Skip to main content
Top
Published in: Respiratory Research 1/2020

01-12-2020 | Artificial Intelligence | Research

Diagnosis of ventilator-associated pneumonia using electronic nose sensor array signals: solutions to improve the application of machine learning in respiratory research

Authors: Chung-Yu Chen, Wei-Chi Lin, Hsiao-Yu Yang

Published in: Respiratory Research | Issue 1/2020

Login to get access

Abstract

Background

Ventilator-associated pneumonia (VAP) is a significant cause of mortality in the intensive care unit. Early diagnosis of VAP is important to provide appropriate treatment and reduce mortality. Developing a noninvasive and highly accurate diagnostic method is important. The invention of electronic sensors has been applied to analyze the volatile organic compounds in breath to detect VAP using a machine learning technique. However, the process of building an algorithm is usually unclear and prevents physicians from applying the artificial intelligence technique in clinical practice. Clear processes of model building and assessing accuracy are warranted. The objective of this study was to develop a breath test for VAP with a standardized protocol for a machine learning technique.

Methods

We conducted a case-control study. This study enrolled subjects in an intensive care unit of a hospital in southern Taiwan from February 2017 to June 2019. We recruited patients with VAP as the case group and ventilated patients without pneumonia as the control group. We collected exhaled breath and analyzed the electric resistance changes of 32 sensor arrays of an electronic nose. We split the data into a set for training algorithms and a set for testing. We applied eight machine learning algorithms to build prediction models, improving model performance and providing an estimated diagnostic accuracy.

Results

A total of 33 cases and 26 controls were used in the final analysis. Using eight machine learning algorithms, the mean accuracy in the testing set was 0.81 ± 0.04, the sensitivity was 0.79 ± 0.08, the specificity was 0.83 ± 0.00, the positive predictive value was 0.85 ± 0.02, the negative predictive value was 0.77 ± 0.06, and the area under the receiver operator characteristic curves was 0.85 ± 0.04. The mean kappa value in the testing set was 0.62 ± 0.08, which suggested good agreement.

