Surfactant and budesonide for respiratory distress syndrome: an observational study

Kothe, T Brett; Sadiq, F; Burleyson, Nikki; Williams, Howard L.; Anderson, Connie D.; Hillman, Noah H.

doi:10.1038/s41390-019-0663-6

Cited by 44 publications

(85 citation statements)

References 34 publications

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“…The use of surfactant as a vehicle to deliver steroids to the lungs of premature infants has been the subject of increasing clinical interest. 20 Several clinical studies have investigated the efficacy of this steroid delivery mode in preventing BPD 32 and chronic respiratory diseases 33 or in treating neonatal ARDS 34,35 in premature infants. Two recent meta-analysis studies reported that intratracheal instillation of steroid-surfactant combination was an effective therapy for preventing BPD in preterm infants with neonatal ARDS, but its benefit in reducing mortality was inconsistent.…”

Section: Discussionmentioning

confidence: 99%

“…[21][22][23][24] In animal studies, this steroid delivery mode has been used to investigate its efficacy in reducing ALI in animal models of surfactant-depleted lung diseases, 23,25 MAS, 26 hyperoxia 27 , and injurious mechanical ventilation. 28,29 In clinical studies, this steroid delivery mode has been used to prevent BPD [30][31][32] and chronic diseases 33 or to treat neonatal ARDS 34,35 in premature infants. However, no study has been conducted to investigate the therapeutic effect of this steroid delivery approach on LPS-induced ALI in surfactant-insufficiency lungs.…”

mentioning

confidence: 99%

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Efficacy of Intratracheal Budesonide-Surfactant Combined Therapy in Surfactant-Insufficient Rat Lungs with Lipopolysaccharide Insult

Tsao

Lin

Lee

et al. 2021

Preprint

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Objectives: Intratracheal steroid therapy for lipopolysaccharide (LPS)-induced acute lung injury (ALI) remains challenging particularly in surfactant-deficiency lungs, a common problem of preterm infants. Surfactant has been used as a vehicle for intratracheal steroid in the treatment of other types of ALI. This study investigated the efficacy of intratracheal budesonide (BUD) delivered by two concentrations of surfactant in the treatment of LPS-induced ALI in surfactant-insufficiency rat lungs. Methods: Male adult rats were anesthetized and ventilated. Our ALI model was established by repeated saline lavage to produce surfactant insufficiency, followed by intratracheal LPS instillation. Five study groups (n=5 for each) with different intratracheal treatments following ALI were used: Control (no treatment), BUD (IT-NS-BUD; BUD in saline); IT-DS-BUD (BUD in diluted surfactant); IT-FS-BUD (BUD in full-strength surfactant); IT-FS (full-strength surfactant). Cardiopulmonary variables were monitored 4 h post injury. Histological and immunohistochemical assessments of the lungs were performed. Results: The IT-FS-BUD and IT-FS groups presented better gas exchange, less metabolic acidosis, less oxygen index, and more stable hemodynamic changes than the IT-DS-BUD, IT-NS-BUD, and Control groups. The total lung injury scores assessed by histological examination were ordered as follows: IT-FS-BUD < IT-DS-BUD or IT-FS < IT-NS-BUD < Control. The immunostaining intensities of lung myeloperoxidase showed the following order: IT-NS-BUD, IT-DS-BUD, or IT-FS-BUD < Control or IT-FS. Only the IT-FS-BUD group displayed a smaller immunostaining intensity of lung TNF-α than the control group. Conclusion: Among our therapeutic strategies, intratracheal BUD delivered by full-strength surfactant confers an optimal protection against LPS-induced ALI in surfactant-insufficiency rat lungs.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Efficacy of Intratracheal Budesonide-Surfactant Combined Therapy in Surfactant-Insufficient Rat Lungs with Lipopolysaccharide Insult

Tsao

Lin

Lee

et al. 2021

Preprint

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“…21 This release of budesonide into systemic circulation has also been found in preterm infants and could have implications in the systemic responses in preterm infants. 15 , 17 , 22 We selected the clinically used budesonide dose of 0.25 mg/kg dose for these experiments because our previous experiments with lower dosing (0.1 mg/kg) had less consistent responses. Budesonide is a very potent glucocorticoid and in pilot studies in preterm infant decreased markers of adrenal function in the serum, thus further study is necessary on systemic effects of the combination.…”

