Mucus and mucus flake composition and abundance reflect inflammatory and infection status in cystic fibrosis

Matthew R Markovetz¹, Ian C Garbarine², Cameron B Morrison², William J Kissner², Ian Seim³, M Gregory Forest⁴, Micah J Papanikolas⁵, Ronit Freeman⁶, Agathe Ceppe², Andrew Ghio⁷, Neil E Alexis⁸, Stephen M Stick⁹, Camille Ehre², Richard C Boucher², Charles R Esther¹⁰, Marianne S Muhlebach¹⁰, David B Hill¹¹

Affiliations

¹ Marsico Lung Institute, University of North Carolina, Chapel Hill, USA. Electronic address: matthew_markovetz@med.unc.edu.
² Marsico Lung Institute, University of North Carolina, Chapel Hill, USA.
³ Department of Mathematics, University of North Carolina, Chapel Hill, USA; Department of Applied Physical Sciences, University of North Carolina, Chapel Hill, USA.
⁴ Department of Mathematics, University of North Carolina, Chapel Hill, USA; Department of Applied Physical Sciences, University of North Carolina, Chapel Hill, USA; Department of Biomedical Engineering, University of North Carolina, Chapel Hill, USA.
⁵ Department of Applied Physical Sciences, University of North Carolina, Chapel Hill, USA.
⁶ Marsico Lung Institute, University of North Carolina, Chapel Hill, USA; Department of Applied Physical Sciences, University of North Carolina, Chapel Hill, USA.
⁷ National Health and Environmental Effects Research Laboratory, United States Environmental Protection Agency, University of North Carolina, Chapel Hill, USA.
⁸ Center for Environmental Medicine Asthma and Lung Biology, University of North Carolina, Chapel Hill, USA.
⁹ Telethon Kids Institute, University of Western Australia, Perth, Australia; Division of Pediatrics, University of Western Australia, Perth, Australia; Princess Margaret Hospital for Children, Perth, Australia.
¹⁰ Marsico Lung Institute, University of North Carolina, Chapel Hill, USA; Division of Pediatric Pulmonology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
¹¹ Marsico Lung Institute, University of North Carolina, Chapel Hill, USA; Department of Physics and Astrophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA. Electronic address: david_b_hill@med.unc.edu.

PMID: 35437233
DOI: 10.1016/j.jcf.2022.04.008

Free article

Mucus and mucus flake composition and abundance reflect inflammatory and infection status in cystic fibrosis

Matthew R Markovetz et al. J Cyst Fibros. 2022 Nov.

Free article

. 2022 Nov;21(6):959-966.

doi: 10.1016/j.jcf.2022.04.008. Epub 2022 Apr 16.

Authors

Affiliations

¹ Marsico Lung Institute, University of North Carolina, Chapel Hill, USA. Electronic address: matthew_markovetz@med.unc.edu.
² Marsico Lung Institute, University of North Carolina, Chapel Hill, USA.
³ Department of Mathematics, University of North Carolina, Chapel Hill, USA; Department of Applied Physical Sciences, University of North Carolina, Chapel Hill, USA.
⁴ Department of Mathematics, University of North Carolina, Chapel Hill, USA; Department of Applied Physical Sciences, University of North Carolina, Chapel Hill, USA; Department of Biomedical Engineering, University of North Carolina, Chapel Hill, USA.
⁵ Department of Applied Physical Sciences, University of North Carolina, Chapel Hill, USA.
⁶ Marsico Lung Institute, University of North Carolina, Chapel Hill, USA; Department of Applied Physical Sciences, University of North Carolina, Chapel Hill, USA.
⁷ National Health and Environmental Effects Research Laboratory, United States Environmental Protection Agency, University of North Carolina, Chapel Hill, USA.
⁸ Center for Environmental Medicine Asthma and Lung Biology, University of North Carolina, Chapel Hill, USA.
⁹ Telethon Kids Institute, University of Western Australia, Perth, Australia; Division of Pediatrics, University of Western Australia, Perth, Australia; Princess Margaret Hospital for Children, Perth, Australia.
¹⁰ Marsico Lung Institute, University of North Carolina, Chapel Hill, USA; Division of Pediatric Pulmonology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
¹¹ Marsico Lung Institute, University of North Carolina, Chapel Hill, USA; Department of Physics and Astrophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA. Electronic address: david_b_hill@med.unc.edu.

PMID: 35437233
DOI: 10.1016/j.jcf.2022.04.008

Abstract

Background: Mucus hyperconcentration in cystic fibrosis (CF) lung disease is marked by increases in both mucin and DNA concentration. Additionally, it has been shown that half of the mucins present in bronchial alveolar lavage fluid (BALF) from preschool-aged CF patients are present in as non-swellable mucus flakes. This motivates us to examine the utility of mucus flakes, as well as mucin and DNA concentrations in BALF as markers of infection and inflammation in CF airway disease.

Methods: In this study, we examined the mucin and DNA concentration, as well as mucus flake abundance, composition, and biophysical properties in BALF from three groups; healthy adult controls, and two CF cohorts, one preschool aged and the other school aged. BALFs were characterized via refractometry, PicoGreen, immunofluorescence microscopy, particle tracking microrheology, and fluorescence image tiling.

Results: Mucin and DNA BALF concentrations increased progressively from healthy young adult controls to preschool-aged people and school-aged people with CF. Notably, mucin concentrations were increased in bronchoalveolar lavage fluid (BALF) from preschool-aged patients with CF prior to decreased pulmonary function. Infrequent small mucus flakes were identified in normal subjects. A progressive increase in the abundance of mucus flakes in preschool and school-aged CF patients was observed. Compositionally, MUC5B dominated flakes from normal subjects, whereas an increase in MUC5AC was observed in people with CF, reflected in a reduced flaked MUC5B/MUC5AC mucin ratio.

Conclusion: These findings suggest mucus composition and flake properties are useful markers of inflammatory and infection-based changes in CF airways.

Keywords: Airway mucus; Gel-forming mucins; Infection; Microrheology; Mucus flakes.

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Conflict of interest statement

Declaration of Competing Interest The authors have no competing or conflicting interests to disclose that are relevant to this work.

Comment in

Is CF airway inflammation still relevant in the era of highly effective modulators?
Bengtson CD, Kim MD, Salathe M. Bengtson CD, et al. J Cyst Fibros. 2022 Nov;21(6):901-903. doi: 10.1016/j.jcf.2022.08.013. Epub 2022 Aug 24. J Cyst Fibros. 2022. PMID: 36028422 No abstract available.

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Mucus and mucus flake composition and abundance reflect inflammatory and infection status in cystic fibrosis

Affiliations

Mucus and mucus flake composition and abundance reflect inflammatory and infection status in cystic fibrosis

Authors

Affiliations

Abstract

Conflict of interest statement

Comment in

Publication types

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Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical