Pirfenidone, nintedanib and N-acetylcysteine for the treatment of idiopathic pulmonary fibrosis: A systematic review and meta-analysis

Rogliani, Paola; Calzetta, Luigino; Cavalli, Francesco; Matera, Maria Gabriella; Cazzola, Mario

doi:10.1016/j.pupt.2016.07.009

Cited by 141 publications

(109 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Similarly, Nintedanib is a triple kinase inhibitor thought to downregulate mitogenic factors [132]. Although both treatments are viable options for patients suffering from IPF, they do not stop the progression of IPF and their long term effects on disease progression and lung homeostasis are still unknown [133]. Additionally, Pirfenidone and Nintedanib treatments come with an array of side effects including nausea, diarrhea, and fatigue, which are reported to lower quality of life and in some cases require cessation of treatment [134][135][136][137].…”

Section: Treatment Of Ipfmentioning

confidence: 99%

Regulation of MUC5B Expression in Idiopathic Pulmonary Fibrosis

Helling

Gerber

Kadiyala

et al. 2017

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

Idiopathic pulmonary fibrosis (IPF) is the most common and the most aggressive fibrosing interstitial lung disease (ILD). Despite recent promising clinical trials, IPF remains incurable and largely untreatable. Genetic studies have identified several risk loci for both sporadic and familial forms of IPF. A single variant upstream of MUC5B is predicted to account for more than 30% of all IPF risk. This variant, rs35705950, is associated with expression of MUC5B in healthy lung tissue. However, the mechanism underlying the relationship between rs35705950 and MUC5B expression remains unclear.The first goal of my thesis research was to determine whether rs35705950 is also a risk factor for other forms of ILD. Genomic DNA from individuals with IPF, HP, COPD, iNSIP, and RB-ILD was obtained and genotyped for the common MUC5B promoter variant. In these populations the risk allele was associated with IPF and iNSIP which suggested a potential shared disease mechanism. Additionally, I showed that in the IPF and control populations rs35705950 is associated with lung MUC5B expression.The second goal of my thesis research was to investigate MUC5B promoter DNA methylation which has previously been shown to play a role in MUC5B expression.Methylation analysis of the 4KB region upstream of MUC5B identified two differentially methylated regions (DMRs) associated with IPF, one DMR associated with MUC5B iv expression, and one DMR associated with rs35705950. The IPF, MUC5B expression, and rs35705950 associated DMRs are all differentially methylated at a cluster of 11 CpG motifs. overlapping DMR, including the motif disrupted by rs35705950. These findings suggest that DNA methylation may play a role in MUC5B gene regulation and IPF risk.Next, I used cross species analysis to identify highly conserved domains within the overlapping DMR. Evolutionary conservation indicated selective pressures to maintain sequences overtime and suggests biological importance. The overlapping DMR contains a highly conserved binding motif for FOXA2, a transcription factor. Further analysis using ChIP-qPCR, reporter constructs, and siRNA, established a role for FOXA2 in regulation of MUC5B expression in lung tissue. Additionally, siRNA knock down identified 3 other transcription factors which are associated with MUC5B expression; STAT3, HOXA9 and ZBTB7A. These transcriptional regulators provide insight into possible therapeutic intervention for MUC5B dysregulation and IPF.The form and content of this abstract are approved. I recommend its publication.

show abstract

Section: Treatment Of Ipfmentioning

confidence: 99%

Regulation of MUC5B Expression in Idiopathic Pulmonary Fibrosis

Helling

Gerber

Kadiyala

et al. 2017

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

show abstract

“…Although the novel antifibrotic agents pirfenidone and nintedanib attenuate the progressive decline in lung function characteristic of IPF [1], reduce the risk of hospitalisation or exacerbation [2,3], and reduce the risk of death [3][4][5], IPF is a very severe disease where clinical decline is common. IPF is of particular interest to the lung physiologist because its clinical expression, which ranges from exertional dyspnoea occurring early in the disease to end-stage respiratory failure, is directly related to alterations in lung physiology.…”

