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Archives of Pathology & Laboratory... Mar 2016Three distinct patterns of pulmonary fibrosis, including usual interstitial pneumonia, fibrotic nonspecific interstitial pneumonia, and airway-centered fibrosis, can be... (Comparative Study)
Comparative Study Review
CONTEXT
Three distinct patterns of pulmonary fibrosis, including usual interstitial pneumonia, fibrotic nonspecific interstitial pneumonia, and airway-centered fibrosis, can be identified on surgical lung biopsies.
OBJECTIVES
To compare the pathologic definitions, clinical and radiographic presentations, etiologies and differential diagnoses, treatments, and prognoses of usual interstitial pneumonia, fibrotic nonspecific interstitial pneumonia, and airway-centered fibrosis patterns, and to address the challenges and controversies related to pulmonary fibrosis.
DATA SOURCES
Data were derived from published literature and clinical experience.
CONCLUSIONS
Although there may be overlap, identification of the dominant form of fibrosis in a particular case can provide a general category of disease and assist in identifying an etiology.
Topics: Alveolitis, Extrinsic Allergic; Biopsy; Connective Tissue Diseases; Diagnosis, Differential; Humans; Idiopathic Pulmonary Fibrosis; Lung; Lung Diseases, Interstitial; Prognosis; Pulmonary Fibrosis; Radiography; Respiratory Mucosa; Terminology as Topic
PubMed: 26927716
DOI: 10.5858/arpa.2015-0288-SA -
Current Opinion in Pulmonary Medicine Sep 2016Up to twenty percent of patients with sarcoidosis develop pulmonary fibrosis, transforming an often benign disease into a highly morbid and potentially fatal one. We... (Review)
Review
PURPOSE OF REVIEW
Up to twenty percent of patients with sarcoidosis develop pulmonary fibrosis, transforming an often benign disease into a highly morbid and potentially fatal one. We highlight the fibrotic pulmonary sarcoidosis phenotype as an area of intense clinical and translational investigation, review recent developments in treatment, and provide a roadmap for future research in sarcoidosis associated pulmonary fibrosis.
RECENT FINDINGS
Granulomatous inflammation in a lymphatic distribution is the hallmark finding of pulmonary sarcoidosis and the nidus for fibrosis. Recent research demonstrates that fibrotic sarcoidosis begins in the setting of persistent, uncontrolled inflammation, and is aided by pro-fibrotic genetic features and immune responses. Comparison to other fibrotic lung diseases also reveals key features that inform our understanding of common pathways in fibrosis.
SUMMARY
Understanding the mechanisms of fibrotic transformation in sarcoidosis enhances clinical care and facilitates development of novel therapeutic options. The impact of these findings in fibrotic sarcoidosis may be amplified through application to other interstitial lung diseases marked by inflammatory to fibrotic transformation. Important aspects of clinical management of fibrotic sarcoidosis include surveillance for co-morbidities, such as pulmonary hypertension, airway disease, and infection, and assessment for pulmonary disease activity that may benefit from immunosuppression.
Topics: Granuloma; Humans; Pulmonary Fibrosis; Sarcoidosis, Pulmonary
PubMed: 27379967
DOI: 10.1097/MCP.0000000000000301 -
Redox Biology Oct 2016Redox signaling and oxidative stress are associated with tissue fibrosis and aging. Aging is recognized as a major risk factor for fibrotic diseases involving multiple... (Review)
Review
Redox signaling and oxidative stress are associated with tissue fibrosis and aging. Aging is recognized as a major risk factor for fibrotic diseases involving multiple organ systems, including that of the lung. A number of oxidant generating enzymes are upregulated while antioxidant defenses are deficient with aging and cellular senescence, leading to redox imbalance and oxidative stress. However, the precise mechanisms by which redox signaling and oxidative stress contribute to the pathogenesis of lung fibrosis are not well understood. Tissue repair is a highly regulated process that involves the interactions of several cell types, including epithelial cells, fibroblasts and inflammatory cells. Fibrosis may develop when these interactions are dysregulated with the acquisition of pro-fibrotic cellular phenotypes. In this review, we explore the roles of redox mechanisms that promote and perpetuate fibrosis in the context of cellular senescence and aging.
