The Value of Serum KL-6 Level as An Diagnostic Indicator in Patients with Interstitial Lung Diseases_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

RenDenghua ¹ ,  DingJingjing ² ,  CaiHourong ^1,2 , GuiXianhua ² , DaiJinghong ² , ZhangYingwei ² , HuangMei ² , CaoMin ²

1. Department of Respiratory Medicine, The Drum Tower Clinical Medical College of NJMU, Nanjing, Jiangsu, 210008, China;
2. ;

Corresponding?author：

DingJingjing, Email: dingflower@hotmail.com; CaiHourong, Email: caihourong2013@163.com

Keywords：

Interstitial lung diseases; Idiopathic pulmonary fibrosis; Pulmonary alveolar proteinosis; KL-6; Diagnosis

DOI：

10.7507/1671-6205.2015114

Video：

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Objective To determine the diagnostic value of serum KL-6 level in patients with interstitial lung diseases (ILD). Methods All the ILD patients enrolled were hospitalized from April 2013 to April 2014. Patients with other pulmonary diseases and healthy subjects were chosen as control groups simultaneously. Serum KL-6 concentrations were measured by chemiluminescent enzyme immunoassay. The association with serum KL-6 level and pulmonary function was analyzed. Results There were 149 ILD patients, 155 patients with other pulmonary diseases, and 64 healthy subjects. The average serum levels of KL-6 were (1 801.86±2 831.36) U/mL, (267.00±124.41) U/mL, (201.28±81.18) U/mL in the patients with ILD, the patients with other pulmonary diseases and the healthy controls, respectively. The sensitivity and the specificity of the serum KL-6 for the diagnosis of ILD was 83.89% and 92.24% respectively when the cut-off level was set at 500 U/mL. The Kappa value was 0.767 (P < 0.001). The best cut-off value of KL-6 was 469.5 U/mL. Serum KL-6 levels in the patients with ILD were significantly higher compared with the patients with chronic obstructive pulmonary disease, pneumonia, tuberculosis, bronchiectasis and the healthy controls, respectively (all P < 0.001). The KL-6 levels in the pulmonary alveolar proteinosis patients were significantly higher compared with the patients with cryptogenic organizing pneumonia (COP), the patients with idiopathic pulmonary fibrosis (IPF) and the patients with connective tissue disease (CTD-ILD) (all P < 0.001). While the KL-6 concentration in IPF and CTD-ILD were significantly higher than that in COP (P=0.003 and P=0.008, respectively). Significant negative correlations were found between the levels of serum KL-6 and vital capacity as a percentage of the predicted value, forced vital capacity as a percentage of the predicted value, forced expiratory volume in one second as a percentage of the predicted value and carbon monoxide diffusing capacity as a percentage of the predicted value (all P < 0.001). Follow-up study showed the levels of serum KL-6 were consistent with clinical efficacy. Conclusion Serum KL-6 level is a reliable serum marker for ILD, and is related with the severity of disease and clinical efficacy.

Citation： RenDenghua, DingJingjing, CaiHourong, GuiXianhua, DaiJinghong, ZhangYingwei, HuangMei, CaoMin. The Value of Serum KL-6 Level as An Diagnostic Indicator in Patients with Interstitial Lung Diseases. Chinese Journal of Respiratory and Critical Care Medicine, 2015, 14(5): 468-473. doi: 10.7507/1671-6205.2015114 Copy

