fluticasone and Bronchopulmonary-Dysplasia

Bronchopulmonary dysplasia (BPD), defined as oxygen dependence at 36 weeks postmenstrual age (PMA), remains an important complication of prematurity. Pulmonary inflammation plays a central role in the pathogenesis of BPD. Attenuating pulmonary inflammation with postnatal systemic corticosteroids reduces the incidence of BPD in preterm infants but may be associated with an increased risk of adverse neurodevelopmental outcomes. Local administration of corticosteroids via inhalation might be an effective and safe alternative.. To determine if administration of inhalation corticosteroids after the first week of life until 36 weeks PMA to preterm infants at high risk of developing BPD is effective and safe in reducing the incidence of death and BPD as separate or combined outcomes.. We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue 4), MEDLINE via PubMed (1966 to 19 May 2017), Embase (1980 to 19 May 2017), and CINAHL (1982 to 19 May 2017). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.. We included randomised controlled trials comparing inhalation corticosteroids, started ≥ 7 days postnatal age (PNA) but before 36 weeks PMA, to placebo in ventilated and non-ventilated infants at risk of BPD. We excluded trials investigating systemic corticosteroids versus inhalation corticosteroids.. We collected data on participant characteristics, trial methodology, and inhalation regimens. The primary outcome was death or BPD at 36 weeks PMA. Secondary outcomes were the combined outcome death or BPD at 28 days PNA, the seperate outcomes of death and BPD at both 28 days PNA, and at 36 weeks PMA, and short-term respiratory outcomes, such as failure to extubate; total days of mechanical ventilation and oxygen use; and the need for systemic corticosteroids. We contacted the original trialists to verify the validity of extracted data and to provide missing data. We analysed all data using Review Manager 5. When possible, we performed meta-analysis using typical risk ratio (RR) for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes along with their 95% confidence intervals (CI). We analysed ventilated and non-ventilated participants separately.We used the GRADE approach to assess the quality of the evidence.. We included eight trials randomising 232 preterm infants in this review. Inhalation corticosteroids did not reduce the separate or combined outcomes of death or BPD. The meta-analyses of the studies showed a reduced risk in favor of inhalation steroids regarding failure to extubate at seven days (typical RR (TRR) 0.80, 95% CI 0.66 to 0.98; 5 studies, 79 infants) and at the latest reported time point after treatment onset (TRR 0.60, 95% CI 0.45 to 0.80; 6 studies, 90 infants). However, both analyses showed increased statistical heterogeneity (I. Based on the results of the currently available evidence, inhalation corticosteroids initiated at ≥ 7 days of life for preterm infants at high risk of developing BPD cannot be recommended at this point in time. More and larger randomised, placebo-controlled trials are needed to establish the efficacy and safety of inhalation corticosteroids.

Topics: Administration, Inhalation; Anti-Inflammatory Agents; Beclomethasone; Bronchopulmonary Dysplasia; Budesonide; Dexamethasone; Fluocinolone Acetonide; Fluticasone; Glucocorticoids; Humans; Infant, Newborn; Infant, Premature; Pneumonia; Randomized Controlled Trials as Topic

Bronchopulmonary dysplasia (BPD), defined as oxygen dependence at 36 weeks postmenstrual age (PMA), remains an important complication of prematurity. Pulmonary inflammation plays a central role in the pathogenesis of BPD. Attenuating pulmonary inflammation with postnatal systemic corticosteroids reduces the incidence of BPD in preterm infants but may be associated with an increased risk of adverse neurodevelopmental outcomes. Local administration of corticosteroids via inhalation might be an effective and safe alternative.. To determine if administration of inhalation corticosteroids after the first week of life to preterm infants at high risk of developing BPD is effective and safe in reducing the incidence of death and BPD as separate or combined outcomes.. We identified randomised, controlled trials by searching the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), PubMed (from 1966), EMBASE (from 1974), CINAHL (from 1982), references from retrieved trials and handsearches of journals, all assessed to February 2012.. Randomised controlled trials comparing inhalation corticosteroids, started ≥ 7 days postnatal age (PNA) but before 36 weeks PMA, to placebo in ventilated and non-ventilated infants at risk of BPD were included. Trials investigating systemic corticosteroids versus inhalation corticosteroids were excluded.. Data on patient characteristics, trial methodology, and inhalation regimens were collected. The primary outcomes were death or BPD, or both, at 28 days PNA or 36 weeks PMA. Secondary outcomes were short-term respiratory outcomes, such as failure to extubate, total days of mechanical ventilation and oxygen use, and the need for systemic corticosteroids. The original trialists were contacted to verify the validity of extracted data and to provide missing data. All data were analysed using RevMan 5.0.24. When possible, meta-analysis was performed using typical risk ratio (TRR) for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes along with their 95% confidence intervals (CI). Ventilated and non-ventilated participants were analysed separately.. Eight trials randomising 232 preterm infants were included in this review. Inhalation corticosteroids did not reduce the separate or combined outcomes of death or BPD. Furthermore, inhalation steroids did not impact short-term respiratory outcomes such as failure to extubate and total duration of mechanical ventilation or oxygen dependency. There was a trend to a reduced use of systemic corticosteroids in favour of inhalation corticosteroids (TRR 0.51; 95% CI 0.26 to 1.00). There was a paucity of data on short-term and long-term adverse effects. These results should be interpreted with caution because the total number of randomised patients is relatively small and most trials differed considerably in patient characteristics, inhalation therapy and outcome definitions.. Based on the results of the currently available evidence, inhalation corticosteroids initiated at ≥ 7 days of life for preterm infants at high risk of developing BPD cannot be recommended at this point in time. More and larger randomised, placebo-controlled trials are needed to establish the efficacy and safety of inhalation corticosteroids.

