PT  - JOURNAL ARTICLE
AU  - Jane F. Chisholm
AU  - Siddharth K. Shenoy
AU  - Julie K. Shade
AU  - Victor Kim
AU  - Nirupama Putcha
AU  - Kathryn A. Carson
AU  - Robert Wise
AU  - Nadia N. Hansel
AU  - Justin S. Hanes
AU  - Jung Soo Suk
AU  - Enid Neptune
TI  - Nanoparticle diffusion in spontaneously expectorated sputum as a biophysical tool to probe disease severity in COPD
AID  - 10.1183/13993003.00088-2019
DP  - 2019 Jan 01
TA  - European Respiratory Journal
PG  - 1900088
4099  - http://erj.ersjournals.com/content/early/2019/05/08/13993003.00088-2019.short
4100  - http://erj.ersjournals.com/content/early/2019/05/08/13993003.00088-2019.full
AB  - 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.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Chisholm has nothing to disclose.Conflict of interest: Dr. Shenoy has nothing to disclose.Conflict of interest: Dr. Shade has nothing to disclose.Conflict of interest: Dr. Kim reports personal fees from Medscape, personal fees from CSA Medical, personal fees from Concert Pharmaceuticals, personal fees from Gala Therapeuatics, personal fees from ABIM Critical Care Testwriting Committee, grants from NHLBI K23HL094696, personal fees from AstraZeneca, personal fees from Boehringer Ingelheim, outside the submitted work.Conflict of interest: Dr. Putcha reports grants from NIH/NHLBI, outside the submitted work.Conflict of interest: Dr. Carson has nothing to disclose.Conflict of interest: Dr. Wise reports grants and personal fees from AstraZeneca/Medimmune, grants and personal fees from Boehringer Ingelheim, personal fees from Contrafect, personal fees from Pulmonx, personal fees from Roche/Genentech, personal fees from Spiration, personal fees from Sunovion, grants from Pearl Therapeutics, personal fees from Merck, personal fees from Circassia, grants and personal fees from GSK, personal fees from Pneuma, personal fees from Verona, personal fees from Bonti, personal fees from Denali, personal fees from Aradigm, personal fees from Mylan, personal fees from Theravance, personal fees from Propeller Health, personal fees from Kiniksa, outside the submitted work.Conflict of interest: Dr. Hansel reports grants and personal fees from AstraZeneca, grants and personal fees from GSK, grants from Boehringer Ingelheim, grants from NIH, grants from COPD Foundation, personal fees from Mylan, outside the submitted work.Conflict of interest: Dr. Hanes reports grants from NIH, during the conduct of the study.Conflict of interest: Dr. Suk reports grants from NIH, during the conduct of the study.Conflict of interest: Dr. Neptune has nothing to disclose.