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Inflammation Feb 2020Idiopathic pulmonary fibrosis is characterised by abnormal reepithelialisation and remodelling consequent to persistent stimuli or injury. The involvement of oxidative... (Review)
Review
Idiopathic pulmonary fibrosis is characterised by abnormal reepithelialisation and remodelling consequent to persistent stimuli or injury. The involvement of oxidative stress in alveolar injury, inflammation and fibrosis development has been suggested. Increased concentrations of lipid peroxidation products, oxidised proteins and an altered antioxidant enzyme status with the depletion of glutathione, the most abundant low-molecular-weight antioxidant, have often been reported in epithelial lining fluid of IPF patients. This review describes the sources of free radical generation, ROS-induced signalling pathways and mechanisms of oxidative stress damages in the pathogenesis of idiopathic pulmonary fibrosis.
Topics: Animals; Antioxidants; Glutathione; Humans; Idiopathic Pulmonary Fibrosis; Lipid Peroxidation; Lung; Oxidative Stress; Protein Carbonylation; Reactive Oxygen Species; Signal Transduction
PubMed: 31297749
DOI: 10.1007/s10753-019-01059-1 -
Respiratory Medicine Jan 2022Pleuroparenchymal fibroelastosis (PPFE) is a rare, generally idiopathic form of interstitial pneumonia with unique clinical, radiological and histopathological features.... (Review)
Review
Pleuroparenchymal fibroelastosis (PPFE) is a rare, generally idiopathic form of interstitial pneumonia with unique clinical, radiological and histopathological features. It is named after the presence of upper lobe pleural and subjacent parenchymal fibrosis, with accompanying elastic fibers. Although it is usually an idiopathic disease, it has been linked to other co-existent diseases. Diagnostic suspicion of PPFE is based on the identification of typical abnormalities on chest CT scan, which are prevailingly located in the upper lobes, adjacent to the apex of the lungs. Diagnosis can be confirmed by histological analysis, although biopsy is not always feasible. The disease is generally progressive, but not uniformly. The course of the disease is frequently slow and involves a progressive loss of upper lobe volume, which results in platythorax, associated with a significant reduction of body mass. PPFE concomitant to other interstitial lung diseases is associated with a poorer prognosis. The disease occasionally progresses rapidly causing irreversible respiratory insufficiency, which leads to death. Currently, there is no effective pharmacological therapy available, and lung transplantation is the best therapeutic option. The purpose of this review is to draw the attention to PPFE, describe its clinical, radiological and histopathological features, analyze its diagnostic criteria, and provide an update on the management of the disease.
Topics: Humans; Lung; Lung Diseases, Interstitial; Lung Transplantation; Pleura; Tomography, X-Ray Computed
PubMed: 33992495
DOI: 10.1016/j.rmed.2021.106437 -
International Journal of Molecular... Aug 2023Lung fibrosis is a progressive fatal disease in which deregulated wound healing of lung epithelial cells drives progressive fibrotic changes. Persistent lung injury due... (Review)
Review
Lung fibrosis is a progressive fatal disease in which deregulated wound healing of lung epithelial cells drives progressive fibrotic changes. Persistent lung injury due to oxidative stress and chronic inflammation are central features of lung fibrosis. Chronic cigarette smoking causes oxidative stress and is a major risk factor for lung fibrosis. The objective of this manuscript is to develop an adverse outcome pathway (AOP) that serves as a framework for investigation of the mechanisms of lung fibrosis due to lung injury caused by inhaled toxicants, including cigarette smoke. Based on the weight of evidence, oxidative stress is proposed as a molecular initiating event (MIE) which leads to increased secretion of proinflammatory and profibrotic mediators (key event 1 (KE1)). At the cellular level, these proinflammatory signals induce the recruitment of inflammatory cells (KE2), which in turn, increase fibroblast proliferation and myofibroblast differentiation (KE3). At the tissue level, an increase in extracellular matrix deposition (KE4) subsequently culminates in lung fibrosis, the adverse outcome. We have also defined a new KE relationship between the MIE and KE3. This AOP provides a mechanistic platform to understand and evaluate how persistent oxidative stress from lung injury may develop into lung fibrosis.
Topics: Humans; Pulmonary Fibrosis; Adverse Outcome Pathways; Lung Injury; Lung; Oxidative Stress; Fibrosis
PubMed: 37569865
DOI: 10.3390/ijms241512490 -
Medical Physics Apr 2021Computed tomography (CT)-derived ventilation methods compute respiratory induced volume changes as a surrogate for pulmonary ventilation. Currently, there are no known...
PURPOSE
Computed tomography (CT)-derived ventilation methods compute respiratory induced volume changes as a surrogate for pulmonary ventilation. Currently, there are no known methods to derive perfusion information from noncontrast CT. We introduce a novel CT-Perfusion (CT-P) method for computing the magnitude mass changes apparent on dynamic noncontrast CT as a surrogate for pulmonary perfusion.
