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COPD Jun 2009Emphysema is characterized by the destruction of alveolar parenchymal tissue and the concordant loss of lung epithelial cells, endothelial cells, and interstitial... (Review)
Review
Emphysema is characterized by the destruction of alveolar parenchymal tissue and the concordant loss of lung epithelial cells, endothelial cells, and interstitial mesenchymal cells. Key features in the pathobiology of emphysema include inflammation, alveolar epithelial cell injury/apoptosis, and excessive activation of extracellular matrix (ECM) proteases. Mesenchymal cells are versatile connective tissue cells that are critical effectors of wound-repair. The excessive loss of connective tissue and the destruction of alveolar septae in emphysema suggest that the mesenchymal cell reparative response to epithelial injury is impaired. Yet, the mechanisms regulating mesenchymal cell (dys)function in emphysema remain poorly understood. We propose that mesenchymal cell fate, modulated by transforming growth factor beta-1 (TGF-beta1) and the balance of ECM proteases and antiproteases, is a critical determinant of the emphysema phenotype. We examine emphysema in the context of wound-repair responses, with a focus on the regulation of mesenchymal cell fate and phenotype. We discuss the emerging evidence supporting that genetic factors, inflammation and environmental factors, including cigarette smoke itself, collectively impair mesenchymal cell survival and function, thus contributing to the pathogenesis of emphysema.
Topics: Epithelial Cells; Fibroblasts; Humans; Mesoderm; Phenotype; Pulmonary Emphysema; Smoking; Transforming Growth Factor beta1
PubMed: 19811376
DOI: 10.1080/15412550902905953 -
Proceedings of the American Thoracic... May 2008Potential candidates for lung volume reduction surgery should undergo extensive evaluation and preparation to minimize perioperative risks and optimize surgical... (Review)
Review
Potential candidates for lung volume reduction surgery should undergo extensive evaluation and preparation to minimize perioperative risks and optimize surgical outcomes. Initial screening includes spirometry, diffusion capacity, lung volumes by body plethysmography, and high-resolution computerized tomography scanning. Patients who have been successfully screened must complete a preoperative pulmonary rehabilitation program of 6-10 weeks duration. During the pulmonary rehabilitation program, medical therapy should be maximized. Postrehabilitation studies include cardiopulmonary exercise testing, arterial blood gas analysis, oxygen titration, six-minute walk, and cardiac testing. The evaluation process aims at defining the severity and distribution of emphysema and attempts to eliminate those who do not meet criteria outlined by the National Emphysema Treatment Trial. Optimal candidates have upper-lobe-predominant emphysema and acceptable operative risks.
Topics: Blood Gas Analysis; Exercise Test; Humans; Patient Selection; Pneumonectomy; Postoperative Complications; Preoperative Care; Pulmonary Emphysema; Randomized Controlled Trials as Topic; Respiratory Function Tests; Risk Factors; Tomography, X-Ray Computed
PubMed: 18453350
DOI: 10.1513/pats.200707-087ET -
PloS One 2020Combined pulmonary fibrosis with emphysema (CPFE) is a clinically meaningful syndrome characterized by coexisting upper-lobe emphysema and lower-lobe interstitial...
Objective quantitative multidetector computed tomography assessments in patients with combined pulmonary fibrosis with emphysema: Relationship with pulmonary function and clinical events.
BACKGROUND
Combined pulmonary fibrosis with emphysema (CPFE) is a clinically meaningful syndrome characterized by coexisting upper-lobe emphysema and lower-lobe interstitial fibrosis. However, ambiguous diagnostic criteria and, particularly, the absence of objective methods to quantify emphysematous/fibrotic lesions in patients with CPFE confound the interpretation of the pathophysiology of this syndrome. We analyzed the relationship between objectively quantified computed tomography (CT) measurements and the results of pulmonary function testing (PFT) and clinical events in CPFE patients.
MATERIALS AND METHODS
We enrolled 46 CPFE patients who underwent CT and PFT. The extent of emphysematous lesions was obtained by calculating the percent of low attenuation area (%LAA). The extent of fibrotic lesions was calculated as the percent of high attenuation area (%HAA). %LAA and %HAA values were combined to yield the percent of abnormal area (%AA). We assessed the relationships between CT parameters and other clinical indices, including PFT results. Multivariate analysis was performed to examine the association between the CT parameters and clinical events.
