Generic placeholder image

Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Metabolomics of Exhaled Breath Condensate by Nuclear Magnetic Resonance Spectroscopy and Mass Spectrometry: A Methodological Approach

Author(s): Mauro Maniscalco*, Adele Cutignano, Debora Paris, Dominique J. Melck, Antonio Molino, Salvatore Fuschillo and Andrea Motta*

Volume 27, Issue 14, 2020

Page: [2381 - 2399] Pages: 19

DOI: 10.2174/0929867325666181008122749

Price: $65


Respiratory diseases present a very high prevalence in the general population, with an increase in morbidity, mortality and health-care expenses worldwide. They are complex and heterogeneous pathologies that may present different pathological facets in different subjects, often with personal evolution. Therefore, there is a need to identify patients with similar characteristics, prognosis or treatment, defining the so-called phenotype, but also to mark specific differences within each phenotype, defining the endotypes.

Biomarkers are very useful to study respiratory phenotypes and endotypes. Metabolomics, one of the recently introduced “omics”, is becoming a leading technique for biomarker discovery. For the airways, metabolomics appears to be well suited as the respiratory tract offers a natural matrix, the Exhaled Breath Condensate (EBC), in which several biomarkers can be measured. In this review, we will discuss the main methodological issues related to the application of Nuclear Magnetic Resonance (NMR) spectroscopy and Mass Spectrometry (MS) to EBC metabolomics for investigating respiratory diseases.

Keywords: Airway diseases, exhaled breath condensate, lung, rehabilitation, mass spectrometry, metabolomics, NMR spectroscopy.

« Previous
Agusti, A.; Sobradillo, P.; Celli, B. Addressing the complexity of chronic obstructive pulmonary disease: from phenotypes and biomarkers to scale-free networks, systems biology, and P4 medicine. Am. J. Respir. Crit. Care Med., 2011, 183(9), 1129-1137.
[] [PMID: 21169466]
van Mastrigt, E.; de Jongste, J.C.; Pijnenburg, M.W. The analysis of volatile organic compounds in exhaled breath and biomarkers in exhaled breath condensate in children - clinical tools or scientific toys? Clin. Exp. Allergy, 2015, 45(7), 1170-1188.
[] [PMID: 25394891]
Maniscalco, M.; Motta, A. Metabolomics of exhaled breath condensate: a means for phenotyping respiratory diseases? Biomarkers Med., 2017, 11(6), 405-407.
[] [PMID: 28617073]
Mastrangelo, A.; Barbas, C. Chronic diseases and lifestyle biomarkers identification by metabolomics. Adv. Exp. Med. Biol., 2017, 965, 235-263.
[] [PMID: 28132183]
Urbanczyk-Wochniak, E.; Luedemann, A.; Kopka, J.; Selbig, J.; Roessner-Tunali, U.; Willmitzer, L.; Fernie, A.R. Parallel analysis of transcript and metabolic profiles: a new approach in systems biology. EMBO Rep., 2003, 4(10), 989-993.
[] [PMID: 12973302]
Sauer, U.; Heinemann, M.; Zamboni, N. Genetics. Getting closer to the whole picture. Science, 2007, 316(5824), 550-551.
[] [PMID: 17463274]
Horváth, I.; Hunt, J.; Barnes, P.J.; Alving, K.; Antczak, A.; Baraldi, E.; Becher, G.; van Beurden, W.J.; Corradi, M.; Dekhuijzen, R.; Dweik, R.A.; Dwyer, T.; Effros, R.; Erzurum, S.; Gaston, B.; Gessner, C.; Greening, A.; Ho, L.P.; Hohlfeld, J.; Jöbsis, Q.; Laskowski, D.; Loukides, S.; Marlin, D.; Montuschi, P.; Olin, A.C.; Redington, A.E.; Reinhold, P.; van Rensen, E.L.; Rubinstein, I.; Silkoff, P.; Toren, K.; Vass, G.; Vogelberg, C.; Wirtz, H. Exhaled breath condensate: methodological recommendations and unresolved questions. Eur. Respir. J., 2005, 26(3), 523-548.
[] [PMID: 16135737]
Sofia, M.; Maniscalco, M.; de Laurentiis, G.; Paris, D.; Melck, D.; Motta, A. Exploring airway diseases by NMR-based metabonomics: a review of application to exhaled breath condensate. J. Biomed. Biotechnol., 2011, 2011403260
[] [PMID: 21437214]
Horváth, I.; Barnes, P.J.; Loukides, S.; Sterk, P.J.; Högman, M.; Olin, A.C.; Amann, A.; Antus, B.; Baraldi, E.; Bikov, A.; Boots, A.W.; Bos, L.D.; Brinkman, P.; Bucca, C.; Carpagnano, G.E.; Corradi, M.; Cristescu, S.; de Jongste, J.C.; Dinh-Xuan, A.T.; Dompeling, E.; Fens, N.; Fowler, S.; Hohlfeld, J.M.; Holz, O.; Jöbsis, Q.; Van De Kant, K.; Knobel, H.H.; Kostikas, K.; Lehtimäki, L.; Lundberg, J.; Montuschi, P.; Van Muylem, A.; Pennazza, G.; Reinhold, P.; Ricciardolo, F.L.M.; Rosias, P.; Santonico, M.; van der Schee, M.P.; van Schooten, F.J.; Spanevello, A.; Tonia, T.; Vink, T.J. A European Respiratory Society technical standard: exhaled biomarkers in lung disease. Eur. Respir. J., 2017, 49(4), 49.