Topics: Age Factors; Aging; Animals; Apoptosis; Cellular Senescence; Epithelial Cells; Epithelial-Mesenchymal Transition; Fibroblasts; Humans; Molecular Targeted Therapy; Oxidation-Reduction; Oxidative Stress; Phenotype; Pulmonary Fibrosis; Reactive Oxygen Species
PubMed: 27394680
DOI: 10.1016/j.redox.2016.06.005 -
The Yale Journal of Biology and Medicine Jun 2017Pulmonary fibrosis is a form of lung disease that develops due to aberrant wound-healing following repeated alveoli injury in genetically susceptible individuals,... (Review)
Review
Pulmonary fibrosis is a form of lung disease that develops due to aberrant wound-healing following repeated alveoli injury in genetically susceptible individuals, resulting in chronic inflammation, excess deposition of the extracellular matrix components, mainly collagen, and scarring of lung tissue. In addition to irradiation, environmental agents such occupational inhalants, and chemotherapeutic agents, microbial agents also play a role in the etiology of the disease. While viruses have received the most attention, emerging evidence suggest that bacteria and fungi also play a part in the etiology of pulmonary fibrosis. Furthermore, successful use of antibiotics, antiviral and antifungal drugs in several studies to attenuate fibrosis progression is also an indication of microbial involvement in the pathogenesis of the disease and could be a promising therapeutic modality for treating pulmonary fibrosis initiated or exacerbated by infectious agents.
Topics: Animals; Anti-Infective Agents; Bacterial Infections; Disease Models, Animal; Humans; Mice; Mycoses; Pulmonary Fibrosis; Vaccination; Virus Diseases
PubMed: 28656009
DOI: No ID Found -
Environmental Health Perspectives Apr 1984The lung is a primary target of cell injury in patients receiving cytotoxic drugs, and in many cases the reaction is severe enough to produce diffuse pulmonary fibrosis.... (Review)
Review
The lung is a primary target of cell injury in patients receiving cytotoxic drugs, and in many cases the reaction is severe enough to produce diffuse pulmonary fibrosis. Although many different agents may damage the lung, the patterns of cellular injury and repair are relatively constant. Using bleomycin toxicity as an example, it has been shown that, after IV injection, the selective site of lung injury is the vascular endothelium; this is followed by the accumulation of interstitial edema and later by necrosis of Type I epithelial cells. In normal repair, rapid proliferation of Type II cells, followed by differentiation to Type I, restores the epithelial surface without fibrosis. However, after bleomycin, Type II cell proliferation is frequently followed by abnormal differentiation to a metaplastic form of epithelium. Fibroblast proliferation accompanies this abnormal epithelial response which is related either to selective retention of bleomycin by epithelial cells or to the toxic effects of administering more drug at the time of Type II cell division. It is concluded that diffuse interstitial fibrosis results from prolonged disturbance of the normal epithelial-mesenchymal interrelationships at the alveolar wall. Disruption of the fibroblastic control system by extensive epithelial necrosis or by delayed or inappropriate repair may be the key factor in instigating fibroblast proliferation and subsequent deposition of collagen. This mechanism may account for the development of diffuse fibrosis or fibrosing alveolitis in response to a variety of pulmonary toxins.
Topics: Animals; Bleomycin; Humans; Lung; Mitosis; Pulmonary Fibrosis; Species Specificity; Thymidine; Wound Healing
PubMed: 6203733
DOI: 10.1289/ehp.845525 -
Clinical Medicine (London, England) Dec 2014Idiopathic pulmonary fibrosis (IPF) is a devastating condition with a poor prognosis and few treatment options. However, recent research into this condition has led to... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) is a devastating condition with a poor prognosis and few treatment options. However, recent research into this condition has led to considerable insights into the pathophysiology of the disease, resulting in the identification of potential biomarkers to aid diagnosis and stratification of patients and the development of novel therapies. In this review we will discuss the recent developments in this field and review how this knowledge has been translated into clinical trials and a paradigm shift in our approach to patients with IPF.