METHODS
CT-Perfusion is based on a mass conservation model which describes the unknown mass change as a linear combination of spatially corresponding inhale and exhale HU estimated voxel densities. CT-P requires a deformable image registration (DIR) between the inhale/exhale lung CT pair, a preprocessing lung volume segmentation, and an estimate for the Jacobian of the DIR transformation. Given this information, the CT-P image, which provides the magnitude mass change for each voxel within the lung volume, is formulated as the solution to a constrained linear least squares problem defined by a series of subregional mean magnitude mass change measurements. Similar to previous robust CT-ventilation methods, the amount of uncertainty in a subregional sample mean measurement is related to measurement resolution and can be characterized with respect to a tolerance parameter . Spatial Spearman correlation between single photon emission CT perfusion (SPECT-P) and the proposed CT-P method was assessed in two patient cohorts via a parameter sweep of . The first cohort was comprised of 15 patients diagnosed with pulmonary embolism (PE) who had SPECT-P and 4DCT imaging acquired within 24 h of PE diagnosis. The second cohort was comprised of 15 nonsmall cell lung cancer patients who had SPECT-P and 4DCT images acquired prior to radiotherapy. For each test case, CT-P images were computed for 30 different uncertainty parameter values, uniformly sampled from the range [0.01, 0.125], and the Spearman correlation between the SPECT-P and the resulting CT-P images were computed.
RESULTS
The median correlations between CT-P and SPECT-P taken over all 30 test cases ranged between 0.49 and 0.57 across the parameter sweep. For the optimal tolerance τ = 0.0385, the CT-P and SPECT-P correlations across all 30 test cases ranged between 0.02 and 0.82. A one-sample sign test was applied separately to the PE and lung cancer cohorts. A low Spearmen correlation of 15% was set as the null median value and two-sided alternative was tested. The PE patients showed a median correlation of 0.57 (IQR = 0.305). One-sample sign test was statistically significant with 96.5 % confidence interval: 0.20-0.63, P < 0.00001. Lung cancer patients had a median correlation of 0.57(IQR = 0.230). Again, a one-sample sign test for median was statistically significant with 96.5 percent confidence interval: 0.45-0.71, P < 0.00001.
CONCLUSION
CT-Perfusion is the first mechanistic model designed to quantify magnitude blood mass changes on noncontrast dynamic CT as a surrogate for pulmonary perfusion. While the reported correlations with SPECT-P are promising, further investigation is required to determine the optimal CT acquisition protocol and numerical method implementation for CT-P imaging.
Topics: Carcinoma, Non-Small-Cell Lung; Four-Dimensional Computed Tomography; Humans; Lung; Lung Neoplasms; Perfusion; Pulmonary Ventilation; Tomography, Emission-Computed, Single-Photon
PubMed: 33608933
DOI: 10.1002/mp.14792 -
Cancer Cytopathology Jun 2020Sclerosing pneumocytoma (SP) is a rare, benign pulmonary neoplasm. To the authors' knowledge, the current study is the first to evaluate the cytomorphology and...
BACKGROUND
Sclerosing pneumocytoma (SP) is a rare, benign pulmonary neoplasm. To the authors' knowledge, the current study is the first to evaluate the cytomorphology and immunoprofile of SP in a series.
METHODS
A total of 9 fine-needle aspiration cases of SP (7 of which were computed tomography guided and 2 of which were endobronchial ultrasound guided) including histopathology and immunohistochemistry were collected from 5 institutions.
RESULTS
The female-to-male ratio was 3.5:1, and the mean age of the patients was 54 years (range, 27-73 years). All cases presented as lung nodules, with a mean size of 2.2 cm (range, 1.1-5 cm), and were interpreted as atypical on rapid on-site evaluation. The final diagnoses were favor adenocarcinoma (1 case), well-differentiated lung adenocarcinoma (2 cases), low-grade epithelial neoplasm (2 cases), and sclerosing pneumocytoma (4 cases). Samples were moderately cellular, and consisted of round epithelioid cells with clear cell features, columnar cells, and spindle cells. A papillary arrangement with prominent hyalinized fibrovascular cores was the most common architectural pattern, followed by flat sheets and acinar formations. Tumor cells demonstrated mild, focally moderate nuclear pleomorphism with prominent nucleoli, hyperchromasia, nuclear elongation, nuclear overlap, and occasional nuclear inclusions and grooves. The background consisted of foamy macrophages (9 cases), hemosiderin pigment (6 cases), and lymphoid aggregates (3 cases) with no mitoses and/or necrosis. The surface cells and underlying round cells were positive for both thyroid transcription factor 1 and epithelial membrane antigen in all cases, which was the most notable immunohistochemical finding.
