Serum and BALF YKL-40 levels are predictors of survival in idiopathic pulmonary fibrosis.
BACKGROUND
The chitinase-like protein YKL-40 is a serum biomarker in diseases with fibrosis, inflammation and tissue remodelling. Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease that is hallmarked by these processes. The aim of this study was to investigate the potential of YKL-40 as a prognostic biomarker for survival in IPF patients.


METHODS
Serum and bronchoalveolar lavage fluid (BALF) levels of YKL-40 at the time of diagnosis and a promoter polymorphism in CHI3L1, the gene encoding YKL-40, were determined in 85 IPF patients and 126 controls. The relationship between YKL-40 levels and clinical parameters was evaluated. Kaplan-Meier and Cox regression analyses were used to examine the association between YKL-40 levels and survival.


RESULTS
Serum and BALF YKL-40 levels were significantly higher in patients than in healthy controls (p < 0.001). The - 329 A/G polymorphism had a significant influence on BALF YKL-40 levels and the influence on serum YKL-40 levels showed a trend towards significance in IPF patients. IPF patients with high (> 79 ng/ml) serum or high BALF YKL-40 (> 17 ng/ml) levels had significantly shorter survival than those with low YKL-40 levels in serum or BALF. In patients with both low serum and low BALF YKL-40 levels no IPF related mortality was observed. Cox regression modelling showed that there were no confounding factors.


CONCLUSIONS
The - 329 polymorphism was associated with serum and BALF YKL-40 levels in IPF patients. High serum and BALF YKL-40 levels are associated with poor survival in IPF patients and could be useful prognostic markers for survival in IPF.
Korthagen
Nicoline M
NM
Department of Pulmonology, St Antonius Hospital, Nieuwegein, The Netherlands. n.korthagen@antoniusziekenhuis.nl
van Moorsel
Coline H M
CH
Barlo
Nicole P
NP
Ruven
Henk J T
HJ
Kruit
Adrian
A
Heron
Michiel
M
van den Bosch
Jules M M
JM
Grutters
Jan C
JC
D054392:Adipokines; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D000071451:Chitinase-3-Like Protein 1; D005260:Female; D006023:Glycoproteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000378:metabolism* / Q000401:mortality; D037102:Lectins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D016016:Proportional Hazards Models
D054392:Adipokines; D015415:Biomarkers; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; D037102:Lectins