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.

Respiratory Implications of Pediatric Neuromuscular Disease

“…99 Additionally, there was no improvement in lung mechanics or chest radiographic appearance following hypertonic saline administration, but 2 subjects had to be removed from the study because of hypoxemia that developed after hypertonic saline administration. Radioisotope studies of mucociliary clearance in healthy subjects treated with 3% inhaled hypertonic saline showed an initial acceleration of mucociliary clearance over the first 30 min after hypertonic saline inhalation but a slowing in mucociliary clearance at 3-6 h. 100 The authors speculated that the reduction in clearance was the result of depletion of mucus in the central airways. Once again, these data collectively suggest that caution should be used when considering hypertonic saline therapy for patients with NMD.…”

Effect of hypertonic saline on mucociliary clearance and clinical outcomes in chronic bronchitis

“…Thirty-three healthy, nonsmoking control subjects underwent a single MCC scan. These data were recently reported but are provided for comparison purposes [20,21].…”

“…Radiolabelled (Tc99m-sulfur colloid) aerosols were inhaled with a SILP (slow inhalation (80 mL•s −1 ), large particle (9.5 μm mass median aerodynamic diameter)) methodology [20,21]. To adjust for the smaller ventilated volume in CB and to reduce dyspnoea during this very slow inspiratory manoeuvre, a 6-s inhalation time was used in CB subjects, rather than the 10-s inhalation previously used in healthy subjects [20,21]. After tracer inhalation, serial 2-min particle retention images were acquired via gamma scintigraphy.…”

“…Serial measurements of radioactive counts (decay and background corrected) over time in the right lung characterised whole, central, and peripheral lung clearances as a fraction of initial deposited counts. The average rate of clearance through 60 min (AveClr60) in the whole right lung was calculated using clearance values at 10-min intervals [21]. Cough-dominated clearance (60-90 min; Ave60-90Clr) and regional clearance rates were similarly calculated.…”

A randomised controlled trial on the effect of inhaled hypertonic saline on quality of life in primary ciliary dyskinesia

“…Third, it directly stimulates coughing [7,15,16]. Although results from in vitro and in vivo studies suggest that these effects are relatively short lasting, twice-daily nebulisations with hypertonic saline have shown clinical benefit in patients with CF and non-CF bronchiectasis [7,8,11,[17][18][19]. As epithelial cilia are dysfunctional in PCD, patients are largely dependent on coughing for their mucus clearance.…”