Epidemiology and risk factors of IPF: Can we dare to ask, "what are the possible causes?"

Abstract

Idiopathic pulmonary fibrosis (IPF) is the most common disease among idiopathic interstitial pneumonias (IIPs). The prognosis of idiopathic pulmonary fibrosis (IPF) is worse than any form of other IIPs, because there are few effective treatments clinically approved. Although many risk factors are recognized, the etiologies of fibrotic lung diseases are not clear. Genetic background and environmental factors are thought to be involved in the etiological factors. There are a number of candidate genes associated with the IPF; however, precise functional significances have not been verified yet. Alveolar epithelial cells are thought to be the initial lesion of lung injury caused by environmental factors, such as smoking, inhalational agents, drugs, oxygen radicals, toxins, and viruses. There is now growing evidence that repeated injury to alveolar epithelial cells leads to apoptosis, necrosis, or senescence. Surfactant gene mutations induce endoplasmic reticulum (ER) stress response in epithelial cells, and telomere shortening induces epithelial cell apoptosis and senescence. The failure of tissue repair due to impaired homeostasis and deregulated immunological mechanisms leads to disordered epithelialmesenchymal interactions and finally results in pulmonary fibrosis. These results may explain the increase of IPF associated with aging and also suggest the involvement of cellular senescence in the pathogenesis of IPF. Although the etiological agents or factors are various and not completely understood, the mechanisms how these etiological agents trigger fibrosis and the understanding of the mechanisms of deregulated homeostasis after initial injury may lead to the development of effective treatment strategy against IPF.