Expiratory flow rate, breath hold and anatomic dead space influence electronic nose ability to detect lung cancer

BMC Pulmonary Medicine

Ildiko Horvath³  Gyorgy Losonczy³  David Laszlo Tarnoki¹  Adam Domonkos Tarnoki¹  Zoltan Sutto³  Gabriella Zsamboki³  Laszlo Kunos³  Beata Zita Korosi³  Marton Hernadi²  Andras Bikov³ 

[1] Department of Radiology and Oncotherapy, Semmelweis University, 78/a Ulloi street, Budapest 1082, Hungary;Department of Pediatrics, Heim Pal Children’s Hospital, 86 Ulloi street, Budapest 1082, Hungary;Department of Pulmonology, Semmelweis University, 1/C Dios arok, Budapest 1125, Hungary

关键词: Volatile organic compounds;    Lung cancer;    Electronic nose;    Breath test;    Biomarkers;   

Others  :  1090765
DOI  :  10.1186/1471-2466-14-202

 received in 2013-10-12, accepted in 2014-12-11,  发布年份 2014

【 摘 要 】

Background

Electronic noses are composites of nanosensor arrays. Numerous studies showed their potential to detect lung cancer from breath samples by analysing exhaled volatile compound pattern (“breathprint”). Expiratory flow rate, breath hold and inclusion of anatomic dead space may influence the exhaled levels of some volatile compounds; however it has not been fully addressed how these factors affect electronic nose data. Therefore, the aim of the study was to investigate these effects.

Methods

37 healthy subjects (44 ± 14 years) and 27 patients with lung cancer (60 ± 10 years) participated in the study. After deep inhalation through a volatile organic compound filter, subjects exhaled at two different flow rates (50 ml/sec and 75 ml/sec) into Teflon-coated bags. The effect of breath hold was analysed after 10 seconds of deep inhalation. We also studied the effect of anatomic dead space by excluding this fraction and comparing alveolar air to mixed (alveolar + anatomic dead space) air samples. Exhaled air samples were processed with Cyranose 320 electronic nose.

Results

Expiratory flow rate, breath hold and the inclusion of anatomic dead space significantly altered “breathprints” in healthy individuals (p < 0.05), but not in lung cancer (p > 0.05). These factors also influenced the discrimination ability of the electronic nose to detect lung cancer significantly.

Conclusions

We have shown that expiratory flow, breath hold and dead space influence exhaled volatile compound pattern assessed with electronic nose. These findings suggest critical methodological recommendations to standardise sample collections for electronic nose measurements.

