h-hydrogen

We recently developed a novel, noninvasive method for sampling nonvolatile material from the distal airways. The method is based on the collection of endogenous particles in exhaled air (PEx). The aim of this study was to characterize the protein composition of PEx and to verify that the origin of PEx is respiratory tract lining fluid (RTLF).

Healthy individuals exhaled into the sampling device, which collected PEx onto a silicon plate inside a 3-stage impactor. After their extraction from the plates, PEx proteins were separated by SDS-PAGE and then analyzed by LC-MS. Proteins were identified by searching the International Protein Index human database with the Mascot search engine.

Analysis of the pooled samples identified 124 proteins. A comparison of the identified PEx proteins with published bronchoalveolar lavage (BAL) proteomic data showed a high degree of overlap, with 103 (83%) of the PEx proteins having previously been detected in BAL. The relative abundances of the proteins were estimated according to the Mascot exponentially modified protein abundance index protocol and were in agreement with the expected protein composition of RTLF. No amylase was detected, indicating the absence of saliva protein contamination with our sampling technique.

Our data strongly support that PEx originate from RTLF and reflect the composition of undiluted RTLF.

Growth differentiation factor-15 (GDF-15) is a stress-responsive marker that might aid in the early diagnosis and risk stratification of patients with suspected acute myocardial infarction (AMI).

In a prospective, international multicenter study, GDF-15, high-sensitivity cardiac troponin T (hs-cTnT), and B-type natriuretic peptide (BNP) were measured in 646 unselected patients presenting to the emergency department with acute chest pain. The final diagnosis was adjudicated by 2 independent cardiologists. The primary prognostic end point was all-cause mortality during a median follow-up of 26 months.

AMI was the adjudicated final diagnosis in 115 patients (18%). GDF-15 concentrations at presentation were significantly higher in AMI patients compared to patients with other diagnoses. The diagnostic accuracy of GDF-15 at presentation for the diagnosis of AMI as quantified by the area under the ROC curve (AUC) was lower (AUC 0.69, 95% CI 0.64–0.74) compared to hs-cTnT (AUC 0.96, 95% CI 0.94–0.98, P < 0.001) and BNP (AUC 0.74, 95% CI 0.69–0.80, P = 0.02). A total of 55 deaths occurred during follow-up. GDF-15 predicted all-cause mortality independently of and more accurately than hs-cTnT [AUC 0.85 (95% CI 0.81–0.90) vs 0.77 (95% CI 0.72–0.83), P = 0.002] and BNP (AUC 0.75, 95% CI 0.68–0.82, P = 0.007). Net reclassification improvement was 0.15 (P = 0.01), and the absolute integrated discrimination improvement was 0.07, yielding a relative integrated discrimination improvement of 0.36 (P = 0.07).

GDF-15 predicts all-cause mortality in unselected patients with acute chest pain independently of and more accurately than hs-cTnT and BNP. However, GDF-15 does not seem to help in the early diagnosis of AMI.

The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is most accurate for estimating glomerular filtration rate (GFR) but requires an adjustment for African-American patients. Estimation equations are also improved with the use of serum cystatin C combined with standardized creatinine. Combination equations have been derived by the CKD-EPI and Chinese investigators. We investigated whether these cystatin C–based equations improve estimation adequately, so that adjustments for ethnicity are not required in a multiethnic Asian population with chronic kidney disease (CKD).

This was a cross-sectional study of 232 stable CKD patients who underwent GFR measurements using 3-sample plasma clearances of ^99mTc-DTPA, and for whom serum cystatin C and creatinine were quantified.

For all patients, the median biases with cystatin C equations were generally greater than with the CKD-EPI equation, and precision and root mean square error (RMSE) were not significantly better. However, the combination serum creatinine and cystatin C equation improved the precision, RMSE, and percentage of estimated GFR to within 15% and 30% of the measured GFR (57.3% vs 50.0%, 88.4% vs 82.8%, respectively). The derived ethnicity coefficients for the combination equation were all >1 (1.009–1.082) but small, suggesting that coefficients are not required. The Chinese-specific equations were more biased and performed more poorly than the CKD-EPI equation.

The use of a cystatin C and creatinine combination equation for estimating GFR in a multiethnic Asian population with CKD does not require ethnicity coefficients because the derived coefficients are very close to each other.

The diagnostic accuracy of serum creatinine and cystatin C (Cys) as early predictors of contrast-induced nephropathy (CIN) has been debated. We investigated the diagnostic sensitivities, diagnostic specificities, and variations from baseline for serum creatinine and Cys in CIN.

We prospectively evaluated 166 patients at risk for CIN at baseline, and at 12, 24, and 48 h after exposure to contrast media. CIN occurred in 30 patients (18%). Changes () compared to baseline in serum creatinine and Cys were evaluated at the predefined time points. ROC curve analysis was performed for the 12-h basal serum creatinine and Cys.

The serum creatinine at 12 h from baseline was the earliest predictor of CIN [area under the ROC curve (AUC) = 0.80; P < 0.001]. The serum creatinine 15% variation [0.15 mg/dL (13.2 μmol/L)] yielded 43% diagnostic sensitivity and 93% diagnostic specificity. The Cys at 12 h from baseline performed significantly worse than serum creatinine (AUC = 0.48; P = 0.74).

Variations from the serum creatinine baseline offer better diagnostic accuracy for predicting CIN at an earlier stage than similar variations in Cys. An additional diagnostic value of Cys over the determination of serum creatinine in the setting of CIN was not observed.

Cell-free fetal DNA (cffDNA) in maternal plasma can be clinically useful for detecting prenatal disorders and pregnancy monitoring. More sensitive, specific, and quantitative detection of cffDNA in maternal plasma may expand the clinical utility of such measurements.

We developed a quantitative real-time PCR (qPCR) assay [Y chromosome repetitive sequence (YRS) assay] based on a highly repetitive short sequence specific for the Y chromosome. Both standard qPCR and digital qPCR were performed to compare the sensitivity and specificity of this new assay against already established male DNA–specific assays.

The YRS assay was at least 10-fold more sensitive than the currently most sensitive DYS14 assay. The YRS assay was able to detect 0.5 genome equivalents (GE) per PCR reaction when fetal DNA was present at 0.2% of the total DNA. The background noise for the YRS assay was much lower than for the DYS14 assay in analyses of plasma samples from pregnancies with female fetuses.

The YRS assay is a substantial improvement for quantifying rare male fetal DNA in maternal plasma. The higher sensitivity and specificity may expand the clinical and research utility of cffDNA.