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Chest CT Scan in a Patient with Idiopathic Pulmonary Fibrosis. A representative high-resolution chest CT image from the patient whose radiograph is depicted in Figure 3 is shown. High-resolution CT images of the lung parenchyma are best obtained with the patient lying prone to reduce gravitational effects on lower-lobe lung density. There is prominent irregular septal thickening (arrowhead), subpleural honeycombing (asterisk), and a dilated airway, representing traction bronchiectasis (arrow). Open-lung biopsy confirmed pathological changes typical of usual interstitial pneumonia.
Source publication
Idiopathic pulmonary fibrosis is a rapidly progressive illness of unknown cause characterized by sequential acute lung injury with subsequent scarring and end-stage lung disease. Treatment at present remains largely supportive, with evidence that patients' satisfaction and survival may be improved by referral to centers specializing in the evaluati...
Context in source publication
Context 1
... This improved imaging allows experienced readers to characterize anatomical patterns in interstitial lung diseases. The typical CT features of idiopathic pulmonary fibrosis include patchy peripheral reticular abnormalities with intralobular lin- ear opacities, irregular septal thickening, subpleural honeycombing, and traction bronchiectasis (Fig. 4). These findings are always most prominent in the low- er lung zones, but they may involve all lobes in ad- vanced disease. The extent of disease on high-resolu- tion CT correlates with fibrosis on biopsy and with physiological impairment. 43 A study examined the ability of physicians expert in the diagnosis of interstitial lung ...
Citations
... Pulmonary fibrosis (PF) is a progressively fatal disease characterized by massive proliferation of lung fibroblasts, accumulation of extracellular matrix, massive deposition of collagen matrix and the production of proinflammatory cytokines [1,2]. In recent years, its morbidity has gradually increased; moreover, its prognosis is poor, and its mortality rate is high [3,4]. ...
Background and objective
Pulmonary fibrosis caused by lung injury is accompanied by varying degrees of inflammation, and diazepam can reduce the levels of inflammatory factors. Therefore, the purpose of this study was to determine whether diazepam can inhibit inflammation and ameliorate pulmonary fibrosis by regulating the let-7a-5p/myeloid differentiation factor 88 (MYD88) axis.
Methods
Lipopolysaccharide (LPS) was used to induce cell pyroptosis in an animal model of pulmonary fibrosis. After treatment with diazepam, changes in cell proliferation and apoptosis were observed, and the occurrence of inflammation and pulmonary fibrosis in the mice was detected.
Results
The results showed that LPS can successfully induce cell pyroptosis and inflammatory responses and cause lung fibrosis in mice. Diazepam inhibits the expression of pyroptosis-related factors and inflammatory factors; moreover, it attenuates the occurrence of pulmonary fibrosis in mice. Mechanistically, diazepam can upregulate the expression of let-7a-5p, inhibit the expression of MYD88, and reduce inflammation and inhibit pulmonary fibrosis by regulating the let-7a-5p/MYD88 axis.
Conclusion
Our findings indicated that diazepam can inhibit LPS-induced pyroptosis and inflammatory responses and alleviate pulmonary fibrosis in mice by regulating the let-7a-5p/MYD88 axis.
... We are talking about such factors as connective tissue diseases, occupational diseases, exposure to harmful agents and toxic effects of drugs. Laboratory tests can be helpful in ruling out these causes, but do not play a significant role in making the diagnosis of IPF [11,13]. High-resolution computed tomography (CTWR) plays a dominant role in the diagnosis of IPF. ...
