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Sample records for emphysema show independent

  1. MEDIASTINAL EMPHYSEMA

    PubMed Central

    Summers, John E.

    1959-01-01

    Mediastinal emphysema may occur due to migration of air from the lungs, from the esophagus or tracheobronchial tree and from the abdomen. Of especial interest is the mechanism starting with the rupture of the perivascular alveoli due to a rapid decrease in intrathoracic pressure from any cause, the development of pulmonary interstitial emphysema and migration of the air into the mediastinum. In one case the patient had severe interstitial emphysema of the left lung, mediastinal emphysema and subcutaneous emphysema without pneumothorax and rapid improvement followed tracheotomy. In another case the patient had interstitial emphysema of the left lung that did not progress to mediastinal emphysema and subcutaneous emphysema. Pneumothorax was not present. Recovery was more rapid than in the first patient. ImagesFigure 1 (Case 1).Figure 2 (Case 1).Figure 3 (Case 1).Figure 4 (Case 1).Figure 5 (Case 1).Figure 7 (Case 2).Figure 6 (Case 2).Figure 8 (Case 2). PMID:13651959

  2. [Dissecting emphysema].

    PubMed

    Gurtner, B

    1991-10-29

    We report six observations of pneumomediastinum, due to dental extraction and use of high speed air turbine drill, aspiration of a nut with air trapping, labor in delivery, status asthmaticus, mechanical ventilation, and rectal perforation. Some patients showed widespread extension of dissecting air presenting as subcutaneous emphysema, pneumopericardium or pneumoretroperitoneum. The mediastinum is thought to be a central pump, the diaphragm and the lung acting like bellows, which distribute interstitial air from and into communicating layers on both sides of the diaphragm. Pneumomediastinum does not prove an air leak in the thoracic cage nor does pneumoretroperitoneum absolutely indicate bowel rupture. Review of the literature.

  3. [Epidural emphysema complicating bronchial asthma].

    PubMed

    Rouetbi, N; Ben Saad, A; Joobeur, S; Skhiri, N; Cheikh Mhamed, S; Mribah, H; El Kamel, A

    2012-12-01

    Epidural emphysema is an exceptional complication of bronchial asthma, revealed by an incidental finding in chest tomography. We report a case of a 21-year-old man admitted with asthma attack complicated by subcutaneous and mediastinal emphysema. Chest tomography confirmed the mediastinal emphysema and also revealed the epidural emphysema within the vertebral canal. Neurological examination was negative. The patient showed complete recovery 10days after the onset of symptoms. The epidural emphysema is a rare complication during asthma attacks. The benignity of this complication should not require a systematic chest tomography.

  4. Impaired colony-forming capacity of circulating endothelial progenitor cells in patients with emphysema.

    PubMed

    Kim, Eun-Kyung; Lee, Ji-Hyun; Jeong, Hye-Cheol; Oh, Doyeon; Hwang, Seong-Gyu; Cho, Yong-Wook; Lee, Seon-Ju; Oh, Yeon-Mok; Lee, Sang-Do

    2012-01-01

    Chronic obstructive pulmonary disease (COPD) is classified into emphysema and chronic bronchitis, which are thought to result from different pathophysiological pathways. Smoking-induced lung parenchymal destruction and inadequate repair are involved in the pathogenesis of emphysema. In addition, decreased expression of vascular endothelial growth factor and increased endothelial cell apoptosis in the lung may participate in emphysema pathogenesis. As stem cells, circulating endothelial progenitor cells (EPCs) may play a key role in the maintenance of vascular integrity by replacing and repairing the damaged endothelial cells in the tissues. To determine whether the lack of appropriate repair by circulating EPCs in cases of smoking-induced endothelial cell injury participates in emphysema pathogenesis, we determined the association between the colony-forming or migratory capacity of circulating EPCs and the presence of emphysema in 51 patients with COPD. The patients were divided into emphysema (n = 23) and non-emphysema groups (n = 28) based on high-resolution computed tomography. Twenty-two smokers with normal lung function and 14 normal non-smokers served as controls. Circulating EPCs isolated from patients with emphysema showed significantly lower colony-forming units (CFUs) than those from patients with non-emphysema group, smokers with normal lung function, and normal non-smokers. EPCs from patients with emphysema showed significantly lower migratory capacity than those from normal non-smoking controls (p < 0.05). On multivariate analysis, the EPC-CFU was independently associated with emphysema (OR 0.944, 95% CI = 0.903-0.987, p = 0.011). Thus, impaired functions of circulating EPCs may contribute to the development of emphysema.

  5. New World cattle show ancestry from multiple independent domestication events

    PubMed Central

    McTavish, Emily Jane; Decker, Jared E.; Schnabel, Robert D.; Taylor, Jeremy F.; Hillis, David M.

    2013-01-01

    Previous archeological and genetic research has shown that modern cattle breeds are descended from multiple independent domestication events of the wild aurochs (Bos primigenius) ∼10,000 y ago. Two primary areas of domestication in the Middle East/Europe and the Indian subcontinent resulted in taurine and indicine lines of cattle, respectively. American descendants of cattle brought by European explorers to the New World beginning in 1493 generally have been considered to belong to the taurine lineage. Our analyses of 47,506 single nucleotide polymorphisms show that these New World cattle breeds, as well as many related breeds of cattle in southern Europe, actually exhibit ancestry from both the taurine and indicine lineages. In this study, we show that, although European cattle are largely descended from the taurine lineage, gene flow from African cattle (partially of indicine origin) contributed substantial genomic components to both southern European cattle breeds and their New World descendants. New World cattle breeds, such as Texas Longhorns, provide an opportunity to study global population structure and domestication in cattle. Following their introduction into the Americas in the late 1400s, semiferal herds of cattle underwent between 80 and 200 generations of predominantly natural selection, as opposed to the human-mediated artificial selection of Old World breeding programs. Our analyses of global cattle breed population history show that the hybrid ancestry of New World breeds contributed genetic variation that likely facilitated the adaptation of these breeds to a novel environment. PMID:23530234

  6. New World cattle show ancestry from multiple independent domestication events.

    PubMed

    McTavish, Emily Jane; Decker, Jared E; Schnabel, Robert D; Taylor, Jeremy F; Hillis, David M

    2013-04-09

    Previous archeological and genetic research has shown that modern cattle breeds are descended from multiple independent domestication events of the wild aurochs (Bos primigenius) ∼10,000 y ago. Two primary areas of domestication in the Middle East/Europe and the Indian subcontinent resulted in taurine and indicine lines of cattle, respectively. American descendants of cattle brought by European explorers to the New World beginning in 1493 generally have been considered to belong to the taurine lineage. Our analyses of 47,506 single nucleotide polymorphisms show that these New World cattle breeds, as well as many related breeds of cattle in southern Europe, actually exhibit ancestry from both the taurine and indicine lineages. In this study, we show that, although European cattle are largely descended from the taurine lineage, gene flow from African cattle (partially of indicine origin) contributed substantial genomic components to both southern European cattle breeds and their New World descendants. New World cattle breeds, such as Texas Longhorns, provide an opportunity to study global population structure and domestication in cattle. Following their introduction into the Americas in the late 1400s, semiferal herds of cattle underwent between 80 and 200 generations of predominantly natural selection, as opposed to the human-mediated artificial selection of Old World breeding programs. Our analyses of global cattle breed population history show that the hybrid ancestry of New World breeds contributed genetic variation that likely facilitated the adaptation of these breeds to a novel environment.

  7. Variation of quantitative emphysema measurements from CT scans

    NASA Astrophysics Data System (ADS)

    Keller, Brad M.; Reeves, Anthony P.; Henschke, Claudia I.; Barr, R. Graham; Yankelevitz, David F.

    2008-03-01

    Emphysema is a lung disease characterized by destruction of the alveolar air sacs and is associated with long-term respiratory dysfunction. CT scans allow for imaging of the anatomical basis of emphysema, and several measures have been introduced for the quantification of the extent of disease. In this paper we compare these measures for repeatability over time. The measures of interest in this study are emphysema index, mean lung density, histogram percentile, and the fractal dimension. To allow for direct comparisons, the measures were normalized to a 0-100 scale. These measures have been computed for a set of 2,027 scan pairs in which the mean interval between scans was 1.15 years (σ: 93 days). These independent pairs were considered with respect to three different scanning conditions (a) 223 pairs where both were scanned with a 5 mm slice thickness protocol, (b) 695 with the first scanned with the 5 mm protocol and the second with a 1.25 mm protocol, and (c) 1109 pairs scanned both times using a 1.25 mm protocol. We found that average normalized emphysema index and histogram percentiles scores increased by 5.9 and 11 points respectively, while the fractal dimension showed stability with a mean difference of 1.2. We also found, a 7 point bias introduced for emphysema index under condition (b), and that the fractal dimension measure is least affected by scanner parameter changes.

  8. Image Processing Diagnostics: Emphysema

    NASA Astrophysics Data System (ADS)

    McKenzie, Alex

    2009-10-01

    Currently the computerized tomography (CT) scan can detect emphysema sooner than traditional x-rays, but other tests are required to measure more accurately the amount of affected lung. CT scan images show clearly if a patient has emphysema, but is unable by visual scan alone, to quantify the degree of the disease, as it appears merely as subtle, barely distinct, dark spots on the lung. Our goal is to create a software plug-in to interface with existing open source medical imaging software, to automate the process of accurately diagnosing and determining emphysema severity levels in patients. This will be accomplished by performing a number of statistical calculations using data taken from CT scan images of several patients representing a wide range of severity of the disease. These analyses include an examination of the deviation from a normal distribution curve to determine skewness, a commonly used statistical parameter. Our preliminary results show that this method of assessment appears to be more accurate and robust than currently utilized methods which involve looking at percentages of radiodensities in air passages of the lung.

  9. National Emphysema Foundation

    MedlinePlus

    National Emphysema Foundation (NEF) Skip to content Jump to main navigation and login Nav view search Navigation Search Javascript ... ru - free templates joomla Welcome to the National Emphysema Foundation (NEF) This site is for the benefit ...

  10. Severity of pulmonary emphysema and lung cancer: analysis using quantitative lobar emphysema scoring.

    PubMed

    Bae, Kyungsoo; Jeon, Kyung Nyeo; Lee, Seung Jun; Kim, Ho Cheol; Ha, Ji Young; Park, Sung Eun; Baek, Hye Jin; Choi, Bo Hwa; Cho, Soo Buem; Moon, Jin Il

    2016-11-01

    The aim of this study was to determine the relationship between lobar severity of emphysema and lung cancer using automated lobe segmentation and emphysema quantification methods.This study included 78 patients (74 males and 4 females; mean age of 72 years) with the following conditions: pathologically proven lung cancer, available chest computed tomographic (CT) scans for lobe segmentation, and quantitative scoring of emphysema. The relationship between emphysema and lung cancer was analyzed using quantitative emphysema scoring of each pulmonary lobe.The most common location of cancer was the left upper lobe (LUL) (n = 28), followed by the right upper lobe (RUL) (n = 27), left lower lobe (LLL) (n = 13), right lower lobe (RLL) (n = 9), and right middle lobe (RML) (n = 1). Emphysema ratio was the highest in LUL, followed by that in RUL, LLL, RML, and RLL. Multivariate logistic regression analysis revealed that upper lobes (odds ratio: 1.77; 95% confidence interval: 1.01-3.11, P = 0.048) and lobes with emphysema ratio ranked the 1st or the 2nd (odds ratio: 2.48; 95% confidence interval: 1.48-4.15, P < 0.001) were significantly and independently associated with lung cancer development.In emphysema patients, lung cancer has a tendency to develop in lobes with more severe emphysema.

  11. Persistent diffuse pulmonary interstitial emphysema mimicking pulmonary emphysema.

    PubMed

    Demura, Y; Ishizaki, T; Nakanishi, M; Ameshima, S; Itoh, H

    2009-01-01

    A 69-year-old male non-smoker with a history of atopic asthma presented with symptoms suggestive of chronic obstructive pulmonary disease and this appeared to be corroborated by lung function testing and a chest radiograph. However, a chest CT showed no evidence of pulmonary emphysema and instead demonstrated free air along the bronchovascular sheaths indicative of pulmonary interstistial emphysema, possibly caused by repeated prior exacerbations of asthma. His lung function tests and symptoms improved within months of being treated for his airways disease but the CT findings were unchanged after 2 years.

