Relationship between airway ion transport and a mild pulmonary disease mutation in CFTR

Am J Respir Crit Care Med. 1997 May;155(5):1684-9. doi: 10.1164/ajrccm.155.5.9154877.


Patients with cystic fibrosis (CF) display defects in airway ion transport, but the influence of airway transport phenotype on improved prognosis is not known. We studied airway bioelectric properties in five CF patients with the rare A455E mutation that is associated with mild pulmonary disease. We also evaluated five patients possessing premature truncation mutations (G542X and R553X) for which an association with mild pulmonary disease has not been as well established. We found no evidence in vivo that a mild lung disease mutation in the CF transmembrane regulator gene (CFTR) led to correction or partial correction of: (1) unstimulated Cl- secretion; (2) beta-agonist-activated Cl- secretion; (3) basal sodium reabsorption; or (4) amiloride-sensitive airway sodium transport. Early phase therapeutic trials in CF, including human gene transfer trials, rely heavily on improvements in airway potential difference to identify promising interventions and an improved prognosis. Based on our findings in a naturally occurring group of CF patients with an improved pulmonary prognosis (A455E), one can argue that marked clinical benefit might be possible without any improvement whatsoever in airway bioelectric phenotype. Moreover, if genetic modifiers exist that influence the severity of a particular CFTR mutation (e.g., A455E), these may be independent of human airway Cl-secretion in vivo, since we detected minimal Cl--secretory responses in patients with A455E.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adrenergic beta-Agonists / pharmacology
  • Adult
  • Amiloride / pharmacology
  • Animals
  • COS Cells / metabolism
  • Child
  • Chlorides / metabolism
  • Cyclic AMP / pharmacology
  • Cystic Fibrosis / genetics*
  • Cystic Fibrosis / metabolism*
  • Cystic Fibrosis / physiopathology
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • Female
  • Genotype
  • Humans
  • Ion Transport* / drug effects
  • Isoproterenol / pharmacology
  • Male
  • Membrane Potentials
  • Mutation*
  • Nasal Mucosa / metabolism*
  • Nasal Mucosa / physiopathology
  • Prognosis
  • Sodium / metabolism


  • Adrenergic beta-Agonists
  • CFTR protein, human
  • Chlorides
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Amiloride
  • Sodium
  • Cyclic AMP
  • Isoproterenol