title: Potential difference measurements in the lower airway of children with and without cystic fibrosis.
abstract: Nasal potential difference measurements are valuable endpoint assays in clinical studies of novel treatments for cystic fibrosis (CF). Similar measurements made on the lower airway via the bronchoscope have been successful in adults, but have not been reported in children, the group most likely to benefit from such therapies. Here we report the design and validation of a small, single-lumen catheter technique allowing baseline potential difference and chloride secretion to be assessed in the distal airways of children as young as 1 year of age. Tracheal baseline values were significantly higher in children with CF than those without, although this was not the case more distally. In airways between the third and seventh generation, perfusion with a zero chloride solution containing isoprenaline led to a significant change in potential difference in children without CF, whereas no change was seen in those with CF. This measure provided a reliable distinguishing test between the two disease groups. We confirm that invasive bronchoscopic techniques can be performed safely and reliably in small children. Potential difference measurements could form a useful functional endpoint assay for future studies of either the CFTR gene or protein-based therapies in future trials in the pediatric age group.
authors.affiliation: Department of Gene Therapy, National Heart and Lung Institute, Imperial College London, Emmanuel Kaye Building, Manresa Road, London SW3 6LR, UK. j.c.davies@imperial.ac.uk
authors.forename: Jane C
authors.initials: JC
authors.lastname: Davies
authors.forename: Michael
authors.initials: M
authors.lastname: Davies
authors.forename: Donna
authors.initials: D
authors.lastname: McShane
authors.forename: Stephen
authors.initials: S
authors.lastname: Smith
authors.forename: Sharon
authors.initials: S
authors.lastname: Chadwick
authors.forename: Adam
authors.initials: A
authors.lastname: Jaffe
authors.forename: Raymond
authors.initials: R
authors.lastname: Farley
authors.forename: Louise
authors.initials: L
authors.lastname: Collins
authors.forename: Andrew
authors.initials: A
authors.lastname: Bush
authors.forename: Michael
authors.initials: M
authors.lastname: Scallon
authors.forename: John
authors.initials: J
authors.lastname: Pepper
authors.forename: Duncan M
authors.initials: DM
authors.lastname: Geddes
authors.forename: Eric W F W
authors.initials: EW
authors.lastname: Alton
mesh_terms: D001980:Bronchi / Q000502:physiology* / Q000503:physiopathology*; D001999:Bronchoscopy; D002404:Catheterization / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D002712:Chlorides / Q000032:analysis*; D003550:Cystic Fibrosis / Q000503:physiopathology*; D006801:Humans; D007223:Infant; D017136:Ion Transport; D008564:Membrane Potentials; D014132:Trachea / Q000502:physiology* / Q000503:physiopathology*
chemical_list: D002712:Chlorides