A Novel Association between YKL-40, a Marker of Structural Lung Disease, and Short Telomere Length in 10-Year-Old Children with Bronchopulmonary Dysplasia

Abstract

Extremely preterm infants are born with immature lungs and are exposed to an inflammatory environment as a result of oxidative stress. This may lead to airway remodeling, cellular aging and the development of bronchopulmonary dysplasia (BPD). Reliable markers that predict the long-term consequences of BPD in infancy are still lacking. We analyzed two biomarkers of cellular aging and lung function, telomere length and YKL-40, respectively, at 10 years of age in children born preterm with a history of BPD (n = 29). For comparison, these markers were also evaluated in sex-and-age-matched children born at term with childhood asthma (n = 28). Relative telomere length (RTL) was measured in whole blood with qPCR and serum YKL-40 with ELISA, and both were studied in relation to gas exchange and the regional ventilation/perfusion ratio using three-dimensional V/Q-scintigraphy (single photon emission computer tomography, SPECT) in children with BPD. Higher levels of YKL-40 were associated with shorter leukocyte RTL (Pearson’s correlation: −0.55, p = 0.002), but were not associated with a lower degree of matching between ventilation and perfusion within the lung. Serum YKL-40 levels were significantly higher in children with BPD compared to children with asthma (17.7 vs. 13.2 ng/mL, p < 0.01). High levels of YKL-40 and short RTLs were associated to the need for ventilatory support more than 1 month in the neonatal period (p < 0.01). The link between enhanced telomere shortening in childhood and structural remodeling of the lung, as observed in children with former BPD but not in children with asthma at the age of 10 years, suggests altered lung development related to prematurity and early life inflammatory exposure. In conclusion, relative telomere length and YKL-40 may serve as biomarkers of altered lung development as a result of early-life inflammation in children with a history of prematurity.

Genetic, Environmental and Lifestyle Determinants of Accelerated Telomere Attrition as Contributors to Risk and Severity of Multiple Sclerosis

“…Plasma levels of acutephase proteins such as C-reactive protein (CRP) and serum amyloid A (SAA) and of other indicators of inflammation such as TNF-α and IL-6 have also been associated with shorter LTL [8,10]. Moreover, chitinase 3-like protein levels were found to correlate negatively with spleen TL in mice (r = −0.636) [11] and with LTL in humans (r = −0.547) [12]. Chitinase enzyme activity in blood plasma is a biomarker of human aging and is elevated in agingassociated and inflammatory diseases [13].…”

Serum YKL-40 as a Potential Biomarker for Sepsis in Term Neonates—A Pilot Study

“…Similarly, a group of researchers from Egypt [41] concluded that the diagnostic value of urine YKL-40 was higher than that of urine neutrophil gelatinaseassociated lipocalin (NGAL), proposing that it could be a valuable biomarker for the diagnosis of a UTI in febrile pediatric patients. More recently, Henckel et al [42], in a cross-sectional study that included 29 10-year-old children who had been born preterm and were diagnosed with bronchopulmonary dysplasia, nominated YKL-40 as being a novel biomarker of altered lung development due to early-life inflammation in children with a history of prematurity. Furthermore, in children with juvenile idiopathic arthritis, YKL-40 was proposed as a marker of the efficacy of biologic treatment [43], whereas in children with human immunodeficiency virus (HIV) infection, YKL-40 levels were associated with viral load and poor virologic control, as well as immune dysregulation and microbial translocation [44].…”

Unravelling the respiratory health path across the lifespan for survivors of preterm birth

“…82 Additional proposed mechanisms underpinning active disease in survivors born preterm include altered immune programming, microbiome dysbiosis, epithelial abnormalities, accelerated cellular ageing, and host genetics. [82][83][84][85][86][87][88] External exposures, including tobacco smoke, air pollution and repeated viral respiratory infections, may similarly initiate cellular injury and remodelling, resulting in worsening of existing lung disease. [89][90][91] Limited data exist to draw firm conclusions about underlying mechanisms associated with PLD; although it is clear that numerous active pathways and pathologies are implicated (see Figure 2 for summary).…”