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Zhang S, Liu H, Ouyang Z, Xu T, Yang Q, Zhu Y, Wan M, Xiao X, Yang X, Chen S, Yuan L, Bei Y, Wang J, Guo J, Chen H, Tang B, Luo S, Jiao B, Shen L. Accurate Diagnosis of Alzheimer's Disease Using Specific Breath Volatile Organic Compounds. ACS Sens 2025; 10:2699-2711. [PMID: 40107845 DOI: 10.1021/acssensors.4c03329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/22/2025]
Abstract
Whether volatile organic compounds (VOCs) from exhaled breath can be used as a novel biomarker for Alzheimer's disease (AD) diagnosis is unclear. To determine the significantly distinctive VOCs for AD, a total of 970 participants were enrolled, including 60 individuals in data set 1 (AD, 30; controls, 30), 164 individuals in data set 2 (AD, 82; controls, 82), 637 individuals in data set 3 (AD, 31; controls, 606), and 109 individuals in data set 4 (frontotemporal dementia, 19; vascular dementia, 21; Parkinson's disease, 69). The participants in data sets 1, 2, and 4 were from Xiangya Hospital, Central South University. Participants in data set 3 were from a two-year follow-up cohort. VOCs in breath and plasma, neuropsychological scores, plasma p-tau181 levels, metabolites in plasma, and brain functional connectivity were detected. We found that six VOCs were significantly different between the two groups in data set 1 and were verified in data set 2 and data set 3. Ethanol (m/z = 46) and pyrrole (m/z = 67) presented AUC values of 0.907 and 0.895 in data sets 1 and 2 (clinical data sets) and 0.849 and 0.974 in data set 3 (community data set), respectively. The six VOCs were associated with cognitive decline as reflected by neuropsychological tests; five of them were correlated with plasma p-tau181, and these five plasma VOCs were consistently altered as breath VOCs. Correlation between metabolites and five VOCs in plasma was noted, and the five VOCs may originate from blood metabolites. Moreover, four breath VOCs were associated with altered brain connectivity. In conclusion, specific breath VOCs may be used as biomarkers for AD detection.
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Affiliation(s)
- Sizhe Zhang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Haokun Liu
- Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Ziyu Ouyang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Tianyan Xu
- Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Qijie Yang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Yuan Zhu
- Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Meidan Wan
- Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Xuewen Xiao
- Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
- Engineering Research Center of Hunan Province in Cognitive Impairment Disorders, Central South University, Changsha 410008, China
- Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Xuan Yang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Shuliang Chen
- Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Li Yuan
- Department of Neurology, Liuyang Jili Hospital, Changsha 410399, China
| | - Yuzhang Bei
- Department of Neurology, Liuyang Jili Hospital, Changsha 410399, China
| | - Junling Wang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
- Engineering Research Center of Hunan Province in Cognitive Impairment Disorders, Central South University, Changsha 410008, China
- Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Jifeng Guo
- Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
- Engineering Research Center of Hunan Province in Cognitive Impairment Disorders, Central South University, Changsha 410008, China
- Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Haibin Chen
- Breax Laboratory, PCAB Research Center of Breath and Metabolism, Beijing 100000, China
| | - Beisha Tang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
- Engineering Research Center of Hunan Province in Cognitive Impairment Disorders, Central South University, Changsha 410008, China
- Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Shilin Luo
- Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
- Engineering Research Center of Hunan Province in Cognitive Impairment Disorders, Central South University, Changsha 410008, China
- Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Bin Jiao
- Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
- Engineering Research Center of Hunan Province in Cognitive Impairment Disorders, Central South University, Changsha 410008, China
- Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Lu Shen
- Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
- Engineering Research Center of Hunan Province in Cognitive Impairment Disorders, Central South University, Changsha 410008, China
- Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Xiangya Hospital, Central South University, Changsha 410008, China
- Brain Research Center, Central South University, Changsha 410008, Hunan, China
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Brinkman P, Wilde M, Ahmed W, Wang R, van der Schee M, Abuhelal S, Schaber C, Cunoosamy D, Clarke GW, Maitland-van der Zee AH, Dahlén SE, Siddiqui S, Fowler SJ. Fulfilling the Promise of Breathomics: Considerations for the Discovery and Validation of Exhaled Volatile Biomarkers. Am J Respir Crit Care Med 2024; 210:1079-1090. [PMID: 38889337 PMCID: PMC11544359 DOI: 10.1164/rccm.202305-0868tr] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Accepted: 06/14/2024] [Indexed: 06/20/2024] Open
Abstract
The exhaled breath represents an ideal matrix for noninvasive biomarker discovery, and exhaled metabolomics have the potential to be clinically useful in the era of precision medicine. In this concise translational review, we specifically address volatile organic compounds in the breath, with a view toward fulfilling the promise of these as actionable biomarkers, in particular, for lung diseases. We review the literature paying attention to seminal work linked to key milestones in breath research; discuss potential applications for breath biomarkers across disease areas and healthcare systems, including the perspectives of industry; and outline critical aspects of study design that will need to be considered for any pivotal research going forward if breath analysis is to provide robust validated biomarkers that meet the requirements for future clinical implementation.
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Affiliation(s)
- Paul Brinkman
- Department of Pulmonary Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
- Amsterdam Institute for Infection and Immunity, Amsterdam, the Netherlands
- Amsterdam Public Health, Amsterdam, the Netherlands
| | - Michael Wilde
- School of Geography, Earth and Environmental Sciences, Faculty of Science and Engineering, University of Plymouth, Plymouth, United Kingdom
| | - Waqar Ahmed
- Division of Immunology, Immunity to Infection & Respiratory Medicine, School of Biological Sciences, The University of Manchester, Manchester, United Kingdom
| | - Ran Wang
- Division of Immunology, Immunity to Infection & Respiratory Medicine, School of Biological Sciences, The University of Manchester, Manchester, United Kingdom
- National Institute for Health and Care Research Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester, United Kingdom
| | | | - Shahd Abuhelal
- National Heart and Lung Institute, Imperial College London, London, United Kingdom
| | - Chad Schaber
- Owlstone Medical Ltd., Cambridge, United Kingdom
| | | | - Graham W. Clarke
- Translational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
- Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King’s College London, London, United Kingdom
| | - Anke-Hilse Maitland-van der Zee
- Department of Pulmonary Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
- Amsterdam Institute for Infection and Immunity, Amsterdam, the Netherlands
- Amsterdam Public Health, Amsterdam, the Netherlands
| | - Sven-Erik Dahlén
- The Department of Medicine Huddinge and the Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden; and
- Department of Respiratory Medicine, Karolinska University Hospital, Stockholm, Sweden
| | - Salman Siddiqui
- National Heart and Lung Institute, Imperial College London, London, United Kingdom
| | - Stephen J. Fowler
- Division of Immunology, Immunity to Infection & Respiratory Medicine, School of Biological Sciences, The University of Manchester, Manchester, United Kingdom
- National Institute for Health and Care Research Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester, United Kingdom
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Jiang Z, Bakker OJ, Bartolo PJ. Industry 4.0-Compliant Occupational Chronic Obstructive Pulmonary Disease Prevention: Literature Review and Future Directions. SENSORS (BASEL, SWITZERLAND) 2024; 24:5734. [PMID: 39275645 PMCID: PMC11398138 DOI: 10.3390/s24175734] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Revised: 08/29/2024] [Accepted: 09/01/2024] [Indexed: 09/16/2024]
Abstract
Chronic obstructive pulmonary disease (COPD) is among prevalent occupational diseases, causing early retirement and disabilities. This paper looks into occupational-related COPD prevention and intervention in the workplace for Industry 4.0-compliant occupation health and safety management. The economic burden and other severe problems caused by COPD are introduced. Subsequently, seminal research in relevant areas is reviewed. The prospects and challenges are introduced and discussed based on critical management approaches. An initial design of an Industry 4.0-compliant occupational COPD prevention system is presented at the end.
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Affiliation(s)
- Zhihao Jiang
- Faculty of Science & Engineering, The University of Manchester, Manchester M13 9PL, UK
| | - Otto Jan Bakker
- Faculty of Science & Engineering, The University of Manchester, Manchester M13 9PL, UK
| | - Paulo Jds Bartolo
- School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore 639798, Singapore
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Hu JC, Sethi S. New methods to detect bacterial or viral infections in patients with chronic obstructive pulmonary disease. Expert Rev Respir Med 2024; 18:693-707. [PMID: 39175157 PMCID: PMC11583054 DOI: 10.1080/17476348.2024.2396413] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 07/22/2024] [Accepted: 08/21/2024] [Indexed: 08/24/2024]
Abstract
INTRODUCTION Patients with chronic obstructive pulmonary disease (COPD) are frequently colonized and infected by respiratory pathogens. Identifying these infectious etiologies is critical for understanding the microbial dynamics of COPD and for the appropriate use of antimicrobials during exacerbations. AREAS COVERED Traditional methods, such as bacterial and viral cultures, have been standard in diagnosing respiratory infections. However, these methods have significant limitations, including lack of sensitivity and prolonged turnaround time. Modern molecular approaches offer rapid, sensitive, and specific detection, though they also come with their own challenges. This review explores and evaluates the clinical utility of the latest advancements in detecting bacterial and viral respiratory infections in COPD, encompassing molecular techniques, biomarkers, and emerging technologies. EXPERT OPINION In the evolving landscape of COPD management, integrating molecular diagnostics and emerging technologies holds great promise. The enhanced sensitivity of molecular techniques has significantly advanced our understanding of the role of microbes in COPD. However, many of these technologies have primarily been developed for pneumonia diagnosis or research applications, and their clinical utility in managing COPD requires further evaluation.
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Affiliation(s)
- John C Hu
- Division of Infectious Diseases, Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, USA
| | - Sanjay Sethi
- Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, USA
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Li L, Chen H, Shi J, Chai S, Yan L, Meng D, Cai Z, Guan J, Xin Y, Zhang X, Sun W, Lu X, He M, Li Q, Yan X. Exhaled breath analysis for the discrimination of asthma and chronic obstructive pulmonary disease. J Breath Res 2024; 18:046002. [PMID: 38834048 DOI: 10.1088/1752-7163/ad53f8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Accepted: 06/04/2024] [Indexed: 06/06/2024]
Abstract
Chronic obstructive pulmonary disease (COPD) and asthma are the most common chronic respiratory diseases. In middle-aged and elderly patients, it is difficult to distinguish between COPD and asthma based on clinical symptoms and pulmonary function examinations in clinical practice. Thus, an accurate and reliable inspection method is required. In this study, we aimed to identify breath biomarkers and evaluate the accuracy of breathomics-based methods for discriminating between COPD and asthma. In this multi-center cross-sectional study, exhaled breath samples were collected from 89 patients with COPD and 73 with asthma and detected on a high-pressure photon ionization time-of-flight mass spectrometry (HPPI-TOFMS) platform from 20 October 2022, to 20 May 2023, in four hospitals. Data analysis was performed from 15 June 2023 to 16 August 2023. The sensitivity, specificity, and accuracy were calculated to assess the overall performance of the volatile organic component (VOC)-based COPD and asthma discrimination models. Potential VOC markers related to COPD and asthma were also analyzed. The age of all participants ranged from to 18-86 years, and 54 (33.3%) were men. The age [median (minimum, maximum)] of COPD and asthma participants were 66.0 (46.0, 86.0), and 44.0 (17.0, 80.0). The male and female ratio of COPD and asthma participants were 14/75 and 40/33, respectively. Based on breathomics feature selection, ten VOCs were identified as COPD and asthma discrimination biomarkers via breath testing. The joint panel of these ten VOCs achieved an area under the curve of 0.843, sensitivity of 75.9%, specificity of 87.5%, and accuracy of 80.0% in COPD and asthma discrimination. Furthermore, the VOCs detected in the breath samples were closely related to the clinical characteristics of COPD and asthma. The VOC-based COPD and asthma discrimination model showed good accuracy, providing a new strategy for clinical diagnosis. Breathomics-based methods may play an important role in the diagnosis of COPD and asthma.
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Affiliation(s)
- Lan Li
- The First Department of Pulmonary and Critical Care Medicine, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Respiratory Critical Care Medicine, Hebei Institute of Respiratory Diseases, No. 215 Heping West Road, Shijiazhuang, Hebei 050000, People's Republic of China
- Shijiazhuang People's Hospital, No. 365 Jianhua Street, Shijiazhuang, Hebei 050000, People's Republic of China
| | - Haibin Chen
- Breax Laboratory, PCAB Research Center of Breath and Metabolism, Beijing 100071, People's Republic of China
- Digital Medicine Division, Guangzhou Sinohealth Digital Technology Co., Ltd, Guangzhou 510000, People's Republic of China
| | - Jinying Shi
- Shijiazhuang People's Hospital, No. 365 Jianhua Street, Shijiazhuang, Hebei 050000, People's Republic of China
| | - Shukun Chai
- Shijiazhuang People's Hospital, No. 365 Jianhua Street, Shijiazhuang, Hebei 050000, People's Republic of China
| | - Li Yan
- Hebei General Hospital, No. 348 Heping West Road, Shijiazhuang, Hebei 050000, People's Republic of China
| | - Deyang Meng
- Hebei General Hospital, No. 348 Heping West Road, Shijiazhuang, Hebei 050000, People's Republic of China
| | - Zhigang Cai
- The First Department of Pulmonary and Critical Care Medicine, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Respiratory Critical Care Medicine, Hebei Institute of Respiratory Diseases, No. 215 Heping West Road, Shijiazhuang, Hebei 050000, People's Republic of China
| | - Jitao Guan
- The First Department of Pulmonary and Critical Care Medicine, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Respiratory Critical Care Medicine, Hebei Institute of Respiratory Diseases, No. 215 Heping West Road, Shijiazhuang, Hebei 050000, People's Republic of China
| | - Yunwei Xin
- The First Department of Pulmonary and Critical Care Medicine, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Respiratory Critical Care Medicine, Hebei Institute of Respiratory Diseases, No. 215 Heping West Road, Shijiazhuang, Hebei 050000, People's Republic of China
| | - Xu Zhang
- The First Department of Pulmonary and Critical Care Medicine, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Respiratory Critical Care Medicine, Hebei Institute of Respiratory Diseases, No. 215 Heping West Road, Shijiazhuang, Hebei 050000, People's Republic of China
| | - Wuzhuang Sun
- The First Hospital of Hebei Medical University, No. 68 Donggang Road, Shijiazhuang, Hebei 050000, People's Republic of China
| | - Xi Lu
- The First Hospital of Hebei Medical University, No. 68 Donggang Road, Shijiazhuang, Hebei 050000, People's Republic of China
| | - Mengqi He
- Breax Laboratory, PCAB Research Center of Breath and Metabolism, Beijing 100071, People's Republic of China
| | - Qingyun Li
- Breax Laboratory, PCAB Research Center of Breath and Metabolism, Beijing 100071, People's Republic of China
| | - Xixin Yan
- The First Department of Pulmonary and Critical Care Medicine, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Respiratory Critical Care Medicine, Hebei Institute of Respiratory Diseases, No. 215 Heping West Road, Shijiazhuang, Hebei 050000, People's Republic of China
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Srikrishnarka P, Haapasalo J, Hinestroza JP, Sun Z, Nonappa. Wearable Sensors for Physiological Condition and Activity Monitoring. SMALL SCIENCE 2024; 4:2300358. [PMID: 40212111 PMCID: PMC11935081 DOI: 10.1002/smsc.202300358] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Revised: 04/10/2024] [Indexed: 04/13/2025] Open
Abstract
Rapid technological advancements have transformed the healthcare sector from traditional diagnosis and treatment to personalized health management. Biofluids such as teardrops, sweat, interstitial fluids, and exhaled breath condensate offer a rich source of metabolites that can be linked to the physiological status of an individual. More importantly, these biofluids contain biomarkers similar to those in the blood. Therefore, developing sensors for the noninvasive determination of biofluid-based metabolites can overcome traditionally invasive and laborious blood-test-based diagnostics. In this context, wearable devices offer real-time and continuous physiological conditions and activity monitoring. The first-generation wearables included wristwatches capable of tracking heart rate variations, breathing rate, body temperature, stress responses, and sleeping patterns. However, wearable sensors that can accurately measure the metabolites are needed to achieve real-time analysis of biomarkers. In this review, recent progresses in wearable sensors utilized to monitor metabolites in teardrops, breath condensate, sweat, and interstitial fluids are thoroughly analyzed. More importantly, how metabolites can be selectively detected, quantified, and monitored in real-time is discussed. Furthermore, the review includes a discussion on the utility of, multifunctional sensors that combine metabolite sensing, human activity monitoring, and on-demand drug delivery system for theranostic applications.
