Correlation between nasal potential difference measurements, genotype and clinical condition in patients with cystic fibrosis
Correlation between nasal potential difference measurements, genotype and clinical condition in patients with cystic fibrosis
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DOI：
10.1183/09031936.97.10092018
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发表时间：
1997-09-01
影响因子：
24.3
通讯作者：
Innes, JA
中科院分区：
文献类型：
--
作者：
Ho, LP;Samways, JM;Innes, JA
在囊性纤维化(CF)中，患者的临床状况与基因相关性较差。一种可能的解释是，临床状态受净保留的氯化物分泌的影响，而不是CP突变。我们用鼻电位差(PD)和突变类型(表达顶囊性纤维化跨膜传导调节蛋白(CFTR)蛋白的基因型与不表达CFTR蛋白的基因型)和临床状态之间的关系进行了测试。22例CF患者(平均年龄25.7岁，女性11例，男性11例，平均一秒用力呼气量(FEV1)为预测值的53.1%)。用钠通道阻滞剂(阿米洛利)灌流鼻黏膜上皮，然后用低氯溶液灌流，最后用异丙肾上腺素灌流，用标准的方法测量鼻腔PD。有表面CFTR蛋白的患者比没有CFTR蛋白的患者有更高的残余氯分泌(阿米洛利对异丙肾上腺素的值分别为4.59和0.56 mV，p=0.01)。突变类型与临床症状无相关性。当这些患者被重新分类为“高”(10 mV阿米洛利对异丙肾上腺素的反应)或“低”(10 mV或更低)氯化物分泌物时，我们发现前者的FEV1显著更高(67.7比48.3%pred)和更好的肺部放射学评分(4.14比7.07，根据Northern评分系统)。这些结果表明，一些囊性纤维化患者，无论基因型，在氯离子分泌剂刺激下都有分泌氯离子的能力，这与更好的肺功能有关。这些结果对在新型囊性纤维化跨膜电导调节剂替代试验中使用电势差测量也有一定的意义。
In cystic fibrosis (CF), the clinical condition of patients correlates poorly with genotype. One possible explanation is that clinical status is influenced by net preserved chloride secretion rather than the CP mutation. We tested the relationships between residual chloride secretion, as measured by nasal potential difference (PD) and the type of mutation (genotypes expressing apical cystic fibrosis transmembrane conductance regulator (CFTR) protein versus those that do not) and clinical status.Twenty two CF patients (mean age 25.7 yrs, 11 females and 11 males, mean forced expiratory volume in one second (FEV1) 53.1% of predicted) with defined genotypes mere recruited. Nasal PD was measured using a standard protocol involving the perfusion of the nasal epithelium with a sodium channel blocker (amiloride), followed by a solution of low chloride and finally with isoprenaline.Patients with epical CFTR protein showed higher residual chloride secretion than those without (amiloride to isoprenaline value of 4.59 and 0.56 mV, respectively, p = 0.01). There was no correlation between mutation type and clinical condition. When these patients were recategorized as ''high'' (>10 mV amiloride to isoprenaline response) or ''low'' (10 mV or less) chloride secretors, we found that the former group had a significantly higher FEV1 (67.7 versus 48.3% pred) and a better pulmonary radiological score (4.14 versus 7.07, by Northern scoring system).These results suggest that some cystic fibrosis patients, regardless of genotype, have an ability to secrete chloride when stimulated with chloride secretatagogues, and this is correlated with a better lung function. These results also have implications for the use of potential difference measurements in novel cystic fibrosis transmembrane conductance regulator replacement trials.