Idiopathic pulmonary fibrosis (IPF) is a chronic, rare disease characterized by continuous fibrosis of the lung parenchyma. It mainly affects the elderly; however, it is increasingly being diagnosed in younger patients as well. Risk factors include smoking, occupational dust exposure and genetic factors. Symptoms of IPF include shortness of breath, dry cough and reduced exercise tolerance, leading to a reduced quality of life for patients. Diagnosis is based on imaging, mainly high-resolution CT scans, and the exclusion of other causes of interstitial lung disease. Two antifibrotic drugs, nintedanib and pirfenidone, are now approved to slow disease progression. Nintedanib acts as a tyrosine kinase inhibitor, blocking the signaling pathways of lung fibroblasts. Pirfenidone, on the other hand, has anti-inflammatory and anti-fibrotic effects by inhibiting TGF-b signaling pathways. Clinical trials have confirmed their efficacy in reducing the decline in increased vital capacity and the risk of disease progression. In Poland, patients with IPF can benefit from nintedanib and pirfenidone therapy under the drug program. Despite advances in treatment, more research is needed on new IPF therapies. Clinical trials of zinpentraxin, ziritaxestat and pambrevalumab have not confirmed their efficacy in treating IPF. Results from initial studies of bexotegrast show promise, but further studies are needed and are ongoing. Despite advances in the treatment of IPF, further research into new therapies is needed to improve therapeutic outcomes and patient quality of life.
... Klinik olarak ilerleyen nefes darlığı, kronik öksürük ve bazallerde insipiriyumda raller olur. Hastaların 2/3'ünde çomak parmak izlenirken, SFT'de azalmış akciğer hacmi ile karakterize restriktif patern ve azalmış difüzyon kapasitesi olur [6,29]. ...
... Although the pathogenesis of IPF has not yet been fully elucidated, it is generally accepted that this condition is caused by repeated damage and abnormal repair of alveolar epithelial cells, occurring mainly during the process of epithelial-mesenchymallike transition (EMT). 23 Pulmonary fibroblasts are important effector cells in the fibrosis stage of IPF, 24 and myofibroblasts are important cells that promote the development of pulmonary fibrotic disease. 25 α-SMA is an important marker of differentiation of fibroblasts to myofibroblasts. ...
Objective: The Traditional Chinese Medicine Qingzao Jiufei Tang decoction (QZJFD) is effective for the treatment of idiopathic pulmonary fibrosis (IPF). In this study, we explored the anti-pulmonary fibrosis effect of QZJFD and the underlying mechanism. Methods: The effects of QZJFD at low, medium, and high doses were investigated in a rat model of lung fibrosis induced by tracheal injection of bleomycin; pirfenidone was included as a positive control. Serum levels of interleukin-6 (IL-6), tumor necrosis factors (TNF-α), and IL-1β in rats were detected by enzyme-linked immunosorbent assay (ELISA). Expression of α-smooth muscle actin (α-SMA), TGF-β1, p-Jun N-terminal kinase (p-JNK), JNK, p-P38 mitogen-activated protein kinase (MAPK), P38 MAPK, collagen I, and fibronectin-1 (FN1) in lung tissues was detected by immunofluorescence labeling and western blot analysis. Results: QZJFD contained 209 main components and 575 corresponding targets. In total, 3875 disease action targets were related to IPF, with 308 common targets shared by drugs and diseases. The key targets included albumin (ALB), recombinant protein, TNF, IL-6, and tumor protein p53. In total, 3061 items were identified in the gene ontology enrichment analysis ( P < .05) and 197 signaling pathways in the Kyoto encyclopedia of genes and genomes ( P < .05), including MAPK, calcium, advanced glycosylation end products - receptors, TNF, and IL-17. Molecular docking simulation showed that the 2 predominant compounds of QZJFD, naringenin, and kaempferol, bound with high affinity to ALB. Serum levels of IL-6, TNF-α, and IL-1β and the expression levels of α-SMA, TGF-β1, p-JNK, p-P38 MAPK, collagen I, and FN1 in lung tissues were significantly increased in the model rats ( P < .001). After treatment with pirfenidone and QZJFD at the medium and high doses, serum levels of IL-6, TNF-α, and IL-1β and expression levels of α-SMA, p-JNK, p-P38 MAPK, collagen I, and FN1 in lung tissues of rats were significantly lower than those in the model group ( P < .05). Conclusions: QZJFD may exert antifibrotic and anti-inflammatory effects that improve the status of IPF by regulating the MAPK signaling pathway.
... As its name suggests, the etiology of IPF is largely unknown. Repeated cycles of subclinical epithelial injury and aberrant lung repair (6) as well as the activation of development pathways (7) have been proposed to explain the pathogenesis. Recent advances in genomics and bioinformatics are starting to unlock its genetic component and, in turn, refine our molecular understanding of this disease (8). ...
