Acute inhalation of hypertonic saline does not improve mucociliary clearance in all children with cystic fibrosis

Abstract

Background: Little is known of how mucociliary clearance (MCC) in children with cystic fibrosis (CF) and normal pulmonary function compares with healthy adults, or how an acute inhalation of 7% hypertonic saline (HS) aerosol affects MCC in these same children.

Methods: We compared MCC in 12 children with CF and normal pulmonary function after an acute inhalation of 0.12% saline (placebo), or HS, admixed with the radioisotope 99 mtechnetium sulfur colloid in a double-blind, randomized, cross-over study. Mucociliary clearance on the placebo day in the children was also compared to MCC in 10 healthy, non-CF adults. Mucociliary clearance was quantified over a 90 min period, using gamma scintigraphy, and is reported as MCC at 60 min (MCC60) and 90 min (MCC90).

Results: Median [interquartile range] MCC60 and MCC90 in the children on the placebo visit were 15.4 [12.4-24.5]% and 19.3 [17.3-27.8%]%, respectively, which were similar to the adults with 17.8 [6.4-28.7]% and 29.6 [16.1-43.5]%, respectively. There was no significant improvement in MCC60 (2.2 [-6.2-11.8]%) or MCC90 (2.3 [-1.2-10.5]%) with HS, compared to placebo. In addition, 5/12 and 4/12 of the children showed a decrease in MCC60 and MCC90, respectively, after inhalation of HS. A post hoc subgroup analysis of the change in MCC90 after HS showed a significantly greater improvement in MCC in children with lower placebo MCC90 compared to those with higher placebo MCC90 (p = 0.045).

Conclusions: These data suggest that percent MCC varies significantly between children with CF lung disease and normal pulmonary functions, with some children demonstrating MCC values within the normal range and others showing MCC values that are below normal values. In addition, although MCC did not improve in all children after inhalation of HS, improvement did occur in children with relatively low MCC values after placebo. This finding suggests that acute inhalation of hypertonic saline may benefit a subset of children with low MCC values.

Trial registration: ClinicalTrials.gov NCT01293084.

Figures

Figure 1

Effect of hypertonic saline inhalation on mucociliary clearance in individual children (Red - Female patients; Blue - Male patients).

Figure 2

Box plots showing median and interquartile range for mucociliary clearance at 60 min on the placebo and HS visits for all children and for subgroups of children with less than or greater than the median MCC60 after placebo. The "whiskers" represent the 10th and 90th percentiles. Open circles represent data outside the 10th and 90th percentiles. The change in MCC with HS was not significantly different from placebo for all children, or for the subgroup comparison.

Figure 3

Box plots showing median and interquartile range for mucociliary clearance at 90 min on the placebo and HS visits for all children and for children with less than or greater than the median MCC90 after placebo. The "whiskers" represent the 10th and 90th percentiles. Open circles represent data outside the 10th and 90th percentiles. The change in MCC with HS was not significantly different from placebo for all children, but was significantly different for the comparison of the subgroups (p = 0.045).