  12. Body height as risk factor for emphysema in COPD

    PubMed Central

    Miniati, Massimo; Bottai, Matteo; Pavlickova, Ivana; Monti, Simonetta

    2016-01-01

    Pulmonary emphysema is a phenotypic component of chronic obstructive pulmonary disease (COPD) which carries substantial morbidity and mortality. We explored the association between emphysema and body height in 726 patients with COPD using computed tomography as the reference diagnostic standard for emphysema. We applied univariate analysis to look for differences between patients with emphysema and those without, and multivariate logistic regression to identify significant predictors of the risk of emphysema. As covariates we included age, sex, body height, body mass index, pack-years of smoking, and forced expiratory volume in one second (FEV1) as percent predicted. The overall prevalence of emphysema was 52%. Emphysemic patients were significantly taller and thinner than non-emphysemic ones, and featured significantly higher pack-years of smoking and lower FEV1 (P < 0.001). The prevalence of emphysema rose linearly by 10-cm increase in body height (r2 = 0.96). In multivariate analysis, the odds of emphysema increased by 5% (95% confidence interval, 3 to 7%) along with one-centimeter increase in body height, and remained unchanged after adjusting for all the potential confounders considered (P < 0.001). The odds of emphysema were not statistically different between males and females. In conclusion, body height is a strong, independent risk factor for emphysema in COPD. PMID:27874046

  13. Emphysema and Airflow Obstruction in Non-Smoking Coal Miners with Pneumoconiosis

    PubMed Central

    Altınsoy, Bülent; Öz, İbrahim İlker; Erboy, Fatma; Tor, Meltem; Atalay, Figen

    2016-01-01

    Background Accumulating evidence shows that functional impairment in subjects with coal workers’ pneumoconiosis (CWP) is principally due to emphysema and airflow obstruction, rather than underlying restrictive mechanisms. However, cigarette smoking has remained a major confounder. The aim of this study was to assess whether coal dust exposure was associated with emphysema and/or airflow obstruction in the absence of smoking history. Material/Method The subjects evaluated for possible pneumoconiosis between 2013 and 2015 were retrospectively enrolled into this study. After excluding those with history of smoking, tuberculosis, or lung cancer, the study population was a total of 57 subjects. The emphysema severity and airflow obstruction were quantified by computed tomographic densitometry analysis and spirometry, respectively. For comparability regarding emphysema, 9 age- and sex-matched nonsmoker (n=9) control subjects without known lung disease were randomly selected from a radiology database. Results Emphysema severity was significantly higher in the CWP group compared with the control group (15% vs. 4%, p<0.001). The median percent emphysema and percentage of those with FEV1/FVC <0.7 was 13% and 37% in subjects with simple CWP and 18% and 67% in subjects with complicated CWP, respectively. Percent emphysema and Perc15 (15th percentile of the attenuation curve) was correlated with FEV1/FVC (r=−0.45, r=−0.47) and FEF25–75 (r=−0.36, r=−0.56), respectively, but not with perfusion score. A linear regression analysis showed that factors associated with emphysema were FEV1/FVC (β=−0.24, p=0.009) and large opacity (β=−3.97, p=0.079), and factors associated with FEV1/FVC were percent emphysema (β=−0.51, p=0.018) and tenure (β=−0.63, p=0.044). Conclusions Our results support the observation that coal dust exposure is associated with emphysema and airflow obstruction, independent of smoking status. PMID:27956734

  14. Camouflaging Facial Emphysema: a new syndrome.

    PubMed

    Martínez-Carpio, Pedro A; del Campillo, Ángel F Bedoya; Leal, María Jesús; Lleopart, Núria; Marrón, María T; Trelles, Mario A

    2012-10-10

    Camouflaging Facial Emphysema, as is defined in this paper, is the result of a simple technique used by the patient to deform his face in order to prevent recognition at a police identity parade. The patient performs two punctures in the mucosa at the rear of the upper lip and, after several Valsalva manoeuvres, manages to deform his face in less than 15 min by inducing subcutaneous facial emphysema. The examination shows an accumulation of air in the face, with no laterocervical, mediastinal or thoracic affectations. The swelling is primarily observed in the eyelids and the orbital and zygomatic regions, whereas it is less prominent in other areas of the face. Patients therefore manage to avoid recognition in properly conducted police identity parades. Only isolated cases of self-induced facial emphysema have been reported to date among psychiatric patients and prison inmates. However, the facial emphysema herein described exhibits specific characteristics of significant medical, deontological, social, police-related, and legal implications.

  15. Cervicofacial subcutaneous and mediastinal emphysema caused by air cooling spray of dental laser.

    PubMed

    Mitsunaga, Sachiyo; Iwai, Toshinori; Aoki, Noriaki; Yamashita, Yosuke; Omura, Susumu; Matsui, Yoshiro; Maegawa, Jiro; Hirota, Makoto; Mitsudo, Kenji; Tohnai, Iwai

    2013-06-01

    Cervicofacial subcutaneous emphysema is a rare complication of dental procedures with an air turbine or syringe, and dentists and oral surgeons sometimes encounter mediastinal emphysema following the presentation of extensive subcutaneous emphysema. Most emphysema occurs incidentally during tooth extraction, restorative treatment, or endodontic treatment, with only a few cases reported of cervicofacial subcutaneous emphysema associated with dental laser treatment. We report a case of cervicofacial subcutaneous and mediastinal emphysema caused by the air cooling spray of dental laser during dental treatment in a 76-year-old woman. After she underwent dental laser treatment, cervicofacial swelling was noted and she was referred to our department. Computed tomography showed both cervicofacial subcutaneous emphysema and mediastinal emphysema. Antibiotics were administered prophylactically and the emphysema disappeared 5 days after the dental laser treatment, without any complications.

  16. Molecular pathogenesis of emphysema.

    PubMed

    Taraseviciene-Stewart, Laimute; Voelkel, Norbert F

    2008-02-01

    Emphysema is one manifestation of a group of chronic, obstructive, and frequently progressive destructive lung diseases. Cigarette smoking and air pollution are the main causes of emphysema in humans, and cigarette smoking causes emphysema in rodents. This review examines the concept of a homeostatically active lung structure maintenance program that, when attacked by proteases and oxidants, leads to the loss of alveolar septal cells and airspace enlargement. Inflammatory and noninflammatory mechanisms of disease pathogenesis, as well as the role of the innate and adaptive immune systems, are being explored in genetically altered animals and in exposure models of this disease. These recent scientific advances support a model whereby alveolar destruction resulting from a coalescence of mechanical forces, such as hyperinflation, and more recently recognized cellular and molecular events, including apoptosis, cellular senescence, and failed lung tissue repair, produces the clinically recognized syndrome of emphysema.

  17. Molecular pathogenesis of emphysema

    PubMed Central

    Taraseviciene-Stewart, Laimute; Voelkel, Norbert F.

    2008-01-01

    Emphysema is one manifestation of a group of chronic, obstructive, and frequently progressive destructive lung diseases. Cigarette smoking and air pollution are the main causes of emphysema in humans, and cigarette smoking causes emphysema in rodents. This review examines the concept of a homeostatically active lung structure maintenance program that, when attacked by proteases and oxidants, leads to the loss of alveolar septal cells and airspace enlargement. Inflammatory and noninflammatory mechanisms of disease pathogenesis, as well as the role of the innate and adaptive immune systems, are being explored in genetically altered animals and in exposure models of this disease. These recent scientific advances support a model whereby alveolar destruction resulting from a coalescence of mechanical forces, such as hyperinflation, and more recently recognized cellular and molecular events, including apoptosis, cellular senescence, and failed lung tissue repair, produces the clinically recognized syndrome of emphysema. PMID:18246188

  18. Patterns of Emphysema Heterogeneity

    PubMed Central

    Valipour, Arschang; Shah, Pallav L.; Gesierich, Wolfgang; Eberhardt, Ralf; Snell, Greg; Strange, Charlie; Barry, Robert; Gupta, Avina; Henne, Erik; Bandyopadhyay, Sourish; Raffy, Philippe; Yin, Youbing; Tschirren, Juerg; Herth, Felix J.F.

    2016-01-01

    Background Although lobar patterns of emphysema heterogeneity are indicative of optimal target sites for lung volume reduction (LVR) strategies, the presence of segmental, or sublobar, heterogeneity is often underappreciated. Objective The aim of this study was to understand lobar and segmental patterns of emphysema heterogeneity, which may more precisely indicate optimal target sites for LVR procedures. Methods Patterns of emphysema heterogeneity were evaluated in a representative cohort of 150 severe (GOLD stage III/IV) chronic obstructive pulmonary disease (COPD) patients from the COPDGene study. High-resolution computerized tomography analysis software was used to measure tissue destruction throughout the lungs to compute heterogeneity (≥ 15% difference in tissue destruction) between (inter-) and within (intra-) lobes for each patient. Emphysema tissue destruction was characterized segmentally to define patterns of heterogeneity. Results Segmental tissue destruction revealed interlobar heterogeneity in the left lung (57%) and right lung (52%). Intralobar heterogeneity was observed in at least one lobe of all patients. No patient presented true homogeneity at a segmental level. There was true homogeneity across both lungs in 3% of the cohort when defining heterogeneity as ≥ 30% difference in tissue destruction. Conclusion Many LVR technologies for treatment of emphysema have focused on interlobar heterogeneity and target an entire lobe per procedure. Our observations suggest that a high proportion of patients with emphysema are affected by interlobar as well as intralobar heterogeneity. These findings prompt the need for a segmental approach to LVR in the majority of patients to treat only the most diseased segments and preserve healthier ones. PMID:26430783

  19. Prothymosin α overexpression contributes to the development of pulmonary emphysema.

    PubMed

    Su, Bing-Hua; Tseng, Yau-Lin; Shieh, Gia-Shing; Chen, Yi-Cheng; Shiang, Ya-Chieh; Wu, Pensee; Li, Kuo-Jung; Yen, Te-Hsin; Shiau, Ai-Li; Wu, Chao-Liang

    2013-01-01

    Emphysema is one of the disease conditions that comprise chronic obstructive pulmonary disease. Prothymosin α transgenic mice exhibit an emphysema phenotype, but the pathophysiological role of prothymosin α in emphysema remains unclear. Here we show that prothymosin α contributes to the pathogenesis of emphysema by increasing acetylation of histones and nuclear factor-kappaB, particularly upon cigarette smoke exposure. We find a positive correlation between prothymosin α levels and the severity of emphysema in prothymosin α transgenic mice and emphysema patients. Prothymosin α overexpression increases susceptibility to cigarette smoke-induced emphysema, and cigarette smoke exposure further enhances prothymosin α expression. We show that prothymosin α inhibits the association of histone deacetylases with histones and nuclear factor-kappaB, and that prothymosin α overexpression increases expression of nuclear factor-kappaB-dependent matrix metalloproteinase 2 and matrix metalloproteinase 9, which are found in the lungs of patients with chronic obstructive pulmonary disease. These results demonstrate the clinical relevance of prothymosin α in regulating acetylation events during the pathogenesis of emphysema.

  20. Emphysema: an autoimmune vascular disease?

    PubMed

    Voelkel, Norbert; Taraseviciene-Stewart, Laima

    2005-01-01

    We propose that an endogenous maintenance program controls lung cell turnover, apoptosis, and tissue repair, and that emphysema is a manifestation of the breakdown of the lung structure maintenance program. Emphysema can be induced experimentally in rats by three methods: blockade of vascular endothelial growth factor receptors using SU5416, a small molecule-tyrosine kinase inhibitor; methylprednisolone, which activates matrix metalloproteinase-9 and decreases Akt phosphorylation; and antibodies directed against endothelial cells (autoimmune emphysema). SU5416-induced emphysema is associated with lung induction of cytochrome P450 and oxidant stress, and a superoxide dismutase mimetic or N-acetylcysteine prevents this form of emphysema. A broad-spectrum metalloproteinase inhibitor prevents methylprednisolone-induced emphysema and, finally, autoimmune emphysema is associated with increased lung tissue metalloproteinase-9 expression and alveolar septal cell apoptosis. Athymic rats, which lack CD4+ T cells, are protected against autoimmune emphysema, whereas adoptive transfer of CD4+ T cells causes autoimmune emphysema in naive adult rats. It appears that vascular endothelial growth factor and signaling via its receptors plays a central role in the lung structural maintenance program, and oxidative stress, proteolysis, and apoptosis may coincide in the moment of lung cell destruction. Interestingly, the methylprednisolone model illustrates that inflammation is not necessary for the development of emphysema.

  1. Prognostic significance of CT-emphysema score in patients with advanced squamous cell lung cancer

    PubMed Central

    Kim, Young Saing; Ahn, Hee Kyung; Cho, Eun Kyung; Jeong, Yu Mi; Kim, Jeong Ho

    2016-01-01

    Background Although emphysema is a known independent risk factor of lung cancer, no study has addressed the prognostic impact of computed tomography (CT)-emphysema score in advanced stage lung cancer. Methods For 84 consecutive patients with stage IIIB and IV squamous cell lung cancer that underwent palliative chemotherapy, severity of emphysema was semi-quantitatively scored using baseline chest CT images according to the Goddard scoring system (possible scores range, 0–24). The cutoff of high CT-emphysema score was determined using the maximum chi-squared test and the prognostic significance of the high CT-emphysema score was evaluated using Kaplan-Meier analysis and Cox proportional hazards analysis. Results The median CT-emphysema score was 5 (range, 0–22). Patients with a high CT-emphysema score (≥4) tended to have poorer overall survival (OS) (median: 6.3 vs. 13.7 months) than those with a score of <4 (P=0.071). Multivariable analysis revealed that a higher CT-emphysema score was a significant independent prognostic factor for poor OS [hazard ratio (HR) =2.06; 95% confidence interval (CI), 1.24–3.41; P=0.005), along with no response to first-line therapy (P=0.009) and no second-line therapy (P<0.001). Conclusions CT-emphysema score is significantly associated with poor prognosis in patients with advanced squamous cell lung cancer. PMID:27621848

  2. Emphysema and dust exposure in a group of coal workers

    SciTech Connect

    Ruckley, V.A.; Gauld, S.J.; Chapman, J.S.; Davis, J.M.; Douglas, A.N.; Fernie, J.M.; Jacobsen, M.; Lamb, D.

    1984-04-01

    The lungs of 450 coal miners who had been studied previously in a long-term epidemiologic project at 24 British mines have been examined post-mortem for signs of dust-related fibrosis and emphysema. Reliable estimates of cumulative (working-life) exposures to respirable mine dust were available for 342 of the men. The relative frequency of emphysema increased with age at death, and both panacinar and centriacinar emphysema occurred more frequently in smokers than in nonsmokers. The proportion of subjects with any emphysema was 47% in 92 men with no palpable dust lesions, 65% in 183 with small, simple pneumoconiotic lesions, and 83% in 175 miners with massive fibrosis (PMF). The chance of finding centriacinar emphysema in those with PMF increased significantly with increasing exposure to coal dust in life (p less than 0.025). A similar but less convincing relationship was found in those with simple pneumoconiosis (p less than 0.11), but in both groups, increasing amounts of ash with a given exposure to coal reduced the probability of finding centriacinar emphysema. The occurrence of centriacinar emphysema was associated also with increasing amounts of dust retained in the lungs. A preliminary exploration of this association did not support the hypothesis that emphysematous lungs clear dust less efficiently. We conclude that the association observed between exposure to respirable coal dust and emphysema in coal miners indicates a causal relationship. However, because it can be demonstrated only for men whose lungs show some dust-related fibrosis, it is suggested that the extent and nature of such fibrosis may be a crucial factor in determining the presence of centriacinar emphysema.

  3. Unilateral orbital emphysema after sneezing.

    PubMed

    Koçak, Nilüfer; Oztürk, Taylan; Zengin, Mehmet Ozgür; Kaynak, Süleyman; Men, Süleyman

    2009-01-01

    We report a case who developed unilateral orbital emphysema after sneezing in a 30-year-old man presented with left crepitant eyelid swelling and progressive ptosis. Sneezing may cause orbital emphysema in cases with a history of minor periorbital trauma. While periodical followup without any medication is considered satisfactory, needle decompression may provide early cure.

  4. Pulmonary emphysema and proteolysis: 1986

    SciTech Connect

    Taylor, J.C.; Mittman, C. )

    1987-01-01

    This book deals with the topic of pulmonary emphysema. Included are the following chapters: Abnormality of secretion of Z Alpha-1-antitrypsin, Proteases, antiproteases, and oxidants in the pathogenesis of pulmonary emphysema, Alveolar Leukocytes and protease responses with continuous vs. intermittent exposures to NO{sub 2}.