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Affiliation(s)
| | - Joonas Haapasalo
- Department of NeurosurgeryTampere University Hospital and Tampere UniversityKuntokatu 233520TampereFinland
| | - Juan P. Hinestroza
- Department of Fiber Science and Apparel DesignCornell UniversityIthacaNY14853USA
| | - Zhipei Sun
- Department of Electronics and NanoengineeringAalto UniversityP.O. Box 13500FI‐00076AaltoFinland
- QTF Center of ExcellenceDepartment of Applied PhysicsAalto University00076AaltoFinland
| | - Nonappa
- Faculty of Engineering and Natural SciencesKorkeakoulunkatu 6FI‐33720TampereFinland
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Dragonieri S, Marco MD, Ahroud M, Quaranta VN, Portacci A, Iorillo I, Montagnolo F, Carpagnano GE. Electronic nose based analysis of exhaled volatile organic compounds spectrum reveals asthmatic shifts and consistency in controls post-exercise and spirometry. J Breath Res 2024; 18:036006. [PMID: 38876093 DOI: 10.1088/1752-7163/ad5864] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Accepted: 06/14/2024] [Indexed: 06/16/2024]
Abstract
Analyzing exhaled volatile organic compounds (VOCs) with an electronic nose (e-nose) is emerging in medical diagnostics as a non-invasive, quick, and sensitive method for disease detection and monitoring. This study investigates if activities like spirometry or physical exercise affect exhaled VOCs measurements in asthmatics and healthy individuals, a crucial step for e-nose technology's validation for clinical use. The study analyzed exhaled VOCs using an e-nose in 27 healthy individuals and 27 patients with stable asthma, before and after performing spirometry and climbing five flights of stairs. Breath samples were collected using a validated technique and analyzed with a Cyranose 320 e-nose. In healthy controls, the exhaled VOCs spectrum remained unchanged after both lung function test and exercise. In asthmatics, principal component analysis and subsequent discriminant analysis revealed significant differences post-spirometry (vs. baseline 66.7% cross validated accuracy [CVA],p< 0.05) and exercise (vs. baseline 70.4% CVA,p< 0.05). E-nose measurements in healthy individuals are consistent, unaffected by spirometry or physical exercise. However, in asthma patients, significant changes in exhaled VOCs were detected post-activities, indicating airway responses likely due to constriction or inflammation, underscoring the e-nose's potential for respiratory condition diagnosis and monitoring.
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Affiliation(s)
| | | | - Madiha Ahroud
- Respiratory Diseases, University of Bari, Bari, Italy
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Aerts R, Feys S, Mercier T, Lagrou K. Microbiological Diagnosis of Pulmonary Aspergillus Infections. Semin Respir Crit Care Med 2024; 45:21-31. [PMID: 38228164 DOI: 10.1055/s-0043-1776777] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2024]
Abstract
As microbiological tests play an important role in our diagnostic algorithms and clinical approach towards patients at-risk for pulmonary aspergillosis, a good knowledge of the diagnostic possibilities and especially their limitations is extremely important. In this review, we aim to reflect critically on the available microbiological diagnostic modalities for diagnosis of pulmonary aspergillosis and formulate some future prospects. Timely start of adequate antifungal treatment leads to a better patient outcome, but overuse of antifungals should be avoided. Current diagnostic possibilities are expanding, and are mainly driven by enzyme immunoassays and lateral flow device tests for the detection of Aspergillus antigens. Most of these tests are directed towards similar antigens, but new antibodies towards different targets are under development. For chronic forms of pulmonary aspergillosis, anti-Aspergillus IgG antibodies and precipitins remain the cornerstone. More studies on the possibilities and limitations of molecular testing including targeting resistance markers are ongoing. Also, metagenomic next-generation sequencing is expanding our future possibilities. It remains important to combine different test results and interpret them in the appropriate clinical context to improve performance. Test performances may differ according to the patient population and test results may be influenced by timing, the tested matrix, and prophylactic and empiric antifungal therapy. Despite the increasing armamentarium, a simple blood or urine test for the diagnosis of aspergillosis in all patient populations at-risk is still lacking. Research on diagnostic tools is broadening from a pathogen focus on biomarkers related to the patient and its immune system.
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Affiliation(s)
- Robina Aerts
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- Department of Internal Medicine, University Hospitals Leuven, Leuven, Belgium
| | - Simon Feys
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- Medical Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium
| | - Toine Mercier
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- Department of Oncology-Hematology, AZ Sint-Maarten, Mechelen, Belgium
| | - Katrien Lagrou
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- Department of Laboratory Medicine and National Reference Center for Mycosis, University Hospitals Leuven, Leuven, Belgium
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9
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Brener S, Snitz K, Sobel N. An electronic nose can identify humans by the smell of their ear. Chem Senses 2024; 49:bjad053. [PMID: 38237638 PMCID: PMC10810274 DOI: 10.1093/chemse/bjad053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Indexed: 01/27/2024] Open
Abstract
Terrestrial mammals identify conspecifics by body odor. Dogs can also identify humans by body odor, and in some instances, humans can identify other humans by body odor as well. Despite the potential for a powerful biometric tool, smell has not been systematically used for this purpose. A question arising in the application of smell to biometrics is which bodily odor source should we measure. Breath is an obvious candidate, but the associated humidity can challenge many sensing devices. The armpit is also a candidate source, but it is often doused in cosmetics. Here, we test the hypothesis that the ear may provide an effective source for odor-based biometrics. The inside of the ear has relatively constant humidity, cosmetics are not typically applied inside the ear, and critically, ears contain cerumen, a potent source of volatiles. We used an electronic nose to identify 12 individuals within and across days, using samples from the armpit, lower back, and ear. In an identification setting where chance was 8.33% (1 of 12), we found that we could identify a person by the smell of their ear within a day at up to ~87% accuracy (~10 of 12, binomial P < 10-5), and across days at up to ~22% accuracy (~3 of 12, binomial P < 0.012). We conclude that humans can indeed be identified from the smell of their ear, but the results did not imply a consistent advantage over other bodily odor sources.
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Affiliation(s)
- Stephanie Brener
- The Azrieli National Center for Human Brain Imaging and Research, Weizmann Institute of Science, Rehovot 7610001, Israel
- The Department for Brain Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel
| | - Kobi Snitz
- The Azrieli National Center for Human Brain Imaging and Research, Weizmann Institute of Science, Rehovot 7610001, Israel
- The Department for Brain Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel
| | - Noam Sobel
- The Azrieli National Center for Human Brain Imaging and Research, Weizmann Institute of Science, Rehovot 7610001, Israel
- The Department for Brain Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel
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Sola-Martínez RA, Zeng J, Awchi M, Gisler A, Arnold K, Singh KD, Frey U, Díaz MC, de Diego Puente T, Sinues P. Preservation of exhaled breath samples for analysis by off-line SESI-HRMS: proof-of-concept study. J Breath Res 2023; 18:011002. [PMID: 38029449 DOI: 10.1088/1752-7163/ad10e1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Accepted: 11/29/2023] [Indexed: 12/01/2023]
Abstract
Secondary electrospray ionization-high resolution mass spectrometry (SESI-HRMS) is an established technique in the field of breath analysis characterized by its short analysis time, as well as high levels of sensitivity and selectivity. Traditionally, SESI-HRMS has been used for real-time breath analysis, which requires subjects to be at the location of the analytical platform. Therefore, it limits the possibilities for an introduction of this methodology in day-to-day clinical practice. However, recent methodological developments have shown feasibility on the remote sampling of exhaled breath in Nalophan® bags prior to measurement using SESI-HRMS. To further explore the range of applications of this method, we conducted a proof-of-concept study to assess the impact of the storage time of exhaled breath in Nalophan® bags at different temperatures (room temperature and dry ice) on the relative intensities of the compounds. In addition, we performed a detailed study of the storage effect of 27 aldehydes related to oxidative stress. After 2 h of storage, the mean of intensity of allm/zsignals relative to the samples analyzed without prior storage remained above 80% at both room temperature and dry ice. For the 27 aldehydes, the mean relative intensity losses were lower than 20% at 24 h of storage, remaining practically stable since the first hour of storage following sample collection. Furthermore, the mean relative intensity of most aldehydes in samples stored at room temperature was higher than those stored in dry ice, which could be related to water vapor condensation issues. These findings indicate that the exhaled breath samples could be preserved for hours with a low percentage of mean relative intensity loss, thereby allowing more flexibility in the logistics of off-line SESI-HRMS studies.
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Affiliation(s)
- Rosa A Sola-Martínez
- Department of Biochemistry and Molecular Biology B and Immunology, University of Murcia, Murcia, Spain
| | - Jiafa Zeng
- University of Basel Children's Hospital (UKBB), Basel, Switzerland
- Department of Biomedical Engineering, University of Basel, Allschwil, Switzerland
| | - Mo Awchi
- University of Basel Children's Hospital (UKBB), Basel, Switzerland
- Department of Biomedical Engineering, University of Basel, Allschwil, Switzerland
| | - Amanda Gisler
- University of Basel Children's Hospital (UKBB), Basel, Switzerland
| | - Kim Arnold
- University of Basel Children's Hospital (UKBB), Basel, Switzerland
- Department of Biomedical Engineering, University of Basel, Allschwil, Switzerland
| | - Kapil Dev Singh
- University of Basel Children's Hospital (UKBB), Basel, Switzerland
- Department of Biomedical Engineering, University of Basel, Allschwil, Switzerland
| | - Urs Frey
- University of Basel Children's Hospital (UKBB), Basel, Switzerland
- Pediatric Respiratory Medicine, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Department of Biomedical Engineering, University of Basel, Allschwil, Switzerland
| | - Manuel Cánovas Díaz
- Department of Biochemistry and Molecular Biology B and Immunology, University of Murcia, Murcia, Spain
| | - Teresa de Diego Puente
- Department of Biochemistry and Molecular Biology B and Immunology, University of Murcia, Murcia, Spain
| | - Pablo Sinues
- University of Basel Children's Hospital (UKBB), Basel, Switzerland
- Department of Biomedical Engineering, University of Basel, Allschwil, Switzerland
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11
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Jiao B, Zhang S, Bei Y, Bu G, Yuan L, Zhu Y, Yang Q, Xu T, Zhou L, Liu Q, Ouyang Z, Yang X, Feng Y, Tang B, Chen H, Shen L. A detection model for cognitive dysfunction based on volatile organic compounds from a large Chinese community cohort. Alzheimers Dement 2023; 19:4852-4862. [PMID: 37032600 DOI: 10.1002/alz.13053] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 02/17/2023] [Accepted: 02/21/2023] [Indexed: 04/11/2023]
Abstract
INTRODUCTION We explored whether volatile organic compound (VOC) detection can serve as a screening tool to distinguish cognitive dysfunction (CD) from cognitively normal (CN) individuals. METHODS The cognitive function of 1467 participants was assessed and their VOCs were detected. Six machine learning algorithms were conducted and the performance was determined. The plasma neurofilament light chain (NfL) was measured. RESULTS Distinguished VOC patterns existed between CD and CN groups. The CD detection model showed good accuracy with an area under the receiver-operating characteristic curve (AUC) of 0.876. In addition, we found that 10 VOC ions showed significant differences between CD and CN individuals (p < 0.05); three VOCs were significantly related to plasma NfL (p < 0.005). Moreover, a combination of VOCs with NfL showed the best discriminating power (AUC = 0.877). DISCUSSION Detection of VOCs from exhaled breath samples has the potential to provide a novel solution for the dilemma of CD screening.
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Affiliation(s)
- Bin Jiao
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Engineering Research Center of Hunan Province in Cognitive Impairment Disorders, Central South University, Changsha, China
- Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha, China
- Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, China
| | - Sizhe Zhang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
| | - Yuzhang Bei
- Department of Neurology, Liuyang Jili Hospital, Changsha, China
| | - Guiwen Bu
- Department of Neurology, Liuyang Jili Hospital, Changsha, China
| | - Li Yuan
- Department of Neurology, Liuyang Jili Hospital, Changsha, China
| | - Yuan Zhu
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
| | - Qijie Yang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
| | - Tianyan Xu
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
| | - Lu Zhou
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
| | - Qianqian Liu
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
| | - Ziyu Ouyang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
| | - Xuan Yang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
| | - Yong Feng
- Breax Laboratory, PCAB Research Center of Breath and Metabolism, Beijing, China
| | - Beisha Tang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Engineering Research Center of Hunan Province in Cognitive Impairment Disorders, Central South University, Changsha, China
- Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha, China
- Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, China
| | - Haibin Chen
- Breax Laboratory, PCAB Research Center of Breath and Metabolism, Beijing, China
| | - Lu Shen
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Engineering Research Center of Hunan Province in Cognitive Impairment Disorders, Central South University, Changsha, China
- Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha, China
- Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, China
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China
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12
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Vanstraelen S, Jones DR, Rocco G. Breathprinting analysis and biomimetic sensor technology to detect lung cancer. J Thorac Cardiovasc Surg 2023; 166:357-361.e1. [PMID: 36997463 DOI: 10.1016/j.jtcvs.2023.02.029] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Revised: 02/15/2023] [Accepted: 02/28/2023] [Indexed: 03/11/2023]
Affiliation(s)
- Stijn Vanstraelen
- Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - David R Jones
- Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY; Fiona and Stanley Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Gaetano Rocco
- Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY; Fiona and Stanley Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY.