[] [PMID: 28446552]
Accordino, R.; Visentin, A.; Bordin, A.; Ferrazzoni, S.; Marian, E.; Rizzato, F.; Canova, C.; Venturini, R.; Maestrelli, P. Long-term repeatability of exhaled breath condensate pH in asthma. Respir. Med., 2008, 102(3), 377-381.
[] [PMID: 18061423]
Davis, M.D.; Montpetit, A.J. Exhaled Breath Condensate: An Update. Immunol. Allergy Clin. North Am., 2018, 38(4), 667-678.
[] [PMID: 30342587]
Ahmadzai, H.; Huang, S.; Hettiarachchi, R.; Lin, J.L.; Thomas, P.S.; Zhang, Q. Exhaled breath condensate: a comprehensive update. Clin. Chem. Lab. Med., 2013, 51(7), 1343-1361.
[] [PMID: 23420285]
Rosias, P. Methodological aspects of exhaled breath condensate collection and analysis. J. Breath Res., 2012, 6(2)027102
[] [PMID: 22522968]
de Laurentiis, G.; Paris, D.; Melck, D.; Maniscalco, M.; Marsico, S.; Corso, G.; Motta, A.; Sofia, M. Metabonomic analysis of exhaled breath condensate in adults by nuclear magnetic resonance spectroscopy. Eur. Respir. J., 2008, 32(5), 1175-1183.
[] [PMID: 18653649]
Bell, J.D.; Brown, J.C.; Sadler, P.J. NMR studies of body fluids. NMR Biomed., 1989, 2(5-6), 246-256.
[] [PMID: 2701808]
Gaber, F.; Acevedo, F.; Delin, I.; Sundblad, B.M.; Palmberg, L.; Larsson, K.; Kumlin, M.; Dahlén, S.E. Saliva is one likely source of leukotriene B4 in exhaled breath condensate. Eur. Respir. J., 2006, 28(6), 1229-1235.
[] [PMID: 16971403]
Motta, A.; Paris, D.; D’Amato, M.; Melck, D.; Calabrese, C.; Vitale, C.; Stanziola, A.A.; Corso, G.; Sofia, M.; Maniscalco, M. NMR metabolomic analysis of exhaled breath condensate of asthmatic patients at two different temperatures. J. Proteome Res., 2014, 13(12), 6107-6120.
[] [PMID: 25393672]
Nicholson, J.K.; Lindon, J.C. Systems biology: Metabonomics. Nature, 2008, 455(7216), 1054-1056.
[] [PMID: 18948945]
Kaiser, K.A.M.C.; Fang, F.; Larive, C.K. Metabolic profiling In: NMR spectroscopy in pharmaceutical analysis, 2010, 233-267.
Nguyen, B.D.; Meng, X.; Donovan, K.J.; Shaka, A.J. SOGGY: solvent-optimized double gradient spectroscopy for water suppression. A comparison with some existing techniques. J. Magn. Reson., 2007, 184(2), 263-274.
[] [PMID: 17126049]
Araníbar, N.; Ott, K.H.; Roongta, V.; Mueller, L. Metabolomic analysis using optimized NMR and statistical methods. Anal. Biochem., 2006, 355(1), 62-70.
[] [PMID: 16762305]
Palmer Iii, A.G.; Cavanagh, J.; Wright, P.E.; Rance, M. Sensitivity improvement in proton-detected two-dimensional heteronuclear correlation NMR spectroscopy. J. Magn. Reson., 1969, 1991(93), 151-170.
Beltran, A.; Suarez, M.; Rodríguez, M.A.; Vinaixa, M.; Samino, S.; Arola, L.; Correig, X.; Yanes, O. Assessment of compatibility between extraction methods for NMR- and LC/MS-based metabolomics. Anal. Chem., 2012, 84(14), 5838-5844.
[] [PMID: 22697410]
Bhardwaj, C.; Hanley, L. Ion sources for mass spectrometric identification and imaging of molecular species. Nat. Prod. Rep., 2014, 31(6), 756-767.
[] [PMID: 24473154]
Nadler, W.M.; Waidelich, D.; Kerner, A.; Hanke, S.; Berg, R.; Trumpp, A.; Rösli, C. MALDI versus ESI: The impact of the ion source on peptide identification. J. Proteome Res., 2017, 16(3), 1207-1215.
