Breath Biomarker Analysis: The Future Point of Care Non-invasive Diagnostic Technology
DOI:
https://doi.org/10.12974/2312-5470.2014.01.02.3Keywords:
Breath analysis, laboratory medicine, non invasive diagnostics, point of care technology.Abstract
Medicine is the science and art of healing. It requires objective analysis of disease conditions to reach a meaningful conclusion. Laboratory medicine is the integral part of today’s healthcare. A classical clinical laboratory requires sample collection, sample transport, sample analysis and transfer of the report to the end user and so vital information of critical parameters are available for patient care after quite some time. Therefore, considerable current interest has been generated for non-invasive diagnostics that can be performed at the point of care. Analysis of breath biomarkers is currently understood as a topic that will be the major future point of care diagnostic methodology and this aspect is reviewed in the current manuscript to highlight the work so far done on the subject.
References
Shirasu M, Touhara K. The scent of disease: volatile organic compounds of the human body related to disease and disorder. J Biochem 2011; 150(3): 257-66. http://dx.doi.org/10.1093/jb/mvr090
Global strategy for asthma management and prevention. Global Initiative for Asthma (GINA); 2012. Available @ http://www.ginasthma.org/documents/4.
Masoli M, Fabian D, Holt S, Beasley R. The global burden of asthma: executive summary of the GINA dissemination committee report. Allergy 2004; 59(5): 469-78. http://dx.doi.org/10.1111/j.1398-9995.2004.00526.x
Vijverberg SJ, Hilvering B, Raaijmakers JA, Lammers JW, Maitland-van der Zee AH, Koenderman L. Clinical utility of asthma biomarkers: from bench to bedside. Biologics 2013; 7: 199-210.
Pronk-Admiraal CJ, Haitjema T, Horikx P, Bartels PC. Surplus value of eosinophil count and ECP to diagnose and monitor asthmatic patients. Neth J Med 2001; 58(1): 9-17. http://dx.doi.org/10.1016/S0300-2977(00)00087-5
Ullmann N, Bossley CJ, Fleming L, Silvestri M, Bush A, Saglani S. Blood eosinophil counts rarely reflect airway eosinophilia in children with severe asthma. Allergy 2013; 68(3): 402-6. http://dx.doi.org/10.1111/all.12101
Sears MR, Burrows B, Flannery EM, Herbison GP, Hewitt CJ, Holdaway MD. Relation between airway responsiveness and serum IgE in children with asthma and in apparently normal children. N Engl J Med 1991; 325(15): 1067-71. http://dx.doi.org/10.1056/NEJM199110103251504
Kumar R, Singh BP, Srivastava P, Sridhara S, Arora N, Gaur SN. Relevance of serum IgE estimation in allergic bronchial asthma with special reference to food allergy. Asian Pac J Allergy Immunol 2006; 24(4): 191-9.
Ahmad Al Obaidi AH, Mohamed Al Samarai AG, Yahya Al Samarai AK, Al Janabi JM. The predictive value of IgE as biomarker in asthma. J Asthma 2008; 45(8): 654-63. http://dx.doi.org/10.1080/02770900802126958
Graif Y, Yigla M, Tov N, Kramer MR. Value of a negative aeroallergen skin-prick test result in the diagnosis of asthma in young adults: correlative study with methacholine challenge testing. Chest 2002; 122(3): 821-5. http://dx.doi.org/10.1378/chest.122.3.821
Chan EY, Dundas I, Bridge PD, Healy MJR, S.A. McKenzie SA. Skin-prick testing as a diagnostic aid for childhood asthma. Pediatr Pulmonol 2005; 39(6): 558-62. http://dx.doi.org/10.1002/ppul.20227
Kharitonov SA, Yates D, Robbins RA, Logan-Sinclair R, Shinebourne EA, Barnes PJ. Increased nitric oxide in exhaled air of asthmatic patients. Lancet 1994; 343(8890): 133-5. http://dx.doi.org/10.1016/S0140-6736(94)90931-8
Persson MG, Zetterström O, Agrenius V, Ihre E, Gustafsson LE. Single-breath nitric oxide measurements in asthmatic patients and smokers. Lancet 1994; 343(8890): 146-7. http://dx.doi.org/10.1016/S0140-6736(94)90935-0
Cheepsattayakorn A, Cheepsattayakorn R. Breath tests in respiratory and critical care medicine: from research to practice in current perspectives. Biomed Res Int 2013; 2013: 702896.
Rutgers SR, Meijer RJ, Kerstjens HA, van der Mark TW, Koëter GH, Postma DS. Nitric oxide measured with singlebreath and tidal-breathing methods in asthma and COPD. Eur Respir J. 1998; 12(4): 816-9. http://dx.doi.org/10.1183/09031936.98.12040816
Yates DH. Role of exhaled nitric oxide in asthma. Immunol Cell Biol 2001; 79(2): 178-90. http://dx.doi.org/10.1046/j.1440-1711.2001.00990.x
Zayasu K, Sekizawa K, Okinaga S, Yamaya M, Ohrui T, Sasaki H. Increased carbon monoxide in exhaled air of asthmatic patients. Am J Respir Crit Care Med 1997; 156(4 Pt 1): 1140-3. http://dx.doi.org/10.1164/ajrccm.156.4.96-08056
Horváth I, Donnelly LE, Kiss A, Paredi P, Kharitonov SA, Barnes PJ. Raised levels of exhaled carbon monoxide are associated with an increased expression of heme oxygenase- 1 in airway macrophages in asthma: a new marker of oxidative stress. Thorax 1998; 53(8): 668-72. http://dx.doi.org/10.1136/thx.53.8.668
Kharitonov SA. Exhaled nitric oxide and carbon monoxide in respiratory diseases other than asthma. Eur Respir J 1999; 9: 223-226.