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13
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Savito L, Scarlata S, Bikov A, Carratù P, Carpagnano GE, Dragonieri S. Exhaled volatile organic compounds for diagnosis and monitoring of asthma. World J Clin Cases 2023; 11:4996-5013. [PMID: 37583852 PMCID: PMC10424019 DOI: 10.12998/wjcc.v11.i21.4996] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Revised: 06/08/2023] [Accepted: 07/06/2023] [Indexed: 07/26/2023] Open
Abstract
The asthmatic inflammatory process results in the generation of volatile organic compounds (VOCs), which are subsequently secreted by the airways. The study of these elements through gas chromatography-mass spectrometry (GC-MS), which can identify individual molecules with a discriminatory capacity of over 85%, and electronic-Nose (e-NOSE), which is able to perform a quick onboard pattern-recognition analysis of VOCs, has allowed new prospects for non-invasive analysis of the disease in an "omics" approach. In this review, we aim to collect and compare the progress made in VOCs analysis using the two methods and their instrumental characteristics. Studies have described the potential of GC-MS and e-NOSE in a multitude of relevant aspects of the disease in both children and adults, as well as differential diagnosis between asthma and other conditions such as wheezing, cystic fibrosis, COPD, allergic rhinitis and last but not least, the accuracy of these methods compared to other diagnostic tools such as lung function, FeNO and eosinophil count. Due to significant limitations of both methods, it is still necessary to improve and standardize techniques. Currently, e-NOSE appears to be the most promising aid in clinical practice, whereas GC-MS, as the gold standard for the structural analysis of molecules, remains an essential tool in terms of research for further studies on the pathophysiologic pathways of the asthmatic inflammatory process. In conclusion, the study of VOCs through GC-MS and e-NOSE appears to hold promise for the non-invasive diagnosis, assessment, and monitoring of asthma, as well as for further research studies on the disease.
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Affiliation(s)
- Luisa Savito
- Department of Internal Medicine, Unit of Respiratory Pathophysiology and Thoracic Endoscopy, Fondazione Policlinico Universitario Campus Bio Medico, Rome 00128, Italy
| | - Simone Scarlata
- Department of Internal Medicine, Unit of Respiratory Pathophysiology and Thoracic Endoscopy, Fondazione Policlinico Universitario Campus Bio Medico, Rome 00128, Italy
| | - Andras Bikov
- Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, United Kingdom
- Division of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M13 9PT, United Kingdom
| | - Pierluigi Carratù
- Department of Internal Medicine "A.Murri", University of Bari "Aldo Moro", Bari 70124, Italy
| | | | - Silvano Dragonieri
- Department of Respiratory Diseases, University of Bari, Bari 70124, Italy
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14
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Xu T, Wang J, Tan J, Huang T, Han G, Li Y, Yu H, Zhou J, Xu M. Gas chromatography-mass spectrometry pilot study to identify volatile organic compound biomarkers of childhood obesity with dyslipidemia in exhaled breath. J Transl Int Med 2023; 11:81-89. [DOI: 10.2478/jtim-2022-0035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/29/2023] Open
Abstract
Abstract
Objectives
Childhood obesity affects multiple organs in the body and is associated with both significant morbidity and ultimately premature mortality. Childhood obesity, especially dyslipidemia, can lead to early atherosclerosis and premature cardiovascular disease (CVD) in adulthood. The detection of exhaled volatile organic compounds (VOCs) in the breath offers the opportunity for the discovery of novel disease-specific biomarkers. This study aimed to identify VOCs that correlate with childhood obesity accompanied by dyslipidemia.
Methods
A total of 82 overweight or obese children between the ages of 8 and 12 years were recruited from the exercise on obesity adolescents in Peking (EXCITING) study (NCT04984005). The breath VOCs of the participants were measured by gas chromatography-mass spectrometry (GC-MS). The classification was performed using principal component analysis (PCA) of the relative abundance of VOCs. The difference between the obese and overweight groups with or without dyslipidemia was analyzed.
Results
Among the 82 children, 25 were overweight, of whom 10 had dyslipidemia. The other 57 children were obese, and 17 of them had dyslipidemia. Obese children with dyslipidemia had higher triglycerides and elevated non–high-density lipoprotein-cholesterol compared to overweight children without dyslipidemia. We confirmed 13 compounds based on database well matches (average score > 80) for mass spectra and refractive index. These 13 VOCs were grouped into three chemical functional groups: saturated hydrocarbons, aromatic hydrocarbons and unsaturated aldehydes. For obese children with dyslipidemia, the PCA scatter plot of the three chemical groups was obviously separated from the other groups. Some of the candidates, including heptadecane, naphthalene, and cis-6-nonnenol, were significantly higher in obese children with dyslipidemia than in overweight groups with or without dyslipidemia.
Conclusion
A suite of VOCs from three chemical function groups, saturated hydrocarbons, aromatic hydrocarbons, and unsaturated aldehydes, were separated in the obese children with dyslipidemia. Heptadecane, naphthalene, and cis-6-nonenol were significantly elevated in obese children with dyslipidemia. Our findings underscore the potential value of the candidate VOCs for future risk categorization.
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15
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Wilson AD, Forse LB. Potential for Early Noninvasive COVID-19 Detection Using Electronic-Nose Technologies and Disease-Specific VOC Metabolic Biomarkers. SENSORS (BASEL, SWITZERLAND) 2023; 23:2887. [PMID: 36991597 PMCID: PMC10054641 DOI: 10.3390/s23062887] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Revised: 02/19/2023] [Accepted: 03/03/2023] [Indexed: 06/12/2023]
Abstract
The established efficacy of electronic volatile organic compound (VOC) detection technologies as diagnostic tools for noninvasive early detection of COVID-19 and related coronaviruses has been demonstrated from multiple studies using a variety of experimental and commercial electronic devices capable of detecting precise mixtures of VOC emissions in human breath. The activities of numerous global research teams, developing novel electronic-nose (e-nose) devices and diagnostic methods, have generated empirical laboratory and clinical trial test results based on the detection of different types of host VOC-biomarker metabolites from specific chemical classes. COVID-19-specific volatile biomarkers are derived from disease-induced changes in host metabolic pathways by SARS-CoV-2 viral pathogenesis. The unique mechanisms proposed from recent researchers to explain how COVID-19 causes damage to multiple organ systems throughout the body are associated with unique symptom combinations, cytokine storms and physiological cascades that disrupt normal biochemical processes through gene dysregulation to generate disease-specific VOC metabolites targeted for e-nose detection. This paper reviewed recent methods and applications of e-nose and related VOC-detection devices for early, noninvasive diagnosis of SARS-CoV-2 infections. In addition, metabolomic (quantitative) COVID-19 disease-specific chemical biomarkers, consisting of host-derived VOCs identified from exhaled breath of patients, were summarized as possible sources of volatile metabolic biomarkers useful for confirming and supporting e-nose diagnoses.
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Affiliation(s)
- Alphus Dan Wilson
- Pathology Department, Center for Forest Health & Disturbance, Forest Genetics and Ecosystems Biology, Southern Research Station, USDA Forest Service, Stoneville, MS 38776, USA
| | - Lisa Beth Forse
- Southern Hardwoods Laboratory, Southern Research Station, USDA Forest Service, Stoneville, MS 38776, USA
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16
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Weber R, Kaeslin J, Moeller S, Perkins N, Micic S, Moeller A. Effects of a Volatile Organic Compound Filter on Breath Profiles Measured by Secondary Electrospray High-Resolution Mass Spectrometry. Molecules 2022; 28:45. [PMID: 36615240 PMCID: PMC9822030 DOI: 10.3390/molecules28010045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 12/08/2022] [Accepted: 12/08/2022] [Indexed: 12/24/2022] Open
Abstract
Environmental volatile organic compounds (VOCs) from the ambient air potentially influence on-line breath analysis measurements by secondary electrospray ionization high-resolution mass spectrometry (SESI-HRMS). The aim of this study was to investigate how inhaling through a VOC filter affects the detected breath profiles and whether it is feasible to integrate such filters into routine measurements. A total of 24 adult participants performed paired breath analysis measurements with and without the use of an activated carbon filter for inspiration. Concordance correlation coefficients (CCCs) and the Bland−Altman analysis were used to assess the agreement between the two methods. Additionally, the effect on a selection of known metabolites and contaminants was analyzed. Out of all the detected features, 78.3% showed at least a moderate agreement before and after filter usage (CCC > 0.9). The decrease in agreement of the remaining m/z features was mostly associated with reduced signal intensities after filter usage. Although a moderate-to-substantial concordance was found for almost 80% of the m/z features, the filter still had an effect by decreasing signal intensities, not only for contaminants, but also for some of the studied metabolites. Operationally, the use of the filter complicated and slowed down the conductance of measurements, limiting its applicability in clinical studies.
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Affiliation(s)
- Ronja Weber
- Department of Respiratory Medicine and Childhood Research Center, University Children’s Hospital Zurich, Steinwiesstrasse 75, 8032 Zurich, Switzerland
| | - Jérôme Kaeslin
- Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology, Vladimir-Prelog Weg 1-5/10, 8093 Zurich, Switzerland
| | - Sophia Moeller
- Department of Respiratory Medicine and Childhood Research Center, University Children’s Hospital Zurich, Steinwiesstrasse 75, 8032 Zurich, Switzerland
| | - Nathan Perkins
- Division of Clinical Chemistry and Biochemistry, University Children’s Hospital Zurich, Steinwiesstrasse 75, 8032 Zurich, Switzerland
| | - Srdjan Micic
- Department of Respiratory Medicine and Childhood Research Center, University Children’s Hospital Zurich, Steinwiesstrasse 75, 8032 Zurich, Switzerland
| | - Alexander Moeller
- Department of Respiratory Medicine and Childhood Research Center, University Children’s Hospital Zurich, Steinwiesstrasse 75, 8032 Zurich, Switzerland
- Faculty of Medicine, University of Zurich, Raemistrasse 71, 8006 Zurich, Switzerland
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17
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Westphal K, Dudzik D, Waszczuk-Jankowska M, Graff B, Narkiewicz K, Markuszewski MJ. Common Strategies and Factors Affecting Off-Line Breath Sampling and Volatile Organic Compounds Analysis Using Thermal Desorption-Gas Chromatography-Mass Spectrometry (TD-GC-MS). Metabolites 2022; 13:8. [PMID: 36676933 PMCID: PMC9866406 DOI: 10.3390/metabo13010008] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 12/14/2022] [Accepted: 12/16/2022] [Indexed: 12/24/2022] Open
Abstract
An analysis of exhaled breath enables specialists to noninvasively monitor biochemical processes and to determine any pathological state in the human body. Breath analysis holds the greatest potential to remold and personalize diagnostics; however, it requires a multidisciplinary approach and collaboration of many specialists. Despite the fact that breath is considered to be a less complex matrix than blood, it is not commonly used as a diagnostic and prognostic tool for early detection of disordered conditions due to its problematic sampling, analysis, and storage. This review is intended to determine, standardize, and marshal experimental strategies for successful, reliable, and especially, reproducible breath analysis.
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Affiliation(s)
- Kinga Westphal
- Department of Hypertension and Diabetology, Medical University of Gdansk, 80-214 Gdansk, Poland
| | - Danuta Dudzik
- Department of Biopharmaceutics and Pharmacodynamics, Faculty of Pharmacy, Medical University of Gdansk, 80-416 Gdansk, Poland
| | - Małgorzata Waszczuk-Jankowska
- Department of Biopharmaceutics and Pharmacodynamics, Faculty of Pharmacy, Medical University of Gdansk, 80-416 Gdansk, Poland
| | - Beata Graff
- Department of Hypertension and Diabetology, Medical University of Gdansk, 80-214 Gdansk, Poland
| | - Krzysztof Narkiewicz
- Department of Hypertension and Diabetology, Medical University of Gdansk, 80-214 Gdansk, Poland
| | - Michał Jan Markuszewski
- Department of Biopharmaceutics and Pharmacodynamics, Faculty of Pharmacy, Medical University of Gdansk, 80-416 Gdansk, Poland
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18
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Development of an Algorithm for Cervical High-Grade Squamous Intraepithelial Lesion Based on Breath Print Analysis. J Low Genit Tract Dis 2022; 27:7-11. [PMID: 36196881 DOI: 10.1097/lgt.0000000000000707] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVES This study was designed to develop an algorithm for the diagnosis of cervical high-grade squamous intraepithelial lesions (HSIL), based on patterns of volatile organic compounds, evaluated using an e-nose. METHODS For this pilot study, the study population consisted of a group of 25 patients with histologically confirmed HSIL and a group of 26 controls. Controls consisted of women visiting the outpatient department for gynecological complaints unrelated to cancer. Women had a negative high-risk human papillomavirus and/or normal cytology (negative for intraepithelial lesions of malignancy) of their most recent test performed in the context of participation in routine cervical cancer screening. Breath tests were performed and labeled with the correct diagnosis. Machine-learning techniques were used to develop a model for predicting HSIL. Based on the receiver operating characteristics curve, both sensitivity and specificity were calculated. RESULTS Individual classifications of all patients with HSIL and controls, as calculated by the model, showed a sensitivity of 0.88 (95% CI = 0.68-0.97) and specificity of 0.92 (95% CI = 0.73-0.99). The positive predictive value and the negative predictive value were 0.92 (95% CI = 0.72-0.99) and 0.89 (95% CI = 0.70-0.97), respectively. The Cohen κ coefficient was 0.80. CONCLUSIONS E-nose can detect distinctive patterns of volatile organic compounds between cervical HSIL patients and controls. Validation of the algorithm in further studies is necessary before possible implementation into daily practice.
