Postnatal steroids in extreme preterm infants: Intra-tracheal instillation using surfactant as a vehicle

Boel, Lieve; Banerjee, Sujoy; Chakraborty, Mallinath

doi:10.1016/j.prrv.2017.05.002

Cited by 6 publications

(11 citation statements)

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“…Specifically, it adds to previous clinical studies that explored exogenous surfactant or glucocorticoids as preventative treatments for poor pulmonary outcomes and respiratory conditions like Bronchopulmonary Dysplasia [29,30]. For example, there are a number of clinical trials which have found that administering surfactant multiple times or using it as a vehicle for budesonide may reduce the risk of Bronchopulmonary Dysplasia [31,32]. Similarly, there have also been clinical trials that have found intratracheal instillations of budesonide, with a surfactant vehicle helped to prevent the development of chronic lung disease among preterm infants [33].…”

Section: Discussionmentioning

confidence: 99%

Exogenous Surfactant as a Pulmonary Delivery Vehicle for Budesonide In Vivo

Baer

McCaig

Yamashita

et al. 2020

Lung

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Background Lung inflammation is associated with many respiratory conditions. Consequently, anti-inflammatory medications, like glucocorticoids, have become mainstay intrapulmonary therapeutics. However, their effectiveness for treating inflammation occurring in the alveolar regions of the lung is limited by suboptimal delivery. To improve the pulmonary distribution of glucocorticoids, such as budesonide to distal regions of the lung, exogenous surfactant has been proposed as an ideal delivery vehicle for such therapies. It was therefore hypothesized that fortifying an exogenous surfactant (BLES) with budesonide would enhance efficacy for treating pulmonary inflammation in vivo. Methods An intratracheal instillation of heat-killed bacteria was used to elicit an inflammatory response in the lungs of male and female rats. Thirty minutes after this initial instillation, either budesonide or BLES combined with budesonide was administered intratracheally. To evaluate the efficacy of surfactant delivery, various markers of inflammation were measured in the bronchoalveolar lavage and lung tissue. Results Although budesonide exhibited anti-inflammatory effects when administered alone, delivery with BLES enhanced those effects by lowering the lavage neutrophil counts and myeloperoxidase activity in lung tissue. Combining budesonide with BLES was also shown to reduce several other pro-inflammatory mediators. These results were shown across both sexes, with no observed sex differences. Conclusion Based on these findings, it was concluded that exogenous surfactant can enhance the delivery and efficacy of budesonide in vivo.

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Section: Discussionmentioning

confidence: 99%

Exogenous Surfactant as a Pulmonary Delivery Vehicle for Budesonide In Vivo

Baer

McCaig

Yamashita

et al. 2020

Lung

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“…20 For this reason, surfactant has been proposed as a vehicle for intratracheal steroid administration. 20 This notion is supported by the stable biophysical and chemical properties of the surfactant/steroid mixtures under ex vivo condition [21][22][23] and enhanced pulmonary distribution of steroid in vivo when using a surfactant as the vehicle. [21][22][23][24] In our study, IT-FS provided certain benefits against ALI but was ineffective in reducing lung inflammation.…”

Section: Discussionmentioning

confidence: 99%

“…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%

“…To this end, intratracheal administration of surfactant is an effective treatment for surfactant-deficiency lung diseases or PARDS. 19,20 Additionally, growing evidence suggests that surfactants can be used as a vehicle for intratracheal steroid administration. 20 This delivery mode distributes the steroid well in the lungs without changing the biophysical and chemical properties of the drug.…”

mentioning

confidence: 99%

“…19,20 Additionally, growing evidence suggests that surfactants can be used as a vehicle for intratracheal steroid administration. 20 This delivery mode distributes the steroid well in the lungs without changing the biophysical and chemical properties of the drug. [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.…”

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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