Highlights
- •Mucus flakes in CF BALF were larger and more abundant than flakes in normal BALF.
- •Mucin and DNA content were also elevated in CF BALF.
- •Insoluble CF flakes contained a greater proportion of mucins, which were mostly soluble in normal subjects.
- •MUC5B/MUC5AC ratio is altered in CF mucus flakes compared to normal subjects.
- •The biophysical properties of mucus flakes were also altered in CF flakes.
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
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Article info
Publication history
Published online: April 15, 2022
Accepted:
April 6,
2022
Received in revised form:
March 11,
2022
Received:
November 10,
2021
Identification
Copyright
© 2022 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
