Heart allograft rejection: detection with breath alkanes in low levels (the HARDBALL study)

The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation
Michael PhillipsMark J Zucker

Abstract

We evaluated a new marker of heart transplant rejection, the breath methylated alkane contour (BMAC). Rejection is accompanied by oxidative stress that degrades membrane polyunsaturated fatty acids, evolving alkanes and methylalkanes, which are excreted in the breath as volatile organic compounds (VOCs). Breath VOC samples (n = 1,061) were collected from 539 heart transplant recipients before scheduled endomyocardial biopsy. Breath VOCs were analyzed by gas chromatography and mass spectroscopy, and BMAC was derived from the abundance of C4-C20 alkanes and monomethylalkanes. The "gold standard" of rejection was the concordant set of International Society for Heart and Lung Transplantation (ISHLT) grades in biopsies read by 2 reviewers. Concordant biopsies were: Grade 0, 645 of 1,061 (60.8%); 1A, 197 (18.6%); 1B, 84 (7.9%); 2, 93 (8.8%); and 3A, 42 (4.0%). A combination of 9 VOCs in the BMAC identified Grade 3 rejection (sensitivity 78.6%, specificity 62.4%, cross-validated sensitivity 59.5%, cross-validated specificity 58.8%, positive predictive value 5.6%, negative predictive value 97.2%). Site pathologists identified the same cases with sensitivity of 42.4%, specificity 97.0%, positive predictive value 45.2% and negative predi...Continue Reading

References

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Citations

Oct 22, 2009·Analytical and Bioanalytical Chemistry·Audrey N MartinMatthias Frank
Jan 9, 2007·The International Journal of Cardiovascular Imaging·Andrew L RivardNorbert Wilke
Apr 15, 2008·Transplantation·Iman M HamourNicholas R Banner
Apr 7, 2011·American Journal of Physiology. Endocrinology and Metabolism·Timothy D C MinhPietro R Galassetti
Oct 1, 2009·BMC Cancer·Amel BajtarevicAnton Amann
Sep 17, 2014·Biomarkers in Medicine·Jenna F McMinnRoy S Gardner
Nov 10, 2009·Expert Review of Molecular Diagnostics·Anil S Modak
May 31, 2006·Expert Opinion on Pharmacotherapy·Juan F DelgadoCarlos S de la Calzada
Jul 25, 2012·Progress in Cardiovascular Diseases·Frank S Cikach, Raed A Dweik
Mar 14, 2012·Diabetes Research and Clinical Practice·Timothy Do Chau MinhPietro Renato Galassetti
Mar 20, 2012·Translational Research : the Journal of Laboratory and Clinical Medicine·Carlos A Labarrere, Beate R Jaeger
May 10, 2011·The Surgeon : Journal of the Royal Colleges of Surgeons of Edinburgh and Ireland·Jignesh K PatelJon A Kobashigawa
Mar 2, 2010·Tuberculosis·Michael PhillipsJames Wai
Apr 19, 2008·Clinica Chimica Acta; International Journal of Clinical Chemistry·Michael PhillipsJames Wai
Apr 17, 2007·Annals of the New York Academy of Sciences·Chris L WhittleGeorge Preti
Apr 14, 2007·Pediatric Transplantation·Seema Mital
Jul 30, 2010·IEEE Transactions on Bio-medical Engineering·Dongmin GuoJianhua Yang
Dec 14, 2004·The American Journal of Cardiology·Michael PhillipsMark J Zucker
Apr 26, 2006·Tuberculosis·Michael PhillipsOlaf Tietje
Apr 12, 2015·Free Radical Biology & Medicine·M E DolchG Schelling
Apr 29, 2014·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Paweł MochalskiAnton Amann
Sep 1, 2015·Journal of Biomarkers·Kamila Schmidt, Ian Podmore
Dec 23, 2014·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Alexandra Hengerics SzabóAnton Amann
Jun 8, 2012·International Journal of Toxicology·Paweł MochalskiAnton Amann
Apr 6, 2017·Sensors·Lu KouDongxu Liu
Jul 21, 2017·Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society·Mohammed AshrafiArdeshir Bayat
Sep 1, 2007·Journal of Breath Research·Anil S Modak
Mar 9, 2011·Journal of Breath Research·Michael PhillipsJames Wai
May 25, 2010·Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society·Alexis N ThomasArdeshir Bayat
Feb 14, 2006·Current Opinion in Cardiology·Jignesh K Patel, Jon A Kobashigawa
Apr 10, 2019·Journal of Breath Research·Edoardo GaudeMarc P van der Schee
Jul 20, 2019·Kardiologiia·A A BykovaPh Yu Kopylov
Sep 6, 2017·Journal of Breath Research·M Metsälä
Mar 4, 2020·Biosensors·Emma DaultonJoseph Hardwicke
Mar 1, 2013·Journal of Breath Research·Dorottya KovacsIldiko Horvath
Feb 8, 2018·Journal of Breath Research·Kapil Dev SinghPablo M-L Sinues

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