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Intermittent CPAP limits hyperoxia-induced lung damage in a rabbit model of bronchopulmonary dysplasia
Andre George Gie1, Thomas Salaets1, Janne Vignero2
1Department of Development and Regeneration, KU Leuven, Leuven, Belgium.
Insights
Continuous positive airway pressure (CPAP) ventilation in preterm infants may reduce bronchopulmonary dysplasia (BPD). This study found CPAP improved lung function and structure in a rabbit model of BPD, suggesting a protective role.
Area of Science:
- Neonatology
- Pediatric Pulmonology
- Respiratory Physiology
Background:
- Bronchopulmonary dysplasia (BPD) is a common complication in preterm infants, leading to chronic respiratory issues.
- Continuous positive airway pressure (CPAP) is a limited treatment option for BPD, but its effects on developing lungs under hyperoxia are unclear.
Purpose of the Study:
- To investigate the functional and structural impacts of CPAP on the developing lung in a preterm rabbit model exposed to hyperoxia.
- To assess how CPAP influences lung mechanics, histology, and inflammatory markers in the context of hyperoxia-induced BPD.
Main Methods:
- Premature rabbits were exposed to normoxia, hyperoxia, or hyperoxia with daily CPAP treatment.
- Pulmonary function tests (pressure-volume, forced oscillation) and histological analyses were performed on day 7.
- Evaluated alveolar and vascular morphology, airway smooth muscle, epithelium height, extracellular matrix, and cytokine expression.
Main Results:
- Hyperoxia led to restrictive lungs with thickened alveolar walls, increased parenchymal tissue, collagen, airway smooth muscle, and pulmonary artery wall thickness.
- CPAP improved alveolar recruitment and mitigated hyperoxia's detrimental effects on respiratory epithelium and pulmonary arteries.
- CPAP enhanced lung function, reducing respiratory system resistance, tissue damping, and tissue elastance.
Conclusions:
- Hyperoxia significantly disrupts functional and structural lung development in preterm infants.
- Intermittent CPAP demonstrated protective effects, improving lung function and attenuating structural damage without adverse alveolar consequences.
- Further research is needed to elucidate the precise mechanisms behind CPAP's beneficial effects in BPD.
Abstract:
A significant proportion of preterm infants develop bronchopulmonary dysplasia (BPD) leading to poor lifelong respiratory health. Limited treatment options exist with continuous positive airway pressure (CPAP) ventilation being one of the few associated with diminished BPD. However, little is known about the effect of the distending pressure of CPAP on the developing lung exposed to hyperoxia. We aimed to identify the functional and structural effects of CPAP in a preterm hyperoxia rabbit model of BPD. Premature rabbit pups were randomized to normoxia, hyperoxia (≥95% O2), or hyperoxia plus 4 h daily CPAP [fraction of inspired oxygen (FiO) 0.95, 5 cmH2O]. On day 7 postdelivery we performed invasive pressure-volume- and forced oscillation-based pulmonary function tests, before lung harvest for histological evaluation. Alveolar and vascular morphology, airway smooth muscle content, respiratory epithelium height, extracellular matrix components, and inflammatory cytokine expression were quantified. Hyperoxia-reared pups had restrictive lungs: alveolar walls were thickened, with the lung parenchymal tissue, collagen content, and airway smooth muscle content increased. In addition, peripheral pulmonary artery wall thickness was increased. CPAP increased alveolar recruitment and limited the structural effect of hyperoxia on the respiratory epithelium and pulmonary arteries. Additionally, CPAP improved lung function, mitigating hyperoxia-associated changes to respiratory system resistance, tissue damping, and tissue elastance. Hyperoxia disrupted functional and structural lung development. Daily intermittent CPAP limited hyperoxia-associated decreased lung function and attenuated structural changes to pulmonary arteries and respiratory epithelium while having no structural alveolar consequences. The mechanism by which CPAP has these beneficial effects needs further investigation.
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