  5. PCOS women show significantly higher homocysteine level, independent to glucose and E2 level

    PubMed Central

    Eskandari, Zahra; Sadrkhanlou, Rajab-Ali; Nejati, Vahid; Tizro, Gholamreza

    2016-01-01

    Background: It is reasonable to think that some biochemical characteristics of follicular fluid (FF) surrounding the oocyte may play a critical role in determining the quality of oocyte and the subsequent potential needed to achieve fertilization and embryo development. Objective: This study was carried out to evaluate the levels of FF homocysteine (Hcy) in IVF candidate polycystic ovary syndrome (PCOS) women and any relationships with FF glucose and estradiol (E2) levels. Materials and Methods: In this case control study which was performed in Dr. Tizro Day Care and IVF Center 70 infertile patients were enrolled in two groups: comprising 35 PCOS and 35 non PCOS women. Long protocol was performed for all patients. FF Hcy, glucose and E2 levels were analyzed at the time of oocyte retrieval. Results: It was observed that FF Hcy level was significantly higher in PCOS patients compared with non PCOSs (p<0.01). Observations demonstrated that in PCOS group, the Hcy level increased independent to E2, glucose levels, BMI and age, while the PCOS group showed significantly higher BMI compared with non-PCOS group (p=0.03). However, no significant differences were revealed between groups for FF glucose and E2 levels. Conclusion: Present data showed that although FF glucose and E2 levels were constant in PCOS and non PCOS patients, but the FF Hcy levels in PCOS were significantly increased (p=0.01). PMID:27679823

  6. [Subcutaneous cervical emphysema secondary to tooth extraction].

    PubMed

    Calvo Boizas, E; Sancipriano Hernández, J A; Rincón Esteban, L; Diego Pérez, C; Santiago Andrés, J; Hermosa Finamor, P; Gómez Toranzo, F

    1997-01-01

    Cervical emphysema is rare and its diagnosis involves the ENT specialist. A case of cervical subcutaneous emphysema secondary to lower molar extraction is reported. The patient had no signs or symptoms other than cervical emphysema. Simple radiography and CT are recommended for early diagnosis. The etiopathogenic mechanisms of subcutaneous cervical emphysema are reviewed. Recent literature contains few cases of dental origin.

  7. Emphysema Predicts Hospitalisation and Incident Airflow Obstruction among Older Smokers: A Prospective Cohort Study

    PubMed Central

    McAllister, David A.; Ahmed, Firas S.; Austin, John H. M.; Henschke, Claudia I.; Keller, Brad M.; Lemeshow, Adina; Reeves, Anthony P.; Mesia-Vela, Sonia; Pearson, G. D. N.; Shiau, Maria C.; Schwartz, Joseph E.; Yankelevitz, David F.; Barr, R. Graham

    2014-01-01

    Background Emphysema on CT is common in older smokers. We hypothesised that emphysema on CT predicts acute episodes of care for chronic lower respiratory disease among older smokers. Materials and Methods Participants in a lung cancer screening study age ≥60 years were recruited into a prospective cohort study in 2001–02. Two radiologists independently visually assessed the severity of emphysema as absent, mild, moderate or severe. Percent emphysema was defined as the proportion of voxels ≤ −910 Hounsfield Units. Participants completed a median of 5 visits over a median of 6 years of follow-up. The primary outcome was hospitalization, emergency room or urgent office visit for chronic lower respiratory disease. Spirometry was performed following ATS/ERS guidelines. Airflow obstruction was defined as FEV1/FVC ratio <0.70 and FEV1<80% predicted. Results Of 521 participants, 4% had moderate or severe emphysema, which was associated with acute episodes of care (rate ratio 1.89; 95% CI: 1.01–3.52) adjusting for age, sex and race/ethnicity, as was percent emphysema, with similar associations for hospitalisation. Emphysema on visual assessment also predicted incident airflow obstruction (HR 5.14; 95% CI 2.19–21.1). Conclusion Visually assessed emphysema and percent emphysema on CT predicted acute episodes of care for chronic lower respiratory disease, with the former predicting incident airflow obstruction among older smokers. PMID:24699215

  8. Pulmonary rehabilitation in emphysema.

    PubMed

    Ries, Andrew L; Make, Barry J; Reilly, John J

    2008-05-01

    Pulmonary rehabilitation is an established treatment for patients with chronic lung disease. Benefits include improvement in exercise tolerance, symptoms, and quality of life, with a reduction in the use of health care resources. As an adjunct to surgical programs, such as lung volume reduction surgery, pulmonary rehabilitation plays an important role not just in preparing patients for surgery and facilitating recovery but also in selecting patients and ensuring informed choices about treatment options after optimal medical care. In the National Emphysema Treatment Trial (NETT), subjects completed 6-10 weeks of comprehensive pulmonary rehabilitation before randomization and continued rehabilitation throughout the trial, both at home and with intermittent supervision at either an NETT center or an NETT-certified satellite center. Sessions included a combination of upper and lower extremity exercise, education, and psychosocial support. Before randomization, pulmonary rehabilitation resulted in highly significant changes in exercise capacity, dyspnea, and quality of life. As expected, improvements were significantly greater in those without prior rehabilitation experience. Results for patients completing rehabilitation at satellites were similar to those at NETT centers. Prerandomization pulmonary rehabilitation had a significant effect on outcome after lung volume reduction surgery. NETT identified subgroups with differential outcome by treatment (surgical vs. nonsurgical), defined in part by postrehabilitation maximum exercise capacity. Overall, NETT demonstrated the effectiveness of pulmonary rehabilitation in improving function, symptoms, and health status in a large cohort of patients with advanced emphysema treated in a cross-section of programs in the United States.

  9. Towards exaggerated emphysema stereotypes

    NASA Astrophysics Data System (ADS)

    Chen, C.; Sørensen, L.; Lauze, F.; Igel, C.; Loog, M.; Feragen, A.; de Bruijne, M.; Nielsen, M.

    2012-03-01

    Classification is widely used in the context of medical image analysis and in order to illustrate the mechanism of a classifier, we introduce the notion of an exaggerated image stereotype based on training data and trained classifier. The stereotype of some image class of interest should emphasize/exaggerate the characteristic patterns in an image class and visualize the information the employed classifier relies on. This is useful for gaining insight into the classification and serves for comparison with the biological models of disease. In this work, we build exaggerated image stereotypes by optimizing an objective function which consists of a discriminative term based on the classification accuracy, and a generative term based on the class distributions. A gradient descent method based on iterated conditional modes (ICM) is employed for optimization. We use this idea with Fisher's linear discriminant rule and assume a multivariate normal distribution for samples within a class. The proposed framework is applied to computed tomography (CT) images of lung tissue with emphysema. The synthesized stereotypes illustrate the exaggerated patterns of lung tissue with emphysema, which is underpinned by three different quantitative evaluation methods.

  10. Combined pulmonary fibrosis and emphysema: an increasingly recognized condition* **

    PubMed Central

    Dias, Olívia Meira; Baldi, Bruno Guedes; Costa, André Nathan; Carvalho, Carlos Roberto Ribeiro

    2014-01-01

    Combined pulmonary fibrosis and emphysema (CPFE) has been increasingly recognized in the literature. Patients with CPFE are usually heavy smokers or former smokers with concomitant lower lobe fibrosis and upper lobe emphysema on chest HRCT scans. They commonly present with severe breathlessness and low DLCO, despite spirometry showing relatively preserved lung volumes. Moderate to severe pulmonary arterial hypertension is common in such patients, who are also at an increased risk of developing lung cancer. Unfortunately, there is currently no effective treatment for CPFE. In this review, we discuss the current knowledge of the pathogenesis, clinical characteristics, and prognostic factors of CPFE. Given that most of the published data on CPFE are based on retrospective analysis, more studies are needed in order to address the role of emphysema and its subtypes; the progression of fibrosis/emphysema and its correlation with inflammation; treatment options; and prognosis. PMID:25029654

  11. Iatrogenic subcutaneous cervicofacial emphysema with pneumomediastinum after class V restoration

    PubMed Central

    2017-01-01

    Subcutaneous facial emphysema after dental treatment is an uncommon complication caused by the invasion of high-pressure air; in severe cases, it can spread to the neck, mediastinum, and thorax, resulting in cervical emphysema, pneumomediastinum, and pneumothorax. The present case showed subcutaneous cervicofacial emphysema with pneumomediastinum after class V restoration. The patient was fully recovered after eight days of conservative treatment. The cause of this case was the penetration of high-pressure air through the gingival sulcus, which had a weakened gingival attachment. This case indicated that dentists should be careful to prevent subcutaneous emphysema during common dental treatments using a high-speed hand piece and gingival retraction cord. PMID:28280711

  12. Teaching Independent Eating to a Developmentally Handicapped Child Showing Chronic Food Refusal and Disruption at Mealtimes.

    ERIC Educational Resources Information Center

    MacArthur, Judy; And Others

    1986-01-01

    A successful intervention to establish independent eating behaviors in a developmentally handicapped, autistic-like three-year-old involved teaching appropriate behavior in a hospital setting (where he was being treated for dehydration and malnutrition) and then teaching his mother to implement the strategies at home. Skills were maintained at…

  13. Cardiovascular Function in Pulmonary Emphysema

    PubMed Central

    Visca, Dina; Aiello, Marina; Chetta, Alfredo

    2013-01-01

    Chronic obstructive pulmonary disease (COPD) and chronic cardiovascular disease, such as coronary artery disease, congestive heart failure, and cardiac arrhythmias, have a strong influence on each other, and systemic inflammation has been considered as the main linkage between them. On the other hand, airflow limitation may markedly affect lung mechanics in terms of static and dynamic hyperinflation, especially in pulmonary emphysema, and they can in turn influence cardiac performance as well. Skeletal mass depletion, which is a common feature in COPD especially in pulmonary emphysema patients, may have also a role in cardiovascular function of these patients, irrespective of lung damage. We reviewed the emerging evidence that highlights the role of lung mechanics and muscle mass impairment on ventricular volumes, stroke volume, and stroke work at rest and on exercise in the presence of pulmonary emphysema. Patients with emphysema may differ among COPD population even in terms of cardiovascular function. PMID:24369007

  14. Cardiovascular function in pulmonary emphysema.

    PubMed

    Visca, Dina; Aiello, Marina; Chetta, Alfredo

    2013-01-01

    Chronic obstructive pulmonary disease (COPD) and chronic cardiovascular disease, such as coronary artery disease, congestive heart failure, and cardiac arrhythmias, have a strong influence on each other, and systemic inflammation has been considered as the main linkage between them. On the other hand, airflow limitation may markedly affect lung mechanics in terms of static and dynamic hyperinflation, especially in pulmonary emphysema, and they can in turn influence cardiac performance as well. Skeletal mass depletion, which is a common feature in COPD especially in pulmonary emphysema patients, may have also a role in cardiovascular function of these patients, irrespective of lung damage. We reviewed the emerging evidence that highlights the role of lung mechanics and muscle mass impairment on ventricular volumes, stroke volume, and stroke work at rest and on exercise in the presence of pulmonary emphysema. Patients with emphysema may differ among COPD population even in terms of cardiovascular function.

  15. Massive surgical emphysema after perineal proctosigmoidectomy.

    PubMed

    Angehrn, Fiorenzo Valente Ernst Jakob; Däster, Silvio; Antonescu, Marius

    2014-10-07

    An 83-year-old woman underwent an elective perineal proctosigmoidectomy (Altemeier procedure) for a rectal prolapse. On postoperative day 1, the patient presented with impressive subcutaneous emphysema involving the chest, neck and face without any other symptoms. A CT scan showed free air in the retroperitoneum, the intraperitoneal cavity, the mediastinum and a subcutaneous emphysema of the neck and the face. Air was also found around the coloanal anastomosis and an anastomotic leak was proven by rectal contrast agent. In this situation, a rectoscopy followed by a laparoscopy were immediately performed. The leak could not be visualised. Peritoneal lavage and drainage, followed by protective sigmoidostomy were carried out. After surgery, the follow-up was uneventful except a persistent but asymptomatic leak with a presacral cavity. The coloanal dehiscence was later proven in rectoscopy. Although sutured, it is still present and colostomy closure will eventually be possible in a few months.

  16. Using Image Processing to Determine Emphysema Severity

    NASA Astrophysics Data System (ADS)

    McKenzie, Alexander; Sadun, Alberto

    2010-10-01

    Currently X-rays and computerized tomography (CT) scans are used to detect emphysema, but other tests are required to accurately quantify the amount of lung that has been affected by the disease. These images clearly show if a patient has emphysema, but are unable by visual scan alone, to quantify the degree of the disease, as it presents as subtle, dark spots on the lung. Our goal is to use these CT scans to accurately diagnose and determine emphysema severity levels in patients. This will be accomplished by performing several different analyses of CT scan images of several patients representing a wide range of severity of the disease. In addition to analyzing the original CT data, this process will convert the data to one and two bit images and will then examine the deviation from a normal distribution curve to determine skewness. Our preliminary results show that this method of assessment appears to be more accurate and robust than the currently utilized methods, which involve looking at percentages of radiodensities in the air passages of the lung.

