, Volume 195, Issue 2, pp 247–254 | Cite as

Volatile Organic Compounds in Exhaled Breath of Idiopathic Pulmonary Fibrosis for Discrimination from Healthy Subjects

  • Yu-ichi Yamada
  • Gen Yamada
  • Mitsuo Otsuka
  • Hirotaka Nishikiori
  • Kimiyuki Ikeda
  • Yasuaki Umeda
  • Hirofumi Ohnishi
  • Koji Kuronuma
  • Hirofumi Chiba
  • Jörg Ingo Baumbach
  • Hiroki Takahashi
Interstitial lung disease


Purpose Human breath analysis is proposed with increasing frequency as a useful tool in clinical application. We performed this study to find the characteristic volatile organic compounds (VOCs) in the exhaled breath of patients with idiopathic pulmonary fibrosis (IPF) for discrimination from healthy subjects. Methods VOCs in the exhaled breath of 40 IPF patients and 55 healthy controls were measured using a multi-capillary column and ion mobility spectrometer. The patients were examined by pulmonary function tests, blood gas analysis, and serum biomarkers of interstitial pneumonia. Results We detected 85 VOC peaks in the exhaled breath of IPF patients and controls. IPF patients showed 5 significant VOC peaks; p-cymene, acetoin, isoprene, ethylbenzene, and an unknown compound. The VOC peak of p-cymene was significantly lower (p < 0.001), while the VOC peaks of acetoin, isoprene, ethylbenzene, and the unknown compound were significantly higher (p < 0.001 for all) compared with the peaks of controls. Comparing VOC peaks with clinical parameters, negative correlations with VC (r =−0.393, p = 0.013), %VC (r =−0.569, p < 0.001), FVC (r = −0.440, p = 0.004), %FVC (r =−0.539, p < 0.001), DLco (r =−0.394, p = 0.018), and %DLco (r =−0.413, p = 0.008) and a positive correlation with KL-6 (r = 0.432, p = 0.005) were found for p-cymene. Conclusion We found characteristic 5 VOCs in the exhaled breath of IPF patients. Among them, the VOC peaks of p-cymene were related to the clinical parameters of IPF. These VOCs may be useful biomarkers of IPF.


Idiopathic pulmonary fibrosis Volatile organic compound Multi-capillary column Ion mobility spectrometer Exhaled breath 



The authors thank Mr. Yusuke Yonemura (Harada Corp, Osaka, Japan) for his technical supports. A part of the work on this paper (JIBB) has been supported by Deutsche Forschungsgemeinschaft (DFG) within the Collaborative Research Center (Sonderforschungsbereich) SFB 876 “Providing Information by Resource-Constrained Analysis”, project TB1 “Resource-Constrained Analysis of Spectrometry Data”.

Compliance with Ethical Standards

Conflict of interest

The authors have declared no conflicts of interest in connection with this article.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consent was obtained from all individual participants included in this study.

Supplementary material

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Supplementary material 1 (PPT 194 KB)
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Supplementary material 2 (PPT 194 KB)
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Supplementary material 3 (DOCX 22 KB)
408_2017_9979_MOESM4_ESM.docx (22 kb)
Supplementary material 4 (DOCX 21 KB)


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Yu-ichi Yamada
    • 1
    • 4
  • Gen Yamada
    • 1
  • Mitsuo Otsuka
    • 1
  • Hirotaka Nishikiori
    • 1
  • Kimiyuki Ikeda
    • 1
  • Yasuaki Umeda
    • 1
  • Hirofumi Ohnishi
    • 2
  • Koji Kuronuma
    • 1
  • Hirofumi Chiba
    • 1
  • Jörg Ingo Baumbach
    • 3
  • Hiroki Takahashi
    • 1
  1. 1.Department of Respiratory Medicine and AllergologySapporo Medical University School of MedicineSapporoJapan
  2. 2.Department of Public HealthSapporo Medical University School of MedicineSapporoJapan
  3. 3.Department of Chemistry & Center for Research and Education “Process Analysis & Technology”Reutlingen UniversityReutlingenGermany
  4. 4.Department of Respiratory MedicineHakodate Goryoukaku HospitalHakodateJapan

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