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Published on: September 13, 2018
Evaluation of the intestinal current measurement method as a diagnostic test for cystic fibrosis
Malena Cohen-Cymberknoh1, Yasmin Yaakov, David Shoseyov
1CF Center and Department of Pediatrics, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
Insights
Intestinal current measurement (ICM) shows high diagnostic reliability for cystic fibrosis (CF). This method effectively differentiates CF patients from controls, offering a promising tool for CF diagnosis, especially in young children.
Area of Science:
- Biomedical diagnostics
- Gastroenterology
- Pediatric medicine
Background:
- Established cystic fibrosis (CF) diagnostic tools include sweat tests and nasal potential difference measurements.
- Intestinal current measurement (ICM) is being considered as an adjunctive diagnostic method for CF, particularly in pediatric cases.
Purpose of the Study:
- To evaluate the diagnostic reliability and accuracy of intestinal current measurement (ICM) for cystic fibrosis (CF).
Main Methods:
- Rectal biopsies were obtained from CF patients, healthy controls, and individuals suspected of having CF.
- Intestinal current measurements (ICMs) were performed using Ussing chamber technique with sequential addition of secretagogues.
- Current changes were recorded to assess ion transport function in rectal tissues.
Main Results:
- Significant differences in current responses to carbachol, histamine, and cAMP/forskolin were observed between CF patients and controls.
- A combination parameter derived from these secretagogues demonstrated 100% sensitivity and specificity in differentiating normal from abnormal results (Area Under Curve = 1.00).
- Application of the ICM model to 71 suspected CF patients correctly identified 66 as normal and 5 as abnormal based on the established criteria.
Conclusions:
- Intestinal current measurement (ICM) is a valuable tool for differentiating patients suspected of having cystic fibrosis (CF).
- Further confirmation is needed before ICM can be fully integrated into established diagnostic algorithms for CF.
Background:
The sweat test and nasal potential difference measurement are now established tools in the diagnostic work up of cystic fibrosis (CF). Intestinal current measurement (ICM) is under consideration as an aid in the diagnosis of CF especially in young children. The aim of this study is to evaluate the diagnostic reliability of ICM.
Methods:
Rectal biopsies were obtained from three groups: CF patients, controls, and patients who were suspected for CF. ICMs were performed by mounting the rectal biopsy in an Ussing chamber and sequentially adding secretagogues while recording current changes.
Results:
Twenty-one CF patients (aged 3.0 ± 3.8 years) and 16 controls (aged 15.6 ± 15.1 years) were examined and have remarkably different results (presented as µA/cm(2) ): carbachol 16.3 ± 6.9, histamine 13.2 ± 8.9, and cAMP/forskolin 4.8 ± 4.0 for control group and carbachol -1.5 ± 5.3 (P < 0.0001), histamine -1.5 ± 3.1 (P < 0.0001), and cAMP/forskolin 0.36 ± 0.67 (P < 0.0001) for the CF group. Our suggested reference values are: +5.40, +3.52, +2.19 for carbachol, histamine, and cAMP/forskolin, respectively. The combination parameter (the arithmetic sum of carbachol, histamine, and cAMP/forskolin) of +7.19 differentiates normal from abnormal (ROC curve analysis, area under the curve = 1.00, both sensitivity and specificity are 100%). This statistical model was applied to 71 patients suspected for CF and revealed that 66 patients had normal ICM results (combination >7.19) and five patients had abnormal ICM results (combination <7.19).
Conclusion:
We have shown that ICM tests may be useful to differentiate between patients suspected to have CF. These results require confirmation so that ICM may be included in diagnostic algorithms.
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