Duration of action of hypertonic saline on mucociliary clearance in the normal lung

Abstract

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.

Keywords: airway secretions; hypertonic saline; mucus clearance.

Fig. 1.

Whole lung retention vs. time. Individual baselines are the mean of two measurements in each subject.

Fig. 2.

Central lung retention vs. time. Individual baselines are the mean of two measurements in each subject.

Fig. 3.

Peripheral lung retention vs. time. Individual baselines are the mean of two measurements in each subject.

Fig. 4.

Central to Peripheral (C/P) ratio as a function of time postradiolabel deposition. Baseline is the mean of the two baseline measures. *P < 0.05 for baseline vs. 4-h post-HS treatment.

Fig. 5.

AveClr90 for two baseline measures in each individual. Line of identity is shown for perfect repeatability.

Fig. 6.

A schematic representation of the distribution of mucus “islands” on an airway surface. The velocity of these mucus islands is faster (indicated by the size of the arrows) than the airway fluid devoid of these mucus islands (and the associated particle tracers residing within these regions).