Skip to main content
Thorax logoLink to Thorax
. 2003 Oct;58(10):872–875. doi: 10.1136/thorax.58.10.872

Circulating KL-6 levels in patients with drug induced pneumonitis

H Ohnishi 1, A Yokoyama 1, Y Yasuhara 1, A Watanabe 1, T Naka 1, H Hamada 1, M Abe 1, K Nishimura 1, J Higaki 1, J Ikezoe 1, N Kohno 1
PMCID: PMC1746480  PMID: 14514942

Abstract

Background: The circulating level of KL-6/MUC1 is a sensitive marker for various interstitial lung diseases. Previous case reports have suggested that KL-6 may also be increased in some patients with drug induced pneumonitis. A study was undertaken to determine whether serum KL-6 could be a marker for particular types of drug induced pneumonitis.

Methods: The findings of high resolution computed tomographic (HRCT) chest scans of 30 patients with drug induced pneumonitis were reviewed separately by two independent observers. The pneumonitis was classified into four predominant patterns: widespread bilateral consolidation (diffuse alveolar damage, DAD; n=7), fibrosis with or without consolidation (chronic interstitial pneumonia, CIP; n=11), consolidation without fibrosis (bronchiolitis obliterans organising pneumonia or eosinophilic pneumonia, BOOP/EP; n=8), and diffuse ground glass opacities without fibrosis (hypersensitivity pneumonitis, HP; n=4). Serum KL-6 levels were measured by a sandwich enzyme linked immunosorbent assay.

Results: The overall sensitivity of serum KL-6 in detecting drug induced lung disease was 53.3%, which was lower than its sensitivity in detecting other interstitial lung diseases. However, the KL-6 level was increased in most patients with a DAD or CIP pattern (16/18; 88.9%) and was closely correlated with their clinical course. In contrast, serum KL-6 levels were within the normal range in all patients with a BOOP/EP or HP pattern.

Conclusions: Particular patterns detected by HRCT scanning, such as DAD and CIP but not the BOOP/EP or HP patterns, are associated with increased circulating KL-6 levels in drug induced pneumonitis. Serum KL-6 levels may reflect the clinical activity of the particular disorders.

