, the lung tumor yield was rather low. In the present study, we evaluated the protective effects of the glucocorticoid budesonide and of the dietary agent phenethyl isothiocyanate in mice exposed to ECS for 9 months followed by 2 months of recovery. After weanling, the mice exposed to ECS since birth underwent a variety of alterations of molecular and cytogenetical end points, and 11 months after birth, they exhibited significant histopathologic changes, such as pulmonary anthracosis, emphysema, hemorrhagic areas, alveolar bronchiolarization, bronchial hyperplasia, and tumors, both benign and malignant. The carcinogenic response was less evident in dams exposed to ECS under identical conditions. Both phenethyl isothiocyanate and budesonide, administered daily with the diet after weanling, attenuated several alterations of ECS-related biomarkers and moderately protected the lungs from histopathologic alterations, including tumors. Thus, although not as efficiently as the bioassay in mainstream cigarette smoke-exposed mice, the model in neonatal mice is suitable to evaluate both ECS carcinogenicity and its modulation by chemopreventive agents.

Topics: Adenoma; Age Factors; Animals; Animals, Newborn; Anticarcinogenic Agents; Apoptosis; Bone Marrow Cells; Budesonide; Carcinoma; DNA Adducts; Drug Screening Assays, Antitumor; Epithelial Cells; Female; Isothiocyanates; Lung; Lung Diseases; Lung Neoplasms; Male; Mice; Precancerous Conditions; Pregnancy; Time Factors; Tobacco Smoke Pollution

Combination of low-dose budesonide and low-dose aminophylline may improve lung function in reduced adverse effects compared with high-dose monotherapy. Adult rabbits intratracheally received 4 ml/kg of saline or meconium (25 mg/ml). Meconium-injured rabbits were treated at 0.5 and 2.5 h after meconium instillation by intravenous aminophylline (1.0 mg/kg), by intratracheal budesonide (0.125 mg/kg) followed by intravenous aminophylline (1.0 mg/kg), or were untreated. Although aminophylline improved some respiratory parameters, budesonide+aminophylline more effectively reduced intrapulmonary shunts and improved gas exchange, without significant cardiovascular effects. Combined treatment reduced lung edema and number of lung neutrophils to a higher extent than aminophylline alone. Both treatments reduced lung peroxidation and in vitro airway reactivity to histamine, with a better effect after aminophylline alone. Combination of budesonide and aminophylline enhanced respiratory parameters more effectively, having fewer side effects than aminophylline alone. However, no additive effect of budesonide was observed on lung peroxidation and in vitro airway reactivity.

Topics: Aminophylline; Animals; Animals, Newborn; Blood Pressure; Bronchodilator Agents; Budesonide; Humans; Immunoassay; Infant, Newborn; Injections, Intravenous; Leukocyte Count; Lipid Peroxidation; Lung Diseases; Meconium Aspiration Syndrome; Neutrophil Infiltration; Oxygen; Rabbits; Respiratory Function Tests; Thiobarbituric Acid Reactive Substances; Trachea

Inhaled corticosteroids (ICSs) are used by patients of all ages, but older patients may have difficulty with conventional inhalation devices and therefore may benefit from the easy-to-use delivery mechanism of the nebulizer.. To compare the outcomes, resource use, and health care costs of patients prescribed nebulized ICSs before and after treatment.. All patients 50 years and older prescribed nebulized ICSs were identified from a nationally representative managed care claims database (1999-2003). Patients with 1 year of continuous enrollment were analyzed using a retrospective cohort design; outcomes, resource use, and costs were measured and compared 6 months before and 6 months after the initial nebulized ICS prescription.. A total of 2,178 patients were identified for participation in the study, of whom 668 were analyzed. Patients were prescribed nebulized ICSs primarily for asthma (57.4%) and chronic obstructive pulmonary disease (52.1%). Nebulized ICSs were prescribed mostly by primary care physicians and pulmonologists. More than 40% of patients used nebulized ICSs persistently (at least 1 refill); persistent users averaged 123.4 days of use during 6 months of follow-up. There was a significant decrease in systemic corticosteroid use among persistent users (48.0% vs 38.8%; odds ratio, 0.7; 95% confidence interval, 0.5-1.0; P = .03). There was an emergency department visit in 20.2% and 15.0% of persistent users before and after the index date, respectively (odds ratio, 0.7; 95% confidence interval, 0.45-1.09; P = .12); 20.5% and 17.5% were hospitalized before and after the index date, respectively (odds ratio, 0.8; 95% confidence interval, 0.54-1.27; P = .38). No significant difference occurred in total health care costs during follow-up compared with baseline.. In this retrospective cohort study, older patients who used nebulized ICSs persistently demonstrated fewer emergency department visits and systemic corticosteroid use than before nebulized ICS use. These improved outcomes were not associated with an increase in health care costs.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Aged; Aged, 80 and over; Anti-Asthmatic Agents; Asthma; Budesonide; Emergency Service, Hospital; Female; Health Services; Hospitalization; Humans; Lung Diseases; Male; Middle Aged; Nebulizers and Vaporizers; Retrospective Studies; Treatment Outcome

