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Mucus and mucus flake composition and abundance reflect inflammatory and infection status in cystic fibrosis.
Markovetz, Matthew R; Garbarine, Ian C; Morrison, Cameron B; Kissner, William J; Seim, Ian; Forest, M Gregory; Papanikolas, Micah J; Freeman, Ronit; Ceppe, Agathe; Ghio, Andrew; Alexis, Neil E; Stick, Stephen M; Ehre, Camille; Boucher, Richard C; Esther, Charles R; Muhlebach, Marianne S; Hill, David B.
Affiliation
  • Markovetz MR; Marsico Lung Institute, University of North Carolina, Chapel Hill, USA. Electronic address: matthew_markovetz@med.unc.edu.
  • Garbarine IC; Marsico Lung Institute, University of North Carolina, Chapel Hill, USA.
  • Morrison CB; Marsico Lung Institute, University of North Carolina, Chapel Hill, USA.
  • Kissner WJ; Marsico Lung Institute, University of North Carolina, Chapel Hill, USA.
  • Seim I; Department of Mathematics, University of North Carolina, Chapel Hill, USA; Department of Applied Physical Sciences, University of North Carolina, Chapel Hill, USA.
  • Forest MG; 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.
  • Papanikolas MJ; Department of Applied Physical Sciences, University of North Carolina, Chapel Hill, USA.
  • Freeman R; Marsico Lung Institute, University of North Carolina, Chapel Hill, USA; Department of Applied Physical Sciences, University of North Carolina, Chapel Hill, USA.
  • Ceppe A; Marsico Lung Institute, University of North Carolina, Chapel Hill, USA.
  • Ghio A; National Health and Environmental Effects Research Laboratory, United States Environmental Protection Agency, University of North Carolina, Chapel Hill, USA.
  • Alexis NE; Center for Environmental Medicine Asthma and Lung Biology, University of North Carolina, Chapel Hill, USA.
  • Stick SM; 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.
  • Ehre C; Marsico Lung Institute, University of North Carolina, Chapel Hill, USA.
  • Boucher RC; Marsico Lung Institute, University of North Carolina, Chapel Hill, USA.
  • Esther CR; 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.
  • Muhlebach MS; 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.
  • Hill DB; 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.
J Cyst Fibros ; 21(6): 959-966, 2022 11.
Article in En | MEDLINE | ID: mdl-35437233
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cystic Fibrosis Type of study: Prognostic_studies Limits: Adult / Child / Child, preschool / Humans Language: En Journal: J Cyst Fibros Year: 2022 Document type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cystic Fibrosis Type of study: Prognostic_studies Limits: Adult / Child / Child, preschool / Humans Language: En Journal: J Cyst Fibros Year: 2022 Document type: Article
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