Low CC16 mRNA Expression Levels in Bronchial Epithelial Cells Are Associated with Asthma Severity

被引：27

作者：

Li, Xingnan ^{[1
]}

Guerra, Stefano ^{[2
]}

Ledford, Julie G. ^{[2
]}

Kraft, Monica ^{[2
]}

Li, Huashi ^{[1
]}

Hastie, Annette T. ^{[3
]}

Castro, Mario ^{[4
]}

Denlinger, Loren C. ^{[5
]}

Erzurum, Serpil C. ^{[6
,7
]}

Fahy, John, V ^{[8
]}

Gaston, Benjamin ^{[9
,10
]}

Israel, Elliot ^{[11
,12
]}

Jarjour, Nizar N. ^{[5
]}

Levy, Bruce D. ^{[11
,12
]}

Mauger, David T. ^{[13
]}

Moore, Wendy C. ^{[3
]}

Zein, Joe ^{[6
,7
]}

Kaminski, Naftali ^{[14
]}

Wenzel, Sally E. ^{[15
]}

Woodruff, Prescott G. ^{[8
]}

Meyers, Deborah A. ^{[1
]}

Bleecker, Eugene R. ^{[1
]}

机构：

[1] Univ Arizona, Div Genet Genom & Precis Med, Dept Med, 1230 N Cherry Ave, Tucson, AZ 85719 USA

[2] Univ Arizona, Asthma & Airway Dis Res Ctr, Dept Med, Tucson, AZ 85719 USA

[3] Wake Forest Sch Med, Dept Med, Winston Salem, NC 27101 USA

[4] Univ Kansas, Sch Med, Div Pulm Crit Care & Sleep Med, Kansas City, KS USA

[5] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI USA

[6] Cleveland Clin, Lerner Res Inst, Cleveland, OH 44106 USA

[7] Cleveland Clin, Resp Inst, Cleveland, OH 44106 USA

[8] Univ Calif San Francisco, Dept Med, Div Pulm Crit Care Sleep & Allergy, San Francisco, CA 94143 USA

[9] Indiana Univ, Wells Ctr Pediat Res, Indianapolis, IN 46204 USA

[10] Indiana Univ, Riley Hosp Children, Indianapolis, IN 46204 USA

[11] Brigham & Womens Hosp, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA

[12] Harvard Med Sch, Boston, MA 02115 USA

[13] Penn State Univ, Coll Med, Dept Publ Hlth Sci, Hershey, PA USA

[14] Yale Sch Med, Dept Internal Med, Div Pulm Crit Care & Sleep Med, New Haven, CT USA

[15] Univ Pittsburgh, Dept Environm & Occupat Hlth, Pittsburgh, PA USA

来源：

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE | 2023年 / 207卷 / 04期

基金：

美国国家卫生研究院;

关键词：

asthma severity; asthma exacerbations; bronchial epithelial cells; CC16; T2; inflammation; SECRETORY PROTEIN; BRONCHOALVEOLAR LAVAGE; LUNG-FUNCTION; SERUM-LEVELS; A38G POLYMORPHISM; ALVEOLAR-LAVAGE; NATIONAL HEART; CLARA; BIOMARKER; GENE;

D O I：

10.1164/rccm.202206-1230OC

中图分类号：

R4 [临床医学];

学科分类号：

1002 ; 100602 ;

摘要：

Rationale: CC16 is a protein mainly produced by nonciliated bronchial epithelial cells (BECs) that participates in host defense. Reduced CC16 protein concentrations in BAL and serum are associated with asthma susceptibility. Objectives: Few studies have investigated the relationship between CC16 and asthma progression, and none has focused on BECs. In this study, we sought to determine if CC16 mRNA expression levels in BECs are associated with asthma severity. Methods: Association analyses between CC16 mRNA expression levels in BECs (242 asthmatics and 69 control subjects) and asthma-related phenotypes in Severe Asthma Research Program were performed using a generalized linear model. Measurements and Main Results: Low CC16 mRNA expression levels in BECs were significantly associated with asthma susceptibility and asthma severity, high systemic corticosteroids use, high retrospective and prospective asthma exacerbations, and low pulmonary function. Low CC16 mRNA expression levels were significantly associated with high T2 inflammation biomarkers (fractional exhaled nitric oxide and sputum eosinophils). CC16 mRNA expression levels were negatively correlated with expression levels of Th2 genes (IL1RL1, POSTN, SERPINB2, CLCA1, NOS2, and MUC5AC) and positively correlated with expression levels of Th1 and inflammation genes (IL12A and MUC5B). A combination of two nontraditional T2 biomarkers (CC16 and IL-6) revealed four asthma endotypes with different characteristics of T2 inflammation, obesity, and asthma severity. Conclusions: Our findings indicate that low CC16 mRNA expression levels in BECs are associated with asthma susceptibility, severity, and exacerbations, partially through immunomodulation of T2 inflammation. CC16 is a potential nontraditional T2 biomarker for asthma development and progression.

引用

页码：438 / 451

页数：14

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