Newer developments in idiopathic pulmonary fibrosis in the era of anti-fibrotic medications

Nair, Girish B.; Matela, Ajsza; Kurbanov, Daniel; Raghu, Ganesh

doi:10.1080/17476348.2016.1177461

Cited by 13 publications

(7 citation statements)

References 114 publications

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“…In agreement with other studies, our study showed that IPF is predominantly a disease of elderly people, and several important findings emerged from our study. IPF is associated with a poor prognosis, but survival is difficult to predict for individual patients [7,36].…”

Section: Discussionmentioning

confidence: 99%

Independent Clinical Factors Relevant to Prognosis of Patients with Idiopathic Pulmonary Fibrosis

et al. 2019

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Background The prognosis of idiopathic pulmonary fibrosis (IPF) is the worst among all interstitial lung diseases, and is related to the disease itself. Comorbidities or complications can worsen IPF. We assessed the effect of comorbidities on the survival of IPF patients. A retrospective review of patients with IPF was completed. Material/Methods Information on demographic features, clinical examination, and comorbidities at baseline were obtained. Then, median, 1-year, and 5-year survival was calculated. A total of 380 patients with IPF admitted to Beijing Chao-Yang Hospital from 1 April 2002 to 31 March 2015 were followed up until December 2016. Results Of these 380 patients, 71.9% died during the study period. Median survival was 2.25 years and overall 5-year survival was 28.5%. Also, 86.3% of patients were males. A total of 248 cases underwent lung function tests, and 178 patients underwent bronchoalveolar lavage (BAL). Multivariate analyses showed that forced expiratory volume in 1 second/forced vital capacity (FVC), diffusing capacity of the lungs for carbon monoxide percent predicted, FVC% predicted, the number of macrophages, neutrophils, and lymphocytes in BAL fluid, pulmonary hypertension, hypoxemia, and hydropower disorder were independent prognostic indicators of IPF, GAP gender (G), age (A), and 2 pulmonary physiological parameters (P) model can help to predict prognosis of IPF. Conclusions Spirometry, GAP model, and BAL are helpful to forecast the prognosis of IPF. IPF patients also suffering from pulmonary arterial hypertension, hypoxemia, and hydropower disorder have a poor prognosis.

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Section: Discussionmentioning

confidence: 99%

Independent Clinical Factors Relevant to Prognosis of Patients with Idiopathic Pulmonary Fibrosis

et al. 2019

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“…[3][4][5] Conventionally, the IPF clinical course can be categorized into three types based on the rate of the forced ventilation capacity (FVC) decline: slow deterioration (less than 10% decline in FVC over 6 months or no changes in the disease indicators for many months), intermittent deterioration with episodes of exacerbations and rapid deterioration (more than 10% decline in FVC for 6 months). 3,6,7 For the last type, before the era of antifibrotic medications, the life expectancy of patients did not usually exceed 2 years from the time of diagnosis. [6][7][8] Besides acute exacerbations, a poor prognosis might be suspected in patients with IPF with such predictors as low values of FVC and diffusing capacity of the lung for carbon monoxide (DLCO), old age, and a high rate of pulmonary function decline.…”

Section: Introductionmentioning

confidence: 99%

“…3,6,7 For the last type, before the era of antifibrotic medications, the life expectancy of patients did not usually exceed 2 years from the time of diagnosis. [6][7][8] Besides acute exacerbations, a poor prognosis might be suspected in patients with IPF with such predictors as low values of FVC and diffusing capacity of the lung for carbon monoxide (DLCO), old age, and a high rate of pulmonary function decline. 3,9 The majority of clinical studies on the drug therapy of IPF did not evaluate the pretreatment functional reduction rate 10,11 ; therefore, it is difficult to judge its efficiency in patients with a fast lung function decline.…”

Section: Introductionmentioning

confidence: 99%

First-in-human high-cumulative-dose stem cell therapy in idiopathic pulmonary fibrosis with rapid lung function decline

