Abstract

Bronchopulmonary dysplasia (BPD) is the most common complication of extremely preterm birth. This study was aimed at detecting cytokine and fractional exhaled nitric oxide (FeNO) levels to evaluate their mechanisms and predicted significance for BPD. Preterm infants born at gestational age ≤ 32 weeks were recruited, and clinical data were collected. We detected ten cytokines, including IFN-γ, IL-10, IL-12p70, IL-13, IL-1β, IL-2, IL-4, IL-6, IL-8, and TNF-α on Days 1–3, Days 7–14, and Days 21–28 after birth by using the Meso Scale Discovery (MSD) technology. The FeNO levels of infants were measured when they met the discharge criteria. A total of 46 preterm infants were enrolled, consisting of 14 infants in BPD group and 32 infants in the control group. The gestational age (27.5 ± 1.3 vs. 29.9 ± 1.3 weeks) and birth weight (1021 ± 261 g vs. 1489 ± 357 g) were lower in the BPD group. The following were high-risk factors for BPD, as determined by multivariate logistic regression analysis: gestational age < 30 weeks, birth weight < 1000 g, PDA, longer mechanical ventilation, and higher FeNO. The cytokines of IL-6 and IL-8 on Days 7–14 and IL-4, IL-6, IL-8, and TNF-α on Days 21–28 were also high-risk factors for BPD. IL-6 contributed to BPD disease severity. Conclusion. The preterm infants with PDA and prolonged mechanical ventilation tended to develop BPD. The IL-6 and IL-8 were significantly increased on Days 7–14 and were high-risk factors for BPD. Moreover, the IL-6 level was associated with BPD disease severity. We speculated that NO was related to BPD via Th2 cell-mediated inflammatory responses such as IL-4 and IL-6. Cytokines might predict the occurrence of BPD.

Highlights

  • Bronchopulmonary dysplasia (BPD) is the most frequently reported complication of extremely preterm birth

  • Our study found that fractional exhaled nitric oxide (FeNO) and eosinophil levels were higher in the BPD group than in the non-BPD group

  • Pathological findings of the n/i/endothelial NOS (eNOS)-/- mice revealed significant decreases in bronchial eosinophilic inflammation, bronchial thickening, mucus secretion, and mRNA levels of IL-4, IL-5, and IL-13. These results indicated that NO played an important role in promoting eosinophilic inflammation and mucus hypersecretion that might be related to an increase in Th2 cytokine such as IL-4, IL-5, and IL-13 [28]

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Summary

Introduction

Bronchopulmonary dysplasia (BPD) is the most frequently reported complication of extremely preterm birth. BPD is currently regarded as a result of an aberrant respiratory distress response to the developing lungs. Mechanical ventilation and long-term use of oxygen may contribute to the onset of BPD [1]. Despite multiple strategies to provide ventilation and oxygen therapy, the incidence of BPD has not decreased. Significant advances in the development of animal BPD models have been made. Regardless, clinical research still needs to be conducted to explore the pathogenesis and treatment of BPD

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