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BMC Pulmonary Medicine Jan 2024Pulmonary fibrosis (PF) is a progressive fibrosing interstitial pneumonia that leads to respiratory failure and other complications, which is ultimately fatal....
BACKGROUND
Pulmonary fibrosis (PF) is a progressive fibrosing interstitial pneumonia that leads to respiratory failure and other complications, which is ultimately fatal. Mesenchymal stem cells (MSCs) transplant is a promising strategy to solve this problem, while the procurement of MSCs from the patient for autotransplant remains a challenge.
METHODS
Here, we presented olfactory mucosa mesenchymal stem cells (OM-MSCs) from mouse turbinate and determined the preventing efficacy of allotransplant for PF. We demonstrated the antiinflammation and immunomodulatory effects of OM-MSCs. Flow cytometric analysis was used to verify the effect of OM-MSCs on monocyte-derived macrophage populations in the lung.
RESULTS
Administration of OM-MSCs reduces inflammation, attenuates the matrix metallopeptidase 13 (MMP13) expression level and restores the bleomycin (BLM)-induced pulmonary fibrosis by assessing the architecture of lung, collagen type I; (COL1A1), actin alpha 2, smooth muscle, aorta (ACTA2/α-SMA) and hydroxyproline. This therapeutic effect of OM-MSCs was related to the increase in the ratio of nonclassical monocytes to proinflammatory monocytes in the lung.
CONCLUSIONS
This study suggests that transplant of OM-MSCs represents an effective and safe treatment for PF.
Topics: Humans; Mice; Animals; Pulmonary Fibrosis; Inflammation; Mesenchymal Stem Cells; Immunomodulation; Olfactory Mucosa
PubMed: 38178092
DOI: 10.1186/s12890-023-02834-5 -
Respiratory Research Dec 2022Hypersensitivity pneumonitis (HP) is a type of interstitial lung disease (ILD) with a variable disease course and prognosis ranging from inflammatory and self-limiting...
BACKGROUND
Hypersensitivity pneumonitis (HP) is a type of interstitial lung disease (ILD) with a variable disease course and prognosis ranging from inflammatory and self-limiting to irreversible and progressive pulmonary fibrosis. Comorbidities are common in HP and may have an impact on prognosis. Due to the heterogeneity of HP presentation and progression, the identification of specific phenotypes in relationship to disease course and outcome is essential. The aim of this study was to identify clusters of comorbidities which could represent phenotypes in fibrotic HP and examine their impact on prognosis.
METHODS
Patients diagnosed with fibrotic HP at a tertiary referral center for ILD were included. Comorbidities were systematically registered and clusters of comorbidities were identified using cluster analyses. Disease progression and survival was estimated for each cluster.
RESULTS
The cohort comprised 211 patients with 53.6% males, mean age 63.0, baseline FVC 72.7%, DLCO 44.1%. Median follow-up time was 1.8 years (IQR 0.7-3.9). Three clusters with distinct comorbidity profiles and clinical characteristics were identified. One cluster dominated by elder male patients with predominantly cardiovascular diseases was associated with more respiratory hospitalizations and a worse prognosis. Differences in pulmonary function or exercise capacity trajectories between clusters were not observed.
CONCLUSIONS
Three clusters with distinct comorbidities were identified and could represent phenotypes in fibrotic HP not previously recognized. The worst prognosis was observed in a cluster dominated by elder males with cardiovascular diseases. Increased focus on prevention and treatment of comorbidities could potentially improve the prognosis of patients with fibrotic HP.