The recent European Respiratory Society statement on familial pulmonary fibrosis (FPF) supports the need of genetic testing in the care of patients and their relatives. However, no solution (i.e., a concrete test) was provided to implemented genetic testing in daily practice. Herein, we tabulated and standardized the nomenclature of 128 genetic variants in 20 genes implicated in adult-onset pulmonary fibrosis. The objective was to develop a laboratory developed test (LDT) based on standard Sanger sequencing in order to capture all known FPF-associated variants. Targeted DNA fragments were amplified with harmonized PCR conditions to perform the LDT in a single 96-well plate. The new genetic test was evaluated in 62 sporadic cases of idiopathic pulmonary fibrosis (IPF). As expected in this population, we observed a low yield of disease-causing mutations. More importantly, 100% of targeted variants by the LDT were successfully evaluated. Furthermore, four variants of uncertain significance with in silico-predicted deleterious scores were identified in three patients, suggesting novel pathogenic variants in genes known to cause IPF. Finally, the MUC5B promoter variant rs35705950 was strongly enriched in these patients with a minor allele frequency of 41.1% compared to 10.6% in a matched population-based cohort (n=29,060), leading to an estimation that this variant may explain up to 35% of the population-attributable risk. This LDT provides a solution for rapid clinical translation. Technical laboratory details are provided so that specialised pulmonary centers can implement the LDT in-house in order to expedite the clinical recommendations of experts' panel. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
... [7] Inflammation can prompt numerous hereditary modifications influencing cell development, separation, and endurance, including the mutation of genes that suppress tumors (such as p53), the activation of oncogenes, and the turnover of genes that cause apoptosis. [8] The proto-oncogene B-Raf (BRAF) gene on chromosome 7 (7q34) encodes the BRAF protein, which shares in the mitogen-actuated protein kinase (MAPK)/extracellular signal-regulated kinases signaling pathway. This pathway directs significant cell capacities including cell development, separation, multiplication, senescence, and apoptosis. ...
Background
Many studies demonstrating a high predominance of pulmonary disease among individuals with interstitial lung disease (ILD), genomic examinations have recognized and initiated mutations in proto-oncogene B-Raf (BRAF) among patients with lung malignant growth. To support our hypothesis of being ILD could show a more vital event for framing into bronchogenic threat BRAFV600E change was examined.
Objectives
To inquire about the frequency of BRAF (V600E) mutation in ILD with the possible evaluation of the presence of BRAF V600 mutation and such parameters as patient’s age, gender, and histopathological type.
Materials and Methods
From January 2017 to April 2019, a review study was led in a few confidential labs and the Teeba respiratory focus in Hilla city, Babylon region. Sixty patients with interstitial lung issues’ clarifying data were recuperated, formalin-fixed paraffin-embedded (FFPE) tissue portions were furthermore collected, all of the results were surveyed by three expert histopathologists, and the last attestation of the examination was done. Equivalent number (60) of healthy lung tissues were also involved and used as control tests for polymerase chain reaction review.
Results
Only two (3.3%) of ILD tests harbored BRAF V600E change, all of them were between 41 and 50 years and were the usual interstitial pneumonitis (UIP) type.
Conclusions
BRAF V600E mutation likely could be identified in ILD especially UIP. Prognosis of such patients with mutated BRAF gene should be observed.
... The public health, economic, and societal burden of emerging respiratory pathogens such as coronaviruses and influenza viruses, that are capable of causing epidemics and pandemics, further underlines the importance of pulmonary disorders. In addition, there are patients with rare pathologies such as pulmonary arterial hypertension (PAH) and idiopathic pulmonary fibrosis (IPF) that are progressive and often present with poor prognosis and lack curing agents (Ainscough et al., 2022;Asmani et al., 2018;Farber and Loscalzo, 2004;Gross and Hunninghake, 2001;Richeldi et al., 2017;Si et al., 2021). Thus, there is a pressing need to better understand mechanisms of disease biogenesis and identify new therapies for human lung diseases. ...
