Background/Purpose: Interstitial lung disease (ILD) is the leading cause of morbidity and mortality in patients with systemic sclerosis (SSc). However, only a subset of SSc patients with ILD develops end-stage lung disease (ESLD). The presence of significant fibrosis on high-resolution computed tomography and percent predicted forced vital capacity (%FVC) <70% were shown to be variables associated with a greater decline in pulmonary function, but these findings are rarely detected in patients with early SSc. In our institution, we principally did not treat ILD in SSc patients before 2000. Therefore, our cohorts of untreated patients are extremely useful in assessing the natural history of pulmonary function in SSc patients with ILD. Using this cohort, we evaluated initial factors that predict development to ESLD.

Methods: We enrolled 50 patients with SSc, who were diagnosed as having SSc between 1980 and 1995. These patients were selected from our database based on the following criteria: they had ILD as determined by chest radiographs at diagnosis, had disease duration <3 years at diagnosis, were followed for 10 or more years unless death due to ILD-related causes, had at least 4 serial pulmonary function tests, and had never received immunosuppressants, >10 mg daily prednisolone, or other potential disease-modifying drugs. ESLD was defined as having at least one of the following: <50% FVC, required oxygen supplementation in the absence of pulmonary hypertension, or death due to ILD-related causes. We performed statistical analyses stratified by development to ESLD and multivariate analysis to assess factors that predict the ESLD development. Survival analysis was performed using the Kaplan-Meier method combined with log-rank test.

Results: Disease duration at diagnosis was 14.2 ± 7.2 months and %FVC was 83.7 ± 14.2%. The patients were followed for 173.5 ± 64.7 months, and 16 patients (32%) developed ESLD. The decline in %FVC during the 12-month period was 4.6 ± 2.4% in patients who developed ESLD and 0.5 ± 0.8% in patients who did not (P < 0.0001). Cumulative survival rates were significantly worse in patients who developed ESLD than in those who did not (P < 0.0001). Initial characteristics associated with development to ESLD included diffuse cutaneous SSc (P = 0.006), anti-topoisomerase I antibody (P = 0.004), exertional dyspnea (P = 0.03), elevated KL-6 (P < 0.0001), reduced %FVC (P = 0.007), and reduced %DLco (P = 0.001). Multivariate analysis revealed that elevated KL-6 at diagnosis was the sole parameter independently associated with the ESLD development (P = 0.0002, odds ratio = 88). Cumulative rates free of ESLD and death were significantly greater in patients with normal KL-6 than in those with elevated KL-6 (P < 0.0001 for both comparisons). Finally, the rate of decline in %FVC was negatively correlated with KL-6 at diagnosis (r = 0.71, P < 0.0001).

Conclusion: SSc patients with ILD are heterogeneous in terms of deterioration of pulmonary function. Elevated KL-6 at baseline is an independent predictor of %FVC decline and mortality. SSc patients with ILD and elevated KL-6 at early disease course are candidates for aggressive therapeutic intervention.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/elevation-of-kl-6-at-early-disease-course-predicts-subsequent-deterioration-of-pulmonary-function-in-patients-with-systemic-sclerosis-and-interstitial-lung-disease/