Conclusions

There was good accuracy in detecting VAP by sensor array and machine learning techniques. Artificial intelligence has the potential to assist the physician in making a clinical diagnosis. Clear protocols for data processing and the modeling procedure needed to increase generalizability.
Literature
1.
go back to reference Melsen WG, Rovers MM, Koeman M, Bonten MJ. Estimating the attributable mortality of ventilator-associated pneumonia from randomized prevention studies. Crit Care Med. 2011;39:2736–42.PubMedCrossRef Melsen WG, Rovers MM, Koeman M, Bonten MJ. Estimating the attributable mortality of ventilator-associated pneumonia from randomized prevention studies. Crit Care Med. 2011;39:2736–42.PubMedCrossRef
2.
go back to reference Richards MJ, Edwards JR, Culver DH, Gaynes RP. Nosocomial infections in combined medical-surgical intensive care units in the United States. Infect Control Hosp Epidemiol. 2000;21:510–5.PubMedCrossRef Richards MJ, Edwards JR, Culver DH, Gaynes RP. Nosocomial infections in combined medical-surgical intensive care units in the United States. Infect Control Hosp Epidemiol. 2000;21:510–5.PubMedCrossRef
3.
go back to reference Chen YY, Chen LY, Lin SY, Chou P, Liao SY, Wang FD. Surveillance on secular trends of incidence and mortality for device-associated infection in the intensive care unit setting at a tertiary medical center in Taiwan, 2000-2008: a retrospective observational study. BMC Infect Dis. 2012;12:209.PubMedPubMedCentralCrossRef Chen YY, Chen LY, Lin SY, Chou P, Liao SY, Wang FD. Surveillance on secular trends of incidence and mortality for device-associated infection in the intensive care unit setting at a tertiary medical center in Taiwan, 2000-2008: a retrospective observational study. BMC Infect Dis. 2012;12:209.PubMedPubMedCentralCrossRef
4.
go back to reference Rello J, Ollendorf DA, Oster G, Vera-Llonch M, Bellm L, Redman R, Kollef MH, Group VAPOSA. Epidemiology and outcomes of ventilator-associated pneumonia in a large US database. Chest. 2002;122:2115–21.CrossRefPubMed Rello J, Ollendorf DA, Oster G, Vera-Llonch M, Bellm L, Redman R, Kollef MH, Group VAPOSA. Epidemiology and outcomes of ventilator-associated pneumonia in a large US database. Chest. 2002;122:2115–21.CrossRefPubMed
5.
go back to reference Iregui M, Ward S, Sherman G, Fraser VJ, Kollef MH. Clinical importance of delays in the initiation of appropriate antibiotic treatment for ventilator-associated pneumonia. Chest. 2002;122:262–8.PubMedCrossRef Iregui M, Ward S, Sherman G, Fraser VJ, Kollef MH. Clinical importance of delays in the initiation of appropriate antibiotic treatment for ventilator-associated pneumonia. Chest. 2002;122:262–8.PubMedCrossRef
6.
go back to reference Torres A, Fabregas N, Ewig S, de la Bellacasa JP, Bauer TT, Ramirez J. Sampling methods for ventilator-associated pneumonia: validation using different histologic and microbiological references. Crit Care Med. 2000;28:2799–804.PubMedCrossRef Torres A, Fabregas N, Ewig S, de la Bellacasa JP, Bauer TT, Ramirez J. Sampling methods for ventilator-associated pneumonia: validation using different histologic and microbiological references. Crit Care Med. 2000;28:2799–804.PubMedCrossRef
7.
go back to reference Neuhauser MM, Weinstein RA, Rydman R, Danziger LH, Karam G, Quinn JP. Antibiotic resistance among gram-negative bacilli in US intensive care units: implications for fluoroquinolone use. JAMA. 2003;289:885–8.PubMedCrossRef Neuhauser MM, Weinstein RA, Rydman R, Danziger LH, Karam G, Quinn JP. Antibiotic resistance among gram-negative bacilli in US intensive care units: implications for fluoroquinolone use. JAMA. 2003;289:885–8.PubMedCrossRef
8.
go back to reference Douglas IS. New diagnostic methods for pneumonia in the ICU. Curr Opin Infect Dis. 2016;29:197–204.PubMedCrossRef Douglas IS. New diagnostic methods for pneumonia in the ICU. Curr Opin Infect Dis. 2016;29:197–204.PubMedCrossRef
