Updated total IgE reference intervals in Norwegian adults.

BACKGROUND: It is important and expected of laboratories to provide updated reference intervals to the clinician. As no recent publications report adult total IgE reference intervals on a Scandinavian population, the aim of our study was therefore to provide an estimate on healthy Norweigian adults. METHODS: A reference interval study was conducted in accordance to CLSI guidelines. Samples were collected from n = 252 presumably healthy adult participants enrolled through the regional blood donation program. Total IgE measurements were performed on the ImmunoCAPTM platform (Thermo Fisher Diagnostics) traceable to the WHO-reference standard (75/502) for total IgE measurements. RESULTS: An upper 95% total IgE reference limit was estimated to 302 kU/L (90% CI 177-388 kU/L), and the 97.5% percentile was estimated to 391 kU/L (90% CI 344-560 kU/L). No significant differences were found between participants who self-reported having an allergic disease and participants who did not self-report having an allergic disease. CONCLUSION: Our results and other recent publications find markedly higher values than adult reference intervals established four decades ago which still remain widely used by clinical laboratories. We therefore recommend total IgE reference intervals should be critically reviewed and updated.

Biological variation of cardiac myosin-binding protein C in healthy individuals.

OBJECTIVES: Cardiac myosin-binding protein C (cMyC) is a novel biomarker of myocardial injury, with a promising role in the triage and risk stratification of patients presenting with acute cardiac disease. In this study, we assess the weekly biological variation of cMyC, to examine its potential in monitoring chronic myocardial injury, and to suggest analytical quality specification for routine use of the test in clinical practice. METHODS: Thirty healthy volunteers were included. Non-fasting samples were obtained once a week for ten consecutive weeks. Samples were tested in duplicate on the Erenna® platform by EMD Millipore Corporation. Outlying measurements and subjects were identified and excluded systematically, and homogeneity of analytical and within-subject variances was achieved before calculating the biological variability (CVI and CVG), reference change values (RCV) and index of individuality (II). RESULTS: Mean age was 38 (range, 21-64) years, and 16 participants were women (53%). The biological variation, RCV and II with 95% confidence interval (CI) were: CVA (%) 19.5 (17.8-21.6), CVI (%) 17.8 (14.8-21.0), CVG (%) 66.9 (50.4-109.9), RCV (%) 106.7 (96.6-120.1)/-51.6 (-54.6 to -49.1) and II 0.42 (0.29-0.56). There was a trend for women to have lower CVG. The calculated RCVs were comparable between genders. CONCLUSIONS: cMyC exhibits acceptable RCV and low II suggesting that it could be suitable for disease monitoring, risk stratification and prognostication if measured serially. Analytical quality specifications based on biological variation are similar to those for cardiac troponin and should be achievable at clinically relevant concentrations.

Estimating the within-subject (CVI ) and between-subject (CVG ) biological variation of serum tryptase.

BACKGROUND: Tryptase is used as a biomarker to support the diagnosis of anaphylaxis and hematologic diseases. In the event of a mast cell activation during anaphylaxis, a temporary increase in the concentration of tryptase may be seen. On the basis of clinical studies, an increase of 2 µg/L + 20% from basis level has been proposed as significant. To evaluate the increase in tryptase levels, the within-subject (CVI ) and between-subject (CVG ) biological variations should be known. This study was conducted to estimate the biological variation of tryptase and to identify the reference change value (RCV). METHODS: Blood samples were collected from healthy volunteers once a week consecutively over a 10-week period. Tryptase was measured by the use of a fluoroenzyme immunoassay (ImmunoCAPTM ; Thermo Fisher Scientific), and linear mixed-effects models were used to calculate the biological variation and RCV for both nontransformed and log-transformed tryptase. RESULTS: Fourteen presumably healthy young adults (six males and eight females, age 23-35 years) were included. The CVI was 5.6% and the CVG was 31.5% (nontransformed data). Log-transformed data showed similar results. The analytical variation (CVA ) was 6.3% and the RCV was 23.5%. CONCLUSIONS: Young healthy adults without ongoing allergic reactions show low within-subject biological variation. Higher biological variation was observed between subjects.

Biological variation of secretoneurin; a novel cardiovascular biomarker implicated in arrhythmogenesis.

BACKGROUND: Secretoneurin is a novel prognostic biomarker that may predict mortality in heart failure and the occurrence of ventricular arrhythmias. This study reports the within subject variation (CVI), between subject variation (CVG), reference change values (RCV) and index of individuality (II) of secretoneurin. METHODS: Thirty healthy volunteers were included. Non-fasting samples were obtained between 8 and 10 am once a week for ten weeks. Secretoneurin was analyzed in duplicate using ELISA. No outliers were present according to Burnett and Reeds' criteria. Simple linear regression did not identify significant trends. Variance homogeneity in the analytical variance and CVI were tested using Cochrane's and Bartlett's tests and four participants were excluded. Calculation of CVI, CVG and RCV were done on ln transformed data as described by Fokkema, the II was calculated using retransformed data. RESULTS: The median age of the participants was 36 years and 53% were female. Non-fasting glucose, eGFR(CKD-EPI), cTnT and NT-proBNP concentrations were within the normal range. Median secretoneurin concentrations were 38 pmol/L (women) and 33 pmol/L (men), p-value < 0.001. CVI and CVG were 9.8% (CI 8.7% to 11.0%) and 20.0 (CI 15.4% to 28.0%), respectively. RCV were 38.7% (CI 35.5% to 42.7%) and -27.9 (CI -29.9 to -26.2) and the II were 0.60 (CI 0.42-0.78). No gender differences were present. CONCLUSION: Secretoneurin has a fairly low CVI, CVG, RCV and II, indicating that it could be suitable as a diagnostic or prognostic biomarker and that delta values in serial samplings may be preferable for identifying clinical changes.

The use of error and uncertainty methods in the medical laboratory.

Error methods - compared with uncertainty methods - offer simpler, more intuitive and practical procedures for calculating measurement uncertainty and conducting quality assurance in laboratory medicine. However, uncertainty methods are preferred in other fields of science as reflected by the guide to the expression of uncertainty in measurement. When laboratory results are used for supporting medical diagnoses, the total uncertainty consists only partially of analytical variation. Biological variation, pre- and postanalytical variation all need to be included. Furthermore, all components of the measuring procedure need to be taken into account. Performance specifications for diagnostic tests should include the diagnostic uncertainty of the entire testing process. Uncertainty methods may be particularly useful for this purpose but have yet to show their strength in laboratory medicine. The purpose of this paper is to elucidate the pros and cons of error and uncertainty methods as groundwork for future consensus on their use in practical performance specifications. Error and uncertainty methods are complementary when evaluating measurement data.