The protective effect of nedocromil sodium and other drugs on airway narrowing provoked by hyperosmolar stimuli: a role for the airway epithelium?
The airways of persons with asthma are sensitive to acute changes in airway osmolarity and to dehydration. In reviewing the literature it is clear that airway narrowing provoked by these stimuli is blocked acutely by inhaling aerosols of nedocromil sodium, cromolyn sodium, frusemide, bumetanide, and antihistamines and by chronic use of aerosol corticosteroids. The responses are unaffected by inhalation of amiloride and verapamil. We have previously proposed that increases in the osmolarity of airway surface liquid (ASL) occur as a result of the water lost by evaporation during hyperpnea with dry air. An increase or decrease in osmolarity of the ASL will also occur with deposition of hyperosmolar and hypoosmolar droplets. Changes in osmolarity of the ASL result in the movement of water out of (shrinkage) and into (swelling) the epithelial cell, and this necessitates regulatory volume increase or decrease by the cell. We propose that nedocromil sodium and cromolyn sodium can affect water transport into and out of the epithelial cell by an action on chloride ion channels. A unifying hypothesis to explain the protective effect of these drugs may be their capacity to affect regulatory volume increase or decrease in a variety of cell types.
Anderson
S D
SD
Department of Respiratory Medicine, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
Rodwell
L T
LT
Daviskas
E
E
Spring
J F
JF
du Toit
J
J
D000293:Adolescent; D000328:Adult; D000336:Aerosols; D001249:Asthma / Q000503:physiopathology*; D001980:Bronchi / Q000166:cytology; D048429:Cell Size / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells; D005541:Forced Expiratory Volume; D006801:Humans; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D017835:Nedocromil / Q000008:administration & dosage / Q000494:pharmacology*; D009994:Osmolar Concentration
D000336:Aerosols; D017835:Nedocromil