Averyanov

Koroleva

Konoplyannikov

et al. 2019

Stem Cells Translational Medicine

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Previous phase I studies demonstrated safety and some beneficial effects of mesenchymal stem cells (MSCs) in patients with mild to moderate idiopathic pulmonary fibrosis (IPF). The aim of our study was to evaluate the safety, tolerability, and efficacy of a high cumulative dose of bone marrow MSCs in patients with rapid progressive course of severe to moderate IPF. Twenty patients with forced ventilation capacity (FVC) ≥40% and diffusing capacity of the lung for carbon monoxide (DLCO) ≥20% with a decline of both >10% over the previous 12 months were randomized into two groups: one group received two intravenous doses of allogeneic MSCs (2 × 10 8 cells) every 3 months, and the second group received a placebo. A total amount of 1.6 × 10 9 MSCs had been administered to each patient after the study completion. There were no significant adverse effects after administration of MSCs in any patients. In the group of MSC therapy, we observed significantly better improvement for the 6-minute walk distance in 13 weeks, for DLCO in 26 weeks, and for FVC in 39 weeks compared with placebo.FVC for 12 months in the MSCs therapy group increased by 7.8% from baseline, whereas it declined by 5.9% in the placebo group. We did not find differences between the groups in mortality (two patients died in each group) or any changes in the high-resolution computed tomography fibrosis score. In patients with IPF and a rapid pulmonary function decline, therapy with high doses of allogeneic MSCs is a safe and promising method to reduce disease progression.

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“…Particulate matter with an aerodynamic diameter of < 2.5 µm (PM2.5) is involved in the pathogenesis of various respiratory diseases because of the toxicity of these particles, which originate from various sources [1,2]. Harmful environmental factors can reportedly induce pulmonary brosis (PF) [3], which is associated with epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM) [4,5]. As an important pathway of stromal cell production and excess ECM deposition, EMT can promote scar tissue formation in the lungs, eventually leading to the development of PF [6].…”

Section: Introductionmentioning

confidence: 99%

N6-methyladenosine-mediated Nrf2 Regulates the Defense Mechanism Against PM2.5-induced Pulmonary Fibrosis

Ding¹,

Hu²,

Ning³

et al. 2021

Preprint

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Background: It has been reported that particulate matter with an aerodynamic diameter of < 2.5 µm (PM2.5) could induce epithelial–mesenchymal transition (EMT)- and extracellular matrix (ECM)-related pulmonary fibrosis (PF). The transcription factor Nrf2 alleviated PM2.5-induced PF by antagonizing oxidative stress. The N6-methyladenosine (m6A) modifications play a significant role in the stress response. However, the effect of m6A modification on the mechanisms of Nrf2-mediated defense against PM2.5-induced PF remain unknown. Here, we investigated the role and the underlying molecular mechanisms of m6A methylation of Nrf2 mRNA in PM2.5-induced PF. Results: Male C57BL/6 mice were exposed to filtered air (FA), unfiltered air (UA) and concentrated air (CA)for 16 weeks. 16HBE cells were treated with 0, 50, or 100 µg/mL PM2.5 for 24 h. Our data showed that chronic PM2.5 exposure could induce fibrosis in lung and increase Nrf2 signals. In Nrf2 deficient cells, α-SMA expression was significantly upregulated whereas E-cadherin decreased compared with WT cells after PM2.5 treatment which implied the aggravated fibrosis. m6A methyltransferase METTL3 was upregulated after PM2.5 treatment. m6A-methylated RNA immunoprecipitation (MeRIP) and qRT-PCR results showed that METTL3 improved the m6A modification of Nrf2 mRNA in PM2.5-exposed 16HBE cells. MeRIP-Seq and single-base T3 ligase-based PCR results showed that the m6A-modified sites of Nrf2 mRNA were 1317, 1376, and 935 in lung of mice after PM2.5 exposure. RIP results suggested that the m6A binding proteins YTHDF1/IGF2BP1 promoted Nrf2 translation by binding to Nrf2 mRNA m6A residues.Conclusions: Our results revealed the mechanism by which m6A regulated the activities of the Nrf2-mediated signaling pathway against PM2.5-induced PF.

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Newer developments in idiopathic pulmonary fibrosis in the era of anti-fibrotic medications

Cited by 13 publications

References 114 publications

Independent Clinical Factors Relevant to Prognosis of Patients with Idiopathic Pulmonary Fibrosis

Independent Clinical Factors Relevant to Prognosis of Patients with Idiopathic Pulmonary Fibrosis

First-in-human high-cumulative-dose stem cell therapy in idiopathic pulmonary fibrosis with rapid lung function decline

N6-methyladenosine-mediated Nrf2 Regulates the Defense Mechanism Against PM2.5-induced Pulmonary Fibrosis

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