Mucociliary Clearance Differs in Mild Asthma by Levels of Type 2 Inflammation.
Adult
Asthma
/ diagnosis
Bronchial Provocation Tests
/ methods
Bronchoscopy
/ methods
Cell Adhesion Molecules
Chemokine CCL26
/ antagonists & inhibitors
Correlation of Data
Cross-Sectional Studies
Female
Gene Expression Profiling
Humans
Inflammation
/ immunology
Male
Mucociliary Clearance
/ immunology
Mucus
/ metabolism
Nitric Oxide Synthase Type II
/ analysis
Radiopharmaceuticals
/ pharmacology
Respiratory Function Tests
/ methods
Respiratory Tract Absorption
/ immunology
Severity of Illness Index
asthma
cilia
lung imaging
mucociliary clearance
mucus
scintigraphy
type 2 inflammation
Journal
Chest
ISSN: 1931-3543
Titre abrégé: Chest
Pays: United States
ID NLM: 0231335
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
received:
21
11
2020
revised:
30
04
2021
accepted:
03
05
2021
pubmed:
25
5
2021
medline:
14
1
2022
entrez:
24
5
2021
Statut:
ppublish
Résumé
Although mucus plugging is a well-reported feature of asthma, whether asthma and type 2 inflammation affect mucociliary clearance (MCC) is unknown. Does type 2 inflammation influence mucus clearance rates in patients with mild asthma who are not receiving corticosteroids? The clearance rates of inhaled radiolabeled particles were compared between patients with mild asthma with low (n = 17) and high (n = 18) levels of T2 inflammation. Fraction exhaled nitric oxide (Feno) was used to prospectively segregate subjects into T2 Lo (Feno < 25 ppb) and T2 Hi (Feno > 35 ppb) cohorts. Bronchial brush samples were collected with fiber-optic bronchoscopy, and quantitative polymerase chain reaction was performed to measure expression of genes associated with T2 asthma. MCC rate comparisons were also made with a historical group of healthy control subjects (HCs, n = 12). The T2 Lo cohort demonstrated increased MCC when compared with both T2 Hi and historic HCs. MCC within the T2 Hi group varied significantly, with some subjects having low or zero clearance. MCC decreased with increasing expression of several markers of T2 airway inflammation (CCL26, NOS2, and POSTN) and with Feno. MUC5AC and FOXJ1 expression was similar between the T2Lo and T2Hi cohorts. Increasing T2 inflammation was associated with decreasing MCC. High rates of MCC in T2 Lo subjects may indicate a compensatory mechanism present in mild disease but lost with high levels of inflammation. Future studies are required to better understand mechanisms and whether impairments in MCC in more severe asthma drive worse clinical outcomes.
Sections du résumé
BACKGROUND
Although mucus plugging is a well-reported feature of asthma, whether asthma and type 2 inflammation affect mucociliary clearance (MCC) is unknown.
RESEARCH QUESTION
Does type 2 inflammation influence mucus clearance rates in patients with mild asthma who are not receiving corticosteroids?
STUDY DESIGN AND METHODS
The clearance rates of inhaled radiolabeled particles were compared between patients with mild asthma with low (n = 17) and high (n = 18) levels of T2 inflammation. Fraction exhaled nitric oxide (Feno) was used to prospectively segregate subjects into T2 Lo (Feno < 25 ppb) and T2 Hi (Feno > 35 ppb) cohorts. Bronchial brush samples were collected with fiber-optic bronchoscopy, and quantitative polymerase chain reaction was performed to measure expression of genes associated with T2 asthma. MCC rate comparisons were also made with a historical group of healthy control subjects (HCs, n = 12).
RESULTS
The T2 Lo cohort demonstrated increased MCC when compared with both T2 Hi and historic HCs. MCC within the T2 Hi group varied significantly, with some subjects having low or zero clearance. MCC decreased with increasing expression of several markers of T2 airway inflammation (CCL26, NOS2, and POSTN) and with Feno. MUC5AC and FOXJ1 expression was similar between the T2Lo and T2Hi cohorts.
INTERPRETATION
Increasing T2 inflammation was associated with decreasing MCC. High rates of MCC in T2 Lo subjects may indicate a compensatory mechanism present in mild disease but lost with high levels of inflammation. Future studies are required to better understand mechanisms and whether impairments in MCC in more severe asthma drive worse clinical outcomes.
Identifiants
pubmed: 34029561
pii: S0012-3692(21)00906-5
doi: 10.1016/j.chest.2021.05.013
pmc: PMC8628176
pii:
doi:
Substances chimiques
CCL26 protein, human
0
Cell Adhesion Molecules
0
Chemokine CCL26
0
POSTN protein, human
0
Radiopharmaceuticals
0
NOS2 protein, human
EC 1.14.13.39
Nitric Oxide Synthase Type II
EC 1.14.13.39
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1604-1613Informations de copyright
Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.
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