Simulation-based optimisation to quantify heterogeneity of specific ventilation and perfusion in the lung by the Inspired Sinewave Test

M C Tran,R Bruce,S J Payne,P A Phan,V Nguyen,A D Farmery,D C Crockett,F Formenti

doi:10.1038/s41598-021-92062-w

Abstract

The degree of specific ventilatory heterogeneity (spatial unevenness of ventilation) of the lung is a useful marker of early structural lung changes which has the potential to detect early-onset disease. The Inspired Sinewave Test (IST) is an established noninvasive ‘gas-distribution’ type of respiratory test capable of measuring the cardiopulmonary parameters. We developed a simulation-based optimisation for the IST, with a simulation of a realistic heterogeneous lung, namely a lognormal distribution of spatial ventilation and perfusion. We tested this method in datasets from 13 anaesthetised pigs (pre and post-lung injury) and 104 human subjects (32 healthy and 72 COPD subjects). The 72 COPD subjects were classified into four COPD phenotypes based on ‘GOLD’ classification. This method allowed IST to identify and quantify heterogeneity of both ventilation and perfusion, permitting diagnostic distinction between health and disease states. In healthy volunteers, we show a linear relationship between the ventilatory heterogeneity versus age ({R}^{2}=0.42). In a mechanically ventilated pig, IST ventilatory heterogeneity in noninjured and injured lungs was significantly different (p < 0.0001). Additionally, measured indices could accurately identify patients with COPD (area under the receiver operating characteristic curve is 0.76, p < 0.0001). The IST also could distinguish different phenotypes of COPD with 73% agreement with spirometry.

Highlights

There is renewed interest in simple bedside/clinic-based measures of ventilatory heterogeneity as a new maker of early lung abnormality and guide for treatment[9,10]
There were no significant differences in the mean values of the lognormal distributions of either ventilation or perfusion between the normal and abnormal lung in both animal and human studies, i.e. there was no left–right shift in the position of the distributions
The standard deviations of the lognormal distributions differ significantly between the normal and the diseased lung, i.e. the distributions widen with disease

Summary

Introduction

There is renewed interest in simple bedside/clinic-based measures of ventilatory heterogeneity as a new maker of early lung abnormality and guide for treatment[9,10]. Several lung tests have been claimed to accurately measure ventilatory heterogeneity[9,11] These are not yet amenable to widespread use at the bedside or clinic. There is potential for further developing the IST to be able to characterise heterogeneity intrinsically, and independently of a second standard measure by using a simulation-based optimisation. We developed a simulation-based optimisation for the IST to estimate heterogeneity of specific ventilation and perfusion. We implemented the optimisation in two IST data sets, including human COPD data and experimental animal ARDS data. This is the first study to use IST to evaluate changes in lung heterogeneity in different lung conditions

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Conclusion