CORRELATION BETWEEN NASAL POTENTIAL DIFFERENCE MEASUREMENTS, GENOTYPEAND CLINICAL CONDITION IN PATIENTS WITH CYSTIC-FIBROSIS

In cystic fibrosis (CF), the clinical condition of patients correlates poorly with genotype, One possible explanation is that clinical statu s is influenced by net preserved chloride secretion rather than the CP mutation, We tested the relationships between residual chloride secre tion, as measured by nasal potential. difference (PD) and the type of mutation (genotypes expressing apical cystic fibrosis transmembrane co nductance regulator (CFTR) protein versus those that do not) and clini cal 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 measure d using a standard protocol involving the perfusion of the nasal epith elium with a sodium channel blocker (amiloride), followed by a solutio n of low chloride and finally with isoprenaline. Patients with epical CFTR protein showed higher residual chloride secretion than those with out (amiloride to isoprenaline value of 4.59 and 0.56 mV, respectively , p = 0.01). There was no correlation between mutation type and clinic al condition, When these patients were recategorized as ''high'' (>10 mV amiloride to isoprenaline response) or ''low'' (10 mV or less) chlo ride secretors, we found that tile former group had a significantly hi gher FEV1 (67.7 versus 48.3% pred) and a better pulmonary radiological score (4.14 versus 7.07, by Northern scoring system). These results s uggest that some cystic fibrosis patients, regardless of genotype, hav e an ability to secrete chloride when stimulated with chloride secreta tagogues, and this is correlated with a better lung function, These re sults also have implications for the use of potential difference measu rements in novel cystic fibrosis transmembrane conductance regulator r eplacement trials.