Interstitial lung disease in connective tissue diseases: evolving concepts of pathogenesis and management

Abstract

Interstitial lung disease (ILD) is a challenging clinical entity associated with multiple connective tissue diseases, and is a significant cause of morbidity and mortality. Effective therapies for connective tissue disease-associated interstitial lung disease (CTD-ILD) are still lacking. Multidisciplinary clinics dedicated to the early diagnosis and improved management of patients with CTD-ILD are now being established. There is rapid progress in understanding and identifying the effector cells, the proinflammatory and profibrotic mediators, and the pathways involved in the pathogenesis of CTD-ILD. Serum biomarkers may provide new insights as risk factors for pulmonary fibrosis and as measures of disease progression. Despite these recent advances, the management of patients with CTD-ILD remains suboptimal. Further studies are therefore urgently needed to better understand these conditions, and to develop effective therapeutic interventions.

Figure 1

Characteristic radiographic findings on high-resolution computed tomography. High-resolution computed tomography of the chest reveals (a) subpleural ground glass opacities (white arrow) and traction bronchiectasis suggestive of nonspecific interstitial pneumonia, and (b) honeycombing (black arrows) with ground glass opacities suggestive of usual interstitial pneumonia.

Figure 2

Mechanisms perpetuating pulmonary fibrosis. Pathogenesis of pulmonary fibrosis is initiated by microvascular injury, which leads to endothelial cell damage and alveolar epithelial injury. This leads to activation of the coagulation cascade, release of various cytokines and growth factors, and ultimately activation of fibroblasts, a key event in the development of fibrosis. CTGF, connective tissue growth factor; IGF-1, insulin-like growth factor-1; LPA, lysophosphatidic acid; TGF-β, transforming growth factor beta.