Abstract

Introduction: Poor airway epithelial repair and deficient barrier integrity may contribute to reduced lung function after preterm birth. Azithromycin (AZM) has been shown to improve epithelial wound repair and barrier function in other chronic lung diseases. We hypothesised that AZM would improve repair as well as barrier function of primary nasal epithelial cells (NECs) of preterm birth survivors. 
Methods: Very preterm NECs (<32 weeks gestation, n=12, 1.4±0.1 years corrected postnatal age) were cultured as monolayers, wounded, AZM treated (10, 1 and 0.1 µg/ml), and imaged frequently over 72h to assess wound repair. Differentiated cultures were also established from term (n=8, 2.7±0.6 years) and preterm (n=12, 1.4±0.1 year) NECs and treated with AZM (0.4 µg/ml) for 10 days. Barrier integrity was measured via transepithelial electrical resistance (TEER) and cell permeability.
Results: Preterm NECs showed variable wound repair and were classed as repairers (n=7, 98.6±3.5% repair) or non-repairers (n=5, 61.1±21.9% repair). AZM enhanced wound repair of non-repairers at all doses (p<0.01), with the greatest improvement seen at 1 µg/ml (29.3±7.4%, p<0.0001). Although TEER did not differ between cohorts, differentiated cultures were significantly more permeable in the preterm group (2.3 fold; p<0.0001). AZM did not change permeability in the preterm cohort (p>0.05).
Conclusions: Preterm NECs have impaired wound repair and increased permeability. AZM improves the defective wound repair but does not resolve the permeability. AZM may be a candidate for future clinical studies to improve lung health in survivors of preterm birth, but further investigation is required.