Abstract
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 the dynamics of microorganisms and immune cells in the COPD lungs are yet to be investigated.
We hypothesised that a tightened mesh structure of spontaneously expectorated mucus (i.e.sputum) would contribute to increased 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.
The microstructure of COPD sputum was assessed based on the mean squared displacement (MSD) of variously sized MIPs measured by multiple particle tracking. MSD values were correlated with sputum composition and spirometry. In total, 33 samples collected from COPD or non-COPD individuals were analysed.
We found that 100 nm MIPs differentiated microstructural features of COPD sputum. The mobility of MIPs was more hindered in sputum samples from patients with severe COPD, suggesting a tighter mucus mesh size. Specifically, MSD values inversely correlated with lung function.
这些发现表明,痰组织可以作为COPD进展和严重程度的新危险因素。
Abstract
Microstructural properties of COPD sputum probed by motility of 100 nm muco-inert particles correlate with disease severity characterised by pulmonary lung functionhttp://bit.ly/2wof7yf.
脚注
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Conflict of interest: J.F. Chisholm has nothing to disclose.
Conflict of interest: S.K. Shenoy has nothing to disclose.
Conflict of interest: J.K. Shade has nothing to disclose.
Conflict of interest: V. Kim reports personal fees for peer review from Medscape, personal fees for advisory board work from CSA Medical, Concert Pharmaceuticals, Gala Therapeutics, AstraZeneca and Boehringer Ingelheim, personal fees for chairing meetings from ABIM Critical Care Testwriting Committee, and grants from NHLBI (K23HL094696), outside the submitted work.
Conflict of interest: N. Putcha reports grants from NIH/NHLBI (K23), outside the submitted work.
Conflict of interest: K.A. Carson has nothing to disclose.
Conflict of interest: R. Wise reports grants and personal fees for data monitoring committee work and consultancy from AstraZeneca/Medimmune and GSK, grants and personal fees for data monitoring and steering committee work from Boehringer Ingelheim, personal fees for clinical end-point committee work from Contrafect, personal fees for data safety monitoring committee work from Pulmonx, personal fees for data monitoring committee work from Roche/Genentech and Merck, personal fees for steering committee work from Spiration, personal fees for chairing workshops from Sunovion, grants from Pearl Therapeutics, personal fees for consultancy from Circassia, Pneuma, Verona, Denali, Aradigm, Mylan, Theravance and Propeller Health, and personal fees for safety review committee work from Bonti and Kiniksa, outside the submitted work.
Conflict of interest: N.N. Hansel reports grants and personal fees for advisory board work from AstraZeneca and GSK, grants from Boehringer Ingelheim, NIH and COPD Foundation, and personal fees for advisory board work from Mylan, outside the submitted work.
Conflict of interest: J.S. Hanes reports grants from NIH, during the conduct of the study. The muco-inert particle technology described in this publication is being developed by Kala Pharmaceuticals. J.S. Hanes declares a financial, a management/advisor, and a paid consulting relationship with Kala Pharmaceuticals; is a cofounder of Kala Pharmaceuticals and owns company stock, which is subject to certain restrictions under Johns Hopkins University policy.
Conflict of interest: J.S. Suk reports grants from NIH, during the conduct of the study.
Conflict of interest: E. Neptune has nothing to disclose.
Support statement: This work was supported by the National Institutes of Health (R01HL127413 and R01HL125169) and the Cystic Fibrosis Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. SPIROMICS was supported by contracts from the NIH/NHLBI (HHSN268200900013C, HHSN268200900014C, HHSN268200900015C, HHSN268200900016C, HHSN268200900017C, HHSN268200900018C HHSN268200900019C, HHSN268200900020C), which were supplemented by contributions made through the foundation for the NIH from AstraZeneca; Bellerophon Pharmaceuticals; Boehringer Ingelheim Pharmaceuticals, Inc; Chiesi Farmaceutici SpA; Forest Research Institute, Inc; GSK; Grifols Therapeutics, Inc; Ikaria, Inc; Nycomed GmbH; Takeda Pharmaceutical Company; Novartis Pharmaceuticals Corporation; Regeneron Pharmaceuticals, Inc; and Sanofi. Funding information for this article has been deposited with theCrossref Funder Registry.
- 收到April 16, 2018.
- AcceptedApril 26, 2019.
- 复制right ©ERS 2019
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