New insights into the pathogenesis and treatment of idiopathic pulmonary fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) is the most common and lethal of the idiopathic interstitial pneumonias. There are currently no effective pharmacological therapies approved for the treatment of IPF. Despite the focus on targeting fibrogenic pathways, recent clinical trials have been largely disappointing. Progress is being made in elucidating key cellular processes and molecular pathways critical to IPF pathogenesis, and this should facilitate the development of more effective therapeutics for this recalcitrant disease. Emerging pathobiological concepts include the role of aging and cellular senescence, oxidative stress, endoplasmic reticulum stress, cellular plasticity, microRNAs and mechanotransduction. Therapeutic approaches that target molecular pathways to modulate aberrant cellular phenotypes and promote tissue homeostasis in the lung must be developed. Heterogeneity in biological and clinical phenotypes of IPF warrants a personalized medicine approach to diagnosis and treatment of this lung disorder.

Figure 1. Pathogenesis of IPF

Host-environmental interactions result in the generation of abnormal cell types and interactions between these cells of the lower respiratory tract. Host factors include age, genetic/epigenetic influences, and co-morbidities such as gastroesophageal reflux and diabetes. Environmental factors include noxious agents (e.g. cigarette smoke) and infectious agents (e.g. viruses). Ultimately, altered communication between aberrant epithelial and mesenchymal cells leads to a loss of tissue homeostasis, culminating in tissue remodeling, contraction, and fibrosis.