The CF salt controversy: in vivo observations and therapeutic approaches.
There is controversy over whether abnormalities in the salt concentration or volume of airway surface liquid (ASL) initiate cystic fibrosis (CF) airway disease. In vivo studies of CF mouse nasal epithelia revealed an increase in goblet cell number that was associated with decreased ASL volume rather than abnormal [Cl(-)]. Aerosolization of osmolytes in vivo failed to raise ASL volume. In vitro studies revealed that osmolytes and pharmacological agents were effective in producing isotonic volume responses in human airway epithelia but were typically short acting and less effective in CF cultures with prolonged volume hyperabsorption and mucus accumulation. These data show that (1) therapies can be designed to normalize ASL volume, without producing deleterious compositional changes in ASL, and (2) therapeutic efficacy will likely depend on development of long-acting pharmacologic agents and/or an increased efficiency of osmolyte delivery.
Tarran
R
R
Cystic Fibrosis/Pulmonary Research and Treatment Center, The University of North Carolina at Chapel Hill, 27599, USA.
Grubb
B R
BR
Parsons
D
D
Picher
M
M
Hirsh
A J
AJ
Davis
C W
CW
Boucher
R C
RC
D000336:Aerosols; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D003550:Cystic Fibrosis / Q000503:physiopathology* / Q000628:therapy; D004195:Disease Models, Animal; D004232:Diuretics / Q000494:pharmacology; D020397:Goblet Cells / Q000473:pathology; D006801:Humans; D017136:Ion Transport / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D017551:Microdialysis; D018613:Microscopy, Confocal; D009093:Mucus / Q000737:chemistry / Q000378:metabolism; D009297:Nasal Mucosa / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D009994:Osmolar Concentration; D011663:Pulmonary Surfactants / Q000737:chemistry* / Q000378:metabolism; D011887:Raffinose / Q000494:pharmacology; D020545:Respiratory Mucosa / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology / Q000648:ultrastructure; D012965:Sodium Chloride / Q000378:metabolism* / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000494:pharmacology
D000336:Aerosols; D004232:Diuretics; D011663:Pulmonary Surfactants; D012965:Sodium Chloride; D000584:Amiloride; D011887:Raffinose; D014544:Uridine Triphosphate