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Persistent bronchiolar remodeling following brief ventilation of the very immature ovine lung
Megan O'Reilly1, Stuart B Hooper, Beth J Allison
1Department of Anatomy and Developmental Biology, Building 76, Monash University, Victoria 3800, Australia.
Insights
Brief mechanical ventilation of premature lungs can cause lasting airway remodeling. These changes, including airway smooth muscle and collagen increases, may lead to reduced lung function in infants.
Area of Science:
- Neonatal Physiology
- Respiratory Medicine
- Pediatric Pulmonology
Background:
- Mechanical ventilation is crucial for preterm infants but may cause lung injury.
- Small airway dysfunction is linked to reduced lung function after preterm birth.
- The effects of brief mechanical ventilation on immature lungs require further investigation.
Purpose of the Study:
- To investigate the impact of short-term positive-pressure ventilation on small airways in immature, surfactant-deficient lungs.
- To determine if ventilation-induced airway changes persist after ventilation cessation.
- To characterize the specific airway remodeling processes involved.
Main Methods:
- Fetal sheep (0.75 term) underwent in utero mechanical ventilation (6 or 12 hours) or served as controls.
- Tissues were analyzed immediately after ventilation and 7 days post-ventilation.
- Histological analysis focused on epithelial injury, airway smooth muscle (ASM), collagen, mucin, cell proliferation, and apoptosis.
Main Results:
- Immediately post-ventilation, epithelial injury was observed, with increased ASM and mucin, and reduced collagen.
- Seven days after ventilation, epithelium thickened with increased cell turnover, and bronchiolar collagen and ASM increased.
- Increased ASM was attributed to cellular hypertrophy, and alveolar attachments were reduced.
Conclusions:
- Brief mechanical ventilation of the immature lung induces persistent bronchiolar remodeling.
- These airway changes, including epithelial and wall remodeling, last at least 7 days.
- Such remodeling may contribute to the reduced lung function observed in mechanically ventilated preterm infants.
Abstract:
Children and adults who were mechanically ventilated following preterm birth are at increased risk of reduced lung function, suggesting small airway dysfunction. We hypothesized that short periods of mechanical ventilation of very immature lungs can induce persistent bronchiolar remodeling that may adversely affect later lung function. Our objectives were to characterize the effects of brief, positive-pressure ventilation per se on the small airways in very immature, surfactant-deficient lungs and to determine whether the effects persist after the cessation of ventilation. Fetal sheep (0.75 of term) were mechanically ventilated in utero with room air (peak inspiratory pressure 40 cmH2O, positive end-expiratory pressure 4 cmH2O, 65 breaths/min) for 6 or 12 h, after which tissues were collected; another group was studied 7 days after 12-h ventilation. Age-matched unventilated fetuses were controls. The mean basement membrane perimeter of airways analyzed was 548.6+/-8.5 microm and was not different between groups. Immediately after ventilation, 21% of airways had epithelial injury; in airways with intact epithelium, there was more airway smooth muscle (ASM) and less collagen, and the epithelium contained more mucin-containing and apoptotic cells and fewer proliferating cells. Seven days after ventilation, epithelial injury was absent but the epithelium was thicker, with greater cell turnover; there were increased amounts of bronchiolar collagen and ASM and fewer alveolar attachments. The increase in ASM was likely due to cellular hypertrophy rather than hyperplasia. We conclude that brief mechanical ventilation of the very immature lung induces remodeling of the bronchiolar epithelium and walls that lasts for at least 7 days; such changes could contribute to later airway dysfunction.