Kharitonov SA, Barnes PJ. Exhaled markers of pulmonary disease. Am J Respir Crit Care Med 2001; 163(7): 1693-722. http://dx.doi.org/10.1164/ajrccm.163.7.2009041
Olopade CO, Zakkar M, Swedler WI, Rubinstein I. Exhaled pentane levels in acute asthma. Chest 1997; 111(4): 862-5. http://dx.doi.org/10.1378/chest.111.4.862
Paredi P, Kharitonov SA, Barnes PJ. Elevation of exhaled ethane concentration in asthma. Am J Respir Crit Care Med 2000; 162(4 Pt 1): 1450-4. http://dx.doi.org/10.1164/ajrccm.162.4.2003064
Ip MS, Lam B, Chan LY, et al. Circulating nitric oxide is suppressed in obstructive sleep apnea and is reversed by nasal continuous positive airway pressure. Am J Respir Crit Care Med 2000; 162(6): 2166-71. http://dx.doi.org/10.1164/ajrccm.162.6.2002126
Olopade CO, Christon JA, Zakkar M, et al. Exhaled pentane and nitric oxide levels in patients with obstructive sleep apnea. Chest 1997; 111(6): 1500-4. http://dx.doi.org/10.1378/chest.111.6.1500
Horváth I, Donnelly LE, Kiss A, et al. Combined use of exhaled hydrogen peroxide and nitric oxide in monitoring asthma. Am J Respir Crit Care Med 1998; 158(4): 1042-6. http://dx.doi.org/10.1164/ajrccm.158.4.9710091
Dohlman AW, Black HR, Royall JA. Expired breath hydrogen peroxide is a marker of acute airway inflammation in pediatric patients with asthma. Am Rev Respir Dis 1993; 148(4 Pt 1): 955-60. http://dx.doi.org/10.1164/ajrccm/148.4_Pt_1.955
Antczak A, Nowak D, Shariati B, Król M, Piasecka G, Kurmanowska Z. Increased hydrogen peroxide and thiobarbituric acid-reactive products in expired breath condensate of asthmatic patients. Eur Respir J 1997; 10(6): 1235-41. http://dx.doi.org/10.1183/09031936.97.10061235
Jöbsis Q, Raatgeep HC, Schellekens SL, Hop WC, Hermans PW, de Jongste JC. Hydrogen peroxide in exhaled air of healthy children: reference values. Eur Respir J. 1998; 12(2): 483-5. http://dx.doi.org/10.1183/09031936.98.12020483
Antczak A, Nowak D, Bialasiewicz P, Kasielski M. Hydrogen peroxide in expired air condensate correlates positively with early steps of peripheral neutrophil activation in asthmatic patients. Arch Immunol Ther Exp (Warsz) 1999; 47(2): 119- 26.
Montuschi P, Corradi M, Ciabattoni G, Nightingale J, Kharitonov SA, Barnes PJ. Increased 8-isoprostane, a marker of oxidative stress, in exhaled condensate of asthma patients. Am J Respir Crit Care Med 1999; 160(1): 216-20. http://dx.doi.org/10.1164/ajrccm.160.1.9809140
Lehtonen H, Oksa P, Lehtimäki L, et al. Increased alveolar nitric oxide concentration and high levels of leukotriene B(4) and 8-isoprostane in exhaled breath condensate in patients with asbestosis. Thorax 2007; 62(7): 602-7. http://dx.doi.org/10.1136/thx.2006.067868
Dhalla NS, Golfman L, Takeda S, Takeda N, Nagano M. Evidence for the role of oxidative stress in acute ischemic heart disease: a brief review. Can J Cardiol 1999; 15(5): 587- 93.
Chandra M, Chandra N, Agrawal R, Kumar A, Ghatak A, Pandey VC. The free radical system in ischemic heart disease. Int J Cardiol 1994; 43(2): 121-5. http://dx.doi.org/10.1016/0167-5273(94)90001-9
Kneepkens CM, Ferreira C, Lepage G, Roy CC. The hydrocarbon breath test in the study of lipid peroxidation: principles and practice. Clin Invest Med 1992; 15(2): 163-86.
Kneepkens CM, Lepage G, Roy CC. The potential of the hydrocarbon breath test as a measure of lipid peroxidation. Free Radic Biol Med 1994; 17(2): 127-60. http://dx.doi.org/10.1016/0891-5849(94)90110-4
Phillips M, Cataneo RN, Greenberg J, Grodman R, Salazar M. Breath markers of oxidative stress in patients with unstable angina. Heart Dis 2003; 5(2): 95-9. http://dx.doi.org/10.1097/01.hdx.0000061701.99611.e8
Weitz ZW, Birnbaum AJ, Sobotka PA, Zarling EJ, Skosey JL. High breath pentane concentrations during acute myocardial infarction. Lancet 1991; 337(8747): 933-5. http://dx.doi.org/10.1016/0140-6736(91)91569-G
Sobotka PA, Brottman MD, Weitz Z, Birnbaum AJ, Skosey JL, Zarling EJ. Elevated breath pentane in heart failure reduced by free radical scavenger. Free Radic Biol Med 1993; 14(6): 643-7. http://dx.doi.org/10.1016/0891-5849(93)90145-K
Phillips M, Cataneo RN, Greenberg J, Gunawardena R, Naidu A, Rahbari-Oskoui F. Effect of age on the breath methylated alkane contour, a display of apparent new markers of oxidative stress. J Lab Clin Med 2000; 136(3): 243-9. http://dx.doi.org/10.1067/mlc.2000.108943
Phillips M, Boehmer JP, Cataneo RN, et al. Heart allograft rejection: detection with breath alkanes in low levels (the HARDBALL study). J Heart Lung Transplant 2004; 23(6): 701-8. http://dx.doi.org/10.1016/j.healun.2003.07.017
