371 - Urine F2-isoprostanes: A Potential Biomarker for Severity of Viral Acute Respiratory Infections in Infancy

Publication Number: 2360.371

Brooke Quertermous, Vanderbilt University Medical Center, Nashville, TN, United States; Tebeb Gebretsadik, Vanderbilt University Medical Center, Nashville, TN, United States; Brittney Snyder, Vanderbilt University School of Medicine, Nashville, TN, United States; Ginger L.. Milne, Vanderbilt University Medical Center, Nashville, TN, United States; James Chappell, Vanderbilt University School of Medicine, Nashville, TN, United States; Larry J. Anderson, Emory University School of Medicine, Atlanta, GA, United States; Stokes Peebles, Vanderbilt University Medical Center, Nashville, Tennessee, TN, United States; Tina Hartert, Center for Asthma Research, Nashville, TN, United States; Christian Rosas-Salazar, Vanderbilt University School of Medicine, Nashville, TN, United States

Background: F2-isoprostanes (F2-isoPs) are reliable markers of oxidative stress and have been associated with acute and chronic pulmonary diseases in adults. However, little is known about the relationship between F2-isoPs and clinical outcomes of viral acute respiratory infections (ARI) in young children.

Objective: To examine the association between urine F2-isoPs and the severity of viral ARIs during infancy.

Design/Methods: F2-IsoPs were measured using liquid chromatography-mass spectrometry in a subset of urine samples collected during a viral ARI from previously healthy, term infants from discovery (INSPIRE, a population-based birth cohort; n=331) and validation (TCRI, a cohort of children enrolled during an acute care encounter for bronchiolitis; n=51) cohorts. Viral ARI severity was ascertained using the validated Respiratory Severity Score (RSS) and need for supplemental oxygen. Bivariate tests and multivariate regression analyses were performed to assess the association between urine F2-isoPs (normalized for creatinine concentration) and markers of viral ARI severity in each cohort.

Results: Median urine F2-IsoPs during viral ARI were 5.1 (interquartile range [IQR]=3.1-7.7) and 6.6 (IQR=3.9-9.9) ng/mg of creatinine in INSPIRE and TCRI, respectively. The median RSS was 3.0 (IQR=2.0-4.0) and 6.0 (IQR=4.0-7.8) in INSPIRE and TCRI, respectively. After adjusting for age, sex, maternal asthma, and household exposure to tobacco smoke, an IQR increase in urine F2-IsoPs was associated with a higher RSS (β =0.31; 95%CI=0.02, 0.61) in INSPIRE. We found a similar association in TCRI, although this did not reach statistical significance (β=0.5, 95%CI=-0.25, 1.19). In bivariate analyses, urine F2-IsoPs during a viral ARI were significantly higher among infants requiring supplemental oxygen than those who did not in both cohorts (7.6 [IQR=4.6-9.6] vs. 5.5 [IQR 3.5-8.3] ng/mg of creatinine [p=0.02] in INSPIRE; and 7.1 [IQR=5.3-10.4] vs. 3.7 [IQR = 2.7-6.7] ng/mg of creatinine [p=0.033] in TCRI).

Conclusion(s): Urine F2-IsoPs were positively associated with the severity of viral ARIs during infancy. Despite differences in study populations, we replicated the magnitude and directionality of the effect across independent pediatric cohorts. Urine F2-IsoPs might serve as a non-invasive biomarker of viral ARI severity during early life. Further studies in larger and diverse populations are required to validate these associations and establish the accuracy , reproducibility, and clinical utility of urine F2-IsoPs quantification in predicting short- and long-term morbidity in infants with viral ARIs.