Seasonal variation of serum KL-6 concentrations is greater in patients with hypersensitivity pneumonitis

BMC Pulmonary Medicine

Akihito Yokoyama¹  Tetsuya Kubota¹  Shigeo Kawase¹  Shintaro Miyamoto¹  Hiroshi Ohnishi¹ 

[1] Department of Hematology and Respiratory Medicine, Kochi Medical School, Kochi University, Oko-cho, Kohasu, Nankoku, Kochi 783-8505, Japan

关键词: Seasonal variation;    KL-6;    Interstitial lung disease;    Hypersensitivity Pneumonitis;    Biomarker;   

Others  :  1109556
DOI  :  10.1186/1471-2466-14-129

 received in 2014-04-25, accepted in 2014-07-29,  发布年份 2014

【 摘 要 】

Background

Serum KL-6 is a useful biomarker for the diagnosis of interstitial lung diseases (ILD). However, KL-6 has not been used to discriminate different types of ILD. Serum KL-6 concentrations can vary depending on antigen exposure levels in patients with hypersensitivity pneumonitis (HP); however, seasonal changes in serum KL-6 concentrations in ILD have not been determined. We hypothesized that seasonal variation of serum KL-6 is greater in HP than for the other ILD. The aim of this study was to determine seasonal variation of serum KL-6 concentrations in various ILD.

Methods

Serum KL-6 concentrations in the summer season from June 1 to September 30 and the winter season from November 1 to February 28 were retrospectively analyzed in patients with idiopathic pulmonary fibrosis (IPF, n = 16), non-specific interstitial pneumonia (NSIP, n = 16), collagen vascular disease-associated interstitial pneumonia (CVD-IP, n = 33), house-related HP (House-HP, n = 9), bird-related HP (Bird-HP, n = 9), and combined pulmonary fibrosis and emphysema (CPFE, n = 13).

Results

Bird-HP and House-HP showed greater seasonal serum KL-6 variation than the other ILD. Serum KL-6 concentrations in Bird-HP were significantly increased in the winter and KL-6 concentrations in House-HP were significantly increased in the summer. Serum KL-6 variation was significantly greater in acute HP than chronic HP. Receiver operating characteristic curve analysis revealed that greater seasonal variation in serum KL-6 concentrations is diagnostic for Bird-HP.

Conclusion

HP should be considered in ILD with greater seasonal changes in serum KL-6 concentrations.