[] [PMID: 28176526]
Fernández-Peralbo, M.A.; Calderón Santiago, M.; Priego-Capote, F.; Luque de Castro, M.D. Study of exhaled breath condensate sample preparation for metabolomics analysis by LC-MS/MS in high resolution mode. Talanta, 2015, 144, 1360-1369.
[] [PMID: 26452970]
Effros, R.M.; Dunning, M.B., III; Biller, J.; Shaker, R. The promise and perils of exhaled breath condensates. Am. J. Physiol. Lung Cell. Mol. Physiol., 2004, 287(6), L1073-L1080.
[] [PMID: 15531756]
Gessner, C.; Kuhn, H.; Seyfarth, H.J.; Pankau, H.; Winkler, J.; Schauer, J.; Wirtz, H. Factors influencing breath condensate volume. Pneumologie, 2001, 55(9), 414-419.
[] [PMID: 11536064]
Dwyer, T.M. Sampling airway surface liquid: non-volatiles in the exhaled breath condensate. Lung, 2004, 182(4), 241-250.
[] [PMID: 15636196]
Baker, E.H.; Clark, N.; Brennan, A.L.; Fisher, D.A.; Gyi, K.M.; Hodson, M.E.; Philips, B.J.; Baines, D.L.; Wood, D.M. Hyperglycemia and cystic fibrosis alter respiratory fluid glucose concentrations estimated by breath condensate analysis. J. Appl. Physiol., 2007, 102(5), 1969-1975.
[] [PMID: 17303703]
Peralbo-Molina, A.; Calderón-Santiago, M.; Priego-Capote, F.; Jurado-Gámez, B.; Luque de Castro, M.D. Development of a method for metabolomic analysis of human exhaled breath condensate by gas chromatography-mass spectrometry in high resolution mode. Anal. Chim. Acta, 2015, 887, 118-126.
[] [PMID: 26320793]
Nizio, K.D.; Perrault, K.A.; Troobnikoff, A.N.; Ueland, M.; Shoma, S.; Iredell, J.R.; Middleton, P.G.; Forbes, S.L. In vitro volatile organic compound profiling using GC×GC-TOFMS to differentiate bacteria associated with lung infections: a proof-of-concept study. J. Breath Res., 2016, 10(2)026008
[] [PMID: 27120170]
Martin, A.N.; Farquar, G.R.; Jones, A.D.; Frank, M. Human breath analysis: methods for sample collection and reduction of localized background effects. Anal. Bioanal. Chem., 2010, 396(2), 739-750.
[] [PMID: 19844696]
Vas, G.; Vékey, K. Solid-phase microextraction: a powerful sample preparation tool prior to mass spectrometric analysis. J. Mass Spectrom., 2004, 39(3), 233-254.
[] [PMID: 15039931]
Amorim, L.C.; de L Cardeal, Z. Breath air analysis and its use as a biomarker in biological monitoring of occupational and environmental exposure to chemical agents. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2007, 853(1-2), 1-9.
[] [PMID: 17418649]
Aksenov, A.A.; Zamuruyev, K.O.; Pasamontes, A.; Brown, J.F.; Schivo, M.; Foutouhi, S.; Weimer, B.C.; Kenyon, N.J.; Davis, C.E. Analytical methodologies for broad metabolite coverage of exhaled breath condensate. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2017, 1061-1062, 17-25.
[] [PMID: 28697414]
Pauling, L.; Robinson, A.B.; Teranishi, R.; Cary, P. Quantitative analysis of urine vapor and breath by gas-liquid partition chromatography. Proc. Natl. Acad. Sci. USA, 1971, 68(10), 2374-2376.
[] [PMID: 5289873]
Phillips, M.; Gleeson, K.; Hughes, J.M.; Greenberg, J.; Cataneo, R.N.; Baker, L.; McVay, W.P. Volatile organic compounds in breath as markers of lung cancer: a cross-sectional study. Lancet, 1999, 353(9168), 1930-1933.
[] [PMID: 10371572]
Prado, C.; Marín, P.; Periago, J.F. Application of solid-phase microextraction and gas chromatography-mass spectrometry to the determination of volatile organic compounds in end-exhaled breath samples. J. Chromatogr. A, 2003, 1011(1-2), 125-134.
[] [PMID: 14518769]
Pleil, J.D.; Hubbard, H.F.; Sobus, J.R.; Sawyer, K.; Madden, M.C. Volatile polar metabolites in exhaled breath condensate (EBC): collection and analysis. J. Breath Res., 2008, 2(2)026001
[] [PMID: 21383442]
Bean, H.D.; Dimandja, J.M.; Hill, J.E. Bacterial volatile discovery using solid phase microextraction and comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2012, 901, 41-46.
[] [PMID: 22727751]
Mansoor, J.K.; Schelegle, E.S.; Davis, C.E.; Walby, W.F.; Zhao, W.; Aksenov, A.A.; Pasamontes, A.; Figueroa, J.; Allen, R. Analysis of volatile compounds in exhaled breath condensate in patients with severe pulmonary arterial hypertension. PLoS One, 2014, 9(4)e95331
[] [PMID: 24748102]
Figueroa, J.A.; Mansoor, J.K.; Allen, R.P.; Davis, C.E.; Walby, W.F.; Aksenov, A.A.; Zhao, W.; Lewis, W.R.; Schelegle, E.S. Exhaled volatile organic compounds in individuals with a history of high altitude pulmonary edema and varying hypoxia-induced responses. J. Breath Res., 2015, 9(2)026004
[] [PMID: 25891856]
Devillier, P.; Salvator, H.; Naline, E.; Couderc, L.J.; Grassin-Delyle, S. Metabolomics in the diagnosis and pharmacotherapy of lung diseases. Curr. Pharm. Des., 2017, 23(14), 2050-2059.
[] [PMID: 28137216]
Phillips, M.; Herrera, J.; Krishnan, S.; Zain, M.; Greenberg, J.; Cataneo, R.N. Variation in volatile organic compounds in the breath of normal humans. J. Chromatogr. B Biomed. Sci. Appl., 1999, 729(1-2), 75-88.
[] [PMID: 10410929]
Hubbard, H.F.; Sobus, J.R.; Pleil, J.D.; Madden, M.C.; Tabucchi, S. Application of novel method to measure endogenous VOCs in exhaled breath condensate before and after exposure to diesel exhaust. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2009, 877(29), 3652-3658.
[] [PMID: 19797001]
Peralbo-Molina, A.; Calderón-Santiago, M.; Priego-Capote, F.; Jurado-Gámez, B.; Luque de Castro, M.D. Metabolomics analysis of exhaled breath condensate for discrimination between lung cancer patients and risk factor individuals. J. Breath Res., 2016, 10(1)016011
[] [PMID: 26866403]
Cáp, P.; Chládek, J.; Pehal, F.; Malý, M.; Petrů, V.; Barnes, P.J.; Montuschi, P. Gas chromatography/mass spectrometry analysis of exhaled leukotrienes in asthmatic patients. Thorax, 2004, 59(6), 465-470.
[] [PMID: 15170025]
Sanak, M.; Gielicz, A.; Bochenek, G.; Kaszuba, M.; Niżankowska-Mogilnicka, E.; A, targeted. eicosanoid lipidomics of exhaled breath condensate provide a distinct pattern in the aspirin-intolerant asthma phenotype. J. Allergy Clin. Immunol., 2011, 127(5), 1141-1147.
[] [PMID: 21315430]
Sanak, M.; Gielicz, A.; Nagraba, K.; Kaszuba, M.; Kumik, J.; Szczeklik, A. Targeted eicosanoids lipidomics of exhaled breath condensate in healthy subjects. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2010, 878(21), 1796-1800.
[] [PMID: 20627827]
Mastalerz, L.; Sanak, M.; Kumik, J.; Gawlewicz-Mroczka, A.; Celejewska-Wójcik, N.; Cmiel, A.; Szczeklik, A. Exhaled Eicosanoids following Bronchial Aspirin Challenge in Asthma Patients with and without Aspirin Hypersensitivity: The Pilot Study. J. Allergy (Cairo), 2012, 2012696792
[] [PMID: 22291720]
Milne, G.L.; Gao, B.; Terry, E.S.; Zackert, W.E.; Sanchez, S.C. Measurement of F2- isoprostanes and isofurans using gas chromatography-mass spectrometry. Free Radic. Biol. Med., 2013, 59, 36-44.
[] [PMID: 23044261]
Lärstad, M.; Söderling, A.S.; Caidahl, K.; Olin, A.C. Selective quantification of free 3-nitrotyrosine in exhaled breath condensate in asthma using gas chromatography/tandem mass spectrometry. Nitric Oxide, 2005, 13(2), 134-144.
[] [PMID: 16006156]
Tsikas, D.; Duncan, M.W. Mass spectrometry and 3-nitrotyrosine: strategies, controversies, and our current perspective. Mass Spectrom. Rev., 2014, 33(4), 237-276.
[] [PMID: 24167057]
Celio, S.; Troxler, H.; Durka, S.S.; Chládek, J.; Wildhaber, J.H.; Sennhauser, F.H.; Heizmann, C.W.; Moeller, A. Free 3-nitrotyrosine in exhaled breath condensates of children fails as a marker for oxidative stress in stable cystic fibrosis and asthma. Nitric Oxide, 2006, 15(3), 226-232.
[] [PMID: 16931075]
Boots, A.W.; Bos, L.D.; van der Schee, M.P.; van Schooten, F.J.; Sterk, P.J. Exhaled Molecular Fingerprinting in Diagnosis and Monitoring: Validating Volatile Promises. Trends Mol. Med., 2015, 21(10), 633-644.