Topics: Male; Female; Humans; Cardiovascular Diseases; Lung Diseases, Interstitial; Alveolitis, Extrinsic Allergic; Pulmonary Fibrosis; Comorbidity
PubMed: 36539821
DOI: 10.1186/s12931-022-02291-4 -
Respiration; International Review of... 2017
Topics: Humans; Idiopathic Pulmonary Fibrosis; Pulmonary Fibrosis
PubMed: 28445891
DOI: 10.1159/000473884 -
American Heart Journal Aug 2020Cardiovascular disease has an increased prevalence among patients with idiopathic pulmonary fibrosis (IPF). Cardiovascular disease and IPF share similar symptoms with... (Review)
Review
Cardiovascular disease has an increased prevalence among patients with idiopathic pulmonary fibrosis (IPF). Cardiovascular disease and IPF share similar symptoms with overlapping demographics and risk factors for disease development. Common cellular mediators leading to disease development and progression have been identified in both the cardiovascular and pulmonary organ systems. In this context, discovery of new therapeutic targets and medical therapies could be mutually beneficial across cardiopulmonary diseases. Here we present (1) a clinical review of IPF for the cardiovascular clinician and (2) common cellular mechanisms responsible for fibrosis in the heart and lungs and (3) highlight future research considerations and the potential role of novel therapeutic agents which may be mutually beneficial in cardiac and pulmonary fibrosis.
Topics: Algorithms; Cardiovascular Diseases; Humans; Idiopathic Pulmonary Fibrosis
PubMed: 32521292
DOI: 10.1016/j.ahj.2020.04.027 -
Journal of Ethnopharmacology Jan 2024Pulmonary fibrosis (PF) is a chronic, progressive, and often fatal interstitial lung disease. Traditional Chinese medicine formulations and their active ingredients have...
ETHNOPHARMACOLOGICAL RELEVANCE
Pulmonary fibrosis (PF) is a chronic, progressive, and often fatal interstitial lung disease. Traditional Chinese medicine formulations and their active ingredients have shown potential in the treatment of PF. Panax notoginseng saponin (PNS) is extracted from the widely used traditional Chinese medicinal herb Panax notoginseng (Burkill) F. H. Chen, exhibiting therapeutic effects in pulmonary diseases treatment.
AIM OF THE STUDY
This study aimed to investigate the effects and elucidate possible potential mechanisms of PNS on bleomycin (BLM)-induced PF in rats.
MATERIALS AND METHODS
PF was induced in rats by intratracheal administration of bleomycin (BLM, 5 mg/kg). After disease model induction, the rats were treated with PNS (50, 100, or 200 mg/kg per day) or pirfenidone (PFD, 50 mg/kg per day) for 28 days. Lung function, histopathological changes, collagen deposition, and E- and N-cadherin levels in lung tissue were evaluated. The mechanism of action of PNS was investigated using tandem mass tag-based quantitative proteomics analysis. Immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and Western blot analysis were performed to verify the proteomic results.
RESULTS
PNS treatment improved lung function, ameliorated the BLM-induced increase in the lung coefficient, attenuated the degree of alveolar inflammation and fibrosis, and reduced the elevated collagen level in PF rats. PNS treatment also down-regulated the expression of N-cadherin while up-regulating the expression of E-cadherin. Proteomic and bioinformatic analyses revealed that the renin-angiotensin system (RAS) was closely related to the therapeutic effect of PNS. Immunohistochemistry, Western blot, and ELISA results indicated that PNS exerted its anti-fibrotic effect via regulation of the balance between the angiotensin-converting enzyme (ACE)-angiotensin (Ang)II-AngII receptor type 1 (AT1R) and ACE2-Ang(1-7)-MasR axes.
CONCLUSIONS
PNS ameliorates BLM-induced PF in rats by modulating the RAS homeostasis, and is a new potential therapeutic agent for PF.
