Antifibrotic therapy for fibrotic lung disease beyond idiopathic pulmonary fibrosis

Abstract

Two antifibrotic medications (nintedanib and pirfenidone) were recommended (conditionally) for the treatment of patients with idiopathic pulmonary fibrosis (IPF) in the 2015 IPF evidence-based guidelines. These medications have been shown to reduce the rate of decline in forced vital capacity among patients with IPF over time and are the only two disease-modulating pharmacological agents approved by regulatory agencies and available for clinical use worldwide. With the evolved standard of care for interstitial lung disease evaluation including routine use of high-resolution computed tomography, fibrotic lung diseases other than IPF are increasingly recognised. In addition, it is becoming evident that genetic and pathophysiological mechanisms as well as disease behaviour in patients manifesting other “non-IPF progressive fibrotic interstitial lung diseases” (non-IPF-PF) may be similar to those in patients with IPF. Thus, it is biologically plausible that pharmacological agents with antifibrotic properties may be efficacious in non-IPF-PF. Indeed, studies are underway or planned to assess the safety and efficacy of nintedanib or pirfenidone among patients with several non-IPF fibrotic lung diseases. In this review, we briefly summarise the use of pirfenidone and nintedanib in IPF as well as the rationale and potential for use of these medications in non-IPF-PF that are being investigated in ongoing and upcoming clinical trials.

Sphingosine Kinase 1/S1P Signaling Contributes to Pulmonary Fibrosis by Activating Hippo/YAP Pathway and Mitochondrial Reactive Oxygen Species in Lung Fibroblasts

“…Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease of unknown etiology that is characterized by the inflammation of the pulmonary interstitium, the deposition of extracellular matrix proteins, and fibrosis that destroys the alveolar architecture [1][2][3]. While two FDA approved drugs for the treatment of pulmonary fibrosis (PF) slow the disease's progression, neither is curative [4,5]. Lung transplantation is an option for a minority of patients [6], but the outcomes after the lung transplant are far worse than for other organs [7].…”

A novel approach to the treatment of fibrosing interstitial lung diseases

“…В начале XXI века для лечения идиопатического легочного фиброза, характеризующегося рентгенологической и гистологической картиной обычной интерстициальной пневмонии, были зарегистрированы два препарата с доказанным антифиброзным действием -нинтеданиб и пирфенидон [2,3]. Общность механизмов развития легочного фиброза при обычной интерстициальной пневмонии и других вариантах фиброзирующих ИЗЛ позволили предположить, что эти препараты могут найти применение и при других заболевания [4].…”

Prognostic impact of typical and probable usual interstitial pneumonia pattern in idiopathic pulmonary fibrosis: is the debate about biopsy aStar Warssaga?

“…In the context of suspected idiopathic pulmonary fibrosis (IPF), accurate non-invasive diagnosis requires recognition of the hallmark usual interstitial pneumonia (UIP) pattern on imaging, obviating lung biopsy [1,2]. When the imaging pattern is "probable UIP", the need for histopathology confirmation of a UIP pattern in surgical lung biopsy (SLB) is often debated, despite concordance between expert groups that SLB is not mandated for IPF diagnosis when the clinical setting is appropriate and multidisciplinary discussion has taken place [1][2][3]. It is the radiographic pattern of "probable UIP" that is at the centre of this debate, and the question of whether a biopsy is required in order to diagnose a specific fibrotic ILD.…”