[] [PMID: 26432020]
Wang, C.J.; Yang, N.H.; Liou, S.H.; Lee, H.L. Fast quantification of the exhaled breath condensate of oxidative stress 8-iso-prostaglandin F2alpha using on-line solid-phase extraction coupled with liquid chromatography/electrospray ionization mass spectrometry. Talanta, 2010, 82(4), 1434-1438.
[] [PMID: 20801352]
García-Gómez, D.; Martínez-Lozano Sinues, P.; Barrios-Collado, C.; Vidal-de-Miguel, G.; Gaugg, M.; Zenobi, R. Identification of 2-alkenals, 4-hydroxy-2-alkenals, and 4-hydroxy-2,6-alkadienals in exhaled breath condensate by UHPLC-HRMS and in breath by real-time HRMS. Anal. Chem., 2015, 87(5), 3087-3093.
[] [PMID: 25646646]
Montuschi, P.; Santini, G.; Valente, S.; Mondino, C.; Macagno, F.; Cattani, P.; Zini, G.; Mores, N. Liquid chromatography-mass spectrometry measurement of leukotrienes in asthma and other respiratory diseases. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2014, 964, 12-25.
[] [PMID: 24656639]
Rosa, M.J.; Yan, B.; Chillrud, S.N.; Acosta, L.M.; Divjan, A.; Jacobson, J.S.; Miller, R.L.; Goldstein, I.F.; Perzanowski, M.S. Domestic airborne black carbon levels and 8-isoprostane in exhaled breath condensate among children in New York City. Environ. Res., 2014, 135, 105-110.
[] [PMID: 25262082]
Pelclová, D.; Fenclová, Z.; Vlcková, S.; Lebedová, J.; Syslová, K.; Pecha, O.; Belácek, J.; Navrátil, T.; Kuzma, M.; Kacer, P. Leukotrienes B4, C4, D4 and E4 in the exhaled breath condensate (EBC), blood and urine in patients with pneumoconiosis. Ind. Health, 2012, 50(4), 299-306.
[] [PMID: 22785421]
Larsson, P.; Bake, B.; Wallin, A.; Hammar, O.; Almstrand, A.C.; Lärstad, M.; Ljungström, E.; Mirgorodskaya, E.; Olin, A.C. The effect of exhalation flow on endogenous particle emission and phospholipid composition. Respir. Physiol. Neurobiol., 2017, 243, 39-46.
[] [PMID: 28502893]
Montesi, S.B.; Mathai, S.K.; Brenner, L.N.; Gorshkova, I.A.; Berdyshev, E.V.; Tager, A.M.; Shea, B.S. Docosatetraenoyl LPA is elevated in exhaled breath condensate in idiopathic pulmonary fibrosis. BMC Pulm. Med., 2014, 14, 5.
[] [PMID: 24468008]
Monge, M.E.; Pérez, J.J.; Dwivedi, P.; Zhou, M.; McCarty, N.A.; Stecenko, A.A.; Fernández, F.M. Ion mobility and liquid chromatography/mass spectrometry strategies for exhaled breath condensate glucose quantitation in cystic fibrosis studies. Rapid Commun. Mass Spectrom., 2013, 27(20), 2263-2271.
[] [PMID: 24019192]
Lucca, F.; Da Dalt, L.; Ros, M.; Gucciardi, A.; Pirillo, P.; Naturale, M.; Perilongo, G.; Giordano, G.; Baraldi, E. Asymmetric dimethylarginine and related metabolites in exhaled breath condensate of children with cystic fibrosis. Clin. Respir. J., 2016.
[PMID: 27216780]
van der Sluijs, K.F.; van de Pol, M.A.; Kulik, W.; Dijkhuis, A.; Smids, B.S.; van Eijk, H.W.; Karlas, J.A.; Molenkamp, R.; Wolthers, K.C.; Johnston, S.L.; van der Zee, J.S.; Sterk, P.J.; Lutter, R. Systemic tryptophan and kynurenine catabolite levels relate to severity of rhinovirus-induced asthma exacerbation: a prospective study with a parallel-group design. Thorax, 2013, 68(12), 1122-1130.
[] [PMID: 23882022]
Patel, K.; Davis, S.D.; Johnson, R.; Esther, C.R., Jr Exhaled breath condensate purines correlate with lung function in infants and preschoolers. Pediatr. Pulmonol., 2013, 48(2), 182-187.
[] [PMID: 22615171]
Esther, C.R., Jr; Olsen, B.M.; Lin, F.C.; Fine, J.; Boucher, R.C. Exhaled breath condensate adenosine tracks lung function changes in cystic fibrosis. Am. J. Physiol. Lung Cell. Mol. Physiol., 2013, 304(7), L504-L509.
[] [PMID: 23355385]
Rodriguez-Aller, M.; Gurny, R.; Veuthey, J.L.; Guillarme, D. Coupling ultra high-pressure liquid chromatography with mass spectrometry: constraints and possible applications. J. Chromatogr. A, 2013, 1292, 2-18.