Topics: Rats; Animals; Pulmonary Fibrosis; Renin-Angiotensin System; Panax notoginseng; Saponins; Proteomics; Fibrosis; Collagen; Bleomycin; Angiotensins
PubMed: 37532070
DOI: 10.1016/j.jep.2023.116979 -
European Respiratory Review : An... Dec 2021Acute manifestations of SARS-CoV-2 infection continue to impact the lives of many across the world. Post-acute sequelae of coronavirus disease 2019 (COVID-19) may affect... (Review)
Review
Acute manifestations of SARS-CoV-2 infection continue to impact the lives of many across the world. Post-acute sequelae of coronavirus disease 2019 (COVID-19) may affect 10-30% of survivors of COVID-19, and post-acute sequelae of COVID-19 (PASC)-pulmonary fibrosis is a long-term outcome associated with major morbidity. Data from prior coronavirus outbreaks (severe acute respiratory syndrome and Middle East respiratory syndrome) suggest that pulmonary fibrosis will contribute to long-term respiratory morbidity, suggesting that PASC-pulmonary fibrosis should be thoroughly screened for through pulmonary function testing and cross-sectional imaging. As data accumulates on the unique pathobiologic mechanisms underlying critical COVID-19, a focus on corollaries to the subacute and chronic profibrotic phenotype must be sought as well. Key aspects of acute COVID-19 pathobiology that may account for increased rates of pulmonary fibrosis include monocyte/macrophage-T-cell circuits, profibrotic RNA transcriptomics, protracted elevated levels of inflammatory cytokines, and duration of illness and ventilation. Mechanistic understanding of PASC-pulmonary fibrosis will be central in determining therapeutic options and will ultimately play a role in transplant considerations. Well-designed cohort studies and prospective clinical registries are needed. Clinicians, researchers and healthcare systems must actively address this complication of PASC to minimise disability, maximise quality of life and confront a post-COVID-19 global health crisis.
Topics: COVID-19; Humans; Pandemics; Prospective Studies; Pulmonary Fibrosis; Quality of Life; SARS-CoV-2
PubMed: 34911696
DOI: 10.1183/16000617.0194-2021 -
BMC Pulmonary Medicine May 2021Several studies demonstrate that endoplasmic reticulum (ER) stress-mediated epithelial-mesenchymal transition (EMT) is involved in the process of bleomycin (BLM)-induced...
BACKGROUND
Several studies demonstrate that endoplasmic reticulum (ER) stress-mediated epithelial-mesenchymal transition (EMT) is involved in the process of bleomycin (BLM)-induced pulmonary fibrosis. Tauroursodeoxycholic acid (TUDCA), a bile acid with chaperone properties, is an inhibitor of ER stress. This study aimed to investigate the preventive effects of TUDCA on BLM-induced EMT and lung fibrosis.
METHODS
The model of lung fibrosis was established by intratracheal injection with a single dose of BLM (3.0 mg/kg). In TUDCA + BLM group, mice were intraperitoneally injected with TUDCA (250 mg/kg) daily.
RESULTS
BLM-induced alveolar septal destruction and inflammatory cell infiltration were alleviated by TUDCA. BLM-induced interstitial collagen deposition, as determined by Sirius Red staining, was attenuated by TUDCA. BLM-induced elevation of pulmonary α-smooth muscle actin (α-SMA) and reduction of pulmonary E-cadherin were attenuated by TUDCA. BLM-induced pulmonary Smad2/3 phosphorylation was suppressed by TUDCA. BLM-induced elevation of Ki67 and PCNA was inhibited by TUDCA in mice lungs. In addition, BLM-induced elevation of HO-1 (heme oxygenase-1) and 3-NT (3-nitrotyrosine) was alleviated by TUDCA. Finally, BLM-induced upregulation of pulmonary GRP78 and CHOP was attenuated by TUDCA.
CONCLUSIONS
These results provide evidence that TUDCA pretreatment inhibits Smad2/3-medited EMT and subsequent lung fibrosis partially through suppressing BLM-induced ER stress and oxidative stress.
