Skip to main content

Exhaled Breath Condensate pH in Lung Cancer, the Impact of Clinical Factors

Lung volume 193, pages 957–963 (2015)Cite this article

Abstract

Purpose

Lung cancer may be associated with airway acidification due to enhanced airway inflammation and oxidative stress. Exhaled breath condensate (EBC) pH is a non-invasive indicator of airway acidity; however, it is still unclear how EBC pH changes in lung cancer. The aim of the study was to investigate EBC pH in lung cancer together with clinical variables.

Methods

Thirty-five patients with lung cancer and 37 control subjects (21 patients with stable COPD and 16 non-COPD smokers) were enrolled. EBC was collected for pH, which was determined with the argon-purging method, compared among the groups and correlated with clinical variables of patients with lung cancer.

Results

No difference was found in EBC pH between patients with lung cancer and control subjects. However, endobronchial tumour localisation, squamous-cell carcinoma subtype and gastro-oesophageal reflux were associated with low EBC pH values. No relationship was observed between EBC pH and the presence of COPD, lung function variables or smoking history.

Conclusions

Although, EBC pH is unchanged in lung cancer, lower EBC pH values are associated with distinct phenotypes. Our findings could facilitate further research on airway acidity in lung cancer.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  1. Siegel R, Naishadham D, Jemal A (2013) Cancer statistics. CA Cancer J Clin 63(1):11–30. doi:10.3322/caac.21166

    Article  PubMed  Google Scholar 

  2. Horvath I, Hunt J, Barnes PJ et al (2005) Exhaled breath condensate: methodological recommendations and unresolved questions. Eur Respir J 26(3):523–548. doi:10.1183/09031936.05.00029705

    CAS  Article  PubMed  Google Scholar 

  3. Dalaveris E, Kerenidi T, Katsabeki-Katsafli A et al (2009) VEGF, TNF-alpha and 8-isoprostane levels in exhaled breath condensate and serum of patients with lung cancer. Lung Cancer 64(2):219–225. doi:10.1016/j.lungcan.2008.08.015

    Article  PubMed  Google Scholar 

  4. Gessner C, Rechner B, Hammerschmidt S et al (2010) Angiogenic markers in breath condensate identify non-small cell lung cancer. Lung Cancer 68(2):177–184. doi:10.1016/j.lungcan.2009.06.010

    CAS  Article  PubMed  Google Scholar 

  5. Brussino L, Culla B, Bucca C et al (2014) Inflammatory cytokines and VEGF measured in exhaled breath condensate are correlated with tumor mass in non-small cell lung cancer. J Breath Res 8(2):027110. doi:10.1088/1752-7155/8/2/027110

    Article  PubMed  Google Scholar 

  6. Yang Ai SS, Hsu K, Herbert C et al (2013) Mitochondrial DNA mutations in exhaled breath condensate of patients with lung cancer. Respir Med 107(6):911–918. doi:10.1016/j.rmed.2013.02.007

    Article  PubMed  Google Scholar 

  7. Kullmann T, Barta I, Csiszer E et al (2008) Differential cytokine pattern in the exhaled breath of patients with lung cancer. Pathol Oncol Res 14(4):481–483. doi:10.1007/s12253-008-9046-8

    Article  PubMed  Google Scholar 

  8. Zhou F, Chen J, Tao G et al (2014) Increased levels of exhaled sICAM1, sVCAM1, and sE-selectin in patients with non-small cell lung cancer. Respir Med 108(11):1670–1676. doi:10.1016/j.rmed.2014.08.003

    Article  PubMed  Google Scholar 

  9. Ricciardolo FL, Gaston B, Hunt J (2004) Acid stress in the pathology of asthma. J Allergy Clin Immunol 113(4):610–619. doi:10.1016/j.jaci.2003.12.034

    CAS  Article  PubMed  Google Scholar 

  10. Kostikas K, Papatheodorou G, Ganas K et al (2002) pH in expired breath condensate of patients with inflammatory airway diseases. Am J Respir Crit Care Med 165(10):1364–1370. doi:10.1164/rccm.200111-068OC

