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Nasal Ventilation Alters Mesenchymal Cell Turnover and Improves Alveolarization in Preterm Lambs

¹ Department of Pediatrics, School of Medicine, University of Utah, Salt Lake City, Utah

Correspondence and requests for reprints should be addressed to Kurt H. Albertine, Ph.D., Department of Pediatrics, Division of Neonatology, University of Utah Health Sciences Center, Williams Building, P.O. Box 581289, Salt Lake City, UT 84158. E-mail: kurt.albertine{at}hsc.utah.edu

Rationale: Bronchopulmonary dysplasia (BPD) is a frequent cause of morbidity in preterm infants that is characterized by prolonged need for ventilatory support in an intensive care environment. BPD is characterized histopathologically by persistently thick, cellular distal airspace walls. In normally developing lungs, by comparison, remodeling of the immature parenchymal architecture is characterized by thinning of the future alveolar walls, a process predicated on cell loss through apoptosis.

Objectives: We hypothesized that minimizing lung injury, using high-frequency nasal ventilation to provide positive distending pressure with minimal assisted tidal volume displacement, would increase apoptosis and decrease proliferation among mesenchymal cells in the distal airspace walls compared with a conventional mode of support (intermittent mandatory ventilation).

Methods: Accordingly, we compared two groups of preterm lambs: one group managed by high-frequency nasal ventilation and a second group managed by intermittent mandatory ventilation. Each group was maintained for 3 days.

Measurements and Main Results: Oxygenation and ventilation targets were sustained with lower airway pressures and less supplemental oxygen in the high-frequency nasal ventilation group, in which alveolarization progressed. Thinning of the distal airspace walls was accompanied by more apoptosis, and less proliferation, among mesenchymal cells of the high-frequency nasal ventilation group, based on morphometric, protein abundance, and mRNA expression indices of apoptosis and proliferation.

Conclusions: Our study shows that high-frequency nasal ventilation preserves the balance between mesenchymal cell apoptosis and proliferation in the distal airspace walls, such that alveolarization progresses.

Key Words: alveolar formation • bronchopulmonary dysplasia • chronic lung disease of prematurity • morphometry • stereology

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Growing clinical evidence suggests that nasal continuous positive airway pressure (nCPAP) reduces the risk for premature infants to develop bronchopulmonary dysplasia, but this remains controversial. The biological basis for differences between the effects of nCPAP and standard mechanical ventilation are uncertain. What This Study Adds to the Field We report that high frequency nasal ventilation, which is similar to nCPAP, alters the pattern of apoptosis and proliferation of mesenchymal cells in the distal airspace walls in the immature lung, which may account for differences in outcomes.