pulmicort and Infant--Premature--Diseases

Antenatal steroid treatment to enhance fetal lung maturity and surfactant treatment to prevent or treat respiratory distress syndrome have been major advances in perinatal medicine in the past 40 years contributing to improved outcomes for preterm infants. Use of postnatal steroids to prevent or treat chronic lung disease in preterm infants has been less successful and associated with adverse neurodevelopmental outcomes. Although early (in the first week of life) postnatal steroid treatment facilitates earlier extubation and reduces the risk of chronic lung disease, it is associated with adverse effects, such as hyperglycemia, hypertension, gastrointestinal bleeding and perforation, hypertrophic cardiomyopathy, growth failure, and cerebral palsy, and cannot be recommended. Early treatment with hydrocortisone may also improve survival without chronic lung disease, but concerns remain about possible adverse effects such as gastrointestinal perforation and sepsis, particularly in very preterm infants. Early inhaled budesonide also reduces the incidence of chronic lung disease but there are concerns that this may occur at the expense of increased risk of death. More studies of early low-dose steroids with adequate long-term follow-up are needed before they can be recommended for the prevention of chronic lung disease. Late (after the first week of life) postnatal steroids may have a better benefit-to-harm ratio than early steroids. A Cochrane Review shows that late steroid treatment reduces chronic lung disease, the combination of death and chronic lung disease at both 28 days and 36 weeks' corrected age, and the need for later rescue dexamethasone. Adverse effects include hyperglycemia, hypertension, hypertrophic cardiomyopathy, and severe retinopathy of prematurity but without an increase in blindness. Long-term neurodevelopmental effects are not significantly increased by late postnatal steroid treatment. Current recommendations are that postnatal steroid treatment should be reserved for preterm infants who are ventilator-dependent after the first 7-14 days of life and any course should be low dose and of short duration to facilitate endotracheal extubation. Budesonide/surfactant mixtures show some promise as a means of reducing chronic lung disease in preterm infants with severe respiratory distress syndrome, but further larger studies with long-term follow-up are needed before this treatment can be recommended as a routine intervention.

Topics: Anti-Inflammatory Agents; Budesonide; Chronic Disease; Dexamethasone; Drug Administration Schedule; Humans; Hydrocortisone; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Randomized Controlled Trials as Topic; Respiratory Distress Syndrome, Newborn; Steroids

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

The long-term effects on neurodevelopment of the use of inhaled glucocorticoids in extremely preterm infants for the prevention or treatment of bronchopulmonary dysplasia are uncertain.. We randomly assigned 863 infants (gestational age, 23 weeks 0 days to 27 weeks 6 days) to receive early (within 24 hours after birth) inhaled budesonide or placebo. The prespecified secondary long-term outcome was neurodevelopmental disability among survivors, defined as a composite of cerebral palsy, cognitive delay (a Mental Development Index score of <85 [1 SD below the mean of 100] on the Bayley Scales of Infant Development, Second Edition, with higher scores on the scale indicating better performance), deafness, or blindness at a corrected age of 18 to 22 months.. Adequate data on the prespecified composite long-term outcome were available for 629 infants. Of these infants, 148 (48.1%) of 308 infants assigned to budesonide had neurodevelopmental disability, as compared with 165 (51.4%) of 321 infants assigned to placebo (relative risk, adjusted for gestational age, 0.93; 95% confidence interval [CI], 0.80 to 1.09; P=0.40). There was no significant difference in any of the individual components of the prespecified outcome. There were more deaths in the budesonide group than in the placebo group (82 [19.9%] of 413 infants vs. 58 [14.5%] of 400 infants for whom vital status was available; relative risk, 1.37; 95% CI, 1.01 to 1.86; P=0.04).. Among surviving extremely preterm infants, the rate of neurodevelopmental disability at 2 years did not differ significantly between infants who received early inhaled budesonide for the prevention of bronchopulmonary dysplasia and those who received placebo, but the mortality rate was higher among those who received budesonide. (Funded by the European Union and Chiesi Farmaceutici; ClinicalTrials.gov number, NCT01035190 .).

