Journal
JOURNAL OF CYSTIC FIBROSIS
Volume 21, Issue 6, Pages 959-966Publisher
ELSEVIER
DOI: 10.1016/j.jcf.2022.04.008
Keywords
Airway mucus; Gel-forming mucins; Mucus flakes; Microrheology; Infection
Categories
Funding
- Cystic Fibrosis Foundation [MARKOV18F0, EHRE16XX0, HILL16XX0, BOUCHE15R0, FREEMA19G0, HILL19G0, HILL20Y2-OUT]
- NSF [DMS 1664645, 1816630, 2028758, CISE 1931516]
- Cancer Center Core Support Grant [P30 CA016086]
- Direct For Mathematical & Physical Scien
- Division Of Mathematical Sciences [2028758] Funding Source: National Science Foundation
- Direct For Mathematical & Physical Scien
- Division Of Mathematical Sciences [1816630] Funding Source: National Science Foundation
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The study reveals that the concentration of mucin and DNA in bronchoalveolar lavage fluid (BALF) progressively increases in cystic fibrosis (CF) patients, along with the presence of non-swellable mucus flakes. The composition and properties of these mucus flakes serve as useful markers for evaluating inflammatory and infection-based changes in CF airways.
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. (c) 2022 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
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