    Article  PubMed  Google Scholar 

  11. Chan HP, Tran V, Lewis C et al (2009) Elevated levels of oxidative stress markers in exhaled breath condensate. J Thorac Oncol 4(2):172–178. doi:10.1097/JTO.0b013e3181949eb9

    Article  PubMed  Google Scholar 

  12. Bikov A, Antus B, Losonczy G et al (2010) Exhaled breath condensate pH. European Respiratory Society Monograph 49:173–182

    Google Scholar 

  13. Antus B, Barta I (2012) Exhaled breath condensate pH in patients with lung cancer. Lung Cancer 75(2):178–180. doi:10.1016/j.lungcan.2011.07.007

    Article  PubMed  Google Scholar 

  14. Bikov A, Galffy G, Tamasi L et al (2012) Exhaled breath condensate pH is influenced by respiratory droplet dilution. J Breath Res. doi:10.1088/1752-7155/6/4/046002

    PubMed  Google Scholar 

  15. Faul F, Erdfelder E, Buchner A et al (2009) Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses. Behav Res Methods 41(4):1149–1160. doi:10.3758/brm.41.4.1149

    Article  PubMed  Google Scholar 

  16. Clary-Meinesz C, Mouroux J, Cosson J et al (1998) Influence of external pH on ciliary beat frequency in human bronchi and bronchioles. Eur Respir J 11(2):330–333

    CAS  Article  PubMed  Google Scholar 

  17. Helyes Z, Elekes K, Sandor K et al (2010) Involvement of preprotachykinin A gene-encoded peptides and the neurokinin 1 receptor in endotoxin-induced murine airway inflammation. Neuropeptides 44(5):399–406. doi:10.1016/j.npep.2010.05.004

    CAS  Article  PubMed  Google Scholar 

  18. Jacoby DB, Costello RM, Fryer AD (2001) Eosinophil recruitment to the airway nerves. J Allergy Clin Immunol 107(2):211–218. doi:10.1067/mai.2001.112940

    CAS  Article  PubMed  Google Scholar 

  19. Simchowitz L (1985) Intracellular pH modulates the generation of superoxide radicals by human neutrophils. J Clin Invest 76(3):1079–1089. doi:10.1172/jci112061

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  20. Bidani A, Heming TA (1995) Effects of bafilomycin A1 on functional capabilities of LPS-activated alveolar macrophages. J Leukoc Biol 57(2):275–281

    CAS  PubMed  Google Scholar 

  21. Bikov A, Lazar Z, Schandl K et al (2011) Exercise changes volatiles in exhaled breath assessed by an electronic nose. Acta Physiol Hung 98(3):321–328. doi:10.1556/APhysiol.98.2011.3.9

    CAS  Article  PubMed  Google Scholar 

  22. Bikov A, Galffy G, Tamasi L et al (2014) Exhaled breath condensate pH decreases during exercise-induced bronchoconstriction. Respirology. doi:10.1111/resp.12248

    PubMed  Google Scholar 

  23. Borrill Z, Starkey C, Vestbo J et al (2005) Reproducibility of exhaled breath condensate pH in chronic obstructive pulmonary disease. Eur Respir J 25(2):269–274. doi:10.1183/09031936.05.00085804

    CAS  Article  PubMed  Google Scholar 

  24. Carpagnano GE, Foschino Barbaro MP, Cagnazzo M et al (2005) Use of exhaled breath condensate in the study of airway inflammation after hypertonic saline solution challenge. Chest 128(5):3159–3166. doi:10.1378/chest.128.5.3159

    Article  PubMed  Google Scholar 

  25. Koczulla R, Dragonieri S, Schot R et al (2009) Comparison of exhaled breath condensate pH using two commercially available devices in healthy controls, asthma and COPD patients. Respir Res 10:78. doi:10.1186/1465-9921-10-78

    PubMed Central  Article  PubMed  Google Scholar 

  26. MacNee W, Rennard SI, Hunt JF et al (2011) Evaluation of exhaled breath condensate pH as a biomarker for COPD. Respir Med 105(7):1037–1045. doi:10.1016/j.rmed.2011.02.009

