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Current Opinion in Pulmonary Medicine Sep 2020Mortality in patients with sarcoidosis has primarily been attributed to advanced pulmonary sarcoidosis. This review aims to provide an update on recent clinical studies... (Review)
Review
PURPOSE OF REVIEW
Mortality in patients with sarcoidosis has primarily been attributed to advanced pulmonary sarcoidosis. This review aims to provide an update on recent clinical studies that help to better phenotype these patients, discuss new treatment options, and suggest areas where additional research is needed.
RECENT FINDINGS
Diagnosis and management of advanced pulmonary sarcoidosis has changed as new technologies and treatment options have emerged. Clinical phenotypes of advanced disease have evolved to show overlap in presentation with other interstitial lung diseases. Assessment involves more advanced imaging modalities. New promising treatment options are being studied. Pulmonary rehabilitation and lung transplantation are being utilized to improve health-related quality of life and survival.
SUMMARY
Patients with advanced pulmonary fibrosis can have variable clinical, radiographic, histopathologic presentation. Given the poor health-related quality of life and high rates of mortality, medical therapy and pulmonary rehabilitation may benefit these patients. Lung transplantation should be considered in those with end-stage disease.
Topics: Bronchiectasis; Disease Progression; Exercise Therapy; Humans; Lung Diseases, Interstitial; Lung Transplantation; Pulmonary Fibrosis; Quality of Life; Sarcoidosis, Pulmonary; Survival Rate
PubMed: 32740378
DOI: 10.1097/MCP.0000000000000705 -
The Lancet. Respiratory Medicine Aug 2022
Topics: Humans; Idiopathic Pulmonary Fibrosis
PubMed: 35760077
DOI: 10.1016/S2213-2600(22)00223-5 -
Advances in Pharmacology (San Diego,... 2023Idiopathic pulmonary fibrosis (IPF) results from the dysregulated process of injury and repair, which promotes scarring of the lung tissue and deposition of...
Idiopathic pulmonary fibrosis (IPF) results from the dysregulated process of injury and repair, which promotes scarring of the lung tissue and deposition of collagen-rich extracellular matrix (ECM) components, that make the lung unphysiologically stiff. IPF presents a serious concern as its pathogenesis remains elusive, and current anti-fibrotic treatments are only effective in slowing rather than halting disease progression. The IPF disease pathogenesis is incompletely defined, complex and incorporates interplay between different fibrogenesis signaling pathways. Preclinical IPF experimental models used to validate drug candidates present significant limitations in modeling IPF pathobiology, with their limited time frame, simplicity and inaccurate representation of the disease and the mechanical influences of IPF. Potentially more accurate mimetic disease models that capture the cell-cell and cell-matrix interaction, such as 3D cultures, organoids and precision-cut lung slices (PCLS), may yield more meaningful clinical predictions for drug candidates. Recent advances in developing anti-fibrotic compounds have positioned drug towards targeting components of the fibrogenesis signaling pathway of IPF or the extracellular microenvironment. The major goals in this area of research focus on finding ways to reverse or halt the disease progression by utilizing more disease-relevant experimental models to improve the qualification of potential drug targets for treating pulmonary fibrosis.
Topics: Humans; Fibrosis; Idiopathic Pulmonary Fibrosis; Disease Progression
PubMed: 37524487
DOI: 10.1016/bs.apha.2023.04.002 -
Molecular & Cellular Proteomics : MCP Apr 2023The heterogeneity of idiopathic pulmonary fibrosis (IPF) limits its diagnosis and treatment. The association between the pathophysiological features and the serum...
The heterogeneity of idiopathic pulmonary fibrosis (IPF) limits its diagnosis and treatment. The association between the pathophysiological features and the serum protein signatures of IPF currently remains unclear. The present study analyzed the specific proteins and patterns associated with the clinical parameters of IPF based on a serum proteomic dataset by data-independent acquisition using MS. Differentiated proteins in sera distinguished patients with IPF into three subgroups in signal pathways and overall survival. Aging-associated signatures by weighted gene correlation network analysis coincidently provided clear and direct evidence that aging is a critical risk factor for IPF rather than a single biomarker. Expression of LDHA and CCT6A, which was associated with glucose metabolic reprogramming, was correlated with high serum lactic acid content in patients with IPF. Cross-model analysis and machine learning showed that a combinatorial biomarker accurately distinguished patients with IPF from healthy individuals with an area under the curve of 0.848 (95% CI = 0.684-0.941) and validated from another cohort and ELISA assay. This serum proteomic profile provides rigorous evidence that enables an understanding of the heterogeneity of IPF and protein alterations that could help in its diagnosis and treatment decisions.
