Hypertonic saline has a prolonged effect on mucociliary clearance in adults with cystic fibrosis

Abstract

Background: Inhaled hypertonic saline (HS) has been shown to increase mucociliary clearance (MCC) and improve clinical outcomes in adults and adolescents with cystic fibrosis (CF). However, in younger children with CF, a large study failed to demonstrate clinical benefits. This discrepancy could reflect pharmacodynamic differences in the MCC response to HS in different populations. We previously demonstrated the absence of a sustained effect of HS on MCC in healthy adults and in this study sought to characterize the durability of the MCC response to HS in adults with CF.

Methods: At two study sites, MCC was measured in CF adults using gamma scintigraphy during three separate visits: at baseline, 15 min, and 4 h after a single dose of HS (7% NaCl, 4 mL). Particle clearance rates at these visits were used to assess the durability of the MCC response to HS.

Results: The average 90-minute clearance rate measured 4 h after HS was significantly increased (21.81% ± 12.8) when compared to baseline (13.77% ± 8.7, p = .048) and showed no apparent slowing relative to the rate measured 15 min after HS. While not all subjects responded to HS, the acute response strongly predicted the sustained effect in these subjects (r = 0.896, p < .0001).

Conclusions: These results suggest that, in contrast to healthy adults, a single dose of HS has a prolonged effect on MCC in adults with CF, which lasts at least 4 h. This may explain its clinical efficacy in this population.

Keywords: Airway hydration; Hypertonic saline; Mucociliary clearance; Pharmacokinetics.

Figure 1

Curves demonstrating average isotope clearance across all subjects versus time (± SEM) from the whole lung compartment at each visit. The first 60 minutes represents cilia-driven clearance, whereas cough-assisted clearance is assessed between 60 −90 minutes after isotope inhalation.

Figure 2

A plot showing individual average 90-minute clearance (Ave90Clr) in the whole right lung compartment at baseline, 15 minutes, and 4 hours after inhaling HS. Individual responses are connected with grey lines. In a paired analysis, Ave90Clr was significantly faster at 4 hours compared to baseline (p=0.048).

Figure 3

A: Waterfall plot of the acute (black bars) and sustained (grey bars) change in clearance after HS in individual subjects, ordered by the acute response. B: Plot of sustained versus acute clearance showing a significant correlation (r = 0.896, p < 0.0001) approaching the line of identity (dotted line).