Background: Bronchopulmonary dysplasia (BPD) is a chronic lung disease and major pulmonary complication after premature birth. We have previously shown that increased intermittent hypoxemia (IH) events have been correlated to adverse outcomes and mortality in extremely premature infants. We hypothesize that early IH patterns are associated with the development of BPD. Methods: IH frequency, duration, and nadirs were assessed using oxygen saturation (SpO 2 ) waveforms in a retrospective cohort of 137 extremely premature newborns (<28 weeks gestation). Daily levels of inspired oxygen and mean airway pressure exposures were also recorded. Results: Diagnosis of BPD at 36 weeks postmenstrual age was associated with increased daily IH, longer IH duration, and a higher IH nadir. Significant differences were detected through day 7 to day 26 of life. Infants who developed BPD had lower mean SpO 2 despite their expose to increased inspired oxygen and increased mean airway pressure. Conclusions: BPD was associated with more frequent, longer, and less severe IH events in addition to increased oxygen and pressure exposure within the first 26 days of life. Early IH patterns may contribute to the development of BPD or aid in identification of neonates at high-risk.

Objective: Extremely premature infants are at risk for childhood wheezing. Early respiratory support and intermittent hypoxemia (IH) events may be associated with adverse breathing outcomes. Study Design: A single-center retrospective cohort study of 137 premature infants <28 weeks gestational age characterized the associations of cumulative oxygen, cumulative mean airway pressure, IH, and oxygen saturation (SpO 2 ) on the primary outcome of prescription asthma medication use at 2 year follow-up. Relative risk was calculated by generalized estimating equations. Results: Reported asthma medication use was 46%. At 1–3 days of age, elevated cumulative oxygen exposure, increased daily IH, and lower mean SpO 2 (adjusted for gestational age and sex) and increased cumulative mean airway pressure exposure (unadjusted) were associated with asthma medication use. Conclusion: Increased oxygen and frequent IH events during just the first three days of age may help identify extremely premature newborns at risk for symptomatic childhood wheezing requiring prescription asthma medications.

Bronchopulmonary dysplasia (BPD) is characterized by lifelong obstructive lung disease and profound, refractory bronchospasm. It is observed among survivors of premature birth who have been treated with prolonged supplemental oxygen. Therapeutic options are limited. Using a neonatal mouse model of BPD, we show that hyperoxia increases activity and expression of a mediator of endogenous bronchoconstriction, S-nitrosoglutathione (GSNO) reductase. MicroRNA-342-3p, predicted in silico and shown in this study in vitro to suppress expression of GSNO reductase, was decreased in hyperoxia-exposed pups. Both pretreatment with aerosolized GSNO and inhibition of GSNO reductase attenuated airway hyperresponsiveness in vivo among juvenile and adult mice exposed to neonatal hyperoxia. Our data suggest that neonatal hyperoxia exposure causes detrimental effects on airway hyperreactivity through microRNA-342-3p–mediated upregulation of GSNO reductase expression. Furthermore, our data demonstrate that this adverse effect can be overcome by supplementing its substrate, GSNO, or by inhibiting the enzyme itself. Rates of BPD have not improved over the past two decades; nor have new therapies been developed. GSNO-based therapies are a novel treatment of the respiratory problems that patients with BPD experience.