Altered sputum microstructure as a marker of airway obstruction in cystic fibrosis patients
Presentation Date and Time
October 14, 2015 (Wednesday) 6:05
Track / Room
Poster Session / Atrium/Harborview
- Duncan, Gregg A. (Johns Hopkins School of Medicine, Center for Nanomedicine)
- Jung, James (Johns Hopkins School of Medicine, Center for Nanomedicine)
- Boyle, Michael P. (Johns Hopkins School of Medicine, Adult Cystic Fibrosis Program)
- West, Natalie E. (Johns Hopkins School of Medicine, Adult Cystic Fibrosis Program)
- Suk, Jung Soo (Johns Hopkins School of Medicine, Center for Nanomedicine)
- Hanes, Justin (Johns Hopkins School of Medicine, Center for Nanomedicine)
Author and Affiliation Lines
Gregg A. Duncan1, James Jung1, Michael P. Boyle2, Natalie E. West2, Jung Soo Suk1, and Justin Hanes1
1Center for Nanomedicine, Johns Hopkins School of Medicine, Baltimore, MD; 2Adult Cystic Fibrosis Program, Johns Hopkins School of Medicine, Baltimore, MD
Speaker / Presenter
Duncan, Gregg A.
Text of Abstract
Introduction: Highly viscoelastic mucus secretions of CF patients that remain stagnant in the lung leads to obstructed airways prone to recurrent infections. To date, conventional rheological measurements are primarily used to assess the pathological features of mucus in the airway. However, this approach is limited in detecting microscopic properties of mucus on the length scale of viruses, bacteria, and neutrophils. We have shown in prior work based on the transport of muco-inert nanoparticle (MIP) probes in CF sputum that patients can carry significantly different microstructural properties. In this study, we aim to determine the factors leading to the patient-to-patient variations in CF sputum microstructure and their clinical implications.
Results: 100 nm MIP transport was sensitive to patient-to-patient difference in CF sputum microstructure. Elevated mucus and DNA content most significantly altered CF sputum microstructure. Reduction in sputum mesh pore size is characteristic of CF patients with highly obstructed airways as indicated by measured FEV1. Treatment of CF sputum with dornase alfa leads to significant increases in the pore size of the sputum mesh structure.
Conclusion: We developed a novel method to sensitively detect patient-to-patient differences in CF sputum microstructure using muco-inert nanoparticles as probes. This microstructural read-out may potentially serve as a novel biomarker for airway obstruction in CF and as an additional parameter for assessing mucolytic activity.
We acknowledge the support of NIH P01HL51811, NHLBI R01HL105847, and CFF HANES07XX0.