Pediatrics: Pediatric Pulmonary |

Increased MMP-9 Activity Measured in Nasal Secretions of Hospitalized Children With RSV Infection Is Predictive of Disease Severity FREE TO VIEW

Wei Wei Zhang, BS; Kate Sewell, RN; Chad Steele, PhD; Mark Prichard, PhD; Richard Whitley, MD; Michele Kong, MD
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UAB, Birmingham, AL

Copyright 2016, American College of Chest Physicians. All Rights Reserved.

Chest. 2016;150(4_S):961A. doi:10.1016/j.chest.2016.08.1064
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SESSION TITLE: Pediatric Pulmonary

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Tuesday, October 25, 2016 at 02:45 PM - 04:15 PM

PURPOSE: Introduction: Respiratory Syncytial Virus (RSV) infection is the leading cause of hospital admission in children. Despite the global burden of RSV disease, management remains supportive. We have previously identified dysregulated protease activity, in particular, matrix metalloproteinase (MMP)-9 in children with RSV-induced respiratory failure. In children who were intubated and receiving mechanical ventilation, high levels of MMP-9 correlated with worse clinical measures of disease severity. The purpose of our study is to test the hypothesis that high levels of MMP-9 activity is measured early in the course of RSV infection, prior to the onset of respiratory failure (necessitating mechanical ventilation) and is predictive of disease severity.

METHODS: Nasal secretions were collected from 67 pediatric patients admitted to the Intensive Care Unit, Special Care Unit (SCU) and Respiratory Unit (all units provide a higher level of care for moderate to severe respiratory illness) with RSV infection, and 36 pediatric patients who had viral symptoms but tested negative for RSV (controls). Nasal samples were analyzed for total concentrations of MMP-9 (including pro-MMP-9) and active MMP-9; regulators of MMP-9 activity such as Tissue Inhibitor of Matrix Metalloproteinase (TIMP)-1, and other inflammatory biomarkers and cytokines linked with RSV infection [such as interleukin (IL)-1, IL-4, IL-8, IL-10, and interferon gamma (IFN)]. MMP-9 and the other cytokine activities were measured by ELISA and multiplexed assays, and correlated with clinical indicators of disease severity and outcome measures.

RESULTS: 61.2% of our RSV patients had bronchiolitis, while the remainder had RSV pneumonia. The mean duration of oxygen support was 7.0 days ± 0.9 days, while the mean length of hospitalization was 9.8 ± 1.2 days. In this cohort of patients, 29%, 23% and 48% of RSV patients were admitted to the ICU, SCU and Respiratory Floor, respectively. High levels of active MMP-9 (endogenously present) were measured in the nasal secretions of hospitalized infants and children, during the first day of their hospital admission (regardless of unit). Total MMP-9 (includes pro-MMP-9) was similarly increased, and compared to the controls, higher MMP-9:TIMP-1 ratios were consistently measured in the nasal secretions. In contrast to the control subjects, higher levels of nasal IL-1, IL-4, IL-8 and IL-10 were measured in RSV patients. INFs (α/γ) were also increased, likely representing the host response to the RSV infection. Patients who had the longest duration of oxygen requirement had the highest levels of nasal MMP-9 activity. In the control non-RSV group, no correlation was observed between all the measured biomarkers and clinical markers of disease severity and outcome measures.

CONCLUSIONS: Dysregulated MMP-9 activity, and an increased pro-inflammatory state is present early on in RSV lung disease. High levels of active MMP-9 correlated with duration of oxygen requirement in pediatric subjects with RSV infection.

CLINICAL IMPLICATIONS: Our findings identify MMP-9 as a potential early biomarker of disease severity in pediatric RSV infection.

DISCLOSURE: The following authors have nothing to disclose: Wei Wei Zhang, Kate Sewell, Chad Steele, Mark Prichard, Richard Whitley, Michele Kong

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