【 授权许可】

   
2014 Ohnishi et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]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.
• [2]Ohnishi H, Yokoyama A, Kondo K, Hamada H, Abe M, Nishimura K, Hiwada K, Kohno N: Comparative study of KL-6, surfactant protein-A, surfactant protein-D, and monocyte chemoattractant protein-1 as serum markers for interstitial lung diseases. Am J Respir Crit Care Med 2002, 165:378-381.
• [3]Ishikawa N, Hattori N, Yokoyama A, Kohno N: Utility of KL-6/MUC1 in the clinical management of interstitial lung diseases. Respir Investig 2012, 50:3-13.
• [4]Ohnishi H, Yokoyama A, Yasuhara Y, Watanabe A, Naka T, Hamada H, Abe M, Nishimura K, Higaki J, Ikezoe J, Kohno N: Circulating KL-6 levels in patients with drug induced pneumonitis. Thorax 2003, 58:872-875.
• [5]Takahashi T, Munakata M, Ohtsuka Y, Satoh-Kamachi A, Sato R, Homma Y, Kawakami Y: Serum KL-6 concentrations in dairy farmers. Chest 2000, 118:445-450.
• [6]Janssen R, Grutters JC, Sato H, van Velzen-Blad H, Zanen P, Kohno N, Welsh KI, du Bois RM, van den Bosch JM: Analysis of KL-6 and SP-D as disease markers in bird fancier’s lung. Sarcoidosis Vasc Diffuse Lung Dis 2005, 22:51-57.
• [7]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.
• [8]Yokoyama A, Kondo K, Nakajima M, Matsushima T, Takahashi T, Nishimura M, Bando M, Sugiyama Y, Totani Y, Ishizaki T, Ichiyasu H, Suga M, Hamada H, Kohno N: Prognostic value of circulating KL-6 in idiopathic pulmonary fibrosis. Respirology 2006, 11:164-168.
• [9]Ishizaka A, Matsuda T, Albertine KH, Koh H, Tasaka S, Hasegawa N, Kohno N, Kotani T, Morisaki H, Takeda J, Nakamura M, Fang X, Martin TR, Matthay MA, Hashimoto S: 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-L1094.
• [10]Selman M, Pardo A, King TE Jr: Hypersensitivity pneumonitis: insights in diagnosis and pathobiology. Am J Respir Crit Care Med 2012, 186:314-324.
• [11]Inase N, Ohtani Y, Sumi Y, Umino T, Usui Y, Miyake S, Yoshizawa Y: A clinical study of hypersensitivity pneumonitis presumably caused by feather duvets. Ann Allergy Asthma Immunol 2006, 96:98-104.
• [12]Ando M, Konishi K, Yoneda R, Tamura M: Difference in the phenotypes of bronchoalveolar lavage lymphocytes in patients with summer-type hypersensitivity pneumonitis, farmer’s lung, ventilation pneumonitis, and bird fancier’s lung: report of a nationwide epidemiologic study in Japan. J Allergy Clin Immunol 1991, 87:1002-1009.
• [13]Okamoto T, Miyazaki Y, Ogura T, Chida K, Kohno N, Kohno S, Taniguchi H, Akagawa S, Mochizuki Y, Yamauchi K, Takahashi H, Johkoh T, Homma S, Kishi K, Ikushima S, Konno S, Mishima M, Ohta K, Nishioka Y, Yoshimura N, Munakata M, Watanabe K, Miyashita Y, Inase N: A nationwide epidemiological survey of chronic hypersensitivity pneumonitis in Japan. Respir Investig 2013, 51:191-199.
• [14]Hara Y, Kobayashi H, Osoreda H, Kanoh S, Motoyoshi K, Ozeki Y: Bird-related chronic hypersensitivity pneumonitis demonstrating the fluctuation of disease activity accompanied with environmental changes. Nihon Kokyuki Gakkai Zasshi 2008, 46:1045-1049. Japanese
• [15]Takao T, Hanehira T, Zenke Y, Shikama J, Igei H, Inoue E, Yoshizawa Y: The sequential changes of the serum levels of KL-6, SP-D, and DLCO were followed for a long term in a case of acute bird fancier’s lung. Arerugi 2009, 58:1433-1440. Japanese
• [16]American Thoracic Society; European Respiratory Society: American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001. Am J Respir Crit Care Med 2002, 165:277-304.
• [17]Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, Colby TV, Cordier JF, Flaherty KR, Lasky JA, Lynch DA, Ryu JH, Swigris JJ, Wells AU, Ancochea J, Bouros D, Carvalho C, Costabel U, Ebina M, Hansell DM, Johkoh T, Kim DS, King TE Jr, Kondoh Y, Myers J, Müller NL, Nicholson AG, Richeldi L, Selman M, Dudden RF, Griss BS, Protzko SL, Schünemann HJ, ATS/ERS/JRS/ALAT Committee on Idiopathic Pulmonary Fibrosis: 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.
• [18]Cottin V, Nunes H, Brillet PY, Delaval P, Devouassoux G, Tillie-Leblond I, Israel-Biet D, Court-Fortune I, Valeyre D, Cordier JF, Groupe d’Etude et de Recherche sur les Maladies Orphelines Pulmonaires (GERM O P): Combined pulmonary fibrosis and emphysema: a distinct underrecognised entity. Eur Respir J 2005, 26:586-593.
• [19]Ohnishi H, Yokoyama A, Hamada H, Manabe S, Ito R, Watanabe A, Katayama H, Yasuhara Y, Ikezoe J, Higaki J: Humidifier lung: possible contribution of endotoxin-induced lung injury. Intern Med 2002, 41:1179-1182.
• [20]Inase N, Ohtani Y, Usui Y, Miyazaki Y, Takemura T, Yoshizawa Y: Chronic summer-type hypersensitivity pneumonitis: clinical similarities to idiopathic pulmonary fibrosis. Sarcoidosis Vasc Diffuse Lung Dis 2007, 24:141-147.
• [21]Silva CI, Müller NL, Lynch DA, Curran-Everett D, Brown KK, Lee KS, Chung MP, Churg A: Chronic hypersensitivity pneumonitis: differentiation from idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia by using thin-section CT. Radiology 2008, 246:288-297.
• [22]Morell F, Villar A, Montero MÁ, Muñoz X, Colby TV, Pipvath S, Cruz MJ, Raghu G: Chronic hypersensitivity pneumonitis in patients diagnosed with idiopathic pulmonary fibrosis: a prospective case-cohort study. Lancet Respir Med 2013, 1:685-694.
• [23]Ohtani Y, Saiki S, Sumi Y, Inase N, Miyake S, Costabel U, Yoshizawa Y: Clinical features of recurrent and insidious chronic bird fancier’s lung. Ann Allergy Asthma Immunol 2003, 90:604-610.
• [24]Linssen KC, Jacobs JA, Poletti VE, van Mook W, Cornelissen EI, Drent M: Reactive type II pneumocytes in bronchoalveolar lavage fluid. Acta Cytol 2004, 48:497-504.