Osmolytes and ion transport modulators: new strategies for airway surface rehydration.
Mucociliary clearance (MCC) in CF lung disease is limited by airway dehydration, leading to persistent bacterial infection and inflammation in the airways. Agents designed to rehydrate the airway mucosa lead to improved MCC. Hyperosmolar agents, such as hypertonic saline and mannitol, create a luminal osmotic gradient, drawing water into the dehydrated ASL. Ion transport modulators function to activate alternative chloride channels and/or to block sodium hyperabsorption that occurs through a dysregulated ENaC channel. Combinations of these therapies may result in a synergistic improvement in airway hydration, and thus, restore MCC. Active ongoing phase II and III trials of new pharmacotherapeutics are covered in this review.
Goralski
Jennifer L
JL
Division of Pulmonary and Critical Care Medicine, University of North Carolina at Chapel Hill, 130 Mason Farm Road, CB#7020, Chapel Hill, NC 27599-7020, United States.
Boucher
Richard C
RC
Button
Brian
B
D000818:Animals; D002986:Clinical Trials as Topic; D003550:Cystic Fibrosis / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D004234:Diuretics, Osmotic / Q000494:pharmacology / Q000627:therapeutic use; D004357:Drug Synergism; D006801:Humans; D017136:Ion Transport / Q000187:drug effects; D008353:Mannitol / Q000494:pharmacology / Q000627:therapeutic use; D009079:Mucociliary Clearance / Q000187:drug effects*; D020545:Respiratory Mucosa / Q000187:drug effects*; D012462:Saline Solution, Hypertonic / Q000494:pharmacology / Q000627:therapeutic use
D004234:Diuretics, Osmotic; D012462:Saline Solution, Hypertonic; D008353:Mannitol