Phillips M, Cataneo RN, Greenberg J, Grodman R, Gunawardena R, Naidu A. Effect of oxygen on breath markers of oxidative stress. Eur Respir J 2003; 21(1): 48-51. http://dx.doi.org/10.1183/09031936.02.00053402
Dekhuijzen PN, Aben KK, Dekker I, et al. Increased exhalation of hydrogen peroxide in patients with stable and unstable chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1996; 154(3 Pt 1): 813-6. http://dx.doi.org/10.1164/ajrccm.154.3.8810624
Nowak D, Kasielski M, Antczak A, Pietras T, Bialasiewicz P. Increased content of thiobarbituric acid-reactive substances and hydrogen peroxide in the expired breath condensate of patients with stable chronic obstructive pulmonary disease: no significant effect of cigarette smoking. Respir Med 1999; 93(6): 389-96. http://dx.doi.org/10.1053/rmed.1999.0574
Lases EC, Duurkens VA, Gerritsen WB, Haas FJ. Oxidative stress after lung resection therapy: A pilot study. Chest 2000; 117(4): 999-1003. http://dx.doi.org/10.1378/chest.117.4.999
Montuschi P, Collins JV, Ciabattoni G, et al. Exhaled 8- isoprostane as an in vivo biomarker of lung oxidative stress in patients with COPD and healthy smokers. Am J Respir Crit Care Med 2000; 162(3 Pt 1): 1175-7. http://dx.doi.org/10.1164/ajrccm.162.3.2001063
Kostikas K, Papatheodorou G, Psathakis K, Panagou P, Loukides S. Oxidative stress in expired breath condensate of patients with COPD. Chest 2003; 124(4): 1373-80. http://dx.doi.org/10.1378/chest.124.4.1373
Montuschi P. Exhaled breath condensate analysis in patients with COPD. Clin Chim Acta 2005; 356(1-2): 22-34. http://dx.doi.org/10.1016/j.cccn.2005.01.012
Kharitonov SA, Robbins RA, Yates D, Keatings V, Barnes PJ. Acute and chronic effects of cigarette smoking on exhaled nitric oxide. Am J Respir Crit Care Med 1995; 152(2): 609-12. http://dx.doi.org/10.1164/ajrccm.152.2.7543345
Robbins RA, Floreani AA, Von Essen SG, et al. Measurement of exhaled nitric oxide by three different techniques. Am J Respir Crit Care Med 1996; 153(5): 1631-5. http://dx.doi.org/10.1164/ajrccm.153.5.8630613
Rutgers SR, van der Mark TW, Coers W, et al. Markers of nitric oxide metabolism in sputum and exhaled air are not increased in chronic obstructive pulmonary disease. Thorax 1999; 54(7): 576-80. http://dx.doi.org/10.1136/thx.54.7.576
Kharitonov SA, Barnes PJ. Exhaled markers of pulmonary disease. Am J Respir Crit Care Med 2001; 163(7): 1693-722. http://dx.doi.org/10.1164/ajrccm.163.7.2009041
Verleden GM, Dupont LJ, Verpeut AC, Demedts MG. The effect of cigarette smoking on exhaled nitric oxide in mild steroid-naive asthmatics. Chest 1999; 116(1): 59-64. http://dx.doi.org/10.1378/chest.116.1.59
Su Y, Han W, Giraldo C, De Li Y, Block ER. Effect of cigarette smoke extract on nitric oxide synthase in pulmonary artery endothelial cells. Am J Respir Cell Mol Biol 1998; 19(5): 819-25.
Jeejeebhoy KN. In vivo breath alkane as an index of lipid peroxidation. Free Radic Biol Med 1991; 10(3-4): 191-3. http://dx.doi.org/10.1016/0891-5849(91)90075-E
Do BK, Garewal HS, Clements NC Jr, Peng YM, Habib MP. Exhaled ethane and antioxidant vitamin supplements in active smokers. Chest 1996; 110(1): 159-64. http://dx.doi.org/10.1378/chest.110.1.159
Foster WM, Jiang L, Stetkiewicz PT, Risby TH. Breath isoprene: temporal changes in respiratory output after exposure to ozone. J Appl Physiol (1985) 1996; 80(2): 706- 10.
Paredi P, Kharitonov SA, Leak D, Ward S, Cramer D, Barnes PJ. Exhaled ethane, a marker of lipid peroxidation, is elevated in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000; 162(2 Pt 1): 369-73. http://dx.doi.org/10.1164/ajrccm.162.2.9909025
Praticò D, Basili S, Vieri M, Cordova C, Violi F, Fitzgerald GA. Chronic obstructive pulmonary disease is associated with an increase in urinary levels of isoprostane F2alpha-III, an index of oxidant stress. Am J Respir Crit Care Med 1998; 158(6): 1709-14. http://dx.doi.org/10.1164/ajrccm.158.6.9709066
Thomas SR, Kharitonov SA, Scott SF, Hodson ME, Barnes PJ. Nasal and exhaled nitric oxide is reduced in adult patients with cystic fibrosis and does not correlate with cystic fibrosis genotype. Chest 2000; 117(4): 1085-9. http://dx.doi.org/10.1378/chest.117.4.1085
Balfour-Lynn IM, Laverty A, Dinwiddie R. Reduced upper airway nitric oxide in cystic fibrosis. Arch Dis Child 1996; 75(4): 319-22. http://dx.doi.org/10.1136/adc.75.4.319
Jones KL, Bryan TW, Jinkins PA, et al. Superoxide released from neutrophils causes a reduction in nitric oxide gas. Am J Physiol 1998; 275(6 Pt 1): L1120-6.
