Microstructural alterations of sputum in cystic fibrosis lung disease.
The stasis of mucus secretions in the lungs of cystic fibrosis (CF) patients leads to recurrent infections and pulmonary exacerbations, resulting in decreased survival. Prior studies have assessed the biochemical and biophysical features of airway mucus in individuals with CF. However, these measurements are unable to probe mucus structure on microscopic length scales relevant to key players in the progression of CF-related lung disease, namely, viruses, bacteria, and neutrophils. In this study, we quantitatively determined sputum microstructure based on the diffusion of muco-inert nanoparticle probes in CF sputum and found that a reduction in sputum mesh pore size is characteristic of CF patients with reduced lung function, as indicated by measured FEV1. We also discovered that the effect of ex vivo treatment of CF sputum with rhDNase I (Pulmozyme) on microstructure is dependent upon the time interval between the most recent inhaled rhDNase I treatment and the sample collection. Microstructure of mucus may serve as a marker for the extent of CF lung disease and as a parameter for assessing the effectiveness of mucus-altering agents.
Center for Nanomedicine and.|Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Gregg A
GA
Duncan
Center for Nanomedicine and.|Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
James
J
Jung
Center for Nanomedicine and.|Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
Andrea
A
Joseph
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Abigail L
AL
Thaxton
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Natalie E
NE
West
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|Cystic Fibrosis Foundation, Bethesda, Maryland, USA.
Michael P
MP
Boyle
Center for Nanomedicine and.|Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland, USA.|Departments of Biomedical Engineering, Environmental and Health Sciences, Oncology, Neurosurgery, and Pharmacology and Molecular Sciences, Johns Hopkins University, Baltimore, Maryland, USA.
Justin
J
Hanes
Center for Nanomedicine and.|Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Jung Soo
JS
Suk
D003550:Cystic Fibrosis / Q000175:diagnosis*; D003850:Deoxyribonuclease I / Q000627:therapeutic use; D006801:Humans; D008168:Lung; D009093:Mucus / Q000737:chemistry*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012138:Respiratory Therapy; D013183:Sputum / Q000737:chemistry*
D011994:Recombinant Proteins; D003850:Deoxyribonuclease I