[] [PMID: 23062879]
Fumagalli, M.; Ferrari, F.; Luisetti, M.; Stolk, J.; Hiemstra, P.S.; Capuano, D.; Viglio, S.; Fregonese, L.; Cerveri, I.; Corana, F.; Tinelli, C.; Iadarola, P. Profiling the proteome of exhaled breath condensate in healthy smokers and COPD patients by LC-MS/MS. Int. J. Mol. Sci., 2012, 13(11), 13894-13910.
[] [PMID: 23203040]
Muccilli, V.; Saletti, R.; Cunsolo, V.; Ho, J.; Gili, E.; Conte, E.; Sichili, S.; Vancheri, C.; Foti, S. Protein profile of exhaled breath condensate determined by high resolution mass spectrometry. J. Pharm. Biomed. Anal., 2015, 105, 134-149.
[] [PMID: 25555262]
Kononikhin, A.S.; Ryndin, A.Y.; Starodubtseva, N.L.; Chagovets, V.V.; Burov, A.A.; Bugrova, A.E.; Kostyukevich, Y.I.; Popov, I.A.; Frankevich, V.E.; Ionov, O.V.; Zubkov, V.V.; Nikolaev, E.N. Studying the Proteomic Composition of Expired Air Condensate in Newborns on Breathing Support. Bull. Exp. Biol. Med., 2016, 160(6), 861-863.
[] [PMID: 27165072]
Conrad, D.H.; Goyette, J.; Thomas, P.S. Proteomics as a method for early detection of cancer: a review of proteomics, exhaled breath condensate, and lung cancer screening. J. Gen. Intern. Med., 2008, 23(Suppl. 1), 78-84.
[] [PMID: 18095050]
Bloemen, K.; Van Den Heuvel, R.; Govarts, E.; Hooyberghs, J.; Nelen, V.; Witters, E.; Desager, K.; Schoeters, G. A new approach to study exhaled proteins as potential biomarkers for asthma. Clin. Exp. Allergy, 2011, 41(3), 346-356.
[] [PMID: 21105917]
Liang, Y.; Yeligar, S.M.; Brown, L.A. Exhaled breath condensate: a promising source for biomarkers of lung disease. ScientificWorldJournal, 2012, 2012217518
[] [PMID: 23365513]
Wold, S.; Sjostrom, M.; Eriksson, L. PLS-regression: a basic tool of chemometrics. Chemom. Intell. Lab. Syst., 2001, 58, 109-130.
Rinnan, A.; Munck, L. Significance of the structure of data in partial least squares regression predictions involving both natural and human experimental design. J. Chemometr., 2012, 26, 487-495.
Trygg, J.; Wold, S. Orthogonal projections to latent structures (O-PLS). J. Chemometr., 2002, 16, 119-128.
Trygg, J.; Wold, S. O2-PLS, a two-block (X-Y) latent variable regression (LVR) method with an integral OSC filter. J. Chemometr., 2003, 17, 53-64.
Stocchero, M.; Paris, D. Post-transformation of PLS2 (ptPLS2) by orthogonal matrix: a new approach for generating predictive and orthogonal latent variables. J. Chemometr., 2016, 30, 242-251.
Spraul, M.; Neidig, P.; Klauck, U.; Kessler, P.; Holmes, E.; Nicholson, J.K.; Sweatman, B.C.; Salman, S.R.; Farrant, R.D.; Rahr, E. Automatic reduction of NMR spectroscopic data for statistical and pattern recognition classification of samples. J. Pharm. Biomed. Anal., 1994, 12(10), 1215-1225.
[] [PMID: 7841215]
Castillo, S.; Gopalacharyulu, P.; Yetukuri, L.; Oresic, M. Algorithms and tools for the preprocessing of LC-MS metabolomics data. Chemom. Intell. Lab. Syst., 2011, 108, 23-32.
Goodacre, R.; Broadhurst, D.; Smilde, A.K.; Kristal, B.S.; Baker, J.D.; Beger, R.; Bessant, C.; Connor, S.; Calmani, G.; Craig, A. Proposed minimum reporting standards for data analysis in metabolomics. Metabolomics, 2007, 3, 231-241.
Lange, E.; Tautenhahn, R.; Neumann, S.; Gröpl, C. Critical assessment of alignment procedures for LC-MS proteomics and metabolomics measurements. BMC Bioinformatics, 2008, 9, 375.
[] [PMID: 18793413]
Katajamaa, M.; Oresic, M. Data processing for mass spectrometry-based metabolomics. J. Chromatogr. A, 2007, 1158(1-2), 318-328.
[] [PMID: 17466315]
Pfeuffer, J.; Sachsenberg, T.; Alka, O.; Walzer, M.; Fillbrunn, A.; Nilse, L.; Schilling, O.; Reinert, K.; Kohlbacher, O.; Open, M.S.; Open, M.S. OpenMS - A platform for reproducible analysis of mass spectrometry data. J. Biotechnol., 2017, 261, 142-148.
