Efficacy of sequential early systemic and inhaled corticosteroid therapy in the prevention of chronic lung disease of prematurity. A randomized trial of inhaled versus intravenous steroids in ventilator-dependent preterm infants. Randomised controlled study of early use of inhaled corticosteroid in preterm infants with respiratory distress syndrome. The response to inhaled and oral steroids in patients with stable chronic obstructive pulmonary disease. Open randomised controlled trial of inhaled nitric oxide and early dexamethasone in high risk preterm infants. Failure of early postnatal dexamethasone to prevent chronic lung disease in infants with respiratory distress syndrome. Effect of dexamethasone on tracheobronchial aspirate fluid cytology and pulmonary mechanics in preterm infants. Dexamethasone therapy in neonatal chronic lung disease: an international placebo-controlled trial. Collaborative Dexamethasone Trial Group. Early postnatal dexamethasone for the prevention of chronic lung disease in high-risk preterm infants.
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. Intravenous steroids improve the respiratory course in ventilator-dependent preterm infants but have adverse effects. We hypothesized that inhaled steroids would be as effective, but with less systemic effects.
                We conducted a randomized, prospective trial comparing inhaled beclomethasone, either 400 or 800 microg/d, to intravenous dexamethasone in preterm infants dependent on conventional mechanical ventilation and supplemental oxygen at 2 weeks of age.
                Seventy-eight infants were randomized. By day three of therapy, the intravenous steroid group had significantly decreased ventilator and oxygen requirements compared to either inhaled group. The inhaled 800-microg/d group trended toward more rapid decreases in ventilator and oxygen requirements than the 400-microg/d group. By day 14, all groups had similar reductions in ventilator and oxygen requirements. The incidence of adverse effects did not differ between groups.
                In this small, randomized study, inhaled steroids conferred no advantages to intravenous steroids in the management of ventilator-dependent preterm infants. To investigate the therapeutic efficacy of inhaled fluticasone propionate, started on day 1 of age, on ventilated preterm infants with respiratory distress syndrome.
                Starting within 24 hours of age, ventilated preterm infants (gestation < 32 weeks, birthweight < 1.5 kg) with respiratory distress syndrome were given a 14 day course (two puffs, 12 hourly) of either fluticasone propionate (250 microg/puff) (group 1, n=27) or placebo (group 2, n=26) with a metered dose inhaler-spacer device. Response to treatment was assessed by the rate of successful extubation by days 7 and 14 of age, changes in respiratory system mechanics, death, occurrence of chronic lung disease, and other neonatal complications.
                More infants in the treatment group were successfully extubated by 14 days of age than those in the placebo group (17/27 vs 8/26; p = 0.038). The treated infants also showed a more significant improvement in respiratory system compliance during the first 14 days of life. The two groups, however, did not differ significantly in their need for systemic steroids after day 14 of age, death, or the occurrence of chronic lung disease. The treatment was not associated with any increase in neonatal complications, including those attributable to steroid induced side effects.
                These results provide preliminary evidence that early treatment with inhaled corticosteroids may be beneficial to ventilated preterm infants with respiratory distress. Further study of its use in a large scale randomised trial is warranted. A significant minority of patients with COPD have favourable response to corticosteroid treatment. In addition, the benefit of corticosteroid treatment may be outweighed by the side-effects. Long-term administration of inhaled steroids is a safe means of treatment. However, only a few studies have addressed the role of inhaled steroids in patients with COPD, with conflicting results.
                Forty-four patients with stable COPD were defined as 'responders to bronchodilators' (increase in FEV1 > or = 20% following administration of beta 2-agonist) (group A), and 124 as 'non-responders to bronchodilators' (group B). All patients were randomized to receive a 6-week course of either a daily dose of 800 micrograms of inhaled budesonide or placebo, separated by 4 weeks when no medication was taken; were randomized again to receive a 6-week course of either 1600 micrograms day-1 of inhaled budesonide, or 800 micrograms day-1 of inhaled budesonide plus placebo; and were randomized once again to receive a 6-week course of either 40 mg day-1 of prednisone or placebo. All stages were performed in a double-blind cross-over design.
                Following administration of 800 micrograms day-1 of inhaled budesonide, there was an increase in the mean FEV1 from 1.40 +/- 0.20 to 1.92 +/- 0.22 L (P < 0.001) and a significant decrease in inhaled beta 2 agonist consumption in group A. These changes remained almost stable during the increased dose of inhaled budesonide or during prednisone treatment. The mean FEV1 did not change during the placebo period, or in group B in either treatments.
                Treatment with inhaled steroids improved spirometry data and inhaled beta 2-agonist consumption in about one-quarter of patients with stable COPD, and this rate increased to about three-quarters in patients who responded to beta 2-agonist inhalation. There was no additional benefit in using a higher dose of inhaled budesonide or prednisone. To determine whether treatment with inhaled nitric oxide (NO) and/or dexamethasone reduces the incidence of chronic lung disease (CLD) and/or death in high risk preterm infants.
                Infants below 32 weeks of gestation were recruited at 96 hours of age if they were deemed to be at high risk of developing CLD. Infants were randomly assigned to one of four treatment groups using a factorial design: (1) 5-20 parts per million inhaled NO for 72 hours; (2) 0.5-1 mg/kg/day intravenous dexamethasone for 6 days; (3) both drugs together; (4) continued conventional management.