Topics: Adult; Anti-Bacterial Agents; Asthma; Bronchodilator Agents; Budesonide; Diagnosis, Differential; Humans; Lung Diseases; Male; Mycobacterium fortuitum; Mycobacterium Infections; Tomography, X-Ray Computed

Two CF patients developed Cushing's syndrome during administration of inhaled budesonide (400 microg/d) with oral itraconazole in one and with clarithromycin in the other patient. Clinical features appeared respectively after 2 and 6 weeks of drug co-administration, with prolonged adrenal suppression, and a slow recovery after ceasing the drugs. Inhibitors of the cytochrome P450 interfere with the metabolism of corticosteroids. Combination of these drugs even with moderate doses of budesonide should be closely monitored.

Topics: Administration, Inhalation; Adult; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Aspergillus fumigatus; Bronchodilator Agents; Budesonide; Clarithromycin; Cushing Syndrome; Cystic Fibrosis; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Drug Synergism; Drug Therapy, Combination; Escherichia coli Infections; Fatal Outcome; Female; Humans; Iatrogenic Disease; Infant, Newborn; Itraconazole; Lung Diseases; Male; Mycobacterium Infections, Nontuberculous

A novel multi-dose inhaler has been developed to closely approach the characteristics of an "ideal" inhaler. The new device, Airmax, uses proprietary technologies known as the X-ACT system to provide accurate and consistent dosing and excellent lung deposition--even at low inspiratory flow rates--combined with ease of use by the patient. Dose delivery was close to label claim, with relative standard deviation of typically around 5% for through-life emitted mass and around 10% for dose per actuation. At a flow rate (60-70 l/min), which corresponds to 4 kPa pressure drop across the device, the mean fine particle (<5 microm) dose (FPD) from 100, 200 and 400 microg strength budesonide Airmax was around 46, 98 and 244 microg, respectively. The mean FPD from 100 microg strength salbutamol Airmax was approximately 50 microg at the same flow rate. At 30 l/min, the delivered dose from Airmax is over 85% label claim with fine particle fraction of over 35%. Performance was unaffected by shaking or orientation, provided the device was not used completely upside down, and priming was not required. There was no change in dose content uniformity and aerodynamic particle-size distribution after the devices have been stored unwrapped at 30 degrees C/60% RH up to 24 months. Airmax is robust, portable and intuitive to use.

Topics: Administration, Inhalation; Albuterol; Bronchodilator Agents; Budesonide; Equipment Design; Humans; Lung Diseases; Nebulizers and Vaporizers; Particle Size; Powders