... Idiopathic pulmonary fibrosis (IPF) is a rare, progressive lung disease that is predominantly characterized by excessive deposition of ECM proteins in lung parenchyma and increased tissue stiffness, which cause irreversible scarring and can ultimately lead to respiratory failure and death (Adams et al., 2020;Gross and Hunninghake, 2001). IPF still remains an unmet need as only two anti-fibrotic agents (pirfenidone and nintedanib) have been clinically approved for its treatment. ...
Preclinical human-relevant modeling of organ-specific vasculature offers a unique opportunity to recreate pathophysiological intercellular, tissue-tissue, and cell-matrix interactions for a broad range of applications. Lung vasculature is particularly important due to its involvement in genesis and progression of rare, debilitating disorders as well as common chronic pathologies. Here, we provide an overview of the latest advances in the development of pulmonary vascular (PV) models using emerging microfluidic tissue engineering technology Organs-on-Chips (so-called PV-Chips). We first review the currently reported PV-Chip systems and their key features, and then critically discuss their major limitations in reproducing in vivo-seen and disease-relevant cellularity, localization, and microstructure. We conclude by presenting latest efforts to overcome such technical and biological limitations and future directions.
... The heterogeneous pulmonary fibroblasts (pFBs) play vital role during the progression of fibrosis (Xie et al., 2018). Lung tissues from IPF (idiopathic pulmonary fibrosis) patients display excessive accumulation of ACTA2 + myofibroblasts, which can deposit extracellular matrix (ECM) proteins, leading to the destruction of the lung architecture (Gross and Hunninghake, 2001). In the bleomycininduced murine model of lung fibrosis, lipofibroblasts transdifferentiate into myofibroblasts through activation of the TGFβ signaling pathway (El Agha et al., 2017). ...
Background and objectives: The heterogeneity of pulmonary fibroblasts, a critical aspect of both murine and human models under physiological and pathological conditions, is well-documented. Yet, consensus remains elusive on the subtypes, lineage, biological attributes, signal transduction pathways, and plasticity of these fibroblasts. This ambiguity significantly impedes our understanding of the fibrotic processes that transpire in lung tissue during aging. This study aims to elucidate the transcriptional profiles, differentiation pathways, and potential roles of fibroblasts within aging pulmonary tissue.
Methods: We employed single-cell transcriptomic sequencing via the 10x Genomics platform. The downstream data were processed and analyzed using R packages, including Seurat. Trajectory and stemness of differentiation analyses were conducted using the Monocle2 and CytoTRACE R packages, respectively. Cell interactions were deciphered using the CellChat R package, and the formation of collagen and muscle fibers was identified through Masson and Van Geison staining techniques.
Results: Our analysis captured a total of 22,826 cells, leading to the identification of fibroblasts and various immune cells. We observed a shift in fibroblasts from lipogenic and immune-competent to fibrotic and myofibroblast-like phenotype during the aging process. In the aged stage, fibroblasts exhibited a diminished capacity to express chemokines for immune cells. Experimental validation confirmed an increase of collagen and muscle fiber in the aged compared to young lung tissues. Furthermore, we showed that TGFβ treatment induced a fibrotic, immunodeficient and lipodystrophic transcriptional phenotype in young pulmonary fibroblasts.
Conclusion: We present a comprehensive single-cell transcriptomic landscape of lung tissue from aging mice at various stages, revealing the differentiation trajectory of fibroblasts during aging. Our findings underscore the pivotal role of fibroblasts in the regulation of immune cells, and provide insights into why age increases the risk of pulmonary fibrosis.
... Idiopathic pulmonary fibrosis (IPF) is a group of lung diseases that are defined by the lack of an underlying cause and are characterised by the presence of usual interstitial pneumonia (UIP) and pathological fibroblastic activity [1]. UIP is spatially heterogeneous, both macroscopically and microscopically, with a peripheral and basal predominant distribution. ...