【 授权许可】

   
2014 Bikov et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]Pauling L, Robinson AB, Teranishi R, Cary P: Quantitative analysis of urine vapor and breath by gas–liquid partition chromatography. Proc Natl Acad Sci U S A 1971, 68:2374-2376.
• [2]Phillips M, Gleeson K, Hughes JM, Greenberg J, Cataneo RN, Baker L, McVay WP: Volatile organic compounds in breath as markers of lung cancer: a cross-sectional study. Lancet 1999, 353:1930-1933.
• [3]Ulanowska A, Kowalkowski T, Trawinska E, Buszewski B: The application of statistical methods using VOCs to identify patients with lung cancer. J Breath Res 2011, 5:046008.
• [4]Bajtarevic A, Ager C, Pienz M, Klieber M, Schwarz K, Ligor M, Ligor T, Filipiak W, Denz H, Fiegl M, Hilbe W, Weiss W, Lukas P, Jamnig H, Hackl M, Haidenberger A, Buszewski B, Miekisch W, Schubert J, Amann A: Noninvasive detection of lung cancer by analysis of exhaled breath. BMC Cancer 2009, 9:348. BioMed Central Full Text
• [5]D’Amico A, Pennazza G, Santonico M, Martinelli E, Roscioni C, Galluccio G, Paolesse R, Di Natale C: An investigation on electronic nose diagnosis of lung cancer. Lung Cancer 2010, 68:170-176.
• [6]Dragonieri S, Annema JT, Schot R, van der Schee MP, Spanevello A, Carratu P, Resta O, Rabe KF, Sterk PJ: An electronic nose in the discrimination of patients with non-small cell lung cancer and COPD. Lung Cancer 2009, 64:166-170.
• [7]Machado RF, Laskowski D, Deffenderfer O, Burch T, Zheng S, Mazzone PJ, Mekhail T, Jennings C, Stoller JK, Pyle J, Duncan J, Dweik RA, Erzurum SC: Detection of lung cancer by sensor array analyses of exhaled breath. Am J Respir Crit Care Med 2005, 171:1286-1291.
• [8]Peng G, Tisch U, Adams O, Hakim M, Shehada N, Broza YY, Billan S, Abdah-Bortnyak R, Kuten A, Haick H: Diagnosing lung cancer in exhaled breath using gold nanoparticles. Nat Nanotechnol 2009, 4:669-673.
• [9]Hubers AJ, Brinkman P, Boksem RJ, Rhodius RJ, Witte BI, Zwinderman AH, Heideman DA, Duin S, Koning R, Steenbergen RD, Snijders PJ, Smit EF, Sterk PJ, Thunnissen E: Combined sputum hypermethylation and eNose analysis for lung cancer diagnosis. J Clin Pathol 2014, 67:707-711.
• [10]Dragonieri S, van der Schee MP, Massaro T, Schiavulli N, Brinkman P, Pinca A, Carratu P, Spanevello A, Resta O, Musti M, Sterk PJ: An electronic nose distinguishes exhaled breath of patients with Malignant Pleural Mesothelioma from controls. Lung Cancer 2012, 75:326-331.
• [11]Chapman EA, Thomas PS, Stone E, Lewis C, Yates DH: A breath test for malignant mesothelioma using an electronic nose. Eur Respir J 2012, 40:448-454.
• [12]Fens N, Roldaan AC, van der Schee MP, Boksem RJ, Zwinderman AH, Bel EH, Sterk PJ: External validation of exhaled breath profiling using an electronic nose in the discrimination of asthma with fixed airways obstruction and chronic obstructive pulmonary disease. Clin Exp Allergy 2011, 41:1371-1378.
• [13]Fens N, Zwinderman AH, van der Schee MP, de Nijs SB, Dijkers E, Roldaan AC, Cheung D, Bel EH, Sterk PJ: Exhaled breath profiling enables discrimination of chronic obstructive pulmonary disease and asthma. Am J Respir Crit Care Med 2009, 180:1076-1082.
• [14]Dragonieri S, Schot R, Mertens BJ, Le Cessie S, Gauw SA, Spanevello A, Resta O, Willard NP, Vink TJ, Rabe KF, Bel EH, Sterk PJ: An electronic nose in the discrimination of patients with asthma and controls. J Allergy Clin Immunol 2007, 120:856-862.
