Predicting risk of pulmonary fibrosis and pulmonary hypertension is an urgent priority in systemic sclerosis. Lung function often declines rapidly in the first years after diagnosis, and interstitial lung disease (ILD), although highly variable in severity and disease coruse, is a major cause of mortality in systemic sclerosis.
Two ILD specialists at London's Brompton Hospital identify two biomarkers in peripheral blood as possibly simpler and better alternatives to the current best standard for prognosis, a staging system based on a combination of CT imaging and forced expiratory volume measurements.
Decreased FEV and decreased diffusing capacity of the lung for carbon monoxide are sensitive for interstitial lung disease, note the authors of the review in the International Journal of Rheumatology, but may indicate pulmonary vascular disease rather than ILD. The most promising tests specific for ILD in systemic sclerosis are KL-6, a glycoprotein in alveolar and bronchiolar epithelial cells whose serum levels rise after cellular injury, and CCL-18, an immune-system regulator in lung cells that is increased in a number of fibrotic lung diseases.
Serum levels of KL-6 are significantly higher in systemic sclerosis patients who have ILD than in those who don't, according to the review. The molecule has been used routinely to predict ILD in systemic sclerosis patients in Japan, but requires validation in prospective studies. In the first large study to test a prognostic biomarker for pulmonary decline in systemic sclerosis while adjusting for severity of lung disease, increased levels of CCL-18 were independently predictive of decreasing lung function and death.
Like many proposed biomarkers, these require validation by separate studies. At least two multicenter trials are currently under way to identify markers of prognosis in idiopathic pulmonary fibrosis. No such study has yet been launched for ILD in systemic sclerosis.