Chronic lung disease (CLD) remains a major cause of morbidity for the prematurely born infant. The pathogenesis of CLD is complex and has not been defined entirely. Infection and lung inflammatory events have been thought to play a key role in the development of CLD. However, the contribution of Ureaplasma urealyticum to the development of CLD is debated and steroids produce some improvement in neonates with this disease. The aim of this study was to investigate if U. urealyticum could stimulate macrophages to produce vascular endothelial growth factor (VEGF) and intercellular adhesion molecule-1 (ICAM-1) in vitro, which are potentially associated with both early and later pathological changes in the lung during the development of CLD. In addition, the impact of dexamethasone and budesonide on these processes was examined. We found that U. urealyticum antigen (>/=4 x 10(7) color-changing units/ml) stimulated human macrophages (phorbol 12-myristate 13-acetate-differentiated THP-1 cell line) to produce VEGF and soluble ICAM-1 in a dose-dependent manner (p < 0.05) measured by ELISA. Likewise, cell surface ICAM-1 (CD54) measured by flow cytometry was increased after stimulation with U. urealyticum. This effect was attenuated by budesonide and dexamethasone (p < 0.05). The mRNA expressions of VEGF and ICAM-1 detected by a semi-quantitative reverse transcriptase polymerase chain reaction were also induced in response to U. urealyticum and inhibited by the steroids (p < 0.05). The expression of ICAM-1 was reduced by 85.5% when the TNF-alpha production was neutralized with an anti-TNF-alpha antibody. Our findings imply that U. urealyticum might be involved in the development of CLD of prematurity.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antibodies; Antigens, Bacterial; Budesonide; Cell Line; Dexamethasone; Down-Regulation; Endothelial Growth Factors; Flow Cytometry; Humans; Intercellular Adhesion Molecule-1; Intercellular Signaling Peptides and Proteins; Lung Diseases; Lymphokines; Macrophages; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Necrosis Factor-alpha; Ureaplasma Infections; Ureaplasma urealyticum; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

We present a case with diagnosis of pulmonary alveolar microlithiasis that illustrates the appearance of this rare chronic lung disease on conventional chest X-ray, high-resolution CT, and transbronchial lung biopsy. This is the first case reported which developed pulmonary alveolar microlithiasis after Varicella zoster infection in a patient with antiphospholipid antibodies and discoid lupus.

Topics: Administration, Inhalation; Antiphospholipid Syndrome; Budesonide; Female; Follow-Up Studies; Herpes Zoster; Humans; Lithiasis; Lung Diseases; Lupus Erythematosus, Discoid; Middle Aged; Pulmonary Alveoli; Radiography, Thoracic; Rare Diseases; Risk Assessment; Tomography, X-Ray Computed; Treatment Outcome

The amount of nebulized budesonide and terbutaline delivered through an endotracheal tube (ETT) was measured in vitro using a test lung and filters in a neonatal ventilator circuit. Budesonide suspension (1 mg) was used in a concentration of 0.5 mg/mL and terbutaline solution (5 mg) in a concentration of 2.5 mg/mL.. The median amount of terbutaline deposited on the inspiratory filters was significantly higher than that of budesonide: 0.4% vs 0.3% of the nominal doses with the nebulizer connected 8 cm upstream of the ETT and nebulization performed in a constant output mode (setup A), and 2.8% vs 1.0% with the nebulizer connected directly to the ETT and nebulization performed in a breath-synchronized mode (setup B) (p < 0.05 for both). The corresponding amounts of drug deposited on the waste filters with setup A were 19.2% for terbutaline and 12.6% for budesonide, and with setup B 16.2% for terbutaline and 6.2% for budesonide (p < 0.05 for both).. The ratio between drug delivery to the inspiratory and waste filters, describing the relationship between lung deposition and wastage of drug to the ventilator circuit, was setup-dependent but not drug-dependent. The ratio with setup A was 0.02 for both budesonide and terbutaline. The respective ratios were significantly (p < 0.05) higher for budesonide (0.16) and for terbutaline (0.17) with setup B. The differences in the delivered doses of the two drugs through the ETT seems to be a function of both the drug formulation and the nebulizer-ETT setup. With the nebulizer connected directly to the ETT and nebulization in breath-synchronized mode, the differences between the two drugs were enhanced, compared with the nebulizer connected upstream of the ETT and nebulization in constant output mode. The results indicate that a solution is superior to a suspension in terms of drug delivery through an ETT.

Topics: Aerosols; Bronchodilator Agents; Budesonide; Humans; Infant, Newborn; Infant, Premature, Diseases; Intubation, Intratracheal; Lung Diseases; Models, Structural; Nebulizers and Vaporizers; Solutions; Suspensions; Terbutaline; Ventilators, Mechanical