10.
go back to reference Filipiak W, Sponring A, Baur MM, Ager C, Filipiak A, Wiesenhofer H, Nagl M, Troppmair J, Amann A. Characterization of volatile metabolites taken up by or released from Streptococcus pneumoniae and Haemophilus influenzae by using GC-MS. Microbiology. 2012;158:3044–53.PubMedCrossRef Filipiak W, Sponring A, Baur MM, Ager C, Filipiak A, Wiesenhofer H, Nagl M, Troppmair J, Amann A. Characterization of volatile metabolites taken up by or released from Streptococcus pneumoniae and Haemophilus influenzae by using GC-MS. Microbiology. 2012;158:3044–53.PubMedCrossRef
11.
go back to reference Zhu J, Bean HD, Wargo MJ, Leclair LW, Hill JE. Detecting bacterial lung infections: in vivo evaluation of in vitro volatile fingerprints. J Breath Res. 2013;7:016003.PubMedPubMedCentralCrossRef Zhu J, Bean HD, Wargo MJ, Leclair LW, Hill JE. Detecting bacterial lung infections: in vivo evaluation of in vitro volatile fingerprints. J Breath Res. 2013;7:016003.PubMedPubMedCentralCrossRef
12.
go back to reference Filipiak W, Beer R, Sponring A, Filipiak A, Ager C, Schiefecker A, Lanthaler S, Helbok R, Nagl M, Troppmair J, Amann A. Breath analysis for in vivo detection of pathogens related to ventilator-associated pneumonia in intensive care patients: a prospective pilot study. J Breath Res. 2015;9:016004.PubMedCrossRef Filipiak W, Beer R, Sponring A, Filipiak A, Ager C, Schiefecker A, Lanthaler S, Helbok R, Nagl M, Troppmair J, Amann A. Breath analysis for in vivo detection of pathogens related to ventilator-associated pneumonia in intensive care patients: a prospective pilot study. J Breath Res. 2015;9:016004.PubMedCrossRef
13.
go back to reference Gao J, Zou Y, Wang Y, Wang F, Lang L, Wang P, Zhou Y, Ying K. Breath analysis for noninvasively differentiating Acinetobacter baumannii ventilator-associated pneumonia from its respiratory tract colonization of ventilated patients. J Breath Res. 2016;10:027102.PubMedCrossRef Gao J, Zou Y, Wang Y, Wang F, Lang L, Wang P, Zhou Y, Ying K. Breath analysis for noninvasively differentiating Acinetobacter baumannii ventilator-associated pneumonia from its respiratory tract colonization of ventilated patients. J Breath Res. 2016;10:027102.PubMedCrossRef
14.
go back to reference Queralto N, Berliner AN, Goldsmith B, Martino R, Rhodes P, Lim SH. Detecting cancer by breath volatile organic compound analysis: a review of array-based sensors. J Breath Res. 2014;8:027112.PubMedCrossRef Queralto N, Berliner AN, Goldsmith B, Martino R, Rhodes P, Lim SH. Detecting cancer by breath volatile organic compound analysis: a review of array-based sensors. J Breath Res. 2014;8:027112.PubMedCrossRef
16.
go back to reference Fens N, van der Schee MP, Brinkman P, Sterk PJ. Exhaled breath analysis by electronic nose in airways disease. Established issues and key questions. Clin Exp Allergy. 2013;43:705–15.PubMedCrossRef Fens N, van der Schee MP, Brinkman P, Sterk PJ. Exhaled breath analysis by electronic nose in airways disease. Established issues and key questions. Clin Exp Allergy. 2013;43:705–15.PubMedCrossRef
17.
go back to reference Jiang F, Jiang Y, Zhi H, Dong Y, Li H, Ma S, Wang Y, Dong Q, Shen H, Wang Y. Artificial intelligence in healthcare: past, present and future. Stroke Vasc Neurol. 2017;2:230–43.PubMedPubMedCentralCrossRef Jiang F, Jiang Y, Zhi H, Dong Y, Li H, Ma S, Wang Y, Dong Q, Shen H, Wang Y. Artificial intelligence in healthcare: past, present and future. Stroke Vasc Neurol. 2017;2:230–43.PubMedPubMedCentralCrossRef
18.
go back to reference Chastre J, Fagon JY. Ventilator-associated pneumonia. Am J Respir Crit Care Med. 2002;165:867–903.CrossRefPubMed Chastre J, Fagon JY. Ventilator-associated pneumonia. Am J Respir Crit Care Med. 2002;165:867–903.CrossRefPubMed