1.	陳紅梅, 張建華, 徐侖.KL-6與呼吸系統疾病.國際兒科學雜志, 2008, 35:137-139.
2.	Kondo T, Hattori N, Ishikawa N, et al. KL-6 concentration in pulmonary epithelial lining fluid is a useful prognostic indicator in patients with acute respiratory distress syndrome. Respir Res, 2011, 12:32-38.
3.	杜玉秀, 多力坤·木扎帕爾, 馬香萍.病毒性肺炎患兒血清糖蛋白KL-6水平與影響因素相關性.中華實用診斷與治療雜志, 2011, 25:460-462.
4.	Kawase S, Hattori N, Ishikawa N, et al. Change in serum KL-6 level from baseline is useful for predicting life-threatening EGFR-TKIs induced interstitial lung disease. Respir Res, 2011, 12:97-107.
5.	Xu L, Yan DR, Zhu SL, et al. KL-6 regulated the expression of HGF, collagen and myofibroblast differentiation. Eur Rev Med Pharmacol Sci, 2013, 17:3073-3077.
6.	Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement:idiopathic pulmonary fibrosis:evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med, 2011, 183:788-824.
7.	蔡后榮.2011年特發性肺纖維化診斷和治療循證新指南解讀.中國呼吸與危重監護雜志, 2011, 10:313-316.
8.	Cordier JF. Cryptogenic organising pneumonia. Eur Respir J, 2006, 28:422-446.
9.	Seymour JF, Presneill JJ. Pulmonary alveolar proteinosis:progress in the first 44 years. Am J Respir Crit Care Med, 2002, 166:215-235.
10.	中華醫學會.臨床診療指南:風濕病分冊.北京:人民衛生出版社, 2005, 2.
11.	Ohtsuki Y, Fujita J, Hachisuka Y, et al. Immunohistochemical and immunoelectron microscopic studies of the localization of KL-6 and epithelial membrane antigen (EMA) in presumably normal pulmonary tissue and in interstitial pneumonia. Med Mol Morphol, 2007, 40:198-202.
12.	Ohshimo S, Yokoyama A, Hattori N, et al. KL-6, a human MUC1 mucin, promotes proliferation and survival of lung fibroblasts. Biochem Biophys Res Commun, 2005, 338:1845-1852.
13.	Ishikawa N, Hattori N, Yokoyama A, et al. Utility of KL-6/MUC1 in the clinical management of interstitial lung diseases. Respir Investig, 2012, 50:3-13.
14.	Doishita S, Inokuma S, Asashima H, et al. Serum KL-6 level as an indicator of active or inactive interstitial pneumonitis associated with connective tissue diseases. Intern Med, 2011, 50:2889-2892.
15.	Bonella F, Ohshimo S, Miaotian C, et al. Serum KL-6 is a predictor of outcome in pulmonary alveolar proteinosis. Orphanet J Rare Dis, 2013, 8:53-62.
16.	趙亞東, 李振華, 康健, 等.特發性肺纖維化患者血清及支氣管肺泡灌洗液中KL-6水平及其意義.中華內科雜志, 2007, 46:151-152.
17.	Hisata S, Kimura Y, Shibata N, et al. A normal range of KL-6/MUC1 independent of elevated SP-D indicates a better prognosis in the patients with honeycombing on high-resolution computed tomography. Pulm Med, 2011:806014.
18.	Ohshimo S, Ishikawa N, Horimasu Y, et al. Baseline KL-6 predicts increased risk for acute exacerbation of idiopathic pulmonary fibrosis. Respir Med, 2014, 108:1031-1039.
19.	郭強, 顧越英, 陳曉翔, 等.血清KL-6對狼瘡性間質性肺炎與肺部感染的鑒別意義.診斷學理論與實踐, 2004, 3:246-248.
20.	盧昕, 謝瑤, 王國春.血清KL-6檢測在特發性炎性肌病伴肺間質病變診斷中的價值.中華風濕病學雜志, 2006, 10:416-419.
21.	Fathi M, Barbasso Helmers S, Lundberg IE. KL-6:a serological biomarker for interstitial lung disease in patients with polymyositis and dermatomyositis. J Intern Med, 2012, 271:589-597.
22.	Lota HK, Renzoni EA. Circulating biomarkers of interstitial lung disease in systemic sclerosis. Int J Rheumatol, 2012:121439.
23.	Kida Y, Ohshimo S, Ota K, et al. KL-6, a human MUC1 mucin, as a prognostic marker for diffuse alveolar hemorrhage syndrome. Orphanet J Rare Dis, 2012, 7:99-106.
24.	Ohnishi H, Yokoyama A, Yasuhara Y, et al. Circulating KL-6 levels in patients with drug induced pneumonitis. Thorax, 2003, 58:872-875.
25.	Okada F, Ando Y, Honda K, et al. Comparison of pulmonary CT findings and serum KL-6 levels in patients with cryptogenic organizing pneumonia. Br J Radiol, 2009, 82:212-218.

