Intestinal current measurement for diagnostic classification of patients with questionable cystic fibrosis: validation and reference data
Intestinal current measurement for diagnostic classification of patients with questionable cystic fibrosis: validation and reference data
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DOI：
10.1136/thx.2009.125088
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发表时间：
2010-07-01
期刊：
影响因子：
10
通讯作者：
Ballmann, Manfred
中科院分区：
文献类型：
--
作者：
Derichs, Nico;Sanz, Javier;Ballmann, Manfred
背景在可疑的囊性纤维化（CF）中，尽管有详细的算法，但轻度或单症状表型经常导致诊断困难。通过肠电流测量（ICM），可以研究CF跨膜传导调节剂（CFTR）介导的离子在直肠活组织检查中的体外转运。目的描述ICM在所有年龄的可疑CF诊断分类中的参考值并验证其有效性。方法对130例婴儿、儿童和成人的309例直肠活检进行ICM，包括已知的PI -CF （n=34）、PS -CF （n=7）、诊断不明确的轻度CF症状、中间汗液试验和/或CFTR突变筛查（n=61）和健康对照（n=28）。诊断组的ICM与汗液氯化物、广泛的CFTR基因型和转录本分析相关。将结果与CF、先天性双侧输精管缺失、杂合子和对照组的先前ICM数据进行比较。结果Delta I（sc,carbachol）、Delta I（sc,cAMP/forskolin）和Delta I（sc，组胺）的累积氯化物分泌反应是最佳的ICM诊断参数（已知PS-CF患者与对照组的截止值为34 μ A/cm(2)），可将可疑CF患者区分为PS-CF （n=6）和“不太可能CF”（n=55）组。广泛的基因型分析在100%被分类为PS-CF的个体中检测到两个突变（40%致病），而在被分类为“不太可能”的个体中检测到1.8%的突变。结论对CFTR功能和基因型的综合研究强调了ICM的诊断价值，特别是在没有两种致病CFTR突变的情况下确诊CF，在中间汗液试验排除CF以及不适合鼻电位差测量的年龄组。ICM是一种重要的功能评估工具，用于临床相关性未知的CFTR突变。
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 Delta I(sc,carbachol), Delta I(sc,cAMP/forskolin) and Delta I(sc,histamine) was the best diagnostic ICM parameter (cut-off 34 mu A/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.