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19
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Azim A, Rezwan FI, Barber C, Harvey M, Kurukulaaratchy RJ, Holloway JW, Howarth PH. Measurement of Exhaled Volatile Organic Compounds as a Biomarker for Personalised Medicine: Assessment of Short-Term Repeatability in Severe Asthma. J Pers Med 2022; 12:1635. [PMID: 36294774 PMCID: PMC9604907 DOI: 10.3390/jpm12101635] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 09/14/2022] [Accepted: 09/26/2022] [Indexed: 11/07/2022] Open
Abstract
The measurement of exhaled volatile organic compounds (VOCs) in exhaled breath (breathomics) represents an exciting biomarker matrix for airways disease, with early research indicating a sensitivity to airway inflammation. One of the key aspects to analytical validity for any clinical biomarker is an understanding of the short-term repeatability of measures. We collected exhaled breath samples on 5 consecutive days in 14 subjects with severe asthma who had undergone extensive clinical characterisation. Principal component analysis on VOC abundance across all breath samples revealed no variance due to the day of sampling. Samples from the same patients clustered together and there was some separation according to T2 inflammatory markers. The intra-subject and between-subject variability of each VOC was calculated across the 70 samples and identified 30.35% of VOCs to be erratic: variable between subjects but also variable in the same subject. Exclusion of these erratic VOCs from machine learning approaches revealed no apparent loss of structure to the underlying data or loss of relationship with salient clinical characteristics. Moreover, cluster evaluation by the silhouette coefficient indicates more distinct clustering. We are able to describe the short-term repeatability of breath samples in a severe asthma population and corroborate its sensitivity to airway inflammation. We also describe a novel variance-based feature selection tool that, when applied to larger clinical studies, could improve machine learning model predictions.
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Affiliation(s)
- Adnan Azim
- Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK
- NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton SO16 6YD, UK
| | - Faisal I. Rezwan
- Department of Computer Science, Aberystwyth University, Aberystwyth SY23 3DB, UK
- Human Development and Health, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK
| | - Clair Barber
- Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK
- NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton SO16 6YD, UK
| | - Matthew Harvey
- NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton SO16 6YD, UK
| | - Ramesh J. Kurukulaaratchy
- Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK
- NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton SO16 6YD, UK
- David Hide Asthma and Allergy Research Centre, Isle of Wight NHS Trust, Newport PO30 5TG, UK
| | - John W. Holloway
- NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton SO16 6YD, UK
- Human Development and Health, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK
| | - Peter H. Howarth
- Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK
- NIHR Southampton Biomedical Research Centre, University Hospital Southampton, Southampton SO16 6YD, UK
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20
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Abumeeiz M, Elliott L, Olla P. Use of Breath Analysis for Diagnosing COVID-19: Opportunities, Challenges, and Considerations for Future Pandemic Responses. Disaster Med Public Health Prep 2022; 16:2137-2140. [PMID: 34649631 PMCID: PMC8576132 DOI: 10.1017/dmp.2021.317] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Revised: 08/31/2021] [Accepted: 10/03/2021] [Indexed: 01/01/2023]
Abstract
Due to the coronavirus disease 2019 (COVID-19) pandemic, there is currently a need for accurate, rapid, and easy-to-administer diagnostic tools to help communities manage local outbreaks and assess the spread of disease. The use of artificial intelligence within the domain of breath analysis techniques has shown to have potential in diagnosing a variety of diseases, such as cancer and lung disease, by analyzing volatile organic compounds (VOCs) in exhaled breath. This combined with their rapid, easy-to-use, and noninvasive nature makes them a good candidate for use in diagnosing COVID-19 in large scale public health operations. However, there remains issues with their implementation when it comes to the infrastructure currently available to support their use on a broad scale. This includes issues of standardization, and whether or not a characteristic VOC pattern can be identified for COVID-19. Despite these difficulties, breathalyzers offer potential to assist in pandemic responses and their use should be investigated.
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21
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Keogh RJ, Riches JC. The Use of Breath Analysis in the Management of Lung Cancer: Is It Ready for Primetime? Curr Oncol 2022; 29:7355-7378. [PMID: 36290855 PMCID: PMC9600994 DOI: 10.3390/curroncol29100578] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 09/22/2022] [Accepted: 09/28/2022] [Indexed: 11/07/2022] Open
Abstract
Breath analysis is a promising non-invasive method for the detection and management of lung cancer. Exhaled breath contains a complex mixture of volatile and non-volatile organic compounds that are produced as end-products of metabolism. Several studies have explored the patterns of these compounds and have postulated that a unique breath signature is emitted in the setting of lung cancer. Most studies have evaluated the use of gas chromatography and mass spectrometry to identify these unique breath signatures. With recent advances in the field of analytical chemistry and machine learning gaseous chemical sensing and identification devices have also been created to detect patterns of odorant molecules such as volatile organic compounds. These devices offer hope for a point-of-care test in the future. Several prospective studies have also explored the presence of specific genomic aberrations in the exhaled breath of patients with lung cancer as an alternative method for molecular analysis. Despite its potential, the use of breath analysis has largely been limited to translational research due to methodological issues, the lack of standardization or validation and the paucity of large multi-center studies. It is clear however that it offers a potentially non-invasive alternative to investigations such as tumor biopsy and blood sampling.
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Avian C, Mahali MI, Putro NAS, Prakosa SW, Leu JS. Fx-Net and PureNet: Convolutional Neural Network architecture for discrimination of Chronic Obstructive Pulmonary Disease from smokers and healthy subjects through electronic nose signals. Comput Biol Med 2022; 148:105913. [PMID: 35940164 DOI: 10.1016/j.compbiomed.2022.105913] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 06/28/2022] [Accepted: 07/23/2022] [Indexed: 11/03/2022]
Abstract
As one of the most reliable and significant indicators, Chronic Obstructive Pulmonary Disease (COPD) becomes a robust predictor of lung cancer early detection, the world's leading cause of cancer death. One of the methods is to analyze the Volatile Organic Compounds (VOCs) in exhaled breath using electronic noses (E-noses), which have become emerging tools for analyzing breath because of their potential and promising technology for diagnosing. However, the signal processing of the E-Nose sensor becomes vital in exposing information about the subject condition, which most researchers strive to accomplish. We proposed a Convolutional Neural Network (CNN) architecture to classify COPD in smokers and non-smokers, healthy subjects, and smokers from E-Nose signals to contribute to this field. Two models were constructed following E-Nose signal processing state-of-the-arts. One was by combined feature extraction and classifier, and the second was by CNN, which directly processed the raw signal. In addition, various feature extraction and classifier (Machine Learning and CNN) used in prior research were investigated. Using 3K and 5K Fold cross-validation results demonstrated that our proposed models outperformed in Kernel Principal Component Analysis (KPCA) with Fx-ConvNet and Pure-ConvNet. They all reached maximum F1-Score with zero standard deviation values indicating a consistent result. Further experiments also showed that KPCA contributed to the increasing performance of some classifiers with average F1-Score 0.933 and 0.068 as standard deviation values.
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Affiliation(s)
- Cries Avian
- Department of Electronic and Computer Engineering, National Taiwan University of Science and Technology, Taiwan
| | - Muhammad Izzuddin Mahali
- Department of Electronic and Computer Engineering, National Taiwan University of Science and Technology, Taiwan; Department of Electronics and Informatics Engineering, Faculty of Engineering, Universitas Negeri Yogyakarta, Indonesia
| | - Nur Achmad Sulistyo Putro
- Department of Electronic and Computer Engineering, National Taiwan University of Science and Technology, Taiwan; Department of Computer Science and Electronics, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Indonesia
| | - Setya Widyawan Prakosa
- Department of Electronic and Computer Engineering, National Taiwan University of Science and Technology, Taiwan
| | - Jenq-Shiou Leu
- Department of Electronic and Computer Engineering, National Taiwan University of Science and Technology, Taiwan.
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Kaloumenou M, Skotadis E, Lagopati N, Efstathopoulos E, Tsoukalas D. Breath Analysis: A Promising Tool for Disease Diagnosis-The Role of Sensors. SENSORS (BASEL, SWITZERLAND) 2022; 22:1238. [PMID: 35161984 PMCID: PMC8840008 DOI: 10.3390/s22031238] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 01/30/2022] [Accepted: 02/01/2022] [Indexed: 05/07/2023]
Abstract
Early-stage disease diagnosis is of particular importance for effective patient identification as well as their treatment. Lack of patient compliance for the existing diagnostic methods, however, limits prompt diagnosis, rendering the development of non-invasive diagnostic tools mandatory. One of the most promising non-invasive diagnostic methods that has also attracted great research interest during the last years is breath analysis; the method detects gas-analytes such as exhaled volatile organic compounds (VOCs) and inorganic gases that are considered to be important biomarkers for various disease-types. The diagnostic ability of gas-pattern detection using analytical techniques and especially sensors has been widely discussed in the literature; however, the incorporation of novel nanomaterials in sensor-development has also proved to enhance sensor performance, for both selective and cross-reactive applications. The aim of the first part of this review is to provide an up-to-date overview of the main categories of sensors studied for disease diagnosis applications via the detection of exhaled gas-analytes and to highlight the role of nanomaterials. The second and most novel part of this review concentrates on the remarkable applicability of breath analysis in differential diagnosis, phenotyping, and the staging of several disease-types, which are currently amongst the most pressing challenges in the field.
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Affiliation(s)
- Maria Kaloumenou
- Department of Applied Physics, National Technical University of Athens, 15780 Athens, Greece; (M.K.); (D.T.)
| | - Evangelos Skotadis
- Department of Applied Physics, National Technical University of Athens, 15780 Athens, Greece; (M.K.); (D.T.)
| | - Nefeli Lagopati
- Medical School, National and Kapodistrian University of Athens, 75, Mikras Asias Str., Goudi, 11527 Athens, Greece; (N.L.); (E.E.)
| | - Efstathios Efstathopoulos
- Medical School, National and Kapodistrian University of Athens, 75, Mikras Asias Str., Goudi, 11527 Athens, Greece; (N.L.); (E.E.)
| | - Dimitris Tsoukalas
- Department of Applied Physics, National Technical University of Athens, 15780 Athens, Greece; (M.K.); (D.T.)
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Predicting Early Hospital Readmissions in COPD Patients Using an Electronic Nose. ARCHIVOS DE BRONCONEUMOLOGÍA 2022; 58:663-665. [DOI: 10.1016/j.arbres.2022.01.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 01/11/2022] [Accepted: 01/17/2022] [Indexed: 11/23/2022]
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[Translated article] Study of diffuse interstitial lung disease with the analysis of volatile particles in exhaled air. Arch Bronconeumol 2022. [DOI: 10.1016/j.arbres.2021.03.023] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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van der Sar IG, Wijbenga N, Nakshbandi G, Aerts JGJV, Manintveld OC, Wijsenbeek MS, Hellemons ME, Moor CC. The smell of lung disease: a review of the current status of electronic nose technology. Respir Res 2021; 22:246. [PMID: 34535144 PMCID: PMC8448171 DOI: 10.1186/s12931-021-01835-4] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Accepted: 08/26/2021] [Indexed: 02/08/2023] Open
Abstract
There is a need for timely, accurate diagnosis, and personalised management in lung diseases. Exhaled breath reflects inflammatory and metabolic processes in the human body, especially in the lungs. The analysis of exhaled breath using electronic nose (eNose) technology has gained increasing attention in the past years. This technique has great potential to be used in clinical practice as a real-time non-invasive diagnostic tool, and for monitoring disease course and therapeutic effects. To date, multiple eNoses have been developed and evaluated in clinical studies across a wide spectrum of lung diseases, mainly for diagnostic purposes. Heterogeneity in study design, analysis techniques, and differences between eNose devices currently hamper generalization and comparison of study results. Moreover, many pilot studies have been performed, while validation and implementation studies are scarce. These studies are needed before implementation in clinical practice can be realised. This review summarises the technical aspects of available eNose devices and the available evidence for clinical application of eNose technology in different lung diseases. Furthermore, recommendations for future research to pave the way for clinical implementation of eNose technology are provided.
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Affiliation(s)
- I G van der Sar
- Department of Respiratory Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - N Wijbenga
- Department of Respiratory Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - G Nakshbandi
- Department of Respiratory Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - J G J V Aerts
- Department of Respiratory Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - O C Manintveld
- Department of Cardiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - M S Wijsenbeek
- Department of Respiratory Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - M E Hellemons
- Department of Respiratory Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - C C Moor
- Department of Respiratory Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
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Ibrahim W, Natarajan S, Wilde M, Cordell R, Monks PS, Greening N, Brightling CE, Evans R, Siddiqui S. A systematic review of the diagnostic accuracy of volatile organic compounds in airway diseases and their relation to markers of type-2 inflammation. ERJ Open Res 2021; 7:00030-2021. [PMID: 34476250 PMCID: PMC8405872 DOI: 10.1183/23120541.00030-2021] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Accepted: 03/27/2021] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Asthma and COPD continue to cause considerable diagnostic and treatment stratification challenges. Volatile organic compounds (VOCs) have been proposed as feasible diagnostic and monitoring biomarkers in airway diseases. AIMS To 1) conduct a systematic review evaluating the diagnostic accuracy of VOCs in diagnosing airway diseases; 2) understand the relationship between reported VOCs and biomarkers of type-2 inflammation; 3) assess the standardisation of reporting according to STARD and TRIPOD criteria; 4) review current methods of breath sampling and analysis. METHODS A PRISMA-oriented systematic search was conducted (January 1997 to December 2020). Search terms included: "asthma", "volatile organic compound(s)", "VOC" and "COPD". Two independent reviewers examined the extracted titles against review objectives. RESULTS 44 full-text papers were included; 40/44 studies were cross-sectional and four studies were interventional in design; 17/44 studies used sensor-array technologies (e.g. eNose). Cross-study comparison was not possible across identified studies due to the heterogeneity in design. The commonest airway diseases differentiating VOCs belonged to carbonyl-containing classes (i.e. aldehydes, esters and ketones) and hydrocarbons (i.e. alkanes and alkenes). Although individual markers that are associated with clinical biomarkers of type-2 inflammation were recognised (i.e. ethane and 3,7-dimethylnonane for asthma and α-methylstyrene and decane for COPD), these were not consistently identified across studies. Only 3/44 reported following STARD or TRIPOD criteria for diagnostic accuracy and multivariate reporting, respectively. CONCLUSIONS Breath VOCs show promise as diagnostic biomarkers of airway diseases and for type-2 inflammation profiling. However, future studies should focus on transparent reporting of diagnostic accuracy and multivariate models and continue to focus on chemical identification of volatile metabolites.