  17. Blastocystis Mitochondrial Genomes Appear to Show Multiple Independent Gains and Losses of Start and Stop Codons

    PubMed Central

    Jacob, Alison S.; Andersen, Lee O’Brien; Bitar, Paulina Pavinski; Richards, Vincent P.; Shah, Sarah; Stanhope, Michael J.; Stensvold, C. Rune; Clark, C. Graham

    2016-01-01

    Complete mitochondrion-related organelle (MRO) genomes of several subtypes (STs) of the unicellular stramenopile Blastocystis are presented. Complete conservation of gene content and synteny in gene order is observed across all MRO genomes, comprising 27 protein coding genes, 2 ribosomal RNA genes, and 16 transfer RNA (tRNA) genes. Despite the synteny, differences in the degree of overlap between genes were observed between subtypes and also between isolates within the same subtype. Other notable features include unusual base-pairing mismatches in the predicted secondary structures of some tRNAs. Intriguingly, the rps4 gene in some MRO genomes is missing a start codon and, based on phylogenetic relationships among STs, this loss has happened twice independently. One unidentified open reading frame (orf160) is present in all MRO genomes. However, with the exception of ST4 where the feature has been lost secondarily, orf160 contains variously one or two in-frame stop codons. The overall evidence suggests that both the orf160 and rps4 genes are functional in all STs, but how they are expressed remains unclear. PMID:27811175

  18. Visual search for conjunctions of physical and numerical size shows that they are processed independently.

    PubMed

    Sobel, Kenith V; Puri, Amrita M; Faulkenberry, Thomas J; Dague, Taylor D

    2017-03-01

    The size congruity effect refers to the interaction between numerical magnitude and physical digit size in a symbolic comparison task. Though this effect is well established in the typical 2-item scenario, the mechanisms at the root of the interference remain unclear. Two competing explanations have emerged in the literature: an early interaction model and a late interaction model. In the present study, we used visual conjunction search to test competing predictions from these 2 models. Participants searched for targets that were defined by a conjunction of physical and numerical size. Some distractors shared the target's physical size, and the remaining distractors shared the target's numerical size. We held the total number of search items fixed and manipulated the ratio of the 2 distractor set sizes. The results from 3 experiments converge on the conclusion that numerical magnitude is not a guiding feature for visual search, and that physical and numerical magnitude are processed independently, which supports a late interaction model of the size congruity effect. (PsycINFO Database Record

  19. [Lung volume reduction surgery for emphysema and bullous pulmonary emphysema].

    PubMed

    Le Pimpec-Barthes, F; Das Neves-Pereira, J-C; Cazes, A; Arame, A; Grima, R; Hubsch, J-P; Zukerman, C; Hernigou, A; Badia, A; Bagan, P; Delclaux, C; Dusser, D; Riquet, M

    2012-04-01

    The improvement of respiratory symptoms for emphysematous patients by surgery is a concept that has evolved over time. Initially used for giant bullae, this surgery was then applied to patients with diffuse microbullous emphysema. The physiological and pathological concepts underlying these surgical procedures are the same in both cases: improve respiratory performance by reducing the high intrapleural pressure. The functional benefit of lung volume reduction surgery (LVRS) in the severe diffuse emphysema has been validated by the National Emphysema Treatment Trial (NETT) and the later studies which allowed to identify prognostic factors. The quality of the clinical, morphological and functional data made it possible to develop recommendations now widely used in current practice. Surgery for giant bullae occurring on little or moderately emphysematous lung is often a simpler approach but also requires specialised support to optimize its results.

  20. CT Metrics of Airway Disease and Emphysema in Severe COPD

    PubMed Central

    Kim, Woo Jin; Silverman, Edwin K.; Hoffman, Eric; Criner, Gerard J.; Mosenifar, Zab; Sciurba, Frank C.; Make, Barry J.; Carey, Vincent; Estépar, Raúl San José; Diaz, Alejandro; Reilly, John J.; Martinez, Fernando J.; Washko, George R.

    2009-01-01

    Background: CT scan measures of emphysema and airway disease have been correlated with lung function in cohorts of subjects with a range of COPD severity. The contribution of CT scan-assessed airway disease to objective measures of lung function and respiratory symptoms such as dyspnea in severe emphysema is less clear. Methods: Using data from 338 subjects in the National Emphysema Treatment Trial (NETT) Genetics Ancillary Study, densitometric measures of emphysema using a threshold of −950 Hounsfield units (%LAA-950) and airway wall phenotypes of the wall thickness (WT) and the square root of wall area (SRWA) of a 10-mm luminal perimeter airway were calculated for each subject. Linear regression analysis was performed for outcome variables FEV1 and percent predicted value of FEV1 with CT scan measures of emphysema and airway disease. Results: In univariate analysis, there were significant negative correlations between %LAA-950 and both the WT (r = −0.28, p = 0.0001) and SRWA (r = −0.19, p = 0.0008). Airway wall thickness was weakly but significantly correlated with postbronchodilator FEV1% predicted (R = −0.12, p = 0.02). Multivariate analysis showed significant associations between either WT or SRWA (β = −5.2, p = 0.009; β = −2.6, p = 0.008, respectively) and %LAA-950 (β = −10.6, p = 0.03) with the postbronchodilator FEV1% predicted. Male subjects exhibited significantly thicker airway wall phenotypes (p = 0.007 for WT and p = 0.0006 for SRWA). Conclusions: Airway disease and emphysema detected by CT scanning are inversely related in patients with severe COPD. Airway wall phenotypes were influenced by gender and associated with lung function in subjects with severe emphysema. PMID:19411295

  1. DERIVATION OF A TEST STATISTIC FOR EMPHYSEMA QUANTIFICATION

    PubMed Central

    Vegas-Sanchez-Ferrero, Gonzalo; Washko, George; Rahaghi, Farbod N.; Ledesma-Carbayo, Maria J.; Estépar, R. San José

    2016-01-01

    Density masking is the de-facto quantitative imaging phenotype for emphysema that is widely used by the clinical community. Density masking defines the burden of emphysema by a fixed threshold, usually between −910 HU and −950 HU, that has been experimentally validated with histology. In this work, we formalized emphysema quantification by means of statistical inference. We show that a non-central Gamma is a good approximation for the local distribution of image intensities for normal and emphysema tissue. We then propose a test statistic in terms of the sample mean of a truncated non-central Gamma random variable. Our results show that this approach is well-suited for the detection of emphysema and superior to standard density masking. The statistical method was tested in a dataset of 1337 samples obtained from 9 different scanner models in subjects with COPD. Results showed an increase of 17% when compared to the density masking approach, and an overall accuracy of 94.09%. PMID:27974952

  2. Treatment of emphysema using bronchoscopic lung volume reduction coil technology: an update on efficacy and safety.

    PubMed

    Hartman, Jorine E; Klooster, Karin; Ten Hacken, Nick H T; Slebos, Dirk-Jan

    2015-10-01

    In the last decade several promising bronchoscopic lung volume reduction (BLVR) treatments were developed and investigated. One of these treatments is BLVR treatment with coils. The advantage of this specific treatment is that it works independently of collateral flow, and also shows promise for patients with a more homogeneous emphysema disease distribution. Seven years ago, the very first patients were treated with BLVR coil treatment and currently large randomized, controlled trials are underway. The aim of this article is to review the available literature and provide an update on the current knowledge on the efficacy and safety of BLVR treatment with coils.

  3. A Low Peripheral Blood CD4/CD8 Ratio Is Associated with Pulmonary Emphysema in HIV

    PubMed Central

    Attia, Engi F.; Akgün, Kathleen M.; Soo Hoo, Guy W.; Freiberg, Matthew S.; Butt, Adeel A.; Wongtrakool, Cherry; Goetz, Matthew Bidwell; Brown, Sheldon T.; Graber, Christopher J.; Huang, Laurence; Crothers, Kristina

    2017-01-01

    Objectives The prevalence of emphysema is higher among HIV-infected (HIV+) individuals compared to HIV-uninfected persons. While greater tobacco use contributes, HIV-related effects on immunity likely confer additional risk. Low peripheral blood CD4+ to CD8+ T-lymphocyte (CD4/CD8) ratio may reflect chronic inflammation in HIV and may be a marker of chronic lung disease in this population. Therefore, we sought to determine whether the CD4/CD8 ratio was associated with chronic obstructive pulmonary disease (COPD), particularly the emphysema subtype, in a cohort of HIV+ subjects. Methods We performed a cross-sectional analysis of 190 HIV+ subjects enrolled in the Examinations of HIV Associated Lung Emphysema (EXHALE) study. Subjects underwent baseline laboratory assessments, pulmonary function testing and chest computed tomography (CT) analyzed for emphysema severity and distribution. We determined the association between CD4/CD8 ratio and emphysema, and the association between CD4/CD8 ratio and pulmonary function markers of COPD. Results Mild or greater emphysema (>10% lung involvement) was present in 31% of subjects. Low CD4/CD8 ratio was associated with >10% emphysema in multivariable models, adjusting for risk factors including smoking, current and nadir CD4 count and HIV RNA level. Those with CD4/CD8 ratio <0.4 had 6.3 (1.1–39) times the odds of >10% emphysema compared to those with a ratio >1.0 in fully adjusted models. A low CD4/CD8 ratio was also associated with reduced diffusion capacity (DLCO). Conclusions A low CD4/CD8 ratio was associated with emphysema and low DLCO in HIV+ subjects, independent of other risk factors and clinical markers of HIV. The CD4/CD8 ratio may be a useful, clinically available, marker for risk of emphysema in HIV+ subjects in the antiretroviral therapy (ART) era. PMID:28122034

  4. Computer quantification of airway collapse on forced expiration to predict the presence of emphysema

    PubMed Central

    2013-01-01

    Background Spirometric parameters are the mainstay for diagnosis of COPD, but cannot distinguish airway obstruction from emphysema. We aimed to develop a computer model that quantifies airway collapse on forced expiratory flow–volume loops. We then explored and validated the relationship of airway collapse with computed tomography (CT) diagnosed emphysema in two large independent cohorts. Methods A computer model was developed in 513 Caucasian individuals with ≥15 pack-years who performed spirometry, diffusion capacity and CT scans to quantify emphysema presence. The model computed the two best fitting regression lines on the expiratory phase of the flow-volume loop and calculated the angle between them. The collapse was expressed as an Angle of collapse (AC) which was then correlated with the presence of emphysema. Findings were validated in an independent group of 340 individuals. Results AC in emphysema subjects (N = 251) was significantly lower (131° ± 14°) compared to AC in subjects without emphysema (N = 223), (152° ± 10°) (p < 0.0001). Multivariate regression analysis revealed AC as best indicator of visually scored emphysema (R2 = 0.505, p < 0.0001) with little significant contribution of KCO, %predicted and FEV1, %predicted to the total model (total R2 = 0.626, p < 0.0001). Similar associations were obtained when using CT-automated density scores for emphysema assessment. Receiver operating characteristic (ROC) curves pointed to 131° as the best cut-off for emphysema (95.5% positive predictive value, 97% specificity and 51% sensitivity). Validation in a second group confirmed the significant difference in mean AC between emphysema and non-emphysema subjects. When applying the 131° cut-off, a positive predictive value of 95.6%, a specificity of 96% and a sensitivity of 59% were demonstrated. Conclusions Airway collapse on forced expiration quantified by a computer model correlates with emphysema. An AC below

  5. A probabilistic model of emphysema based on granulometry analysis

    NASA Astrophysics Data System (ADS)

    Marcos, J. V.; Nava, R.; Cristobal, G.; Munoz-Barrutia, A.; Escalante-Ramírez, B.; Ortiz-de-Solórzano, C.

    2013-11-01

    Emphysema is associated with the destruction of lung parenchyma, resulting in abnormal enlargement of airspaces. Accurate quantification of emphysema is required for a better understanding of the disease as well as for the assessment of drugs and treatments. In the present study, a novel method for emphysema characterization from histological lung images is proposed. Elastase-induced mice were used to simulate the effect of emphysema on the lungs. A database composed of 50 normal and 50 emphysematous lung patches of size 512 x 512 pixels was used in our experiments. The purpose is to automatically identify those patches containing emphysematous tissue. The proposed approach is based on the use of granulometry analysis, which provides the pattern spectrum describing the distribution of airspaces in the lung region under evaluation. The profile of the spectrum was summarized by a set of statistical features. A logistic regression model was then used to estimate the probability for a patch to be emphysematous from this feature set. An accuracy of 87% was achieved by our method in the classification between normal and emphysematous samples. This result shows the utility of our granulometry-based method to quantify the lesions due to emphysema.

  6. Quantitative characterization of airspace enlargement in emphysema.

    PubMed

    Parameswaran, Harikrishnan; Majumdar, Arnab; Ito, Satoru; Alencar, Adriano M; Suki, Béla

    2006-01-01

    The mean linear intercept (L(m)) can be used to estimate the surface area for gas exchange in the lung. However, in recent years, it is most commonly used as an index for characterizing the enlargement of airspaces in emphysema and the associated severity of structural destruction in the lung. Specifically, an increase in L(m) is thought to result from an increase in airspace sizes. In this paper, we examined how accurately L(m) measures the linear dimensions of airspaces from histological sections and a variety of computer-generated test images. To this end, we developed an automated method for measuring linear intercepts from digitized images of tissue sections and calculate L(m) as their mean. We examined how the shape of airspaces and the variability of their sizes influence L(m) as well as the distribution of linear intercepts. We found that, for a relatively homogeneous enlargement of airspaces, L(m) was a reliable index for detecting emphysema. However, in the presence of spatial heterogeneities with a large variability of airspace sizes, L(m) did not significantly increase and sometimes even decreased compared with its value in normal tissue. We also developed an automated method for measuring the area and computed an equivalent diameter of each individual airspace that is independent of shape. Finally, we introduced new indexes based on the moments of diameter that we found to be more reliable than L(m) to characterize airspace enlargement in the presence of heterogeneities.

  7. [Measles and subcutaneous emphysema. Presentation of 3 cases].

    PubMed

    Montesano-Delfín, J R; Mascareñas-Ponce, A

    1991-03-01

    This is a three case study report of children with measles which later progressed to bronchopneumonia and subcutaneous emphysema. All three children were from farming families, and none had been previously vaccinate against measles. For a period of six months, 183 cases of measles were treated at our hospital of which only three worsened to subcutaneous emphysema, demonstrating an incidence rate of 1.6%; they also showed to have bronchopneumonia, with severe coughing episodes; which made us recall the possible physiopathology principle of the pressure gradient theory behind this complication proposed by Bloch in 1968. The factors related to our patients suggested a more severe and aggresive type of measles with a greater probability of having complications. The prognostic value of the severity of this type of measles in the presence of subcutaneous emphysema is limited and its management should be primarly focused on treating the added bronchial problem.