Ho LP, Innes JA, Greening AP. Nitrite levels in breath condensate of patients with cystic fibrosis is elevated in contrast to exhaled nitric oxide. Thorax 1998; 53(8): 680-4. http://dx.doi.org/10.1136/thx.53.8.680
Linnane SJ, Keatings VM, Costello CM, et al. Total sputum nitrate plus nitrite is raised during acute pulmonary infection in cystic fibrosis. Am J Respir Crit Care Med 1998; 158(1): 207-12. http://dx.doi.org/10.1164/ajrccm.158.1.9707096
Antuni JD, Kharitonov SA, Hughes D, Hodson ME, Barnes PJ. Increase in exhaled carbon monoxide during exacerbations of cystic fibrosis. Thorax 2000; 55(2): 138-42. http://dx.doi.org/10.1136/thorax.55.2.138
Paredi P, Shah PL, Montuschi P, et al. Increased carbon monoxide in exhaled air of patients with cystic fibrosis. Thorax 1999; 54(10): 917-20. http://dx.doi.org/10.1136/thx.54.10.917
Montuschi P, Kharitonov SA, Ciabattoni G, et al. Exhaled 8- isoprostane as a new non-invasive biomarker of oxidative stress in cystic fibrosis. Thorax 2000; 55(3): 205-9. http://dx.doi.org/10.1136/thorax.55.3.205
Paredi P, Kharitonov SA, Leak D, et al. Exhaled ethane is elevated in cystic fibrosis and correlates with carbon monoxide levels and airway obstruction. Am J Respir Crit Care Med 2000; 161(4 Pt 1): 1247-51. http://dx.doi.org/10.1164/ajrccm.161.4.9906122
Collins CE, Quaggiotto P, Wood L, O'Loughlin EV, Henry RL, Garg ML. Elevated plasma levels of F2 alpha isoprostane in cystic fibrosis. Lipids 1999; 34(6): 551-6. http://dx.doi.org/10.1007/s11745-999-0397-1
Grasemann H, Gaston B, Fang K, Paul K, Ratjen F. Decreased levels of nitrosothiols in the lower airways of patients with cystic fibrosis and normal pulmonary function. J Pediatr 1999; 135(6): 770-2. http://dx.doi.org/10.1016/S0022-3476(99)70101-0
Worlitzsch D, Herberth G, Ulrich M, Döring G. Catalase, myeloperoxidase and hydrogen peroxide in cystic fibrosis. Eur Respir J 1998; 11(2): 377-83. http://dx.doi.org/10.1183/09031936.98.11020377
Ho LP, Faccenda J, Innes JA, Greening AP. Expired hydrogen peroxide in breath condensate of cystic fibrosis patients. Eur Respir J 1999; 13(1): 103-6. http://dx.doi.org/10.1183/09031936.99.13110399
Shestivska V, Nemec A, D????evínek P, Sovová K, Dryahina K, Span????l P. Quantification of methyl thiocyanate in the headspace of Pseudomonas aeruginosa cultures and in the breath of cystic fibrosis patients by selected ion flow tube mass spectrometry. Rapid Commun Mass Spectrom 2011; 25(17): 2459-67. http://dx.doi.org/10.1002/rcm.5146
Dummer J, Storer M, Sturney S, et al. Quantification of hydrogen cyanide (HCN) in breath using selected ion flow tube mass spectrometry--HCN is not a biomarker of Pseudomonas in chronic suppurative lung disease. J Breath Res 2013; 7(1): 017105. http://dx.doi.org/10.1088/1752-7155/7/1/017105
IDF Diabetes Atlas Sixth Edition, International Diabetes Federation 2013.
[Cited 2014 March 2] Available from http://www.idf.org/diabetesatlas
HENDERSON MJ, KARGER BA, WREN SHALL GA. Acetone in the breath; a study of acetone exhalation in diabetic and nondiabetic human subjects. Diabetes 1952; 1(3): 188-93.
Sulway MJ, Malins JM. Acetone in diabetic ketoacidosis. Lancet 1970; 1: 736–40. http://dx.doi.org/10.1016/S0140-6736(70)90218-7
Crofford OB, Mallard RE, Winton RE, Rogers NL, Jackson JC, Keller U. Acetone in breath and blood. Trans Am Clin Climatol Assoc 1977; 88: 128-39.
Choi SJ, Jang BH, Lee SJ, Min BK, Rothschild A, Kim ID. Selective Detection of Acetone and Hydrogen Sulfide for the Diagnosis of Diabetes and Halitosis Using SnO2 Nanofibers Functionalized with Reduced Graphene Oxide Nanosheets. ACS Appl Mater Interfaces 2014; 6(4): 2588-97. http://dx.doi.org/10.1021/am405088q
Paredi P, Biernacki W, Invernizzi G, Kharitonov SA, Barnes PJ. Exhaled carbon monoxide levels elevated in diabetes and correlated with glucose concentration in blood: a new test for monitoring the disease? Chest 1999; 116: 1007–1011. http://dx.doi.org/10.1378/chest.116.4.1007
Smith D, Span????l P, Fryer AA, Hanna F, Ferns GA. Can volatile compounds in exhaled breath be used to monitor control in diabetes mellitus? J Breath Res 2011; 5(2): 022001. http://dx.doi.org/10.1088/1752-7155/5/2/022001
Perman JA. Clinical application of breath hydrogen measurements. Can J Physiol Pharmacol 1991; 69(1): 111-5. http://dx.doi.org/10.1139/y91-016
Bauer TM, Schwacha H, Steinbrückner B, et al. Diagnosis of small intestinal bacterial overgrowth in patients with cirrhosis of the liver: poor performance of the glucose breath hydrogen test. J Hepatol 2000; 33(3): 382-6. http://dx.doi.org/10.1016/S0168-8278(00)80273-1
Nieminen N, Gylling H, Icen A, Farkkila MA. Lactose malabsorption: use of breath hydrogen test and serum glucose analyses in diagnostics. Gastroenterology 2000; 118(4): A1132. http://dx.doi.org/10.1016/S0016-5085(00)80335-2
Kokoszka J, Nelson RL, Swedler WI, Skosey J, Abcarian H. Determination of inflammatory bowel disease activity by breath pentane analysis. Dis Colon Rectum 1993; 36(6): 597- 601. http://dx.doi.org/10.1007/BF02049868
Dryahina K, ????pan????l P, Pospí????ilová V, et al. Quantification of pentane in exhaled breath, a potential biomarker of bowel disease, using selected ion flow tube mass spectrometry. Rapid Commun Mass Spectrom 2013; 27(17): 1983-92. http://dx.doi.org/10.1002/rcm.6660
Katici???? M, Presecki V, Kaleni???? S, Dominis M. Helicobacter pylori--introduction and review of research. Lijec Vjesn 2002; 124(Suppl 1): 1-5.
