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 OJRA  Vol.4 No.1 , February 2014
Predicting Lung Function Decline with Serum Pneumoproteins: A Case Control Study
Abstract: 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.
References

[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. http://dx.doi.org/10.1016/0002-9343(82)90732-X

[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. http://dx.doi.org/10.1056/NEJMoa055120

[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. http://dx.doi.org/10.1164/rccm.200702-326OC

[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. http://dx.doi.org/10.1002/art.22204

[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. http://dx.doi.org/10.1002/1529-0131(200106)44:6<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. http://dx.doi.org/10.3899/jrheum.080633

[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. http://dx.doi.org/10.1159/000018382

[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. http://dx.doi.org/10.1111/j.1440-1843.2006.00834.x

[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. http://dx.doi.org/10.1164/rccm.200706-877OC

[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. http://dx.doi.org/10.1186/ar3125

[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. http://dx.doi.org/10.1002/art.1780370903

[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. http://dx.doi.org/10.1378/chest.105.2.489

[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. http://dx.doi.org/10.1002/9781444312829

[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.

 
 
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