Predicting Lung Function Decline with Serum Pneumoproteins: A Case Control Study

Abstract Full-Text HTML XML Download Download as PDF (Size:137KB) PP. 52-57
DOI: 10.4236/ojra.2014.41008    3,465 Downloads   4,941 Views  


Introduction: Predictors of lung function decline in systemic sclerosis (SSc) are unknown. Serum pneumoprotein levels, surfactant protein-D (SP-D) and Krebs von den Lungen-6 (KL-6), correlate with pulmonary damage. We aimed to test whether levels can predict rapid lung function decline in SSc. Methods: SSc patients who had serial pulmonary function tests (PFT) were analyzed for SP-D and KL-6 levels by enzyme linked immunosorbent assay. Levels were correlated with an annual rate of decline in % predicted forced vital capacity (FVC) of >﹣2% (out-come); controls did not experience this FVC decline. Uni- and multi-variate analysis, adjusting for age, disease duration, gender, baseline % predicted FVC, SP-D, and KL-6, was performed. Results are reported as mean ± SD. Results: Thirty three cases and 25 controls had a disease duration of 8.8 ± 7.3 and 8.3 ± 6.1 years, respectively. In adjusted analyses, lung function decline correlated with greater baseline FVC OR = 1.03 [95% CI of 1.00-1.07]; a trend towards significance was observed for greater levels of SP-D with FVC decline, OR = 1.37 [95% CI of 0.96-2.12]. Conclusion: Our data provide evidence that SSc patients with long-standing disease are still at risk for lung function decline and SP-D levels may predict lung function decline.

