In cystic fibrosis (CF), sweat chloride concentration has been proposed as an 
index of CFTR function for testing systemic drugs designed to activate mutant 
CFTR. This suggestion arises from the assumption that greater residual CFTR 
function should lead to a lower sweat chloride concentration, as well as 
protection against severe lung disease. This logic gives rise to the hypothesis 
that the lower the sweat chloride concentration, the less severe the lung 
disease. In order to test this hypothesis, we studied 230 patients homozygous 
for the DeltaF508 allele, and 34 patients with at least one allele associated 
with pancreatic sufficiency, born since January 1, 1955, who have pulmonary 
function data and sweat chloride concentrations recorded in our CF center 
database, and no culture positive for B. cepacia. We calculated a severity index 
for pulmonary disease, using an approach which takes into account all available 
pulmonary function data as well as the patient's current age and survival 
status. Patients with alleles associated with pancreatic sufficiency had 
significantly better survival (P = 0.0083), lower sweat chloride concentration 
(81.4 +/- 23.8 vs. 103.2 +/- 14.2 mEq/l, P < 0.0001), slower rate of decline of 
FEV(1) % predicted (-0.75 +/- 0.34 vs. -2.34 +/- 0.17% predicted per year), and 
a better severity index than patients homozygous for the DeltaF508 allele 
(median 73rd percentile vs. median 55th percentile, P = 0.0004). However, the 
sweat chloride concentration did not correlate with the severity index, either 
in the population as a whole, or in the population of patients with alleles 
associated with pancreatic sufficiency, who are thought to have some residual 
CFTR function. These data suggest that, by itself, sweat chloride concentration 
does not necessarily predict a milder pulmonary course in patients with cystic 
fibrosis.