Publications

Interstitial lung disease (ILD) is a commonly encountered complication of systemic sclerosis (SSc) and accounts for a significant proportion of SSc-associated morbidity and mortality. Its pathogenesis remains poorly understood, and therapies that treat SSc ILD are suboptimal, at best. SSc ILD pathogenesis may share some common mechanisms with other fibrotic lung diseases, in which dysregulation of lung epithelium can contribute to pathologic fibrosis via recruitment or in situ generation and activation of fibroblasts. TGFβ, a master regulator of fibrosis, is tightly regulated in the lung by the integrin αvβ6, which is expressed at low levels on healthy alveolar epithelial cells but is highly induced in the setting of lung injury or fibrosis. Here we discuss the biology of αvβ6 and present this integrin as a potentially attractive target for inhibition in the setting of SSc ILD.

This review will focus on the evaluation of biomarkers and surrogate endpoints in chronic disease risk with a focus on cardiovascular disease. It provides an example of how identification of relevant biomarkers might be useful in sleep research and clinical care. Much of this review is derived from work performed by the Institute of Medicine (IOM) Committee on Qualification of Biomarkers and Surrogate Endpoints in Chronic Disease (see footnote in the Acknowledgments). This discussion will review the committee charge, definitions of biomarkers and other endpoints, biomarker evaluation framework, case studies of representative biomarkers, recommendations, and conclusions.