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Korean Journal of Radiology May 2021Following the introduction of a novel pathological concept of usual interstitial pneumonia (UIP) by Liebow and Carrington in 1969, diffuse interstitial pneumonia has... (Review)
Review
Spectrum of Pulmonary Fibrosis from Interstitial Lung Abnormality to Usual Interstitial Pneumonia: Importance of Identification and Quantification of Traction Bronchiectasis in Patient Management.
Following the introduction of a novel pathological concept of usual interstitial pneumonia (UIP) by Liebow and Carrington in 1969, diffuse interstitial pneumonia has evolved into UIP, nonspecific interstitial pneumonia (NSIP), and interstitial lung abnormality (ILA); the histopathological and CT findings of these conditions reflect the required multidisciplinary team approach, involving pulmonologists, radiologists, and pathologists, for their diagnosis and management. Concomitantly, traction bronchiectasis and bronchiolectasis have been recognized as the most persistent and important indices of the severity and prognosis of fibrotic lung diseases. The traction bronchiectasis index (TBI) can stratify the prognoses of patients with ILAs. In this review, the evolutionary concepts of UIP, NSIP, and ILAs are summarized in tables and figures, with a demonstration of the correlation between CT findings and pathologic evaluation. The CT-based UIP score is being proposed to facilitate a better understanding of the spectrum of pulmonary fibrosis, from ILAs to UIP, with emphasis on traction bronchiectasis/bronchiolectasis.
Topics: Bronchiectasis; Diagnosis, Differential; Humans; Idiopathic Pulmonary Fibrosis; Kaplan-Meier Estimate; Lung Diseases, Interstitial; Prognosis; Pulmonary Fibrosis; Tomography, X-Ray Computed
PubMed: 33543848
DOI: 10.3348/kjr.2020.1132 -
American Journal of Respiratory Cell... Jul 2017
Topics: Animals; Collagen; Humans; Indoles; Pulmonary Fibrosis; Pyridones
PubMed: 28665219
DOI: 10.1165/rcmb.2017-0079ED -
PloS One 2018Pulmonary fibrosis is a chronic and irreversible scarring disease in the lung with poor prognosis. Few therapies are available; therefore it is critical to identify new...
Pulmonary fibrosis is a chronic and irreversible scarring disease in the lung with poor prognosis. Few therapies are available; therefore it is critical to identify new therapeutic targets. Our lab has previously identified the enzyme lactate dehydrogenase-A (LDHA) as a potential therapeutic target in pulmonary fibrosis. We found increases in LDHA protein and its metabolic product, lactate, in patients with idiopathic pulmonary fibrosis (IPF). Importantly, we described lactate as a novel pro-fibrotic mediator by acidifying the extracellular space, and activating latent transforming growth factor beta (TGF-β1) in a pH-dependent manner. We propose a pro-fibrotic feed-forward loop by which LDHA produces lactate, lactate decreases pH in the extracellular space and activates TGF-β1 which can further perpetuate fibrotic signaling. Our previous work also demonstrates that the LDHA inhibitor gossypol inhibits TGF-β1-induced myofibroblast differentiation and collagen production in vitro. Here, we employed a mouse model of bleomycin-induced pulmonary fibrosis to test whether gossypol inhibits pulmonary fibrosis in vivo. We found that gossypol dose-dependently inhibits bleomycin-induced collagen accumulation and TGF-β1 activation in mouse lungs when treatment is started on the same day as bleomycin administration. Importantly, gossypol was also effective at treating collagen accumulation when delayed 7 days following bleomycin. Our results demonstrate that inhibition of LDHA with the inhibitor gossypol is effective at both preventing and treating bleomycin-induced pulmonary fibrosis, and suggests that LDHA may be a potential therapeutic target for pulmonary fibrosis.
Topics: Animals; Antibiotics, Antineoplastic; Bleomycin; Cell Differentiation; Cells, Cultured; Contraceptive Agents, Male; Enzyme Inhibitors; Gossypol; L-Lactate Dehydrogenase; Male; Mice; Mice, Inbred C57BL; Pulmonary Fibrosis; Signal Transduction
PubMed: 29795645
DOI: 10.1371/journal.pone.0197936 -
International Journal of Molecular... May 2023The pathological features of pulmonary fibrosis (PF) are the abnormal activation and proliferation of myofibroblasts and the extraordinary deposition of the... (Review)
Review
The pathological features of pulmonary fibrosis (PF) are the abnormal activation and proliferation of myofibroblasts and the extraordinary deposition of the extracellular matrix (ECM). However, the pathogenesis of PF is still indistinct. In recent years, many researchers have realized that endothelial cells had a crucial role in the development of PF. Studies have demonstrated that about 16% of the fibroblasts in the lung tissue of fibrotic mice were derived from endothelial cells. Endothelial cells transdifferentiated into mesenchymal cells via the endothelial-mesenchymal transition (E(nd)MT), leading to the excessive proliferation of endothelial-derived mesenchymal cells and the accumulation of fibroblasts and ECM. This suggested that endothelial cells, a significant component of the vascular barrier, played an essential role in PF. Herein, this review discusses E(nd)MT and its contribution to the activation of other cells in PF, which could provide new ideas for further understanding the source and activation mechanism of fibroblasts and the pathogenesis of PF.
