ARTICLE: Nanoparticle diffusion in spontaneously expectorated sputum as a biophysical tool to probedisease severity in COPD

AUTHORS: Jane F. Chisholm, Siddharth K. Shenoy, Julie K. Shade, Victor Kim, Nirupama Putcha, Kathryn A. Carson, Robert WiseNadia Hansel, Justin S. Hanes, Jung Soo Suk, Enid Neptune

JOURNAL: Eur Respir J. 2019 Jun 4. pii: 1900088. doi: 10.1183/13993003.00088-2019. [Epub ahead of print]

Abstract

RATIONALE: Perturbations in airway mucus properties contribute to lung function decline in patients with chronic obstructive pulmonary disease (COPD). While alterations in bulk mucus rheology have been widely explored, microscopic mucus properties that directly impact on dynamics of microorganisms and immune cells in the COPD lungs are yet to be investigated.

OBJECTIVES: We hypothesised that a tightened mesh structure of spontaneously expectorated mucus (i.e. sputum) would contribute to COPD disease severity. Here, we investigated whether the mesh size of COPD sputum, quantified by muco-inert nanoparticle (MIP) diffusion, correlated with sputum composition and lung function measurements.

METHODS: The microstructure of COPD sputum was assessed based on the mean-squared displacement (MSD) of variously sized MIP measured by multiple particle tracking. MSD values were correlated with sputum composition and spirometry. Thirty-three samples collected from COPD or non-COPD individuals were analysed.

RESULTS: We found that 100 nm MIP differentiated microstructural features of COPD sputum. The mobility of MIP was more hindered in sputum samples from severe COPD patients, suggesting tighter mucus mesh size. Specifically, MSD values inversely correlated with lung function.

CONCLUSIONS: These findings suggest that sputum microstructure may serve as a novel risk factor for COPD progression and severity.

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