Assessment of Neutrophilic Function in Neonates with Respiratory Distress Syndrome

Abstract

Infant respiratory distress syndrome (RDS) is a syndrome in premature infants caused by developmental insufficiency of surfactant production and structural immaturity in the lungs resulting in significant hypoxemia. Polymorphonuclear leukocytes (PMNs) are the most abundant cellular component of the host immune system and primary mediators of the innate immune response to invading microorganisms. PMN function includes recruitment to sites of inflammation involving a dynamic series of events including chemotaxis, rolling, activation, adhesion, firm adhesion, transendothelial migration, pathogen recognition and phagocytosis followed by intracellular killing. Most studies of neutrophil function have been conducted under conditions of ambient oxygen, but inflamed sites where neutrophils operate may be extremely hypoxic and lack of molecular oxygen at sites of infection may influence profoundly the interaction between the invading pathogen and the host phagocytic cell tasked with eliminating or confining infection. The aim of this cross-sectional case-control study is to assess neutrophil number and function including cellular adhesion, activation and capability for intracellular killing in late preterm neonates with respiratory distress syndrome. Late preterm age was selected to abolish the effect of significant prematurity on maturation of the immune system. The study sample included 30 late gestational preterm with respiratory distress (after consideration of inclusion and exclusion criteria) in addition to 15 term apparently healthy neonates and 15 normal adults. The patients were evaluated clinically and laboratorially including complete blood counts with manual differential counts, in addition to tests of neutrophil functions. Three measures of neutrophil functions were performed in all enrolled subjects including CD11b (for neutrophil adhesion), CD62L (for neutrophil activation) and DHR 123 (for generation of superoxide radicals essential for intracellular killing). The severity of RDS was assessed clinically and radiologically. The 30 patients in the studied group included 11 patients who were born at the gestational age of 35 weeks and 19 patients at the gestational age of 36 weeks. Mothers of patients who were born by cesarean section (C.S) have received antenatal steroids 24-48 hours before delivery. Radiological assessment of the RDS group showed that grade II was the most frequent (50%) and grade I was the least frequent (23.3%), while none of the enrolled patients had grade IV RDS. The studied patient group (n = 30) included 12 females and 18 males. Comparisons between RDS group and the control group were insignificant regarding gender, mode of delivery, frequency of parity and gravidity. Also there were no significant differences between different radiographic grades of RDS among patients in terms of gender, mode of delivery, gestational age, frequency of gravidity and frequency of parity. DHR, CD 11b and CD62L were the lowest among the patients groups followed by the neonates control group then the adult control group. There were no significant correlations between neutrophils count, DHR, CD11b and CD62L among patients’ group. Only CD11b, but not DHR or CD62L, was significantly lower with higher grades of respiratory distress. Using ROC curves, cutoff values were obtained for the three markers: DHR, CD 11b and CD62L that could differentiate patients from neonate and adult controls with sensitivity and specificity values approaching or exceeding 90%. In conclusion, neonates with RDS shows variable affection of neutrophil functions which could be attributed to several factors including the disease itself with its resultant hypoxia, the gestational age, the postnatal age at time of assessment and the use of antenatal steroids. The defects in neutrophil function may pose those neonates at an increased risk of infections and septicemia. Further studies on larger scales are recommended to elucidate the effect of RDS on neutrophils function and whether these effects are associated with increased infections or other complications like bronchopulmonary dysplasia.