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Intestinal current measurement for diagnostic classification of patients with questionable cystic fibrosis: validation and reference data.
Thorax. 2010 Jul; 65(7):594-9.T

Abstract

BACKGROUND

In questionable cystic fibrosis (CF), mild or monosymptomatic phenotypes frequently cause diagnostic difficulties despite detailed algorithms. CF transmembrane conductance regulator (CFTR)-mediated ion transport can be studied ex vivo in rectal biopsies by intestinal current measurement (ICM).

OBJECTIVES

To describe reference values and validate ICM for the diagnostic classification of questionable CF at all patient ages.

METHODS

ICM was performed in 309 rectal biopsies from 130 infants, children and adults including patients with known pancreatic-insufficient (PI)-CF (n=34), pancreatic-sufficient (PS)-CF (n=7), patients with an unclear diagnosis with mild CF symptoms, intermediate sweat test and/or CFTR mutation screening (n=61) and healthy controls (n=28). ICM was correlated to sweat chloride, extensive CFTR genotype and transcript analysis in the diagnostic group. The results were compared with previous ICM data in subjects with CF, congenital bilateral absence of the vas deferens, heterozygotes and controls.

RESULTS

The cumulative chloride secretory response of DeltaI(sc,carbachol), DeltaI(sc,cAMP/forskolin) and DeltaI(sc,histamine) was the best diagnostic ICM parameter (cut-off 34 muA/cm(2) between patients with known PS-CF and controls), differentiating patients with questionable CF into PS-CF (n=6) and 'CF unlikely' (n=55) groups. Extensive genotype analysis detected two mutations (40% disease-causing) in 100% of individuals classified as PS-CF compared with 1.8% in those classified as 'CF unlikely'.

CONCLUSIONS

This comprehensive investigation of CFTR function and genotype underlines the diagnostic value of ICM, especially for confirmation of CF in the absence of two disease-causing CFTR mutations, exclusion of CF despite intermediate sweat test and age groups unsuitable for nasal potential difference measurements. ICM is an important tool for functional assessment in CFTR mutations of unknown clinical relevance.

Authors+Show Affiliations

Cystic Fibrosis Centre, Department of Pediatric Pulmonology and Neonatology, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. derichs.nico@mh-hannover.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Validation Study

Language

eng

PubMed ID

20627915

Citation

Derichs, Nico, et al. "Intestinal Current Measurement for Diagnostic Classification of Patients With Questionable Cystic Fibrosis: Validation and Reference Data." Thorax, vol. 65, no. 7, 2010, pp. 594-9.
Derichs N, Sanz J, Von Kanel T, et al. Intestinal current measurement for diagnostic classification of patients with questionable cystic fibrosis: validation and reference data. Thorax. 2010;65(7):594-9.
Derichs, N., Sanz, J., Von Kanel, T., Stolpe, C., Zapf, A., Tümmler, B., Gallati, S., & Ballmann, M. (2010). Intestinal current measurement for diagnostic classification of patients with questionable cystic fibrosis: validation and reference data. Thorax, 65(7), 594-9. https://doi.org/10.1136/thx.2009.125088
Derichs N, et al. Intestinal Current Measurement for Diagnostic Classification of Patients With Questionable Cystic Fibrosis: Validation and Reference Data. Thorax. 2010;65(7):594-9. PubMed PMID: 20627915.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intestinal current measurement for diagnostic classification of patients with questionable cystic fibrosis: validation and reference data. AU - Derichs,Nico, AU - Sanz,Javier, AU - Von Kanel,Thomas, AU - Stolpe,Cornelia, AU - Zapf,Antonia, AU - Tümmler,Burkhard, AU - Gallati,Sabina, AU - Ballmann,Manfred, PY - 2010/7/15/entrez PY - 2010/7/16/pubmed PY - 2010/8/6/medline SP - 594 EP - 9 JF - Thorax JO - Thorax VL - 65 IS - 7 N2 - BACKGROUND: In questionable cystic fibrosis (CF), mild or monosymptomatic phenotypes frequently cause diagnostic difficulties despite detailed algorithms. CF transmembrane conductance regulator (CFTR)-mediated ion transport can be studied ex vivo in rectal biopsies by intestinal current measurement (ICM). OBJECTIVES: To describe reference values and validate ICM for the diagnostic classification of questionable CF at all patient ages. METHODS: ICM was performed in 309 rectal biopsies from 130 infants, children and adults including patients with known pancreatic-insufficient (PI)-CF (n=34), pancreatic-sufficient (PS)-CF (n=7), patients with an unclear diagnosis with mild CF symptoms, intermediate sweat test and/or CFTR mutation screening (n=61) and healthy controls (n=28). ICM was correlated to sweat chloride, extensive CFTR genotype and transcript analysis in the diagnostic group. The results were compared with previous ICM data in subjects with CF, congenital bilateral absence of the vas deferens, heterozygotes and controls. RESULTS: The cumulative chloride secretory response of DeltaI(sc,carbachol), DeltaI(sc,cAMP/forskolin) and DeltaI(sc,histamine) was the best diagnostic ICM parameter (cut-off 34 muA/cm(2) between patients with known PS-CF and controls), differentiating patients with questionable CF into PS-CF (n=6) and 'CF unlikely' (n=55) groups. Extensive genotype analysis detected two mutations (40% disease-causing) in 100% of individuals classified as PS-CF compared with 1.8% in those classified as 'CF unlikely'. CONCLUSIONS: This comprehensive investigation of CFTR function and genotype underlines the diagnostic value of ICM, especially for confirmation of CF in the absence of two disease-causing CFTR mutations, exclusion of CF despite intermediate sweat test and age groups unsuitable for nasal potential difference measurements. ICM is an important tool for functional assessment in CFTR mutations of unknown clinical relevance. SN - 1468-3296 UR - https://www.unboundmedicine.com/medline/citation/20627915/Intestinal_current_measurement_for_diagnostic_classification_of_patients_with_questionable_cystic_fibrosis:_validation_and_reference_data_ L2 - http://thorax.bmj.com/cgi/pmidlookup?view=long&pmid=20627915 DB - PRIME DP - Unbound Medicine ER -