19.
go back to reference Bikov A, Lazar Z, Horvath I. Established methodological issues in electronic nose research: how far are we from using these instruments in clinical settings of breath analysis? J Breath Res. 2015;9:034001.PubMedCrossRef Bikov A, Lazar Z, Horvath I. Established methodological issues in electronic nose research: how far are we from using these instruments in clinical settings of breath analysis? J Breath Res. 2015;9:034001.PubMedCrossRef
20.
go back to reference Huang CH, Zeng C, Wang YC, Peng HY, Lin CS, Chang CJ, Yang HY. A study of diagnostic accuracy using a chemical sensor array and a machine learning technique to detect lung cancer. Sensors. 2018;18:2845.CrossRefPubMedCentral Huang CH, Zeng C, Wang YC, Peng HY, Lin CS, Chang CJ, Yang HY. A study of diagnostic accuracy using a chemical sensor array and a machine learning technique to detect lung cancer. Sensors. 2018;18:2845.CrossRefPubMedCentral
21.
go back to reference Bofan M, Mores N, Baron M, Dabrowska M, Valente S, Schmid M, Trove A, Conforto S, Zini G, Cattani P, et al. Within-day and between-day repeatability of measurements with an electronic nose in patients with COPD. J Breath Res. 2013;7:017103.PubMedCrossRef Bofan M, Mores N, Baron M, Dabrowska M, Valente S, Schmid M, Trove A, Conforto S, Zini G, Cattani P, et al. Within-day and between-day repeatability of measurements with an electronic nose in patients with COPD. J Breath Res. 2013;7:017103.PubMedCrossRef
22.
go back to reference Lewis NS. Comparisons between mammalian and artificial olfaction based on arrays of carbon black-polymer composite vapor detectors. Acc Chem Res. 2004;37:663–72.PubMedCrossRef Lewis NS. Comparisons between mammalian and artificial olfaction based on arrays of carbon black-polymer composite vapor detectors. Acc Chem Res. 2004;37:663–72.PubMedCrossRef
23.
go back to reference Lu Y, Partridge C, Meyyappan M, Li J. A carbon nanotube sensor array for sensitive gas discrimination using principal component analysis. J Electroanal Chem. 2006;593:105–10.CrossRef Lu Y, Partridge C, Meyyappan M, Li J. A carbon nanotube sensor array for sensitive gas discrimination using principal component analysis. J Electroanal Chem. 2006;593:105–10.CrossRef
24.
go back to reference Kuhn M. Building predictive models in R using the caret package. J Stat Softw. 2008;28:1–26.CrossRef Kuhn M. Building predictive models in R using the caret package. J Stat Softw. 2008;28:1–26.CrossRef
25.
26.
go back to reference Marco S. The need for external validation in machine olfaction: emphasis on health-related applications. Anal Bioanal Chem. 2014;406:3941–56.PubMedCrossRef Marco S. The need for external validation in machine olfaction: emphasis on health-related applications. Anal Bioanal Chem. 2014;406:3941–56.PubMedCrossRef
27.
go back to reference Lantz B. Machine Learning with R. 2nd ed. Birmingham, UK: Packt Publishing Ltd.; 2015. Lantz B. Machine Learning with R. 2nd ed. Birmingham, UK: Packt Publishing Ltd.; 2015.
28.
go back to reference Venables WN, Ripley BD. Modern applied statistics with S. 4th ed: Springer; 2002. Venables WN, Ripley BD. Modern applied statistics with S. 4th ed: Springer; 2002.
29.
go back to reference Weihs C, Ligges U, Luebke K, Raabe N. klaR Analyzing German Business Cycles. In: Baier D, Decker R, Schmidt-Thieme L, eds. Data Analysis and Decision Support. Berlin: Springer-Verlag; 2005;335-43. Weihs C, Ligges U, Luebke K, Raabe N. klaR Analyzing German Business Cycles. In: Baier D, Decker R, Schmidt-Thieme L, eds. Data Analysis and Decision Support. Berlin: Springer-Verlag; 2005;335-43.
32.
go back to reference Karatzoglou A, Meyer D, Hornik K. Support vector Machines in R. J Stat Softw. 2006;15. Karatzoglou A, Meyer D, Hornik K. Support vector Machines in R. J Stat Softw. 2006;15.
34.
