A patient-specific in silico model of inflammation and healing tested in acute vocal fold injury.

Nicole Y K Li,Qi Mi,Gilles Clermont,Katherine Verdolini,Elaine N Rubinstein,Yoram Vodovotz,Patricia A Hebda,Marie Csete

doi:10.1371/journal.pone.0002789

Abstract

The development of personalized medicine is a primary objective of the medical community and increasingly also of funding and registration agencies. Modeling is generally perceived as a key enabling tool to target this goal. Agent-Based Models (ABMs) have previously been used to simulate inflammation at various scales up to the whole-organism level. We extended this approach to the case of a novel, patient-specific ABM that we generated for vocal fold inflammation, with the ultimate goal of identifying individually optimized treatments. ABM simulations reproduced trajectories of inflammatory mediators in laryngeal secretions of individuals subjected to experimental phonotrauma up to 4 hrs post-injury, and predicted the levels of inflammatory mediators 24 hrs post-injury. Subject-specific simulations also predicted different outcomes from behavioral treatment regimens to which subjects had not been exposed. We propose that this translational application of computational modeling could be used to design patient-specific therapies for the larynx, and will serve as a paradigm for future extension to other clinical domains.

Highlights

The vocal folds are exposed to nearly continuous biomechanical stress during phonation
Our recent in vitro data from vocal fold fibroblast cultures and human data derived from concentrations of inflammatory mediators in laryngeal secretions suggest that contrary to clinical wisdom, some forms of vocal fold tissue mobilization— mobilization in so-called ‘‘resonant voice’’ exercises may be able to modulate the inflammatory and healing process by blunting the cells’ pro-inflammatory responses as well as enhancing their anti-inflammatory responses
Positive answers to these experimental questions would strengthen confidence in the eventual utility of mathematical modeling in general, and of Agent-Based Models (ABMs) in particular, for understanding the complex vocal fold wound healing system and for predicting the healing outcome after phonotrauma and varied treatment approaches

Summary

Introduction

The vocal folds are exposed to nearly continuous biomechanical stress during phonation. From the wound healing perspective, this modulation may optimize the healing outcomes of the stressed/ traumatized tissue in acute phonotrauma [19,20] Important, both in vitro and human clinical data suggest that the benefits of these tissue mobilization exercises for acute vocal fold inflammation are dose-dependent [19]. Both in vitro and human clinical data suggest that the benefits of these tissue mobilization exercises for acute vocal fold inflammation are dose-dependent [19] These observations suggest a commonality across tissue types in the response to injury, given that active rehabilitation is used to treat many types of injuries [21,22,23,24,25,26,27,28,29,30,31,32,33,34]. The cumbersome nature of data collection complicates the potential for biologically oriented clinical trials on the value of therapeutic interventions for phonotrauma in humans

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