The immune response with generation of neutralizing antiviral antibodies is an obstacle to effective repeated adenoviral gene transfer. Different immunosuppressive drugs facilitate repeat administration of adenovectors, but the clinical utility is uncertain because of systemic side effects. We investigated the use of topical corticosteroid in improving gene expression after repeated injection of adenovectors into mouse lungs. Using a vector expressing murine interleukin-6 (mIL-6) as a marker cytokine for gene expression, we show that budesonide given around exposure to adenovirus to the lung significantly maintained high levels of expressed transgene protein in bronchoalveolar lavage fluid (BALF) after as many as four consecutive injections of virus at two weekly intervals (p = 0.02 versus saline). Differences between treatment groups were most obvious 4 and 6 wk after the initial exposure to adenovirus (equivalent to three and four total exposures). In Week 4, transgene mIL-6 concentration was 2,327 +/- 955 pg/ml in budesonide compared with 336 +/- 246 pg/ml in saline-treated mice (p = 0.001). However, budesonide did not significantly protect transgene expression beyond Week 8 (four prior exposures). The improved transgene expression in budesonide-treated compared with saline-treated animals was associated with a reduction, but not prevention of neutralizing antiviral antibodies (BALF p < 0.001, serum p = 0.04). We conclude that budesonide can be valuable in gene therapy of the lung where repeated transient gene transfer is necessary.

Topics: Adenoviridae; Administration, Topical; Animals; Anti-Inflammatory Agents; Antibodies, Viral; Bronchoalveolar Lavage Fluid; Budesonide; Gene Expression; Gene Transfer Techniques; Genetic Therapy; Glucocorticoids; Immunoglobulin G; Interleukin-6; Lung Diseases; Mice; Mice, Inbred BALB C

The use of corticosteroids in toxic lung injury caused by exposure to an irritating gas such as ammonia has not been adequately studied.. To evaluate the effects of budesonide inhalation in a rabbit model of toxic lung injury induced by ammonia.. Randomized, blind placebo-controlled laboratory investigation employing 16 New Zealand White rabbits. Lung injury was induced by inhalation of a defined amount of aerosolized ammonia. Thirty minutes later, the rabbits were randomized to receive either inhalation therapy with 0.5 mg budesonide or placebo. After another 2 hours, a second treatment inhalation, identical to the first one, was administered.. Airway pressures, hemodynamics, and gas exchange were measured at baseline, 5, and 15 minutes after ammonia administration and every 30 minutes during a 6-hour period after the first blind inhalation of corticosteroids or placebo. The ammonia inhalation resulted in an acute severe lung injury, detected after 15 minutes as a decrease in Pao2 from 23.3 (+/- 3.6) to 11.0 (+/- 3.6) kPa (p < 0.005) and an increase in peak airway pressure from 13 (+/- 2) to 17 (+/- 2) cm H2O (p < 0.005). During the 6-hour observation period, the blood gas parameters improved gradually in all rabbits. In comparison with placebo, budesonide did not result in improved gas exchange or reduced airway pressure levels during the observation period.. In this animal model corticosteroid inhalation therapy had no effect on ammonia-induced lung injury.

Topics: Administration, Inhalation; Airway Resistance; Ammonia; Animals; Anti-Inflammatory Agents; Blood Gas Analysis; Budesonide; Hemodynamics; Lung Diseases; Rabbits; Respiratory Function Tests

Idiopathic pulmonary haemosiderosis (IPH) is a disorder characterised by the triad of haemoptysis, diffuse parenchymal infiltrates on chest roentgenogram and iron-deficiency anaemia. It is a diagnosis of exclusion and the prognosis is bleak despite the varied management options. We report a case of IPH occurring in a child who presented at four months of age with cough, wheeze, haemoptysis and pallor and whose symptoms are currently controlled with high-dose inhaled budesonide and low-dose oral prednisolone.

Topics: Anti-Inflammatory Agents; Budesonide; Drug Therapy, Combination; Hemosiderosis; Humans; Infant; Lung Diseases; Male; Prednisolone; Prognosis

