Oxygen and mechanical stretch in the developing lung: risk factors for neonatal and pediatric lung disease

Abstract

Chronic airway diseases, such as wheezing and asthma, remain significant sources of morbidity and mortality in the pediatric population. This is especially true for preterm infants who are impacted both by immature pulmonary development as well as disproportionate exposure to perinatal insults that may increase the risk of developing airway disease. Chronic pediatric airway disease is characterized by alterations in airway structure (remodeling) and function (increased airway hyperresponsiveness), similar to adult asthma. One of the most common perinatal risk factors for development of airway disease is respiratory support in the form of supplemental oxygen, mechanical ventilation, and/or CPAP. While clinical practice currently seeks to minimize oxygen exposure to decrease the risk of bronchopulmonary dysplasia (BPD), there is mounting evidence that lower levels of oxygen may carry risk for development of chronic airway, rather than alveolar disease. In addition, stretch exposure due to mechanical ventilation or CPAP may also play a role in development of chronic airway disease. Here, we summarize the current knowledge of the impact of perinatal oxygen and mechanical respiratory support on the development of chronic pediatric lung disease, with particular focus on pediatric airway disease. We further highlight mechanisms that could be explored as potential targets for novel therapies in the pediatric population.

BMAL1 sex‐specific effects in the neonatal mouse airway exposed to moderate hyperoxia

“…In our recent in vitro study using human fetal ASM, we showed clock gene expression sensitivity to O 2 such that O 2 may indeed be altering the clock (Bartman et al., 2021 ). Clinically, when neonates are administered supplemental O 2 , they experience shifts in O 2 saturation leading to intermittent hypoxia‐hyperoxia (Zhang et al., 2023 ). It is therefore important to consider not only the percentage of oxygen in experimental studies, but also the timing (e.g., chronic versus intermittent) and cyclicity of it as well.…”

Prevalence, Prevention and Management of Bronchopulmonary Dysplasia

“…117 There are, however, legitimate concerns regarding the impact of long-term continuous distending pressure on the developing lung. 247 The utility of routine extension of CPAP until 32 weeks PMA or 1250g versus gradual weaning from CPAP to HFNC will be tested objectively in a clinical trial that is currently recruiting patients (NCT05557139). Information from this study may help further inform NRS practices used beyond 7 days of life.…”