• [15]Dragonieri S, Brinkman P, Mouw E, Zwinderman AH, Carratu P, Resta O, Sterk PJ, Jonkers RE: An electronic nose discriminates exhaled breath of patients with untreated pulmonary sarcoidosis from controls. Respir Med 2013, 107:1073-1078.
• [16]Benedek P, Lazar Z, Bikov A, Kunos L, Katona G, Horvath I: Exhaled biomarker pattern is altered in children with obstructive sleep apnoea syndrome. Int J Pediatr Otorhinolaryngol 2013, 77:1244-1247.
• [17]Greulich T, Hattesohl A, Grabisch A, Koepke J, Schmid S, Noeske S, Nell C, Wencker M, Jorres RA, Vogelmeier CF, Kohler U, Koczulla AR: Detection of obstructive sleep apnoea by an electronic nose. Eur Respir J 2013, 42:145-155.
• [18]Kunos L, Bikov A, Lazar Z, Korosi BZ, Benedek P, Losonczy G, Horvath I: Evening and morning exhaled volatile compound patterns are different in obstructive sleep apnoea assessed with electronic nose. Sleep Breath 2014. in press
• [19]Bos LD, de Jong MD, Sterk PJ, Schultz MJ: How integration of global omics-data could help preparing for pandemics - a scent of influenza. Front Genet 2014, 5:80.
• [20]Chambers ST, Scott-Thomas A, Epton M: Developments in novel breath tests for bacterial and fungal pulmonary infection. Curr Opin Pulm Med 2012, 18:228-232.
• [21]Kovacs D, Bikov A, Losonczy G, Murakozy G, Horvath I: Follow up of lung transplant recipients using an electronic nose. J Breath Res 2013, 7:017117.
• [22]Henschke CI, Yankelevitz DF, Libby DM, Pasmantier MW, Smith JP, Miettinen OS: Survival of patients with stage I lung cancer detected on CT screening. N Engl J Med 2006, 355:1763-1771.
• [23]Horvath I, Lazar Z, Gyulai N, Kollai M, Losonczy G: Exhaled biomarkers in lung cancer. Eur Respir J 2009, 34:261-275.
• [24]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, 43:705-715.
• [25]van de Kant KD, van der Sande LJ, Jobsis Q, van Schayck OC, Dompeling E: Clinical use of exhaled volatile organic compounds in pulmonary diseases: a systematic review. Respir Res 2012, 13:117. BioMed Central Full Text
• [26]Doleman BJ, Lewis NS: Comparison of odor detection thresholds and odor discriminablities of a conducting polymer composite electronic nose versus mammalian olfaction. Sensor Actuator B Chem 2001, 72:41-50.
• [27]Miekisch W, Kischkel S, Sawacki A, Liebau T, Mieth M, Schubert JK: Impact of sampling procedures on the results of breath analysis. J Breath Res 2008, 2:026007.
• [28]Buszewski B, Ulanowska A, Kowalkowski T, Cieslinski K: Investigation of lung cancer biomarkers by hyphenated separation techniques and chemometrics. Clin Chem Lab Med 2012, 50:573-581.
• [29]Steeghs MM, Cristescu SM, Munnik P, Zanen P, Harren FJ: An off-line breath sampling and analysis method suitable for large screening studies. Physiol Meas 2007, 28:503-514.
• [30]Ligor M, Ligor T, Bajtarevic A, Ager C, Pienz M, Klieber M, Denz H, Fiegl M, Hilbe W, Weiss W, Lukas P, Jamnig H, Hackl M, Buszewski B, Miekisch W, Schubert J, Amann A: 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, 47:550-560.
• [31]Kushch I, Schwarz K, Schwentner L, Baumann B, Dzien A, Schmid A, Unterkofler K, Gastl G, Spanel P, Smith D, Amann A: Compounds enhanced in a mass spectrometric profile of smokers’ exhaled breath versus non-smokers as determined in a pilot study using PTR-MS. J Breath Res 2008, 2:026002.
• [32]Filipiak W, Ruzsanyi V, Mochalski P, Filipiak A, Bajtarevic A, Ager C, Denz H, Hilbe W, Jamnig H, Hackl M, Dzien A, Amann A: Dependence of exhaled breath composition on exogenous factors, smoking habits and exposure to air pollutants. J Breath Res 2012, 6:036008.