  8. Erythromycin ameliorates cigarette-smoke-induced emphysema and inflammation in rats.

    PubMed

    Zhou, Yan; Tan, Xianshu; Kuang, Wenjuan; Liu, Litao; Wan, Lihong

    2012-06-01

    The exposure to cigarette smoke (CS) is associated with emphysema. In addition to chronic lung inflammation, emphysema is known mainly for the complex pathogenesis associated with imbalance of proteolytic and antiproteolytic activities, oxidative stress, and apoptosis of lung structural cells. Increasing evidence shows that erythromycin, which is a macrolide antibiotic, ameliorates chronic inflammation via mechanisms independent of its antibacterial activity. We hypothesize that erythromycin protects against CS-induced emphysema and inflammation in rats via its anti-inflammation and antiapoptosis action. Sprague-Dawley (SD) rats were administered lipopolysaccharide (LPS) intratracheally solution twice and exposed to the CS, the control rats were administered saline intratracheally and exposed to ambient air for 3 weeks. Then, all the CS rats were distributed randomly into 3 groups and, respectively, treated orally with saline (LPS + CS + saline), Guilongkechuanning capsule (450 mg/kg) (LPS + CS + GLKCN), or erythromycin (100 mg/kg) (LPS + CS + ERY) 0.5 h before CS exposure for 2 weeks. On day 36, the rats were killed. The cytokines in serum were measured by enzyme-linked immunosorbent assay (ELISA). The middle lobe of the right lung was removed for histology and apoptosis analyses, respectively. Emphysematous lesions and inflammatory cell infiltrations in the CS group were evident by a histologic analysis. Erythromycin protected significantly against the alveolar enlargement levels (P = 0.0017), reduced the pathologic apoptosis (P = 0.0023) related with Bcl-2 (P = 0.0002) and Bax (P = 0.0002), and inhibited the expressions of matrix metalloproteinase (MMP)-9 (P = 0.0019) and TIMP-1 protein (P = 0.04) and the MMP-9/TIMP-1 ratio (P = 0.0002) in the lungs of CS-induced emphysema in rats. The protective effect of erythromycin on CS-induced emphysema and inflammation in rats is associated with a reduction in inflammation, imbalance of MMP-9/TIMP-1, and apoptosis of

  9. Soft-tissue calcification after subcutaneus emphysema in a neonate

    SciTech Connect

    Naidech, H.J.; Chawla, H.S.

    1982-08-01

    Bilateral, almost symmetric, calcifications of the soft tissues after subcutaneous emphysema have not, to our knowledge, been described. Because of the close clinical and radiographic evaluation in our case, the finding of calcinosis was not a diagnostic problem. Several 1.5 mm computed tomographic (CT) sections of the thorax were scanned and they were confirmatory in showing the distribution of the calcifications. Since subcutaneous emphysema is commonplace, and calcification after it is apparently unknown, the literature was reviewed and an additional cause of soft-tissue calcinosis is presented.

  10. Array CGH reveals genomic aberrations in human emphysema.

    PubMed

    Choi, Jin Soo; Lee, Woon Jeong; Baik, Seung Ho; Yoon, Hyoung Kyu; Lee, Kweon-Haeng; Kim, Yeul Hong; Lim, Young; Wang, Young-Pil

    2009-01-01

    Emphysema is the major component of chronic obstructive pulmonary disease (COPD), which is the fourth leading cause of death in the world. Several epidemiologic studies suggest that genetic factors may have an important role in the pathogenesis of emphysema. We analyzed the gene expression profiles of chromosomal aberrations using array comparative genomic hybridization (array CGH) in 32 patients with emphysema to identify the candidate genes that might be causally involved in the pathogenesis of emphysema. Copy number gains and losses were detected in chromosomal regions, and the corresponding genes were confirmed by real-time polymerase chain reaction. Several frequently altered loci were found, including a gain at 5p15.33 (60% of the study subjects), and a loss at 7q22.1 (31% of the study subjects). DNA gains were identified at a high frequency at 1p, 5p, 11p, 12p, 15q, 17p, 18q, 21q, and 22q, whereas DNA losses were frequently found at 7q and 22q. We found that the fold change levels were highest at the CYP4B1 (1p33), JUN (1p32.1), NOTCH2 (1p12-p11.2), SDHA (5p15.33), KCNQ1 (11p15.5-p15.4), NINJ2 (12p13.33), PCSK6 (15q26.3), ABR (17p13.3), CTDP1 (18q23), RUNX1 (21q22.12) and HDAC10 (22q13.33) gene loci. We also observed losses in the MUC17 (7q22.1), COMT (22q11.21) and GSTT1 (22q11.2) genes. These studies show that array CGH is a useful tool for the identification of gene alterations in cases of emphysema and that the aforementioned genes might represent potential candidate genes involved in the pathogenesis of emphysema.

  11. Subcutaneous Emphysema and Pneumomediastinum after Tonsillectomy

    PubMed Central

    Koukoutsis, George; Balatsouras, Dimitrios G.; Ganelis, Panayotis; Fassolis, Alexandros; Moukos, Antonis; Katotomichelakis, Michael; Kaberos, Antonis

    2013-01-01

    Cervicofacial subcutaneous emphysema is a rare complication of tonsillectomy that often resolves spontaneously but may progress to obstruct upper airways or spread to the thorax causing pneumomediastinum or pneumothorax. The mechanisms by which subcutaneous emphysema and pneumomediastinum may develop after tonsillectomy are poorly understood. A case of a 21-year-old female undergoing routine adenotonsillectomy, who developed cervicofacial emphysema and pneumomediastinum, is presented. Possible pathogenetic mechanisms and treatment options are discussed. PMID:24379978

  12. Spontaneous orbital subcutaneous emphysema after sneezing.

    PubMed

    Chiu, Wei-Chieh; Lih, Ma; Huang, Tien-Yi; Ku, Wan-Chen; Wang, Warren

    2008-03-01

    Orbital subcutaneous emphysema develops when air enters the surrounding soft tissue. This occurs as a result facial bone trauma, iatrogenic dental and otolaryngeal procedures, and gas-producing infectious microorganisms. Case reports regarding this phenomenon after sneezing are very uncommon. Although orbital subcutaneous emphysema is not a true emergency, it can be distressful to patients. This case serves to bring awareness to emergency department physicians regarding the possibility of a nontraumatic orbital subcutaneous emphysema and its related complications.

  13. Real-time monitoring of oxygen uptake in hepatic bioreactor shows CYP450-independent mitochondrial toxicity of acetaminophen and amiodarone.

    PubMed

    Prill, Sebastian; Bavli, Danny; Levy, Gahl; Ezra, Elishai; Schmälzlin, Elmar; Jaeger, Magnus S; Schwarz, Michael; Duschl, Claus; Cohen, Merav; Nahmias, Yaakov

    2016-05-01

    Prediction of drug-induced toxicity is complicated by the failure of animal models to extrapolate human response, especially during assessment of repeated dose toxicity for cosmetic or chronic drug treatments. In this work, we present a 3D microreactor capable of maintaining metabolically active HepG2/C3A spheroids for over 28 days in vitro under stable oxygen gradients mimicking the in vivo microenvironment. Mitochondrial respiration was monitored using two-frequency phase modulation of phosphorescent microprobes embedded in the tissue. Phase modulation is focus independent and unaffected by cell death or migration. This sensitive measurement of oxygen dynamics revealed important information on the drug mechanism of action and transient subthreshold effects. Specifically, exposure to antiarrhythmic agent, amiodarone, showed that both respiration and the time to onset of mitochondrial damage were dose dependent showing a TC50 of 425 μm. Analysis showed significant induction of both phospholipidosis and microvesicular steatosis during long-term exposure. Importantly, exposure to widely used analgesic, acetaminophen, caused an immediate, reversible, dose-dependent loss of oxygen uptake followed by a slow, irreversible, dose-independent death, with a TC50 of 12.3 mM. Transient loss of mitochondrial respiration was also detected below the threshold of acetaminophen toxicity. The phenomenon was repeated in HeLa cells that lack CYP2E1 and 3A4, and was blocked by preincubation with ascorbate and TMPD. These results mark the importance of tracing toxicity effects over time, suggesting a NAPQI-independent targeting of mitochondrial complex III might be responsible for acetaminophen toxicity in extrahepatic tissues.

  14. Emphysema Distribution and Diffusion Capacity Predict Emphysema Progression in Human Immunodeficiency Virus Infection

    PubMed Central

    Leung, Janice M; Malagoli, Andrea; Santoro, Antonella; Besutti, Giulia; Ligabue, Guido; Scaglioni, Riccardo; Dai, Darlene; Hague, Cameron; Leipsic, Jonathon; Sin, Don D.; Man, SF Paul; Guaraldi, Giovanni

    2016-01-01

    Background Chronic obstructive pulmonary disease (COPD) and emphysema are common amongst patients with human immunodeficiency virus (HIV). We sought to determine the clinical factors that are associated with emphysema progression in HIV. Methods 345 HIV-infected patients enrolled in an outpatient HIV metabolic clinic with ≥2 chest computed tomography scans made up the study cohort. Images were qualitatively scored for emphysema based on percentage involvement of the lung. Emphysema progression was defined as any increase in emphysema score over the study period. Univariate analyses of clinical, respiratory, and laboratory data, as well as multivariable logistic regression models, were performed to determine clinical features significantly associated with emphysema progression. Results 17.4% of the cohort were emphysema progressors. Emphysema progression was most strongly associated with having a low baseline diffusion capacity of carbon monoxide (DLCO) and having combination centrilobular and paraseptal emphysema distribution. In adjusted models, the odds ratio (OR) for emphysema progression for every 10% increase in DLCO percent predicted was 0.58 (95% confidence interval [CI] 0.41–0.81). The equivalent OR (95% CI) for centrilobular and paraseptal emphysema distribution was 10.60 (2.93–48.98). Together, these variables had an area under the curve (AUC) statistic of 0.85 for predicting emphysema progression. This was an improvement over the performance of spirometry (forced expiratory volume in 1 second to forced vital capacity ratio), which predicted emphysema progression with an AUC of only 0.65. Conclusion Combined paraseptal and centrilobular emphysema distribution and low DLCO could identify HIV patients who may experience emphysema progression. PMID:27902753

  15. A new high resolution computed tomography scoring system for pulmonary fibrosis, pleural disease, and emphysema in patients with asbestos related disease.

    PubMed Central

    Jarad, N A; Wilkinson, P; Pearson, M C; Rudd, R M

    1992-01-01

    The aim of this study was to describe a scoring system for high resolution computed tomographic (HRCT) scans analogous to the International Labour Office (ILO) scoring system for plain chest radiographs in patients with asbestos related disease. Interstitial fibrosis, pleural disease, and emphysema were scored, the reproducibility and the interobserver agreement using this scoring system were examined, and the extent of the various types of disease was correlated with measurements of lung function. Sixty asbestos workers (five women and 55 men) mean age 59 (range 34-78) were studied. The lungs were divided into upper, middle, and lower thirds. An HRCT score for the extent of pleural disease and pulmonary disease in each third was recorded in a way analogous to the International Labour Office (ILO) method of scoring pleural and parenchymal disease on chest radiographs. A CT score for the extent of emphysema was also recorded. Pleural disease and interstitial fibrosis on the plain chest radiographs were assessed according to the ILO scoring system. A chest radiographic score for emphysema analogous to that used for HRCT was also recorded. Two independent readers assigned HRCT scores that differed by two categories or less in 96%, 92%, and 85% compared with 90%, 78%, and 79% of cases for chest radiographs for fibrosis, emphysema, and pleural disease respectively. There was better intraobserver repeatability for the HRCT scores than for the chest radiograph scores for all disorders. Multiple regression analysis showed that scores for interstitial fibrosis, emphysema, and pleural disease on chest radiographs and HRCT correlated to a similar degree with impairment of lung function. Images PMID:1536823

  16. Adaptive Quantification and Longitudinal Analysis of Pulmonary Emphysema with a Hidden Markov Measure Field Model

    PubMed Central

    Häme, Yrjö; Angelini, Elsa D.; Hoffman, Eric A.; Barr, R. Graham; Laine, Andrew F.

    2014-01-01

    The extent of pulmonary emphysema is commonly estimated from CT images by computing the proportional area of voxels below a predefined attenuation threshold. However, the reliability of this approach is limited by several factors that affect the CT intensity distributions in the lung. This work presents a novel method for emphysema quantification, based on parametric modeling of intensity distributions in the lung and a hidden Markov measure field model to segment emphysematous regions. The framework adapts to the characteristics of an image to ensure a robust quantification of emphysema under varying CT imaging protocols and differences in parenchymal intensity distributions due to factors such as inspiration level. Compared to standard approaches, the present model involves a larger number of parameters, most of which can be estimated from data, to handle the variability encountered in lung CT scans. The method was used to quantify emphysema on a cohort of 87 subjects, with repeated CT scans acquired over a time period of 8 years using different imaging protocols. The scans were acquired approximately annually, and the data set included a total of 365 scans. The results show that the emphysema estimates produced by the proposed method have very high intra-subject correlation values. By reducing sensitivity to changes in imaging protocol, the method provides a more robust estimate than standard approaches. In addition, the generated emphysema delineations promise great advantages for regional analysis of emphysema extent and progression, possibly advancing disease subtyping. PMID:24759984

  17. Telomere Length Is a Determinant of Emphysema Susceptibility

    PubMed Central

    Alder, Jonathan K.; Guo, Nini; Kembou, Frant; Parry, Erin M.; Anderson, Collin J.; Gorgy, Amany I.; Walsh, Michael F.; Sussan, Thomas; Biswal, Shyam; Mitzner, Wayne; Tuder, Rubin M.

    2011-01-01

    Rationale: Germline mutations in the enzyme telomerase cause telomere shortening, and have their most common clinical manifestation in age-related lung disease that manifests as idiopathic pulmonary fibrosis. Short telomeres are also a unique heritable trait that is acquired with age. Objectives: We sought to understand the mechanisms by which telomerase deficiency contributes to lung disease. Methods: We studied telomerase null mice with short telomeres. Measurements and Main Results: Although they have no baseline histologic defects, when mice with short telomeres are exposed to chronic cigarette smoke, in contrast with controls, they develop emphysematous air space enlargement. The emphysema susceptibility did not depend on circulating cell genotype, because mice with short telomeres developed emphysema even when transplanted with wild-type bone marrow. In lung epithelium, cigarette smoke exposure caused additive DNA damage to telomere dysfunction, which limited their proliferative recovery, and coincided with a failure to down-regulate p21, a mediator of cellular senescence, and we show here, a determinant of alveolar epithelial cell cycle progression. We also report early onset of emphysema, in addition to pulmonary fibrosis, in a family with a germline deletion in the Box H domain of the RNA component of telomerase. Conclusions: Our data indicate that short telomeres lower the threshold of cigarette smoke–induced damage, and implicate telomere length as a genetic susceptibility factor in emphysema, potentially contributing to its age-related onset in humans. PMID:21757622

  18. Classification of pulmonary emphysema from chest CT scans using integral geometry descriptors

    NASA Astrophysics Data System (ADS)

    van Rikxoort, E. M.; Goldin, J. G.; Galperin-Aizenberg, M.; Brown, M. S.