Cite this paper

S. Mittoo, M. Hudson, E. Lo, R. Steele, K. Wong, D. Robinson, Z. Bshouty and M. Baron, "Predicting Lung Function Decline with Serum Pneumoproteins: A Case Control Study," Open Journal of Rheumatology and Autoimmune Diseases, Vol. 4 No. 1, 2014, pp. 52-57. doi: 10.4236/ojra.2014.41008.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] P. D. Schneider, R. A. Wise, M. C. Hochberg and F. M. Wigley, “Serial Pulmonary Function in Systemic Sclerosis,” American Journal of Medicine, Vol. 73, No. 3, 1982, pp. 385-394.
[2] D. P. Tashkin, R. Elashoff, P. J. Clements, J. Goldin, M. D. Roth, D. E. Furst, et al., “Cyclophosphamide versus Placebo in Scleroderma Lung Disease,” New England Journal of Medicine, Vol. 354, No. 25, 2006, pp. 2655-2666.
[3] D. P. Tashkin, R. Elashoff, P. J. Clements, M. D. Roth, D. E. Furst, R. M. Silver, et al., “Effects of 1-Year Treatment with Cyclophosphamide on Outcomes at 2 Years in Scleroderma Lung Disease,” American Journal of Respiratory and Critical Care Medicine, Vol. 176, No. 10, 2007, pp. 1026-1034.
[4] R. K. Hoyles, R. W. Ellis, J. Wellsbury, B. Lees, P. Newlands, N. S. Goh, et al., “A Multicenter, Prospective, Randomized, Double-Blind, Placebo-Controlled Trial of Corticosteroids and Intravenous Cyclophosphamide Followed by Oral Azathioprine for the Treatment of Pulmonary Fibrosis in Scleroderma,” Arthritis & Rheumatology, Vol. 54, No. 12, 2006, pp. 3962-3970.
[5] R. Mason, V. Broaddus, J. Murray and J. Nadel, “Murray & Nadel’s Textbook of Respiratory Medicine,” Philadelphia, 2005.
[6] J. Madsen, A. Kliem, I. Tornoe, K. Skjodt, C. Koch and U. Holmskov, “Localization of Lung Surfactant Protein D on Mucosal Surfaces in Human Tissues,” Journal of Immunology, Vol. 164, No. 11, 2000, pp. 5866-5870.
[7] Y. Asano, H. Ihn, K. Yamane, N. Yazawa, M. Kubo, M. Fujimoto, et al., “Clinical Significance of Surfactant Protein D as a Serum Marker for Evaluating Pulmonary Fibrosis in Patients with Systemic Sclerosis,” Arthritis & Rheumatology, Vol. 44, No. 6, 2001, pp. 1363-1369.<1363::AID-ART229>3.0.CO;2-5
[8] K. Yanaba, M. Hasegawa, K. Takehara and S. Sato, “Comparative Study of Serum Surfactant Protein-D and KL-6 Concentrations in Patients with Systemic Sclerosis as Markers for Monitoring the Activity of Pulmonary Fibrosis,” Journal of Rheumatology, Vol. 31, No. 6, 2004, pp. 1112-1120.
[9] K. Yamane, H. Ihn, M. Kubo, N. Yazawa, K. Kikuchi, Y. Soma and K. Tamaki, “Serum Levels of KL-6 as a Useful Marker for Evaluating Pulmonary Fibrosis in Patients with Systemic Sclerosis,” Journal of Rheumatology, Vol. 27, No. 4, 2000, pp. 930-934.
[10] K. Yanaba, M. Hasegawa, Y. Hamaguchi, M. Fujimoto, K. Takehara and S. Sato, “Longitudinal Analysis of Serum KL-6 Levels in Patients with Systemic Sclerosis: Association with the Activity of Pulmonary Fibrosis,” Clinical and Experimental Rheumatology, Vol. 21, No. 4, 2003, pp. 429-436.
[11] F. N. Hant, A. Ludwicka-Bradley, H. J. Wang, N. Li, R. Elashoff, D. P. Tashkin, et al., “Surfactant Protein D and KL-6 as Serum Biomarkers of Interstitial Lung Disease in Patients with Scleroderma,” Journal of Rheumatology, Vol. 36, No. 4, 2009, pp. 773-780.
[12] S. Sato, T. Nagaoka, M. Hasegawa, C. Nishijima and K. Takehara, “Elevated Serum KL-6 Levels in Patients with Systemic Sclerosis: Association with the Severity of Pulmonary Fibrosis,” Dermatology, Vol. 200, No. 3, 2000, pp. 196-201.
[13] Preliminary Criteria for the Classification of Systemic Sclerosis (Scleroderma), “Subcommittee for Scleroderma criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee,” Arthritis & Rheumatology, Vol. 23, No. 5, 1980, pp. 581-590.
[14] E. C. LeRoy, C. Black, R. Fleischmajer, S. Jablonska, T. Krieg, T. A. Medsger Jr., et al., “Scleroderma (Systemic Sclerosis): Classification, Subsets and Pathogenesis,” Jour- nal of Rheumatology, Vol. 15, No. 2, 1988, pp. 202-205.
[15] A. Yokoyama, K. Kondo, M. Nakajima, T. Matsushima, T. Takahashi, M. Nishimura, et al., “Prognostic Value of Circulating KL-6 in Idiopathic Pulmonary Fibrosis,” Respirology, Vol. 11, No. 2, 2006, pp. 164-168.
[16] N. S. Goh, S. R. Desai, S. Veeraraghavan, D. M. Hansell, S. J. Copley, T. M. Maher, et al., “Interstitial Lung Disease in Systemic Sclerosis: A Simple Staging System,” American Journal of Respiratory and Critical Care Medicine, Vol. 177, No. 11, 2008, pp. 1248-1254.
[17] S. Assassi, R. Sharif, R. E. Lasky, T. A. McNearney, Y. M. R. M. Estrada, H. Draeger, et al., “Predictors of Interstitial Lung Disease in Early Systemic Sclerosis: A Prospective Longitudinal Study of the GENISOS Cohort,” Arthritis Research & Therapy, Vol. 12, No. 5, 2010, p. R166.
[18] V. D. Steen, C. Conte, G. R. Owens and T. A. Medsger Jr., “Severe Restrictive Lung Disease in Systemic Sclerosis,” Arthritis & Rheumatology, Vol. 37, No. 9, 1994, pp. 1283-1289.
[19] D. P. Tashkin, P. J. Clements, R. S. Wright, H. Gong Jr., M. S. Simmons, P. A. Lachenbruch, et al., “Interrelationships between Pulmonary and Extrapulmonary Involvement in Systemic Sclerosis. A Longitudinal Analysis,” Chest, Vol. 105, No. 2, 1994, pp. 489-495.
[20] M. Maeda, Y. Ichiki, Y. Aoyama and Y. Kitajima, “Surfactant Protein D (SP-D) and Systemic Scleroderma (SSc),” Journal of Dermatology, Vol. 28, No. 9, 2001, pp. 467-474.
[21] G. Kumanovics, T. Minier, J. Radics, L. Palinkas, T. Berki and L. Czirjak, “Comprehensive Investigation of Novel Serum Markers of Pulmonary Fibrosis Associated with Systemic Sclerosis and Dermato/Polymyositis,” Clinical and Experimental Rheumatology, Vol. 26, No. 3, 2008, pp. 414-420.
[22] J. E. Cotes, D. J. Chinn and M. R. Miller, “Lung Function: Physiology, Measurement, and Application in Medicine,” 6th Edition, Blackwell Publishing, 2006.
[23] H. I. Goldman and M. R. Becklake, “Respiratory Function Tests; Normal Values at Median Altitudes and the Prediction of Normal Results,” American Review of Tuberculosis, Vol. 79, No. 4, 1959, pp. 457-467.

comments powered by Disqus

Copyright © 2020 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.