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Affiliation(s)
- Wadah Ibrahim
- Leicester NIHR Biomedical Research Centre (Respiratory Theme), Glenfield Hospital, Leicester, UK
- Dept of Respiratory Sciences, College of Life Sciences, University of Leicester, Leicester, UK
- These authors contributed equally
| | - Sushiladevi Natarajan
- Leicester NIHR Biomedical Research Centre (Respiratory Theme), Glenfield Hospital, Leicester, UK
- Dept of Respiratory Sciences, College of Life Sciences, University of Leicester, Leicester, UK
- These authors contributed equally
| | - Michael Wilde
- Dept of Chemistry, University of Leicester, Leicester, UK
| | | | - Paul S. Monks
- Dept of Chemistry, University of Leicester, Leicester, UK
| | - Neil Greening
- Leicester NIHR Biomedical Research Centre (Respiratory Theme), Glenfield Hospital, Leicester, UK
- Dept of Respiratory Sciences, College of Life Sciences, University of Leicester, Leicester, UK
| | - Christopher E. Brightling
- Leicester NIHR Biomedical Research Centre (Respiratory Theme), Glenfield Hospital, Leicester, UK
- Dept of Respiratory Sciences, College of Life Sciences, University of Leicester, Leicester, UK
| | - Rachael Evans
- Leicester NIHR Biomedical Research Centre (Respiratory Theme), Glenfield Hospital, Leicester, UK
- Dept of Respiratory Sciences, College of Life Sciences, University of Leicester, Leicester, UK
| | - Salman Siddiqui
- Leicester NIHR Biomedical Research Centre (Respiratory Theme), Glenfield Hospital, Leicester, UK
- Dept of Respiratory Sciences, College of Life Sciences, University of Leicester, Leicester, UK
- See Acknowledgements for contributors
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Yamanaka HR, Cheung C, Mendoza JS, Oliva DJ, Elzey-Aberilla K, Perrault KA. Pilot Study on Exhaled Breath Analysis for a Healthy Adult Population in Hawaii. Molecules 2021; 26:molecules26123726. [PMID: 34207244 PMCID: PMC8234827 DOI: 10.3390/molecules26123726] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 06/09/2021] [Accepted: 06/14/2021] [Indexed: 02/01/2023] Open
Abstract
Fast diagnostic results using breath analysis are an anticipated possibility for disease diagnosis or general health screenings. Tests that do not require sending specimens to medical laboratories possess capabilities to speed patient diagnosis and protect both patient and healthcare staff from unnecessary prolonged exposure. The objective of this work was to develop testing procedures on an initial healthy subject cohort in Hawaii to act as a range-finding pilot study for characterizing the baseline of exhaled breath prior to further research. Using comprehensive two-dimensional gas chromatography (GC×GC), this study analyzed exhaled breath from a healthy adult population in Hawaii to profile the range of different volatile organic compounds (VOCs) and survey Hawaii-specific differences. The most consistently reported compounds in the breath profile of individuals were acetic acid, dimethoxymethane, benzoic acid methyl ester, and n-hexane. In comparison to other breathprinting studies, the list of compounds discovered was representative of control cohorts. This must be considered when implementing proposed breath diagnostics in new locations with increased interpersonal variation due to diversity. Further studies on larger numbers of subjects over longer periods of time will provide additional foundational data on baseline breath VOC profiles of control populations for comparison to disease-positive cohorts.
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29
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Biomarkers in Different Asthma Phenotypes. Genes (Basel) 2021; 12:genes12060801. [PMID: 34070316 PMCID: PMC8226821 DOI: 10.3390/genes12060801] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 04/18/2021] [Accepted: 05/21/2021] [Indexed: 12/16/2022] Open
Abstract
Asthma is the most common respiratory disease. It has multiple phenotypes thatcan be partially differentiated by measuring the disease’s specific characteristics—biomarkers. The pathogenetic mechanisms are complex, and it is still a challenge to choose suitable biomarkers to adequately stratify patients, which became especially important with the introduction of biologicals in asthma treatment. Usage of biomarkers and an understanding of the underlying pathobiological mechanisms lead to the definition of endotypes. Asthma can be broadly divided into two endotypes, T2-high and T2-low. The right combination of various biomarkers in different phenotypes is under investigation, hoping to help researchers and clinicians in better disease evaluation since theindividual approach and personalized medicine are imperative. Multiple biomarkers are superior to a single biomarker.
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30
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Ibrahim W, Carr L, Cordell R, Wilde MJ, Salman D, Monks PS, Thomas P, Brightling CE, Siddiqui S, Greening NJ. Breathomics for the clinician: the use of volatile organic compounds in respiratory diseases. Thorax 2021; 76:514-521. [PMID: 33414240 PMCID: PMC7611078 DOI: 10.1136/thoraxjnl-2020-215667] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2020] [Revised: 10/28/2020] [Accepted: 12/03/2020] [Indexed: 01/17/2023]
Abstract
Exhaled breath analysis has the potential to provide valuable insight on the status of various metabolic pathways taking place in the lungs locally and other vital organs, via systemic circulation. For years, volatile organic compounds (VOCs) have been proposed as feasible alternative diagnostic and prognostic biomarkers for different respiratory pathologies.We reviewed the currently published literature on the discovery of exhaled breath VOCs and their utilisation in various respiratory diseasesKey barriers in the development of clinical breath tests include the lack of unified consensus for breath collection and analysis and the complexity of understanding the relationship between the exhaled VOCs and the underlying metabolic pathways. We present a comprehensive overview, in light of published literature and our experience from coordinating a national breathomics centre, of the progress made to date and some of the key challenges in the field and ways to overcome them. We particularly focus on the relevance of breathomics to clinicians and the valuable insights it adds to diagnostics and disease monitoring.Breathomics holds great promise and our findings merit further large-scale multicentre diagnostic studies using standardised protocols to help position this novel technology at the centre of respiratory disease diagnostics.
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Affiliation(s)
- Wadah Ibrahim
- Department of Respiratory Sciences, University of Leicester, Leicester, UK
- Institute for Lung Health, Leicester NIHR Biomedical Research Centre, Leicester, UK
| | - Liesl Carr
- Institute for Lung Health, Leicester NIHR Biomedical Research Centre, Leicester, UK
| | | | | | - Dahlia Salman
- Department of Chemistry, Loughborough University, Loughborough, UK
| | - Paul S Monks
- School of Chemistry, University of Leicester, Leicester, UK
| | - Paul Thomas
- Department of Chemistry, Loughborough University, Loughborough, UK
| | - Chris E Brightling
- Department of Respiratory Sciences, University of Leicester, Leicester, UK
- Institute for Lung Health, Leicester NIHR Biomedical Research Centre, Leicester, UK
| | - Salman Siddiqui
- Department of Respiratory Sciences, University of Leicester, Leicester, UK
- Institute for Lung Health, Leicester NIHR Biomedical Research Centre, Leicester, UK
| | - Neil J Greening
- Department of Respiratory Sciences, University of Leicester, Leicester, UK
- Institute for Lung Health, Leicester NIHR Biomedical Research Centre, Leicester, UK
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31
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Sola Martínez RA, Pastor Hernández JM, Yanes Torrado Ó, Cánovas Díaz M, de Diego Puente T, Vinaixa Crevillent M. Exhaled volatile organic compounds analysis in clinical pediatrics: a systematic review. Pediatr Res 2021; 89:1352-1363. [PMID: 32919397 DOI: 10.1038/s41390-020-01116-8] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2020] [Revised: 07/09/2020] [Accepted: 08/04/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND Measured exhaled volatile organic compounds (VOCs) in breath also referred to as exhaled volatilome have been long claimed as a potential source of non-invasive and clinically applicable biomarkers. However, the feasibility of using exhaled volatilome in clinical practice remains to be demonstrated, particularly in pediatrics where the need for improved non-invasive diagnostic and monitoring methods is most urgent. This work presents the first formal evidence-based judgment of the clinical potential of breath volatilome in the pediatric population. METHODS A rigorous systematic review across Web of Science, SCOPUS, and PubMed databases following the PRISMA statement guidelines. A narrative synthesis of the evidence was conducted and QUADAS-2 was used to assess the quality of selected studies. RESULTS Two independent reviewers deemed 22 out of the 229 records initially found to satisfy inclusion criteria. A summary of breath VOCs found to be relevant for several respiratory, infectious, and metabolic pathologies was conducted. In addition, we assessed their associated metabolism coverage through a functional characterization analysis. CONCLUSION Our results indicate that current research remains stagnant in a preclinical exploratory setting. Designing exploratory experiments in compliance with metabolomics practice should drive forward the clinical translation of VOCs breath analysis. IMPACT What is the key message of your article? Metabolomics practice could help to achieve the clinical utility of exhaled volatilome analysis. What does it add to the existing literature? This work is the first systematic review focused on disease status discrimination using analysis of exhaled breath in the pediatric population. A summary of the reported exhaled volatile organic compounds is conducted together with a functional characterization analysis. What is the impact? Having noted challenges preventing the clinical translation, we summary metabolomics practices and the experimental designs that are closer to clinical practice to create a framework to guide future trials.
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Affiliation(s)
- Rosa A Sola Martínez
- Department of Biochemistry and Molecular Biology (B) and Immunology, University of Murcia and Murcian Institute of Biosanitary Research Virgen de la Arrixaca (IMIB), Murcia, Spain
| | - José M Pastor Hernández
- Department of Biochemistry and Molecular Biology (B) and Immunology, University of Murcia and Murcian Institute of Biosanitary Research Virgen de la Arrixaca (IMIB), Murcia, Spain
| | - Óscar Yanes Torrado
- Department of Electronic Engineering, Universitat Rovira i Virgili, Tarragona, Spain.,Institut d'Investigació Sanitària Pere Virgili (IISPV), Metabolomics Platform, Reus, Spain.,CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain
| | - Manuel Cánovas Díaz
- Department of Biochemistry and Molecular Biology (B) and Immunology, University of Murcia and Murcian Institute of Biosanitary Research Virgen de la Arrixaca (IMIB), Murcia, Spain
| | - Teresa de Diego Puente
- Department of Biochemistry and Molecular Biology (B) and Immunology, University of Murcia and Murcian Institute of Biosanitary Research Virgen de la Arrixaca (IMIB), Murcia, Spain.
| | - María Vinaixa Crevillent
- Department of Electronic Engineering, Universitat Rovira i Virgili, Tarragona, Spain.,Institut d'Investigació Sanitària Pere Virgili (IISPV), Metabolomics Platform, Reus, Spain.,CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain
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Castillo Villegas D, Barril S, Giner J, Millan-Billi P, Rodrigo-Troyano A, Merino JL, Sibila O. Study of Diffuse Interstitial Lung Disease With the Analysis of Volatile Particles in Exhaled Air. Arch Bronconeumol 2021; 58:99-101. [PMID: 33867204 DOI: 10.1016/j.arbres.2021.03.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Accepted: 03/02/2021] [Indexed: 12/01/2022]
Affiliation(s)
- Diego Castillo Villegas
- Servicio de Neumología, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, España.
| | - Silvia Barril
- Servicio de Neumología, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, España; Servicio de Neumología, Hospital Arnau de Vilanova, Lleida, España
| | - Jordi Giner
- Servicio de Neumología, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, España
| | - Paloma Millan-Billi
- Servicio de Neumología, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, España; Servicio de Neumología, Hospital Arnau de Vilanova, Lleida, España; Servicio de Neumologia, Hospital Germans Trias i Pujol, Badalona, España
| | - Ana Rodrigo-Troyano
- Servicio de Neumología, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, España; Servicio de Neumología, Hospital Arnau de Vilanova, Lleida, España; Servicio de Neumologia, Hospital Germans Trias i Pujol, Badalona, España; Servicio de Neumología, Hospital Son Espases, Palma de Mallorca, España
| | - Jose Luis Merino
- Electronic Systems Group, Universitat de les Illes Balears, Palma de Mallorca, España
| | - Oriol Sibila
- Servicio de Neumología, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, España; Instituto del Tórax, Servicio de Neumología, Hospital Clínic, Universitat de Barcelona, IDIBAPS, CIBERES, Barcelona, España
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33
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Monedeiro F, Monedeiro-Milanowski M, Ratiu IA, Brożek B, Ligor T, Buszewski B. Needle Trap Device-GC-MS for Characterization of Lung Diseases Based on Breath VOC Profiles. Molecules 2021; 26:molecules26061789. [PMID: 33810121 PMCID: PMC8004837 DOI: 10.3390/molecules26061789] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 03/16/2021] [Accepted: 03/19/2021] [Indexed: 01/08/2023] Open
Abstract
Volatile organic compounds (VOCs) have been assessed in breath samples as possible indicators of diseases. The present study aimed to quantify 29 VOCs (previously reported as potential biomarkers of lung diseases) in breath samples collected from controls and individuals with lung cancer, chronic obstructive pulmonary disease and asthma. Besides that, global VOC profiles were investigated. A needle trap device (NTD) was used as pre-concentration technique, associated to gas chromatography-mass spectrometry (GC-MS) analysis. Univariate and multivariate approaches were applied to assess VOC distributions according to the studied diseases. Limits of quantitation ranged from 0.003 to 6.21 ppbv and calculated relative standard deviations did not exceed 10%. At least 15 of the quantified targets presented themselves as discriminating features. A random forest (RF) method was performed in order to classify enrolled conditions according to VOCs' latent patterns, considering VOCs responses in global profiles. The developed model was based on 12 discriminating features and provided overall balanced accuracy of 85.7%. Ultimately, multinomial logistic regression (MLR) analysis was conducted using the concentration of the nine most discriminative targets (2-propanol, 3-methylpentane, (E)-ocimene, limonene, m-cymene, benzonitrile, undecane, terpineol, phenol) as input and provided an average overall accuracy of 95.5% for multiclass prediction.
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Affiliation(s)
- Fernanda Monedeiro
- Interdisciplinary Centre of Modern Technologies, Nicolaus Copernicus University in Toruń, 4 Wileńska St., 87-100 Toruń, Poland; (F.M.); (M.M.-M.); (I.-A.R.); (B.B.)
| | - Maciej Monedeiro-Milanowski
- Interdisciplinary Centre of Modern Technologies, Nicolaus Copernicus University in Toruń, 4 Wileńska St., 87-100 Toruń, Poland; (F.M.); (M.M.-M.); (I.-A.R.); (B.B.)
| | - Ileana-Andreea Ratiu
- Interdisciplinary Centre of Modern Technologies, Nicolaus Copernicus University in Toruń, 4 Wileńska St., 87-100 Toruń, Poland; (F.M.); (M.M.-M.); (I.-A.R.); (B.B.)
