A Follow-up Study of Preterm Infants Given Budesonide Using Surfactant as a Vehicle to Prevent Chronic Lung Disease in Preterm Infants

Kuo, Huang Tsung; Lin, Hung‐Che; Tsai, Chang Hai; Chouc, I.C.; Yeh, Tsu F.

doi:10.1016/j.jpeds.2009.10.049

Cited by 67 publications

(88 citation statements)

References 12 publications

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“…Pilot studies performed by Yeh and colleagues (8,9) used intratracheal instillation of budesonide suspended in surfactant to improve the delivery of budesonide to the lung periphery. They reported a substantially reduced incidence of BPD with no observed immediate or long-term adverse effects (8)(9)(10).…”

Section: Clinical Relevancementioning

confidence: 98%

Antiinflammatory Effects of Budesonide in Human Fetal Lung

Barrette¹,

Roberts

Chapin³

et al. 2016

Am J Respir Cell Mol Biol

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Lung inflammation in premature infants contributes to the development of bronchopulmonary dysplasia (BPD), a chronic lung disease with long-term sequelae. Pilot studies administering budesonide suspended in surfactant have found reduced BPD without the apparent adverse effects that occur with systemic dexamethasone therapy. Our objective was to determine budesonide potency, stability, and antiinflammatory effects in human fetal lung. We cultured explants of second-trimester fetal lung with budesonide or dexamethasone and used microscopy, immunoassays, RNA sequencing, liquid chromatography/tandem mass spectrometry, and pulsating bubble surfactometry. Budesonide suppressed secreted chemokines IL-8 and CCL2 (MCP-1) within 4 hours, reaching a 90% decrease at 12 hours, which was fully reversed 72 hours after removal of the steroid. Half-maximal effects occurred at 0.04-0.05 nM, representing a fivefold greater potency than for dexamethasone. Budesonide significantly induced 3.6% and repressed 2.8% of 14,500 sequenced mRNAs by 1.6-to 95-fold, including 119 genes that contribute to the glucocorticoid inflammatory transcriptome; some are known targets of nuclear factor-kB. By global proteomics, 22 secreted inflammatory proteins were hormonally regulated. Two glucocorticoid-regulated genes of interest because of their association with lung disease are CHI3L1 and IL1RL1. Budesonide retained activity in the presence of surfactant and did not alter its surface properties. There was some formation of palmitate-budesonide in lung tissue but no detectable metabolism to inactive 16a-hydroxy prednisolone. We concluded that budesonide is a potent and stable antiinflammatory glucocorticoid in human fetal lung in vitro, supporting a beneficial antiinflammatory response to lung-targeted budesonide:surfactant treatment of infants for the prevention of BPD.

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Section: Clinical Relevancementioning

confidence: 98%

Antiinflammatory Effects of Budesonide in Human Fetal Lung

Barrette¹,

Roberts

Chapin³

et al. 2016

Am J Respir Cell Mol Biol

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“…No clinically significant adverse effects were observed and the authors called for a large sample multicenter trial to be performed [25]. The same authors reported longer-term outcomes from this study at 2-3 years of age [26]. Physical growth and neurological examinations were comparable between groups, as were indices of mental and psychomotor development.…”

Section: Steroids Administered With Surfactantmentioning

confidence: 92%

Update on Postnatal Steroids

Halliday¹

2017

Neonatology

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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.

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“…The proportion of infants who survived without BPD was significantly higher in the budesonide group. There were no clinically significant adverse effects were reported [19] and follow at between two to three years demonstrated no significant differences in physical growth or neurological examination results [20]. A multicentre RCT was then undertaken including 265 infants with severe RDS.…”

Section: Corticosteroidsmentioning

confidence: 99%

Advances in emerging treatment options to prevent bronchopulmonary dysplasia

Ling

Greenough

2017

Expert Opinion on Orphan Drugs

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Introduction: Bronchopulmonary dysplasia (BPD) is common sequaelae of premature birth.It can be complicated by the development of pulmonary hypertension (PH), which significantly increases mortality. Areas covered: The aim of this review is to evaluate emerging drug therapies for prevention and treatment of BPD and associated PH. These include superoxide dismutase, macrolides, Clara secretary cell protein, -1 protease inhibitors, pentoxifylline, melatonin, inositol, N-acetyl cysteine, allopurinol, cimetidine, pulmonary vasodilators and mesenchymal stem cells (MSC). We have also included discussion on longer standing therapies such as corticosteroids, caffeine and vitamin A.Expert opinion: Corticosteroid administration systemically, but not by inhalation, caffeine and vitamin A reduce BPD. Enhancing endogenous anti-oxidant mechanisms through supplementation with superoxide dismutase or Clara cell secretory protein has yielded encouraging results. Azithromycin, a macrolide used to treat Ureaplasma infection, also has anti-inflammatory properties and has been shown to reduce BPD. Sildenafil reduces the echocardiographic markers of pulmonary hypertension associated with BPD, but has not been shown to prevent BPD. In animal models and a small phase one study MSC administration has resulted in promising results. Appropriately powered studies with long term outcomes are required to assess the efficacy of all these treatments.3

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A Follow-up Study of Preterm Infants Given Budesonide Using Surfactant as a Vehicle to Prevent Chronic Lung Disease in Preterm Infants

Cited by 67 publications

References 12 publications

Antiinflammatory Effects of Budesonide in Human Fetal Lung

Antiinflammatory Effects of Budesonide in Human Fetal Lung

Update on Postnatal Steroids

Advances in emerging treatment options to prevent bronchopulmonary dysplasia

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