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

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.

[1]  A Diagnostic Tool of the Future , 2015 .

[2]  R. Zenobi,et al.  A new strategy based on real-time secondary electrospray ionization and high-resolution mass spectrometry to discriminate endogenous and exogenous compounds in exhaled breath , 2013, Metabolomics.

[3]  Heather D. Bean,et al.  Robust detection of P. aeruginosa and S. aureus acute lung infections by secondary electrospray ionization-mass spectrometry (SESI-MS) breathprinting: from initial infection to clearance , 2013, Journal of breath research.

[4]  Heather D. Bean,et al.  Secondary electrospray ionization-mass spectrometry (SESI-MS) breathprinting of multiple bacterial lung pathogens, a mouse model study. , 2013, Journal of applied physiology.

[5]  Malcolm Kohler,et al.  Human Breath Analysis May Support the Existence of Individual Metabolic Phenotypes , 2013, PloS one.

[6]  P. Montuschi,et al.  Inhaled muscarinic acetylcholine receptor antagonists for treatment of COPD. , 2013, Current medicinal chemistry.

[7]  Jiangjiang Zhu,et al.  Detecting bacterial lung infections: in vivo evaluation of in vitro volatile fingerprints , 2013, Journal of breath research.

[8]  Silvia Conforto,et al.  Within-day and between-day repeatability of measurements with an electronic nose in patients with COPD , 2013, Journal of breath research.

[9]  S. Bandelow,et al.  The effect of a paced auditory serial addition test (PASAT) intervention on the profile of volatile organic compounds in human breath: a pilot study , 2013, Journal of breath research.

[10]  R. Zenobi,et al.  Monitoring diurnal changes in exhaled human breath. , 2013, Analytical chemistry.

[11]  P. Montuschi,et al.  Long-acting beta-agonists and their association with inhaled corticosteroids in COPD. , 2013, Current medicinal chemistry.

[12]  Paolo Montuschi,et al.  The Electronic Nose in Respiratory Medicine , 2012, Respiration.

[13]  Alison J. Montpetit,et al.  Exhaled breath condensate: an overview. , 2007, Immunology and allergy clinics of North America.

[14]  Collection of Aerosolized Human Cytokines Using Teflon® Filters , 2012, PloS one.

[15]  P. Sinues,et al.  Mechanistic study on the ionization of trace gases by an electrospray plume , 2012 .

[16]  P. Montuschi,et al.  Nuclear magnetic resonance-based metabolomics of exhaled breath condensate: methodological aspects , 2012, European Respiratory Journal.

[17]  P. Montuschi,et al.  Non-invasive biomarkers of lung inflammation in smoking subjects. , 2012, Current medicinal chemistry.

[18]  Reyer Zwiggelaar,et al.  Machine learning methods on exhaled volatile organic compounds for distinguishing COPD patients from healthy controls , 2012, Journal of breath research.

[19]  Debora Paris,et al.  NMR spectroscopy metabolomic profiling of exhaled breath condensate in patients with stable and unstable cystic fibrosis , 2011, Thorax.

[20]  T. Walles,et al.  Canine scent detection in the diagnosis of lung cancer: revisiting a puzzling phenomenon , 2011, European Respiratory Journal.

[21]  Brani Vidakovic,et al.  Statistics for Bioengineering Sciences: With MATLAB and WinBUGS Support , 2011 .

[22]  David Smith,et al.  Breath acetone concentration; biological variability and the influence of diet , 2011, Physiological measurement.

[23]  J. Lausmaa,et al.  TOF-SIMS analysis of exhaled particles from patients with asthma and healthy controls , 2011, European Respiratory Journal.

[24]  F H Krouwels,et al.  Exhaled air molecular profiling in relation to inflammatory subtype and activity in COPD , 2011, European Respiratory Journal.

[25]  H. Bean,et al.  Characterizing Bacterial Volatiles using Secondary Electrospray Ionization Mass Spectrometry (SESI-MS) , 2011, Journal of visualized experiments : JoVE.

[26]  Renato Zenobi,et al.  Real-time, in vivo monitoring and pharmacokinetics of valproic acid via a novel biomarker in exhaled breath. , 2011, Chemical communications.

[27]  J. Mora,et al.  Ionization of vapor molecules by an electrospray cloud , 2011 .

[28]  S. Cristoni,et al.  Secondary electrospray ionization-mass spectrometry: breath study on a control group , 2011, Journal of breath research.

[29]  M. Cazzola,et al.  Biomarkers in COPD. , 2010, Pulmonary pharmacology & therapeutics.

[30]  P. Montuschi Toward a Personalized Pharmacotherapy of Respiratory Diseases , 2010, Front. Pharm..

[31]  Sven Rahmann,et al.  Differentiation of chronic obstructive pulmonary disease (COPD) including lung cancer from healthy control group by breath analysis using ion mobility spectrometry , 2010 .

[32]  P. Barnes Future perspectives on exhaled biomarkers , 2010 .

[33]  J W Dallinga,et al.  A profile of volatile organic compounds in breath discriminates COPD patients from controls. , 2009, Respiratory medicine.

