Duration of action of hypertonic saline on mucociliary clearance in the normal lung.
Inhalation of hypertonic saline (HS) acutely enhances mucociliary clearance (MC) in both health and disease. In patients with cystic fibrosis (CF), repeated use of HS causes a sustained improvement in MC as well as clinical benefit. The pharmacodynamic duration of activity on MC may be an important determinant of its therapeutic potential in other airways diseases. Before moving toward testing the clinical benefits of HS for non-CF indications, we sought to assess the duration of pharmacodynamic effects of HS in healthy subjects by performing radiotracer clearance studies at baseline, 30-min post-HS administration, and 4-h post-HS administration. Indeed, acceleration of MC was observed when measured 30 min after HS inhalation. This acceleration was most pronounced in the first 30 min after inhaling the radiotracer in the central lung region (mean Ave30Clr = 15.5 vs. 8.6% for 30-min post-HS treatment vs. mean baseline, respectively, P < 0.005), suggesting that acute HS effects were greatest in the larger bronchial airways. In contrast, when MC was measured 4 h after HS administration, all indices of central lung region MC were slower than at baseline: Ave30Clr = 5.9% vs. 8.6% (P = 0.10); Ave90Clr = 12.4% vs. 16.8% (P < 0.05); clearance through 3 h = 29.4 vs. 43.7% (P < 0.002); and clearance through 6 h = 39.4 vs. 50.2% (P < 0.02). This apparent slowing of MC in healthy subjects 4-h post-HS administration may reflect depletion of airway mucus following acute HS administration.
Center for Environmental Medicine, Asthma, and Lung Biology and william_bennett@med.unc.edu.
W D
WD
Bennett
Center for Environmental Medicine, Asthma, and Lung Biology and.
J
J
Wu
Cystic Fibrosis Research and Treatment Center, University of North Carolina at Chapel Hill, North Carolina;
F
F
Fuller
Cystic Fibrosis Research and Treatment Center, University of North Carolina at Chapel Hill, North Carolina;
J R
JR
Balcazar
Center for Environmental Medicine, Asthma, and Lung Biology and.
K L
KL
Zeman
Center for Environmental Medicine, Asthma, and Lung Biology and.
H
H
Duckworth
Parion Sciences, Incorporated, Durham, North Carolina; and.
K H
KH
Donn
Gilead Sciences, Incorporated, Seattle, Washington.
T G
TG
O'Riordan
Cystic Fibrosis Research and Treatment Center, University of North Carolina at Chapel Hill, North Carolina;
R C
RC
Boucher
Cystic Fibrosis Research and Treatment Center, University of North Carolina at Chapel Hill, North Carolina;
S H
SH
Donaldson
D000280:Administration, Inhalation; D000328:Adult; D001980:Bronchi / Q000187:drug effects; D005260:Female; D005541:Forced Expiratory Volume; D064368:Healthy Volunteers; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging / Q000187:drug effects*; D008297:Male; D009079:Mucociliary Clearance / Q000187:drug effects*; D009093:Mucus / Q000378:metabolism; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D055815:Young Adult
D019275:Radiopharmaceuticals; D012462:Saline Solution, Hypertonic
airway secretions; hypertonic saline; mucus clearance