The patterns of idiopathic pulmonary fibrosis (IPF) lung disease that directly correspond to elevated hyperpolarised gas diffusion-weighted (DW) MRI metrics are currently unknown. This study aims to develop a spatial co-registration framework for a voxel-wise comparison of hyperpolarised gas DW-MRI and CALIPER quantitative CT patterns. Sixteen IPF patients underwent 3He DW-MRI and CT at baseline, and eleven patients had a 1-year follow-up DW-MRI. Six healthy volunteers underwent 129Xe DW-MRI at baseline only. Moreover, 3He DW-MRI was indirectly co-registered to CT via spatially aligned 3He ventilation and structural 1H MRI. A voxel-wise comparison of the overlapping 3He apparent diffusion coefficient (ADC) and mean acinar dimension (LmD) maps with CALIPER CT patterns was performed at baseline and after 1 year. The abnormal lung percentage classified with the LmD value, based on a healthy volunteer 129Xe LmD, and CALIPER was compared with a Bland–Altman analysis. The largest DW-MRI metrics were found in the regions classified as honeycombing, and longitudinal DW-MRI changes were observed in the baseline-classified reticular changes and ground-glass opacities regions. A mean bias of −15.3% (95% interval −56.8% to 26.2%) towards CALIPER was observed for the abnormal lung percentage. This suggests DW-MRI may detect microstructural changes in areas of the lung that are determined visibly and quantitatively normal by CT.
... Patients with PF often present with respiratory distress, which can lead to respiratory failure and death when not treated promptly and effectively. 1 The median survival time after the diagnosis of PF is approximately 2-3 years, 2 with a 5-year survival rate of approximately 50%. 3 After 2019, the antifibrotic drugs nintedanib and pirfenidone are widely used in patients with progressive PF. [4][5][6] However, these drugs could not completely prevent the progression of PF. Currently, the only available effective therapy for progressive PF is lung transplantation but limited survival rate, high cost, and few organ donors limit its scope of application. ...
... Currently, the only available effective therapy for progressive PF is lung transplantation but limited survival rate, high cost, and few organ donors limit its scope of application. 7 Therefore, it is urgent to explore efficient 1 Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing, China methods and medications that can downregulate the progression of PF. ...
Objectives
Peimine (PM), derived from Fritillaria thunbergii Miq, has been demonstrated with protective effects on pulmonary fibrosis (PF). However, the detailed mechanisms of PM on PF remain unknown. The aim of current study was to assess the therapeutic effects and the possible mechanism of PM on PF.
Methods
In this study, mice received bleomycin (BLM) injection to induce PF and then received the treatment of PM orally. The therapeutic effects of PM on PF were firstly assessed through histopathological staining (hematoxylin and eosin and Masson staining) and measuring hydroxyproline (HYP) level in lung. Then, we measured the levels of epithelial-mesenchymal transition (EMT)-related markers (vimentin and E-cadherin), pro-inflammatory factors (interleukin [IL]-1β, IL-6, and tumor necrosis factor alpha [TNF-α]), and oxidative stress-related indicators (superoxide dismutase[SOD], malondialdehyde [MDA] and glutathione peroxidase [GSH-Px]) in lung. Furthermore, untargeted metabolomics were employed to explore the effects of PM on metabolites in lung.
Results
PM treatment improved the pathological changes including reducing the infiltration of inflammatory cells and decreasing collagen deposition, and decreasing the HYP level in lung in PF mice. Moreover, PM treatment up-regulated E-cadherin and down-regulated vimentin, decreased IL-1β, IL-6 and TNF-α expression, increased SOD and GSH-Px activities, and decreased MDA level in lung. Untargeted metabolomics analysis showed that PM altered the metabolites in lung of mice with BLM-induced PF. The differential metabolites were mainly associated with tryptophan metabolism, nicotinate and nicotinamide metabolism, alanine, aspartate and glutamate metabolism, arginine biosynthesis, and D-glutamine and D-glutamate metabolism.
Conclusion
PM exhibited therapeutic effects on BLM-induced PF mice including reducing collagen deposition, inhibiting EMT and reducing inflammation and oxidative stress. The mechanism of PM on PF may be associated with regulating tryptophan metabolism, nicotinate and nicotinamide metabolism, alanine, aspartate and glutamate metabolism, arginine biosynthesis, and D-glutamine and D-glutamate metabolism in lung.