Topics: Biomarkers; Humans; Idiopathic Pulmonary Fibrosis; Indoles; Pyridones
PubMed: 25468919
DOI: 10.7861/clinmedicine.14-6-s45 -
Respiratory Research Aug 2023Pulmonary fibrosis is a progressive disease characterized by lung remodeling due to excessive deposition of extracellular matrix. Although the etiology remains unknown,...
BACKGROUND
Pulmonary fibrosis is a progressive disease characterized by lung remodeling due to excessive deposition of extracellular matrix. Although the etiology remains unknown, aberrant angiogenesis and inflammation play an important role in the development of this pathology. In this context, recent scientific research has identified new molecules involved in angiogenesis and inflammation, such as the prolyl oligopeptidase (PREP), a proteolytic enzyme belonging to the serine protease family, linked to the pathology of many lung diseases such as pulmonary fibrosis. Therefore, the aim of this study was to investigate the effect of a selective inhibitor of PREP, known as KYP-2047, in an in vitro and in an in vivo model of pulmonary fibrosis.
METHODS
The in vitro model was performed using human alveolar A549 cells. Cells were exposed to lipopolysaccharide (LPS) 10 μg/ml and then, cells were treated with KYP-2047 at the concentrations of 1 μM, 10 μM and 50 μM. Cell viability was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) bromide colorimetric assay, while inflammatory protein expression was assessed by western blots analysis. The in vivo model was induced in mice by intra-tracheal administration of bleomycin (1 mg/kg) and then treated intraperitoneally with KYP-2047 at doses of 1, 2.5 and 5 mg/kg once daily for 12 days and then mice were sacrificed, and lung tissues were collected for analyses.
RESULTS
The in vitro results demonstrated that KYP-2047 preserved cell viability, reduced inflammatory process by decreasing IL-18 and TNF-α, and modulated lipid peroxidation as well as nitrosative stress. The in vivo pulmonary fibrosis has demonstrated that KYP-2047 was able to restore histological alterations reducing lung injury. Our data demonstrated that KYP-2047 significantly reduced angiogenesis process and the fibrotic damage modulating the expression of fibrotic markers. Furthermore, KYP-2047 treatment modulated the IκBα/NF-κB pathway and reduced the expression of related pro-inflammatory enzymes and cytokines. Moreover, KYP-2047 was able to modulate the JAK2/STAT3 pathway, highly involved in pulmonary fibrosis.
CONCLUSION
In conclusion, this study demonstrated the involvement of PREP in the pathogenesis of pulmonary fibrosis and that its inhibition by KYP-2047 has a protective role in lung injury induced by BLM, suggesting PREP as a potential target therapy for pulmonary fibrosis. These results speculate the potential protective mechanism of KYP-2047 through the modulation of JAK2/STAT3 and NF-κB pathways.
Topics: Humans; Animals; Mice; Pulmonary Fibrosis; Prolyl Oligopeptidases; Lung Injury; NF-kappa B; Inflammation
PubMed: 37626373
DOI: 10.1186/s12931-023-02519-x -
Aging Oct 2023G protein-coupled receptor kinase-2 (GRK2) is involved in TGF-β1-induced activation of lung fibroblasts, which could give rise to the pathogenesis of pulmonary...