                Forty two infants were randomised: 10 infants received inhaled NO alone; 11 dexamethasone alone; 10 both treatments; and 11 neither treatment. There was no difference in the combined incidence of CLD and/or death before discharge from hospital between either infants treated with inhaled NO and controls (RR 1.05, 95% CI 0.84-1.25), or those treated with dexamethasone and controls (RR 0.95, 95% CI 0.79-1.18).
                At 96 hours of age, neither treatment with inhaled NO nor dexamethasone prevented CLD or death. To study the effect of early postnatal dexamethasone (days 1-3) on the incidence and severity of chronic lung disease in preterm infants with respiratory distress syndrome.
                A multicentre, randomised, placebo controlled, blinded study was carried out in 18 neonatal intensive care units in Israel. The primary outcome measure was survival to discharge without requirement for supplemental oxygen therapy beyond 28 days of life. The secondary outcome measures were requirement for mechanical ventilation at 3 and 7 days, duration of ventilation or oxygen therapy, need for subsequent steroids for established chronic lung disease and incidence of major morbidities.
                The study consisted of 248 infants (dexamethasone n = 132; placebo n = 116). No differences were found in the outcome variables except for a reduction in requirement for mechanical ventilation at age 3 days in treated infants (dexamethasone 44%, placebo 67%; P = 0.001). Gastrointestinal haemorrhage, hypertension, and hyperglycaemia were more common in treated infants, but no life threatening complications, such as gastrointestinal perforation, were encountered.
                These data do no support the routine use of early postnatal steroids, but may justify further study in a selected, high risk group of infants. The changes induced on respiratory mechanics and on tracheobronchial aspirate fluid (TAF) cytology by dexamethasone courses started at two different postnatal ages in preterm infants at risk of chronic lung disease (CLD) were reported in this clinical trial designed in two phases. The first phase of the study included 20 neonates with birth weight < or = 1,250 g and gestational age < or = 32 weeks, who were oxygen and ventilator dependent on the 10th day of life. They were randomly assigned to the moderately early dexamethasone (MED) group or to the control group. The second phase of the study included 20 neonates with the same characteristics, oxygen and ventilator dependent on the 4th day of life, randomly assigned to the early dexamethasone (ED) group or to the control group. Both treated groups received dexamethasone intravenously for 7 days (0.5 mg/kg/day for the first 3 days, 0.25 mg/kg/day for the next 3 days, and 0.125 mg/kg/day for the last day of treatment). The control groups received no steroid treatment. A significantly lower absolute cell count and percentage of neutrophils (PMN) in the TAF and significantly higher dynamic lung compliance (Cdyn) values were observed in both the MED treated compared to the untreated infants and the ED treated infants compared to the control group. Moreover these changes were more precocious in the ED Group compared to the MED Group. Our study suggests that dexamethasone could be more efficacious in reducing effects of ventilator-induced lung injury in preterm infants at high risk of CLD when started earlier.
                Copyright 2004 S. Karger AG, Basel In a multicenter trial of steroid therapy for chronic neonatal oxygen dependence, 287 neonates were randomly allocated from around 3 weeks of age, to dexamethasone or placebo. Active treatment significantly reduced the duration of further assisted ventilation among infants who were ventilator dependent at entry (median days for survivors, 11 vs 17.5). There were no statistically significant differences between the total groups of survivors in time receiving supplemental oxygen and length of stay in hospital, although the trend favored the dexamethasone group. Twenty-five infants in each group died prior to hospital discharge; most were ventilator dependent at trial entry. Open treatment with steroids was later given to 18% in the active group and to 43% in the placebo group. There was no evidence of serious side effects; in particular, infection rates were similar in the two groups. The purpose of this study was to evaluate the effect of early administration of dexamethasone on the incidence of chronic lung disease (CLD) in high risk preterm infants and to evaluate the side effects of the early steroid administration.
                Randomised clinical trial.
                Neonatal intensive care unit.
                50 infants at high risk of CLD were randomly assigned after 72 h of life to the dexamethasone group (n = 25) or to the control group (n = 25). The treated infants received dexamethasone intravenously from the 4th day of life for 7 days (0.5 mg/kg per day for the first 3 days, 0.25 mg/kg per day for the next 3 days and 0.125 mg/kg per day on the 7th day). The control group received no steroid treatment.
                The incidence of CLD at 28 days of life and at 36 weeks' postconceptional age was significantly lower in the dexamethasone group than in the control group (p < 0.001). Moreover, infants in the dexamethasone group remained intubated and required oxygen therapy for a shorter period than those in the control group (p < 0.001). Hyperglycaemia, hypertension, growth failure and mainly hypertrophy of the left ventricle were the transient side effects associated with early steroid administration.
                Early dexamethasone administration may be useful in preventing CLD, but its use should prudently be restricted to preterm infants at high risk of CLD.
Based on this updated review, there is no evidence from the trials reviewed that early administration (in the first two weeks of life) of inhaled steroids to ventilated preterm neonates was effective in reducing the incidence of CLD. Currently, use of inhaled steroids in this population cannot be recommended. Studies are needed to identify the risk/benefit ratio of different delivery techniques and dosing schedules for the administration of these medications. Studies need to address both the short-term and long-term benefits and adverse effects of inhaled steroids with particular attention to neurodevelopmental outcome.