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American Journal of Respiratory and Critical Care Medicine Vol 172. pp. 1060-1061, (2005)
© 2005 American Thoracic Society


Correspondence

Can the Electronic Nose Really Sniff out Lung Cancer?

From the Authors:

As early as 1985, Gordon and colleagues identified discrete diagnostic compounds in the breath of lung cancer patients, and showed that lung cancer discrimination was possible in the absence of identification of the specific compounds (1). They selected 22 peaks from among 49 statistically different peaks on the gas chromatogram of the breath of patients with lung cancer, and used these to develop a statistical system for classifying breath volatile organic compound (VOC) profiles from subjects with lung cancer and control subjects. This provided the rationale for our investigation of a new, simpler technology, an electronic nose (Enose), for lung cancer detection. The Enose detects chemical vapors using a polymer composite sensor array, but does not perform chemical separation and identification of VOCs (2). Rather, the mixture of VOCs in breath is recorded as a pattern, and statistical pattern recognition analysis is used to determine if the pattern is distinctive between subject classes.

Only rough estimates of relative abundance of VOCs were available from previous studies. Thus, we performed gas chromatography/mass spectrometry analyses of breath, not to identify, but to quantitate VOCs. Our rigorous analytical approach used multicomponent gas standards for calibration curves and revealed that many VOCs are present in breath at ppb to ppm levels, a range easily detectable by the Enose (24). With this knowledge, our study aimed to answer the question: Can an Enose distinguish the complex and unique pattern of VOCs present in exhaled breath of lung cancer patients from that of individuals without lung cancer? The answer to this question is yes, and with high statistical confidence as shown by our study and a study by DiNatale and coworkers (5, 6).

We were careful to control for effects of age and smoking through inclusion of control subjects with disease and actively smoking healthy control subjects (5). Our discriminant analyses did not reveal clustering differences between current, former, and never-smokers (5). We controlled for effects of age through inclusion of control subjects with disease (COPD, {alpha}1-antitrypsin deficiency, and chronic beryllium disease) of similar age to patients with cancer. There was no difference in patterns detected between healthy control subjects and control subjects with disease, though their ages were different. Clearly, patients with COPD were a good match for the lung cancer group in regard to age and smoking, and did not display a high false-positive rate. All these factors indicate that age or tobacco smoking did not skew the findings.

Further studies are needed to determine if Enose breath analysis has a role in clinical practice, but the use of pattern recognition in development of clinically applicable technologies for disease detection is a concept at which we definitely should not turn up our nose.

Serpil C. Erzuruma, Timothy Burchb, Daniel Laskowskic, Peter J. Mazzonec, Tarek Mekhailc, Constance Jenningsc, James K. Stollerc, Roberto F. Machadoc, Jacqueline Pylec, Olivia Deffenderferd and Raed A. Dweike

a The Cleveland Clinic Foundation, Cleveland, Ohio
b Smiths Detection, Inc., Pasadena, California
c The Cleveland Clinic Foundation, Cleveland, Ohio
d Smiths Detection, Inc., Pasadena, California
e The Cleveland Clinic Foundation, Cleveland, Ohio

FOOTNOTES

Conflict of Interest Statement: S.C.E. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. T.B. is Director of Research and Development for Smiths Detection, Inc. which provided partial sponsorship for the study through donation of the chemical detectors used. D.L. owns Physiologic Measurement Systems L.L.C., and also is a paid consultant for the Aerocrine company. His company has not yet received any income this year. P.J.M. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. T.M. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. C.J. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. J.K.S. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. R.F.M. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. J.P. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. O.D. is an employee of Smiths Detection, which sponsored the study and loan of an instrument, the Cyranose 320. R.A.D. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

REFERENCES

  1. Gordon SM, Szidon JP, Krotoszynski BK, Gibbons RD, O'Neill HJ. Volatile organic compounds in exhaled air from patients with lung cancer. Clin Chem 1985;31:1278–1282.[Abstract/Free Full Text]
  2. Briglin SM, Freund MS, Tokumaru P, Lewis NS. Exploitation of spatiotemporal information and geometric optimization of signal/noise performance using arrays of carbon black-polymer composite vapor detectors. Sensors and Actuators B Chem 2002;82:54–74.[CrossRef]
  3. Groves WA, Achutan C. Laboratory and field evaluation of a SAW microsensor array for measuring perchloroethylene in breath. J Occup Environ Hyg 2004;1:779–788.[CrossRef][Medline]
  4. Ogawa S, Sugimoto I. Detecting odorous materials in water using quartz crystal microbalance sensors. Water Sci Technol 2002;45:201–206.
  5. Machado RF, Laskowski D, Deffenderfer O, Burch T, Zheng S, Mazzone PJ, Mekhail T, Jennings C, Stoller JK, Pyle J, et al. Detection of lung cancer by sensor array analyses of exhaled breath. Am J Respir Crit Care Med 2005;171:1286–1291.[Abstract/Free Full Text]
  6. Di Natale C, Macagnano A, Martinelli E, Paolesse R, D'Arcangelo G, Roscioni C, Finazzi-Agro A, D'Amico A. Lung cancer identification by the analysis of breath by means of an array of non-selective gas sensors. Biosens Bioelectron 2003;18:1209–1218.[CrossRef][Medline]




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Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 2005 American Thoracic Society