Full Text

The Full Text of this article is available as a PDF (208.7 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Cooper J. A., Jr, White D. A., Matthay R. A. Drug-induced pulmonary disease. Part 1: Cytotoxic drugs. Am Rev Respir Dis. 1986 Feb;133(2):321–340. doi: 10.1164/arrd.1986.133.2.321. [DOI] [PubMed] [Google Scholar]
  2. Cooper J. A., Jr, White D. A., Matthay R. A. Drug-induced pulmonary disease. Part 2: Noncytotoxic drugs. Am Rev Respir Dis. 1986 Mar;133(3):488–505. doi: 10.1164/arrd.1986.133.3.488. [DOI] [PubMed] [Google Scholar]
  3. Endoh Y., Hanai R., Uto K., Uno M., Nagashima H., Narimatsu A., Takizawa T., Onishi S., Kasanuki H. KL-6 as a potential new marker for amiodarone-induced pulmonary toxicity. Am J Cardiol. 2000 Jul 15;86(2):229–231. doi: 10.1016/s0002-9149(00)00864-x. [DOI] [PubMed] [Google Scholar]
  4. Foucher P., Biour M., Blayac J. P., Godard P., Sgro C., Kuhn M., Vergnon J. M., Vervloet D., Pfitzenmeyer P., Ollagnier M. Drugs that may injure the respiratory system. Eur Respir J. 1997 Feb;10(2):265–279. doi: 10.1183/09031936.97.10020265. [DOI] [PubMed] [Google Scholar]
  5. Hamada H., Kohno N., Yokoyama A., Hirasawa Y., Hiwada K., Sakatani M., Ueda E. KL-6 as a serologic indicator of Pneumocystis carinii pneumonia in immunocompromised hosts. Intern Med. 1998 Mar;37(3):307–310. doi: 10.2169/internalmedicine.37.307. [DOI] [PubMed] [Google Scholar]
  6. Israel-Biet D., Labrune S., Huchon G. J. Drug-induced lung disease: 1990 review. Eur Respir J. 1991 Apr;4(4):465–478. [PubMed] [Google Scholar]
  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 Sep;18(3):203–216. [PubMed] [Google Scholar]
  8. Kohno N., Awaya Y., Oyama T., Yamakido M., Akiyama M., Inoue Y., Yokoyama A., Hamada H., Fujioka S., Hiwada K. KL-6, a mucin-like glycoprotein, in bronchoalveolar lavage fluid from patients with interstitial lung disease. Am Rev Respir Dis. 1993 Sep;148(3):637–642. doi: 10.1164/ajrccm/148.3.637. [DOI] [PubMed] [Google Scholar]
  9. Kohno N., Hamada H., Fujioka S., Hiwada K., Yamakido M., Akiyama M. Circulating antigen KL-6 and lactate dehydrogenase for monitoring irradiated patients with lung cancer. Chest. 1992 Jul;102(1):117–122. doi: 10.1378/chest.102.1.117. [DOI] [PubMed] [Google Scholar]
  10. Kohno N., Inoue Y., Hamada H., Fujioka S., Fujino S., Yokoyama A., Hiwada K., Ueda N., Akiyama M. Difference in sero-diagnostic values among KL-6-associated mucins classified as cluster 9. Int J Cancer Suppl. 1994;8:81–83. doi: 10.1002/ijc.2910570717. [DOI] [PubMed] [Google Scholar]
  11. 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 Jul;96(1):68–73. doi: 10.1378/chest.96.1.68. [DOI] [PubMed] [Google Scholar]
  12. Kohno N., Yokoyama A., Hirasawa Y., Kondo K., Fujino S., Abe M., Hiwada K. Comparative studies of circulating KL-6, type III procollagen N-terminal peptide and type IV collagen 7S in patients with interstitial pneumonitis and alveolar pneumonia. Respir Med. 1997 Oct;91(9):558–561. doi: 10.1016/s0954-6111(97)90090-1. [DOI] [PubMed] [Google Scholar]
  13. Matsumoto T., Nakamura K., Sugisaki K., Shigenaga T., Miyazaki E., Sawabe T., Abe Y., Tsuda T. [Misoprostol-induced pneumonitis]. Nihon Kokyuki Gakkai Zasshi. 2000 Jun;38(6):447–451. [PubMed] [Google Scholar]
  14. Miyata Masayuki, Sakuma Fumitaka, Fukaya Etsuko, Kobayashi Hiroko, Rai Takeshi, Saito Hironobu, Kasukawa Reiji, Suzuki Shuzo. Detection and monitoring of methotrexate-associated lung injury using serum markers KL-6 and SP-D in rheumatoid arthritis. Intern Med. 2002 Jun;41(6):467–473. doi: 10.2169/internalmedicine.41.467. [DOI] [PubMed] [Google Scholar]
  15. Nakajima M., Manabe T., Mitekura H., Hashiguchi K., Niki Y., Matsushima T. [Levels of serum KL-6 in a patient with drug-induced pneumonitis]. Nihon Kyobu Shikkan Gakkai Zasshi. 1997 Jul;35(7):813–817. [PubMed] [Google Scholar]
  16. Naranjo C. A., Busto U., Sellers E. M., Sandor P., Ruiz I., Roberts E. A., Janecek E., Domecq C., Greenblatt D. J. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981 Aug;30(2):239–245. doi: 10.1038/clpt.1981.154. [DOI] [PubMed] [Google Scholar]
  17. Obuchowski N. A., Zepp R. C. Simple steps for improving multiple-reader studies in radiology. AJR Am J Roentgenol. 1996 Mar;166(3):517–521. doi: 10.2214/ajr.166.3.8623619. [DOI] [PubMed] [Google Scholar]
  18. Ohnishi Hiroshi, Yokoyama Akihito, Kondo Keiichi, Hamada Hironobu, Abe Masahiro, Nishimura Kazutaka, Hiwada Kunio, Kohno Nobuoki. 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 Feb 1;165(3):378–381. doi: 10.1164/ajrccm.165.3.2107134. [DOI] [PubMed] [Google Scholar]
  19. Padley S. P., Adler B., Hansell D. M., Müller N. L. High-resolution computed tomography of drug-induced lung disease. Clin Radiol. 1992 Oct;46(4):232–236. doi: 10.1016/s0009-9260(05)80161-8. [DOI] [PubMed] [Google Scholar]
  20. Rosenow E. C., 3rd, Myers J. L., Swensen S. J., Pisani R. J. Drug-induced pulmonary disease. An update. Chest. 1992 Jul;102(1):239–250. doi: 10.1378/chest.102.1.239. [DOI] [PubMed] [Google Scholar]
  21. Rossi S. E., Erasmus J. J., McAdams H. P., Sporn T. A., Goodman P. C. Pulmonary drug toxicity: radiologic and pathologic manifestations. Radiographics. 2000 Sep-Oct;20(5):1245–1259. doi: 10.1148/radiographics.20.5.g00se081245. [DOI] [PubMed] [Google Scholar]
  22. Takahashi T., Munakata M., Suzuki I., Kawakami Y. Serum and bronchoalveolar fluid KL-6 levels in patients with pulmonary alveolar proteinosis. Am J Respir Crit Care Med. 1998 Oct;158(4):1294–1298. doi: 10.1164/ajrccm.158.4.9712003. [DOI] [PubMed] [Google Scholar]
  23. 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 Nov;158(5 Pt 1):1680–1684. doi: 10.1164/ajrccm.158.5.9803115. [DOI] [PubMed] [Google Scholar]

Articles from Thorax are provided here courtesy of BMJ Publishing Group

RESOURCES