- “Raluca Ripan” Institute for Research in Chemistry, Babeş-Bolyai University, 30 Fântânele St., RO-400294 Cluj-Napoca, Romania
- Department of Environmental Chemistry and Bioanalytics, Faculty of Chemistry, Nicolaus Copernicus University in Toruń, 7 Gagarina St., 87-100 Toruń, Poland
| | - Beata Brożek
- Department of Lung Diseases, Provincial Polyclinic Hospital in Toruń, 4 Krasińskiego St., 87-100 Toruń, Poland;
| | - Tomasz Ligor
- Interdisciplinary Centre of Modern Technologies, Nicolaus Copernicus University in Toruń, 4 Wileńska St., 87-100 Toruń, Poland; (F.M.); (M.M.-M.); (I.-A.R.); (B.B.)
- Department of Environmental Chemistry and Bioanalytics, Faculty of Chemistry, Nicolaus Copernicus University in Toruń, 7 Gagarina St., 87-100 Toruń, Poland
- Correspondence: ; Tel.: +48-(56)-665-60-58
| | - Bogusław Buszewski
- Interdisciplinary Centre of Modern Technologies, Nicolaus Copernicus University in Toruń, 4 Wileńska St., 87-100 Toruń, Poland; (F.M.); (M.M.-M.); (I.-A.R.); (B.B.)
- Department of Environmental Chemistry and Bioanalytics, Faculty of Chemistry, Nicolaus Copernicus University in Toruń, 7 Gagarina St., 87-100 Toruń, Poland
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Application of chemoresistive gas sensors and chemometric analysis to differentiate the fingerprints of global volatile organic compounds from diseases. Preliminary results of COPD, lung cancer and breast cancer. Clin Chim Acta 2021; 518:83-92. [PMID: 33766555 DOI: 10.1016/j.cca.2021.03.016] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 02/20/2021] [Accepted: 03/18/2021] [Indexed: 12/20/2022]
Abstract
BACKGROUND Analysis of volatile organic compounds (VOCs) in exhaled breath has been proposed as a screening method that discriminates between disease and healthy subjects, few studies evaluate whether these chemical fingerprints are specific when compared between diseases. We evaluated global VOCs and their discrimination capacity in chronic obstructive pulmonary disease (COPD), lung cancer, breast cancer and healthy subjects by chemoresistive sensors and chemometric analysis. METHODS A cross-sectional study was conducted with the participation of 30 patients with lung cancer, 50 with breast cancer, 50 with COPD and 50 control subjects. Each participant's exhaled breath was analyzed with the electronic nose. A multivariate analysis was carried: principal component analysis (PCA) and, canonical analysis of principal coordinates (CAP). Twenty single-blind samples from the 4 study groups were evaluated by CAP. RESULTS A separation between the groups of patients to the controls was achieved through PCA with explanations of >90% of the data and with a correct classification of 100%. In the CAP of the 4 study groups, discrimination between the diseases was obtained with 2 canonical axes with a correct general classification of 91.35%. This model was used for the prediction of the single-blind samples resulting in correct classification of 100%. CONCLUSIONS The application of chemoresistive gas sensors and chemometric analysis can be used as a useful tool for a screening test for lung cancer, breast cancer and COPD since this equipment detects the set of VOCs present in the exhaled breath to generate a characteristic chemical fingerprint of each disease.
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Liu L, Li W, He Z, Chen W, Liu H, Chen K, Pi X. Detection of lung cancer with electronic nose using a novel ensemble learning framework. J Breath Res 2021; 15. [PMID: 33578407 DOI: 10.1088/1752-7163/abe5c9] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Accepted: 02/12/2021] [Indexed: 02/02/2023]
Abstract
Breath analysis based on electronic nose (e-nose) is a promising new technology for the detection of lung cancer that is non-invasive, simple to operate and cost-effective. Lung cancer screening by e-nose relies on predictive models established using machine learning methods. However, using only a single machine learning method to detect lung cancer has some disadvantages, including low detection accuracy and high false negative rate. To address these problems, groups of individual learning models with excellent performance were selected from classic models, including Support Vector Machine, Decision Tree, Random Forest, Logistic Regression and K-nearest neighbor regression, to build an ensemble learning framework (PCA-SVE). The output result of the PCA-SVE framework was obtained by voting. To test this approach, we analyzed 214 breath samples measured by e-nose with 11 gas sensors of four types using the proposed PCA-SVE framework. Experimental results indicated that the accuracy, sensitivity, and specificity of the proposed framework were 95.75%, 94.78%, and 96.96%, respectively. This framework overcomes the disadvantages of a single model, thereby providing an improved, practical alternative for exhaled breath analysis by e-nose.
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Affiliation(s)
- Lei Liu
- Key Laboratory of Biotechnology Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, P.R. China, Chongqing, Chongqing, 400044, CHINA
| | - Wang Li
- School of Pharmacy and Bioengineering, Chongqing University of Technology, No.174 Shazhengjie, Shapingba, Chongqing, Chongqing, 400044, CHINA
| | - ZiChun He
- Chongqing Red Cross Hospital (People's Hospital of Jiangbei District), Chongqing Red Cross Hospital, 168 Hai'er Rd, Chongqing, 400020 , CHINA
| | - Weimin Chen
- Kunming University, No.727 South Jingming Rd, Chenggong District, Kunming, Yunnan, 650500, CHINA
| | - Hongying Liu
- Key Laboratory of Biotechnology Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, No.174 Shazhengjie, Shapingba, Chongqing, Chongqing, 400044, CHINA
| | - Ke Chen
- Key Laboratory of Biotechnology Science and Technology, Ministry of Education, College of Bioengineering, , Chongqing University, No.174 Shazhengjie, Shapingba, Chongqing, Chongqing, 400044, CHINA
| | - Xitian Pi
- Key Laboratory of Biotechnology Science and Technology, Ministry of Education, College of Bioengineering, , Chongqing University, No.174 Shazhengjie, Shapingba, Chongqing, Chongqing, 400044, CHINA
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Tozlu BH, Şimşek C, Aydemir O, Karavelioglu Y. A High performance electronic nose system for the recognition of myocardial infarction and coronary artery diseases. Biomed Signal Process Control 2021. [DOI: 10.1016/j.bspc.2020.102247] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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van Oort PMP, White IR, Ahmed W, Johnson C, Bannard-Smith J, Felton T, Bos LD, Goodacre R, Dark P, Fowler SJ. Detection and quantification of exhaled volatile organic compounds in mechanically ventilated patients - comparison of two sampling methods. Analyst 2021; 146:222-231. [PMID: 33103170 DOI: 10.1039/c9an01134j] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
Exhaled breath analysis is a promising new diagnostic tool, but currently no standardised method for sampling is available in mechanically ventilated patients. We compared two breath sampling methods, first using an artificial ventilator circuit, then in "real life" in mechanically ventilated patients on the intensive care unit. In the laboratory circuit, a 24-component synthetic-breath volatile organic compound (VOC) mixture was injected into the system as air was sampled: (A) through a port on the exhalation limb of the circuit and (B) through a closed endo-bronchial suction catheter. Sorbent tubes were used to collect samples for analysis by thermal desorption-gas chromatography-mass spectrometry. Realistic mechanical ventilation rates and breath pressure-volume loops were established and method detection limits (MDLs) were calculated for all VOCs. Higher yields of VOCs were retrieved using the closed suction catheter; however, for several VOCs MDLs were compromised due to the background signal associated with plastic and rubber components in the catheters. Different brands of suction catheter were compared. Exhaled VOC data from 40 patient samples collected at two sites were then used to calculate the proportion of data analysed above the MDL. The relative performance of the two methods differed depending on the VOC under study and both methods showed sensitivity towards different exhaled VOCs. Furthermore, method performance differed depending on recruitment site, as the centres were equipped with different brands of respiratory equipment, an important consideration for the design of multicentre studies investigating exhaled VOCs in mechanically ventilated patients.
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Affiliation(s)
- Pouline M P van Oort
- Department of Intensive Care, Amsterdam UMC - location Academic Medical Centre (AMC), Amsterdam, the Netherlands
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Lammers A, van Bragt J, Brinkman P, Neerincx A, Bos L, Vijverberg S, Maitland-van der Zee A. Breathomics in Chronic Airway Diseases. SYSTEMS MEDICINE 2021. [DOI: 10.1016/b978-0-12-801238-3.11589-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
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Zhong W, Zhang X, Zeng Y, Lin D, Wu J. Recent applications and strategies in nanotechnology for lung diseases. NANO RESEARCH 2021; 14:2067-2089. [PMID: 33456721 PMCID: PMC7796694 DOI: 10.1007/s12274-020-3180-3] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Revised: 10/11/2020] [Accepted: 10/11/2020] [Indexed: 05/14/2023]
Abstract
Lung diseases, including COVID-19 and lung cancers, is a huge threat to human health. However, for the treatment and diagnosis of various lung diseases, such as pneumonia, asthma, cancer, and pulmonary tuberculosis, are becoming increasingly challenging. Currently, several types of treatments and/or diagnostic methods are used to treat lung diseases; however, the occurrence of adverse reactions to chemotherapy, drug-resistant bacteria, side effects that can be significantly toxic, and poor drug delivery necessitates the development of more promising treatments. Nanotechnology, as an emerging technology, has been extensively studied in medicine. Several studies have shown that nano-delivery systems can significantly enhance the targeting of drug delivery. When compared to traditional delivery methods, several nanoparticle delivery strategies are used to improve the detection methods and drug treatment efficacy. Transporting nanoparticles to the lungs, loading appropriate therapeutic drugs, and the incorporation of intelligent functions to overcome various lung barriers have broad prospects as they can aid in locating target tissues and can enhance the therapeutic effect while minimizing systemic side effects. In addition, as a new and highly contagious respiratory infection disease, COVID-19 is spreading worldwide. However, there is no specific drug for COVID-19. Clinical trials are being conducted in several countries to develop antiviral drugs or vaccines. In recent years, nanotechnology has provided a feasible platform for improving the diagnosis and treatment of diseases, nanotechnology-based strategies may have broad prospects in the diagnosis and treatment of COVID-19. This article reviews the latest developments in nanotechnology drug delivery strategies in the lungs in recent years and studies the clinical application value of nanomedicine in the drug delivery strategy pertaining to the lung.
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Affiliation(s)
- Wenhao Zhong
- Department of Hematology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107 China
| | - Xinyu Zhang
- Department of Hematology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107 China
| | - Yunxin Zeng
- Department of Hematology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107 China
| | - Dongjun Lin
- Department of Hematology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107 China
| | - Jun Wu
- Department of Hematology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107 China
- Key Laboratory of Sensing Technology and Biomedical Instrument of Guangdong Province, School of Biomedical Engineering, Sun Yat-sen University, Guangzhou, 510006 China
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Ettema R, Lenders M, Vliegen J, Slettenaar A, Tjepkema-Cloostermans MC, de Vos C. Detecting Multiple Sclerosis via breath analysis using an eNose, a pilot study. J Breath Res 2020; 15. [PMID: 33271513 DOI: 10.1088/1752-7163/abd080] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Accepted: 12/03/2020] [Indexed: 11/11/2022]
Abstract
OBJECTIVE In the present study we investigated whether Multiple Sclerosis (MS) can be detected via exhaled breath analysis using an electronic nose. The AeonoseTM (an electronic nose, The eNose Company, Zutphen, The Netherlands) is a diagnostic test device to detect patterns of volatile organic compounds in exhaled breath. We evaluated whether the AeonoseTM can make a distinction between the breath patterns of patients with MS and healthy control subjects. METHODS In this mono-center, prospective, non-invasive study, 124 subjects with a confirmed diagnosis of MS and 129 control subjects each breathed into the AeonoseTM for 5 minutes. Exhaled breath data was used to train an artificial neural network (ANN) predictive model. To investigate the influence of medication intake we created a second predictive model with a subgroup of MS patients without medication prescribed for MS. RESULTS The ANN model based on the entire dataset was able to distinguish MS patients from healthy controls with a sensitivity of 0.75 [95% CI: 0.66-0.82] and specificity of 0.60 [0.51-0.69]. The model created with the subgroup of MS patients not using medication and the healthy control subjects had a sensitivity of 0.93 [0.82-0.98] and a specificity of 0.74 [0.65-0.81]. CONCLUSION The study showed that the AeonoseTM is able to make a distinction between MS patients and healthy control subjects, and could potentially provide a quick screening test to assist in diagnosing MS. Further research is needed to determine whether the AeonoseTM is able to differentiate new MS patients from subjects who will not get the diagnosis.
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Affiliation(s)
- Rozemarijn Ettema
- Neurology, Isala Zwolle, Dokter van Heesweg 2, Zwolle, Overijssel, 8025 AB, NETHERLANDS
| | - Mathieu Lenders
- Neurosurgery, Medisch Spectrum Twente, Enschede, Overijssel, NETHERLANDS
| | - Jos Vliegen
- Neurology, Medisch Spectrum Twente, Enschede, Overijssel, NETHERLANDS
| | - Astrid Slettenaar
- Neurology, Medisch Spectrum Twente, Enschede, Overijssel, NETHERLANDS
| | | | - Cecile de Vos
- Anesthesiology, Erasmus Medical Center, Rotterdam, Zuid-Holland, NETHERLANDS
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The Role of Electronic Noses in Phenotyping Patients with Chronic Obstructive Pulmonary Disease. BIOSENSORS-BASEL 2020; 10:bios10110171. [PMID: 33187142 PMCID: PMC7697924 DOI: 10.3390/bios10110171] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 11/05/2020] [Accepted: 11/09/2020] [Indexed: 12/12/2022]
Abstract
Chronic obstructive pulmonary disease (COPD) is a common progressive disorder of the respiratory system which is currently the third leading cause of death worldwide. Exhaled breath analysis is a non-invasive method to study lung diseases, and electronic noses have been extensively used in breath research. Studies with electronic noses have proved that the pattern of exhaled volatile organic compounds is different in COPD. More recent investigations have reported that electronic noses could potentially distinguish different endotypes (i.e., neutrophilic vs. eosinophilic) and are able to detect microorganisms in the airways responsible for exacerbations. This article will review the published literature on electronic noses and COPD and help in identifying methodological, physiological, and disease-related factors which could affect the results.
