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European Respiratory Review : An... Jan 2024Molecular pathways found to be important in pulmonary fibrosis are also involved in cancer pathogenesis, suggesting common pathways in the development of pulmonary... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Molecular pathways found to be important in pulmonary fibrosis are also involved in cancer pathogenesis, suggesting common pathways in the development of pulmonary fibrosis and lung cancer.
RESEARCH QUESTION
Is pulmonary fibrosis from exposure to occupational carcinogens an independent risk factor for lung cancer?
STUDY DESIGN AND METHODS
A comprehensive search of PubMed, Embase, Web of Science and Cochrane databases with over 100 search terms regarding occupational hazards causing pulmonary fibrosis was conducted. After screening and extraction, quality of evidence and eligibility criteria for meta-analysis were assessed. Meta-analysis was performed using a random-effects model.
RESULTS
52 studies were identified for systematic review. Meta-analysis of subgroups identified silicosis as a risk factor for lung cancer when investigating odds ratios for silicosis in autopsy studies (OR 1.47, 95% CI 1.13-1.90) and for lung cancer mortality in patients with silicosis (OR 3.21, 95% CI 2.67-3.87). Only considering studies with an adjustment for smoking as a confounder identified a significant increase in lung cancer risk (OR 1.58, 95% CI 1.34-1.87). However, due to a lack of studies including cumulative exposure, no adjustments could be included. In a qualitative review, no definitive conclusion could be reached for asbestosis and silicosis as independent risk factors for lung cancer, partly because the studies did not take cumulative exposure into account.
INTERPRETATION
This systematic review confirms the current knowledge regarding asbestosis and silicosis, indicating a higher risk of lung cancer in exposed individuals compared to exposed workers without fibrosis. These individuals should be monitored for lung cancer, especially when asbestosis or silicosis is present.
Topics: Humans; Silicon Dioxide; Lung Neoplasms; Pulmonary Fibrosis; Asbestosis; Silicosis; Occupational Exposure
PubMed: 38355151
DOI: 10.1183/16000617.0224-2023 -
Biomedicine & Pharmacotherapy =... Oct 2023Lung injury and pulmonary fibrosis contribute to morbidity and mortality, and, in particular, are characterized as leading cause on confirmed COVID-19 death. To date,...
Lung injury and pulmonary fibrosis contribute to morbidity and mortality, and, in particular, are characterized as leading cause on confirmed COVID-19 death. To date, efficient therapeutic approach for such lung diseases is lacking. N-Acetylglucosamine (NAG), an acetylated derivative of glucosamine, has been proposed as a potential protector of lung function in several types of lung diseases. The mechanism by which NAG protects against lung injury, however, remains unclear. Here, we show that NAG treatment improves pulmonary function in bleomycin (BLM)-induced lung injury model measured by flexiVent system. At early phase of lung injury, NAG treatment results in silenced immune response by targeting ARG1 macrophages activation, and, consequently, blocks KRT8 transitional stem cell in the alveolar region to stimulate PDGF Rβ fibroblasts hyperproliferation, thereby attenuating the pulmonary fibrosis. This combinational depression of immune response and extracellular matrix deposition within the lung mitigates lung injury and pulmonary fibrosis induced by BLM. Our findings provide novel insight into the protective role of NAG in lung injury.
Topics: Humans; Pulmonary Fibrosis; Lung Injury; Acetylglucosamine; Bleomycin; COVID-19
PubMed: 37633052
DOI: 10.1016/j.biopha.2023.115069 -
QJM : Monthly Journal of the... Oct 2023Pulmonary fibrosis is characterized by extracellular deposition in the lung primarily collagen but also other ECM molecules. The primary cell type responsible for this... (Review)
Review
Pulmonary fibrosis is characterized by extracellular deposition in the lung primarily collagen but also other ECM molecules. The primary cell type responsible for this is the myofibroblast, and this can be induced by various stressors and signals. Infections be they bacterial or viral can cause pulmonary fibrosis (PF). In 2019, severe acute respiratory syndrome coronavirus 2 (SAR-CoV-2) originated in Wuhan, China, has led to a worldwide pandemic and can lead to acute respiratory distress and lung fibrosis. The virus itself can be cleared, but patients may develop long-term PF, which can be debilitating and life-limiting. There is a significantly perturbed immune response that shapes the fibrotic response leading to fibrosis. Given the importance of PF irrespective of cause, understanding the similarities and differences in pathogenesis caused by SARS-CoV-2-induced PF may yield new therapeutic targets. This review examines the pathology associated with the disease and discusses possible targets.