Topics: Animals; Bleomycin; Disease Models, Animal; Endoplasmic Reticulum Chaperone BiP; Endoplasmic Reticulum Stress; Epithelial-Mesenchymal Transition; Lung; Male; Mice; Mice, Inbred C57BL; Oxidative Stress; Phosphorylation; Pulmonary Fibrosis; Signal Transduction; Taurochenodeoxycholic Acid; Up-Regulation
PubMed: 33952237
DOI: 10.1186/s12890-021-01514-6 -
Drugs May 2011Idiopathic pulmonary fibrosis (IPF) is the most common and lethal of the idiopathic interstitial pneumonias. There are currently no effective pharmacological therapies... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) is the most common and lethal of the idiopathic interstitial pneumonias. There are currently no effective pharmacological therapies approved for the treatment of IPF. Despite the focus on targeting fibrogenic pathways, recent clinical trials have been largely disappointing. Progress is being made in elucidating key cellular processes and molecular pathways critical to IPF pathogenesis, and this should facilitate the development of more effective therapeutics for this recalcitrant disease. Emerging pathobiological concepts include the role of aging and cellular senescence, oxidative stress, endoplasmic reticulum stress, cellular plasticity, microRNAs and mechanotransduction. Therapeutic approaches that target molecular pathways to modulate aberrant cellular phenotypes and promote tissue homeostasis in the lung must be developed. Heterogeneity in biological and clinical phenotypes of IPF warrants a personalized medicine approach to diagnosis and treatment of this lung disorder.
Topics: Animals; Humans; Idiopathic Pulmonary Fibrosis; Molecular Targeted Therapy; Risk Factors
PubMed: 21668038
DOI: 10.2165/11591490-000000000-00000 -
European Respiratory Review : An... Dec 2018Acute exacerbation of interstitial lung disease (ILD) is associated with a poor prognosis and high mortality. Numerous studies have documented acute exacerbation in... (Review)
Review
Acute exacerbation of interstitial lung disease (ILD) is associated with a poor prognosis and high mortality. Numerous studies have documented acute exacerbation in idiopathic pulmonary fibrosis (IPF), but less is known about these events in other ILDs that may present a progressive-fibrosing phenotype. We propose defining acute exacerbation as an acute, clinically significant respiratory deterioration, typically less than 1 month in duration, together with computerised tomography imaging showing new bilateral glass opacity and/or consolidation superimposed on a background pattern consistent with fibrosing ILDs. Drawing on observations in IPF, it is suspected that epithelial injury or proliferation and autoimmunity are risk factors for acute exacerbation in ILDs that may present a progressive-fibrosing phenotype, but further studies are required. Current acute exacerbation management strategies are based on recommendations in IPF, but no randomised controlled trials of acute exacerbation management have been performed. Although there are no formal strategies to prevent the development of acute exacerbation, possible approaches include antifibrotic drugs (such as nintedanib and pirfenidone), and minimising exposure to infection, airborne irritants and pollutants. This review discusses the current knowledge of acute exacerbation of ILDs that may present a progressive-fibrosing phenotype and acknowledges limitations of the data available.
Topics: Disease Progression; Female; Humans; Lung; Lung Diseases, Interstitial; Male; Middle Aged; Phenotype; Prognosis; Pulmonary Fibrosis; Risk Assessment; Risk Factors
PubMed: 30578331
DOI: 10.1183/16000617.0071-2018 -
The Indian Journal of Tuberculosis Jul 2021After the COVID-19 outbreak, increasing number of patients worldwide who have survived COVID-19 continue to battle the symptoms of the illness, long after they have been... (Review)
Review
After the COVID-19 outbreak, increasing number of patients worldwide who have survived COVID-19 continue to battle the symptoms of the illness, long after they have been clinically tested negative for the disease. As we battle through this pandemic, the challenging part is to manage COVID-19 sequelae which may vary from fatigue and body aches to lung fibrosis. This review addresses underlying mechanism, risk factors, course of disease and treatment option for post covid pulmonary fibrosis. Elderly patient who require ICU care and mechanical ventilation are at the highest risk to develop lung fibrosis. Currently, no fully proven options are available for the treatment of post inflammatory COVID 19 pulmonary fibrosis.
Topics: COVID-19; Humans; Patient Care Management; Pulmonary Fibrosis; Risk Factors; SARS-CoV-2; Post-Acute COVID-19 Syndrome
PubMed: 34099197
DOI: 10.1016/j.ijtb.2020.11.003