Topics: Humans; Proteomics; Idiopathic Pulmonary Fibrosis; Blood Proteins; Biomarkers; Chaperonin Containing TCP-1
PubMed: 36870568
DOI: 10.1016/j.mcpro.2023.100524 -
Pharmacological Research Nov 2021Pulmonary fibrosis (PF) is a progressive and devastating lung disease of unknown etiology, excessive fibroblast proliferation serves as a key event to promote PF....
Pulmonary fibrosis (PF) is a progressive and devastating lung disease of unknown etiology, excessive fibroblast proliferation serves as a key event to promote PF. Transcription factor forkhead box M1 (FOXM1) is not only a well-known proto-oncogene, but also an essential driver of cell proliferation. Recently, 5'-AMP-activated protein kinase (AMPK) is reported to reduce the incidence of PF. However, it remains elusive whether have an underlying relationship between AMPK and FOXM1 in fibroblast proliferation-mediated PF. Here, the progression of lung fibroblast proliferation and the expression levels of AMPK and FOXM1 were observed by intratracheally instilled of bleomycin (BLM) and intraperitoneal injection of metformin in C57BL/6 J mice. Meanwhile, human fetal lung fibroblast1 (HFL1) cells were respectively treated with AMPK activator metformin or AMPK inhibitor Compound C, or FOXM1 depletion by transfected small interfering RNA (siRNA) to unveil roles of AMPK, FOXM1 and the link between them on platelet-derived growth factor (PDGF)-induced fibroblast proliferation. Our results demonstrated that AMPK activated by metformin could down-regulate FOXM1 and alleviate BLM-induced mouse PF model. In vitro, activation of AMPK attenuated PDGF-induced fibroblast proliferation accompanied by the down-regulation of FOXM1. In contrast, inhibition of AMPK enhanced PDGF-induced fibroblast proliferation along with activating FOXM1. These findings suggest that AMPK can ameliorate the progression of fibroblast proliferation during PF via suppressing the expression of FOXM1 and provide new insight into seek PF treatment approaches.
Topics: AMP-Activated Protein Kinases; Animals; Bleomycin; Cell Line; Cell Proliferation; Fibroblasts; Forkhead Box Protein M1; Humans; Lung; Male; Metformin; Mice, Inbred C57BL; Platelet-Derived Growth Factor; Pulmonary Fibrosis; Mice
PubMed: 34450310
DOI: 10.1016/j.phrs.2021.105844 -
Seminars in Respiratory and Critical... Apr 2020Combined pulmonary fibrosis and emphysema (CPFE) is a clinical entity characterized by the combination of upper lobe emphysema and lower lobe fibrosis, the latter owing... (Review)
Review
Combined pulmonary fibrosis and emphysema (CPFE) is a clinical entity characterized by the combination of upper lobe emphysema and lower lobe fibrosis, the latter owing to various interstitial lung diseases. These patients have a characteristic lung function profile, with relatively preserved dynamic and static lung volumes, contrasting with a significant reduction of carbon monoxide transfer. The pathogenic mechanisms leading to the coexistence of emphysema with fibrosis remain unclear and different theories have been proposed. CPFE is frequently complicated by pulmonary hypertension, acute exacerbations, and lung cancer leading to poor natural history and prognosis. The syndrome of CPFE represents a distinct pulmonary manifestation in the spectrum of lung diseases associated with connective tissue diseases. Currently, there are no established recommendations regarding the management of patients with CPFE. We provide a review on the existing knowledge of CPFE regarding the epidemiology, pathogenesis, clinical manifestations, radiologic appearance, complications, prognosis, and possible treatment options.
Topics: Humans; Hypertension, Pulmonary; Lung; Lung Neoplasms; Prognosis; Pulmonary Emphysema; Pulmonary Fibrosis; Smoking
PubMed: 32279289
DOI: 10.1055/s-0040-1708058 -
Clinics in Chest Medicine Jun 2021Idiopathic pulmonary fibrosis (IPF) is a devastating disease for patients and their loved ones. Since initial efforts to characterize this disease in the 1960s,... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) is a devastating disease for patients and their loved ones. Since initial efforts to characterize this disease in the 1960s, understanding of IPF has evolved considerably. Such evolution has continually challenged prior diagnostic and treatment paradigms, ushering in an era of higher confidence diagnoses with less invasive procedures and more effective treatments. This review details how research and clinical experience over the past half century have led to a rethinking of IPF. Here, the evolution in understanding of IPF pathogenesis, diagnostic evaluation and treatment approach is discussed.
Topics: Humans; Idiopathic Pulmonary Fibrosis
PubMed: 34024402
DOI: 10.1016/j.ccm.2021.03.005 -
Nature Communications Dec 2023Pulmonary fibrosis (PF), a condition characterized by inflammation and collagen deposition in the alveolar interstitium, causes dyspnea and fatal outcomes. Although the...
Pulmonary fibrosis (PF), a condition characterized by inflammation and collagen deposition in the alveolar interstitium, causes dyspnea and fatal outcomes. Although the bleomycin-induced PF mouse model has improved our understanding of exogenous factor-induced fibrosis, the mechanism governing endogenous factor-induced fibrosis remains unknown. Here, we find that Ifngr1Rag2 mice, which lack the critical suppression factor for group 2 innate lymphoid cells (ILC2), develop PF spontaneously. The onset phase of fibrosis includes ILC2 subpopulations with a high Il1rl1 (IL-33 receptor) expression, and fibrosis does not develop in ILC-deficient or IL-33-deficient mice. Although ILC2s are normally localized near bronchioles and blood vessels, ILC2s are increased in fibrotic areas along with IL-33 positive fibroblasts during fibrosis. Co-culture analysis shows that activated-ILC2s directly induce collagen production from fibroblasts. Furthermore, increased IL1RL1 and decreased IFNGR1 expressions are confirmed in ILC2s from individuals with idiopathic PF, highlighting the applicability of Ifngr1Rag2 mice as a mouse model for fibrosis research.
Topics: Animals; Mice; Pulmonary Fibrosis; Immunity, Innate; Interleukin-33; Lymphocytes; Fibrosis; Collagen; Lung; Mice, Inbred C57BL; Interleukin-1 Receptor-Like 1 Protein
PubMed: 38097562
DOI: 10.1038/s41467-023-43336-6 -
European Respiratory Review : An... Sep 2023Sarcoidosis is a multisystem granulomatous disorder of unknown aetiology. A minority of patients with sarcoidosis develop sarcoidosis-associated pulmonary fibrosis... (Review)
Review
Sarcoidosis is a multisystem granulomatous disorder of unknown aetiology. A minority of patients with sarcoidosis develop sarcoidosis-associated pulmonary fibrosis (SAPF), which may become progressive. Genetic profiles differ between patients with progressive and self-limiting disease. The mechanisms of fibrosis in SAPF are not fully understood, but SAPF is likely a distinct clinicopathological entity, rather than a continuum of acute inflammatory sarcoidosis. Risk factors for the development of SAPF have been identified; however, at present, it is not possible to make a robust prediction of risk for an individual patient. The bulk of fibrotic abnormalities in SAPF are located in the upper and middle zones of the lungs. A greater extent of SAPF on imaging is associated with a worse prognosis. Patients with SAPF are typically treated with corticosteroids, second-line agents such as methotrexate or azathioprine, or third-line agents such as tumour necrosis factor inhibitors. The antifibrotic drug nintedanib is an approved treatment for slowing the decline in lung function in patients with progressive fibrosing interstitial lung diseases, but more evidence is needed to assess its efficacy in SAPF. The management of patients with SAPF should include the identification and treatment of complications such as bronchiectasis and pulmonary hypertension. Further research is needed into the mechanisms underlying SAPF and biomarkers that predict its clinical course.
Topics: Humans; Pulmonary Fibrosis; Lung; Lung Diseases, Interstitial; Sarcoidosis; Risk Factors; Disease Progression
PubMed: 37758275
DOI: 10.1183/16000617.0085-2023 -
Bioorganic Chemistry Sep 2023Pulmonary fibrosis is the end-stage change of a large class of lung diseases characterized by the proliferation of fibroblasts and the accumulation of a large amount of... (Review)
Review
Pulmonary fibrosis is the end-stage change of a large class of lung diseases characterized by the proliferation of fibroblasts and the accumulation of a large amount of extracellular matrix, accompanied by inflammatory damage and tissue structure destruction, which also shows the normal alveolar tissue is damaged and then abnormally repaired resulting in structural abnormalities (scarring). Pulmonary fibrosis has a serious impact on the respiratory function of the human body, and the clinical manifestation is progressive dyspnea. The incidence of pulmonary fibrosis-related diseases is increasing year by year, and no curative drugs have appeared so far. Nevertheless, research on pulmonary fibrosis have also increased in recent years, but there are no breakthrough results. Pathological changes of pulmonary fibrosis appear in the lungs of patients with coronavirus disease 2019 (COVID-19) that have not yet ended, and whether to improve the condition of patients with COVID-19 by means of the anti-fibrosis therapy, which are the questions we need to address now. This review systematically sheds light on the current state of research on fibrosis from multiple perspectives, hoping to provide some references for design and optimization of subsequent drugs and the selection of anti-fibrosis treatment plans and strategies.
Topics: Humans; Pulmonary Fibrosis; COVID-19; Lung; Fibrosis; Fibroblasts
PubMed: 37178650
DOI: 10.1016/j.bioorg.2023.106592