Topics: Humans; COVID-19; Pulmonary Fibrosis; SARS-CoV-2; Lung; Respiratory Distress Syndrome
PubMed: 37191984
DOI: 10.1093/qjmed/hcad092 -
The International Journal of... Sep 2020Pulmonary fibrosis is characterised by excessive scarring in the lung which leads to compromised lung function, serious breathing problems and in some diseases, death.... (Review)
Review
Pulmonary fibrosis is characterised by excessive scarring in the lung which leads to compromised lung function, serious breathing problems and in some diseases, death. It includes several lung disorders with idiopathic pulmonary fibrosis (IPF) the most common and most severe. Pulmonary fibrosis is considered to be perpetuated by aberrant wound healing which leads to fibroblast accumulation, differentiation and activation, and deposition of excessive amounts of extracellular matrix (ECM) components, in particular, collagen. Recent studies have identified the importance of changes in the composition and structure of lung ECM during the development of pulmonary fibrosis and the interaction between ECM and lung cells. There is strong evidence that increased matrix stiffness induces changes in cell function including proliferation, migration, differentiation and activation. Understanding how changes in the ECM microenvironment influence cell behaviour during fibrogenesis, and the mechanisms regulating these changes, will provide insight for developing new treatments.
Topics: Animals; Collagen; Extracellular Matrix; Humans; Mechanotransduction, Cellular; Pulmonary Fibrosis
PubMed: 32668329
DOI: 10.1016/j.biocel.2020.105802 -
International Immunology Nov 2021Pulmonary fibrosis is caused by the interplay between genetic and environmental factors. Recent studies have revealed various genes associated with idiopathic pulmonary... (Review)
Review
Pulmonary fibrosis is caused by the interplay between genetic and environmental factors. Recent studies have revealed various genes associated with idiopathic pulmonary fibrosis, as well as the causative genes for familial pulmonary fibrosis. Although increased death or dysfunction of type 2 alveolar epithelial (AT2) cells has been detected in lung specimens from pulmonary fibrosis patients, it remains unclear whether and how AT2 cell death or dysfunction is responsible for the progression of pulmonary fibrosis. A recent study showed that increased AT2 cell necroptosis is the initial event in pulmonary fibrosis by analyzing patients with familial pulmonary fibrosis and an animal model that harbors the same mutation as patients. The contribution of AT2 cell necroptosis to the pathogenesis of pulmonary fibrosis has not been identified in animal model studies, which validates the effectiveness of genetic analysis of familial diseases to uncover unknown pathogeneses. Thus, further extensive genetic studies of pulmonary fibrosis along with functional studies based on genetic analysis will be crucial not only in elucidating the precise disease process but also, ultimately, in identifying novel treatment strategies for both familial and non-familial pulmonary fibrosis.
Topics: Animals; Disease Models, Animal; Idiopathic Pulmonary Fibrosis
PubMed: 34049386
DOI: 10.1093/intimm/dxab026 -
Molecular Therapy : the Journal of the... Oct 2023Pirfenidone and nintedanib are only anti-pulmonary fibrosis (PF) drugs approved by the FDA. However, they are not target specific, and unable to modify the disease...
Pirfenidone and nintedanib are only anti-pulmonary fibrosis (PF) drugs approved by the FDA. However, they are not target specific, and unable to modify the disease status. Therefore, it is still desirable to discover more effective agents against PF. Vimentin (VIM) plays key roles in tissue regeneration and wound healing, but its molecular mechanism remains unknown. In this work, we demonstrated that atractylodinol (ATD) significantly inhibits TGF-β1-induced epithelial-mesenchymal transition and fibroblast-to-myofibroblast transition in vitro. ATD also reduces bleomycin-induced lung injury and fibrosis in mice models. Mechanistically, ATD inhibited TGF-β receptor I recycling by binding to VIM (K = 454 nM) and inducing the formation of filamentous aggregates. In conclusion, we proved that ATD (derived from Atractylodes lancea) modified PF by targeting VIM and inhibiting the TGF-β/Smad signaling pathway. Therefore, VIM is a druggable target and ATD is a proper drug candidate against PF. We prove a novel VIM function that TGF-β receptor I recycling. These findings paved the way to develop new targeted therapeutics against PF.
Topics: Animals; Mice; Bleomycin; Epithelial-Mesenchymal Transition; Lung; Pulmonary Fibrosis; Receptor, Transforming Growth Factor-beta Type I; Transforming Growth Factor beta1; Vimentin
PubMed: 37641404
DOI: 10.1016/j.ymthe.2023.08.017 -
Acta Medica Indonesiana Apr 2021Pulmonary fibrosis due to COVID-19 is recognized as sequel of ARDS characterized by failed alveolar re-epithelization, fibroblast activation, excessive collagen... (Review)
Review
Pulmonary fibrosis due to COVID-19 is recognized as sequel of ARDS characterized by failed alveolar re-epithelization, fibroblast activation, excessive collagen deposition and other extracellular matrix components that disrupt the normal lung architecture. There are risk factor for pulmonary fibrosis namely advanced age, severe ARDS infection, mechanical ventilation due to ventilator-induced lung injury, smoking and chronic alcoholism. Diagnosis of post-COVID pulmonary fibrosis can be made by clinical symptoms and characteristic finding from lung CT scan. To date, there is no definitive treatment for post-inflammatory pulmonary fibrosis after COVID-19 infection, however some of antifibrotic therapies may be considered. Beside medical treatment, pulmonary rehabilitation program and long-term oxygen treatment should be included as part of comprehensive treatment for pulmonary fibrosis due to COVID-19.