G protein-coupled receptor kinase-2 (GRK2) is involved in TGF-β1-induced activation of lung fibroblasts, which could give rise to the pathogenesis of pulmonary fibrosis. Paroxetine (PRXT) serves as a selective GRK2 inhibitor which is widely used to treat anxiety and depression for several decades. However, whether PRXT could inhibit TGF-β1-induced activation of lung fibroblasts and combat bleomycin-induced pulmonary fibrosis remains unclear. Here, we investigated the effects of PRXT on pulmonary fibrosis in C57/BL6 caused by bleomycin as well as on the activation of murine primary lung fibroblasts stimulated with TGF-β1. The results demonstrated that PRXT markedly improved the pulmonary function and 21-day survival in bleomycin-induced mice. Meanwhile, PRXT significantly decreased collagen deposition, inflammation, and oxidative stress in lung tissues from bleomycin-induced mice. Furthermore, we found that PRXT could inhibit the protein and mRNA expression of GRK2 and Smad3 in lung tissues from bleomycin-induced mice. experiments also PRXT could inhibit cell activation and collagen synthesis in a concentration-dependent manner in TGF-β1-induced lung fibroblasts. In addition, we found that Smad3 overexpression by adenovirus transfection could offset anti-fibrotic and antioxidative effects from PRXT in TGF-β1-induced lung fibroblasts, which showed no effects on the protein expression of GRK2. In conclusion, PRXT mediates the inhibition of GRK2, which further blocks the transcription of Smad3 in TGF-β1-induced lung fibroblasts, providing an attractive therapeutic target for pulmonary fibrosis.
Topics: Mice; Animals; Pulmonary Fibrosis; Bleomycin; Transforming Growth Factor beta1; Paroxetine; Lung; Fibroblasts; Collagen; Mice, Inbred C57BL
PubMed: 37815883
DOI: 10.18632/aging.205092 -
Orphanet Journal of Rare Diseases Mar 2008Idiopathic pulmonary fibrosis (IPF) is a non-neoplastic pulmonary disease that is characterized by the formation of scar tissue within the lungs in the absence of any... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) is a non-neoplastic pulmonary disease that is characterized by the formation of scar tissue within the lungs in the absence of any known provocation. IPF is a rare disease which affects approximately 5 million persons worldwide. The prevalence is estimated to be slightly greater in men (20.2/100,000) than in women (13.2/100,000). The mean age at presentation is 66 years. IPF initially manifests with symptoms of exercise-induced breathless and dry coughing. Auscultation of the lungs reveals early inspiratory crackles, predominantly located in the lower posterior lung zones upon physical exam. Clubbing is found in approximately 50% of IPF patients. Cor pulmonale develops in association with end-stage disease. In that case, classic signs of right heart failure may be present. Etiology remains incompletely understood. Some environmental factors may be associated with IPF (cigarette smoking, exposure to silica and livestock). IPF is recognized on high-resolution computed tomography by peripheral, subpleural lower lobe reticular opacities in association with subpleural honeycomb changes. IPF is associated with a pathological lesion known as usual interstitial pneumonia (UIP). The UIP pattern consists of normal lung alternating with patches of dense fibrosis, taking the form of collagen sheets. The diagnosis of IPF requires correlation of the clinical setting with radiographic images and a lung biopsy. In the absence of lung biopsy, the diagnosis of IPF can be made by defined clinical criteria that were published in guidelines endorsed by several professional societies. Differential diagnosis includes other idiopathic interstitial pneumonia, connective tissue diseases (systemic sclerosis, polymyositis, rheumatoid arthritis), forme fruste of autoimmune disorders, chronic hypersensitivity pneumonitis and other environmental (sometimes occupational) exposures. IPF is typically progressive and leads to significant disability. The median survival is 2 to 5 years from the time of diagnosis. Medical therapy is ineffective in the treatment of IPF. New molecular therapeutic targets have been identified and several clinical trials are investigating the efficacy of novel medication. Meanwhile, pulmonary transplantation remains a viable option for patients with IPF. It is expected that, during the next decade, considerable progress will be made toward the understanding and treatment of this devastating illness.
Topics: Aged; Aged, 80 and over; Diagnosis, Differential; Female; Humans; Lung; Lung Diseases; Male; Pulmonary Fibrosis; Tomography, X-Ray Computed
PubMed: 18366757
DOI: 10.1186/1750-1172-3-8 -
QJM : Monthly Journal of the... Apr 2022
Topics: COVID-19; Fibrosis; Humans; Pulmonary Fibrosis; ortho-Aminobenzoates
PubMed: 35262694
DOI: 10.1093/qjmed/hcac069