Topics: Mice; Animals; Pulmonary Fibrosis; Endothelial Cells; Fibrosis; Fibroblasts; Myofibroblasts; Risk Factors
PubMed: 37240093
DOI: 10.3390/ijms24108749 -
The European Respiratory Journal Nov 2007Idiopathic pulmonary fibrosis (IPF) is a devastating condition that carries a prognosis worse than that of many cancers. A recent classification of the idiopathic... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) is a devastating condition that carries a prognosis worse than that of many cancers. A recent classification of the idiopathic interstitial pneumonias has redefined the diagnostic criteria necessary to determine a diagnosis of IPF. The present authors believe that this redefinition is incorrect, relying as it does on subtle histological differences for the definition of separate disease categories. A further issue affecting IPF research is the polarisation of views around two competing pathogenetic hypotheses. One argues for the primacy of inflammation as the trigger that initiates fibrosis, and the other proposes that fibrosis arises as a consequence of chronic epithelial injury and failure of repair due to aberrant epithelial-mesenchymal interactions. The present authors believe that this schism is hampering understanding of IPF and skewing research priorities. It is argued here, instead, that abnormalities in multiple pathways involved in wound healing and inflammation lead to the development of idiopathic pulmonary fibrosis, and it is suggested that a new rationale for clinical classification and pathogenesis may be more productive in driving the search for novel therapies in the future.
Topics: Animals; Humans; Prognosis; Pulmonary Fibrosis
PubMed: 17978154
DOI: 10.1183/09031936.00069307 -
Current Opinion in Pulmonary Medicine Jul 2017The pathogenesis of lung cancer and pulmonary fibrotic disorders partially overlaps. This review focuses on the common features of the two disease categories, aimed at... (Review)
Review
PURPOSE OF REVIEW
The pathogenesis of lung cancer and pulmonary fibrotic disorders partially overlaps. This review focuses on the common features of the two disease categories, aimed at advancing our translational understanding of their pathobiology and at fostering the development of new therapies.
RECENT FINDINGS
Both malignant and collagen-producing lung cells display enhanced cellular proliferation, increased resistance to apoptosis, a propensity for invading and distorting the lung parenchyma, as well as stemness potential. These characteristics are reinforced by the tissue microenvironment and inflammation seems to play an important adjuvant role in both types of disorders.
SUMMARY
Unraveling the thread of the common and distinct characteristics of lung fibrosis and cancer might contribute to a more comprehensive approach of the pathobiology of both diseases and to a pathfinder for novel and personalized therapeutic strategies.
Topics: Aging; Apoptosis; Carcinogenesis; Humans; Lung Neoplasms; Pulmonary Fibrosis
PubMed: 28403038
DOI: 10.1097/MCP.0000000000000390 -
Chest Mar 1986The study of animal models of IPF has demonstrated that there is a stereotyped response of the respiratory airspace walls to a wide variety of injuries. Inflammatory and...
The study of animal models of IPF has demonstrated that there is a stereotyped response of the respiratory airspace walls to a wide variety of injuries. Inflammatory and immune effector cells play a major and complex role in the fibrosing process. They may contribute to the injury of the lung beyond the original insult. These cells secrete substances that play an important role in determining cell traffic in the lungs and in controlling the connective tissue-producing cells. Products derived from the inflammatory response may interfere with protection of normal lung matrix, although injury to lung matrix itself does not lead to fibrosis. Injury to endothelial cells and especially type I epithelial cells appears to play a major role in the fibrogenic response. Further understanding of the factors that injure these cells, the development of methods of protecting them from injury, and a clear understanding of their role in the fibrogenic process appear to be key to developing better methods of preventing and treating interstitial pulmonary fibrosis.
Topics: Animals; Connective Tissue; Disease Models, Animal; Dogs; Endothelium; Humans; Leukocytes; Lung; Mice; Mice, Mutant Strains; Primates; Pulmonary Fibrosis; Rabbits
PubMed: 3948572
DOI: 10.1378/chest.89.3_supplement.115s -
Journal of Advanced Nursing May 2015To understand the perceptions, needs and experiences of patients with Idiopathic Pulmonary Fibrosis.
AIMS
To understand the perceptions, needs and experiences of patients with Idiopathic Pulmonary Fibrosis.
BACKGROUND
Idiopathic pulmonary fibrosis is a progressive interstitial lung disease, with a mean life expectancy similar to some forms of cancer of 2-4 years from diagnosis. Unlike the cancer literature, which is rich with studies exploring the needs of their disease group, few publications exist on patient needs with this severe fibrotic lung disease.