To determine the dose of inhaled budesonide suspension in the treatment of preterm infants with ventilator-dependent lung disease, we measured the dose of nebulized budesonide delivered through an endotracheal tube (ETT), using a test lung and filters. The effect of delivering the nebulized aerosol to two different locations in the same ventilatory circuit was evaluated. In addition, a new synchronized jet nebulizer was tested. The median drug delivery to the test lung was 0.3% (range, 0-0.4%) of the nominal dose when the nebulizer activated by continuous gas flow was inserted into the inspiratory line of the circuit. Drug delivery could be increased to 0.7% (range, 0.5-0.8%) by delivering the nebulizer output directly to the ETT. When using the synchronized jet nebulizer, drug delivery was 1.1% (range, 0.8-1.6%). The particle size of aerosol emerging from the ETT was 2.14 microns. The nebulization time with the synchronized nebulizer set-up was 38 min, while the other set-ups delivered an equal volume of solution in 6-7 min. Drug delivery of 0.3-1.1% to the test lung illustrates the problems encountered in aerosol treatment of intubated neonates. We conclude that the delivery of budesonide to the test lung can be increased by delivering the nebulizer output to the ETT directly. Using synchronized nebulization during inspiration only can achieve further increases in drug delivery, and wastage of drug during expiration is decreased. Synchronized nebulization may, therefore, have an important place in the delivery of expensive aerosolized drugs.

Topics: Administration, Intranasal; Bronchodilator Agents; Budesonide; Filtration; Humans; Infant, Premature; Lung Diseases; Nebulizers and Vaporizers

Topics: Administration, Inhalation; Airway Resistance; Bronchodilator Agents; Budesonide; Humans; Infant, Newborn; Lung; Lung Diseases; Lung Volume Measurements; Pregnenediones

The effect of corticosteroid on an acute inflammation in the lungs was studied in guinea pigs exposed to an aerosol of bacterial endotoxin, the subsequent inflammatory response was evaluated counting the number of cells obtained from airway lavage and in the lung interstitium as well as the chemotactic effect of alveolar macrophages. Pretreatment with corticosteroid decreased the number of neutrophils in the airways at 24 hours after exposure but did not influence neutrophils in airways or lung interstitium at 4 hours after exposure, not the secretion of chemotactic factor(s) from alveolar macrophages at that time. It is suggested that the antiinflammatory effect of corticosteroids is a protective effect on the epithelium, preventing the late influx of serum fluid and neutrophils into the airways.

Topics: Animals; Anti-Inflammatory Agents; Bronchoalveolar Lavage Fluid; Budesonide; Chemotaxis, Leukocyte; Eosinophils; Escherichia coli; Female; Guinea Pigs; Inflammation; Lipopolysaccharides; Lung Diseases; Lymphocytes; Macrophages; Male; Neutrophils; Pregnenediones

Corticosteroids are the drugs of choice for treatment of sarcoidosis. Frequently the pulmonary parenchymal lesions with impaired lung function represent the indication for starting treatment. Oral glucocorticosteroids may cause systemic side-effects and therefore treatment is often started too late in the hope of a spontaneous recovery. With the introduction of the locally potent glucocorticosteroid budesonide (Pulmicort) the active alveolitis as well as the pulmonary parenchymal lesions can be treated with only inhaled steroids and without causing systemic effects. If wanted, treatment of pulmonary sarcoidosis can therefore be started early without waiting for a possible spontaneous improvement. Systemic sarcoidosis outside the lungs cannot, however, be treated with locally administered drugs. The most rapid improvement of the pulmonary manifestations is achieved if an initial combination of oral and inhaled steroids is used for 2-3 months. Thereafter the long-term maintenance treatment can be given with only inhaled budesonide.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Animals; Budesonide; Glucocorticoids; Humans; Lung Diseases; Pregnenediones; Sarcoidosis

Twenty patients with active sarcoidosis (increased serum ACE activity) and progressive pulmonary disease (stages 2-3) were treated with inhaled budesonide instead of with oral glucocorticosteroids in an open clinical study. Results after an 18-month treatment are reported. A general improvement in chest roentgenograms and FVC was noted. Serum ACE activity was normalized. The results indicate that pulmonary manifestations of sarcoidosis can be treated with the inhaled steroid, budesonide. In this way the risk of systemic side effects is considerably reduced. The final place of inhaled budesonide in the treatment of sarcoidosis must be determined via placebo-controlled and comparative, double-blinded clinical studies in larger series of patients.

Topics: Adult; Aged; Budesonide; Drug Evaluation; Female; Glucocorticoids; Humans; Lung; Lung Diseases; Male; Middle Aged; Peptidyl-Dipeptidase A; Pregnenediones; Radiography; Respiratory Therapy; Sarcoidosis; Time Factors; Vital Capacity

Topics: Aerosols; Budesonide; Child; Female; Hemosiderosis; Humans; Lung Diseases; Pregnenediones