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 a irway osmolarity and to dehydration. In reviewing the literature it is clear that airway narrowing provoked by these stimuli is blocked acut ely by inhaling aerosols of nedocromil sodium cromolyn sodium, frusemi de, bumetanide, and antihistamines and by chronic use of aerosol corti costeroids. The responses are unaffected by inhalation of amiloride an d verapamil. We have previously proposed that increases in the osmolar ity 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 hyperosmo lar and hypoosmolar droplets. Changes in osmolarity of the ASL result in the movement of water out of (shrinkage) and into (swelling) the ep ithelial cell, and this necessitates regulatory volume increase or dec rease by the cell. We propose that nedocromil sodium and cromolyn sodi um can affect wafer transport into and out of the epithelial cell by a n action on chloride ion channels. A unifying hypothesis to explain th e protective affect of these drugs may be their capacity to affect reg ulatory volume increase of decrease in a variety of cell types.