Henckel Ewa, James Anna, Konradsen Jon R, Nordlund Björn, Kjellberg Malin, Berggren-Broström Eva, Hedlin Gunilla, Degerman Sofie, Bohlin Kajsa
Department of Clinical Science, Intervention and Technology, Karolinska Institutet, 141 86 Stockholm, Sweden.
Department of Women's and Children's Health, Karolinska Institutet, 171 77 Stockholm, Sweden.
Children (Basel). 2021 Jan 24;8(2):80. doi: 10.3390/children8020080.
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 ( = 29). For comparison, these markers were also evaluated in sex-and-age-matched children born at term with childhood asthma ( = 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, = 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, < 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 ( < 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.
极早产儿出生时肺部未发育成熟，由于氧化应激而暴露于炎症环境中。这可能导致气道重塑、细胞衰老以及支气管肺发育不良（BPD）的发生。目前仍缺乏能够预测婴儿期BPD长期后果的可靠标志物。我们分别分析了29例有BPD病史的早产儿童10岁时细胞衰老和肺功能的两种生物标志物——端粒长度和YKL-40。为作比较，还在28例足月出生且患有儿童哮喘的性别和年龄匹配儿童中评估了这些标志物。采用qPCR法检测全血中的相对端粒长度（RTL），用ELISA法检测血清YKL-40，并在患有BPD的儿童中使用三维通气/灌注（V/Q）闪烁扫描（单光子发射计算机断层扫描，SPECT）研究二者与气体交换及局部通气/灌注比的关系。YKL-40水平较高与白细胞RTL较短相关（Pearson相关性：-0.55，P = 0.002），但与肺内通气与灌注的匹配程度较低无关。与哮喘儿童相比，BPD儿童的血清YKL-40水平显著更高（17.7对13.2 ng/mL，P < 0.01）。高水平的YKL-40和较短的RTL与新生儿期需要超过1个月的通气支持相关（P < 0.01）。在10岁时，曾患BPD的儿童出现了儿童期端粒缩短增强与肺结构重塑之间的联系，而哮喘儿童未出现这种情况，这表明与早产和生命早期炎症暴露相关的肺发育改变。总之，相对端粒长度和YKL-40可能作为有早产病史儿童生命早期炎症导致肺发育改变的生物标志物。
