n engl j med
ministered by inhalation, deposition will prefer-
entially occur in areas not obstructed by plugs of
mucus. The most affected areas may therefore not
benefit from this treatment approach. The veri-
fication of this hypothesis would support the early
use of such drugs in cystic fibrosis before mucus
can accumulate extensively in the lung. More-
over, hypertonic droplets undergo hygroscopic
growth in a water-vapor–saturated environment
such as the respiratory tract — a factor that will
increase the size of the particles during inhala-
tion and favor a more central deposition.
finding makes it less likely that an adequate
amount of the substance will enter the smaller
airways, the area where cystic fibrosis lung dis-
ease is thought to originate. In addition, the small
airways have an overall surface area that far ex-
ceeds the surface area of the central airways. It
is not clear what quantity of an osmotic active
agent is needed for the complete restoration of
airway surface liquid in the small airways of pa-
tients with cystic fibrosis. Unless nebulizers could
specifically target this area of the bronchial tree,
the feasibility of this approach may potentially
be limited by the amount of fluid that can safely
be delivered through the larger airways. There-
fore, pharmacologic intervention with a direct
effect on chloride secretion, on sodium hyperab-
sorption, or both may ultimately be more effective
in restoring the volume of airway surface liquid.
In the meantime, hypertonic saline offers a new
treatment strategy for patients and brings us clos-
er to targeting the underlying abnormality, rath-
er than the consequences of defective mucociliary
No potential conflict of interest relevant to this article was
From the Hospital for Sick Children and the University of Toronto,
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