    2011-03-01

    To gain insight into the underlying pathways of emphysema and monitor the effect of treatment, methods to quantify and phenotype the different types of emphysema from chest CT scans are of crucial importance. Current standard measures rely on density thresholds for individual voxels, which is influenced by inspiration level and does not take into account the spatial relationship between voxels. Measures based on texture analysis do take the interrelation between voxels into account and therefore might be useful for distinguishing different types of emphysema. In this study, we propose to use Minkowski functionals combined with rotation invariant Gaussian features to distinguish between healthy and emphysematous tissue and classify three different types of emphysema. Minkowski functionals characterize binary images in terms of geometry and topology. In 3D, four Minkowski functionals are defined. By varying the threshold and size of neighborhood around a voxel, a set of Minkowski functionals can be defined for each voxel. Ten chest CT scans with 1810 annotated regions were used to train the method. A set of 108 features was calculated for each training sample from which 10 features were selected to be most informative. A linear discriminant classifier was trained to classify each voxel in the lungs into a subtype of emphysema or normal lung. The method was applied to an independent test set of 30 chest CT scans with varying amounts and types of emphysema with 4347 annotated regions of interest. The method is shown to perform well, with an overall accuracy of 95%.

  19. Proteomic Analysis of Aortae from Human Lipoprotein(a) Transgenic Mice Shows an Early Metabolic Response Independent of Atherosclerosis

    PubMed Central

    Rodger, Euan J.; Suetani, Rachel J.; Jones, Gregory T.; Kleffmann, Torsten; Carne, Alan; Legge, Michael; McCormick, Sally P. A.

    2012-01-01

    Background Elevated low density lipoprotein (LDL) and lipoprotein(a) are independent risk factors for the development of atherosclerosis. Using a proteomic approach we aimed to determine early changes in arterial protein expression in transgenic mice containing both human LDL and lipoprotein(a) in circulation. Methods and Results Plasma lipid analyses showed the lipoprotein(a) transgenic mice had significantly higher lipid levels than wildtype, including a much increased LDL and high density lipoprotein (HDL) cholesterol. Analysis of aortae from lipoprotein(a) mice showed lipoprotein(a) accumulation but no lipid accumulation or foam cells, leaving the arteries essentially atherosclerosis free. Using two-dimensional gel electrophoresis and mass spectrometry, we identified 34 arterial proteins with significantly altered abundance (P<0.05) in lipoprotein(a) transgenic mice compared to wildtype including 17 that showed a ≥2 fold difference. Some proteins of interest showed a similarly altered abundance at the transcript level. These changes collectively indicated an initial metabolic response that included a down regulation in energy, redox and lipid metabolism proteins and changes in structural proteins at a stage when atherosclerosis had not yet developed. Conclusions Our study shows that human LDL and lipoprotein(a) promote changes in the expression of a unique set of arterial proteins which may be early indicators of the metabolic disturbances preceding atherosclerosis. PMID:22276189

  20. [ENDOSCOPIC LUNG VOLUME REDUCTION IN PULMONARY EMPHYSEMA].

    PubMed

    Duysinx, B; Heinen, V; Louis, R; Corhay, J-L

    2015-12-01

    Emphysema is characterized by an irreversible alveolar destruction, a progressive lung hyperinflation and a dysfunction of respiratory muscles. It induces a respiratory functional limitation and a decrease of quality of life. Endoscopic lung volume reduction represents a potential alternative to surgical treatments for advanced heterogeneous emphysema without concomitant surgical morbidity. The different bronchoscopic systems for lung volume reduction currently under evaluation are presented.

  1. Organic Anion Transporter 1 Is Inhibited by Multiple Mechanisms and Shows a Transport Mode Independent of Exchange.

    PubMed

    Hotchkiss, Adam G; Gao, Tiandai; Khan, Usman; Berrigan, Liam; Li, Mansong; Ingraham, Leslie; Pelis, Ryan M

    2015-12-01

    The mechanism by which drugs inhibit organic anion transporter 1 (OAT1) was examined. OAT1 was stably expressed in Chinese hamster ovary (CHO) cells, and para-aminohippurate (PAH) and 6-carboxyfluorescein were the substrates. Most compounds (10 of 14) inhibited competitively, increasing the Michaelis constant (Km) without affecting the maximal transport rate (Jmax). Others were mixed-type (lowering Jmax and increasing Km) or noncompetitive (lowering Jmax only) inhibitors. The interaction of a noncompetitive inhibitor (telmisartan) with OAT1 was examined further. Binding of telmisartan to OAT1 was observed, but translocation was not. Telmisartan did not alter the plasma membrane expression of OAT1, indicating that it lowers Jmax by reducing the turnover number. PAH transport after telmisartan treatment and its washout recovered faster in the presence of 10% fetal bovine serum in the washout buffer, indicating that binding of telmisartan to OAT1 and its inhibitory effect are reversible. Together, these data suggest that telmisartan binds reversibly to a site distinct from substrate and stabilizes the transporter in a conformation unfavorable for translocation. In the absence of an exchangeable extracellular substrate, PAH efflux from CHO-OAT1 cells was relatively rapid. Telmisartan slowed PAH efflux, suggesting that some transporter-mediated efflux occurs independent of exchange. Although drug-drug interaction predictions at OAT1 assume competitive inhibition, these data show that OAT1 can be inhibited by other mechanisms, which could influence the accuracy of drug-drug interaction predictions at the transporter. Telmisartan was useful for examining how a noncompetitive inhibitor can alter OAT1 transport activity and for uncovering a transport mode independent of exchange.

  2. Female Flinders Sensitive Line rats show estrous cycle-independent depression-like behavior and altered tryptophan metabolism.

    PubMed

    Eskelund, Amanda; Budac, David P; Sanchez, Connie; Elfving, Betina; Wegener, Gregers

    2016-08-04

    Clinical studies suggest a link between depression and dysfunctional tryptophan (TRP) metabolism. Even though depression is twice as prevalent in women as men, the impact of the estrous cycle on TRP metabolism is not well-understood. Here we investigated 13 kynurenine and serotonin metabolites in female Flinders Sensitive Line (FSL) rats, a genetic rat model of depression. FSL rats and controls (Flinders Resistant Line rats), 12-20weeks old, were subject to the forced swim test (FST), a commonly used measure of depression-like behavior. Open field was used to evaluate locomotor ability and agoraphobia. Subsequently, plasma and hemispheres were collected and analyzed for their content of TRP metabolites using liquid chromatography-tandem mass spectrometry. Vaginal saline lavages were obtained daily for ⩾2 cycles. To estimate the effects of sex and FST we included plasma from unhandled, naïve male FSL and FRL rats. Female FSL rats showed a depression-like phenotype with increased immobility in the FST, not confounded by anxiety. In the brain, 3-hydroxykynurenine was increased whereas anthranilate and 5-hydroxytryptophan were decreased. In plasma, anthranilate and quinolinate levels were lower in FSL rats compared to the control line, independent of sex and FST. The estrous cycle neither impacted behavior nor TRP metabolite levels in the FSL rat. In conclusion, the female FSL rat is an interesting preclinical model of depression with altered TRP metabolism, independent of the estrous cycle. The status of the pathway in brain was not reflected in the plasma, which may indicate that an inherent local, cerebral regulation of TRP metabolism occurs.

  3. The role of oxidative processes in emphysema

    SciTech Connect

    Janoff, A.; Carp, H.; Laurent, P.; Raju, L.

    1983-02-01

    Elastase/elastase inhibitor imbalance in the lung has been implicated in the pathogenesis of pulmonary emphysema. In light of this, it may be significant that the activity of two major elastase inhibitors, alpha 1-proteinase inhibitor (alpha 1-antitrypsin, alpha 1Pi) and bronchial mucous proteinase inhibitor, can be decreased by oxidizing agents. The effect can be observed with ozone, substances present in cigarette smoke, and oxygen metabolites generated by lung macrophages as well as peroxidative systems released by other phagocytic cells. Thus alpha 1Pi recovered from lung washings of cigarette smokers has only half the predicted normal activity per mg inhibitor and contains 4 moles of methionine sulfoxide (oxidized methionine) per mole of inactive inhibitor. By contrast, alpha 1Pi purified from nonsmokers' lung washings is fully active and contains only native methionine. At the same time, lung washes from some smokers show significantly greater hydrolytic activity against a specific synthetic elastase substrate than do lung washes of nonsmokers. These findings suggest that some smokers may develop an acquired imbalance between elastase and elastase inhibitor in their lungs, favoring activity of the enzyme. In addition to the potential effect of cigarette smoking on lung elastase/elastase inhibitor balance, smoking also may interfere with elastin repair mechanisms. Specifically, acidic water-soluble gas phase components of cigarette smoke prevent synthesis of desmosine cross-links during elastinogenesis in vitro. This report will attempt to correlate the foregoing information on biochemical changes in the lung induced by cigarette smoking with the development of emphysema in the smoker.

  4. Combined Pulmonary Fibrosis and Emphysema Syndrome

    PubMed Central

    Rounds, Sharon I. S.

    2012-01-01

    There is increasing clinical, radiologic, and pathologic recognition of the coexistence of emphysema and pulmonary fibrosis in the same patient, resulting in a clinical syndrome known as combined pulmonary fibrosis and emphysema (CPFE) that is characterized by dyspnea, upper-lobe emphysema, lower-lobe fibrosis, and abnormalities of gas exchange. This syndrome frequently is complicated by pulmonary hypertension, acute lung injury, and lung cancer. The CPFE syndrome typically occurs in male smokers, and the mortality associated with this condition, especially if pulmonary hypertension is present, is significant. In this review, we explore the current state of the literature and discuss etiologic factors and clinical characteristics of the CPFE syndrome. PMID:22215830

  5. Pulmonary emphysema: when more is less.

    PubMed

    Morris, David G; Sheppard, Dean

    2006-12-01

    Pulmonary emphysema results from the loss of intricate alveolar architecture and progressive simplification of small and highly effective gas-exchanging units into large, inefficient cyst-like spaces. Because of the loss of alveolar gas-exchanging units and the capillary bed within them, blood oxygen levels eventually fall and pressures within the pulmonary circulation rise. Recent insights from genetically manipulated mouse models have refined our understanding of the molecular events that prevent or promote the development of pulmonary emphysema. Capitalizing on an improved molecular understanding of emphysema with improved therapeutics has the potential to enhance both the survival and quality of life of patients with this common lung disease.

  6. Emphysema

    MedlinePlus

    ... sacs weaken and eventually rupture — creating one larger air space instead of many small ones. This reduces the surface area of the lungs and, in turn, the amount of oxygen that reaches ... work properly and old air becomes trapped, leaving no room for fresh, oxygen- ...

  7. Quantitative assessment of smoking-induced emphysema progression in longitudinal CT screening for lung cancer

    NASA Astrophysics Data System (ADS)

    Suzuki, H.; Mizuguchi, R.; Matsuhiro, M.; Kawata, Y.; Niki, N.; Nakano, Y.; Ohmatsu, H.; Kusumoto, M.; Tsuchida, T.; Eguchi, K.; Kaneko, M.; Moriyama, N.

    2015-03-01

    Computed tomography has been used for assessing structural abnormalities associated with emphysema. It is important to develop a robust CT based imaging biomarker that would allow quantification of emphysema progression in early stage. This paper presents effect of smoking on emphysema progression using annual changes of low attenuation volume (LAV) by each lung lobe acquired from low-dose CT images in longitudinal screening for lung cancer. The percentage of LAV (LAV%) was measured after applying CT value threshold method and small noise reduction. Progression of emphysema was assessed by statistical analysis of the annual changes represented by linear regression of LAV%. This method was applied to 215 participants in lung cancer CT screening for five years (18 nonsmokers, 85 past smokers, and 112 current smokers). The results showed that LAV% is useful to classify current smokers with rapid progression of emphysema (0.2%/year, p<0.05). This paper demonstrates effectiveness of the proposed method in diagnosis and prognosis of early emphysema in CT screening for lung cancer.

  8. Neighborhood diversity of large trees shows independent species patterns in a mixed dipterocarp forest in Sri Lanka.

    PubMed

    Punchi-Manage, Ruwan; Wiegand, Thorsten; Wiegand, Kerstin; Getzin, Stephan; Huth, Andreas; Gunatilleke, C V Savitri; Gunatilleke, I A U Nimal

    2015-07-01

    Interactions among neighboring individuals influence plant performance and should create spatial patterns in local community structure. In order to assess the role of large trees in generating spatial patterns in local species richness, we used the individual species-area relationship (ISAR) to evaluate the species richness of trees of different size classes (and dead trees) in circular neighborhoods with varying radius around large trees of different focal species. To reveal signals of species interactions, we compared the ISAR function of the individuals of focal species with that of randomly selected nearby locations. We expected that large trees should strongly affect the community structure of smaller trees in their neighborhood, but that these effects should fade away with increasing size class. Unexpectedly, we found that only few focal species showed signals of species interactions with trees of the different size classes and that this was less likely for less abundant focal species. However, the few and relatively weak departures from independence were consistent with expectations of the effect of competition for space and the dispersal syndrome on spatial patterns. A noisy signal of competition for space found for large trees built up gradually with increasing life stage; it was not yet present for large saplings but detectable for intermediates. Additionally, focal species with animal-dispersed seeds showed higher species richness in their neighborhood than those with gravity- and gyration-dispersed seeds. Our analysis across the entire ontogeny from recruits to large trees supports the hypothesis that stochastic effects dilute deterministic species interactions in highly diverse communities. Stochastic dilution is a consequence of the stochastic geometry of biodiversity in species-rich communities where the identities of the nearest neighbors of a given plant are largely unpredictable. While the outcome of local species interactions is governed for each

  9. Mediastinal bronchogenic cyst mimicking congenital lobar emphysema.

    PubMed

    Arun, Sumitha; Kumar, Manish; Ross, Benjamin Jeyanth

    2016-09-08

    Bronchogenic cyst (BC) is a rare congenital malformation of the lung. Most patients remain asymptomatic until adulthood while some are symptomatic in the first few years of life. However, symptoms in newborn period are rare. We report a case of a 3-day-old preterm baby with respiratory distress diagnosed as congenital lobar emphysema on chest X-ray. A CT scan revealed a mediastinal cyst causing obstructive lobar emphysema. The cyst was excised and pathological examination was suggestive of BC.

