Research article
Predictors of interstitial lung disease in early systemic sclerosis: a prospective longitudinal study of the GENISOS cohort
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* Corresponding author: Shervin Assassi Shervin.assassi@uth.tmc.edu
1 Division of Rheumatology and Clinical Immunogenetics, University of Texas-Houston, 6431 Fannin, Houston, TX 77030, USA
2 Center for Clinical Research and Evidence-Based Medicine, University of Texas-Houston, 6431 Fannin, Houston, TX 77030, USA
3 University of Texas Medical Branch at Galveston, 301 University Boulevard, Galveston, TX 77555, USA
4 Division of Pulmonary, University of Texas - Houston, 6431 Fannin, Houston, TX 77030, USA
5 University of Texas-San Antonio, 4502 Medical Drive, San Antonio, TX 78229, USA
6 University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada
Arthritis Research & Therapy 2010, 12:R166 doi:10.1186/ar3125
Published: 2 September 2010Abstract
Introduction
The objective of the present study was to examine the association of baseline demographic and clinical characteristics with sequentially obtained measurements of forced vital capacity (FVC), expressed as a percentage of the predicted value, and to identify predictors of the decline rate in FVC over time in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS).
Methods
To date, 266 patients have been enrolled in GENISOS, a prospective, observational cohort of patients with early systemic sclerosis. In addition to pulmonary function tests (PFTs), clinical and laboratory data were obtained from each patient. We analyzed 926 FVC measurements utilizing generalized linear mixed models. The predictive significance of baseline variables for the decline rate in FVC was investigated by the interaction term between the variable and the follow-up time within the first 3 years after enrollment as well as throughout the entire follow-up time.
Results
The cohort consisted of 125 white, 54 African American, and 77 Hispanic patients with average disease duration of 2.5 years at enrollment. The mean follow-up time was 3.8 years, ranging up to 11.4 years. A number of baseline variables, including antibody status, African American ethnicity, disease type, baseline PFT values, modified Rodnan Skin Score, fibrosis on chest radiograph, and lung and skin subscores of the Severity Index, were associated with serially measured FVC levels. However, only the presence of anti-topoisomerase I antibodies (ATA) was associated with lower FVC levels (P < 0.001) as well as accelerated decline rate in FVC within the first 3 years of follow-up (P = 0.02). None of the baseline variables predicted the rate of decline in FVC on long-term follow-up. Patients with rapidly progressive ILD, however, were under-represented in the long-term follow-up group because the accelerated rate of decline in FVC was associated with poor survival (P = 0.001).
Conclusions
Presence of ATA was the only baseline variable associated with differential FVC levels, predicting the rate of decline in FVC within the first 3 years of follow-up. The association of faster decline in FVC with poor survival further emphasizes the need for identification of predictive biomarkers by collection of genetic information and serial blood samples in cohort studies.