1. 陳紅梅, 張建華, 徐侖.KL-6與呼吸系統疾病.國際兒科學雜志, 2008, 35:137-139.
2. Kondo T, Hattori N, Ishikawa N, et al. KL-6 concentration in pulmonary epithelial lining fluid is a useful prognostic indicator in patients with acute respiratory distress syndrome. Respir Res, 2011, 12:32-38.
3. 杜玉秀, 多力坤·木扎帕爾, 馬香萍.病毒性肺炎患兒血清糖蛋白KL-6水平與影響因素相關性.中華實用診斷與治療雜志, 2011, 25:460-462.
4. Kawase S, Hattori N, Ishikawa N, et al. Change in serum KL-6 level from baseline is useful for predicting life-threatening EGFR-TKIs induced interstitial lung disease. Respir Res, 2011, 12:97-107.
5. Xu L, Yan DR, Zhu SL, et al. KL-6 regulated the expression of HGF, collagen and myofibroblast differentiation. Eur Rev Med Pharmacol Sci, 2013, 17:3073-3077.
6. Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement:idiopathic pulmonary fibrosis:evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med, 2011, 183:788-824.
7. 蔡后榮.2011年特發性肺纖維化診斷和治療循證新指南解讀.中國呼吸與危重監護雜志, 2011, 10:313-316.
8. Cordier JF. Cryptogenic organising pneumonia. Eur Respir J, 2006, 28:422-446.
9. Seymour JF, Presneill JJ. Pulmonary alveolar proteinosis:progress in the first 44 years. Am J Respir Crit Care Med, 2002, 166:215-235.
10. 中華醫學會.臨床診療指南:風濕病分冊.北京:人民衛生出版社, 2005, 2.
11. Ohtsuki Y, Fujita J, Hachisuka Y, et al. Immunohistochemical and immunoelectron microscopic studies of the localization of KL-6 and epithelial membrane antigen (EMA) in presumably normal pulmonary tissue and in interstitial pneumonia. Med Mol Morphol, 2007, 40:198-202.
12. Ohshimo S, Yokoyama A, Hattori N, et al. KL-6, a human MUC1 mucin, promotes proliferation and survival of lung fibroblasts. Biochem Biophys Res Commun, 2005, 338:1845-1852.
13. Ishikawa N, Hattori N, Yokoyama A, et al. Utility of KL-6/MUC1 in the clinical management of interstitial lung diseases. Respir Investig, 2012, 50:3-13.
14. Doishita S, Inokuma S, Asashima H, et al. Serum KL-6 level as an indicator of active or inactive interstitial pneumonitis associated with connective tissue diseases. Intern Med, 2011, 50:2889-2892.
15. Bonella F, Ohshimo S, Miaotian C, et al. Serum KL-6 is a predictor of outcome in pulmonary alveolar proteinosis. Orphanet J Rare Dis, 2013, 8:53-62.
16. 趙亞東, 李振華, 康健, 等.特發性肺纖維化患者血清及支氣管肺泡灌洗液中KL-6水平及其意義.中華內科雜志, 2007, 46:151-152.
17. Hisata S, Kimura Y, Shibata N, et al. A normal range of KL-6/MUC1 independent of elevated SP-D indicates a better prognosis in the patients with honeycombing on high-resolution computed tomography. Pulm Med, 2011:806014.
18. Ohshimo S, Ishikawa N, Horimasu Y, et al. Baseline KL-6 predicts increased risk for acute exacerbation of idiopathic pulmonary fibrosis. Respir Med, 2014, 108:1031-1039.
19. 郭強, 顧越英, 陳曉翔, 等.血清KL-6對狼瘡性間質性肺炎與肺部感染的鑒別意義.診斷學理論與實踐, 2004, 3:246-248.
20. 盧昕, 謝瑤, 王國春.血清KL-6檢測在特發性炎性肌病伴肺間質病變診斷中的價值.中華風濕病學雜志, 2006, 10:416-419.
21. Fathi M, Barbasso Helmers S, Lundberg IE. KL-6:a serological biomarker for interstitial lung disease in patients with polymyositis and dermatomyositis. J Intern Med, 2012, 271:589-597.
22. Lota HK, Renzoni EA. Circulating biomarkers of interstitial lung disease in systemic sclerosis. Int J Rheumatol, 2012:121439.
23. Kida Y, Ohshimo S, Ota K, et al. KL-6, a human MUC1 mucin, as a prognostic marker for diffuse alveolar hemorrhage syndrome. Orphanet J Rare Dis, 2012, 7:99-106.
24. Ohnishi H, Yokoyama A, Yasuhara Y, et al. Circulating KL-6 levels in patients with drug induced pneumonitis. Thorax, 2003, 58:872-875.
25. Okada F, Ando Y, Honda K, et al. Comparison of pulmonary CT findings and serum KL-6 levels in patients with cryptogenic organizing pneumonia. Br J Radiol, 2009, 82:212-218.

Chinese Journal of Respiratory and Critical Care Medicine

The Value of Serum KL-6 Level as An Diagnostic Indicator in Patients with Interstitial Lung Diseases

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