Liggins Institute


FLORA study

Does bias gas flow in ventilated preterm babies affect lung injury or the risk of bronchopulmonary dysplasia?

Rates of preterm delivery are increasing worldwide with about 1-2% of the babies being born before 28 weeks’ gestation. Half of these babies will develop bronchopulmonary dysplasia (BPD), which means they have an ongoing need for oxygen or respiratory support once they are 36 weeks corrected gestation. These babies generally require longer hospitalisation, more frequent re-admission to hospital and they are at a higher risk of developing asthma. Respiratory disease/BPD contributes significantly to the neonatal health care costs.

BPD has multifactorial origins with factors such as prematurity, infection and mechanical ventilation all playing a role. The adverse effect of some of these factors is likely to be mediated via activation of inflammatory pathways in the preterm lung. An inflammatory response occurs rapidly following onset of mechanical ventilation and increased concentrations of pro-inflammatory cytokines in tracheal secretions are associated with risk of later BPD.

Studies in preterm lambs have demonstrated that higher bias gas flows are associated with increased histological evidence of lung injury, up-regulation of early response genes known to play a role in acute and chronic lung disease in the human, and decreased ventilatory efficiency. These changes occurred following only 2 hours of ventilation at higher bias gas flows. During ventilation of the newborn the flow is typically set at 8-10L/min, although evidence for this to be the correct setting is lacking.

The FLORA study (ACTRN12611000628943) is a multicentre pilot study in preterm babies, born before 28 weeks’ gestation or with a birth weight of less than 1,000 g, who require ventilation in the first week of life. They will be randomly assigned to either the standard gas flow of 10L/min, or a low gas flow of 4L/min. Primary outcomes will be (cytokine) IL-8 concentrations in tracheal aspirates (TA) and number of ventilated days. Secondary outcomes will be clinical outcomes, such as BPD and serious neonatal morbidity, and concentrations of other biomarkers in tracheal aspirates and blood. Further blood samples will be stored in anticipation of the validation of an assay for mRNA levels of acute early response genes.

If feasible, data generated by this pilot study will be used to develop a larger multicentre study powered to detect a difference in BPD.