ABCMdb

PMID: 15516474

Fajac I, Hubert D, Guillemot D, Honore I, Bienvenu T, Volter F, Dall'Ava-Santucci J, Dusser DJ
Nasal airway ion transport is linked to the cystic fibrosis phenotype in adult patients.
Thorax. 2004 Nov;59(11):971-6., [PubMed]

Sentences

No. Mutations Sentence Comment

185 ABCC7 p.Phe508Asp We have previously shown in a group of 95 adult patients with CF that patients with the lowest basal nasal PD had better respiratory function, irrespective of the severity of the genotype.13 Other groups have suggested some correlation between the severity of lung disease and cAMP mediated chloride secretion.14 15 Moreover, in 114 twins and siblings homozygous for the F508D mutation, the most common CFTR mutation, the expression of basal chloride conductance was identified as a positive predictor of milder respiratory disease.16 In contrast, in 51 young CF patients, a recent study showed no correlation between any component of ion transport measurement and respiratory function.17 In the present study we examined whether some components of nasal epithelial ion transport were associated with the pancreatic and respiratory expression of the disease and/or the genotype in adults with CF. Login to comment 219 ABCC7 p.Arg117His ABCC7 p.Arg347His ABCC7 p.Gly542* ABCC7 p.Asp1152His ABCC7 p.Phe508Asp RESULTS Patients Four of the 79 CF patients included in the study had a normal sweat test; three were compound heterozygous for the F508D mutation and the R117H, D1152H and R347H mutations, respectively, and one patient was compound heterozygous for the G542X and 3849+10 kb (C)R (T) mutations. Login to comment 224 ABCC7 p.Phe508Asp The 73 patients for whom two mutations were identified were classified into two genotype groups: the ''severe`` genotype group included 51 patients of whom 25 were homozygous for the F508D mutation, and the ''mild`` genotype group comprised 22 patients. Login to comment 240 ABCC7 p.Arg117His ABCC7 p.Gly85Glu ABCC7 p.Phe508Asp ABCC7 p.Phe508Asp Tracings are shown for two CF patients with pancreatic insufficiency (top panels) and FEV1 ,50% pred (left panel) or FEV1 .50% pred (right panel), both of whom were homozygous for the F508D mutation and belonged to the ''severe`` genotype group; and two CF patients with pancreatic sufficiency (bottom panels) and FEV1 ,50% pred (left panel) or FEV1 .50% pred (right panel), both of whom were compound heterozygous for the F508D mutation and the R117H and G85E mutations, respectively, and belonged to the ''mild`` genotype group. Login to comment 255 ABCC7 p.Phe508Asp A relationship between residual chloride transport in intestinal tissue and a mildly affected phenotype, as assessed by the predicted weight for height and the FEV1, has previously been described in F508D homozygous twins and siblings by Bronsveld et al16 but the reverse-that is, the relationship between nasal airway ion transport and the nutritional status-was not examined by these researchers nor in a recent study of 51 young CF patients of whom only three were pancreatic sufficient.17 The relationship we have observed after both low chloride and isoproterenol solutions may reflect the fact that the pancreatic status in CF is related to the residual function of CFTR. Login to comment 269 ABCC7 p.Phe508Asp In contrast to our results, Bronsveld et al found that, in 114 F508D homozygous twins and siblings, the expression of basal chloride conductance was a positive predictor of milder respiratory disease.16 The discrepancies between our study and that of Bronsveld et al might be due to the different study populations: the respiratory function appears to be related to chloride transport in a highly selected and defined population such as the one studied by Bronsveld et al.16 However, in a population with a wide range of genotypes such as ours, the pulmonary outcome appears to be mostly influenced by increased sodium absorption in the airway epithelium. Login to comment