• [33]Thekedar B, Oeh U, Szymczak W, Hoeschen C, Paretzke HG: Influences of mixed expiratory sampling parameters on exhaled volatile organic compound concentrations. J Breath Res 2011, 5:016001.
• [34]Lewis NS: Comparisons between mammalian and artificial olfaction based on arrays of carbon black-polymer composite vapor detectors. Acc Chem Res 2004, 37:663-672.
• [35]van der Schee MP, Fens N, Brinkman P, Bos LD, Angelo MD, Nijsen TM, Raabe R, Knobel HH, Vink TJ, Sterk PJ: Effect of transportation and storage using sorbent tubes of exhaled breath samples on diagnostic accuracy of electronic nose analysis. J Breath Res 2013, 7:016002.
• [36]Zetterquist W, Marteus H, Johannesson M, Nordval SL, Ihre E, Lundberg JO, Alving K: Exhaled carbon monoxide is not elevated in patients with asthma or cystic fibrosis. Eur Respir J 2002, 20:92-99.
• [37]Larstad MA, Toren K, Bake B, Olin AC: Determination of ethane, pentane and isoprene in exhaled air–effects of breath-holding, flow rate and purified air. Acta Physiol (Oxf) 2007, 189:87-98.
• [38]Bikov A, Paschalaki K, Logan-Sinclair R, Horvath I, Kharitonov SA, Barnes PJ, Usmani OS, Paredi P: Standardised exhaled breath collection for the measurement of exhaled volatile organic compounds by proton transfer reaction mass spectrometry. BMC Pulm Med 2013, 13:43. BioMed Central Full Text
• [39]Bikov A, Lazar Z, Schandl K, Antus BM, Losonczy G, Horvath I: Exercise changes volatiles in exhaled breath assessed by an electronic nose. Acta Physiol Hung 2011, 98:321-328.
• [40]Bikov A, Pako J, Kovacs D, Tamasi L, Lazar Z, Rigo J, Losonczy G, Horvath I: Exhaled breath volatile alterations in pregnancy assessed with electronic nose. Biomarkers 2011, 16:476-484.
• [41]De Maesschalck R, Jouan-Rimbaud D, Massart DL: The Mahalanobis distance. Chemometr Intell Lab Syst 2000, 50:1-18.
• [42]Faul F, Erdfelder E, Buchner A, Lang AG: Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses. Behav Res Methods 2009, 41:1149-1160.
• [43]Silkoff PE, McClean PA, Slutsky AS, Furlott HG, Hoffstein E, Wakita S, Chapman KR, Szalai JP, Zamel N: Marked flow-dependence of exhaled nitric oxide using a new technique to exclude nasal nitric oxide. Am J Respir Crit Care Med 1997, 155:260-267.
• [44]Boshier PR, Priest OH, Hanna GB, Marczin N: Influence of respiratory variables on the on-line detection of exhaled trace gases by PTR-MS. Thorax 2011, 66:919-920.
• [45]West RJ: The effect of duration of breath-holding on expired air carbon monoxide concentration in cigarette smokers. Addict Behav 1984, 9:307-309.
• [46]Paredi P, Loukides S, Ward S, Cramer D, Spicer M, Kharitonov SA, Barnes PJ: Exhalation flow and pressure-controlled reservoir collection of exhaled nitric oxide for remote and delayed analysis. Thorax 1998, 53:775-779.
• [47]Schubert JK, Spittler KH, Braun G, Geiger K, Guttmann J: CO(2)-controlled sampling of alveolar gas in mechanically ventilated patients. J Appl Physiol 2001, 90:486-492.
• [48]Gromski PS, Correa E, Vaughan AA, Wedge DC, Turner ML, Goodacre R: A comparison of different chemometrics approaches for the robust classification of electronic nose data. Anal Bioanal Chem 2014, 406:7581-7590.
• [49]Cheng ZJ, Warwick G, Yates DH, Thomas PS: An electronic nose in the discrimination of breath from smokers and non-smokers: a model for toxin exposure. J Breath Res 2009, 3:036003.
• [50]Lazar Z, Fens N, van der Maten J, van der Schee MP, Wagener AH, de Nijs SB, Dijkers E, Sterk PJ: Electronic nose breathprints are independent of acute changes in airway caliber in asthma. Sensors (Basel) 2010, 10:9127-9138.