[34]  Royston Goodacre,et al.  Non-invasive Metabolomic Analysis of Breath Using Differential Mobility Spectrometry in Patients with Chronic Obstructive Pulmonary Disease and Healthy Smokers , 2022 .

[35]  P. Montuschi,et al.  Measurement of 8-isoprostane in exhaled breath condensate. , 2010, Methods in molecular biology.

[36]  Niki Fens,et al.  Exhaled breath profiling enables discrimination of chronic obstructive pulmonary disease and asthma. , 2009, American journal of respiratory and critical care medicine.

[37]  K. Unterkofler,et al.  Breath acetone—aspects of normal physiology related to age and gender as determined in a PTR-MS study , 2009, Journal of breath research.

[38]  P. Martínez-Lozano,et al.  Secondary electrospray ionization (SESI) of ambient vapors for explosive detection at concentrations below parts per trillion , 2009, Journal of the American Society for Mass Spectrometry.

[39]  L. Freitag,et al.  Ion mobility spectrometry for the detection of volatile organic compounds in exhaled breath of patients with lung cancer: results of a pilot study , 2009, Thorax.

[40]  Jörg Ingo Baumbach,et al.  Ion mobility spectrometry for the detection of volatile organic compounds in exhaled breath of lung cancer patients - Results of a pilot study. , 2009 .

[41]  M. Quirynen,et al.  GC-MS analysis of breath odor compounds in liver patients. , 2008, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[42]  G. Corso,et al.  Metabonomic analysis of exhaled breath condensate in adults by nuclear magnetic resonance spectroscopy , 2008, European Respiratory Journal.

[43]  P. Martínez-Lozano,et al.  Direct analysis of fatty acid vapors in breath by electrospray ionization and atmospheric pressure ionization-mass spectrometry. , 2008, Analytical chemistry.

[44]  Paolo Montuschi,et al.  Exhaled 8-isoprostane and prostaglandin E(2) in patients with stable and unstable cystic fibrosis. , 2008, Free radical biology & medicine.

[45]  B. Ross,et al.  Sub-parts per billion detection of trace volatile chemicals in human breath using Selected Ion Flow Tube Mass Spectrometry , 2008, BMC Research Notes.

[46]  Ivano Bertini,et al.  Evidence of different metabolic phenotypes in humans , 2008, Proceedings of the National Academy of Sciences.

[47]  W. Bailey,et al.  Clinical use of exhaled biomarkers in COPD , 2007, International journal of chronic obstructive pulmonary disease.

[48]  P. Martínez-Lozano,et al.  Electrospray ionization of volatiles in breath , 2007 .

[49]  Huanwen Chen,et al.  Rapid in vivo fingerprinting of nonvolatile compounds in breath by extractive electrospray ionization quadrupole time-of-flight mass spectrometry. , 2007, Angewandte Chemie.

[50]  P. Montuschi Pharmacological treatment of chronic obstructive pulmonary disease , 2006, International journal of chronic obstructive pulmonary disease.

[51]  P. Barnes,et al.  Exhaled biomarkers. , 2006, Chest.

[52]  R. A. van den Berg,et al.  Centering, scaling, and transformations: improving the biological information content of metabolomics data , 2006, BMC Genomics.

[53]  David Smith,et al.  Selected ion flow tube mass spectrometry (SIFT-MS) for on-line trace gas analysis. , 2005, Mass spectrometry reviews.

[54]  P. Montuschi Exhaled breath condensate analysis in patients with COPD. , 2005, Clinica chimica acta; international journal of clinical chemistry.

[55]  P. Španěl,et al.  SELECTED ION FLOW TUBE MASS SPECTROMETRY, SIFT-MS, FOR ON-LINE TRACE GAS ANALYSIS OF BREATH , 2005 .

[56]  P. Montuschi Analysis of Exhaled Breath Condensate , 2004 .

[57]  P. Barnes,et al.  Increased leukotriene B4 and 8-isoprostane in exhaled breath condensate of patients with exacerbations of COPD , 2003, Thorax.

[58]  L. Fabbri,et al.  Cellular and structural bases of chronic obstructive pulmonary disease. , 2001, American journal of respiratory and critical care medicine.

[59]  Christine Jenkins,et al.  GOLD SCIENTIFIC COMMITTEE. GLOBAL STRATEGY FOR THE DIAGNOSIS, MANAGEMENT, AND PREVENTION OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE. NHLBI/WHO GLOBAL INITIATIVE FOR CHRONIC OBSTRUCTIVE LUNG DISEASE (COLD) WORKSHOP SUMMARY , 2001 .

[60]  H H Hill,et al.  Secondary electrospray ionization ion mobility spectrometry/mass spectrometry of illicit drugs. , 2000, Analytical chemistry.

[61]  A. Hansel,et al.  On-line monitoring of volatile organic compounds at pptv levels by means of proton-transfer-reaction mass spectrometry (PTR-MS) medical applications, food control and environmental research , 1998 .

[62]  J. Edward Jackson,et al.  A User's Guide to Principal Components. , 1991 .

[63]  K. Gambhir,et al.  Positions in human serum albumin which involve the indole binding site. Sequence of 107-residue fragment. , 1975, The Journal of biological chemistry.