Section: Discussionmentioning

confidence: 99%

“…The combination of budesonide with surfactant therapy at birth has been shown to decrease the rate or severity of BPD compared to surfactant alone, without affecting surfactant’s surface tension properties. 14 – 17 Budesonide is a very potent glucocorticoid used in asthma and other airway diseases to decrease lung inflammation. 18 In preterm lambs, the combination of budesonide and surfactant decreases lung inflammation from injurious and non-injurious ventilation and decreases systemic inflammatory responses in the liver and brain.…”

Section: Introductionmentioning

confidence: 99%

“…In an observational study of infants receiving budesonide and surfactant compared with a historical cohort, infants with documented histological chorioamnionitis appeared to have less improvement in respiratory markers or BPD than infants without chorioamnionitis. 17 Using a ventilated preterm lamb model of chorioamnionitis, we tested the hypothesis that budesonide at 0.25 mg/kg with surfactant will decrease the acute lung and brain inflammation from IA LPS and mechanical ventilation compared to surfactant alone.…”

Section: Introductionmentioning

confidence: 99%

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Budesonide with surfactant decreases systemic responses in mechanically ventilated preterm lambs exposed to fetal intra-amniotic lipopolysaccharide

et al. 2020

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Intratracheal Budesonide Mixed With Surfactant for Extremely Preterm Infants

Manley,

Kamlin,

Donath

et al. 2024

JAMA

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ImportanceBronchopulmonary dysplasia (BPD) is a common adverse outcome in extremely preterm infants born at less than 28 weeks’ gestation. Systemic corticosteroids are effective against BPD but may be associated with adverse outcomes. Corticosteroids given directly into the lungs may be effective and safer.ObjectiveTo investigate the effectiveness of early intratracheal corticosteroid administration on survival free of BPD in extremely preterm infants.Design, Setting, and ParticipantsDouble-blind randomized clinical trial conducted in 21 neonatal units in 4 countries (Australia, New Zealand, Canada, and Singapore), enrolling infants born at less than 28 weeks’ gestation and less than 48 hours old who were mechanically ventilated (regardless of ventilator settings or oxygen requirements) or who were receiving noninvasive respiratory support and had a clinical decision to treat with surfactant. Recruitment occurred from January 2018 to March 2023. The last participant was discharged from the hospital in August 2023.InterventionsInfants were randomly allocated (1:1) to receive budesonide, 0.25 mg/kg, mixed with surfactant (poractant alfa), administered via an endotracheal tube or thin catheter, or surfactant only.Main Outcomes and MeasuresThe primary outcome was survival free of BPD at 36 weeks’ postmenstrual age. There were 15 secondary outcomes, including the 2 components of the primary outcome (survival at 36 weeks and BPD among survivors), and 9 predefined safety outcomes (adverse events).ResultsThe primary analysis included 1059 infants, 524 in the budesonide and surfactant group and 535 in the surfactant-only group. Overall, infants had a mean gestational age of 25.6 weeks (SD, 1.3 weeks) and a mean birth weight of 775 g (SD, 197 g); 586 (55.3%) were male. Survival free of BPD occurred in 134 infants (25.6%) in the budesonide and surfactant group and 121 infants (22.6%) in the surfactant-only group (adjusted risk difference, 2.7% [95% CI, −2.1% to 7.4%]). At 36 weeks’ postmenstrual age, 83.2% of infants were alive in the budesonide and surfactant group and 80.6% in the surfactant-only group. Of these, 69.3% and 71.9% were diagnosed with BPD, respectively.Conclusions and RelevanceIn extremely preterm infants receiving surfactant for respiratory distress syndrome, early intratracheal budesonide may have little to no effect on survival free of BPD.Trial Registrationanzctr.org.au Identifier: ACTRN12617000322336

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Surfactant and budesonide for respiratory distress syndrome: an observational study

Cited by 44 publications

References 34 publications

Efficacy of Intratracheal Budesonide-Surfactant Combined Therapy in Surfactant-Insufficient Rat Lungs with Lipopolysaccharide Insult

Efficacy of Intratracheal Budesonide-Surfactant Combined Therapy in Surfactant-Insufficient Rat Lungs with Lipopolysaccharide Insult

Budesonide with surfactant decreases systemic responses in mechanically ventilated preterm lambs exposed to fetal intra-amniotic lipopolysaccharide

Intratracheal Budesonide Mixed With Surfactant for Extremely Preterm Infants

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