Practical parameter identifiability of respiratory mechanics in the extremely preterm infant

TL;DR

This study assesses the parameter identifiability of a nonlinear respiratory mechanics model for extremely preterm infants, using sensitivity analysis and data fitting to improve understanding of lung function and health status.

Contribution

It applies advanced sensitivity analysis and subset selection methods to identify key parameters in a nonlinear respiratory model specific to preterm infants.

Findings

Eleven parameters significantly influence model outputs.

The model successfully estimates patient-specific health parameters.

Sensitivity analysis guides effective parameter subset selection.

Abstract

The complexity of mathematical models describing respiratory mechanics has grown in recent years, however, parameter identifiability of such models has only been studied in the last decade in the context of observable data. This study investigates parameter identifiability of a nonlinear respiratory mechanics model tuned to the physiology of an extremely preterm infant, using global Morris screening, local deterministic sensitivity analysis, and singular value decomposition-based subset selection. The model predicts airflow and dynamic pulmonary volumes and pressures under varying levels of continuous positive airway pressure, and a range of parameters characterizing both surfactant-treated and surfactant-deficient lung. Sensitivity analyses indicated eleven parameters influence model outputs over the range of continuous positive airway pressure and lung health scenarios. The model was adapted to data from a spontaneously breathing 1 kg infant using gradient-based optimization to estimate the parameter subset characterizing the patient's state of health.