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Jornal Brasileiro de Pneumologia :... 2023Many interstitial lung diseases (ILDs) share mechanisms that result in a progressive fibrosing phenotype. In Brazil, the most common progressive fibrosing interstitial...
Many interstitial lung diseases (ILDs) share mechanisms that result in a progressive fibrosing phenotype. In Brazil, the most common progressive fibrosing interstitial lung diseases (PF-ILDs) are chronic hypersensitivity pneumonitis, idiopathic pulmonary fibrosis, unclassified ILD, and connective tissue diseases. PF-ILD is seen in approximately 30% of patients with ILD. Because PF-ILD is characterized by disease progression after initiation of appropriate treatment, a diagnosis of the disease resulting in fibrosis is critical. Different criteria have been proposed to define progressive disease, including worsening respiratory symptoms, lung function decline, and radiological evidence of disease progression. Although the time elapsed between diagnosis and progression varies, progression can occur at any time after diagnosis. Several factors indicate an increased risk of progression and death. In the last few years, antifibrotic drugs used in patients with idiopathic pulmonary fibrosis have been tested in patients with PF-ILD. The effects of nintedanib and placebo have been compared in patients with PF-ILD, a mean difference of 107.0 mL/year being observed, favoring nintedanib. The U.S. Food and Drug Administration and the Brazilian Health Regulatory Agency have approved the use of nintedanib in such patients on the basis of this finding. Pirfenidone has been evaluated in patients with unclassified ILD and in patients with other ILDs, the results being similar to those for nintedanib. More studies are needed in order to identify markers of increased risk of progression in patients with ILD and determine the likelihood of response to treatment with standard or new drugs.
Topics: United States; Humans; Idiopathic Pulmonary Fibrosis; Alveolitis, Extrinsic Allergic; Brazil; Phenotype; Disease Progression
PubMed: 37610955
DOI: 10.36416/1806-3756/e20230098 -
Dietary intake and incidence risk of idiopathic pulmonary fibrosis: a Mendelian randomization study.BMC Pulmonary Medicine Oct 2023Dietary intake has been shown to have a causal relationship with various lung diseases, such as lung cancer and asthma. However, the causal relationship between dietary...
BACKGROUND
Dietary intake has been shown to have a causal relationship with various lung diseases, such as lung cancer and asthma. However, the causal relationship between dietary intake and idiopathic pulmonary fibrosis (IPF) remains unclear. We conducted a two-sample Mendelian Randomization (MR) study to investigate the causal relationship between dietary intake and IPF.
METHODS
The exposure datasets included meat, fruit, vegetable, and beverage intake from the UK Biobank. IPF data came from the EBI database of 451,025 individuals. All data in this study were obtained from the IEU Open GWAS Project. The inverse variance weighted (IVW), MR-Egger, and weighted median methods were used as the primary methods. Sensitivity analyses were performed to ensure the validity of the results.
RESULTS
Oily fish intake [odds ratio (OR):0.995; 95% confidence interval (CI): 0.993-0.998; p = 6.458E-05] and Dried fruit intake (OR:0.995;95%CI:0.991-0.998; p = 0.001) were discovered as protective factors. There was also a suggestive correlation between Beef intake (OR:1.006;95%Cl:1.001-1.012; p = 0.023) and IPF. Sensitivity analysis did not reveal any contradictory results. No causal relationship was found between IPF and the rest of the dietary exposures.
CONCLUSIONS
Our study found that Oily fish and Dried fruit intake were associated with the risk of IPF, while Beef intake was suggestively associated with the risk of IPF. Other studies are still needed to confirm the results in the future.
Topics: Cattle; Animals; Incidence; Mendelian Randomization Analysis; Asthma; Databases, Factual; Idiopathic Pulmonary Fibrosis; Genome-Wide Association Study
PubMed: 37803281
DOI: 10.1186/s12890-023-02673-4 -
CD45 alleviates airway inflammation and lung fibrosis by limiting expansion and activation of ILC2s.Proceedings of the National Academy of... Sep 2023Group 2 innate lymphoid cells (ILC2s) are critical for the immune response against parasite infection and tissue homeostasis and involved in the pathogenesis of allergy...