[] [PMID: 28559010]
Vu, T.N.; Laukens, K. Getting your peaks in line: a review of alignment methods for NMR spectral data. Metabolites, 2013, 3(2), 259-276.
[] [PMID: 24957991]
Forshed, J.; Torgrip, R.J.; Aberg, K.M.; Karlberg, B.; Lindberg, J.; Jacobsson, S.P. A comparison of methods for alignment of NMR peaks in the context of cluster analysis. J. Pharm. Biomed. Anal., 2005, 38(5), 824-832.
[] [PMID: 16087044]
van den Berg, R.A.; Hoefsloot, H.C.; Westerhuis, J.A.; Smilde, A.K.; van der Werf, M.J. Centering, scaling, and transformations: improving the biological information content of metabolomics data. BMC Genomics, 2006, 7, 142.
[] [PMID: 16762068]
Craig, A.; Cloarec, O.; Holmes, E.; Nicholson, J.K.; Lindon, J.C. Scaling and normalization effects in NMR spectroscopic metabonomic data sets. Anal. Chem., 2006, 78(7), 2262-2267.
[] [PMID: 16579606]
Szymańska, E.; Saccenti, E.; Smilde, A.K.; Westerhuis, J.A. Double-check: validation of diagnostic statistics for PLS-DA models in metabolomics studies. Metabolomics, 2012, 8(Suppl. 1), 3-16.
[] [PMID: 22593721]
Westerhuis, J.A.; Hoefsloot, H.C.J.; Smit, S.; Vis, D.J.; Smilde, A.K.; van Velzen, E.J.J.; van Duijnhoven, J.P.M.; van Dorsten, F.A. Assessment of PLSDA cross validation. Metabolomics, 2008, 4, 81-89.
Bush, A.; Fleming, L. Phenotypes of refractory/severe asthma. Paediatr. Respir. Rev., 2011, 12(3), 177-181.
[] [PMID: 21722846]
Carraro, S.; Rezzi, S.; Reniero, F.; Héberger, K.; Giordano, G.; Zanconato, S.; Guillou, C.; Baraldi, E. Metabolomics applied to exhaled breath condensate in childhood asthma. Am. J. Respir. Crit. Care Med., 2007, 175(10), 986-990.
[] [PMID: 17303796]
Maniscalco, M.; Motta, A. Biomarkers in allergic asthma: Which matrix should we use? Clin. Exp. Allergy, 2017, 47(8), 1097-1098.
[] [PMID: 28703932]
Bertini, I.; Luchinat, C.; Miniati, M.; Monti, S.; Tenori, L. Phenotyping COPD by H-1 NMR metabolomics of exhaled breath condensate. Metabolomics, 2014, 10, 302-311.
Airoldi, C.; Ciaramelli, C.; Fumagalli, M.; Bussei, R.; Mazzoni, V.; Viglio, S.; Iadarola, P.; Stolk, J. 1H NMR To Explore the Metabolome of Exhaled Breath Condensate in α1-Antitrypsin Deficient Patients: A Pilot Study. J. Proteome Res., 2016, 15(12), 4569-4578.
[] [PMID: 27646345]
de Laurentiis, G.; Paris, D.; Melck, D.; Montuschi, P.; Maniscalco, M.; Bianco, A.; Sofia, M.; Motta, A. Separating smoking-related diseases using NMR-based metabolomics of exhaled breath condensate. J. Proteome Res., 2013, 12(3), 1502-1511.
[] [PMID: 23360153]
Maniscalco, M.; Paris, D.; Melck, D.J.; Molino, A.; Carone, M.; Ruggeri, P.; Caramori, G.; Motta, A. Differential diagnosis between newly diagnosed asthma and COPD using exhaled breath condensate metabolomics: a pilot study. Eur. Respir. J., 2018, 51(3) 1701825
[] [PMID: 29348154]
Maniscalco, M.; Motta, A. Clinical and Inflammatory Phenotyping: Can Electronic Nose and NMR-based Metabolomics Work at the Bedside? Arch. Med. Res, 2018, S0188-4409(18), 30096.
Montuschi, P.; Paris, D.; Montella, S.; Melck, D.; Mirra, V.; Santini, G.; Mores, N.; Montemitro, E.; Majo, F.; Lucidi, V.; Bush, A.; Motta, A.; Santamaria, F. Nuclear magnetic resonance-based metabolomics discriminates primary ciliary dyskinesia from cystic fibrosis. Am. J. Respir. Crit. Care Med., 2014, 190(2), 229-233.
[] [PMID: 25025356]
Montuschi, P.; Paris, D.; Melck, D.; Lucidi, V.; Ciabattoni, G.; Raia, V.; Calabrese, C.; Bush, A.; Barnes, P.J.; Motta, A. NMR spectroscopy metabolomic profiling of exhaled breath condensate in patients with stable and unstable cystic fibrosis. Thorax, 2012, 67(3), 222-228.
