Effects of Pirfenidone and Nintedanib on Markers of Systemic Oxidative Stress and Inflammation in Patients with Idiopathic Pulmonary Fibrosis: A Preliminary Report

Fois, Alessandro Giuseppe; Sotgiu, Elisabetta; Scano, Valentina; Negri, Silvia; Mellino, Sabrina; Zinellu, Elisabetta; Pirina, Pietro; Pintus, Gianfranco; Carru, Ciriaco; Mangoni, Arduino A.; Zinellu, Angelo

doi:10.3390/antiox9111064

Cited by 27 publications

(21 citation statements)

References 57 publications

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“…Although there is no effective treatment to reverse fibrosis, nintedanib and pirfenidone can help to retard its progression ( 41 , 42 ). Additionally, the anti-angiogenic effects of nintedanib, along with anti-inflammatory and antioxidant properties of pirfenidone, are well-known ( 43 ) and may bring similar benefits to CIP patients. Currently, 3 case reports have shown that nintedanib/pirfenidone can bring benefits to CIP ( 44 – 46 ).…”

Section: Discussionmentioning

confidence: 99%

Proposed clinical phases for the improvement of personalized treatment of checkpoint inhibitor–related pneumonitis

Zhou

Yang²,

Lin³

et al. 2022

Front. Immunol.

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BackgroundCheckpoint inhibitor–related pneumonitis (CIP) is a lethal immune-related adverse event. However, the development process of CIP, which may provide insight into more effective management, has not been extensively examined.MethodsWe conducted a multicenter retrospective analysis of 56 patients who developed CIP. Clinical characteristics, radiological features, histologic features, and laboratory tests were analyzed. After a comprehensive analysis, we proposed acute, subacute, and chronic phases of CIP and summarized each phase’s characteristics.ResultsThere were 51 patients in the acute phase, 22 in the subacute phase, and 11 in the chronic phase. The median interval time from the beginning of CIP to the different phases was calculated (acute phase: ≤4.9 weeks; subacute phase: 4.9~13.1 weeks; and chronic phase: ≥13.1 weeks). The symptoms relieved from the acute phase to the chronic phase, and the CIP grade and Performance Status score decreased (P<0.05). The main change in radiologic features was the absorption of the lesions, and 3 (3/11) patients in the chronic phase had persistent traction bronchiectasis. For histologic features, most patients had acute fibrinous pneumonitis in the acute phase (5/8), and most had organizing pneumonia in the subacute phase (5/6). Other histologic changes advanced over time, with the lesions entering a state of fibrosis. Moreover, the levels of interleukin-6, interleukin-10 and high-sensitivity C-reactive protein (hsCRP) increased in the acute phase and decreased as CIP progressed (IL-6: 17.9 vs. 9.8 vs. 5.7, P=0.018; IL-10: 4.6 vs 3.0 vs. 2.0, P=0.041; hsCRP: 88.2 vs. 19.4 vs. 14.4, P=0.005).ConclusionsThe general development process of CIP can be divided into acute, subacute, and chronic phases, upon which a better management strategy might be based devised.

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Section: Discussionmentioning

confidence: 99%

Proposed clinical phases for the improvement of personalized treatment of checkpoint inhibitor–related pneumonitis

Zhou

Yang²,

Lin³

et al. 2022

Front. Immunol.

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“…Although the precise molecular and cellular mechanisms still require full elucidation, there is substantial evidence supporting the concept that a profibrotic environment orchestrated by underlying factors such as genetic predisposition, chronic injury and aging, 2 of 22 oxidative stress [2,3], and impaired regenerative responses may account for disease development and persistence [4]. By producing growth factors, cytokines, chemokines, ECM proteins, and proteases, myofibroblasts play a pivotal role in fibrosis.…”

Section: Introductionmentioning

confidence: 99%

Niclosamide Ethanolamine Salt Alleviates Idiopathic Pulmonary Fibrosis by Modulating the PI3K-mTORC1 Pathway