go back to reference Van Assche A, Vens C, Blockeel H, Dzeroski S. First order random forests: learning relational classifiers with complex aggregates. Mach Learn. 2006;64:149–82.CrossRef Van Assche A, Vens C, Blockeel H, Dzeroski S. First order random forests: learning relational classifiers with complex aggregates. Mach Learn. 2006;64:149–82.CrossRef
37.
go back to reference Robin X, Turck N, Hainard A, Tiberti N, Lisacek F, Sanchez JC, Muller M. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics. 2011;12:77.PubMedPubMedCentralCrossRef Robin X, Turck N, Hainard A, Tiberti N, Lisacek F, Sanchez JC, Muller M. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics. 2011;12:77.PubMedPubMedCentralCrossRef
38.
go back to reference Cohen JF, Korevaar DA, Altman DG, Bruns DE, Gatsonis CA, Hooft L, Irwig L, Levine D, Reitsma JB, de Vet HC, Bossuyt PM. STARD 2015 guidelines for reporting diagnostic accuracy studies: explanation and elaboration. BMJ Open. 2016;6:e012799.PubMedPubMedCentralCrossRef Cohen JF, Korevaar DA, Altman DG, Bruns DE, Gatsonis CA, Hooft L, Irwig L, Levine D, Reitsma JB, de Vet HC, Bossuyt PM. STARD 2015 guidelines for reporting diagnostic accuracy studies: explanation and elaboration. BMJ Open. 2016;6:e012799.PubMedPubMedCentralCrossRef
39.
40.
go back to reference Fend R, Kolk AH, Bessant C, Buijtels P, Klatser PR, Woodman AC. Prospects for clinical application of electronic-nose technology to early detection of mycobacterium tuberculosis in culture and sputum. J Clin Microbiol. 2006;44:2039–45.PubMedPubMedCentralCrossRef Fend R, Kolk AH, Bessant C, Buijtels P, Klatser PR, Woodman AC. Prospects for clinical application of electronic-nose technology to early detection of mycobacterium tuberculosis in culture and sputum. J Clin Microbiol. 2006;44:2039–45.PubMedPubMedCentralCrossRef
41.
go back to reference Lai SY, Deffenderfer OF, Hanson W, Phillips MP, Thaler ER. Identification of upper respiratory bacterial pathogens with the electronic nose. Laryngoscope. 2002;112:975–9.PubMedCrossRef Lai SY, Deffenderfer OF, Hanson W, Phillips MP, Thaler ER. Identification of upper respiratory bacterial pathogens with the electronic nose. Laryngoscope. 2002;112:975–9.PubMedCrossRef
43.
go back to reference van Geffen WH, Bruins M, Kerstjens HA. Diagnosing viral and bacterial respiratory infections in acute COPD exacerbations by an electronic nose: a pilot study. J Breath Res. 2016;10:036001.PubMedCrossRef van Geffen WH, Bruins M, Kerstjens HA. Diagnosing viral and bacterial respiratory infections in acute COPD exacerbations by an electronic nose: a pilot study. J Breath Res. 2016;10:036001.PubMedCrossRef
44.
go back to reference de Heer K, van der Schee MP, Zwinderman K, van den Berk IA, Visser CE, van Oers R, Sterk PJ. Electronic nose technology for detection of invasive pulmonary aspergillosis in prolonged chemotherapy-induced neutropenia: a proof-of-principle study. J Clin Microbiol. 2013;51:1490–5.PubMedPubMedCentralCrossRef de Heer K, van der Schee MP, Zwinderman K, van den Berk IA, Visser CE, van Oers R, Sterk PJ. Electronic nose technology for detection of invasive pulmonary aspergillosis in prolonged chemotherapy-induced neutropenia: a proof-of-principle study. J Clin Microbiol. 2013;51:1490–5.PubMedPubMedCentralCrossRef
45.
go back to reference Hockstein NG, Thaler ER, Lin Y, Lee DD, Hanson CW. Correlation of pneumonia score with electronic nose signature: a prospective study. Ann Otol Rhinol Laryngol. 2005;114:504–8.PubMedCrossRef Hockstein NG, Thaler ER, Lin Y, Lee DD, Hanson CW. Correlation of pneumonia score with electronic nose signature: a prospective study. Ann Otol Rhinol Laryngol. 2005;114:504–8.PubMedCrossRef
46.
