Nasal airway epithelial repair after very preterm birth

Abstract

Preterm birth rates are increasing and now account for >11% of global births. Simultaneously, advances in neonatal care have led to increased survival of lower gestation neonates. A complication of preterm birth, and the biggest determinant of survival, is lung and airway immaturity. After preterm birth, the immature respiratory system is exposed to pro-inflammatory stimuli like injury from resuscitation and oxygen toxicity. The airway epithelium, the physical barrier between insults and the airways, is particularly vulnerable to injury. If epithelial barrier integrity cannot be restored rapidly following damage ( i.e. via aberrant repair), the respiratory system is left unprotected, increasing the risk of infection, inflammation and tissue damage. Altered epithelial repair may play an important role in the ongoing respiratory health problems experienced by preterm survivors, including severe respiratory infections throughout early life, or low and declining lung function [1–3]. Deficits are further exacerbated in those with bronchopulmonary dysplasia (BPD). The mechanisms contributing to ongoing respiratory problems are currently unknown, although probably begin in early life. Until now, understanding the role of the preterm epithelial barrier has been limited by a lack of appropriate cellular models. Our study aimed to assess the reparative capacity of the airway epithelium in survivors of preterm birth and its association with early life outcomes, with the hypothesis that preterm airway epithelial cells have an abnormal repair mechanism.

Unravelling the respiratory health path across the lifespan for survivors of preterm birth

“…82 Additional proposed mechanisms underpinning active disease in survivors born preterm include altered immune programming, microbiome dysbiosis, epithelial abnormalities, accelerated cellular ageing, and host genetics. [82][83][84][85][86][87][88] External exposures, including tobacco smoke, air pollution and repeated viral respiratory infections, may similarly initiate cellular injury and remodelling, resulting in worsening of existing lung disease. [89][90][91] Limited data exist to draw firm conclusions about underlying mechanisms associated with PLD; although it is clear that numerous active pathways and pathologies are implicated (see Figure 2 for summary).…”