TY - JOUR
T1 - Circulating CC16 and Asthma A Population-based, Multicohort Study from Early Childhood through Adult Life
AU - Voraphani, Nipasiri
AU - Stern, Debra A.
AU - Ledford, Julie G.
AU - Spangenberg, Amber L.
AU - Zhai, Jing
AU - Wright, Anne L.
AU - Morgan, Wayne J.
AU - Kraft, Monica
AU - Sherrill, Duane L.
AU - Curtin, John A.
AU - Murray, Clare S.
AU - Custovic, Adnan
AU - Kull, Inger
AU - Hallberg, Jenny
AU - Bergström, Anna
AU - Herrera-Luis, Esther
AU - Halonen, Marilyn
AU - Martinez, Fernando D.
AU - Simpson, Angela
AU - Melén, Erik
AU - Guerra, Stefano
N1 - Publisher Copyright:
Copyright © 2023 by the American Thoracic Society.
PY - 2023/10/1
Y1 - 2023/10/1
N2 - Rationale: Club cell secretory protein (CC16) is an antiinflammatory protein highly expressed in the airways. CC16 deficiency has been associated with lung function deficits, but its role in asthma has not been established conclusively. Objectives: To determine 1) the longitudinal association of circulating CC16 with the presence of active asthma from early childhood through adult life and 2) whether CC16 in early childhood predicts the clinical course of childhood asthma into adult life. Methods: We assessed the association of circulating CC16 and asthma in three population-based birth cohorts: the Tucson Children’s Respiratory Study (years 6–36; total participants, 814; total observations, 3,042), the Swedish Barn/Children, Allergy, Milieu, Stockholm, Epidemiological survey (years 8–24; total participants, 2,547; total observations, 3,438), and the UK Manchester Asthma and Allergy Study (years 5–18; total participants, 745; total observations, 1,626). Among 233 children who had asthma at the first survey in any of the cohorts, baseline CC16 was also tested for association with persistence of symptoms. Measurements and Main Results: After adjusting for covariates, CC16 deficits were associated with increased risk for the presence of asthma in all cohorts (meta-analyzed adjusted odds ratio per 1-SD CC16 decrease, 1.20; 95% confidence interval [CI], 1.12–1.28; P, 0.0001). The association was particularly strong for asthma with frequent symptoms (meta-analyzed adjusted relative risk ratio, 1.40; 95% CI, 1.24–1.57; P, 0.0001), was confirmed for both atopic and nonatopic asthma, and was independent of lung function impairment. After adjustment for known predictors of persistent asthma, children with asthma in the lowest CC16 tertile had a nearly fourfold increased risk for having frequent symptoms persisting into adult life compared with children with asthma in the other two CC16 tertiles (meta-analyzed adjusted odds ratio, 3.72; 95% CI, 1.78–7.76; P, 0.0001). Conclusions: Circulating CC16 deficits are associated with the presence of asthma with frequent symptoms from childhood through midadult life and predict the persistence of asthma symptoms into adulthood. These findings support a possible protective role of CC16 in asthma and its potential use for risk stratification.
AB - Rationale: Club cell secretory protein (CC16) is an antiinflammatory protein highly expressed in the airways. CC16 deficiency has been associated with lung function deficits, but its role in asthma has not been established conclusively. Objectives: To determine 1) the longitudinal association of circulating CC16 with the presence of active asthma from early childhood through adult life and 2) whether CC16 in early childhood predicts the clinical course of childhood asthma into adult life. Methods: We assessed the association of circulating CC16 and asthma in three population-based birth cohorts: the Tucson Children’s Respiratory Study (years 6–36; total participants, 814; total observations, 3,042), the Swedish Barn/Children, Allergy, Milieu, Stockholm, Epidemiological survey (years 8–24; total participants, 2,547; total observations, 3,438), and the UK Manchester Asthma and Allergy Study (years 5–18; total participants, 745; total observations, 1,626). Among 233 children who had asthma at the first survey in any of the cohorts, baseline CC16 was also tested for association with persistence of symptoms. Measurements and Main Results: After adjusting for covariates, CC16 deficits were associated with increased risk for the presence of asthma in all cohorts (meta-analyzed adjusted odds ratio per 1-SD CC16 decrease, 1.20; 95% confidence interval [CI], 1.12–1.28; P, 0.0001). The association was particularly strong for asthma with frequent symptoms (meta-analyzed adjusted relative risk ratio, 1.40; 95% CI, 1.24–1.57; P, 0.0001), was confirmed for both atopic and nonatopic asthma, and was independent of lung function impairment. After adjustment for known predictors of persistent asthma, children with asthma in the lowest CC16 tertile had a nearly fourfold increased risk for having frequent symptoms persisting into adult life compared with children with asthma in the other two CC16 tertiles (meta-analyzed adjusted odds ratio, 3.72; 95% CI, 1.78–7.76; P, 0.0001). Conclusions: Circulating CC16 deficits are associated with the presence of asthma with frequent symptoms from childhood through midadult life and predict the persistence of asthma symptoms into adulthood. These findings support a possible protective role of CC16 in asthma and its potential use for risk stratification.
KW - CC16
KW - asthma
KW - birth cohorts
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U2 - 10.1164/rccm.202301-0041OC
DO - 10.1164/rccm.202301-0041OC
M3 - Article
C2 - 37523710
AN - SCOPUS:85172940549
SN - 1073-449X
VL - 208
SP - 758
EP - 769
JO - American journal of respiratory and critical care medicine
JF - American journal of respiratory and critical care medicine
IS - 7
ER -