Group 2 innate lymphoid cells (ILC2s) are critical for the immune response against parasite infection and tissue homeostasis and involved in the pathogenesis of allergy and inflammatory diseases. Although multiple molecules positively regulating ILC2 development and activation have been extensively investigated, the factors limiting their population size and response remain poorly studied. Here, we found that CD45, a membrane-bound tyrosine phosphatase essential for T cell development, negatively regulated ILC2s in a cell-intrinsic manner. ILC2s in CD45-deficient mice exhibited enhanced proliferation and maturation in the bone marrow and hyperactivated phenotypes in the lung with high glycolytic capacity. Furthermore, CD45 signaling suppressed the type 2 inflammatory response by lung ILC2s and alleviated airway inflammation and pulmonary fibrosis. Finally, the interaction with galectin-9 influenced CD45 signaling in ILC2s. These results demonstrate that CD45 is a cell-intrinsic negative regulator of ILC2s and prevents lung inflammation and fibrosis via ILC2s.
Topics: Animals; Mice; Pulmonary Fibrosis; Immunity, Innate; Lymphocytes; Inflammation; Signal Transduction
PubMed: 37639581
DOI: 10.1073/pnas.2215941120 -
Journal of Ethnopharmacology Nov 2023Pulmonary fibrosis (PF) is a persistent and refractory illness accompanied by inflammation and fibrosis. Gracillin, a natural steroidal saponin, is one of the components...
ETHNOPHARMACOLOGICAL RELEVANCE
Pulmonary fibrosis (PF) is a persistent and refractory illness accompanied by inflammation and fibrosis. Gracillin, a natural steroidal saponin, is one of the components of Dioscorea quinqueloba which has been used in herbal medicines for treating some inflammatory diseases. Therefore, it may be a potential drug candidate for PF management.
AIM OF THE STUDY
This study aims to elucidate and verify the anti-pulmonary fibrosis effect of gracillin.
METHODS
We established an in vivo model of PF by treatment of mice with bleomycin (BLM) and an in vitro model by treatment of NIH-3T3 cells with TGF-β1. Pathological changes to the structure of lung tissue, pulmonary function, inflammatory exudation of bronchoalveolar lavage fluid (BALF) and deposition of collagen were detected in vivo, and extracellular matrix (ECM) deposition and migration were evaluated in vitro. The significance of gracillin on STAT3 phosphorylation and nuclear translocation were evaluated by western blotting, immunohistochemistry and immunofluorescence assays. The STAT3 transcriptional activity was quantified with a dual-luciferase reporter assay. Recovery experiments were performed by plasmid-directed overexpression of STAT3.
RESULTS
We found that gracillin could improve pulmonary function, reduce lung inflammation and mitigate collagen deposition to ameliorate BLM-induced PF in mice. Gracillin also suppressed TGF-β1-induced increases in ECM deposition biomarkers, including COL1A1, fibronectin, α-SMA, N-cad and vimentin, and repressed migration in NIH-3T3 cells. Additionally, gracillin suppressed the phosphorylation, nuclear translocation and transcriptional action of STAT3. Furthermore, the decreased ECM deposition and migration upon gracillin treatment were abrogated upon overexpression of STAT3 in NIH-3T3 cells.
CONCLUSIONS
Gracillin protects against PF by inhibiting the STAT3 axis, providing a safe and efficacious approach to treating PF.
Topics: Mice; Animals; Transforming Growth Factor beta1; Pulmonary Fibrosis; Lung; Collagen; Bleomycin
PubMed: 37257706
DOI: 10.1016/j.jep.2023.116704 -
Biomedicine & Pharmacotherapy =... Oct 2023Fibrotic extracellular matrix (ECM) remodeling characterized different types of pulmonary fibrosis, and its regulation could be a potential shared treatment strategy for...
