What We Know About the Pathogenesis of Idiopathic Pulmonary Fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease of unknown cause, occurring in adults, limited to the lungs and associated with the pathologic and radiologic pattern of usual interstitial pneumonia. Prognosis is poor, and most patients die of respiratory failure within 3 to 6 years from the onset of symptoms. Although our understanding of the pathogenesis of IPF has improved over the past two decades, the mechanisms responsible for this disorder have not been clearly defined. Aging is the single most important risk factor, but genetic, environmental, and diverse exogenous factors such as smoking, viral infections, chronic tissue injury (i.e., gastroesophageal reflux disease, traction injury) play contributory roles. In this review, we focus on pathogenetic mechanisms that we think are crucial for the initiation of the fibrotic process and for its progressive evolution. In the early stage of the disease, in the context of the permissive genetic background combined with the presence of specific risk factors, alveolar epithelial cells play a leading role. Subsequent evolution of the fibrotic process and its lethal progression is likely due to the abnormal tissue repair process that takes place in the lung and to the inability to counteract this process. In this phase of the disease, fibroblasts assume a crucial role. Current pharmacological treatment strategies for IPF have only modest value, principally by slowing the course of disease progression. Unfortunately, improvement or cure has not yet been achieved with pharmacological agents. The challenge for the future is to improve the comprehension of the mechanisms involved in the inception and evolution of IPF and their articulated interactions. This is fundamental not only to conceive and develop new drugs against this dreadful disease but also to apply different therapeutic approaches such as drug repositioning and personalized therapies in the management of IPF.

Imaging Pulmonary Inflammation

“…However, reduced 67 Ga uptake in response to steroid therapy does not correlate with clinical improvement in patients with IPF (69). These results are in line with multiple studies demonstrating the ineffectiveness of steroids and immunosuppression for mitigating ILD progression (70). Therefore, inflammation is less likely to be a causative factor in ILDs.…”

The Role of Infection in Interstitial Lung Diseases

“…4 Many experts theorize that repeated episodes of alveolar injury in a predisposed host with dysfunctional healing mechanisms are central to the development and progression of IPF. 5,6 Environmental factors that are thought to contribute include dust, particulate exposures, aspiration of gastric contents, and infection. [5][6][7] No definitive evidence exists to support the causal role of infections in the pathogenesis of IPF.…”

“…5,6 Environmental factors that are thought to contribute include dust, particulate exposures, aspiration of gastric contents, and infection. [5][6][7] No definitive evidence exists to support the causal role of infections in the pathogenesis of IPF. Moreover, during AEs, infectious triggers are identified in only a minority of patients (possibly due to limitations of testing methods).…”

Artesunate ameliorates lung fibrosis via inhibiting the Notch signaling pathway

“…Idiopathic pulmonary fibrosis (IPF) is a progressive, severely debilitating disease with a high mortality rate (1). However, there are currently no effective treatments for IPF.…”