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Díaz de León-Martínez L, Rodríguez-Aguilar M, Gorocica-Rosete P, Domínguez-Reyes CA, Martínez-Bustos V, Tenorio-Torres JA, Ornelas-Rebolledo O, Cruz-Ramos JA, Balderas-Segura B, Flores-Ramírez R. Identification of profiles of volatile organic compounds in exhaled breath by means of an electronic nose as a proposal for a screening method for breast cancer: a case-control study. J Breath Res 2020; 14:046009. [PMID: 32698165 DOI: 10.1088/1752-7163/aba83f] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The objective of the present study was to identify volatile prints from exhaled breath, termed breath-print, from breast cancer (BC) patients and healthy women by means of an electronic nose and to evaluate its potential use as a screening method. A cross-sectional study was performed on 443 exhaled breath samples from women, of whom 262 had been diagnosed with BC by biopsy and 181 were healthy women (control group). Breath-print analysis was performed utilizing the Cyranose 320 electronic nose. Group data were evaluated by principal component analysis (PCA), canonical discriminant analysis (CDA), and support vector machine (SVM), and the test's diagnostic power was evaluated by means of receiver operating characteristic (ROC) curves. The results obtained using the model generated from the CDA, which best describes the behavior of the assessed groups, indicated that the breath-print of BC patients was different from that of healthy women and that they presented with a variability of up to 98.8% and a correct classification of 98%. The sensitivity, specificity, negative predictive value, and positive predictive value reached 100% according to the ROC curve. The present study demonstrates the capability of the electronic nose to separate between healthy subjects and BC patients. This research could have a beneficial impact on clinical practice as we consider that this test could probably be used at the first point before the application of established gold tests (mammography, ultrasound, and biopsy) and substantially improve screening tests in the general population.
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Affiliation(s)
- Lorena Díaz de León-Martínez
- Center for Applied Research in Environment and Health, CIACYT, Medicine Faculty, Autonomous University of San Luis Potosí, Av. Venustiano Carranza 2405, CP 78210, San Luis Potosí, SLP, Mexico
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Méndez-Rodríguez KB, Figueroa-Vega N, Ilizaliturri-Hernandez CA, Cardona-Alvarado M, Borjas-García JA, Kornhauser C, Malacara JM, Flores-Ramírez R, Pérez-Vázquez FJ. Identification of metabolic markers in patients with type 2 Diabetes by Ultrafast gas chromatography coupled to electronic nose. A pilot study. Biomed Chromatogr 2020; 34:e4956. [PMID: 32706910 DOI: 10.1002/bmc.4956] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Revised: 07/19/2020] [Accepted: 07/22/2020] [Indexed: 12/27/2022]
Abstract
Metabolomics is a potential tool for the discovery of new biomarkers in the early diagnosis of diseases. An ultra-fast gas chromatography system equipped to an electronic nose detector (FGC eNose) was used to identify the metabolomic profile of Volatile Organic Compounds (VOCs) in type 2 diabetes (T2D) urine from Mexican population. A cross-sectional, comparative, and clinical study with translational approach was performed. We recruited twenty T2D patients and twenty-one healthy subjects. Urine samples were taken and analyzed by FGC eNose. Eighty-eight compounds were identified through Kovats's indexes. A natural variation of 30% between the metabolites, expressed by study groups, was observed in Principal Component 1 and 2 with a significant difference (p < 0.001). The model, performed through a Canonical Analysis of Principal coordinated (CAP), allowed a correct classification of 84.6% between healthy and T2D patients, with a 15.4% error. The metabolites 2-propenal, 2-propanol, butane- 2,3-dione and 2-methylpropanal, were increased in patients with T2D, and they were strongly correlated with discrimination between clinically healthy people and T2D patients. This study identified metabolites in urine through FGC eNose that can be used as biomarkers in the identification of T2D patients. However, more studies are needed for its implementation in clinical practice.
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Affiliation(s)
- Karen Beatriz Méndez-Rodríguez
- Coordinación para la Innovación y Aplicación de la Ciencia y la Tecnología (CIACyT), Universidad Autónoma de San Luis Potosí, San Luis Potosí, S.L.P., Mexico
| | - Nicté Figueroa-Vega
- Department of Medical Sciences, University of Guanajuato, León, Gto., Mexico
| | - César Arturo Ilizaliturri-Hernandez
- Coordinación para la Innovación y Aplicación de la Ciencia y la Tecnología (CIACyT), Universidad Autónoma de San Luis Potosí, San Luis Potosí, S.L.P., Mexico
| | | | | | - Carlos Kornhauser
- Department of Medical Sciences, University of Guanajuato, León, Gto., Mexico
| | | | - Rogelio Flores-Ramírez
- Coordinación para la Innovación y Aplicación de la Ciencia y la Tecnología (CIACyT), Universidad Autónoma de San Luis Potosí, San Luis Potosí, S.L.P., Mexico.,CONACYT Research Fellow, Coordinación para la Innovación y Aplicación de la Ciencia y la Tecnología (CIACYT), Universidad Autónoma de San Luis Potosí, San Luis Potosí, S.L.P., Mexico
| | - Francisco Javier Pérez-Vázquez
- Coordinación para la Innovación y Aplicación de la Ciencia y la Tecnología (CIACyT), Universidad Autónoma de San Luis Potosí, San Luis Potosí, S.L.P., Mexico.,CONACYT Research Fellow, Coordinación para la Innovación y Aplicación de la Ciencia y la Tecnología (CIACYT), Universidad Autónoma de San Luis Potosí, San Luis Potosí, S.L.P., Mexico
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Tenero L, Sandri M, Piazza M, Paiola G, Zaffanello M, Piacentini G. Electronic nose in discrimination of children with uncontrolled asthma. J Breath Res 2020; 14:046003. [PMID: 32512553 DOI: 10.1088/1752-7163/ab9ab0] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Measuring biomarkers (e.g. volatile organic compounds [VOCs]) in exhaled breath is an attractive approach to monitor airway inflammation in asthma and other lung diseases. Olfactive technology by electronic nose (e-Nose) has been applied to identify VOCs in exhaled breath. We compared e-Nose respiratory patterns in a pediatric cohort with asthma classificate children with different asthma control. This cross-sectional study involved 38 children: 28 with asthma and 10 healthy controls . The asthmatic patients were categorized as having controlled (AC), partially controlled (APC) or uncontrolled asthma (ANC) based on level of asthma symptom control according to Global Initiative for Asthma (GINA). Clinical exams, exhaled breath collection for generating e-Nose VOC profiles, and spirometry were performed. Exhaled breath samples were obtained using a commercial electronic nose (Cyranose 320; Smith Detections, Pasadena, CA, USA). The discriminative ability of breathprints were investigated by principal component analysis and penalized logistic regression. The e-Nose was able to discriminate between the CON (controls) + AC and the ANC + APC group with an area under the curve [AUC] of 0.85 (95% confidence interval [CI] 0.72 to 0.98) and a cross-validated AUC of 0.80 (95% CI 0.70 to 0.85). Sensitivity and specificity calculated using the Youden index were 0.79 and 0.84, respectively. Exhaled biomarker patterns were easy to obtain with the device and were able to differentiate children with uncontrolled symptomatic asthma from asymptomatic controls.
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Affiliation(s)
- Laura Tenero
- Department of Surgery, Dentistry, Paediatrics and Gynaecology, University of Verona, Verona, Italy
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Farraia M, Cavaleiro Rufo J, Paciência I, Castro Mendes F, Rodolfo A, Rama T, Rocha SM, Delgado L, Brinkman P, Moreira A. Human volatilome analysis using eNose to assess uncontrolled asthma in a clinical setting. Allergy 2020; 75:1630-1639. [PMID: 31997360 DOI: 10.1111/all.14207] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2019] [Revised: 12/18/2019] [Accepted: 01/06/2020] [Indexed: 01/09/2023]
Abstract
BACKGROUND Analyses of exhaled volatile organic compounds (VOCs) have shown promising results when distinguishing individuals with asthma. Currently, there are no biomarkers for uncontrolled asthma. Therefore, we aimed to assess, in a real-life clinical setting, the ability of the exhaled VOC analysis, using an electronic nose (eNose), to identify individuals with uncontrolled asthma. METHODS A cross-sectional study was conducted, and breath samples from 199 participants (130 females, aged 6-78, 66% with asthma) were analysed using an eNose. A multivariate unsupervised cluster analysis, using the resistance data from 32 sensors, could distinguish three clusters of VOC patterns in the training and testing groups. Comparisons between the clusters were performed using the one-way ANOVA, Kruskal-Wallis and chi-squared tests. RESULTS In the training set (n = 121), three different clusters covering asthma, lung function, symptoms in the previous 4 weeks and age were identified. The pairwise comparisons showed significant differences with respect to chest tightness during exercise, dyspnoea and gender. These findings were confirmed in the testing set (n = 78) where the training model identified three clusters. The participants who reported fewer respiratory symptoms (dyspnoea and night-time awakenings) were grouped into one cluster, while the others comprised participants who showed similar poor control over symptoms with the distribution of the individuals with asthma being significantly different between them. CONCLUSIONS In a clinical setting, the analysis of the exhaled VOC profiles using an eNose could be used as a fast and noninvasive complementary assessment tool for the detection of uncontrolled asthma symptoms.
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Affiliation(s)
- Mariana Farraia
- EPIUnit‐Instituto de Saúde Pública Universidade do Porto Porto Portugal
- Serviço de Imunologia Básica e Clínica Departamento de Patologia Faculdade de Medicina da Universidade do Porto Porto Portugal
| | - João Cavaleiro Rufo
- EPIUnit‐Instituto de Saúde Pública Universidade do Porto Porto Portugal
- Serviço de Imunologia Básica e Clínica Departamento de Patologia Faculdade de Medicina da Universidade do Porto Porto Portugal
| | - Inês Paciência
- EPIUnit‐Instituto de Saúde Pública Universidade do Porto Porto Portugal
- Serviço de Imunologia Básica e Clínica Departamento de Patologia Faculdade de Medicina da Universidade do Porto Porto Portugal
- Institute of Science and Innovation in Mechanical Engineering and Industrial Management (INEGI) Porto Portugal
| | - Francisca Castro Mendes
- Serviço de Imunologia Básica e Clínica Departamento de Patologia Faculdade de Medicina da Universidade do Porto Porto Portugal
| | - Ana Rodolfo
- Serviço de Imunologia Básica e Clínica Departamento de Patologia Faculdade de Medicina da Universidade do Porto Porto Portugal
- Departamento de Imunoalergologia Centro Hospitalar Universitário de S. João EPE Porto Portugal
| | - Tiago Rama
- Serviço de Imunologia Básica e Clínica Departamento de Patologia Faculdade de Medicina da Universidade do Porto Porto Portugal
- Departamento de Imunoalergologia Centro Hospitalar Universitário de S. João EPE Porto Portugal
| | - Sílvia M. Rocha
- Departamento de Química & QOPNA‐LAQV‐REQUINTEUniversidade de Aveiro Aveiro Portugal
| | - Luís Delgado
- Serviço de Imunologia Básica e Clínica Departamento de Patologia Faculdade de Medicina da Universidade do Porto Porto Portugal
- Departamento de Imunoalergologia Centro Hospitalar Universitário de S. João EPE Porto Portugal
| | - Paul Brinkman
- Department of Respiratory Medicine Amsterdam UMC University of Amsterdam Amsterdam the Netherlands
| | - André Moreira
- EPIUnit‐Instituto de Saúde Pública Universidade do Porto Porto Portugal
- Serviço de Imunologia Básica e Clínica Departamento de Patologia Faculdade de Medicina da Universidade do Porto Porto Portugal
- Departamento de Imunoalergologia Centro Hospitalar Universitário de S. João EPE Porto Portugal
- Faculdade de Ciências da Nutrição e Alimentação da Universidade do Porto Porto Portugal
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Sinha R, Lockman KA, Homer NZM, Bower E, Brinkman P, Knobel HH, Fallowfield JA, Jaap AJ, Hayes PC, Plevris JN. Volatomic analysis identifies compounds that can stratify non-alcoholic fatty liver disease. JHEP Rep 2020; 2:100137. [PMID: 32775974 PMCID: PMC7397704 DOI: 10.1016/j.jhepr.2020.100137] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Revised: 05/05/2020] [Accepted: 05/31/2020] [Indexed: 12/19/2022] Open
Abstract
Background & aims Analysis of volatile organic compounds (VOCs) in exhaled breath, ‘volatomics’, provides opportunities for non-invasive biomarker discovery and novel mechanistic insights into a variety of diseases. The purpose of this pilot study was to compare breath VOCs in an initial cohort of patients with non-alcoholic fatty liver disease (NAFLD) and healthy controls. Methods Breath samples were collected from 15 participants with Child-Pugh class A NAFLD cirrhosis, 14 with non-cirrhotic NAFLD, and 14 healthy volunteers. Exhaled breath samples were collected using an established methodology and VOC profiles were analysed by gas chromatography-mass spectrometry. The levels of 19 VOCs previously associated with cirrhosis were assessed. Peaks of the VOCs were confirmed and integrated using Xcalibur® software, normalised to an internal standard. Receiver-operating characteristic (ROC) curves were used to determine the diagnostic accuracy of the candidate VOCs. Results Terpinene, dimethyl sulfide, and D-limonene provided the highest predictive accuracy to discriminate between study groups. Combining dimethyl sulfide with D-limonene led to even better discrimination of patients with NAFLD cirrhosis from healthy volunteers (AUROC 0.98; 95% CI 0.93–1.00; p <0.001) and patients with NAFLD cirrhosis from those with non-cirrhotic NAFLD (AUROC 0.91; 95% CI 0.82–1.00; p <0.001). Breath terpinene concentrations discriminated between patients with non-cirrhotic NAFLD and healthy volunteers (AUROC 0.84; 95% CI 0.68–0.99; p = 0.002). Conclusion Breath terpinene, dimethyl sulfide, and D-limonene are potentially useful volatomic markers for stratifying NAFLD; in addition, a 2-stage approach enables the differentiation of patients with cirrhosis from those without. However, these observations require validation in a larger NAFLD population. (ClinicalTrials.gov Identifier: NCT02950610). Lay summary Breath malodour has been associated with a failing liver since the ancient Greeks. Analytical chemistry has provided us an insight into ubiquitous volatile organic compounds associated with liver (and other) diseases. This has vastly improved our understanding of the mechanistic processes of liver damage. Our study aims to identify volatile organic compounds which are specific to non-alcoholic fatty liver disease and that can be exploited for rapid diagnostics.
Metabolic dysfunction in liver disease is reflected in the biocomposition of exhaled breath. Specific volatile organic compounds can be measured in breath samples (volatomics) and have diagnostic potential in chronic liver disease. Levels of alfa-terpinene, dimethyl sulfide, and D-limonene in exhaled breath can be used to stratify patients with non-alcoholic fatty liver disease.
