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Randomized Controlled Trial
. 2017 Sep;52(9):1142-1149.
doi: 10.1002/ppul.23749. Epub 2017 Jul 24.

Overnight delivery of hypertonic saline by nasal cannula aerosol for cystic fibrosis

Timothy E Corcoran  1 , Joseph E Godovchik  1 , Karl H Donn  2 , David R Busick  2 , Jennifer Goralski  3 , Landon W Locke  1 , Matthew R Markovetz  4 , Michael M Myerburg  1 , Ashok Muthukrishnan  5 , Lawrence Weber  5 , Ryan T Lacy  1 , Joseph M Pilewski  1   6   7
Affiliations
Randomized Controlled Trial

Overnight delivery of hypertonic saline by nasal cannula aerosol for cystic fibrosis

Timothy E Corcoran et al. Pediatr Pulmonol. 2017 Sep.

Abstract

Aim: Inhaled hypertonic saline increases mucociliary clearance, improves pulmonary function, and decreases exacerbations in cystic fibrosis (CF) but contributes to the already significant treatment burden of CF. Overnight delivery of inhaled medications via a specially designed nasal cannula-aerosol device (Trans-nasal Pulmonary Aerosol Delivery [tPAD]) is an alternative approach. Here, we test whether overnight inhalation of hypertonic saline via tPAD improves mucociliary clearance and assess the tolerability of the device.

Method: In this study, 12 CF subjects inhaled 7% hypertonic saline (HS) for 8 h overnight using the tPAD system. Safety and tolerability were assessed and measurements of mucociliary and absorptive clearance (MCC/ABS) were performed after the treatment. Comparisons were made versus sham treatment where the same subjects wore the nasal cannula overnight but did not receive aerosol.

Results: Both the HS and sham treatments were well-tolerated. Only one subject did not complete the overnight HS treatment. There were no significant differences in MCC associated with HS inhalation at any time point (90 min, 3 h, 6 h) in any lung zone. Changes in FEV1 on both study days were similar. There were no differences in quality of sleep between HS and sham nights as assessed with the modified Leeds Sleep Evaluation Questionnaire (mLSEQ). Sino-Nasal Outcome Test (SNOT-14) questionnaires demonstrated significant increases (worsening) in 2/14 symptom categories with HS.

Conclusions: The most likely cause for the failure to accelerate MCC was under-dosing of HS relative to the active transport of salt from the airways.

Keywords: cystic fibrosis; hypertonic saline; imaging; mucociliary clearance; mucus disorders; nasal cannula.

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Figures

FIGURE 1
FIGURE 1
Mucociliary clearance (MCC) rate measured after overnight inhalation of 7% HS from the tPAD device or sham delivery. (A) 90 minute measurement, (B) 3 hr, (C) 6hr. Gray symbols indicate values that decreased from sham to HS and white symbols indicate increases. Error bars are ± SD.
FIGURE 1
FIGURE 1
Mucociliary clearance (MCC) rate measured after overnight inhalation of 7% HS from the tPAD device or sham delivery. (A) 90 minute measurement, (B) 3 hr, (C) 6hr. Gray symbols indicate values that decreased from sham to HS and white symbols indicate increases. Error bars are ± SD.
FIGURE 1
FIGURE 1
Mucociliary clearance (MCC) rate measured after overnight inhalation of 7% HS from the tPAD device or sham delivery. (A) 90 minute measurement, (B) 3 hr, (C) 6hr. Gray symbols indicate values that decreased from sham to HS and white symbols indicate increases. Error bars are ± SD.
FIGURE 2
FIGURE 2
Retention curve of Tc-SC (mucociliary clearance=100-retention) shown over 90 minutes and measured after overnight inhalation of 7% HS from the tPAD device or sham delivery. Error bars are ± SEM.
FIGURE 3
FIGURE 3
DTPA absorption rate (ABS) measured after overnight inhalation of 7% HS from the tPAD device or sham delivery. (A) 90 minute measurement, (B) 3 hr, (C) 6hr. Gray symbols indicate values that decreased from sham to HS and white symbols indicate increases. Error bars are ± SD.
FIGURE 3
FIGURE 3
DTPA absorption rate (ABS) measured after overnight inhalation of 7% HS from the tPAD device or sham delivery. (A) 90 minute measurement, (B) 3 hr, (C) 6hr. Gray symbols indicate values that decreased from sham to HS and white symbols indicate increases. Error bars are ± SD.
FIGURE 3
FIGURE 3
DTPA absorption rate (ABS) measured after overnight inhalation of 7% HS from the tPAD device or sham delivery. (A) 90 minute measurement, (B) 3 hr, (C) 6hr. Gray symbols indicate values that decreased from sham to HS and white symbols indicate increases. Error bars are ± SD.
FIGURE 4
FIGURE 4
Individual category results from the Sino-Nasal Outcome Test (SNOT-14). HS vs. sham – need to blow nose (p=0.02), runny nose (p=0.01). “Runny nose” was also increased when comparing HS to screen (p=0.02). For other comparisons p=NS.
FIGURE 5
FIGURE 5
Model predicted effects of saline inhalation on airway surface liquid (ASL) hydration in cystic fibrosis (CF). (A) Effect of aerosol deposition surface area (first 10 or 16 airway generations), fast or slow Na+ absorption, and saline concentration. Model predicts volume relative to human bronchial epithelial cell cultures where dotted line is normal (non-CF) ASL volume. (B) Effect of oral (Pari LC Star) vs. nasal inhalation (tPad), and saline concentration, shown for airway generations 7, 8, and 9. Model predicts relative airway surface liquid height added. Gen or G=airway generation, HS=hypertonic saline.
FIGURE 5
FIGURE 5
Model predicted effects of saline inhalation on airway surface liquid (ASL) hydration in cystic fibrosis (CF). (A) Effect of aerosol deposition surface area (first 10 or 16 airway generations), fast or slow Na+ absorption, and saline concentration. Model predicts volume relative to human bronchial epithelial cell cultures where dotted line is normal (non-CF) ASL volume. (B) Effect of oral (Pari LC Star) vs. nasal inhalation (tPad), and saline concentration, shown for airway generations 7, 8, and 9. Model predicts relative airway surface liquid height added. Gen or G=airway generation, HS=hypertonic saline.
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