Exhaled breath profiling enables discrimination of chronic obstructive pulmonary disease and asthma.

RATIONALE Chronic obstructive pulmonary disease (COPD) and asthma can exhibit overlapping clinical features. Exhaled air contains volatile organic compounds (VOCs) that may qualify as noninvasive biomarkers. VOC profiles can be assessed using integrative analysis by electronic nose, resulting in exhaled molecular fingerprints (breathprints). OBJECTIVES We hypothesized that breathprints by electronic nose can discriminate patients with COPD and asthma. METHODS Ninety subjects participated in a cross-sectional study: 30 patients with COPD (age, 61.6 +/- 9.3 years; FEV(1), 1.72 +/- 0.69 L), 20 patients with asthma (age, 35.4 +/- 15.1 years; FEV(1) 3.32 +/- 0.86 L), 20 nonsmoking control subjects (age, 56.7 +/- 9.3 years; FEV(1), 3.44 +/- 0.76 L), and 20 smoking control subjects (age, 56.1 +/- 5.9 years; FEV(1), 3.58 +/- 0.78). After 5 minutes of tidal breathing through an inspiratory VOC filter, an expiratory vital capacity was collected in a Tedlar bag and sampled by electronic nose. Breathprints were analyzed by discriminant analysis on principal component reduction resulting in cross-validated accuracy values (accuracy). Repeatability and reproducibility were assessed by measuring samples in duplicate by two devices. MEASUREMENTS AND MAIN RESULTS Breathprints from patients with asthma were separated from patients with COPD (accuracy 96%; P < 0.001), from nonsmoking control subjects (accuracy, 95%; P < 0.001), and from smoking control subjects (accuracy, 92.5%; P < 0.001). Exhaled breath profiles of patients with COPD partially overlapped with those of asymptomatic smokers (accuracy, 66%; P = 0.006). Measurements were repeatable and reproducible. CONCLUSIONS Molecular profiling of exhaled air can distinguish patients with COPD and asthma and control subjects. Our data demonstrate a potential of electronic noses in the differential diagnosis of obstructive airway diseases and in the risk assessment in asymptomatic smokers. Clinical trial registered with www.trialregister.nl (NTR 1282).

[1]  E. Vittinghoff,et al.  Glycemic Effects of Postmenopausal Hormone Therapy: The Heart and Estrogen/progestin Replacement Study: A Randomized, Double-Blind, Placebo-Controlled Trial , 2003, Annals of Internal Medicine.

[2]  M. Friedrich,et al.  Scientists seek to sniff out diseases: electronic "noses" may someday be diagnostic tools. , 2009, JAMA.

[3]  E. Wouters,et al.  Chronic obstructive pulmonary disease • 5: Systemic effects of COPD , 2002, Thorax.

[4]  Peter J Sterk,et al.  An electronic nose in the discrimination of patients with asthma and controls. , 2007, The Journal of allergy and clinical immunology.

[5]  Bogusław Buszewski,et al.  Human exhaled air analytics: biomarkers of diseases. , 2007, Biomedical chromatography : BMC.

[6]  David Harel,et al.  On mappings between electronic noses , 2005 .

[7]  D. Jarvis,et al.  The European Community Respiratory Health Survey. , 1994, The European respiratory journal.

[8]  M. Dolhnikoff,et al.  Pathologic similarities and differences between asthma and chronic obstructive pulmonary disease , 2008, Current opinion in pulmonary medicine.

[9]  J. Austin,et al.  Detection of lung cancer using weighted digital analysis of breath biomarkers. , 2008, Clinica chimica acta; international journal of clinical chemistry.

[10]  Christian Gluud,et al.  Evidence based diagnostics , 2005, BMJ : British Medical Journal.

[11]  P. Barnes,et al.  Exhaled markers of pulmonary disease. , 2001, American journal of respiratory and critical care medicine.

[12]  Leroy Hood,et al.  Systems biology, proteomics, and the future of health care: toward predictive, preventative, and personalized medicine. , 2004, Journal of proteome research.

[13]  Károly Héberger,et al.  Metabolomics applied to exhaled breath condensate in childhood asthma. , 2007, American journal of respiratory and critical care medicine.