    Article  PubMed  Google Scholar 

  27. Bajtarevic A, Ager C, Pienz M et al (2009) Noninvasive detection of lung cancer by analysis of exhaled breath. BMC Cancer 9:348. doi:10.1186/1471-2407-9-348

    PubMed Central  Article  PubMed  Google Scholar 

  28. Dragonieri S, Annema JT, Schot R et al (2009) An electronic nose in the discrimination of patients with non-small cell lung cancer and COPD. Lung Cancer 64(2):166–170. doi:10.1016/j.lungcan.2008.08.008

    Article  PubMed  Google Scholar 

  29. Phillips M, Gleeson K, Hughes JM et al (1999) Volatile organic compounds in breath as markers of lung cancer: a cross-sectional study. Lancet 353(9168):1930–1933. doi:10.1016/s0140-6736(98)07552-7

    CAS  Article  PubMed  Google Scholar 

  30. Hunt J, Yu Y, Burns J et al (2006) Identification of acid reflux cough using serial assays of exhaled breath condensate pH. Cough 2:3. doi:10.1186/1745-9974-2-3

    PubMed Central  Article  PubMed  Google Scholar 

  31. Terada K, Muro S, Sato S et al (2008) Impact of gastro-oesophageal reflux disease symptoms on COPD exacerbation. Thorax 63(11):951–955. doi:10.1136/thx.2007.092858

    CAS  Article  PubMed  Google Scholar 

  32. Liu L, Teague WG, Erzurum S et al (2011) Determinants of exhaled breath condensate pH in a large population with asthma. Chest 139(2):328–336. doi:10.1378/chest.10-0163

    PubMed Central  Article  PubMed  Google Scholar 

  33. Shimizu Y, Dobashi K, Zhao JJ et al (2007) Proton pump inhibitor improves breath marker in moderate asthma with gastroesophageal reflux disease. Respiration 74(5):558–564. doi:10.1159/000101437

    CAS  Article  PubMed  Google Scholar 

  34. Timms C, Thomas PS, Yates DH (2012) Detection of gastro-oesophageal reflux disease (GORD) in patients with obstructive lung disease using exhaled breath profiling. J Breath Res 6(1):016003. doi:10.1088/1752-7155/6/1/016003

    Article  PubMed  Google Scholar 

  35. Niimi A, Nguyen LT, Usmani O et al (2004) Reduced pH and chloride levels in exhaled breath condensate of patients with chronic cough. Thorax 59(7):608–612

    PubMed Central  CAS  Article  PubMed  Google Scholar 

Download references

Acknowledgments

The study was supported by Hungarian National Research Fund (OTKA 68808) and Hungarian Respiratory Society (grant to Nora Gyulai). Andras Bikov received sanofi-aventis scholarship.

Author information

Affiliations

  1. Department of Pulmonology, Semmelweis University, 1/C Dios arok, Budapest, 1125, Hungary

    Andras Bikov, Zsofia Lazar, Nora Gyulai, Marton Szentkereszty, Gyorgy Losonczy, Ildiko Horvath & Gabriella Galffy

  2. National Koranyi Institute for TB and Pulmonology, 1 Piheno ut, Budapest, 1121, Hungary

    Ildiko Horvath

Authors
  1. Andras Bikov
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zsofia Lazar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nora Gyulai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marton Szentkereszty
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gyorgy Losonczy
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ildiko Horvath
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Gabriella Galffy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andras Bikov.

Ethics declarations

Conflict of interest

The authors report no conflict of interest.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Bikov, A., Lazar, Z., Gyulai, N. et al. Exhaled Breath Condensate pH in Lung Cancer, the Impact of Clinical Factors. Lung 193, 957–963 (2015). https://doi.org/10.1007/s00408-015-9778-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00408-015-9778-7

Keywords

  • Airway acidity
  • Biomarkers
  • Breath test
  • Exhaled breath condensate
  • Lung cancer