Direct human breath analysis by secondary nano‐electrospray ionization ultrahigh‐resolution mass spectrometry: Importance of high mass resolution and mass accuracy

Li, Xue; Huang, Lei; Zhu, Hui; Zhou, Zhen

doi:10.1002/rcm.7794

Cited by 23 publications

(17 citation statements)

References 33 publications

(40 reference statements)

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“…Given that, low-volatility species such as urea have been detected using this approach, 55,56 there has been some debate regarding whether the metabolites detected in breath following this approach come in aerosol form or simply the method is sensitive enough to detect low-volatility vapors. 17,55,56 The debate is of importance because aerosols and volatiles have different physiological origins and therefore offer different diagnostic opportunities. Aerosols in breath are thought to be generated by the turbulence-induced aerosolization mechanism of the uid lm in the respiratory tract.…”

Section: Breath Analysismentioning

confidence: 99%

“…15,16 Ever since, SESI has been used to detect trace vapors in a wide range of applications by different groups. [17][18][19][20][21][22][23][24] While it is generally accepted that SESI coupled to modern atmospheric pressure mass spectrometry is a sensitive method to detect gases at trace concentrations in real-time, the lack of full understanding of the SESI mechanism prevents making rational choices for the optimal parameters. In addition, with the advent of several ambient mass spectrometry techniques with overlapping features, fundamental aspects of such techniques have been blurred or confused.…”

Section: Introductionmentioning

confidence: 99%

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Secondary electrospray ionization proceeds via gas-phase chemical ionization

2017

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Section: Breath Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Secondary electrospray ionization proceeds via gas-phase chemical ionization

2017

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“…This results in sensitive and selective, yet real-time, analysis of trace vapor species. As a result, despite being the most recently proposed mass spectrometric alternative for real-time gas analysis, it is steadily gaining interest across different research groups [10,[12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]. However, most of the published SESI-MS studies rely on lab-built instrumentation, making it difficult to standardize procedures for this technique.…”

Section: Introductionmentioning

confidence: 99%

Standardization procedures for real-time breath analysis by secondary electrospray ionization high-resolution mass spectrometry

et al. 2019

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Despite the attractiveness of breath analysis as a non-invasive means to retrieve relevant metabolic information, its introduction into routine clinical practice remains a challenge. Among all the different analytical techniques available to interrogate exhaled breath, secondary electrospray ionization high-resolution mass spectrometry (SESI-HRMS) offers a number of advantages (e.g., real-time, yet wide, metabolome coverage) that makes it ideal for untargeted and targeted studies. However, so far, SESI-HRMS has relied mostly on lab-built prototypes, making it difficult to standardize breath sampling and subsequent analysis, hence preventing further developments such as multi-center clinical studies. To address this issue, we present here a number of new developments. In particular, we have characterized a new SESI interface featuring real-time readout of critical exhalation parameters such as CO 2 , exhalation flow rate, and exhaled volume. Four healthy subjects provided breath specimens over a period of 1 month to characterize the stability of the SESI-HRMS system. A first assessment of the repeatability of the system using a gas standard revealed a coefficient of variation (CV) of 2.9%. Three classes of aldehydes, namely 4-hydroxy-2-alkenals, 2-alkenals and 4-hydroxy-2,6-alkedienals-hypothesized to be markers of oxidative stress-were chosen as representative metabolites of interest to evaluate the repeatability and reproducibility of this breath analysis analytical platform. Median and interquartile ranges (IQRs) of CVs for CO 2 , exhalation flow rate, and exhaled volume were 3.2% (1.5%), 3.1% (1.9%), and 5.0% (4.6%), respectively. Despite the high repeatability observed for these parameters, we observed a systematic decay in the signal during repeated measurements for the shorter fatty aldehydes, which eventually reached a steady state after three/four repeated exhalations. In contrast, longer fatty aldehydes showed a steady behavior, independent of the number of repeated exhalation maneuvers. We hypothesize that this highly molecule-specific and individual-independent behavior may be explained by the fact that shorter aldehydes (with higher estimated blood-to-air partition coefficients; approaching 100) mainly get exchanged in the airways of the respiratory system, whereas the longer aldehydes (with smaller estimated blood-to-air partition coefficients; approaching 10) are thought to exchange mostly in the alveoli. Exclusion of the first three exhalations from the analysis led to a median CV (IQR) of 6.7 % (5.5 %) for the said classes of aldehydes. We found that such intra-subject variability is in general much lower than inter-subject variability (median relative differences between subjects 48.2%), suggesting that the system is suitable to capture such differences. No batch effect due to sampling date was observed, overall suggesting that the intra-subject

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“…Real‐time exhaled breath analysis is a technique to obtain insight into human metabolism in a fast, non‐invasive and painless fashion, by detecting trace concentrations of metabolites in breath . Secondary electrospray ionization‐mass spectrometry (SESI‐MS) is a highly sensitive technique to analyse a variety of sample vapours at ambient pressure and has been used in this context to identify biomarkers, monitor pharmacokinetics and metabolic circadian variation . Furthermore, it has proven its strength in obtaining information about metabolic pathways in several studies during recent years …”

Section: Introductionmentioning

confidence: 99%

Molecular breath analysis supports altered amino acid metabolism in idiopathic pulmonary fibrosis

et al. 2019

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Background and objective: Diagnosis of idiopathic pulmonary fibrosis (IPF) is complex and its pathogenesis is poorly understood. Recent findings indicate elevated levels of proline and other amino acids in lung tissue of IPF patients which may also be of diagnostic value. Following these findings, we hypothesized that such altered metabolic profiles would be mirrored in exhaled breath and could therefore be captured non-invasively in real time. Methods: We aimed to validate these results using realtime exhaled breath analysis by secondary electrospray ionization-mass spectrometry, which can provide a non-invasive, painless and fast insight into the metabolism. Breath analysis was performed in a matched 1:1 case-control study involving 21 patients with IPF and 21 control subjects. Results: We found significantly (P < 0.05) elevated levels of proline, 4-hydroxyproline, alanine, valine, leucine/isoleucine and allysine in breath of IPF patients, whereas pyroglutamic acid and phenylalanine did not show significant differences. This coincides with the amino acid's abundance in pulmonary tissue indicating that our observations reflect progressing fibrosis. In addition, amino acid levels correlated across subjects, further supporting a common underlying pathway. We were able to obtain a cross-validated area under the curve of 0.86, suggesting that these increased amino acid levels in exhaled breath have the potential to be used as biomarkers for IPF. Conclusion: We could validate previous findings of elevated lung tissue amino acid levels in IPF and show that online breath analysis might be a practical tool for a rapid screening for IPF.Clinical trial registration: NCT02437448 at ClinicalTrials.gov SUMMARY AT A GLANCECollagen-related amino acids are significantly increased in exhaled breath of idiopathic pulmonary fibrosis (IPF) patients compared with healthy controls. The detection of these amino acids using realtime breath analysis results in a good discrimination between the groups, indicating the possibility for a rapid, non-invasive screening for IPF.

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Direct human breath analysis by secondary nano‐electrospray ionization ultrahigh‐resolution mass spectrometry: Importance of high mass resolution and mass accuracy

Cited by 23 publications

References 33 publications

Secondary electrospray ionization proceeds via gas-phase chemical ionization

Secondary electrospray ionization proceeds via gas-phase chemical ionization

Standardization procedures for real-time breath analysis by secondary electrospray ionization high-resolution mass spectrometry

Molecular breath analysis supports altered amino acid metabolism in idiopathic pulmonary fibrosis

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