Idiopathic Pulmonary Fibrosis: From Common Microscopy to Single-Cell Biology and Precision Medicine

Idiopathic pulmonary fibrosis is a chronic, progressive, and usually fatal lung disease of unknown etiology and is included in the large, complex, and heterogeneous group of interstitial lung diseases (ILD). IPF is characterized by an aberrant activation of epithelial cells and fibroblasts and excessive accumulation of extracellular matrix, resulting in the progressive destruction of the lung architecture. Here we approach the fascinating historical evolution of our knowledge about this disorder from the past century, when most efforts were focused on ILD classification and terminology, until the current century, when the explosive progress in molecular genetics, epigenetics, and multiomics, as well as the development of complex computational tools, resulted in a huge advance in unveiling the pathogenic mechanisms of the disease. Recent advances in artificial intelligence, machine and deep learning, and artificial neural networks show promising results in identifying lung fibrotic patterns in high-resolution computed tomography or helping to create a tissue genomic classifier for specific diagnosis. Finally, incipient approaches to precision medicine are ongoing in the area of pharmacogenetics.