Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Apr 17:25:e00225.
doi: 10.1016/j.plabm.2021.e00225. eCollection 2021 May.

Disease-associated reference intervals for twenty laboratory tests in patients with rheumatoid arthritis, Crohn's disease or ulcerative colitis

Gustav Mikkelsen  1   2 , Børge Lillebo  3   4 , Arild Faxvaag  5   6
Affiliations

Disease-associated reference intervals for twenty laboratory tests in patients with rheumatoid arthritis, Crohn's disease or ulcerative colitis

Gustav Mikkelsen et al. Pract Lab Med. .

Abstract

Background: Population based reference intervals are fundamental for interpreting results for quantitative laboratory tests. In patients with a specific chronic disorder, however, results of various tests may regularly be different than in healthy individuals. Health-associated reference intervals may therefore have limited value in such patients. Instead, disease-associated reference intervals may be useful, as they describe the results distribution in populations resembling the specific patients. Few disease-associated reference intervals are available in the literature. The aim of this study was to estimate reference intervals for common laboratory tests for patient populations with rheumatoid arthritis, Crohn's disease or ulcerative colitis without significant comorbidity, using a novel algorithm.

Material and methods: Laboratory test results and hospital discharge diagnoses were collected for relevant patients. An algorithm was developed to identify discharge diagnoses significantly associated with high or low results for specific tests. After excluding patients with such diagnoses, reference intervals were estimated, representing results distributions in patients with each of the specific chronic disorders, but without significant comorbidity.

Results: Disease-associated reference intervals were estimated for 20 common laboratory tests. Most of the estimated reference limits were significantly different from corresponding health-associated reference limits. Thirty percent of the estimated reference intervals were different from estimates based on crude patient populations, indicating that the algorithm applied managed to exclude patients with relevant comorbidity.

Conclusion: Disease-associated reference intervals could be estimated for a number of tests in patients with rheumatoid arthritis, ulcerative colitis or Crohn's disease using a highly automated algorithm based on routinely recorded patient data.

Keywords: Crohn’s disease; Reference intervals; Rheumatoid arthritis; Ulcerative colitis.

PubMed Disclaimer

Conflict of interest statement

None.

Figures

Fig. 1
Fig. 1
Flowchart describing patient selection. The diagram illustrates how populations used for estimating reference intervals were generated. A “total population” was identified for each of the 20 tests studied as patients having at least one result for the respective test. Individual total populations were defined for males and females separately and for males and females together, i.e. 180 populations in total for the twenty tests and three disorders. From each total population a “sick population” was identified as patients having the specific chronic disorder. Finally, an “included population” was identified as patients in the sick population not having significant comorbidity. The last test result from each patient in the sick populations and the included populations were used to estimate the respective reference intervals.
Fig. 2
Fig. 2
Age distributions. Histograms illustrate age distributions for all patients identified as having RA, CD or UC. RA: rheumatoid arthritis; CD: Crohn’s disease; UC: ulcerative colitis.
Fig. 3
Fig. 3
Time since diagnosis. Histograms illustrate distributions of time between diagnosis and sample collection for each result used for estimating reference intervals. RA: rheumatoid arthritis; CD: Crohn’s disease; UC: ulcerative colitis.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Solberg H.E. International federation of clinical chemistry (IFCC), scientific committee, clinical section, expert panel on theory of reference values, and international committee for standardization in haematology (ICSH), standing committee on reference values. Approved recommendation (1986) on the theory of reference values. Part 1. The concept of reference values. J. Clin. Chem. Clin. Biochem. 1987;25(5):337–342. - PubMed
    1. Horowitz G., Jones G.R.D. Establishment and Use of Reference Intervals. In: Rifai N., Horvath A.R., Wittwer C.T., editors. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. sixth ed. Elsevier Saunders; 2018. pp. 170–194. ISBN: 978-0-323-35921-4.
    1. Adeli K., Ceriotti F., Nieuwesteeg M. Reference Information for the Clinical Laboratory. In: Burtis C.A., Ashwood E.R., Bruns D.E., editors. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. sixth ed. Elsevier Saunders; 2018. pp. 1745–1818. ISBN: 978-0-323-35921-4.
    1. Solberg H.E., PetitClerc C. International federation of clinical chemistry (IFCC), scientific committee, clinical section, expert panel on theory of reference values. Approved recommendation (1988) on the theory of reference values. Part 3. Preparation of individuals and collection of specimens for the production of reference values. J. Clin. Chem. Clin. Biochem. 1988;26(9):593–598. - PubMed
    1. Defining C.L.S.I. third ed. 2008. Establishing, and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline; p. 37. (CLSI Document C28-A3c).

LinkOut - more resources