  10. Sex Differences in Severe Pulmonary Emphysema

    PubMed Central

    Martinez, Fernando J.; Curtis, Jeffrey L.; Sciurba, Frank; Mumford, Jeanette; Giardino, Nicholas D.; Weinmann, Gail; Kazerooni, Ella; Murray, Susan; Criner, Gerard J.; Sin, Donald D.; Hogg, James; Ries, Andrew L.; Han, MeiLan; Fishman, Alfred P.; Make, Barry; Hoffman, Eric A.; Mohsenifar, Zab; Wise, Robert

    2007-01-01

    Rationale: Limited data on sex differences in advanced COPD are available. Objectives: To compare male and female emphysema patients with severe disease. Methods: One thousand fifty-three patients (38.8% female) evaluated for lung volume reduction surgery as part of the National Emphysema Treatment Trial were analyzed. Measurements and Main Results: Detailed clinical, physiological, and radiological assessment, including quantitation of emphysema severity and distribution from helical chest computed tomography, was completed. In a subgroup (n = 101), airway size and thickness was determined by histological analyses of resected tissue. Women were younger and exhibited a lower body mass index (BMI), shorter smoking history, less severe airflow obstruction, lower Dlco and arterial Po2, higher arterial Pco2, shorter six-minute walk distance, and lower maximal wattage during oxygen-supplemented cycle ergometry. For a given FEV1% predicted, age, number of pack-years, and proportion of emphysema, women experienced greater dyspnea, higher modified BODE, more depression, lower SF-36 mental component score, and lower quality of well-being. Overall emphysema was less severe in women, with the difference from men most evident in the outer peel of the lung. Females had thicker small airway walls relative to luminal perimeters. Conclusions: In patients with severe COPD, women, relative to men, exhibit anatomically smaller airway lumens with disproportionately thicker airway walls, and emphysema that is less extensive and characterized by smaller hole size and less peripheral involvement. PMID:17431226

  11. Relation between progressive massive fibrosis, emphysema, and pulmonary dysfunction in coalworkers' pneumoconiosis.

    PubMed Central

    Lyons, J P; Campbell, H

    1981-01-01

    The correlations between progressive massive fibrosis (PMF), emphysema, and impairment of ventilation were studied in 108 dead coalminers, all of whom had suffered with complicated coalworkers' pneumoconiosis (radiological category B or C) during life. The findings indicated that both factors were contributing to impairment of ventilation in proportion to their size or extent, but these contributions were in the main independent of one another. A joint opinion on the types of emphysema found to be present in a random 50 out of the 108 cases was given by two pulmonary pathologists. They found that most of the emphysema was of the centrilobular variety, which appeared to be unrelated to the PMF. The distribution of the PMF throughout the lungs both radiologically and anatomically is shown. Images PMID:7236536

  12. Toll-like receptor 4 deficiency causes pulmonary emphysema.

    PubMed

    Zhang, Xuchen; Shan, Peiying; Jiang, Ge; Cohn, Lauren; Lee, Patty J

    2006-11-01

    TLRs have been studied extensively in the context of pathogen challenges, yet their role in the unchallenged lung is unknown. Given their direct interface with the external environment, TLRs in the lungs are prime candidates to respond to air constituents, namely particulates and oxygen. The mechanism whereby the lung maintains structural integrity in the face of constant ambient exposures is essential to our understanding of lung disease. Emphysema is characterized by gradual loss of lung elasticity and irreversible airspace enlargement, usually in the later decades of life and after years of insult, most commonly cigarette smoke. Here we show Tlr4(-/-) mice exhibited emphysema as they aged. Adoptive transfer experiments revealed that TLR4 expression in lung structural cells was required for maintaining normal lung architecture. TLR4 deficiency led to the upregulation of what we believe to be a novel NADPH oxidase (Nox), Nox3, in lungs and endothelial cells, resulting in increased oxidant generation and elastolytic activity. Treatment of Tlr4(-/- )mice or endothelial cells with chemical NADPH inhibitors or Nox3 siRNA reversed the observed phenotype. Our data identify a role for TLR4 in maintaining constitutive lung integrity by modulating oxidant generation and provide insights into the development of emphysema.

  13. Transforming growth factor-beta receptor-3 is associated with pulmonary emphysema.

    PubMed

    Hersh, Craig P; Hansel, Nadia N; Barnes, Kathleen C; Lomas, David A; Pillai, Sreekumar G; Coxson, Harvey O; Mathias, Rasika A; Rafaels, Nicholas M; Wise, Robert A; Connett, John E; Klanderman, Barbara J; Jacobson, Francine L; Gill, Ritu; Litonjua, Augusto A; Sparrow, David; Reilly, John J; Silverman, Edwin K

    2009-09-01

    Chronic obstructive pulmonary disease (COPD) is a heterogeneous syndrome, including emphysema and airway disease. Phenotypes defined on the basis of chest computed tomography (CT) may decrease disease heterogeneity and aid in the identification of candidate genes for COPD subtypes. To identify these genes, we performed genome-wide linkage analysis in extended pedigrees from the Boston Early-Onset COPD Study, stratified by emphysema status (defined by chest CT scans) of the probands, followed by genetic association analysis of positional candidate genes. A region on chromosome 1p showed strong evidence of linkage to lung function traits in families of emphysema-predominant probands in the stratified analysis (LOD score = 2.99 in families of emphysema-predominant probands versus 1.98 in all families). Association analysis in 949 individuals from 127 early-onset COPD pedigrees revealed association for COPD-related traits with an intronic single-nucleotide polymorphism (SNP) in transforming growth factor-beta receptor-3 (TGFBR3) (P = 0.005). This SNP was significantly associated with COPD affection status comparing 389 cases from the National Emphysema Treatment Trial to 472 control smokers (P = 0.04), and with FEV(1) (P = 0.004) and CT emphysema (P = 0.05) in 3,117 subjects from the International COPD Genetics Network. Gene-level replication of association with lung function was seen in 427 patients with COPD from the Lung Health Study. In conclusion, stratified linkage analysis followed by association testing identified TGFBR3 (betaglycan) as a potential susceptibility gene for COPD. Published human microarray and murine linkage studies have also demonstrated the importance of TGFBR3 in emphysema and lung function, and our group and others have previously found association of COPD-related traits with TGFB1, a ligand for TGFBR3.

  14. Is alveolar destruction and emphysema in chronic obstructive pulmonary disease an immune disease?

    PubMed

    Taraseviciene-Stewart, Laima; Douglas, Ivor S; Nana-Sinkam, Patrick S; Lee, Jong D; Tuder, Rubin M; Nicolls, Mark R; Voelkel, Norbert F

    2006-11-01

    The alveolar destruction leading to airspace enlargement in patients with end-stage chronic obstructive pulmonary disease (COPD) is frequently progressive, despite smoking cessation. Several laboratories have accumulated data demonstrating the presence of immune cells in bronchial biopsy specimens and lung tissue sections from patients with COPD. Recently, the accumulation of T and B lymphocytes, often forming follicles, in the lung parenchyma from patients with severe COPD has been reported. In addition, it has been postulated that there might be an autoimmune component to COPD. T-cell receptor analysis has provided data consistent with the concept of T-cell clones in the lung tissue from patients with COPD. Against this background, we developed a model of autoimmune emphysema in adult rats. Based on published data showing that immunization of mice with human umbilical vein endothelial cells (HUVECs) causes production of anti-vascular endothelial growth factor (VEGF) receptor II (KDR) antibodies, and our own data indicating that administration of a VEGF receptor blocker in adult rats causes emphysema, we reasoned that intraperitoneal injection of HUVECs in rats would generate both anti-VEGF receptor antibodies and emphysema. Indeed, intraperitoneal injection of HUVECs caused emphysema. We further explored the autoimmune nature of this model, identified KDR antibodies in the serum of HUVEC-immunized rats, and injected serum from the emphysematous rats into naive rats and mice, which resulted in emphysema. Presently, we are in the process of investigating whether cigarette smoke extract causes emphysema. We recently identified anti-endothelial cell antibodies in the serum of patients with end-stage emphysema.

  15. VEGF-A Expressing Adipose Tissue Shows Rapid Beiging, Enhanced Survival After Transplantation and Confers IL4-Independent Metabolic Improvements.

    PubMed

    Park, Jiyoung; Kim, Min; Sun, Kai; An, Yu Aaron; Gu, Xue; Scherer, Philipp E

    2017-03-02

    Adipocyte-derived VEGF-A plays a crucial role in angiogenesis and contributes to adipocyte function and systemic metabolism, such as insulin resistance, chronic inflammation and beigeing of subcutaneous adipose tissue. Utilizing a doxycycline (Dox)-inducible adipocyte-specific VEGF-A overexpressing mouse model, we investigated the dynamics of local VEGF-A effects on tissue beiging of adipose tissue transplants. VEGF-A overexpression in adipocytes triggers angiogenesis. We also observe a rapid appearance of beige fat cells in subcutaneous white adipose tissue (sWATs) within as early as 2 days post induction of VEGF-A. In contrast to conventional cold-induced beiging, VEGF-A - induced beiging is independent of IL-4. We subjected metabolically healthy VEGF-A overexpressing adipose tissue to autologous transplantation. Transfer of subcutaneous adipose tissues taken from VEGF-A overexpressing mice into diet-induced obese mice resulted in systemic metabolic benefits, associated with improved survival of adipocytes and a concomitant reduced inflammatory response. These effects of VEGF-A are tissue autonomous, inducing WAT beigeing and angiogenesis within the transplanted tissue. Our findings indicate that manipulation of adipocyte functions with a bona fide angiogenic factor, such as VEGF-A, significantly improves the survival and volume retention of fat grafts and can convey metabolically favorable properties on the recipient on the basis of beiging.

  16. Pulmonary Microvascular Blood Flow in Mild Chronic Obstructive Pulmonary Disease and Emphysema. The MESA COPD Study

    PubMed Central

    Hueper, Katja; Vogel-Claussen, Jens; Parikh, Megha A.; Austin, John H. M.; Bluemke, David A.; Carr, James; Choi, Jiwoong; Goldstein, Thomas A.; Gomes, Antoinette S.; Hoffman, Eric A.; Kawut, Steven M.; Lima, Joao; Michos, Erin D.; Post, Wendy S.; Po, Ming Jack; Prince, Martin R.; Liu, Kiang; Rabinowitz, Dan; Skrok, Jan; Smith, Ben M.; Watson, Karol; Yin, Youbing; Zambeli-Ljepovic, Alan M.

    2015-01-01

    Rationale: Smoking-related microvascular loss causes end-organ damage in the kidneys, heart, and brain. Basic research suggests a similar process in the lungs, but no large studies have assessed pulmonary microvascular blood flow (PMBF) in early chronic lung disease. Objectives: To investigate whether PMBF is reduced in mild as well as more severe chronic obstructive pulmonary disease (COPD) and emphysema. Methods: PMBF was measured using gadolinium-enhanced magnetic resonance imaging (MRI) among smokers with COPD and control subjects age 50 to 79 years without clinical cardiovascular disease. COPD severity was defined by standard criteria. Emphysema on computed tomography (CT) was defined by the percentage of lung regions below −950 Hounsfield units (−950 HU) and by radiologists using a standard protocol. We adjusted for potential confounders, including smoking, oxygenation, and left ventricular cardiac output. Measurements and Main Results: Among 144 participants, PMBF was reduced by 30% in mild COPD, by 29% in moderate COPD, and by 52% in severe COPD (all P < 0.01 vs. control subjects). PMBF was reduced with greater percentage emphysema−950HU and radiologist-defined emphysema, particularly panlobular and centrilobular emphysema (all P ≤ 0.01). Registration of MRI and CT images revealed that PMBF was reduced in mild COPD in both nonemphysematous and emphysematous lung regions. Associations for PMBF were independent of measures of small airways disease on CT and gas trapping largely because emphysema and small airways disease occurred in different smokers. Conclusions: PMBF was reduced in mild COPD, including in regions of lung without frank emphysema, and may represent a distinct pathological process from small airways disease. PMBF may provide an imaging biomarker for therapeutic strategies targeting the pulmonary microvasculature. PMID:26067761

  17. Stochastic simulation of alveolar particle deposition in lungs affected by different types of emphysema.

    PubMed

    Sturm, R; Hofmann, W

    2004-01-01

    In the present study, disease-specific stochastic models were developed for the computation of particle deposition in lungs affected by COPD, emphysema, or both, distinguishing between four types of pulmonary emphysema-centriacinar, paraseptal, panacinar, and bullous. To simulate COPD, airway calibers of the tracheobronchial tree were randomly reduced between 20% and 50% in each airway. For the study of pure COPD ("blue bloaters"), alveolated airway dimensions of the healthy lung were used, while for the simulation of emphysema without COPD ("pink puffers"), normal conductive airway diameters were assumed. Deposition calculations in diseased lungs were carried out by assuming (a) identical inspiration and expiration times (no breath-hold time) and (b) a continuous increase of the functional residual capacity (from 3,300 to 5,000 mL), accompanied by a simultaneous drop of the tidal volume (from 1,000 to 500 mL). Independent of particle size, total alveolar deposition in emphysematous lungs was significantly decreased relative to normal lungs. In particular, the deposition maximum at large particle sizes, which is a characteristic for healthy subjects, completely disappeared. Among the various emphysema models, deposition was smallest in lungs with bullous emphysema due to strongly enhanced settling and diffusion distances within the alveolar structures. A change of the lung volume caused a further decrease in particle deposition. Alveolar deposition in "blue bloaters" and "pink puffers" was very similar to the deposition in patients suffering from COPD and emphysema. Alveolar deposition per acinar airway generation was also strongly reduced in diseased lungs compared to normal lungs. Besides this reduction, deposition patterns became more uniform throughout the alveolar region.

  18. Matrix Remodeling in Pulmonary Fibrosis and Emphysema.

    PubMed

    Kulkarni, Tejaswini; O'Reilly, Philip; Antony, Veena B; Gaggar, Amit; Thannickal, Victor J

    2016-06-01

    Pulmonary fibrosis and emphysema are chronic lung diseases characterized by a progressive decline in lung function, resulting in significant morbidity and mortality. A hallmark of these diseases is recurrent or persistent alveolar epithelial injury, typically caused by common environmental exposures such as cigarette smoke. We propose that critical determinants of the outcome of the injury-repair processes that result in fibrosis versus emphysema are mesenchymal cell fate and associated extracellular matrix dynamics. In this review, we explore the concept that regulation of mesenchymal cells under the influence of soluble factors, in particular transforming growth factor-β1, and the extracellular matrix determine the divergent tissue remodeling responses seen in pulmonary fibrosis and emphysema.