Marshall B, Warren JR. Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet 1983; 1(8336): 1273-5.
Irving CS, Wong WW, Shulman RJ, Smith EO, Klein PD.
C]bicarbonate kinetics in humans: intra- vs. interindividual variations. Am J Physiol 1983; 245(2): R190-202.
Irving CS, Wong WW, Wong WM, et al. Rapid determination of whole-body bicarbonate kinetics by use of a digital infusion. Am J Physiol 1984; 247(4 Pt 2): R709-16.
Irving CS, Lifschitz CH, Wong WW, Boutton TW, Nichols BL, Klein PD. Characterization of HCO3-/CO2 pool sizes and kinetics in infants. Pediatr Res 1985; 19(4): 358-63. http://dx.doi.org/10.1203/00006450-198519040-00009
Genta RM, Graham DY. Comparison of biopsy sites for the histopathologic diagnosis of Helicobacter pylori: a topographic study of H. pylori density and distribution. Gastrointest Endosc 1994; 40(3): 342-5. http://dx.doi.org/10.1016/S0016-5107(94)70067-2
Brown KE, Peura DA. Diagnosis of Helicobacter pylori infection. Gastroenterol Clin North Am 1993; 22(1): 105-15.
Peura DA, Pambianco DJ, Dye KR, et al. Microdose 14Curea breath test offers diagnosis of Helicobacter pylori in 10 minutes. Am J Gastroenterol 1996; 91(2): 233-8.
Cutler AF, Havstad S, Ma CK, Blaser MJ, Perez-Perez GI, Schubert TT. Accuracy of invasive and noninvasive tests to diagnose Helicobacter pylori infection. Gastroenterology 1995; 109(1): 136-41. http://dx.doi.org/10.1016/0016-5085(95)90278-3
Eltumi M, Brueton MJ, Francis N. Diagnosis of Helicobacter pylori gastritis in children using the 13C urea breath test. J Clin Gastroenterol 1999; 28(3): 238-40. http://dx.doi.org/10.1097/00004836-199904000-00010
Thijs JC, van Zwet AA, Thijs WJ, et al. Diagnostic tests for Helicobacter pylori: a prospective evaluation of their accuracy, without selecting a single test as the gold standard. Am J Gastroenterol 1996; 91(10): 2125-9.
Soyer T, Soyer OU, Birben E, Kısa U, Kalaycı O, Cakmak M. Pepsin levels and oxidative stress markers in exhaled breath condensate of patients with gastroesophageal reflux disease. J Pediatr Surg 2013; 48(11): 2247-50. http://dx.doi.org/10.1016/j.jpedsurg.2013.02.100
Shimizu Y, Dobashi K, Nagoshi A, Kawamura O, Mori M. Assessment of airway inflammation by exhaled breath condensate and impedance due to gastroesophageal reflux disease (GERD). Inflamm Allergy Drug Targets 2009; 8(4): 292-6. http://dx.doi.org/10.2174/187152809789352195
Dodig S, Vlasi???? Z, Cepelak I, Zrinski Topi???? R, Turkalj M, Nogalo B. Magnesium and calcium in exhaled breath condensate of children with asthma and gastroesophageal reflux disease. J Clin Lab Anal 2009; 23(1): 34-9. http://dx.doi.org/10.1002/jcla.20286
Banovi???? S, Navratil M, Vla????i???? Z, Topi???? RZ, Dodig S. Calcium and magnesium in exhaled breath condensate of children with endogenous and exogenous airway acidification. J Asthma 2011; 48(7): 667-73. http://dx.doi.org/10.3109/02770903.2011.599907
Loesche WJ, Kazor C. Microbiology and treatment of halitosis. Periodontol 2000 2002; 28: 256-79. http://dx.doi.org/10.1034/j.1600-0757.2002.280111.x
Morisco F, Aprea E, Lembo V, et al. Rapid "breath-print" of liver cirrhosis by proton transfer reaction time-of-flight mass spectrometry. A pilot study. PLoS One 2013; 8(4): e59658. http://dx.doi.org/10.1371/journal.pone.0059658
Fierbinteanu-Braticevici C, Plesca DA, Tribus L, Panaitescu E, Braticevici B. The role of ????????C-methacetin breath test for the non-invasive evaluation of nonalcoholic fatty liver disease. J Gastrointestin Liver Dis 2013; 22(2): 149-56.
Bajtarevic A, Ager C, Pienz M, et al. Noninvasive detection of lung cancer by analysis of exhaled breath. BMC Cancer 2009; 9: 348. http://dx.doi.org/10.1186/1471-2407-9-348
Taivans I, Bukovskis M, Strazda G, Jurka N. Breath testing as a method for detecting lung cancer. Expert Rev Anticancer Ther 2013.