DESIGN
A Qualitative study which took place between 2007-2012.
METHODS
Seventeen patients with a multidisciplinary team confirmed diagnosis of Idiopathic Pulmonary Fibrosis, with moderate to advanced disease severity and six of their informal carers were interviewed. An interview topic guide was developed by the researchers and service user group. The interviews were audio-recorded, semi-structured and took place at a regional respiratory and lung transplant centre in North West England. Interviews were transcribed verbatim and data analysed using Framework Analysis.
FINDINGS
Three main themes were identified: 'Struggling to get a diagnosis'; 'Loss of the life I previously had'; and 'Living with Idiopathic Pulmonary Fibrosis'. Patients reported struggling to get a diagnosis and coping with a life-limiting, rapidly progressive illness with no good treatment and few support structures.
CONCLUSIONS
There is an urgent need for a better understanding of the difficulties faced by people with Idiopathic Pulmonary Fibrosis and their carers. This can be used to develop better supportive care in the United Kingdom and ultimately improve the quality of life of these patients.
Topics: Health Services Needs and Demand; Humans; Idiopathic Pulmonary Fibrosis
PubMed: 25533573
DOI: 10.1111/jan.12587 -
Biomedicine & Pharmacotherapy =... May 2024Idiopathic pulmonary fibrosis (IPF) is a progressive and life-threatening lung disease with high mortality rates. The limited availability of effective drugs for IPF...
BACKGROUND
Idiopathic pulmonary fibrosis (IPF) is a progressive and life-threatening lung disease with high mortality rates. The limited availability of effective drugs for IPF treatment, coupled with concerns regarding adverse effects and restricted responsiveness, underscores the need for alternative approaches. Kefir peptides (KPs) have demonstrated antioxidative, anti-inflammatory, and antifibrotic properties, along with the capability to modulate gut microbiota. This study aims to investigate the impact of KPs on bleomycin-induced pulmonary fibrosis.
METHODS
Mice were treated with KPs for four days, followed by intratracheal injection of bleomycin for 21 days. Comprehensive assessments included pulmonary functional tests, micro-computed tomography (µ-CT), in vivo image analysis using MMPsense750, evaluation of inflammation- and fibrosis-related gene expression in lung tissue, and histopathological examinations. Furthermore, a detailed investigation of the gut microbiota community was performed using full-length 16 S rRNA sequencing in control mice, bleomycin-induced fibrotic mice, and KPs-pretreated fibrotic mice.
RESULTS
In KPs-pretreated bleomycin-induced lung fibrotic mice, notable outcomes included the absence of significant bodyweight loss, enhanced pulmonary functions, restored lung tissue architecture, and diminished thickening of inter-alveolar septa, as elucidated by morphological and histopathological analyses. Concurrently, a reduction in the expression levels of oxidative biomarkers, inflammatory factors, and fibrotic indicators was observed. Moreover, 16 S rRNA sequencing demonstrated that KPs pretreatment induced alterations in the relative abundances of gut microbiota, notably affecting Barnesiella_intestinihominis, Kineothrix_alysoides, and Clostridium_viride.
CONCLUSIONS
Kefir peptides exerted preventive effects, protecting mice against bleomycin-induced lung oxidative stress, inflammation, and fibrosis. These effects are likely linked to modifications in the gut microbiota community. The findings highlight the therapeutic potential of KPs in mitigating pulmonary fibrosis and advocate for additional exploration in clinical settings.
Topics: Animals; Bleomycin; Oxidative Stress; Gastrointestinal Microbiome; Mice; Kefir; Pulmonary Fibrosis; Mice, Inbred C57BL; Inflammation; Male; Peptides; Lung; Anti-Inflammatory Agents; Disease Models, Animal
PubMed: 38522238
DOI: 10.1016/j.biopha.2024.116431 -
CMAJ : Canadian Medical Association... Jul 2004Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal pulmonary fibrotic lung disease. The diagnostic histological changes are called usual interstitial... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal pulmonary fibrotic lung disease. The diagnostic histological changes are called usual interstitial pneumonia and are characterized by histological temporal heterogeneity, whereby normal lung tissue is interspersed with interstitial fibrosis, honeycomb cysts and fibroblast foci. Pulmonary functions show restricted volumes and capacities, preserved flows and evidence of decreased gas exchange. High-resolution computed axial tomography demonstrates evidence of fibrosis and lung remodelling such as honeycomb cysts and traction bronchiectasis. There is no known effective treatment for IPF, but lung transplantation improves survival.
Topics: Adult; Aged; Female; Humans; Lung Diseases, Interstitial; Male; Middle Aged; Prevalence; Pulmonary Fibrosis; Respiratory Function Tests
PubMed: 15262886
DOI: 10.1503/cmaj.1030055