1 | INTRODUCTION
Pediatric pneumonia is a major cause of mortality and morbidity in
children under 5 years old, especially in developing
countries.1,2 Among the cases of pediatric pneumonia,
21.7% occur during the neonatal stage.3 Preterm
infants who have pneumonia may develop acute lung injury (ALI) and its
severe form—acute respiratory distress syndrome
(ARDS).4,5 One major presentation of this form of ALI
is lung inflammation mainly induced by lipopolysaccharide (LPS), a major
pathogenic component of Gram-negative bacilli.6 In
particular, the inflammatory effect of the LPS insult accompanies the
injurious impact of surfactant deficiency in the lungs, a situation that
generally occurs in preterm infants.7,8 Thus,
surfactant deficiency and the lack of ability to cope with inflammation
are the major disadvantages of these infants against LPS-induced
ALI.4,5,7,8 The therapy options for ALI or pediatric
ARDS (PARDS) in this vulnerable population are currently
limited.5,9 Thus, investigations of effective
therapeutic strategies to alleviate LPS-induced ALI in
surfactant-insufficiency lungs are warranted.
Steroid has been long considered a classical therapy for neonatal ARDS
due to its anti-inflammatory effect; however, the side effects of
systemic steroids remain a major concern.10-12 For the
prevention of side effects, several animal or clinical studies used
intratracheal instillation13,14 or
inhalation15-18 of steroids for the treatment of
meconium aspiration syndrome (MAS) or prevention of bronchopulmonary
dysplasia (BPD) and other respiratory morbidities. However, the local
treatment with steroids remains challenging particularly in
surfactant-deficiency lungs with alveolar collapse and diffuse
atelectasis, which is a common problem in preterm
infants7,19. 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.21-24In animal studies, this steroid delivery mode has been used to
investigate its efficacy in reducing ALI in animal models of
surfactant-depleted lung diseases,23,25MAS,26 hyperoxia27, and injurious
mechanical ventilation.28,29 In clinical studies, this
steroid delivery mode has been used to prevent
BPD30-32 and chronic diseases33 or
to treat neonatal ARDS34,35 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.
This study aimed to investigate the therapeutic effects of
intratracheally instilled budesonide (BUD) delivered by two
concentrations of exogenous surfactant on LPS-induced ALI in
surfactant-insufficiency rat lungs. Our ALI model was established by
repeated saline lavage to produce surfactant insufficiency, followed by
an intratracheal LPS insult.