[Epub ahead of print] http://dx.doi.org/10.1586/14737140.2014.866044
Chan HP, Lewis C, Thomas PS. Exhaled breath analysis: novel approach for early detection of lung cancer. Lung Cancer 2009; 63(2): 164-8. http://dx.doi.org/10.1016/j.lungcan.2008.05.020
Mazzone PJ. Analysis of volatile organic compounds in the exhaled breath for the diagnosis of lung cancer. J Thorac Oncol 2008; 3(7): 774-80. http://dx.doi.org/10.1097/JTO.0b013e31817c7439
Phillips M, Cataneo RN, Cummin AR, et al. Detection of lung cancer with volatile markers in the breath. Chest 2003; 123(6): 2115-23. http://dx.doi.org/10.1378/chest.123.6.2115
Phillips M, Gleeson K, Hughes JM, et al. Volatile organic compounds in breath as markers of lung cancer: a crosssectional study. Lancet 1999; 353(9168): 1930-3. http://dx.doi.org/10.1016/S0140-6736(98)07552-7
Liu CY, Wang CH, Chen TC, Lin HC, Yu CT, Kuo HP. Increased level of exhaled nitric oxide and up-regulation of inducible nitric oxide synthase in patients with primary lung cancer. Br J Cancer 1998; 78(4): 534-41. http://dx.doi.org/10.1038/bjc.1998.528
Ligor M, Ligor T, Bajtarevic A, et al. Determination of volatile organic compounds in exhaled breath of patients with lung cancer using solid phase microextraction and gas chromatography mass spectrometry. Clin Chem Lab Med 2009; 47(5): 550-60. http://dx.doi.org/10.1515/CCLM.2009.133
Chen X, Xu F, Wang Y, et al. A study of the volatile organic compounds exhaled by lung cancer cells in vitro for breath diagnosis. Cancer 2007; 110(4): 835-44. http://dx.doi.org/10.1002/cncr.22844
Grabowska-Polanowska B, Faber J, Skowron M, et al. Detection of potential chronic kidney disease markers in breath using gas chromatography with mass-spectral detection coupled with thermal desorption method. J Chromatogr A 2013; 1301: 179-89. http://dx.doi.org/10.1016/j.chroma.2013.05.012
Goerl T, Kischkel S, Sawacki A, Fuchs P, Miekisch W, Schubert JK. Volatile breath biomarkers for patient monitoring during haemodialysis. J Breath Res 2013; 7(1): 017116. http://dx.doi.org/10.1088/1752-7155/7/1/017116
Dye C, Williams BG, Espinal MA, Raviglione MC. Erasing the world's slow stain: strategies to beat multidrug-resistant tuberculosis. Science 2002; 295(5562): 2042-2046. http://dx.doi.org/10.1126/science.1063814
Tomioka H, Namba K. Development of antituberculous drugs: current status and future prospects. Kekkaku 2006; 81(12): 753-774.
Global tuberculosis report 2013, World health Organization.
[Cited 2014 Feb 27]: Available from http://www.who.int/tb/ publication/global_report
Davies PD. Drug-resistant tuberculosis. J R Soc Med 2001; 94(6): 261-3.
Tisdall PA, Roberts GD, Anhalt JP. Identification of clinical isolates of mycobacteria with gas-liquid chromatography alone. J Clin Microbiol 1979; 10(4): 506-14.
Tisdall PA, DeYoung DR, Roberts GD, Anhalt JP. Identification of clinical isolates of mycobacteria with gasliquid chromatography: a 10-month follow-up study. J Clin Microbiol 1982; 16(2): 400-2.
Zhang Y, Zhuang Y, Liu Z, Ruan J. Identification of twentyeight species mycobacteria with their cellular fatty acids by capillary gas chromatography. Wei Sheng Wu Xue Bao 1991; 31(3): 187-97.
Parez JJ, Fauville-Dufaux M, Dossogne JL, de Hoffmann E, Pouthier F. Faster identification of mycobacteria using gas liquid and thin layer chromatography. Eur J Clin Microbiol Infect Dis. 1994 Sep; 13(9): 717-25. http://dx.doi.org/10.1007/BF02276054
Phillips M, Cataneo RN, Condos R, et al. Volatile biomarkers of pulmonary tuberculosis in the breath. Tuberculosis (Edinb) 2007; 87(1): 44-52. http://dx.doi.org/10.1016/j.tube.2006.03.004
Wang CH, Liu CY, Lin HC, Yu CT, Chung KF, Kuo HP. Increased exhaled nitric oxide in active pulmonary tuberculosis due to inducible NO synthase upregulation in alveolar macrophages. Eur Respir J 1998; 11(4): 809-15. http://dx.doi.org/10.1183/09031936.98.11040809
Phillips M, Cataneo RN, Greenberg J, Gunawardena R, Naidu A, Rahbari-Oskoui F. Effect of age on the breath methylated alkane contour, a display of apparent new markers of oxidative stress. J Lab Clin Med 2000; 136(3): 243-9. http://dx.doi.org/10.1067/mlc.2000.108943
Kolk AH, van Berkel JJ, Claassens MM, et al. Breath analysis as a potential diagnostic tool for tuberculosis. Int J Tuberc Lung Dis 2012; 16(6): 777-82.
Jassal MS, Nedeltchev GG, Lee JH, et al. 13[C]-urea breath test as a novel point-of-care biomarker for tuberculosis treatment and diagnosis. PLoS One 2010; 5(8): e12451. http://dx.doi.org/10.1371/journal.pone.0012451
Maiga M, Abaza A, Bishai WR. Current tuberculosis diagnostic tools & role of urease breath test. Indian J Med Res 2012; 135(5): 731-736.
Lundberg JO, Farkas-Szallasi T, Weitzberg E, et al. High nitric oxide production in human paranasal sinuses. Nat Med 1995; 1(4): 370-3. http://dx.doi.org/10.1038/nm0495-370
Turner PJ, Maggs JR, Foreman JC. Induction by inhibitors of nitric oxide synthase of hyperresponsiveness in the human nasal airway. Br J Pharmacol 2000; 131(2): 363-9. http://dx.doi.org/10.1038/sj.bjp.0703561
Kharitonov SA, Wells AU, O'Connor BJ, et al. Elevated levels of exhaled nitric oxide in bronchiectasis. Am J Respir Crit Care Med 1995; 151(6): 1889-93. http://dx.doi.org/10.1164/ajrccm.151.6.7767536
Tracey WR, Xue C, Klinghofer V, et al. Immunochemical detection of inducible NO synthase in human lung. Am J Physiol 1994; 266(6 Pt 1): L722-7.