[14]  P. J. Barnes,et al.  Global strategy for asthma management and prevention: GINA executive summary , 2008, European Respiratory Journal.

[15]  V. Salomaa,et al.  The association of sensitive systemic inflammation markers with bronchial asthma. , 2002, Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology.

[16]  J. Hankinson,et al.  Guidelines for methacholine and exercise challenge testing-1999. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. , 2000, American journal of respiratory and critical care medicine.

[17]  E. Wouters,et al.  Development of accurate classification method based on the analysis of volatile organic compounds from human exhaled air. , 2008, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[18]  D. DeMeo,et al.  Molecular biomarkers for quantitative and discrete COPD phenotypes. , 2009, American journal of respiratory cell and molecular biology.

[19]  S. Guerra Overlap of asthma and chronic obstructive pulmonary disease , 2005, Current opinion in pulmonary medicine.

[20]  L. Corbetta,et al.  Differences in airway inflammation in patients with fixed airflow obstruction due to asthma or chronic obstructive pulmonary disease. , 2003, American journal of respiratory and critical care medicine.

[21]  D. Rennie,et al.  The STARD statement for reporting studies of diagnostic accuracy: explanation and elaboration. , 2003, Annals of internal medicine.

[22]  G. Anderson,et al.  Endotyping asthma: new insights into key pathogenic mechanisms in a complex, heterogeneous disease , 2008, The Lancet.

[23]  A. B. Robinson,et al.  Quantitative analysis of urine vapor and breath by gas-liquid partition chromatography. , 1971, Proceedings of the National Academy of Sciences of the United States of America.

[24]  W. MacNee,et al.  Epithelial permeability, inflammation, and oxidant stress in the air spaces of smokers. , 1999, American journal of respiratory and critical care medicine.

[25]  L. T. Tanoue Detection of Lung Cancer by Sensor Array Analyses of Exhaled Breath , 2007 .

[26]  Onofrio Resta,et al.  An electronic nose in the discrimination of patients with non-small cell lung cancer and COPD. , 2009, Lung cancer.

[27]  Zulfiqur Ali,et al.  Data analysis for electronic nose systems , 2006 .

[28]  M. Decramer,et al.  Asthma and COPD: differences and similarities , 2005, International journal of clinical practice.

[29]  P. Barnes,et al.  Elevation of exhaled ethane concentration in asthma. , 2000, American journal of respiratory and critical care medicine.

[30]  Mario Castro,et al.  Molecular phenotyping of severe asthma using pattern recognition of bronchoalveolar lavage-derived cytokines. , 2008, The Journal of allergy and clinical immunology.

[31]  E. M. Gaspar,et al.  Organic metabolites in exhaled human breath--a multivariate approach for identification of biomarkers in lung disorders. , 2009, Journal of chromatography. A.

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

[33]  N. Lewis Comparisons between mammalian and artificial olfaction based on arrays of carbon black-polymer composite vapor detectors. , 2004, Accounts of chemical research.

[34]  K. Prikk,et al.  Proteomics: is it an approach to understand the progression of chronic lung disorders? , 2004, Journal of proteome research.

[35]  J. Knottnerus,et al.  Assessment of the accuracy of diagnostic tests: the cross-sectional study. , 2003, Journal of clinical epidemiology.

[36]  R. Crameri The potential of proteomics and peptidomics for allergy and asthma research , 2005, Allergy.

[37]  J. Hankinson,et al.  Standardisation of spirometry , 2005, European Respiratory Journal.

[38]  P. Gibson,et al.  The overlap syndrome of asthma and COPD: what are its features and how important is it? , 2009, Thorax.

[39]  Philipp Lirk,et al.  Mass spectrometric profile of exhaled breath—field study by PTR-MS , 2005, Respiratory Physiology & Neurobiology.

[40]  Y. Higashimoto,et al.  Systemic inflammation in chronic obstructive pulmonary disease and asthma: Similarities and differences , 2007, Respirology.

[41]  Y. Tohda,et al.  Serum biomarkers as predictors of lung function decline in chronic obstructive pulmonary disease. , 2009, Respiratory medicine.