Modeling the oxygen uptake kinetics during exercise testing of patients with chronic obstructive pulmonary diseases using nonlinear mixed models.

Florent Baty,Martin Brutsche,Daniel Gerhard,Arnoldus Van Gestel,Christian Ritz

doi:10.1186/s12874-016-0173-8

Florent Baty, Martin Brutsche + Show 3 more

Open Access

https://doi.org/10.1186/s12874-016-0173-8

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Abstract

BackgroundThe six-minute walk test (6MWT) is commonly used to quantify exercise capacity in patients with several cardio-pulmonary diseases. Oxygen uptake (ntttttttdot {mathrm {V}}nttttttO2) kinetics during 6MWT typically follow 3 distinct phases (rest, exercise, recovery) that can be modeled by nonlinear regression. Simultaneous modeling of multiple kinetics requires nonlinear mixed models methodology. To the best of our knowledge, no such curve-fitting approach has been used to analyze multiple ntttttttdot {mathrm {V}}nttttttO2 kinetics in both research and clinical practice so far.MethodsIn the present study, we describe functionality of the R package medrc that extends the framework of the commonly used packages drc and nlme and allows fitting nonlinear mixed effects models for automated nonlinear regression modeling. The methodology was applied to a data set including 6MWT ntttttttdot {mathrm {V}}nttttttO2 kinetics from 61 patients with chronic obstructive pulmonary disease (disease severity stage II to IV). The mixed effects approach was compared to a traditional curve-by-curve approach.ResultsA six-parameter nonlinear regression model was jointly fitted to the set of ntttttttdot {mathrm {V}}nttttttO2 kinetics. Significant differences between disease stages were found regarding steady state ntttttttdot {mathrm {V}}nttttttO2 during exercise, ntttttttdot {mathrm {V}}nttttttO2 level after recovery and ntttttttdot {mathrm {V}}nttttttO2 inflection point in the recovery phase. Estimates obtained by the mixed effects approach showed standard errors that were consistently lower as compared to the curve-by-curve approach.ConclusionsHereby we demonstrate the novelty and usefulness of this methodology in the context of physiological exercise testing.Electronic supplementary materialThe online version of this article (doi:10.1186/s12874-016-0173-8) contains supplementary material, which is available to authorized users.

Highlights

The six-minute walk test (6MWT) is commonly used to quantify exercise capacity in patients with several cardio-pulmonary diseases
Modeling V O2 kinetics during exercise testing in patients with chronic obstructive pulmonary disease (COPD) is a revelant topic
COPD dataset Patients with COPD referred to the Department of Pulmonary Medicine of the University Hospital of Basel (Switzerland) for a 6-Minute Walk Test (6MWT) gave their informed consent to participate to the study

Summary

Introduction

The six-minute walk test (6MWT) is commonly used to quantify exercise capacity in patients with several cardio-pulmonary diseases. Oxygen uptake (VO2) kinetics during 6MWT typically follow 3 distinct phases (rest, exercise, recovery) that can be modeled by nonlinear regression. The 6-Minute Walk Test (6MWT) is routinely used to quantify submaximal exercise capacity in patients with chronic cardio-pulmonary diseases [1]. It is considered as the test of choice to quantify functional capacity and patient’s daily life activities [2]. In the field of pulmonary medicine, there is a growing interest in estimating exercise parameters capable of objectively evaluating the functional capacity of patients with chronic obstructive pulmonary disease (COPD). A modeling approach insures that parameters are estimated in an objective and systematic manner, fully exploiting the information available in the kinetics data

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