Human Neutrophil Elastase and Peptidase Inhibitor 3 for Prediction of Mortality and Severity of Pediatric Acute Respiratory Distress Syndrome

INTRODUCTION: There is lack of prognostic markers in pediatric acute respiratory distress syndrome (PARDS). The role of two newer biomarkers human neutrophil elastase (HNE) and peptidase inhibitor-3 (PI3) in predicting severity and mortality in PARDS is not clear. OBJECTIVES: To study role of human neutrophil elastase (HNE) and peptidase inhibitor-3 (PI3) in predicting severity and mortality in PARDS MATERIALS AND METHODS: In this prospective observational study a total of 35 mechanically ventilated children with PARDS between the ages of 1 month to 18 years were enrolled by convenient sampling technique. We excluded children with perinatal related lung disease like apnea of prematurity, bronchopulmonary dysplasia, chronic lung diseases, history of pneumonectomy, immunodeficiency state, malignancies, post organ transplant and those who developed ARDS prior to ICU admission. On day 1, 3, 7 children were assessed for severity of ARDS and serum levels of HNE, PI3. We used both PALICC-1 and PALICC-2 for definition and severity of PARDS. We followed children for 28 days post enrolment. RESULTS: Most severe PARDS were seen at day 3 (33.3%) as compared to 20% on day 1 and none on day 7. As compared to day 1 and 7; mean levels of HNE(ng/mL) on day 3 in severe PARDS was significantly higher as compared to mild/moderate (34.36±13.79 versus 23.87±1.73 respectively; p =0.03). On day 3, Mean levels of PI3(pg/mL) in severe PARDS was significantly lower as compared to mild/moderate PARDS (953.3±85.82 vs 1275.61± 160.84 respectively; p <0.0001). Mean serum HNE at day 3 in non-survivors was significantly higher as compared to survivors (33.61±13.4 versus 23.79±1.74 respectively; p=0.028). Mean serum PI3 at day 3 in non-survivors was significantly lower as compared to survivors (954.86±82.01 vs 1290.06±149.46; p<0.0001). Area under the ROC curve on day 3 for HNE and PI3 was 0.93 and 0.96 respectively higher than day 1 and 7. DISCUSSIONS/CONCLUSIONS: The levels of HNE and PI3 showed outstanding discriminatory power to predict severity and mortality in PARDS. Wang Z et al conducted a study on these two biomarkers and also noticed similar findings.(1,2) They enrolled two groups of patients; 1) ARDS and 2) At risk of ARDS as control group. They found that patients with ARDS had higher HNE and Lower PI3 levels (p value 0.01 and 0.005 respectively). The difference in ratio of HNE:PI3 was even highly significant (p value 0.0001). With the onset of ARDS, the patients had significantly higher HNE and lower PI3 when compared with patients with no ARDS. However, in this study, they collected samples within 48 hours of ARDS diagnosis and next sample after 3 days of first sample collection. Zhu et al studied both biomarkers in 167 adult patients who were at risk of developing ARDS, documented similar findings i.e. higher HNE levels and lower PI3 levels in patients who died. A combination of HNE and PI3 had the discrimination ability for 28-day mortality (AUC-0.76, 95% CI: 0.69–0.83) which was better than PF ratio and severity scores (APACHE II).