CONCLUSIONS
Cytomorphological findings of SP overlap with those of well-differentiated lung adenocarcinoma. Awareness of these cytomorphologic findings and the distinct immunoprofile of the 2 cell types found in SP should prevent a misdiagnosis and aggressive treatment.
Topics: Adenocarcinoma; Adult; Aged; Biopsy, Fine-Needle; Cytodiagnosis; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Lung; Lung Neoplasms; Male; Middle Aged; Pulmonary Sclerosing Hemangioma; Thyroid Nuclear Factor 1
PubMed: 32022435
DOI: 10.1002/cncy.22251 -
Saudi Medical Journal Oct 2022To present an unusual and a rare pulmonary affection by coronavirus disease-19 (COVID-19), in which only one lung is affected. Coronavirus disease-19 attacks the lungs... (Review)
Review
To present an unusual and a rare pulmonary affection by coronavirus disease-19 (COVID-19), in which only one lung is affected. Coronavirus disease-19 attacks the lungs and interferes seriously with their functions. The attack is usually bilaterally, while a uni lateral pulmonary affection is unusual. The presentation, both clinical and radiological findings, bronchoscopy appearance, the strange operative findings of the resected mass, the uneventful post-operative course, in addition to the histopathological report, will be presented.In conclusion, unilateral lung affection is unusual and post-viral pneumonia COVID-19 should be considered as a possible aftermath, which may not be uncommon in Iraq.
Topics: Humans; COVID-19; Pneumonia, Viral; Lung; Bronchoscopy; Iraq
PubMed: 36261211
DOI: 10.15537/smj.2022.43.10.20220294 -
EBioMedicine Nov 2022COVID-19 is characterized by a heterogeneous clinical presentation, ranging from mild symptoms to severe courses of disease. 9-20% of hospitalized patients with severe...
BACKGROUND
COVID-19 is characterized by a heterogeneous clinical presentation, ranging from mild symptoms to severe courses of disease. 9-20% of hospitalized patients with severe lung disease die from COVID-19 and a substantial number of survivors develop long-COVID. Our objective was to provide comprehensive insights into the pathophysiology of severe COVID-19 and to identify liquid biomarkers for disease severity and therapy response.
METHODS
We studied a total of 85 lungs (n = 31 COVID autopsy samples; n = 7 influenza A autopsy samples; n = 18 interstitial lung disease explants; n = 24 healthy controls) using the highest resolution Synchrotron radiation-based hierarchical phase-contrast tomography, scanning electron microscopy of microvascular corrosion casts, immunohistochemistry, matrix-assisted laser desorption ionization mass spectrometry imaging, and analysis of mRNA expression and biological pathways. Plasma samples from all disease groups were used for liquid biomarker determination using ELISA. The anatomic/molecular data were analyzed as a function of patients' hospitalization time.
FINDINGS
The observed patchy/mosaic appearance of COVID-19 in conventional lung imaging resulted from microvascular occlusion and secondary lobular ischemia. The length of hospitalization was associated with increased intussusceptive angiogenesis. This was associated with enhanced angiogenic, and fibrotic gene expression demonstrated by molecular profiling and metabolomic analysis. Increased plasma fibrosis markers correlated with their pulmonary tissue transcript levels and predicted disease severity. Plasma analysis confirmed distinct fibrosis biomarkers (TSP2, GDF15, IGFBP7, Pro-C3) that predicted the fatal trajectory in COVID-19.
INTERPRETATION
Pulmonary severe COVID-19 is a consequence of secondary lobular microischemia and fibrotic remodelling, resulting in a distinctive form of fibrotic interstitial lung disease that contributes to long-COVID.
FUNDING
This project was made possible by a number of funders. The full list can be found within the Declaration of interests / Acknowledgements section at the end of the manuscript.
Topics: Humans; COVID-19; Lung; Lung Diseases, Interstitial; Fibrosis; Biomarkers; Ischemia; Post-Acute COVID-19 Syndrome
PubMed: 36206625
DOI: 10.1016/j.ebiom.2022.104296 -
Radiographics : a Review Publication of... Jul 2023Diffuse alveolar damage (DAD), which represents the pathologic changes seen after acute lung injury, is caused by damage to all three layers of the alveolar wall and can...
