Plasma KL-6 Predicts the Development and Outcome of Bronchopulmonary Dysplasia

Abstract

Circulating KL-6 is a specific indicator of pulmonary injury affecting the alveolar epithelium and interstitium. Our preliminary study suggested the usefulness of plasma KL-6 as a marker of bronchopulmonary dysplasia (BPD). To confirm the diagnostic value of KL-6 for BPD as well as to determine the reference range, we conducted a larger prospective study in 135 preterm infants Ͻ32 wk GA. Among the infants without oxygen dependence at a postconceptional age of 36 wk, the plasma KL-6 level showed no significant association with GA at any time. Among 42 infants Ͻ28 wk GA, plasma KL-6 levels were significantly higher in those with moderate/ severe BPD compared with those with no/mild BPD. A plasma level of 199 U/mL at 1 wk or 232 U/mL at 2 wk was an excellent predictor of moderate/severe BPD Ͻ28 wk GA (positive predictive value of 83% and 80%, respectively). Unlike nonspecific markers of inflammation or fibrosis, KL-6 objectively reflects the severity of pulmonary injury irrespective of the treatment or the radiographic changes. Therefore, not only as a good marker, measurement of KL-6 may also help to provide new insights into the pathogenesis of BPD.

Neutrophil-Gelatinase-Associated Lipocalin 2, Krebs Von den Lungen-6, Beta 2 Microglobulin, and Adiponectin: Crosstalk in Early Prediction of Bronchopulmonary Dysplasia in Egyptian Preterm

“…In this study cord blood KL-6 level were elevated in preterm with BPD than control so that it may has a role in early prediction and future treatment of BPD. These results were in harmony with results obtained by Kim et al, [7] and Shigemura et al, [18] proved the importance of serum KL-6 as a marker of sarcoidosis and other interstitial lung diseases. Ogihara et al, [19] reported that KL-6, a specific lung injury marker, is increased and reflects BPD disease severity.…”

Antenatal exposure to Ureaplasma species exacerbates bronchopulmonary dysplasia synergistically with subsequent prolonged mechanical ventilation in preterm infants

“…To clarify the effect of antenatal exposure to Ureaplasma species or other bacteria on premature lung tissue, we used KL-6 as a lung injury marker (because serum levels of KL-6 are known to increase after lung injury) correlating with the severity of respiratory distress in infants with BPD (18). Among the infants with MV ≥2 wk, the median KL-6 level in the cord blood of Ureaplasma-positive infants, was higher than in that of the bacteria-negative infants, and this difference in KL-6 levels increased time-dependently after birth (Figure 1a).…”

“…This indication of lung injury was associated with an increased severity of subsequent BPD. Because KL-6 is a mucinous glycoprotein that is expressed by alveolar type II cells and bronchiolar cells and is known to be specifically correlated with the severity of respiratory distress in infants with BPD, increased plasma KL-6 levels at birth are presumed to be due to injury in the immature lungs resulting in the subsequent development of BPD (17,18). However, we could not clarify precisely which microorganism was most likely to play a pathogenic role in the ongoing process of BPD.…”

Predictive values of plasma KL-6 in bronchopulmonary dysplasia in preterm infants

“…Many studies have suggested that lung inflammation is a major contributor to the pathogenesis of BPD (5,6). Various parameters of lung inflammation may be used to show lung inflammation.…”

“…Various parameters of lung inflammation may be used to show lung inflammation. However, most of them such as N-terminal propeptide of type 3 collagen, SP-A, anti-SP-A immune complexes, nitrotyrosine, soluble E-selectin, intercellular adhesion molecule-1, allantoin, and aldehydes are not specific for lung disease or are complicated to measure (6). Krebs yon den Lundgen-6 (KL-6) is a mucinlike high-molecular weight glycoprotein that is classified into cluster 9 (MUC1) of lung tumor and differentiation antigens.…”