Microstructural alterations of sputum in cystic fibrosis lung disease
Gregg A. Duncan, James Jung, Andrea Joseph, Abigail L. Thaxton, Natalie E. West, Michael P. Boyle, Justin Hanes, Jung Soo Suk
Gregg A. Duncan, James Jung, Andrea Joseph, Abigail L. Thaxton, Natalie E. West, Michael P. Boyle, Justin Hanes, Jung Soo Suk
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Research Article Pulmonology

Microstructural alterations of sputum in cystic fibrosis lung disease

Abstract

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.

Authors

Gregg A. Duncan, James Jung, Andrea Joseph, Abigail L. Thaxton, Natalie E. West, Michael P. Boyle, Justin Hanes, Jung Soo Suk

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Figure 2

100-nm muco-inert nanoparticle transport is sensitive to cystic fibrosis patient–specific sputum microstructural properties.

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100-nm muco-inert nanoparticle transport is sensitive to cystic fibrosis...
Box-and-whisker plots of log base 10 of MSD per μm2 at time τ = 1 s (log10[MSD1s]) of 100 nm muco-inert nanoparticles (MIP) in sputum samples from 10 cystic fibrosis (CF) patients (gray bars). The log10[MSD1s] of 100-nm MIP in mucus samples collected from 5 non-CF (N) individuals via an ET tube method is also included for comparison (white bars). A microrheological analysis of MSD was used to determine complex microviscosity (η*) and mesh size (ξ) for each subject. The maximum whisker length is 1.5 times the interquartile range and outliers are shown as dots. CF patients are numbered in ascending order according to median MSD1s of 100-nm MIP. (A) Measured log10[MSD1s] of 100-nm MIP in CF sputum and non-CF mucus samples. (B) Calculated η* at ω = 1 rad/s from microrheological analysis of measured MSD. η* for CF sputum interstitial fluid is indicated by the dashed line and was characterized by centrifuging 4 sputum samples at 21,000 g for 1 hour and measuring the supernatant’s viscosity by MPT. (C) Estimated mesh pore sizes of CF sputum and non-CF mucus samples calculated as ξ ≈ 3√kBTIG′ based on measured elastic modulus (G’) at ω = 1 rad/s from microrheological analysis of measured MSD. Statistical analyses comparing CF sputum and non-CF mucus were not conducted because samples were collected using different methods (i.e., spontaneous expectoration vs. ET tube method).