Biosimulation of acute phonotrauma: An extended model

Authors

  • Nicole Y. K. Li PhD,

    1. Department of Surgery, University of Wisconsin-Madison, Madison, Wisconsin
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  • Yoram Vodovotz PhD,

    1. Department of Surgery, University of Pittsburgh Voice Center, University of Pittsburgh, Pittsburgh
    2. Center for Inflammation and Regenerative Modeling, University of Pittsburgh Voice Center, University of Pittsburgh, Pittsburgh
    3. McGowan Institute for Regenerative Medicine, University of Pittsburgh Voice Center, University of Pittsburgh, Pittsburgh
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  • Kevin H. Kim PhD,

    1. Department of Psychology in Education, University of Pittsburgh Voice Center, University of Pittsburgh, Pittsburgh
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  • Qi Mi PhD,

    1. Center for Inflammation and Regenerative Modeling, University of Pittsburgh Voice Center, University of Pittsburgh, Pittsburgh
    2. Department of Sports Medicine and Nutrition, University of Pittsburgh Voice Center, University of Pittsburgh, Pittsburgh
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  • Patricia A. Hebda PhD,

    1. McGowan Institute for Regenerative Medicine, University of Pittsburgh Voice Center, University of Pittsburgh, Pittsburgh
    2. Department of Otolaryngology, University of Pittsburgh Voice Center, University of Pittsburgh, Pittsburgh
    3. Department of Pathology, University of Pittsburgh Voice Center, University of Pittsburgh, Pittsburgh
    4. Otolaryngology Wound Healing Laboratory, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, U.S.A
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  • Katherine Verdolini Abbott PhD

    Corresponding author
    1. McGowan Institute for Regenerative Medicine, University of Pittsburgh Voice Center, University of Pittsburgh, Pittsburgh
    2. Department of Communication Science and Disorders, University of Pittsburgh Voice Center (K.V.A.), University of Pittsburgh, Pittsburgh
    • Department of Communication Science and Disorders, School of Health and Rehabilitation Sciences, University of Pittsburgh, 4033 Forbes Tower, Pittsburgh, PA 15260
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  • The study was funded by the National Institutes of Health grants R01-DC-008290 and P50-GM-53789. The authors have no other funding, financial relationships, or conflicts of interest to disclose.

Abstract

Objectives/Hypothesis:

Personalized, preemptive, and predictive medicine is a central goal of contemporary medical care. The central aim of the present study was to investigate the utility of mechanistic computational modeling of inflammation and healing to address personalized therapy for patients with acute phonotrauma.

Study Design:

Computer simulation.

Methods:

Previously reported agent-based models (ABMs) of acute phonotrauma were extended with additional inflammatory mediators as well as extracellular matrix components. The models were calibrated with empirical data for a panel of biomarkers—interleukin (IL)-1β, IL-6, IL-8, IL-10, tumor necrosis factor-α and matrix metalloproteinase-8—from individual subjects following experimentally induced phonotrauma and a randomly assigned voice treatment namely voice rest, resonant voice exercise, and spontaneous speech. The models' prediction accuracy for biomarker levels was tested for a 24-hour follow-up time point.

Results:

The extended ABMs reproduced and predicted trajectories of biomarkers seen in experimental data. The simulation results also agreed qualitatively with various known aspects of inflammation and healing. Model prediction accuracy was generally better following individual-based calibration as compared to population-based calibration. Simulation results also suggested that the special form of vocal fold oscillation in resonant voice may accelerate acute vocal fold healing.

Conclusions:

The calibration of inflammation/healing ABMs with subject-specific data appears to optimize the models' prediction accuracy for individual subjects. This translational application of biosimulation might be used to predict individual healing trajectories, the potential effects of different treatment options, and most importantly, provide new understanding of health and healing in the larynx and possibly in other organs and tissues as well.

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