Nasal CPAP increases alveolar number in a rhesus monkey model of moderate prematurity

Most premature human infants are born in the moderate to late preterm (MLP) range, ≥30 to <37 weeks gestation and demonstrate increased incidence of wheeze and respiratory illness as they age. Animal models suggest that mechanical lung distention stimulates lung growth and alveolar development. To determine if nasal continuous positive airway pressure (nCPAP) influences MLP infant lung development, we developed a rhesus monkey model of moderate prematurity, randomized to 9 days of nCPAP or sham nCPAP. Timed-pregnant fetuses were delivered by elective hysterotomy at gestational age (GA) 140±1 days (85% gestation, term=165 days; human equivalent of 32-34 weeks), or at GA-149±1 days (GA-control) as a relative gestational age reference. The day after delivery, the GA-140 animals were treated with nCPAP or sham for 9 days, 12 consecutive hours each day. Pulmonary function testing followed by necropsy for analysis of lung structure and gene expression was performed on the equivalent of GA-150 for all animals. The nCPAP and sham groups were clinically similar but distinct from the gestational control group. Stereological analysis of lung structure showed significantly increased numbers of alveoli in the nCPAP group compared to the sham group. Other functional and anatomic changes were consistent with increased alveolarization. Gene expression between the nCPAP and sham groups remained highly similar and distinct from GA-control animals. We show that nCPAP in MLP infants stimulates alveolarization with relatively few other changes. How this may benefit subsequent infant respiratory health requires further study.