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Key Words
- ALT, alanine aminotransaminase
- APRI, aminotransferase:platelet ratio index
- ARFI, acoustic radiation force impulse
- AST, aspartate aminotransferase
- AUROC, area under the receiver-operating characteristics curve
- BMI, body mass index
- D-limonene
- Dimethyl sulfide
- GAVE, gastric antral vascular ectasia
- GC-MS, gas chromatography mass spectrometry
- GGT, gamma-glutamyltransferase
- HA, hyaluronic acid
- HOMA, homeostatic model assessment
- NAFLD, non-alcoholic fatty liver disease
- NASH, non-alcoholic steatohepatitis
- Non-alcoholic fatty liver disease
- PHG, portal hypertensive gastropathy
- QC, quality control
- T2DM, type 2 diabetes mellitus
- TE, transient elastography
- Terpinene
- VOCs, volatile organic compounds
- Volatile organic compounds
- Volatomics
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Affiliation(s)
- Rohit Sinha
- Hepatology Laboratory and Centre for Liver and Digestive Disorders, Royal Infirmary of Edinburgh and The University of Edinburgh, Edinburgh, UK
| | - Khalida A Lockman
- Edinburgh Acute & General Medicine, Royal Infirmary of Edinburgh and The University of Edinburgh, Edinburgh, UK
| | - Natalie Z M Homer
- Mass Spectrometry Core, Edinburgh Clinical Research Facility, Centre for Cardiovascular Science, The University of Edinburgh, Edinburgh, UK
| | - Edward Bower
- Mass Spectrometry Core, Edinburgh Clinical Research Facility, Centre for Cardiovascular Science, The University of Edinburgh, Edinburgh, UK
| | - Paul Brinkman
- Department of Respiratory Medicine, Amsterdam University Medical Centre, Amsterdam, The Netherlands
| | - Hugo H Knobel
- Eurofins Materials Science Netherlands BV, High Tech Campus, Eindhoven, The Netherlands
| | | | - Alan J Jaap
- Edinburgh Centre for Endocrinology and Diabetes, Royal Infirmary of Edinburgh and The University of Edinburgh, Edinburgh, UK
| | - Peter C Hayes
- Hepatology Laboratory and Centre for Liver and Digestive Disorders, Royal Infirmary of Edinburgh and The University of Edinburgh, Edinburgh, UK
| | - John N Plevris
- Hepatology Laboratory and Centre for Liver and Digestive Disorders, Royal Infirmary of Edinburgh and The University of Edinburgh, Edinburgh, UK
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Freddi S, Emelianov AV, Bobrinetskiy II, Drera G, Pagliara S, Kopylova DS, Chiesa M, Santini G, Mores N, Moscato U, Nasibulin AG, Montuschi P, Sangaletti L. Development of a Sensing Array for Human Breath Analysis Based on SWCNT Layers Functionalized with Semiconductor Organic Molecules. Adv Healthc Mater 2020; 9:e2000377. [PMID: 32378358 DOI: 10.1002/adhm.202000377] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Revised: 04/09/2020] [Indexed: 02/04/2023]
Abstract
A sensor array based on heterojunctions between semiconducting organic layers and single walled carbon nanotube (SWCNT) films is produced to explore applications in breathomics, the molecular analysis of exhaled breath. The array is exposed to gas/volatiles relevant to specific diseases (ammonia, ethanol, acetone, 2-propanol, sodium hypochlorite, benzene, hydrogen sulfide, and nitrogen dioxide). Then, to evaluate its capability to operate with real relevant biological samples the array is exposed to human breath exhaled from healthy subjects. Finally, to provide a proof of concept of its diagnostic potential, the array is exposed to exhaled breath samples collected from subjects with chronic obstructive pulmonary disease (COPD), an airway chronic inflammatory disease not yet investigated with CNT-based sensor arrays, and breathprints are compared with those obtained from of healthy subjects. Principal component analysis shows that the sensor array is able to detect various target gas/volatiles with a clear fingerprint on a 2D subspace, is suitable for breath profiling in exhaled human breath, and is able to distinguish subjects with COPD from healthy subjects based on their breathprints. This classification ability is further improved by selecting the most responsive sensors to nitrogen dioxide, a potential biomarker of COPD.
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Affiliation(s)
- Sonia Freddi
- Mathematics and Physics DepartmentUniversità Cattolica del Sacro Cuore via dei Musei 41 Brescia 25121 Italy
- Surface Science and Spectroscopy Lab @ I‐LampUniversità Cattolica del Sacro Cuore Brescia 25121 Italy
- Department of ChemistryDivision of Molecular Imaging and PhotonicsKU Leuven Celestijnenlaan 200F Leuven 3001 Belgium
| | - Aleksei V. Emelianov
- National Research University of Electronic Technology Zelenograd Moscow 124498 Russia
- P.N. Lebedev Physical Institute of the Russian Academy of Sciences Moscow 119991 Russia
| | - Ivan I. Bobrinetskiy
- National Research University of Electronic Technology Zelenograd Moscow 124498 Russia
- BioSense Institute – Research and Development Institute for Information Technologies in BiosystemsUniversity of Novi Sad Dr Zorana Djindjica 1a Novi Sad 21000 Serbia
| | - Giovanni Drera
- Mathematics and Physics DepartmentUniversità Cattolica del Sacro Cuore via dei Musei 41 Brescia 25121 Italy
- Surface Science and Spectroscopy Lab @ I‐LampUniversità Cattolica del Sacro Cuore Brescia 25121 Italy
| | - Stefania Pagliara
- Mathematics and Physics DepartmentUniversità Cattolica del Sacro Cuore via dei Musei 41 Brescia 25121 Italy
- Surface Science and Spectroscopy Lab @ I‐LampUniversità Cattolica del Sacro Cuore Brescia 25121 Italy
| | | | - Maria Chiesa
- Mathematics and Physics DepartmentUniversità Cattolica del Sacro Cuore via dei Musei 41 Brescia 25121 Italy
| | - Giuseppe Santini
- Department of PharmacologyFaculty of MedicineCatholic University of the Sacred HeartFondazione Policlinico Universitario Agostino GemelliIRCCS Largo Francesco Vito, 1 Roma 00168 Italy
| | - Nadia Mores
- Department of PharmacologyFaculty of MedicineCatholic University of the Sacred HeartFondazione Policlinico Universitario Agostino GemelliIRCCS Largo Francesco Vito, 1 Roma 00168 Italy
| | - Umberto Moscato
- Occupational MedicineFaculty of MedicineCatholic University of the Sacred HeartFondazione Policlinico Universitario Agostino GemelliIRCCS Largo Francesco Vito, 1 Roma 00168 Italy
| | - Albert G. Nasibulin
- Skolkovo Institute of Science and Technology Moscow 121205 Russia
- Aalto University P. O. Box 16100 Aalto FI‐00076 Finland
| | - Paolo Montuschi
- Department of PharmacologyFaculty of MedicineCatholic University of the Sacred HeartFondazione Policlinico Universitario Agostino GemelliIRCCS Largo Francesco Vito, 1 Roma 00168 Italy
| | - Luigi Sangaletti
- Mathematics and Physics DepartmentUniversità Cattolica del Sacro Cuore via dei Musei 41 Brescia 25121 Italy
- Surface Science and Spectroscopy Lab @ I‐LampUniversità Cattolica del Sacro Cuore Brescia 25121 Italy
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Peel AM, Wilkinson M, Sinha A, Loke YK, Fowler SJ, Wilson AM. Volatile organic compounds associated with diagnosis and disease characteristics in asthma - A systematic review. Respir Med 2020; 169:105984. [PMID: 32510334 DOI: 10.1016/j.rmed.2020.105984] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2019] [Revised: 03/30/2020] [Accepted: 04/19/2020] [Indexed: 12/16/2022]
Abstract
BACKGROUND Metabolomics refers to study of the metabolome, the entire set of metabolites produced by a biological system. The application of metabolomics to exhaled breath samples - breathomics - is a rapidly growing field with potential application to asthma diagnosis and management. OBJECTIVES We aimed to review the adult asthma breathomic literature and present a comprehensive list of volatile organic compounds identified by asthma breathomic models. METHODS We undertook a systematic search for literature on exhaled volatile organic compounds in adult asthma. We assessed the quality of studies and performed a qualitative synthesis. RESULTS We identified twenty studies; these were methodologically heterogenous with a variable risk of bias. Studies almost universally reported breathomics to be capable of differentiating - with moderate or greater accuracy - between samples from healthy controls and those with asthma; and to be capable of phenotyping disease. However, there was little concordance in the compounds upon which discriminatory models were based. CONCLUSION Results to-date are promising but validation in independent prospective cohorts is needed. This may be challenging given the high levels of inter-individual variation. However, large-scale, multi-centre studies are underway and validation efforts have been aided by the publication of technical standards likely to increase inter-study comparability. Successful validation of breathomic models for diagnosis and phenotyping would constitute an important step towards personalised medicine in asthma.
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Affiliation(s)
- Adam M Peel
- Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK.
| | - Maxim Wilkinson
- Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, The University of Manchester; Manchester Academic Health Science Centre and NIHR Manchester Biomedical Research Centre, Manchester University Hospitals NHS Foundation Trust, Manchester, UK
| | - Ashnish Sinha
- Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK
| | - Yoon K Loke
- Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK
| | - Stephen J Fowler
- Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, The University of Manchester; Manchester Academic Health Science Centre and NIHR Manchester Biomedical Research Centre, Manchester University Hospitals NHS Foundation Trust, Manchester, UK
| | - Andrew M Wilson
- Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK
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Abstract
Breathing air is a fundamental human need, yet its safety, when challenged by various harmful or lethal substances, is often not properly guarded. For example, air toxicity is currently monitored only for a single or a limited number of known toxicants, thus failing to warn against possible hazardous air fully. Here, we discovered that, within minutes, living rats emitted distinctive profiles of volatile organic compounds (VOCs) via breath when exposed to various airborne toxicants such as endotoxin, O3, ricin, and CO2. Compared to background indoor air, when exposed to ricin or endotoxin aerosols, breath-borne VOC levels, especially that of carbon disulfide, were shown to decrease, while their elevated levels were observed for exposure to O3 and CO2. A clear contrast in breath-borne VOC profiles of rats exposed to different toxicants was observed with a statistical significance. Differences in microRNA regulations such as miR-33, miR-146a, and miR-155 from rats' blood samples revealed different mechanisms used by rats in combating different air toxicant challenges. Similar to dogs, rats were found here to be able to sniff off toxic air by releasing a specific breath-borne VOC profile. The discovered science opens a new arena for online monitoring of air toxicity and health effects of pollutants.
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Affiliation(s)
- Haoxuan Chen
- State Key Joint Laboratory of Environmental Simulation and Pollution Control, College of Environmental Sciences and Engineering, Peking University, Beijing 100871, China
| | - Xinyue Li
- State Key Joint Laboratory of Environmental Simulation and Pollution Control, College of Environmental Sciences and Engineering, Peking University, Beijing 100871, China
| | - Maosheng Yao
- State Key Joint Laboratory of Environmental Simulation and Pollution Control, College of Environmental Sciences and Engineering, Peking University, Beijing 100871, China
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50
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Schleich FN, Zanella D, Stefanuto PH, Bessonov K, Smolinska A, Dallinga JW, Henket M, Paulus V, Guissard F, Graff S, Moermans C, Wouters EFM, Van Steen K, van Schooten FJ, Focant JF, Louis R. Exhaled Volatile Organic Compounds Are Able to Discriminate between Neutrophilic and Eosinophilic Asthma. Am J Respir Crit Care Med 2020; 200:444-453. [PMID: 30973757 DOI: 10.1164/rccm.201811-2210oc] [Citation(s) in RCA: 106] [Impact Index Per Article: 21.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
Rationale: Analysis of exhaled breath for asthma phenotyping using endogenously generated volatile organic compounds (VOCs) offers the possibility of noninvasive diagnosis and therapeutic monitoring. Induced sputum is indeed not widely available and markers of neutrophilic asthma are still lacking.Objectives: To determine whether analysis of exhaled breath using endogenously generated VOCs can be a surrogate marker for recognition of sputum inflammatory phenotypes.Methods: We conducted a prospective study on 521 patients with asthma recruited from the University Asthma Clinic of Liege. Patients underwent VOC measurement, fraction of exhaled nitric oxide (FeNO) spirometry, sputum induction, and gave a blood sample. Subjects with asthma were classified in three inflammatory phenotypes according to their sputum granulocytic cell count.Measurements and Main Results: In the discovery study, seven potential biomarkers were highlighted by gas chromatography-mass spectrometry in a training cohort of 276 patients with asthma. In the replication study (n = 245), we confirmed four VOCs of interest to discriminate among asthma inflammatory phenotypes using comprehensive two-dimensional gas chromatography coupled to high-resolution time-of-flight mass spectrometry. Hexane and 2-hexanone were identified as compounds with the highest classification performance in eosinophilic asthma with accuracy comparable to that of blood eosinophils and FeNO. Moreover, the combination of FeNO, blood eosinophils, and VOCs gave a very good prediction of eosinophilic asthma (area under the receiver operating characteristic curve, 0.9). For neutrophilic asthma, the combination of nonanal, 1-propanol, and hexane had a classification performance similar to FeNO or blood eosinophils in eosinophilic asthma. Those compounds were found in higher levels in neutrophilic asthma.Conclusions: Our study is the first attempt to characterize VOCs according to sputum granulocytic profile in a large population of patients with asthma and provide surrogate markers for neutrophilic asthma.
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Affiliation(s)
| | | | | | - Kirill Bessonov
- 3Medical Genomics-BIO3, GIGA-R, University of Liege, Sart-Tilman, Liege, Belgium
| | - Agnieska Smolinska
- 4Department of Pharmacology and Toxicology, School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands; and
| | - Jan W Dallinga
- 4Department of Pharmacology and Toxicology, School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands; and
| | - Monique Henket
- 1Respiratory Medicine, GIGA I3, CHU Sart-Tilman, Liege, Belgium
| | - Virginie Paulus
- 1Respiratory Medicine, GIGA I3, CHU Sart-Tilman, Liege, Belgium
| | | | - Sophie Graff
- 1Respiratory Medicine, GIGA I3, CHU Sart-Tilman, Liege, Belgium
| | | | - Emiel F M Wouters
- 5Department of Respiratory Medicine, Maastricht University Medical Center, Maastricht, the Netherlands
| | - Kristel Van Steen
- 3Medical Genomics-BIO3, GIGA-R, University of Liege, Sart-Tilman, Liege, Belgium
| | - Frederik-Jan van Schooten
- 4Department of Pharmacology and Toxicology, School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands; and
| | | | - Renaud Louis
- 1Respiratory Medicine, GIGA I3, CHU Sart-Tilman, Liege, Belgium
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