BACKGROUND
Fibrotic extracellular matrix (ECM) remodeling characterized different types of pulmonary fibrosis, and its regulation could be a potential shared treatment strategy for pulmonary fibrosis.
PURPOSE
We aimed to investigate the effect of triptolide on pulmonary fibrosis through the inhibition of several important aspects of fibrotic ECM remodeling.
METHODS
Bleomycin-induced pulmonary fibrosis mice and TGF-β-induced primary lung fibroblasts were used. The effect of triptolide on pulmonary fibrosis was detected using histopathology, immunostaining, RT-qPCR, western blotting, ELISA, and protein activity assay.
RESULTS
Triptolide significantly alleviated bleomycin-induced pulmonary fibrosis in mice. It inhibited the expression of fibrotic genes α-SMA, collagen I, fibronectin, and vimentin and blocked the TGF-β-SMAD signaling pathway both in vivo and in vitro. In addition, triptolide regulated the expression and activity of MMPs during fibrosis. Interestingly, it suppressed the expression of lysyl oxidase, which was responsible for matrix cross-linking and elevated ECM stiffness. Furthermore, triptolide blocked the biomechanical stress transduction pathway integrin-β1-FAK-YAP signaling and attenuated the pro-fibrotic feedback of fibrotic ECM on fibroblasts via integrin inhibition.
CONCLUSION
These findings show that triptolide prevents the key linkages of fibrotic ECM remodeling, including deposition, degradation, cross-linking, and pro-fibrotic feedback and, therefore, has potential therapeutic value for pulmonary fibrosis.
Topics: Animals; Mice; Bleomycin; Extracellular Matrix; Integrins; Protein-Lysine 6-Oxidase; Pulmonary Fibrosis; Transforming Growth Factor beta; Matrix Metalloproteinases
PubMed: 37660647
DOI: 10.1016/j.biopha.2023.115394 -
American Journal of Respiratory and... Sep 2023
Topics: Humans; Adult; Pulmonary Fibrosis; Prevalence; Lung Diseases, Interstitial; Lung; Risk Factors
PubMed: 37552023
DOI: 10.1164/rccm.202307-1287ED -
BMC Pulmonary Medicine Aug 2023Create a timeline of diagnosis and treatment for IPF in the US.
OBJECTIVE
Create a timeline of diagnosis and treatment for IPF in the US.
DESIGN, SETTING, AND PARTICIPANTS
A retrospective analysis was performed in collaboration with the OptumLabs Data Warehouse using an administrative claims database of Medicare Fee for Service beneficiaries. Adults 50 and over with IPF were included (2014 to 2019).
EXPOSURE
To focus on IPF, the following diagnoses were excluded: post-inflammatory fibrosis, hypersensitivity pneumonitis, rheumatoid arthritis, sarcoidosis, scleroderma, and connective tissue disease.
MAIN OUTCOMES AND MEASURES
Data were collected from periods prior, during, and following initial clinical diagnosis of IPF. This included prior respiratory diagnoses, number of respiratory-related hospitalizations, anti-fibrotic and oxygen use, and survival.
RESULTS
A total of 44,891 with IPF were identified. The most common diagnoses prior to diagnosis of IPF were upper respiratory infections (47%), acute bronchitis (13%), other respiratory disease (10%), chronic obstructive pulmonary disease and bronchiectasis (7%), and pneumonia (6%). The average time to a diagnosis of IPF was 2.7 years after initial respiratory diagnosis. Half of patients had two or more respiratory-related hospitalizations prior to IPF diagnosis. Also, 37% of patients were prescribed oxygen prior to diagnosis of IPF. These observations suggest delayed diagnosis. We also observed only 10.4% were treated with anti-fibrotics. Overall survival declined each year after diagnosis with median survival of 2.80 years.
CONCLUSIONS AND RELEVANCE
Our retrospective cohort demonstrates that IPF is often diagnosed late, usually preceded by other respiratory diagnoses and hospitalizations. Use of available therapies is low and outcomes remain poor.