Pei

Zheng

Yin

et al. 2022

Cells

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Idiopathic pulmonary fibrosis (IPF) is an interstitial pneumonia characterized by chronic progressive fibrosis, ultimately leading to respiratory failure and early mortality. Although not fully explored, the major causative factors in IPF pathogenesis are dysregulated fibroblast proliferation and excessive accumulation of extracellular matrix (ECM) deposited by myofibroblasts differentiated from pulmonary fibroblasts. More signalling pathways, including the PI3K-Akt-mTOR and autophagy pathways, are involved in IPF pathogenesis. Niclosamide ethanolamine salt (NEN) is a highly effective multitarget small-molecule inhibitor reported in antitumor studies. Here, we reported that in an IPF animal model treated with NEN for 14 days, attractive relief of pulmonary function and hydroxyproline content were observed. To further explore, the therapeutic effect of NEN in IPF and pathological changes in bleomycin-challenged mouse lung sections were assessed. Additionally, the effects of NEN on abnormal proliferation and ECM production in IPF cell models established with TGF-β1-stimulated A549 cells or DHLF-IPF cells were studied. In nonclinical studies, NEN ameliorated lung function and histopathological changes in bleomycin-challenged mice, and the lung hydroxyproline content was significantly diminished with NEN treatment. In vitro, NEN inhibited PI3K-mTORC1 signalling and arrested the cell cycle to prevent uncontrolled fibroblast proliferation. Additionally, NEN inhibited TGF-β1-induced epithelial–mesenchymal transition (EMT) and ECM accumulation via the mTORC1-4EBP1 axis. Furthermore, NEN-activated noncanonical autophagy resensitized fibroblasts to apoptosis. The above findings demonstrated the potential antifibrotic effect of NEN mediated via modulation of the PI3K-mTORC1 and autophagy pathways. These data provide strong evidence for a therapeutic role for NEN in IPF.

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“…It has been reported that antioxidant activity mediates pirfenidone antifibrotic effects in human pulmonary vascular smooth muscle cells exposed to sera of idiopathic pulmonary fibrosis patients [ 29 ]. Besides, pirfenidone exerts beneficial effects on specific markers of oxidative stress and inflammation in IPF patients [ 30 ]. The results of this meta-analysis have showed that compared with the control group, pirfenidone reduces the risk of IPF progression or death by 35%, and it can significantly improve lung function, including delay the decline of VC and FVC.…”

Section: Discussionmentioning

confidence: 99%

The effects and safety of pirfenidone in the treatment of idiopathic pulmonary fibrosis: a meta-analysis and systematic review

et al. 2021

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Background It is necessary to systematically evaluate the efficacy and adverse reactions of pirfenidone in the treatment of patients with idiopathic pulmonary fibrosis (IPF). Methods Pubmed et al. databases were searched up to March 15, 2021 for randomized controlled trials (RCT) of pirfenidone in the treatment of IPF. Two authors collected and compared the indicators including progression-free survival (PFS), vital capacity (VC), forced vital capacity (FVC), and adverse reactions. RevMan 5.3 software and Stata 15.0 software were used for meta-analysis. Results A total of 8 reports with 9 RCTs involving 1824 IPF patients were included. Meta-analysis results showed that compared with the control group, pirfenidone could prolong the PFS phase of IPF patients (HR = 0.65, 95% CI 0.55 ~ 0.76, P < 0.001), slow down the VC of IPF patients (SMD = 0.43, 95% CI 0.21 ~ 0.66, P < 0.001), and decrease FVC (SMD = 0.31, 95% CI 0.14 ~ 0.48, P < 0.001). The main adverse reactions of pirfenidone were gastrointestinal reactions, photosensitivity and skin rashes. Conclusion Pirfenidone is beneficial to prolong the PFS of IPF patients, improve lung function, and it is safe for clinical use. However, more high-quality RCTs are still needed to provide reliable evidence for the treatment of IPF.

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Effects of Pirfenidone and Nintedanib on Markers of Systemic Oxidative Stress and Inflammation in Patients with Idiopathic Pulmonary Fibrosis: A Preliminary Report

Cited by 27 publications

References 57 publications

Proposed clinical phases for the improvement of personalized treatment of checkpoint inhibitor–related pneumonitis

Proposed clinical phases for the improvement of personalized treatment of checkpoint inhibitor–related pneumonitis

Niclosamide Ethanolamine Salt Alleviates Idiopathic Pulmonary Fibrosis by Modulating the PI3K-mTORC1 Pathway

The effects and safety of pirfenidone in the treatment of idiopathic pulmonary fibrosis: a meta-analysis and systematic review

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