Loukides S, Kharitonov S, Wodehouse T, Cole PJ, Barnes PJ. Effect of arginine on mucociliary function in primary ciliary dyskinesia. Lancet 1998; 352(9125): 371-2. http://dx.doi.org/10.1016/S0140-6736(05)60471-0
Karadag B, James AJ, Gültekin E, Wilson NM, Bush A. Nasal and lower airway level of nitric oxide in children with primary ciliary dyskinesia. Eur Respir J 1999; 13(6): 1402-5. http://dx.doi.org/10.1183/09031936.99.13614069
Kharitonov SA, Cailes JB, Black CM, du Bois RM, Barnes PJ. Decreased nitric oxide in the exhaled air of patients with systemic sclerosis with pulmonary hypertension. Thorax 1997; 52(12): 1051-5. http://dx.doi.org/10.1136/thx.52.12.1051
Rolla G, Colagrande P, Scappaticci E, et al. Exhaled nitric oxide in systemic sclerosis: relationships with lung involvement and pulmonary hypertension. J Rheumatol 2000; 27(7): 1693-8.
Saleh D, Barnes PJ, Giaid A. Increased production of the potent oxidant peroxynitrite in the lungs of patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 1997; 155(5): 1763-9. http://dx.doi.org/10.1164/ajrccm.155.5.9154889
Paredi P, Kharitonov SA, Loukides S, Pantelidis P, du Bois RM, Barnes PJ. Exhaled nitric oxide is increased in active fibrosing alveolitis. Chest 1999; 115(5): 1352-6. http://dx.doi.org/10.1378/chest.115.5.1352
Moodley YP, Chetty R, Lalloo UG. Nitric oxide levels in exhaled air and inducible nitric oxide synthase immunolocalization in pulmonary sarcoidosis. Eur Respir J 1999; 14(4): 822-7. http://dx.doi.org/10.1034/j.1399-3003.1999.14d17.x
O'Donnell DM, Moynihan J, Finlay GA, et al. Exhaled nitric oxide and bronchoalveolar lavage nitrite/nitrate in active pulmonary sarcoidosis. Am J Respir Crit Care Med 1997; 156(6): 1892-6. http://dx.doi.org/10.1164/ajrccm.156.6.9705013
Forrest IA, Small T, Corris PA. Effect of nebulized epoprostenol (prostacyclin) on exhaled nitric oxide in patients with pulmonary hypertension due to congenital heart disease and in normal controls. Clin Sci (Lond) 1999; 97(1): 99-102. http://dx.doi.org/10.1042/CS19990006
Adisesh LA, Kharitonov SA, Yates DH, Snashell DC, Newman-Taylor AJ, Barnes PJ. Exhaled and nasal nitric oxide is increased in laboratory animal allergy. Clin Exp Allergy 1998; 28(7): 876-80. http://dx.doi.org/10.1046/j.1365-2222.1998.00332.x
van Amsterdam JG, Nierkens S, Vos SG, Opperhuizen A, van Loveren H, Steerenberg PA. Exhaled nitric oxide: a novel biomarker of adverse respiratory health effects in epidemiological studies. Arch Environ Health 2000; 55(6): 418-23. http://dx.doi.org/10.1080/00039890009604040
Lund MB, Oksne PI, Hamre R, Kongerud J. Increased nitric oxide in exhaled air: an early marker of asthma in nonsmoking aluminium potroom workers? Occup Environ Med 2000; 57(4): 274-8. http://dx.doi.org/10.1136/oem.57.4.274
Von Essen SG, Scheppers LA, Robbins RA, Donham KJ. Respiratory tract inflammation in swine confinement workers studied using induced sputum and exhaled nitric oxide. J Toxicol Clin Toxicol 1998; 36(6): 557-65. http://dx.doi.org/10.3109/15563659809028049
Haubitz M, Busch T, Gerlach M, et al. Exhaled nitric oxide in patients with Wegener's granulomatosis. Eur Respir J 1999; 14(1): 113-7. http://dx.doi.org/10.1034/j.1399-3003.1999.14a19.x
Kharitonov SA, Yates D, Barnes PJ. Increased nitric oxide in exhaled air of normal human subjects with upper respiratory tract infections. Eur Respir J 1995; 8(2): 295-7. http://dx.doi.org/10.1183/09031936.95.08020295
Ferguson EA, Eccles R. Changes in nasal nitric oxide concentration associated with symptoms of common cold and treatment with a topical nasal decongestant. Acta Otolaryngol 1997; 117(4): 614-7. http://dx.doi.org/10.3109/00016489709113447
Murphy AW, Platts-Mills TA, Lobo M, Hayden F. Respiratory nitric oxide levels in experimental human influenza. Chest 1998; 114(2): 452-6. http://dx.doi.org/10.1378/chest.114.2.452
de Gouw HW, Grunberg K, Schot R, Kroes AC, Dick EC, Sterk PJ. Relationship between exhaled nitric oxide and airway hyperresponsiveness following experimental rhinovirus infection in asthmatic subjects. Eur Respir J 1998; 11: 126–132. http://dx.doi.org/10.1183/09031936.98.11010126
Liu F, Li W, Pauluhn J, Trübel H, Wang C. Rat models of acute lung injury: exhaled nitric oxide as a sensitive, noninvasive real-time biomarker of prognosis and efficacy of intervention. Toxicology 2013; 310: 104-14. http://dx.doi.org/10.1016/j.tox.2013.05.016
Studer SM, Orens JB, Rosas I, et al. Patterns and significance of exhaled-breath biomarkers in lung transplant recipients with acute allograft rejection. J Heart Lung Transplant 2001; 20(11): 1158-66. http://dx.doi.org/10.1016/S1053-2498(01)00343-6
Fisher AJ, Gabbay E, Small T, Doig S, Dark JH, Corris PA. Cross sectional study of exhaled nitric oxide levels following lung transplantation. Thorax 1998; 53(6): 454-8. http://dx.doi.org/10.1136/thx.53.6.454
Miekisch W, Schubert JK, Noeldge-Schomburg GF. Diagnostic potential of breath analysis: focus on volatile organic compounds. Clin Chim Acta 2004; 347(1-2): 25-39. http://dx.doi.org/10.1016/j.cccn.2004.04.023
Holden WE, Wilkins JP, Harris M, Milczuk HA, Giraud GD. Temperature conditioning of nasal air: effects of vasoactive agents and involvement of nitric oxide. J Appl Physiol (1985) 1999; 87(4): 1260-5.