Topics: Administration, Inhalation; Androstadienes; Anti-Inflammatory Agents; Beclomethasone; Bronchopulmonary Dysplasia; Budesonide; Dexamethasone; Fluocinolone Acetonide; Fluticasone; Glucocorticoids; Humans; Infant, Newborn; Infant, Premature; Pneumonia; Randomized Controlled Trials as Topic

This randomized, controlled trial was designed to determine the efficacy of inhaled fluticasone propionate on oxygen therapy weaning in a population of preterm infants who were born at <32 weeks of gestation and experienced moderate bronchopulmonary dysplasia (BPD).. Thirty-two infants who were < or =32 weeks of gestation, had moderate BPD that required supplemental oxygen (fraction of inspired oxygen > or =0.25), and were aged between 28 and 60 days were randomized. Fluticasone propionate 125 microg twice daily for 3 weeks and once daily for a fourth week was delivered to infants who weighed between 500 and 1200 g. The dosage was doubled for infants who weighed > or =1200 g.. Compared with placebo, treatment had no effect on either duration of supplemental O2 therapy or ventilatory support as assessed by survival analysis. At 28 days, a trend toward a lower cortisol/creatinine ratio in the treatment group was noted compared with placebo (25.1 +/- 18.9 vs 43 +/- 14.4). In the fluticasone group at 28 days, the systolic arterial pressure (78 +/- 3 vs 68 +/- 3 mm Hg) and diastolic arterial pressure (43 +/- 3.4 mm Hg vs 38 +/- 2.0 mm Hg) were higher compared with baseline fluticasone values. The chest radiograph score was lower than baseline (2.8 +/- 1.4 vs 3.7 +/- 2.2) in the fluticasone group at 28 days. This study has a statistical power of 1.0 to detect a significant difference in the duration of oxygen supplementation of >21 days between the study groups.. We conclude that fluticasone propionate reduces neither supplemental O2 use nor the need for ventilatory support in this patient population. However, fluticasone does have a positive radiologic effect in lowering chest radiograph scores. In addition, our data point to a possible association among inhaled fluticasone treatment and higher arterial blood pressure. Thus, the results of this investigation do not support the use of inhaled corticosteroids in the treatment of oxygen-dependent infants who have established moderate BPD.

Topics: Administration, Inhalation; Androstadienes; Anti-Inflammatory Agents; Blood Pressure; Bronchopulmonary Dysplasia; Combined Modality Therapy; Double-Blind Method; Female; Fluticasone; Humans; Infant; Infant, Newborn; Infant, Premature; Length of Stay; Male; Oxygen Inhalation Therapy; Respiration, Artificial; Survival Analysis; Treatment Failure

To determine demographic and clinical variables associated with inhaled corticosteroid administration and to evaluate between-hospital variation in inhaled steroid use for infants with bronchopulmonary dysplasia (BPD).. Retrospective Cohort Study.. Neonatal units of 35 US children's hospitals; as recorded in the Pediatric Health Information System (PHIS) database.. 1429 infants with evolving BPD at 28 days who were born at <29 weeks gestation with birth weight <1500 grams, admitted within the first 7 postnatal days, and discharged between January 2007-June 2011.. Inhaled steroids were prescribed to 25% (n = 352) of the cohort with use steadily increasing during the first two months of hospitalization. The most frequently prescribed steroid was beclomethasone (n = 194, 14%), followed by budesonide (n = 125, 9%), and then fluticasone (n = 90, 6%). Birth gestation <24 weeks, birth weight 500-999 grams, and prolonged ventilation all increased the adjusted odds of ever receiving inhaled corticosteroids (p<0.05). Wide variations between hospitals in the frequency of infants ever receiving inhaled steroids (range: 0-60%) and the specific drug prescribed were noted. This variation persisted, even after controlling for observed confounders.. Inhaled corticosteroid administration to infants with BPD is common in neonatal units within U.S. Children's hospitals. However, its utilization varies markedly between centers from no treatment at some institutions to the majority of infants with BPD being treated at others. This supports the need for further research to identify the benefits and potential risks of inhaled steroid usage in infants with BPD.

Topics: Administration, Inhalation; Beclomethasone; Bronchopulmonary Dysplasia; Budesonide; Fluticasone; Glucocorticoids; Humans; Infant; Infant, Low Birth Weight; Infant, Newborn; Inpatients; Retrospective Studies