Diagnostic accuracy of eNose 'breathprints' for therapeutic drug monitoring of Tacrolimus trough levels in lung transplantation.

IF 3.7 4区 医学 Q1 BIOCHEMICAL RESEARCH METHODS
Nynke Wijbenga, Marjolein M Muller, Rogier A S Hoek, Bas J Mathot, Leonard Seghers, Joachim G J V Aerts, Brenda C M de Winter, Daniel Bos, Olivier C Manintveld, Merel E Hellemons
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Abstract

In order to prevent long-term immunity-related complications after lung transplantation, close monitoring of immunosuppressant levels using therapeutic drug monitoring (TDM) is paramount. Novel electronic nose (eNose) technology may be a non-invasive alternative to the current invasive procedures for TDM. We investigated the diagnostic and categorization capacity of eNose breathprints for Tacrolimus trough blood plasma levels (TACtrough) in lung transplant recipients (LTRs). We performed eNose measurements in stable LTR attending the outpatient clinic. We evaluated (1) the correlation between eNose measurements and TACtrough, (2) the diagnostic capacity of eNose technology for TACtrough, and (3) the accuracy of eNose technology for categorization of TACtroughinto three clinically relevant categories (low: <7µg ml-1, medium: 7-10µg ml-1, and high: >10µg ml-1). A total of 186 measurements from 86 LTR were included. There was a weak but statistically significant correlation (r= 0.21,p= 0.004) between the eNose measurements and TACtrough. The root mean squared error of prediction for the diagnostic capacity was 3.186 in the training and 3.131 in the validation set. The accuracy of categorization ranged between 45%-63% for the training set and 52%-69% in the validation set. There is a weak correlation between eNose breathprints and TACtroughin LTR. However, the diagnostic as well as categorization capacity for TACtroughusing eNose breathprints is too inaccurate to be applicable in TDM.

eNose“呼吸指纹”在肺移植中监测他克莫司谷水平的诊断准确性。
为了预防肺移植术后长期的免疫相关并发症,使用治疗性药物监测(TDM)密切监测免疫抑制剂水平至关重要。新型电子鼻(eNose)技术可能是目前创伤性TDM手术的非侵入性替代方案。我们研究了肺移植受者(LTRs)呼气指纹通过血浆水平(TACtrough)对他克莫司的诊断和分类能力。我们对在门诊就诊的稳定LTR患者进行了eNose测量。我们评估了(1)eNose测量值与tac槽之间的相关性,(2)eNose技术对tac槽的诊断能力,以及(3)eNose技术将tac槽分为三个临床相关类别的准确性(低:µg ml-1,中:7-10µg ml-1,高:>10µg ml-1)。共纳入86个LTR的186个测量值。eNose测量值与tacthrough之间存在微弱但有统计学意义的相关性(r= 0.21,p= 0.004)。训练集预测诊断能力的均方根误差为3.186,验证集预测诊断能力的均方根误差为3.131。训练集的分类准确率为45%-63%,验证集的分类准确率为52%-69%。eNose呼气指纹与TACtroughin LTR之间的相关性较弱,然而,TACtroughin呼气指纹的诊断和分类能力太不准确,无法应用于TDM。
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来源期刊
Journal of breath research
Journal of breath research BIOCHEMICAL RESEARCH METHODS-RESPIRATORY SYSTEM
CiteScore
7.60
自引率
21.10%
发文量
49
审稿时长
>12 weeks
期刊介绍: Journal of Breath Research is dedicated to all aspects of scientific breath research. The traditional focus is on analysis of volatile compounds and aerosols in exhaled breath for the investigation of exogenous exposures, metabolism, toxicology, health status and the diagnosis of disease and breath odours. The journal also welcomes other breath-related topics. Typical areas of interest include: Big laboratory instrumentation: describing new state-of-the-art analytical instrumentation capable of performing high-resolution discovery and targeted breath research; exploiting complex technologies drawn from other areas of biochemistry and genetics for breath research. Engineering solutions: developing new breath sampling technologies for condensate and aerosols, for chemical and optical sensors, for extraction and sample preparation methods, for automation and standardization, and for multiplex analyses to preserve the breath matrix and facilitating analytical throughput. Measure exhaled constituents (e.g. CO2, acetone, isoprene) as markers of human presence or mitigate such contaminants in enclosed environments. Human and animal in vivo studies: decoding the ''breath exposome'', implementing exposure and intervention studies, performing cross-sectional and case-control research, assaying immune and inflammatory response, and testing mammalian host response to infections and exogenous exposures to develop information directly applicable to systems biology. Studying inhalation toxicology; inhaled breath as a source of internal dose; resultant blood, breath and urinary biomarkers linked to inhalation pathway. Cellular and molecular level in vitro studies. Clinical, pharmacological and forensic applications. Mathematical, statistical and graphical data interpretation.
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