Purpose of review: The term 'pulmonary fibrosis' encompasses a heterogeneous group of disorders characterized by replacement of the lung parenchyma with scar tissue. Despite many years of research, its pathogenesis remains obscure and a cure remains elusive. The bulk of human data in this area derive from patients with idiopathic pulmonary fibrosis. Pulmonary fibrosis has also emerged as a leading cause of mortality in patients with systemic sclerosis. Because of a lack of effective therapy, better understanding of the mechanism(s) driving this disease has the potential to impact the proximate cause of death in most patients with scleroderma.
Recent findings: Animal modeling and translational human studies lend insight into the pathogenesis of lung fibrosis. Recent developments include the role of epithelial cell injury, endoplasmic reticulum stress and Wnt signaling, the contributions of alternatively activated macrophages and efferocytosis, the extra-mesenchymal origin of fibroblasts including epithelial-mesenchymal transition and fibrocytes, a possible association with senescence and aging, and the emerging role of lymphocytes in the fibrotic response.
Summary: Novel investigations defining the mechanism of epithelial cell injury, alternative macrophage activation and efferocytosis, alternate sources of fibroblasts, cellular senescence, and lymphocyte function may lend new insight into the pathogenesis of scleroderma-related pulmonary fibrosis.