Section: Introductionmentioning

confidence: 99%

Physiology of the lung in idiopathic pulmonary fibrosis

et al. 2018

View full text Add to dashboard Cite

The clinical expression of idiopathic pulmonary fibrosis (IPF) is directly related to multiple alterations in lung function. These alterations derive from a complex disease process affecting all compartments of the lower respiratory system, from the conducting airways to the lung vasculature. In this article we review the profound alterations in lung mechanics (reduced lung compliance and lung volumes), pulmonary gas exchange (reduced diffusing capacity, increased dead space ventilation, chronic arterial hypoxaemia) and airway physiology (increased cough reflex and increased airway volume), as well as pulmonary haemodynamics related to IPF. The relative contribution of these alterations to exertional limitation and dyspnoea in IPF is discussed.

show abstract

“…However, in the current era, separation of UIP/IPF from CHP is crucial because the former is treated with antifibrotic agents (pirfenidone, nintedanib), 6 whereas CHP is treated with immunosuppressive agents. 7 The general definition of hypersensitivity pneumonitis (HP) includes exposure to a sensitizing antigen (sometimes called an inciting agent in the literature), and there is some evidence that removing a patient with CHP from antigen exposure improves survival, 8 although other reports deny that, 9,10 so correct diagnosis of CHP cases may be important to alert the clinician to look for a source of exposure.…”

mentioning

confidence: 99%

Pathology of Chronic Hypersensitivity Pneumonitis What Is It? What Are the Diagnostic Criteria? Why Do We Care?

Churg

Bilawich

Wright

2017

Archives of Pathology &Amp; Laboratory Medicine

View full text Add to dashboard Cite

Context.— Chronic hypersensitivity pneumonitis (CHP) has emerged from obscurity during the past 15 years and is now recognized as a very common form of fibrosing interstitial pneumonia but one that is frequently misdiagnosed both clinically and on surgical lung biopsy as usual interstitial pneumonia/idiopathic pulmonary fibrosis (UIP/IPF) or fibrotic nonspecific interstitial pneumonia. Objective.— To review the pathologic features of CHP. Data Sources.— Clinical, pathology, and radiology literature were used. Conclusions.— Upper lobe–predominant fibrosis and/or air-trapping on computed tomography scan are features of CHP but not UIP/IPF; however, radiologic separation is possible in only about 50% of cases. Morphologically, CHP sometimes mimics UIP/IPF, but CHP often shows isolated foci of peribronchiolar (centrilobular) fibrosis, frequently associated with fibroblast foci, and in CHP, fibrosis may bridge from the centrilobular region to another bronchiole, an interlobular septum, or the pleura (“bridging fibrosis”). This set of findings is uncommon in UIP/IPF. In addition, CHP may produce a picture of fibrotic nonspecific interstitial pneumonia. Although giant cells/granulomas are usually present in subacute hypersensitivity pneumonitis, they are much less frequently found in CHP, and their absence does not contradict the diagnosis. This diagnostic separation is clinically important because CHP is treated differently than UIP/IPF is (immunosuppressive agents versus antifibrotic agents); further, there are some data to suggest that removing the patient from antigen exposure improves outcome, and there is evidence that patients with CHP have a much better survival prognosis after lung transplantation than do patients with UIP/IPF. In most cases, accurate diagnosis of CHP requires consultation among clinicians, radiologists, and pathologists.

show abstract

Pirfenidone, nintedanib and N-acetylcysteine for the treatment of idiopathic pulmonary fibrosis: A systematic review and meta-analysis

Cited by 141 publications

References 57 publications

Regulation of MUC5B Expression in Idiopathic Pulmonary Fibrosis

Regulation of MUC5B Expression in Idiopathic Pulmonary Fibrosis

Physiology of the lung in idiopathic pulmonary fibrosis

Pathology of Chronic Hypersensitivity Pneumonitis What Is It? What Are the Diagnostic Criteria? Why Do We Care?

Contact Info

Product

Resources

About