Topics: Adult; Humans; Aged; United States; Retrospective Studies; Medicare; Idiopathic Pulmonary Fibrosis; Alveolitis, Extrinsic Allergic; Oxygen
PubMed: 37532984
DOI: 10.1186/s12890-023-02565-7 -
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 -
Journal of Nanobiotechnology Jul 2023It is reported that pulmonary fibrosis has become one of the major long-term complications of COVID-19, even in asymptomatic individuals. Currently, despite the best... (Review)
Review
It is reported that pulmonary fibrosis has become one of the major long-term complications of COVID-19, even in asymptomatic individuals. Currently, despite the best efforts of the global medical community, there are no treatments for COVID-induced pulmonary fibrosis. Recently, inhalable nanocarriers have received more attention due to their ability to improve the solubility of insoluble drugs, penetrate biological barriers of the lungs and target fibrotic tissues in the lungs. The inhalation route has many advantages as a non-invasive method of administration and the local delivery of anti-fibrosis agents to fibrotic tissues like direct to the lesion from the respiratory system, high delivery efficiency, low systemic toxicity, low therapeutic dose and more stable dosage forms. In addition, the lung has low biometabolic enzyme activity and no hepatic first-pass effect, so the drug is rapidly absorbed after pulmonary administration, which can significantly improve the bioavailability of the drug. This paper summary the pathogenesis and current treatment of pulmonary fibrosis and reviews various inhalable systems for drug delivery in the treatment of pulmonary fibrosis, including lipid-based nanocarriers, nanovesicles, polymeric nanocarriers, protein nanocarriers, nanosuspensions, nanoparticles, gold nanoparticles and hydrogel, which provides a theoretical basis for finding new strategies for the treatment of pulmonary fibrosis and clinical rational drug use.
Topics: Humans; Pulmonary Fibrosis; Gold; Administration, Inhalation; COVID-19; Metal Nanoparticles; Drug Delivery Systems; Lung; Pharmaceutical Preparations; Nanoparticles
PubMed: 37422665
DOI: 10.1186/s12951-023-01971-7 -
BMC Pulmonary Medicine Aug 2023A prospective study of multiple small samples found that idiopathic pulmonary fibrosis (IPF) is often accompanied by a deficiency in Vitamin D levels. However, the...
BACKGROUND
A prospective study of multiple small samples found that idiopathic pulmonary fibrosis (IPF) is often accompanied by a deficiency in Vitamin D levels. However, the causal relationship between the two remains to be determined. Therefore, our study aims to investigate the causal effect of serum 1,25-hydroxyvitamin D (25(OH)D) on the risk of IPF through a two-sample Mendelian randomization (MR) analysis.
METHODS
Through data analysis from two European ancestry-based genome-wide association studies (GWAS), including 401,460 individuals for 25(OH)D levels and 1028 individuals for IPF, we primarily employed inverse-variance weighted (IVW) to assess the causal effect of 25(OH)D levels on IPF risk. MR-Egger regression test was used to determine pleiotropy, and Cochran's Q test was conducted for heterogeneity testing. Leave-one-out analysis was conducted to examine the robustness of the results.
RESULTS
158 SNPs related to serum 25(OH)D were used as instrumental variables (IVs). The MR analyses revealed no evidence supporting a causal association between the level of circulating 25(OH)D and the risk of IPF. The IVW method [OR 0.891, 95%CI (0.523-1.518), P = 0.670]; There was no significant level of heterogeneity, pleiotropy and bias in IVs. Cochran's Q test for heterogeneity (MR Egger P = 0.081; IVW P = 0.089); MR-Egger regression for pleiotropy (P = 0.774).
CONCLUSIONS
This MR Study suggests that genetically predicted circulating vitamin D concentrations in the general population are not causally related to IPF.
Topics: Humans; Genome-Wide Association Study; Mendelian Randomization Analysis; Prospective Studies; Vitamin D; Vitamins; Idiopathic Pulmonary Fibrosis
PubMed: 37612740
DOI: 10.1186/s12890-023-02589-z