go back to reference Schnabel RM, Boumans ML, Smolinska A, Stobberingh EE, Kaufmann R, Roekaerts PM, Bergmans DC. Electronic nose analysis of exhaled breath to diagnose ventilator-associated pneumonia. Respir Med. 2015;109:1454–9.PubMedCrossRef Schnabel RM, Boumans ML, Smolinska A, Stobberingh EE, Kaufmann R, Roekaerts PM, Bergmans DC. Electronic nose analysis of exhaled breath to diagnose ventilator-associated pneumonia. Respir Med. 2015;109:1454–9.PubMedCrossRef
47.
go back to reference Liao YH, Wang ZC, Zhang FG, Abbod MF, Shih CH, Shieh JS. Machine learning methods applied to predict ventilator-associated pneumonia with Pseudomonas aeruginosa infection via sensor Array of electronic nose in intensive care unit. Sensors (Basel). 2019;19:1866.CrossRef Liao YH, Wang ZC, Zhang FG, Abbod MF, Shih CH, Shieh JS. Machine learning methods applied to predict ventilator-associated pneumonia with Pseudomonas aeruginosa infection via sensor Array of electronic nose in intensive care unit. Sensors (Basel). 2019;19:1866.CrossRef
48.
go back to reference Buszewski B, Kesy M, Ligor T, Amann A. Human exhaled air analytics: biomarkers of diseases. Biomed Chromatogr. 2007;21:553–66.PubMedCrossRef Buszewski B, Kesy M, Ligor T, Amann A. Human exhaled air analytics: biomarkers of diseases. Biomed Chromatogr. 2007;21:553–66.PubMedCrossRef
49.
go back to reference Phillips M, Basa-Dalay V, Bothamley G, Cataneo RN, Lam PK, Natividad MP, Schmitt P, Wai J. Breath biomarkers of active pulmonary tuberculosis. Tuberculosis (Edinb). 2010;90:145–51.CrossRef Phillips M, Basa-Dalay V, Bothamley G, Cataneo RN, Lam PK, Natividad MP, Schmitt P, Wai J. Breath biomarkers of active pulmonary tuberculosis. Tuberculosis (Edinb). 2010;90:145–51.CrossRef
50.
go back to reference Phillip M, Cataneoa RN, Cheema T, Greenberga J. Increased breath biomarkers of oxidative stress in diabetes mellitus. Clin Chim Acta. 2004;344:189–94.CrossRef Phillip M, Cataneoa RN, Cheema T, Greenberga J. Increased breath biomarkers of oxidative stress in diabetes mellitus. Clin Chim Acta. 2004;344:189–94.CrossRef
51.
go back to reference G L. Epidemiology. 5th ed. Philadelphia: Elsevier; 2014. G L. Epidemiology. 5th ed. Philadelphia: Elsevier; 2014.
52.
go back to reference Leopold JH, Bos LD, Sterk PJ, Schultz MJ, Fens N, Horvath I, Bikov A, Montuschi P, Di Natale C, Yates DH, Abu-Hanna A. Comparison of classification methods in breath analysis by electronic nose. J Breath Res. 2015;9:046002.PubMedCrossRef Leopold JH, Bos LD, Sterk PJ, Schultz MJ, Fens N, Horvath I, Bikov A, Montuschi P, Di Natale C, Yates DH, Abu-Hanna A. Comparison of classification methods in breath analysis by electronic nose. J Breath Res. 2015;9:046002.PubMedCrossRef
53.
go back to reference Jimenez-Carvelo AM, Gonzalez-Casado A, Bagur-Gonzalez MG, Cuadros-Rodriguez L. Alternative data mining/machine learning methods for the analytical evaluation of food quality and authenticity - a review. Food Res Int. 2019;122:25–39.PubMedCrossRef Jimenez-Carvelo AM, Gonzalez-Casado A, Bagur-Gonzalez MG, Cuadros-Rodriguez L. Alternative data mining/machine learning methods for the analytical evaluation of food quality and authenticity - a review. Food Res Int. 2019;122:25–39.PubMedCrossRef
54.
go back to reference Lotsch J, Kringel D, Hummel T. Machine learning in human olfactory research. Chem Senses. 2019;44:11–22.PubMedCrossRef Lotsch J, Kringel D, Hummel T. Machine learning in human olfactory research. Chem Senses. 2019;44:11–22.PubMedCrossRef
Metadata
Title
Diagnosis of ventilator-associated pneumonia using electronic nose sensor array signals: solutions to improve the application of machine learning in respiratory research
Authors
Chung-Yu Chen
Wei-Chi Lin
Hsiao-Yu Yang
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2020
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-020-1285-6

Other articles of this Issue 1/2020

Respiratory Research 1/2020 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.