Prediction of heart transplant rejection with a breath test for markers of oxidative stress.

The Heart Allograft Rejection: Detection with Breath Alkanes in Low Levels study evaluated a breath test for oxidative stress in heart transplant recipients, and we report here a mathematical model predicting the probability of grade 3 rejection. The breath test divided the heart transplant recipients into 3 groups: positive for grade 3 rejection, negative for grade 3 rejection, and intermediate. The test was 100% sensitive for grade 3 heart transplant rejection when the p value was >/=0.98, and 100% specific when the p value was

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

BACKGROUND: 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). METHODS: 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. RESULTS: 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 predictive value 96.7%. CONCLUSIONS: A breath test for markers of oxidative stress was more sensitive and less specific for Grade 3 heart transplant rejection than a biopsy reading by a site pathologist, but the negative predictive values of the 2 tests were similar. A screening breath test could potentially identify transplant recipients at low risk of Grade 3 rejection and reduce the number of endomyocardial biopsies.

Increased breath biomarkers of oxidative stress in diabetes mellitus.

BACKGROUND: Oxidative stress has been implicated in the major complications of diabetes mellitus, including retinopathy, nephropathy, neuropathy and accelerated coronary artery disease. There is a clinical need for a marker of oxidative stress which could potentially identify diabetic patients at increased risk for these complications. We measured oxidative age, a new breath marker of oxidative stress, in diabetic patients. METHODS: Three groups were studied: type 1 diabetes mellitus (n=9), type 2 diabetes mellitus (n=53) and non-diabetic normals (n=39). Volatile organic compounds (VOCs) in breath were assayed by gas chromatography and mass spectroscopy to construct the breath methylated alkane contour (BMAC), a three-dimensional display of oxidative stress markers, C4-C20 alkanes and monomethylated alkanes. The collective abundance of these VOCs was reduced to a single value, the oxidative age, comprising the volume under the curve of the BMAC corrected for chronological age. RESULTS: Oxidative age was significantly increased in type 1 diabetes (mean=0.103, S.E.M.=0.119, p<0.01) and type 2 diabetes (mean=0.103, S.E.M.=0.047, p<0.05) compared to age-matched normals (mean=-0.248, S.E.M.=0.079). No significant correlation between oxidative age and blood glucose or hemoglobin A1C was observed in either group. CONCLUSIONS: Oxidative age, a marker of oxidative stress, was significantly increased in both type 1 and type 2 diabetes mellitus. Oxidative age merits further study as a candidate marker of risk for the complications of diabetes mellitus.