Former-preterm lambs have persistent alveolar simplification at 2 and 5 months corrected postnatal age

Area of Science:

• Pulmonary Medicine
• Developmental Biology
• Animal Models

Background:

• Bronchopulmonary dysplasia (BPD) is a common complication of preterm birth and mechanical ventilation (MV).
• Alveolar simplification is a key pathological feature of BPD, but its long-term consequences due to developmental immaturity and injury are poorly understood.
• Lack of suitable animal models has hindered research into the mechanisms of impaired alveolar development.

Purpose of the Study:

• To establish and validate a novel ovine model of former-preterm lambs to investigate persistent alveolar simplification.
• To test the hypothesis that moderate preterm birth followed by MV leads to lasting deficits in alveolar development.
• To provide a platform for studying the pathogenesis of BPD and identifying therapeutic targets.

Main Methods:

• Moderately preterm lambs (~85% gestation) received MV for approximately 6 days before weaning.
• Former-preterm lambs were assessed at corrected postnatal ages (cPNA) equivalent to 1-2 years and ~6 years in humans.
• Alveolar structure was quantified using morphometric and stereological methods, comparing former-preterm lambs to age-matched, unventilated term controls.

Main Results:

• Former-preterm lambs exhibited significantly thicker distal airspace walls at both 2 and 5 months cPNA (P < 0.001 and P < 0.009).
• A lower volume density of secondary septa was observed in former-preterm lambs at both time points (P < 0.007 and P < 0.001).
• Radial alveolar counts were significantly reduced in former-preterm lambs compared to controls (P < 0.003 and P < 0.020), with no sex-specific differences detected.

Conclusions:

• Moderate preterm birth and short-term MV significantly impede the completion of alveolarization in lambs.
• The developed ovine model demonstrates persistent alveolar simplification, mirroring key aspects of BPD.
• This model offers a valuable tool for future research into the mechanisms underlying impaired lung development and for testing novel interventions.