Aaron T Trimble1, A Whitney Brown2, Beth L Laube3, Noah Lechtzin4, Kirby L Zeman5, Jihong Wu5, Agathe Ceppe6, David Waltz7, William D Bennett5, Scott H Donaldson6. 1. Division of Pulmonary and Critical Care Medicine and Marsico Lung Institute, The University of North Carolina at Chapel Hill, 4th Floor Bioinformatics, CB 7020, Chapel Hill, NC 27516, USA. Electronic address: atrimble@med.unc.edu. 2. Advanced Lung Disease and Transplant Program, Department of Medicine, Inova Fairfax Hospital, 3300 Gallows Road, Falls Church, VA 22046, USA. 3. Division of Pediatric Pulmonology, Johns Hopkins University, 200 N Wolfe St, Baltimore, MD 21287, USA. 4. Division of Pulmonary & Critical Care Medicine, Johns Hopkins University, 600 N Wolfe St, Baltimore, MD 21287, USA. 5. Center for Environmental Medicine, Asthma, and Lung Biology, University of North Carolina at Chapel Hill, 104 Mason Farm Road, CB 7310, Chapel Hill, NC 27599, USA. 6. Division of Pulmonary and Critical Care Medicine and Marsico Lung Institute, The University of North Carolina at Chapel Hill, 4th Floor Bioinformatics, CB 7020, Chapel Hill, NC 27516, USA. 7. Novartis Institutes for BioMedical Research, 250 Massachusetts Ave, Cambridge, MA 02139, USA.
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.
RCT Entities:
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.
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