Diffuse alveolar damage (DAD), which represents the pathologic changes seen after acute lung injury, is caused by damage to all three layers of the alveolar wall and can ultimately result in alveolar collapse with loss of the normal pulmonary architecture. DAD has an acute phase that predominantly manifests as airspace disease at CT owing to filling of the alveoli with cells, plasma fluids, and hyaline membranes. DAD then evolves into a heterogeneous organizing phase, with mixed airspace and interstitial disease characterized by volume loss, architectural distortion, fibrosis, and parenchymal loss. Patients with DAD have a severe clinical course and typically require prolonged mechanical ventilation, which may result in ventilator-induced lung injury. In those patients who survive DAD, the lungs will remodel over time, but most will have residual findings at chest CT. Organizing pneumonia (OP) is a descriptive term for a histologic pattern characterized by intra-alveolar fibroblast plugs. The significance and pathogenesis of OP are controversial. Some authors regard it as part of a spectrum of acute lung injury, while others consider it a marker of acute or subacute lung injury. At CT, OP manifests with various forms of airspace disease that are most commonly bilateral and relatively homogeneous in appearance at individual time points. Patients with OP most often have a mild clinical course, although some may have residual findings at CT. In patients with DAD and OP, imaging findings can be combined with clinical information to suggest the diagnosis in many cases, with biopsy reserved for difficult cases with atypical findings or clinical manifestations. To best participate in the multidisciplinary approach to patients with lung injury, radiologists must not only recognize these entities but also describe them with consistent and meaningful terminology, examples of which are emphasized in the article. RSNA, 2023 See the invited commentary by Kligerman et al in this issue. Quiz questions for this article are available in the supplemental material.
Topics: Humans; Lung; Pulmonary Alveoli; Pneumonia; Disease Progression; Tomography, X-Ray Computed; Acute Lung Injury
PubMed: 37289644
DOI: 10.1148/rg.220176 -
Pediatric Radiology Sep 2022Congenital lung lesions are a rare group of developmental pulmonary abnormalities that are often first identified prenatally on routine second-trimester US. Congenital... (Review)
Review
Congenital lung lesions are a rare group of developmental pulmonary abnormalities that are often first identified prenatally on routine second-trimester US. Congenital pulmonary airway malformation (CPAM) is the most common anomaly while others include bronchopulmonary sequestration, congenital lobar overinflation, bronchogenic cyst and bronchial atresia. Clinical presentation is highly variable, ranging from apparent in utero resolution to severe mass effect with resultant hydrops fetalis and fetal demise. Differentiation among these lesions can be challenging because overlapping imaging features are often present. The roles of the radiologist are to identify key imaging findings that help in diagnosing congenital lung lesions and to recognize any ominous features that might require prenatal or perinatal intervention. High-resolution US and complementary rapid-acquisition fetal MRI provide valuable information necessary for lesion characterization. Postnatal US and CT angiography are helpful for lesion evaluation and for possible surgical planning. This article reviews the embryology of the lungs, the normal prenatal imaging appearance of the thorax and its contents, and the prenatal and neonatal imaging characteristics, prognosis and management of various congenital lung lesions.
Topics: Bronchopulmonary Sequestration; Cystic Adenomatoid Malformation of Lung, Congenital; Female; Humans; Infant, Newborn; Lung; Pneumonia; Pregnancy; Respiratory System Abnormalities; Ultrasonography, Prenatal
PubMed: 36002772
DOI: 10.1007/s00247-022-05465-w -
Chinese Medical Journal May 2018Exposure to halogens, such as chlorine or bromine, results in environmental and occupational hazard to the lung and other organs. Chlorine is highly toxic by inhalation,... (Review)
Review
OBJECTIVE
Exposure to halogens, such as chlorine or bromine, results in environmental and occupational hazard to the lung and other organs. Chlorine is highly toxic by inhalation, leading to dyspnea, hypoxemia, airway obstruction, pneumonitis, pulmonary edema, and acute respiratory distress syndrome (ARDS). Although bromine is less reactive and oxidative than chlorine, inhalation also results in bronchospasm, airway hyperresponsiveness, ARDS, and even death. Both halogens have been shown to damage the systemic circulation and result in cardiac injury as well. There is no specific antidote for these injuries since the mechanisms are largely unknown.
DATA SOURCES
This review was based on articles published in PubMed databases up to January, 2018, with the following keywords: "chlorine," "bromine," "lung injury," and "ARDS."
STUDY SELECTION
The original articles and reviews including the topics were the primary references.
RESULTS
Based on animal studies, it is found that inhaled chlorine will form chlorine-derived oxidative products that mediate postexposure toxicity; thus, potential treatments will target the oxidative stress and inflammation induced by chlorine. Antioxidants, cAMP-elevating agents, anti-inflammatory agents, nitric oxide-modulating agents, and high-molecular-weight hyaluronan have shown promising effects in treating acute chlorine injury. Elevated free heme level is involved in acute lung injury caused by bromine inhalation. Hemopexin, a heme-scavenging protein, when administered postexposure, decreases lung injury and improves survival.
CONCLUSIONS
At present, there is an urgent need for additional research to develop specific therapies that target the basic mechanisms by which halogens damage the lungs and systemic organs.
Topics: Acute Lung Injury; Animals; Chlorine; Halogens; Humans; Lung; Respiratory Distress Syndrome
PubMed: 29722341
DOI: 10.4103/0366-6999.231515