Mucus accumulation in the lungs precedes structural changes and infection in children with cystic fibrosis.
Journal
Science translational medicine
ISSN: 1946-6242
Titre abrégé: Sci Transl Med
Pays: United States
ID NLM: 101505086
Informations de publication
Date de publication:
03 04 2019
03 04 2019
Historique:
received:
12
09
2018
accepted:
10
03
2019
entrez:
5
4
2019
pubmed:
5
4
2019
medline:
6
5
2020
Statut:
ppublish
Résumé
Although destructive airway disease is evident in young children with cystic fibrosis (CF), little is known about the nature of the early CF lung environment triggering the disease. To elucidate early CF pulmonary pathophysiology, we performed mucus, inflammation, metabolomic, and microbiome analyses on bronchoalveolar lavage fluid (BALF) from 46 preschool children with CF enrolled in the Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF) program and 16 non-CF disease controls. Total airway mucins were elevated in CF compared to non-CF BALF irrespective of infection, and higher densities of mucus flakes containing mucin 5B and mucin 5AC were observed in samples from CF patients. Total mucins and mucus flakes correlated with inflammation, hypoxia, and oxidative stress. Many CF BALFs appeared sterile by culture and molecular analyses, whereas other samples exhibiting bacterial taxa associated with the oral cavity. Children without computed tomography-defined structural lung disease exhibited elevated BALF mucus flakes and neutrophils, but little/no bacterial infection. Although CF mucus flakes appeared "permanent" because they did not dissolve in dilute BALF matrix, they could be solubilized by a previously unidentified reducing agent (P2062), but not
Identifiants
pubmed: 30944166
pii: 11/486/eaav3488
doi: 10.1126/scitranslmed.aav3488
pmc: PMC6566903
mid: NIHMS1028510
pii:
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIEHS NIH HHS
ID : P30 ES010126
Pays : United States
Organisme : NHLBI NIH HHS
ID : K23 HL089708
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL136961
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL110873
Pays : United States
Organisme : NHLBI NIH HHS
ID : P50 HL107168
Pays : United States
Organisme : NHLBI NIH HHS
ID : UH3 HL123645
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL116228
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL108808
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK065988
Pays : United States
Informations de copyright
Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
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