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Breath Analysis in Real Time by Mass Spectrometry in Chronic Obstructive Pulmonary Disease

Authors:
  • University Children's Hospital Basel, University of Basel

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BACKGROUND: It has been suggested that exhaled breath contains relevant information on health status. OBJECTIVES: We hypothesized that a novel mass spectrometry (MS) technique to analyze breath in real time could be useful to differentiate breathprints from chronic obstructive pulmonary disease (COPD) patients and controls (smokers and nonsmokers). METHODS: We studied 61 participants including 25 COPD patients [Global Initiative for Obstructive Lung Disease (GOLD) stages I-IV], 25 nonsmoking controls and 11 smoking controls. We analyzed their breath by MS in real time. Raw mass spectra were then processed and statistically analyzed. RESULTS: A panel of discriminating mass-spectral features was identified for COPD (all stages; n = 25) versus healthy nonsmokers (n = 25), COPD (all stages; n = 25) versus healthy smokers (n = 11) and mild COPD (GOLD stages I/II; n = 13) versus severe COPD (GOLD stages III/IV; n = 12). A blind classification (i.e. leave-one-out cross validation) resulted in 96% sensitivity and 72.7% specificity (COPD vs. smoking controls), 88% sensitivity and 92% specificity (COPD vs. nonsmoking controls) and 92.3% sensitivity and 83.3% specificity (GOLD I/II vs. GOLD III/IV). Acetone and indole were identified as two of the discriminating exhaled molecules. CONCLUSIONS: We conclude that real-time MS may be a useful technique to analyze and characterize the metabolome of exhaled breath. The acquisition of breathprints in a rapid manner may be valuable to support COPD diagnosis and to gain insight into the disease.
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... Human breath analysis is a novel, easy, instant and non-invasive method to diagnose lung obstruction [1]. Some possible breath biomarkers for detection of obstructive lung diseases are nitric oxide (NO), hydrogen per oxide (H 2 O 2 ) , carbon monoxide (CO), hydrogen sulfide (H 2 S), alcohol (C 2 H 5 OH), acetone(C 2 H 6 CO) and ammonia (NH 3 ) [9][10][11][12][13][14][15]. Previous studies have revealed that the breath levels of nitric oxide, hydrogen peroxide, carbon monoxide and hydrogen sulfide are important for diagnosis of lung obstruction. ...
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... In 2019, we reported the breath test for four healthy subjects by proton transfer reaction mass spectrometry (PTR-MS). In the case of gargling, nine kinds of ions (m/z 33,42,45,47,49,51,57,59,63) were detected to be decreased in the ionic signal intensities [10]. Among them, the possible substances ethanol and methanethiol at m/z 47 and 49 were thought to be produced by oral bacteria and could be removed by gargling. ...
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... [4] and some of them have been validated and approved by regulating authorities for a clinical use [5]. Specifically, exhaled breath acetone (ExA) has been investigated in different diseases (cardiovascular diseases [6], diabetes [7,8], COPD [9], etc). In HF, the ketone body utilization in the myocardium increases together with the whole body ketogenesis [10]. ...
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... Evidence in support of this concept was already "perceived" by Hippocrates (460-370 B.C.), who described fetor hepaticus, the musty breath of subjects undergoing liver failure [40]. The last five decades have seen the evolution of more quantitative and accurate instruments that led to the discovery of a considerable number of breath compounds associated with several diseases [41][42][43], including Alzheimer's [44,45], Parkinson's [44], schizophrenia [46,47], multiple sclerosis [48,49], breast cancer [50,51], colorectal cancer [51][52][53], lung cancer [51,[54][55][56][57][58][59][60], asthma [61][62][63][64][65], chronic obstructive pulmonary disease (COPD) [61,[66][67][68][69][70][71], cystic fibrosis [72][73][74][75][76], and COVID-19 [77,78]. Chen et al. (1970) [79], Kaji et al. (1978) [80], and Tangerman et al. (1994) [81], compared the breath of patients with cirrhosis against that of healthy controls, by using gas chromatography (GC). ...
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Recent work by Zenobi and colleagues [H. Chen, A. Wortmann, W. Zhang, R. Zenobi, Angew. Chem. Int. Ed. 46 (2007) 580] reports that human breath charged by contact with an electrospray (ES) cloud yields many mass peaks of species such as urea, glucose, and other ions, some with molecular weights above 1000Da. All these species are presumed to be involatile, and to originate from breath aerosols by so-called extractive electrospray ionization EESI [H. Chen, A. Venter, R.G. Cooks, Chem. Commun. (2006) 2042]. However, prior work by Fenn and colleagues [C.M. Whitehouse, F. Levin, C.K. Meng, J.B. Fenn, Proceedings of the 34th ASMS Conference on Mass Spectrometry and Allied Topics, Denver, 1986 p. 507; S. Fuerstenau, P. Kiselev, J.B. Fenn, Proceedings of the 47th ASMS Conference on Mass Spectrometry, 1999, Dallas, TX, 1999] and by Hill and colleagues [C. Wu, W.F. Siems, H.H. Hill Jr., Anal. Chem. 72 (2000) 396] have reported the ability of electrospray drops to ionize a variety of low vapor pressure substances directly from the gas phase, without an apparent need for the vapor to be brought into the charging ES in aerosol form. The Ph.D. Thesis of Martínez-Lozano [P. Martínez-Lozano Sinués, Ph.D. Thesis, Department of Thermal and Fluid Engineering, University Carlos III of Madrid; April 5, 2006 (in Spanish); http://hdl.handle.net/10016/655] had also previously argued that the numerous human breath species observed via a similar ES ionization approach were in fact ionized directly from the vapor. Here, we observe that passage of the breath stream through a submicron filter does not eliminate the majority of the breath vapors seen in the absence of the filter. We conclude that direct vapor charging is the leading mechanism in breath ionization by electrospray drops, though aerosol ionization may also play a role.