Topics: COVID-19; Combined Modality Therapy; Humans; Pneumonia, Viral; Pulmonary Fibrosis; Risk Factors; SARS-CoV-2; Tomography, X-Ray Computed
PubMed: 34251354
DOI: No ID Found -
Archives of Pharmacal Research May 2021In 2019, an unprecedented disease named coronavirus disease 2019 (COVID-19) emerged and spread across the globe. Although the rapid transmission of COVID-19 has resulted... (Review)
Review
In 2019, an unprecedented disease named coronavirus disease 2019 (COVID-19) emerged and spread across the globe. Although the rapid transmission of COVID-19 has resulted in thousands of deaths and severe lung damage, conclusive treatment is not available. However, three COVID-19 vaccines have been authorized, and two more will be approved soon, according to a World Health Organization report on December 12, 2020. Many COVID-19 patients show symptoms of acute lung injury that eventually leads to pulmonary fibrosis. Our aim in this article is to present the relationship between pulmonary fibrosis and COVID-19, with a focus on angiotensin converting enzyme-2. We also evaluate the radiological imaging methods computed tomography (CT) and chest X-ray (CXR) for visualization of patient lung condition. Moreover, we review possible therapeutics for COVID-19 using four categories: treatments related and unrelated to lung disease and treatments that have and have not entered clinical trials. Although many treatments have started clinical trials, they have some drawbacks, such as short-term and small-group testing, that need to be addressed as soon as possible.
Topics: Angiotensin-Converting Enzyme 2; Antiviral Agents; COVID-19; Drug Development; Drug Repositioning; Humans; Pulmonary Fibrosis; Radiography, Thoracic; Tomography, X-Ray Computed; COVID-19 Drug Treatment
PubMed: 34047940
DOI: 10.1007/s12272-021-01331-9 -
Clinics in Chest Medicine Jun 2021Fibrotic hypersensitivity pneumonitis (fHP) is a chronic, often progressive fibrosing form of interstitial lung disease caused by inhaled antigenic exposures. fHP can... (Review)
Review
Fibrotic hypersensitivity pneumonitis (fHP) is a chronic, often progressive fibrosing form of interstitial lung disease caused by inhaled antigenic exposures. fHP can lead to impaired respiratory function, reduced disease-related quality of life, and early mortality. Management of fHP should start with exposure remediation where possible, with systemic immunosuppression and antifibrotic therapy considered in patients with symptomatic or progressive disease. Nonpharmacologic and supportive management should be offered and, in cases of treatment-resistant, progressive illness, lung transplant should be considered.
Topics: Alveolitis, Extrinsic Allergic; Humans; Pulmonary Fibrosis
PubMed: 34024406
DOI: 10.1016/j.ccm.2021.03.007 -
Journal of Cellular and Molecular... Dec 2023To investigate the effect and mechanism of polydatin on bleomycin (BLM)-induced pulmonary fibrosis in a mouse model. The lung fibrosis model was induced by BLM. The...
To investigate the effect and mechanism of polydatin on bleomycin (BLM)-induced pulmonary fibrosis in a mouse model. The lung fibrosis model was induced by BLM. The contents of TNF-α, LPS, IL-6 and IL-1β in lung tissue, intestine and serum were detected by ELISA. Gut microbiota diversity was detected by 16S rDNA sequencing; R language was used to analyse species composition, α-diversity, β-diversity, species differences and marker species. Mice were fed drinking water mixed with four antibiotics (ampicillin, neomycin, metronidazole, vancomycin; antibiotics, ABx) to build a mouse model of ABx-induced bacterial depletion; and faecal microbiota from different groups were transplanted into BLM-treated or untreated ABx mice. The histopathological changes and collagen I and α-SMA expression were determined. Polydatin effectively reduced the degree of fibrosis in a BLM-induced pulmonary fibrosis mouse model; BLM and/or polydatin affected the abundance of the dominant gut microbiota in mice. Moreover, faecal microbiota transplantation (FMT) from polydatin-treated BLM mice effectively alleviated lung fibrosis in BLM-treated ABx mice compared with FMT from BLM mice. Polydatin can reduce fibrosis and inflammation in a BLM-induced mouse pulmonary fibrosis model. The alteration of gut microbiota by polydatin may be involved in the therapeutic effect.
Topics: Mice; Animals; Pulmonary Fibrosis; Bleomycin; Gastrointestinal Microbiome; Lung; Fibrosis; Anti-Bacterial Agents; Mice, Inbred C57BL
PubMed: 37665061
DOI: 10.1111/jcmm.17937