[] [PMID: 22106016]
Ibrahim, B.; Marsden, P.; Smith, J.A.; Custovic, A.; Nilsson, M.; Fowler, S.J. Breath metabolomic profiling by nuclear magnetic resonance spectroscopy in asthma. Allergy, 2013, 68(8), 1050-1056.
[] [PMID: 23888905]
Sinha, A.; Desiraju, K.; Aggarwal, K.; Kutum, R.; Roy, S.; Lodha, R.; Kabra, S.K.; Ghosh, B.; Sethi, T.; Agrawal, A. Exhaled breath condensate metabolome clusters for endotype discovery in asthma. J. Transl. Med., 2017, 15(1), 262.
[] [PMID: 29273025]
Paris, D.; Maniscalco, M.; Melck, D.; D’Amato, M.; Sorrentino, N.; Zedda, A.; Sofia, M.; Motta, A. Inflammatory metabolites in exhaled breath condensate characterize the obese respiratory phenotype. Metabolomics, 2015, 11, 1934-1939.
Maniscalco, M.; Paris, D.; Melck, D.J.; D’Amato, M.; Zedda, A.; Sofia, M.; Stellato, C.; Motta, A. Coexistence of obesity and asthma determines a distinct respiratory metabolic phenotype. J. Allergy Clin. Immunol., 2017, 139(5), 1536-1547.e5.
[] [PMID: 27746236]
Kilk, K.; Aug, A.; Ottas, A.; Soomets, U.; Altraja, S.; Altraja, A. Phenotyping of Chronic Obstructive Pulmonary Disease Based on the Integration of Metabolomes and Clinical Characteristics. Int. J. Mol. Sci., 2018, 19(3)E666
[] [PMID: 29495451]
Rindlisbacher, B.; Strebel, C.; Guler, S.; Kollár, A.; Geiser, T.; Martin Fiedler, G.; Benedikt Leichtle, A.; Bovet, C.; Funke-Chambour, M. Exhaled breath condensate as a potential biomarker tool for idiopathic pulmonary fibrosis-a pilot study. J. Breath Res., 2017, 12(1)016003
[] [PMID: 28775244]
Peralbo-Molina, A.; Calderón-Santiago, M.; Priego-Capote, F.; Jurado-Gámez, B.; Luque de Castro, M.D. Identification of metabolomics panels for potential lung cancer screening by analysis of exhaled breath condensate. J. Breath Res., 2016, 10(2)026002
[] [PMID: 27007686]
Zang, X.; Pérez, J.J.; Jones, C.M.; Monge, M.E.; McCarty, N.A.; Stecenko, A.A.; Fernández, F.M. Comparison of Ambient and Atmospheric Pressure Ion Sources for Cystic Fibrosis Exhaled Breath Condensate Ion Mobility-Mass Spectrometry Metabolomics. J. Am. Soc. Mass Spectrom., 2017, 28(8), 1489-1496.
[] [PMID: 28364225]
Carraro, S; Giordano, G; Pirillo, P; Maretti, M; Reniero, F; Cogo, PE; Perilongo, G; Stocchero, M; Baraldi, E Airway metabolic anomalies in adolescents with bronchopulmonary dysplasia: new insights from the metabolomic approach J. Pediatr, 2015, 166(2), 234-239. e231.
Fermier, B.; Blasco, H.; Godat, E.; Bocca, C.; Moënne-Loccoz, J.; Emond, P.; Andres, C.R.; Laffon, M.; Ferrandière, M. Specific Metabolome Profile of Exhaled Breath Condensate in Patients with Shock and Respiratory Failure: A Pilot Study. Metabolites, 2016, 6(3), 6.
[] [PMID: 27598216]
Zang, X.; Monge, M.E.; McCarty, N.A.; Stecenko, A.A.; Fernández, F.M. Feasibility of Early Detection of Cystic Fibrosis Acute Pulmonary Exacerbations by Exhaled Breath Condensate Metabolomics: A Pilot Study. J. Proteome Res., 2017, 16(2), 550-558.
[] [PMID: 28152602]
Carraro, S.; Giordano, G.; Reniero, F.; Carpi, D.; Stocchero, M.; Sterk, P.J.; Baraldi, E. Asthma severity in childhood and metabolomic profiling of breath condensate. Allergy, 2013, 68(1), 110-117.
[] [PMID: 23157191]
Kononikhin, A.S.; Starodubtseva, N.L.; Chagovets, V.V.; Ryndin, A.Y.; Burov, A.A.; Popov, I.A.; Bugrova, A.E.; Dautov, R.A.; Tokareva, A.O.; Podurovskaya, Y.L.; Ionov, O.V.; Frankevich, V.E.; Nikolaev, E.N.; Sukhikh, G.T. Exhaled breath condensate analysis from intubated newborns by nano-HPLC coupled to high resolution MS. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2017, 1047, 97-105.
[] [PMID: 28040456]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy