Early Extubation to Noninvasive Respiratory Support of Former Preterm Lambs Improves Long-Term Respiratory Outcomes

Invasive mechanical ventilation (IMV) and exposure to oxygen-rich gas during early postnatal life are contributing factors to long-term pulmonary morbidities faced by survivors of preterm birth and bronchopulmonary dysplasia. The duration of IMV that leads to long-term pulmonary morbidities is unknown. We compared two durations of IMV (3h versus 6d) during the first 6-7d of postnatal life in preterm lambs to test the hypothesis that minimizing the duration of IMV will improve long-term respiratory system mechanics and structural outcomes later in life. Moderately preterm (~85% gestation) lambs were supported by IMV for either 3h or 6d before weaning from all respiratory support to become former preterm lambs. Respiratory system mechanics and airway reactivity were assessed monthly from 1 to 6 months of chronological postnatal age by the forced oscillation technique. Quantitative morphological measurements were made for smooth muscle accumulation around terminal bronchioles and indices of alveolar formation. Minimizing IMV to 3h led to significantly better (p<0.05) baseline respiratory system mechanics and less reactivity to methacholine in the first 3 months of chronological age (2 months corrected age), significantly less (p<0.05) accumulation of smooth muscle around peripheral resistance airways (terminal bronchioles), and significantly better (p<0.05) alveolarization at the end of 5 months corrected age compared to continuous IMV for 6d. We conclude that limiting the duration of IMV following preterm birth of fetal lambs leads to better respiratory system mechanics and structural outcomes later in life.