The relation of circulating YKL-40 to levels and decline of lung function in adult life.
BACKGROUND
YKL-40 is a chitinase-like protein that, in cross-sectional clinical studies, has been associated with severe asthma and COPD in smokers.


OBJECTIVE
To determine the longitudinal relation of circulating YKL-40 to levels and decline of lung function in the general population.


METHODS
We used longitudinal data from up to 13 surveys from the population-based TESAOD study which was conducted in Tucson, Arizona between 1972 and 1996. In cross-sectional analyses, we also used data from 3 Spanish centers of the multicenter ECRHS study (ECRHS-Sp). Serum YKL-40 was measured at baseline in TESAOD and in survey 2 in ECRHS-Sp using ELISAs. Multivariate linear regression was used to test associations of serum YKL-40 to concomitant lung function. In TESAOD, random coefficients models were used to test associations of serum YKL-40 to subsequent decline of lung function.


RESULTS
Data on YKL-40 and lung function were available from 1088 TESAOD and 854 ECRHS-Sp adult participants (59% and 51% females; respectively). In adjusted multivariate meta-analyses, being in the highest YKL-40 quartile was associated cross-sectionally with significant deficits in FEV1 and FVC %predicted. In adjusted longitudinal analyses, TESAOD participants in the top YKL-40 quartile had an FEV1 decline that was 5 ml/yr (p = 0.05) faster than subjects in the third quartile, 5 ml/yr (p = 0.02) faster than subjects in the second quartile, and 10 ml/yr (p < 0.001) faster than subjects in the lowest YKL-40 quartile. These longitudinal effects were particularly strong in smokers and absent in never smokers. After adjusting for covariates, as compared with the other three quartiles combined, the top YKL-40 quartile was associated with a 9 ml/yr (p = 0.001) faster FEV1 decline among smokers, while no significant effects were found among never smokers (2 ml/yr, p = 0.35).


CONCLUSIONS
Circulating YKL-40 is associated with levels and decline of lung function in the general population and may be a biomarker of susceptibility to the long-term effects of cigarette smoking.
Arizona Respiratory Center, University of Arizona, Tucson, AZ, USA; Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; IMIM (Hospital del Mar Research Institute), Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain. Electronic address: stefano@email.arizona.edu.
Stefano
S
Guerra
Marilyn
M
Halonen
Duane L
DL
Sherrill
Claire
C
Venker
Amber
A
Spangenberg
Anne-elie
AE
Carsin
Lluïsa
L
Tarès
Iris
I
Lavi
Esther
E
Barreiro
Jesús
J
Martínez-Moratalla
Isabel
I
Urrutia
Jordi
J
Sunyer
Josep M
JM
Antó
Fernando D
FD
Martinez
D054392:Adipokines / Q000378:metabolism*; D000328:Adult; D000368:Aged; D001249:Asthma / Q000378:metabolism / Q000503:physiopathology*; D000071451:Chitinase-3-Like Protein 1; D004812:Epidemiologic Methods; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D037102:Lectins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism / Q000503:physiopathology*; D012907:Smoking / Q000378:metabolism / Q000503:physiopathology; D014797:Vital Capacity / Q000502:physiology; D055815:Young Adult
D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D037102:Lectins
Lung function; Smoking; YKL-40