Topics: Administration, Inhalation; Blindness; Bronchopulmonary Dysplasia; Budesonide; Cerebral Palsy; Cognition Disorders; Developmental Disabilities; Female; Follow-Up Studies; Gestational Age; Glucocorticoids; Hearing Loss; Humans; Infant, Extremely Premature; Infant, Newborn; Infant, Premature, Diseases; Male

Systemic glucocorticoids reduce the incidence of bronchopulmonary dysplasia among extremely preterm infants, but they may compromise brain development. The effects of inhaled glucocorticoids on outcomes in these infants are unclear.. We randomly assigned 863 infants (gestational age, 23 weeks 0 days to 27 weeks 6 days) to early (within 24 hours after birth) inhaled budesonide or placebo until they no longer required oxygen and positive-pressure support or until they reached a postmenstrual age of 32 weeks 0 days. The primary outcome was death or bronchopulmonary dysplasia, confirmed by means of standardized oxygen-saturation monitoring, at a postmenstrual age of 36 weeks.. A total of 175 of 437 infants assigned to budesonide for whom adequate data were available (40.0%), as compared with 194 of 419 infants assigned to placebo for whom adequate data were available (46.3%), died or had bronchopulmonary dysplasia (relative risk, stratified according to gestational age, 0.86; 95% confidence interval [CI], 0.75 to 1.00; P=0.05). The incidence of bronchopulmonary dysplasia was 27.8% in the budesonide group versus 38.0% in the placebo group (relative risk, stratified according to gestational age, 0.74; 95% CI, 0.60 to 0.91; P=0.004); death occurred in 16.9% and 13.6% of the patients, respectively (relative risk, stratified according to gestational age, 1.24; 95% CI, 0.91 to 1.69; P=0.17). The proportion of infants who required surgical closure of a patent ductus arteriosus was lower in the budesonide group than in the placebo group (relative risk, stratified according to gestational age, 0.55; 95% CI, 0.36 to 0.83; P=0.004), as was the proportion of infants who required reintubation (relative risk, stratified according to gestational age, 0.58; 95% CI, 0.35 to 0.96; P=0.03). Rates of other neonatal illnesses and adverse events were similar in the two groups.. Among extremely preterm infants, the incidence of bronchopulmonary dysplasia was lower among those who received early inhaled budesonide than among those who received placebo, but the advantage may have been gained at the expense of increased mortality. (Funded by the European Union and Chiesi Farmaceutici; ClinicalTrials.gov number, NCT01035190.).

Topics: Administration, Inhalation; Bronchopulmonary Dysplasia; Budesonide; Drug Administration Schedule; Ductus Arteriosus, Patent; Female; Fibrosis; Gestational Age; Glucocorticoids; Humans; Infant, Extremely Premature; Infant, Newborn; Infant, Premature, Diseases; Length of Stay; Lung; Male; Oxygen Inhalation Therapy; Positive-Pressure Respiration; Respiratory Distress Syndrome, Newborn

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

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

In order to assess the efficacy of a combination of systemic and nebulized corticosteroids in reducing the incidence and severity of chronic lung disease (CLD) in very low birthweight (VLBW) infants, 60 ventilator-dependent infants < or = 1500 g were randomly assigned to receive either steroids or placebo as of 7 d. The steroid group (n = 30, GA = 25.8 +/- 1.6 weeks, BW = 731 +/- 147 g) received systemic dexamethasone for 3 d, followed by nebulized budesonide for 18 d. Control infants (n = 30, GA = 25.9 +/- 1.8 weeks, BW = 796 +/- 199 g) received systemic and inhaled saline. Steroid-treated infants required less ventilatory support between 9 and 17 d (p < 0.01), and had greater lung compliance at 10 d (p = 0.01), but not subsequently. CLD incidence at 36 weeks was 45.5% vs 56.0% in controls, and fewer steroid-treated infants required dexamethasone rescue (23.3% vs 56.7%, p = 0.017). Survival to discharge was similar (73.3% vs 83.3%), as were the durations of mechanical ventilation, supplemental oxygen use, and hospitalization. Tracheal effluent elastase/albumin ratios and serum cortisol values did not differ between groups, and no adverse effects were noted. We conclude that early dexamethasone administration was associated with improved pulmonary function, which was not sustained with nebulized budesonide. However, the steroid regimen studied reduced the need for dexamethasone rescue in infants with CLD.

Topics: Administration, Inhalation; Budesonide; Dexamethasone; Double-Blind Method; Female; Glucocorticoids; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Infusions, Intravenous; Male; Respiratory Distress Syndrome, Newborn; Respiratory Mechanics; Treatment Outcome

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 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