KL-6, a mucinous glycoprotein, as an indicator of chronic lung disease of the newborn

Ogihara, Tohru; Hirano, Kazuya; Morinobu, Takao; Ogawa, Satoshi; Hiroi, Mayo; Ban, Ryoichi; Ogihara, Hiromi; Tamai, Hiroshi

doi:10.1067/mpd.2000.107109

Cited by 19 publications

(22 citation statements)

References 10 publications

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“…Plasma KL-6 was measured using a sandwich-type ELISA kit (Eitest KL-6, Eisai Co. Ltd., Tokyo, Japan) according to the method reported previously (17), which requires 10 L of plasma. The levels of IL-1␤, IL-6, IL-8, TNF-␣, and MIP-1␣ were also measured using ELISA kits (BioSource International, Camarillo, CA).…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2006

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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.

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Section: Methodsmentioning

confidence: 99%

“…We previously found an increase of the plasma KL-6 level in infants with BPD, suggesting that KL-6 was an early marker of BPD and an indicator of its severity (17). The present prospective study was performed on a larger scale to determine the reference range of plasma KL-6 in relation to postnatal age and to confirm the diagnostic value of KL-6 for BPD.…”

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

et al. 2006

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“…The KL-6 levels in cord plasma were measured using a cuptype sandwich ELISA kit (Eitest KL-6, Eisai Co. Ltd., Tokyo, and kindly donated by the Sanko Junyaku Co., Ltd., Tokyo, Japan), as previously described [11,12] . All samples were analyzed in duplicate.…”

Section: Measurementsmentioning

confidence: 99%

“…KL-6 is preferentially expressed on alveolar type II cells in human lungs and is a specific lung injury marker, which is expressed more prominently during the regeneration of alveolar type II cells after alveolar injury [10,11] . In neonatal lung disease, Ogihara et al [12,13] found an increase in plasma KL-6 levels in infants with BPD and suggested that KL-6 is a useful early marker of BPD and an indicator of disease severity.…”

Section: Introductionmentioning

confidence: 99%

Cord Blood KL-6, a Specific Lung Injury Marker, Correlates with the Subsequent Development and Severity of Atypical Bronchopulmonary Dysplasia

Kim

Shim

et al. 2007

Neonatology

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Background: A considerable number of preterm infants may have been exposed to inflammation in utero and may be born with an inflamed lung. Objectives: To determine the impact of antenatal lung injury and inflammatory response on the pathogenesis of bronchopulmonary dysplasia (BPD) according to its clinical pattern, using KL-6 (as a lung injury marker) and C-reactive protein (CRP) (as a marker of inflammatory response). Methods: In this case-control study, a total of 74 infants (<32 weeks of gestation) including BPD with minimal early lung disease (‘atypical’; 21 infants), BPD with significant early lung disease (‘classic’; 29 infants) and the non-BPD (24 infants) groups underwent KL-6 and CRP in cord blood determinations. Results: The cord plasma KL-6 levels were significantly higher in the atypical and the total BPD groups than in the non-BPD group (median = 60.9 vs. 34.5 U/ml, p = 0.031; 43.5 vs. 34.5 U/ml, p = 0.02). However, the cord plasma CRP levels were not significantly different among the study groups. The cord plasma KL-6 levels in patients with atypical BPD were significantly higher in infants with moderate or severe BPD than in infants with mild BPD (median = 88.3 vs. 41.5 U/ml, p = 0.041) and were found to be significantly correlated with the duration of oxygen therapy (r = 0.502, p = 0.024). Conclusions: The present study shows that cord plasma KL-6, a specific lung injury marker, is increased and objectively reflects disease severity in atypical BPD.

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“…To estimate the extent of lung parenchymal injury, we measured the plasma KL-6 concentration. KL-6 is a high-molecular-weight mucinous glycoprotein, and its level is increased in patients with various types of interstitial lung disease, including bronchopulmonary dysplasia and MAS [17][18][19] . Therefore, it is thought to be a specific indicator of pulmonary injury affecting both the alveolar epithelium and interstitium [20] .…”

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Meconium Aspiration Delays Normal Decline of Pulmonary Vascular Resistance Shortly after Birth through Lung Parenchymal Injury

Ban

Ogihara²,

Mori³

et al. 2010

Neonatology

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Background: Persistent pulmonary hypertension of the newborn is often associated with meconium aspiration syndrome (MAS) or perinatal asphyxia. Objective: To determine the effect of meconium or asphyxia on pulmonary arterial pressure and circulating levels of vasoactive substances, we conducted a prospective study of 54 term infants, including infants with meconium-stained amniotic fluid with normal (MSAF) or abnormal (MAS) chest X-ray findings, infants with perinatal asphyxia, and controls. The purpose of this study was to determine the group most likely to have elevated pulmonary arterial pressure and a disturbed balance between vasoactive substances. Methods: To estimate the pulmonary arterial pressure by echocardiography, we used the ratio of the right to left systolic ventricular pressure (RVP/LVP ratio). We measured the plasma concentrations of endothelin-1 (ET-1), cyclic guanosine monophosphate (cGMP) as an indicator of nitric oxide (NO) production, and 6-keto-prostaglandin F₁α (6-keto-PGF₁α) for the estimation of prostacyclin concentration. We also measured KL-6 as a marker of lung injury. Results:The RVP/LVP ratio was significantly higher in the MAS group than the other groups on day 0. Although ET-1 and 6-keto-PGF₁α levels were comparable among all groups, the cGMP level on days 3–5 and the KL-6 level throughout the first postnatal week were significantly higher in the MAS group. Conclusions: It is possible that meconium aspiration delays normal decline of pulmonary vascular resistance shortly after birth through lung parenchymal injury. The subsequent increase of cGMP in MAS may be an adaptive response to prevent further elevation of pulmonary arterial pressure by inducing NO.

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KL-6, a mucinous glycoprotein, as an indicator of chronic lung disease of the newborn

Cited by 19 publications

References 10 publications

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

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

Cord Blood KL-6, a Specific Lung Injury Marker, Correlates with the Subsequent Development and Severity of Atypical Bronchopulmonary Dysplasia

Meconium Aspiration Delays Normal Decline of Pulmonary Vascular Resistance Shortly after Birth through Lung Parenchymal Injury

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