Real-time mass spectrometric identification of metabolites characteristic of chronic obstructive pulmonary disease in exhaled breath

Bregy, Lukas; Nussbaumer-Ochsner, Yvonne; Sinués, Pablo Martínez-Lozano; García-Gómez, Diego; Suter, Yannick; Gaisl, Thomas; Stebler, Nina; Gaugg, Martin Thomas; Kohler, Malcolm; Zenobi, Renato

doi:10.1016/j.clinms.2018.02.003

Cited by 49 publications

(40 citation statements)

References 30 publications

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“…111,179,194 This circumstance is paired with the experience that most of the peaks measured (>99%) are usually not discriminatory for the disease of interest, i.e., the number of false hypotheses outnumber the true hypothesis in this setting by a factor of >100. 111,179,180,194 This low yield is primarily due to the fact that most signals or peaks do not correspond to a VOC or the VOCs identified are mostly of environmental origin. 303 Due to the nature of the applied statistics, this mismatch produces by design a high number of type-I-errors.…”

Section: Statistical Considerationsmentioning

confidence: 99%

On-Line Analysis of Exhaled Breath

et al. 2019

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On-line analysis of exhaled breath offers insight into a person's metabolism without the need for sample preparation or sample collection. Due to its non-invasive nature and the possibility to sample continuously, the analysis of breath has great clinical potential. The unique features of this technology make it an attractive candidate for applications in medicine, beyond the task of diagnosis. We review the current methodologies for on-line breath analysis, discuss current and future applications, and critically evaluate challenges and pitfalls such as the need for standardization. Special emphasis is given to use of the technology in diagnosing respiratory diseases, potential niche applications, and the promise of breath analysis for personalized medicine. The analytical methodologies used range from very small and low-cost chemical sensors, which are ideal for continuous monitoring of disease status, to optical spectroscopy and state-of-the-art, high-resolution mass spectrometry. The latter can be utilized for untargeted analysis of exhaled breath, with the capability to identify hitherto unknown molecules. The interpretation of the resulting big data sets is complex and often constrained due to a limited number of participants. Even larger data sets will be needed for assessing reproducibility and for validation of biomarker candidates. In addition, molecular structures and quantification of compounds are generally not easily available from on-line measurements and require complementary measurements, for example, a separation method coupled to mass spectrometry. Furthermore, lack of standardization still hampers using the technique for screening larger cohorts of patients. The present review summarizes the present status and continuous improvements of the main on-line breath analysis methods, and evaluates obstacles for its wider application.

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Section: Statistical Considerationsmentioning

confidence: 99%

On-Line Analysis of Exhaled Breath

et al. 2019

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“…The investigation of exhaled breath has been studied more intensively compared with other biological samples [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ], and for which a number reviews are available in the literature [ 4 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. However, none of these reviews covers recent studies of VOCs and lung disease undertaken in the last decade.…”

Section: Introductionmentioning

confidence: 99%

Volatile Organic Compounds in Exhaled Breath as Fingerprints of Lung Cancer, Asthma and COPD

Rațiu

Ligor

Bocoş-Binţinţan

et al. 2020

JCM

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Lung cancer, chronic obstructive pulmonary disease (COPD) and asthma are inflammatory diseases that have risen worldwide, posing a major public health issue, encompassing not only physical and psychological morbidity and mortality, but also incurring significant societal costs. The leading cause of death worldwide by cancer is that of the lung, which, in large part, is a result of the disease often not being detected until a late stage. Although COPD and asthma are conditions with considerably lower mortality, they are extremely distressful to people and involve high healthcare overheads. Moreover, for these diseases, diagnostic methods are not only costly but are also invasive, thereby adding to people’s stress. It has been appreciated for many decades that the analysis of trace volatile organic compounds (VOCs) in exhaled breath could potentially provide cheaper, rapid, and non-invasive screening procedures to diagnose and monitor the above diseases of the lung. However, after decades of research associated with breath biomarker discovery, no breath VOC tests are clinically available. Reasons for this include the little consensus as to which breath volatiles (or pattern of volatiles) can be used to discriminate people with lung diseases, and our limited understanding of the biological origin of the identified VOCs. Lung disease diagnosis using breath VOCs is challenging. Nevertheless, the numerous studies of breath volatiles and lung disease provide guidance as to what volatiles need further investigation for use in differential diagnosis, highlight the urgent need for non-invasive clinical breath tests, illustrate the way forward for future studies, and provide significant guidance to achieve the goal of developing non-invasive diagnostic tests for lung disease. This review provides an overview of these issues from evaluating key studies that have been undertaken in the years 2010–2019, in order to present objective and comprehensive updated information that presents the progress that has been made in this field. The potential of this approach is highlighted, while strengths, weaknesses, opportunities, and threats are discussed. This review will be of interest to chemists, biologists, medical doctors and researchers involved in the development of analytical instruments for breath diagnosis.

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“…The exhaled human breath consists almost of 3500 different volatile organic compounds (VOCs), and a single breath consists of around 500 various VOCs ( Figure 1 a), which are typically in the part per million (ppm), part per billion (ppb) range or part per trillion (ppt). The biomarkers present in the exhaled breath are used to indicate several diseases, such as lung cancer [ 14 , 15 ], asthma [ 16 , 17 ], chronic obstructive pulmonary disease (COPD) [ 18 , 19 ], breast cancer [ 20 , 21 ], and diabetes [ 22 , 23 ]. The total number of diseases that can be detected or controlled by exhaled breath analysis is still unknown ( Figure 1 b).…”

Section: Introductionmentioning

confidence: 99%

Sensors for Enhanced Detection of Acetone as a Potential Tool for Noninvasive Diabetes Monitoring

Rydosz

2018

Sensors

121

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Measurement of blood-borne volatile organic compounds (VOCs) occurring in human exhaled breath as a result of metabolic changes or pathological disorders is a promising tool for noninvasive medical diagnosis, such as exhaled acetone measurements in terms of diabetes monitoring. The conventional methods for exhaled breath analysis are based on spectrometry techniques, however, the development of gas sensors has made them more and more attractive from a medical point of view. This review focuses on the latest achievements in gas sensors for exhaled acetone detection. Several different methods and techniques are presented and discussed as well.

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Real-time mass spectrometric identification of metabolites characteristic of chronic obstructive pulmonary disease in exhaled breath

Cited by 49 publications

References 30 publications

On-Line Analysis of Exhaled Breath

On-Line Analysis of Exhaled Breath

Volatile Organic Compounds in Exhaled Breath as Fingerprints of Lung Cancer, Asthma and COPD

Sensors for Enhanced Detection of Acetone as a Potential Tool for Noninvasive Diabetes Monitoring

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