Ayşegül ZENCİROĞLU, Arzu DURSUN, Nurullah OKUMUŞ, Dilek DİLLİ, Serdar BEKEN, Nurdan FETTAH, Ahmet ÖZYAZICI

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

Background/aim: It has been suggested that plasma KL-6 increases in premature infants with bronchopulmonary dysplasia (BPD). We aimed to evaluate the predictive values of KL-6 in BPD. Materials and methods: The study was performed in preterm neonates with birthweight ≤1500 g and gestational age ≤32 weeks. Plasma KL-6 levels were measured on postnatal days 1, 7, and 14. Results: BPD was identified in eight of the 28 study infants. On postnatal days 1 and 7, plasma KL-6 levels were similar in infants with BPD [on day 1: 8.9 (7.5 17.8) U/mL and on day 7: 16.8 (10.5 47.7) U/mL] and without BPD [on day 1: 10.8 (9.4 17.2) U/mL and on day 7: 12.9 (5.8 19.3) U/mL] (P = 0.38 and P = 0.13, respectively). On day 14, KL-6 levels were significantly higher in infants with BPD [155.2 (15.3 545.6) U/mL] than they were in infants without BPD [7.9 (7.7 15.6) U/mL] (P = 0.001). The best predictor was KL-6 levels on postnatal day 14 (area under the ROC curve = 0.88; range 0.75 1.0; P = 0.002). At this point, KL-6 level of 59.7 U/mL showed a specificity of 90.0% and negative predictive value of 85.7% for BPD. Conclusion: High plasma KL-6 levels on postnatal day 14 in premature infants may predict the development of BPD.

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1. Baraldi E, Carraro S, M. Filippone M. Bronchopulmonary dysplasia: definitions and long-term respiratory outcome. Early Hum Dev 2009; 85 (10 Suppl): S1-3.
2. Ambalavanan N, Carlo WA. Ventilatory strategies in the prevention and management of bronchopulmonary dysplasia. Semin Perinatol 2006; 30: 192-199.
3. Bhandari V, Finer NN, Ehrenkranz RA, Saha S, Das A, Walsh MC, Engle WA, VanMeurs KP; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Synchronized nasal intermittent positive-pressure ventilation and neonatal outcomes. Pediatrics 2009; 124: 517-526.
4. Reyburn B, Martin RJ, Prakash YS, MacFarlane PM. Mechanisms of injury to the preterm lung and airway: implications for long-term pulmonary outcome. Neonatology 2012; 101: 345-352.
5. Aghai ZH, Saslow JG, Mody K, Eydelman R, Bhat V, Stahl G, Pyon K, Bhandari V. IFN-γ and IP-10 in tracheal aspirates from premature infants: relationship with bronchopulmonary dysplasia. Pediatr Pulmonol 2013; 48: 8-13.
6. Ogihara T, Hirano K, Morinobu T, Kim HS, Ogawa S, Hiroi M, OUe S, Ban R, Hira S, Hasegawa M et al. Plasma KL-6 preicts the development and outcome of bronchopulmonary dysplasia. Pediatr Res 2006; 60: 613-618.
7. Kohno N, Akiyama M, Kyoizumi S, Hakoda M, Kobuke K, Yamakido M. Detection of soluble tumor-associated antigens in sera and effusions using novel monoclonal antibodies, KL-3 and KL-6, against lung adenocarcinoma. Jpn J Clin Oncol 1988; 18: 203-216.
8. Yokoyama A, Kohno N, Hamada H, Sakatani M, Ueda E, Kondo K, Hirasawa Y, Hiwada K. Circulating KL-6 predicts the outcome of rapidly progressive idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 1998; 158: 1680-1684.
9. Kohno N, Kyoizumi S, Awaya Y, Fukuhara H, Yamakido M, Akiyama M. New serum indicator of interstitial pneumonitis activity. Sialylated carbohydrate antigen KL-6. Chest 1989; 96: 68-73.
10. Kashiwabara K, Semba H, Fujii S, Tsumura S, Aoki R. The ratio KL-6 to SLX in serum for prediction of the occurrence of druginduced interstitial lung disease in lung cancer patients with idiopathic interstitial pneumonias receiving chemotherapy. Cancer Invest 2015:1-6.
11. Hu Y, Wang LS, Jin YP, Du SS, Du YK, He X, Weng D, Zhou Y, Li QH, Shen L, et al. Serum Krebs von den Lungen-6 level as a diagnostic biomarker for interstitial lung disease in Chinese patients. Clin Respir J 2015 Jun 16. doi:10.1111/crj.12341.
12. Ishizaka A, Matsuda T, Albertine KH, Koh H, Tasaka S, Hasegawa N, Kohno N, Kotani T, Morisaki H, Takeda J et al. Elevation of KL-6, a lung epithelial cell marker, in plasma and epithelial lining fluid in acute respiratory distress syndrome. Am J Physiol Lung Cell Mol Physiol 2004; 286: L1088-1094.
13. Al-Salmi QA, Walter JN, Colasurdo GN, Sockrider MM, Smith EO, Takahashi H, Fan LL. Serum KL-6 and surfactant proteins A and D in pediatric interstitial lung disease. Chest 2005; 127: 403-407.
14. Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001; 163: 1723-1729.
15. Sweet D, Carnielli V, Greisen G, Hallman M, Ozek E, Plavka R, Saugstad OD, Simeoni U, Speer CP, Halliday HL. European consensus guidelines on the management of neonatal respiratory distress syndrome in preterm infants2013 update. European Association of Perinatal Medicine. Neonatology 2013; 103: 353-368.
16. Crouch E. Pathobiology of pulmonary fibrosis. Am J Physiol 1990; 259: L159-L184.
17. Kurotobi S, Maekawa S, Hara T, Hamana K, Inada N, Kawakami N, Honda A, Matsuoka T, Fujita H, Nagai T. Serum KL-6 level in newborns with meconium aspiration syndrome. Pediatr Int 2003; 45: 517-521.
18. Uchida Y, Minowa H, Ebisu R, Nishikubo T, Takahashi Y, Yoshioka A. Normal values for KL-6 in cord venous plasma of neonates. Pediatr Int 2007; 49: 167-171.
19. Zhang ZQ, Huang XM, Lu H. Early biomarkers as predictors for bronchopulmonary dysplasia in preterm infants: a systematic review. Eur J Pediatr 2014; 173: 15-23.
20. Wang K, Huang X, Lu H, Zhang Z. A comparison of KL-6 and Clara Cell protein as markers for predicting bronchopulmonary dysplasia in preterm infants. Dis Markers 2014; 2014: 736536.
21. Yamane M, Yokoyama N. Serum KL-6 level and pulmonary function in preterm infants with chronic lung disease. Kobe J Med Sci 2004; 50: 131-140.