Gilbert IA, Fouke JM, McFadden ER Jr. Heat and water flux in the intrathoracic airways and exercise-induced asthma. J Appl Physiol (1985) 1987; 63(4): 1681-91.
Agarkov FT, Agarkova SV. The temperature of exhaled air and the conditioning function of the respiratory apparatus in healthy miners and those with pneumoconiosis. Gig Tr Prof Zabol 1970; 14(2): 31-4.
Ojoo JC, Mulrennan SA, Kastelik JA, Morice AH, Redington AE. Exhaled breath condensate pH and exhaled nitric oxide in allergic asthma and in cystic fibrosis. Thorax 2005; 60(1): 22-6. http://dx.doi.org/10.1136/thx.2003.017327
Brunetti L, Francavilla R, Tesse R, et al. Exhaled breath condensate pH measurement in children with asthma, allergic rhinitis and atopic dermatitis. Pediatr Allergy Immunol 2006; 17(6): 422-7. http://dx.doi.org/10.1111/j.1399-3038.2006.00426.x
Szili B, Bikov A, Kollai M, Horváth I. The pH of the exhaled breath condensate: new method for investigation of inflammatory airway diseases. Orv Hetil 2007; 148(26): 1217- 24. http://dx.doi.org/10.1556/OH.2007.27986
Antus B, Barta I, Kullmann T, et al. Assessment of exhaled breath condensate pH in exacerbations of asthma and chronic obstructive pulmonary disease: A longitudinal study. Am J Respir Crit Care Med 2010; 182(12): 1492-7. http://dx.doi.org/10.1164/rccm.201003-0451OC
Banovi???? S, Navratil M, Vla????i???? Z, Topi???? RZ, Dodig S. Calcium and magnesium in exhaled breath condensate of children with endogenous and exogenous airway acidification. J Asthma 2011; 48(7): 667-73. http://dx.doi.org/10.3109/02770903.2011.599907
Ma W, Liu X and Pawliszyn J. Analysis of human breath with micro extraction techniques and continuous monitoring of carbon dioxide concentration. Analytical and Bioanalytical Chemistry 2006; 385: 1398-1408. http://dx.doi.org/10.1007/s00216-006-0595-y
Buszewski B, Kesy M, Ligor T, Amann A. Human exhaled air analytics: biomarkers of diseases. Biomed Chromatogr 2007; 21(6): 553-66. http://dx.doi.org/10.1002/bmc.835
Di Francesco F, Fuoco R, Trivella MG, Ceccarini A. Breath analysis: trends in techniques and clinical applications. Microchemical Journal 2005; 79: 405-410. http://dx.doi.org/10.1016/j.microc.2004.10.008
Libardoni M, Stevens PT, Waite JH, Sacks R. Analysis of human breath samples with a multi-bed sorption trap and comprehensive two-dimensional gas chromatography (GCxGC). J Chromatogr B Analyt Technol Biomed Life Sci 2006; 842(1): 13-21. http://dx.doi.org/10.1016/j.jchromb.2006.05.008
Shaji J, Jadhav D. Breath biomarker for clinical diagnosis and different analysis technique. RJPBCS 2010; 1(3): 639-53.
Abbott SM, Elder JB, Ípan!l P, Smith D. Quantification of acetonitrile in exhaled breath and urinary headspace using selected ion flow tube mass spectrometry. International Journal of Mass Spectrometry 2003; 228: 655-665. http://dx.doi.org/10.1016/S1387-3806(03)00212-4
Amann A, Span????l P, Smith D. Breath analysis: the approach towards clinical applications. Mini Rev Med Chem 2007; 7(2): 115-29. http://dx.doi.org/10.2174/138955707779802606
Spinhirne JP, Koziel JA, Chirase NK. A device for noninvasive on-site sampling of cattle breath with solid-phase microextraction. Biosystems Engineering 2003; 84(2): 239– 246. http://dx.doi.org/10.1016/S1537-5110(02)00240-4
Mukhopadhyay R. Don't waste your breath. Researchers are developing breath tests for diagnosing diseases, but how well do they work? Anal Chem 2004; 76(15): 273A-276A.
Manolis A. The diagnostic potential of breath analysis. Clin Chem 1983; 29(1): 5-15.
Cao W, Duan Y. Breath analysis: potential for clinical diagnosis and exposure assessment. Clin Chem 2006; 52(5): 800-11. http://dx.doi.org/10.1373/clinchem.2005.063545
Fens N, van der Schee MP, Brinkman P, Sterk PJ. Exhaled breath analysis by electronic nose in airways disease. Established issues and key questions. Clin Exp Allergy 2013; 43(7): 705-15. http://dx.doi.org/10.1111/cea.12052
Dragonieri S, Schot R, Mertens BJ, et al. An electronic nose in the discrimination of patients with asthma and controls. J Allergy Clin Immunol 2007; 120(4): 856-62. http://dx.doi.org/10.1016/j.jaci.2007.05.043
Valera JL, Togores B, Cosio BG. Use of the electronic nose for diagnosing respiratory diseases. Arch Bronconeumol 2012; 48(6): 187-8. http://dx.doi.org/10.1016/j.arbr.2012.03.002
Gardner JW, Shin HW, Author Vitae, Hines EL. An electronic nose system to diagnose illness. Sensors and Actuators B: Chemical 2000; 70(1-3): 19-24. http://dx.doi.org/10.1016/S0925-4005(00)00548-7
Chen S, Wang Y, Choi S. Applications and technology of electronic nose for clinical diagnosis. Open Journal of Applied Biosensor 2013; 2: 39-50. http://dx.doi.org/10.4236/ojab.2013.22005