RESULTS
A greater negative correlation with percent predicted diffusing capacity of the lung for carbon monoxide (DLCO %predicted) existed for %AA (r = -0.73, p < 0.001) than for %LAA or %HAA alone. The %HAA value was inversely correlated with percent predicted forced vital capacity (r = -0.48, p < 0.001), percent predicted total lung capacity (r = -0.48, p < 0.01), and DLCO %predicted (r = -0.47, p < 0.01). Multivariate logistic regression analysis found that %AA showed the strongest association with hospitalization events (odds ratio = 1.20, 95% confidence interval = 1.01-1.54, p = 0.029).
CONCLUSION
Quantitative CT measurements reflected deterioration in pulmonary function and were associated with hospitalization in patients with CPFE. This approach could serve as a useful method to determine the extent of lung morphology, pathophysiology, and the clinical course of patients with CPFE.
Topics: Aged; Female; Humans; Lung; Middle Aged; Multidetector Computed Tomography; Pulmonary Emphysema; Pulmonary Fibrosis; Respiratory Function Tests
PubMed: 32941486
DOI: 10.1371/journal.pone.0239066 -
PloS One 2016Emphysema and idiopathic pulmonary fibrosis (IPF) present either per se or coexist in combined pulmonary fibrosis and emphysema (CPFE). Serum surfactant proteins (SPs)...
INTRODUCTION
Emphysema and idiopathic pulmonary fibrosis (IPF) present either per se or coexist in combined pulmonary fibrosis and emphysema (CPFE). Serum surfactant proteins (SPs) A, B, C and D levels may reflect lung damage. We evaluated serum SP levels in healthy controls, emphysema, IPF, and CPFE patients and their associations to disease severity and survival.
METHODS
122 consecutive patients (31 emphysema, 62 IPF, and 29 CPFE) and 25 healthy controls underwent PFTs, ABG-measurements, 6MWT and chest HRCT. Serum levels of SPs were measured. Patients were followed-up for 1-year.
RESULTS
SP-A and SP-D levels differed between groups (p = 0.006 and p<0.001 respectively). In post-hoc analysis, SP-A levels differed only between controls and CPFE (p<0.05) and CPFE and emphysema (p<0.05). SP-D differed between controls and IPF or CPFE (p<0.001 for both comparisons). In IPF SP-B correlated to pulmonary function while SP-A, correlated to the Composite Physiological Index (CPI). Controls current smokers had higher SP-A and SP-D levels compared to non-smokers (p = 0.026 and p = 0.023 respectively). SP-D levels were higher in CPFE patients with extended emphysema (p = 0.042). In patients with IPF, SP-B levels at the upper quartile of its range (≥26 ng/mL) presented a weak association with reduced survival (p = 0.05).
CONCLUSION
In conclusion, serum SP-A and SP-D levels were higher where fibrosis exists or coexists and related to disease severity, suggesting that serum SPs relate to alveolar damage in fibrotic lungs and may reflect either local overproduction or overleakage. The weak association between high levels of SP-B and survival needs further validation in clinical trials.
Topics: Aged; Case-Control Studies; Female; Fibrosis; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Phenotype; Physical Fitness; Prognosis; Pulmonary Emphysema; Pulmonary Fibrosis; Pulmonary Surfactant-Associated Proteins; Respiratory Function Tests; Smoking
PubMed: 27337142
DOI: 10.1371/journal.pone.0157789 -
Cell and Tissue Research Mar 2017The cellular mechanisms that result in the initiation and progression of emphysema are clearly complex. A growing body of human data combined with discoveries from mouse... (Review)
Review
The cellular mechanisms that result in the initiation and progression of emphysema are clearly complex. A growing body of human data combined with discoveries from mouse models utilizing cigarette smoke exposure or protease administration have improved our understanding of emphysema development by implicating specific cell types that may be important for the pathophysiology of chronic obstructive pulmonary disease. The most important aspects of emphysematous damage appear to be oxidative or protease stress and sustained macrophage activation and infiltration of other immune cells leading to epithelial damage and cell death. Despite the identification of these associated processes and cell types in many experimental studies, the reasons why cigarette smoke and other pollutants result in unremitting damage instead of injury resolution are still uncertain. We propose an important role for macrophages in the sequence of events that lead and maintain this chronic tissue pathologic process in emphysema. This model involves chronic activation of macrophage subtypes that precludes proper healing of the lung. Further elucidation of the cross-talk between epithelial cells that release damage-associated signals and the cellular immune effectors that respond to these cues is a critical step in the development of novel therapeutics that can restore proper lung structure and function to those afflicted with emphysema.
