Abstract
Idiopathic pulmonary fibrosis is a chronic, progressive, and lethal lung disease of unknown etiology. Antifibrotic drugs, including pirfenidone, are currently used for the treatment of the disease. The oral administration of pirfenidone is an effective therapy, as demonstrated by several clinical trials, although it causes severe adverse events in some patients. We hypothesized that low-dose intrapulmonary delivery of pirfenidone is effective in human transforming growth factorβ1-driven pulmonary fibrosis. To demonstrate our hypothesis, we compared the therapeutic efficacy of varying doses of pirfenidone administered by oral and intranasal routes in a human transforming growth factor-β1 transgenic mouse with established pulmonary fibrosis. We found similar amelioration of lung cell infiltration, inflammatory and fibrotic cytokines, lung fibrosis score, and hydroxyproline content in mice with human transforming growth factor-β1-mediated pulmonary fibrosis treated with low-dose intranasal pirfenidone and high-dose oral pirfenidone. This study showed that pirfenidone is a potent inhibitor of human transforming growth factor-β1-driven lung fibrosis and that intrapulmonary delivery of low-dose pirfenidone produces therapeutic responses equivalent to high-dose of oral pirfenidone.
Highlights
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and devastating lung disease of unknown etiology that increases global morbidity and mortality (King et al, 2011; Lederer and Martinez, 2018)
There were no significant differences in Computed tomography (CT) scores among TGFβ1-TG groups before starting oral PFD
The CT scores decreased in all groups treated with oral PFD compared to the TGFβ1-TG/MC, the decrease was not significant (Figure 1A)
Summary
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and devastating lung disease of unknown etiology that increases global morbidity and mortality (King et al, 2011; Lederer and Martinez, 2018). The life expectancy of patients with idiopathic pulmonary fibrosis is only 2–3 years after a confirmed diagnosis of the disease (Barratt et al, 2018). IPF is the most frequent form of fibrotic lung disease (Lederer and Martinez, 2018). Once the disease is triggered, a myriad of pro-fibrotic factors including transforming growth factor (TGF) β1, connective tissue growth factor (CTGF), inflammatory. Intrapulmonary Pirfenidone for Pulmonary Fibrosis cytokines including interleukin-13 (IL-13), interferon (IFN)γ and clotting factors may contribute to disease progression and outcome (King et al, 2011; Barratt et al, 2018). The development of severe pulmonary fibrosis resembling the human disease in mice with lung-specific overexpression of human TGFβ1 is the proof-of-concept of the pivotal role of TGFβ1 in pulmonary fibrosis (D’AlessandroGabazza et al, 2012; Fujiwara et al, 2017; D’AlessandroGabazza et al, 2018)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
