A recombinant fragment of human surfactant protein D reduces lung inflammation in preterm lambs.

BACKGROUND: Bronchopulmonary dysplasia (BPD), the major chronic respiratory morbidity in extremely preterm infants, is largely driven by inflammation. Preterm lungs are deficient of surfactant protein D (SP-D), an immunomodulatory protein absent in current commercial surfactant preparations. We hypothesised that using a recombinant fragment of human SP-D (rfhSP-D) as an adjuvant to exogenous surfactant therapy would reduce ventilator-induced inflammation. METHODS: We utilised a preterm lamb model of ventilator-associated lung injury. Mechanically ventilated preterm lambs were randomised into control and two treated groups, receiving endotracheal surfactant at 15 min post-delivery. Physiological parameters were measured throughout the experiment. Lung tissue was analysed for changes in alveolar architecture and expression levels of pro-inflammatory cytokines. Bronchioalveolar lavage (BAL) was analysed for SP-D concentration, and inflammatory cells. RESULTS: Intratracheal administration of rfhSP-D improved respiratory outcomes, significantly increased airspace and lung compliance in treated groups. Treated lambs also showed a reduction in lung tissue gene expression of inflammatory cytokines and inflammatory cell counts. CONCLUSION: Intratracheal administration of rfhSP-D did not negatively impact standard surfactant therapy and appeared to complement it. The administration of rfhSP-D as an adjuvant to standard surfactant therapy effectively reduced lung inflammation supporting the potential therapeutic use of rfhSP-D for preterm infants at risk of developing BPD. IMPACT: We have successfully developed and tested a novel recombinant fragment of human surfactant protein D (rfhSP-D) capable of reducing ventilator-associated lung inflammation in a pre-term lamb model. These results suggest rfhSP-D may be a novel potentially useful therapy for Bronchopulmonary dysplasia (BPD) in combination with currently available surfactant replacement therapies and serves as justification for a first in human clinical trial in mechanically ventilated infants. If successful, rfhSP-D could become a therapeutic candidate to mitigate pulmonary inflammation and improve lung outcomes, potentially offering a novel therapeutic avenue in the prevention or management of BPD.