Topics: Animals; Disease Models, Animal; Immunity; Inflammation; Mice; Models, Biological; Pulmonary Emphysema
PubMed: 28164246
DOI: 10.1007/s00441-016-2567-7 -
Biological & Pharmaceutical Bulletin Sep 2009Exposure of animals to cigarette smoke for longer than 3 months leads to the development of chronic obstructive pulmonary disease (COPD) showing pulmonary emphysema. We... (Comparative Study)
Comparative Study
Exposure of animals to cigarette smoke for longer than 3 months leads to the development of chronic obstructive pulmonary disease (COPD) showing pulmonary emphysema. We attempted to create a COPD model with emphysema that could be established in a shorter period of time. Guinea pigs were intratracheally treated once a day on days 0-3, 5-8, 10-13 and 15-18 with a cigarette smoke solution (CSS), which was prepared by bubbling a stream of smoke into saline. Additionally, lipopolysaccharide (LPS) was administered intratracheally as an exacerbation factor on days 4, 9 and 14. By day 19, there was a gradual elevation of specific airway resistance (sRaw). In addition, both residual volume and functional residual capacity were found to be significantly higher on day 19. In the lungs, there was a marked increase in leukocytes, especially neutrophils. Histologically, we observed epithelial hyperplasia and emphysema. On the other hand, daily oral administration of theophylline during the administration of CSS and LPS suppressed the sRaw increase and the epithelial hyperplasia, but not other functional structural changes. In conclusion, we established an experimental COPD model in guinea pigs by using intratracheal instillations of CSS and LPS over a considerably shorter term than has been reported for other models.
Topics: Animals; Guinea Pigs; Lipopolysaccharides; Male; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Smoke; Solutions; Nicotiana
PubMed: 19721232
DOI: 10.1248/bpb.32.1559 -
Trends in Molecular Medicine Apr 2009Bronchopulmonary dysplasia of the premature neonate and emphysema of the adult lung are common diseases that are characterized by increased airspace size and respiratory... (Review)
Review
Bronchopulmonary dysplasia of the premature neonate and emphysema of the adult lung are common diseases that are characterized by increased airspace size and respiratory insufficiency and that presently lack efficient treatment. Although the former leads to impaired alveolar development and the latter to alveolar destruction, they have striking similarities in their pathophysiology, including the precipitating effect of oxidative stress, sustained inflammation, enhanced apoptosis, protease-antiprotease imbalance, elastic fiber deterioration and altered microvascularization. This review aims to comparatively analyze their molecular mechanisms to try identify common therapeutic targets. The recent discovery that alveolar developmental and maintenance programs share the same signal molecules and pathways, together with considerable increase in their understanding, have facilitated the development of common innovative strategies that have started to be tested in experimental models and pilot clinical studies.
Topics: Animals; Apoptosis; Bronchopulmonary Dysplasia; Cellular Senescence; Humans; Infant, Newborn; Inflammation; Oxidative Stress; Pulmonary Emphysema
PubMed: 19303361
DOI: 10.1016/j.molmed.2009.02.003 -
The European Respiratory Journal Jul 2010
Topics: Bronchoscopy; Fibrin Tissue Adhesive; Humans; Pneumonectomy; Pulmonary Emphysema; Radiography
PubMed: 20595161
DOI: 10.1183/09031936.00199309 -
Respiratory Care Mar 2012
Topics: Aged; Comorbidity; Humans; Male; Pulmonary Emphysema; Pulmonary Fibrosis; Respiratory Function Tests; Tomography, X-Ray Computed
PubMed: 22004839
DOI: 10.4187/respcare.01319 -
The Journal of the American Osteopathic... Aug 2017
Topics: Adult; Humans; Male; Pulmonary Emphysema; Radiography, Thoracic; Syndrome
PubMed: 28759097
DOI: 10.7556/jaoa.2017.106