  19. Pulmonary fibrosis and emphysema: Is the emphysema type associated with the pattern of fibrosis?

    PubMed Central

    Oikonomou, Anastasia; Mintzopoulou, Paraskevi; Tzouvelekis, Argyris; Zezos, Petros; Zacharis, George; Koutsopoulos, Anastasios; Bouros, Demosthenes; Prassopoulos, Panos

    2015-01-01

    AIM: To investigate whether the predominant emphysema type is associated with the high resolution computed tomography (HRCT) pattern of fibrosis in combined pulmonary fibrosis and emphysema (CPFE). METHODS: Fifty-three smokers with upper lobe emphysema and lower lobe pulmonary fibrosis on - HRCT - were retrospectively evaluated. Patients were stratified into 3 groups according to the predominant type of emphysema: Centrilobular (CLE), paraseptal (PSE), CLE = PSE. Patients were also stratified into 3 other groups according to the predominant type of fibrosis on HRCT: Typical usual interstitial pneumonia (UIP), probable UIP and nonspecific interstitial pneumonia (NSIP). HRCTs were scored at 5 predetermined levels for the coarseness of fibrosis (Coarseness), extent of emphysema (emphysema), extent of interstitial lung disease (TotExtILD), extent of reticular pattern not otherwise specified (RetNOS), extent of ground glass opacity with traction bronchiectasis (extGGOBx), extent of pure ground glass opacity and extent of honeycombing. HRCT mean scores, pulmonary function tests, diffusion capacity (DLCO) and systolic pulmonary arterial pressure were compared among the groups. RESULTS: The predominant type of emphysema was strongly correlated with the predominant type of fibrosis. The centrilobular emphysema group exhibited a significantly higher extent of emphysema (P < 0.001) and a lower extent of interstitial lung disease (P < 0.002), reticular pattern not otherwise specified (P < 0.023), extent of ground glass opacity with traction bronchiectasis (P < 0.002), extent of honeycombing (P < 0.001) and coarseness of fibrosis (P < 0.001) than the paraseptal group. The NSIP group exhibited a significantly higher extent of emphysema (P < 0.05), total lung capacity (P < 0.01) and diffusion capacity (DLCO) (P < 0.05) than the typical UIP group. The typical UIP group exhibited a significantly higher extent of interstitial lung disease, extent of reticular pattern not otherwise

  20. Report: Independent Environmental Sampling Shows Some Properties Designated by EPA as Available for Use Had Some Contamination

    EPA Pesticide Factsheets

    Report #15-P-0221, July 21, 2015. Some OIG sampling results showed contamination was still present at sites designated by the EPA as ready for reuse. This was unexpected and could signal a need to implement changes to ensure human health protection.

  1. Gene replacement therapy for hereditary emphysema

    SciTech Connect

    Skolnick, A.

    1989-11-10

    Investigators suggest that human trials of gene therapy to correct a genetic disorder that usually leads to emphysema early in life may be only a few years away. Speaking at the American Lung Association's Second Annual Science Writers' Forum, R. G. Crystal, chief of the Pulmonary Branch of the National Heart, Lung, and Blood Institute offered an explanation of how hereditary emphysema may be more amenable to genetic therapy than other such diseases. In persons who lack a functioning gene for alpha{sup 1}-antitrypsin, a proteolytic enzyme, neutrophil elastase, attacks the walls of the lungs' alveoli, eventually leading to progressive pulmonary function loss. Two animal models of gene insertion are described.

  2. Subcutaneous emphysema and pneumolabyrinth plus pneumocephalus as complications of middle ear implant and cochlear implant surgery.

    PubMed

    McKinnon, Brian J; Watts, Tamara

    2013-07-01

    We conducted a retrospective case review at a tertiary academic medical center for the complications of pneumolabyrinth with pneumocephalus and subcutaneous emphysema after surgery for middle ear and cochlear implants. Charts of 76 cochlear implant and 2 middle ear implant patients from January 2001 through June 2009 were reviewed. We identified 1 cochlear implant recipient with pneumolabyrinth and pneumocephalus, and 1 middle ear implant recipient with subcutaneous emphysema. Surgical exploration was performed for the pneumolabyrinth with pneumocephalus; the subcutaneous emphysema was managed conservatively. The patient with the cochlear implant, who had had a ventriculoperitoneal shunt placed, experienced pneumolabyrinth with pneumocephalus 6 years after uneventful surgery. Middle ear exploration revealed no residual fibrous tissue seal at the cochleostomy. The middle ear and cochleostomy were obliterated with muscle, fat, and fibrin glue. The ventriculoperitoneal shunt was deactivated, with clinical and radiographic resolution. On postoperative day 5, the patient who had undergone the middle ear implant reported crepitance over the mastoid and implant device site after repeated Valsalva maneuvers. Computed tomography showed air surrounding the internal processor. A mastoid pressure dressing was applied and the subcutaneous emphysema resolved. These 2 cases support the importance of recognizing the clinical presentation of pneumolabyrinth with associated pneumocephalus, as well as subcutaneous emphysema. Securing the internal processor, adequately sealing the cochleostomy, and providing preoperative counseling regarding Valsalva maneuvers and the potential risk of cochlear implantation in the presence of a ventriculoperitoneal shunt may prevent adverse sequelae.

  3. Detecting airway remodeling in COPD and emphysema using low-dose CT imaging

    NASA Astrophysics Data System (ADS)

    Rudyanto, R.; Ceresa, M.; Muñoz-Barrutia, A.; Ortiz-de-Solorzano, C.

    2012-03-01

    In this study, we quantitatively characterize lung airway remodeling caused by smoking-related emphysema and Chronic Obstructive Pulmonary Disease (COPD), in low-dose CT scans. To that end, we established three groups of individuals: subjects with COPD (n=35), subjects with emphysema (n=38) and healthy smokers (n=28). All individuals underwent a low-dose CT scan, and the images were analyzed as described next. First the lung airways were segmented using a fast marching method and labeled according to its generation. Along each airway segment, cross-section images were resampled orthogonal to the airway axis. Next 128 rays were cast from the center of the airway lumen in each crosssection slice. Finally, we used an integral-based method, to measure lumen radius, wall thickness, mean wall percentage and mean peak wall attenuation on every cast ray. Our analysis shows that both the mean global wall thickness and the lumen radius of the airways of both COPD and emphysema groups were significantly different from those of the healthy group. In addition, the wall thickness change starts at the 3rd airway generation in the COPD patients compared with emphysema patients, who display the first significant changes starting in the 2nd generation. In conclusion, it is shown that airway remodeling happens in individuals suffering from either COPD or emphysema, with some local difference between both groups, and that we are able to detect and accurately quantify this process using images of low-dose CT scans.

  4. Mitochondrial DNA and morphology show independent evolutionary histories of bedbug Cimex lectularius (Heteroptera: Cimicidae) on bats and humans.

    PubMed

    Balvín, Ondřej; Munclinger, Pavel; Kratochvíl, Lukáš; Vilímová, Jitka

    2012-07-01

    The bedbug, Cimex lectularius, is a well-known human ectoparasite that is reemerging after a long absence of several decades in developed countries of North America and Western Europe. Bedbugs' original hosts were likely bats, and the bedbugs are still common in their roosts. Using morphometry and sequences of mitochondrial cytochrome oxidase subunit I and 16S genes, we showed that the populations on bats and humans are largely isolated and differ in morphology. The character of the morphological difference suggests it to be due to adaptation to different hosts, namely adaptations to different sensory, feeding, and dispersal needs. Using the molecular data, we estimated the time of splitting into bat- and human-parasitizing groups using the isolation-with-migration model. The estimate is surprisingly long ago and seems to predate the expansion of modern human from Africa. The gene flow between bat- and human-parasitizing bedbugs is limited and asymmetric with prevailing direction from human-parasitizing populations to bat-parasitizing populations. The differentiation of the populations fits the concept of host races and supports the idea of sympatric speciation. Furthermore, our findings contradict recently formulated hypotheses suggesting bat roosts as a source of bedbug's resurgence as a human pest. Also, we extend the known host range of the bedbug by two bat species.

  5. Analysis of pattern precision shows that Drosophila segmentation develops substantial independence from gradients of maternal gene products.

    PubMed

    Holloway, David M; Harrison, Lionel G; Kosman, David; Vanario-Alonso, Carlos E; Spirov, Alexander V

    2006-11-01

    We analyze the relation between maternal gradients and segmentation in Drosophila, by quantifying spatial precision in protein patterns. Segmentation is first seen in the striped expression patterns of the pair-rule genes, such as even-skipped (eve). We compare positional precision between Eve and the maternal gradients of Bicoid (Bcd) and Caudal (Cad) proteins, showing that Eve position could be initially specified by the maternal protein concentrations but that these do not have the precision to specify the mature striped pattern of Eve. By using spatial trends, we avoid possible complications in measuring single boundary precision (e.g., gap gene patterns) and can follow how precision changes in time. During nuclear cleavage cycles 13 and 14, we find that Eve becomes increasingly correlated with egg length, whereas Bcd does not. This finding suggests that the change in precision is part of a separation of segmentation from an absolute spatial measure, established by the maternal gradients, to one precise in relative (percent egg length) units.

  6. ABCA3 mutations led to pulmonary fibrosis and emphysema with pulmonary hypertension in an 8-year-old girl.

    PubMed

    Ota, Chiharu; Kimura, Masato; Kure, Shigeo

    2016-06-01

    ABCA3 is highly expressed in alveolar epithelial type 2 cells and is associated with surfactant homeostasis. Patients with ABCA3 mutations develop various respiratory complications, such as fatal respiratory distress syndrome or interstitial lung disease. We describe a patient with pulmonary fibrosis and emphysema with pulmonary hypertension, associated with compound heterozygous mutations of the ABCA3 gene. This is the first report showing that mutations in the ABCA3 gene lead to pulmonary fibrosis and emphysema, including combined pulmonary fibrosis and emphysema, in childhood. Treatment with prostacyclin analogue, warfarin, and inhaled oxygen was effective to improve patient's hemodynamic condition as well as pulmonary fibrosis and emphysema. Pediatr Pulmonol. 2016;51:E21-E23. © 2016 Wiley Periodicals, Inc.

  7. An advanced case of indium lung disease with progressive emphysema

    PubMed Central

    Nakano, Makiko; Tanaka, Akiyo; Hirata, Miyuki; Kumazoe, Hiroyuki; Wakamatsu, Kentaro; Kamada, Dan; Omae, Kazuyuki

    2016-01-01

    Objectives: To report the occurrence of an advanced case of indium lung disease with severely progressive emphysema in an indium-exposed worker. Case report: A healthy 42-year-old male smoker was employed to primarily grind indium-tin oxide (ITO) target plates, exposing him to indium for 9 years (1998-2008). In 2004, an epidemiological study was conducted on indium-exposed workers at the factory in which he worked. The subject's serum indium concentration (In-S) was 99.7 μg/l, while his serum Krebs von den Lungen-6 level was 2,350 U/ml. Pulmonary function tests showed forced vital capacity (FVC) of 4.17 l (91.5% of the JRS predicted value), forced expiratory volume in 1 s (FEV1) of 3.19 l (80.8% of predicted), and an FEV1-to-FVC ratio of 76.5%. A high-resolution chest computed tomography (HRCT) scan showed mild interlobular septal thickening and mild emphysematous changes. In 2008, he was transferred from the ITO grinding workplace to an inspection work section, where indium concentrations in total dusts had a range of 0.001-0.002 mg/m3. In 2009, the subject's In-S had increased to 132.1 μg/l, and pulmonary function tests revealed obstructive changes. In addition, HRCT scan showed clear evidence of progressive lung destruction with accompanying severe centrilobular emphysema and interlobular septal thickening in both lung fields. The subject's condition gradually worsened, and in 2015, he was registered with the Japan Organ Transplant Network for lung transplantation (LTx). Conclusions: Heavy indium exposure is a risk factor for emphysema, which can lead to a severity level that requires LTx as the final therapeutic option. PMID:27488043

  8. Emphysema quantification from CT scans using novel application of diaphragm curvature estimation: comparison with standard quantification methods and pulmonary function data

    NASA Astrophysics Data System (ADS)

    Keller, Brad M.; Reeves, Anthony P.; Yankelevitz, David F.; Henschke, Claudia I.; Barr, R. Graham

    2009-02-01

    Emphysema is a disease of the lungs that destroys the alveolar air sacs and induces long-term respiratory dysfunction. CT scans allow for the imaging of the anatomical basis of emphysema and quantification of the underlying disease state. Several measures have been introduced for the quantification emphysema directly from CT data; most,however, are based on the analysis of density information provided by the CT scans, which vary by scanner and can be hard to standardize across sites and time. Given that one of the anatomical variations associated with the progression of emphysema is the flatting of the diaphragm due to the loss of elasticity in the lung parenchyma, curvature analysis of the diaphragm would provide information about emphysema from CT. Therefore, we propose a new, non-density based measure of the curvature of the diaphragm that would allow for further quantification methods in a robust manner. To evaluate the new method, 24 whole-lung scans were analyzed using the ratios of the lung height and diaphragm width to diaphragm height as curvature estimates as well as using the emphysema index as comparison. Pearson correlation coefficients showed a strong trend of several of the proposed diaphragm curvature measures to have higher correlations, of up to r=0.57, with DLCO% and VA than did the emphysema index. Furthermore, we found emphysema index to have only a 0.27 correlation to the proposed measures, indicating that the proposed measures evaluate different aspects of the disease.

  9. The National Emphysema Treatment Trial (NETT): Part I: Lessons learned about emphysema.

    PubMed

    Criner, Gerard J; Cordova, Francis; Sternberg, Alice L; Martinez, Fernando J

    2011-10-01

    The National Emphysema Treatment Trial (NETT) was a multicenter prospective randomized controlled trial that compared optimal medical treatment, including pulmonary rehabilitation, with optimal medical treatment plus lung volume reduction surgery (LVRS). It was the largest and most complete collection of patient demographic, clinical, physiological, and radiographic data ever compiled in severe emphysema. NETT investigated the effects of optimal medical management and LVRS on short- and long-term survival, as well as lung function, exercise performance, and quality of life. NETT also provided much information regarding the evaluation and prognosis of severe emphysema; specifically the important negative influences that hyperinflation and small airway disease have on survival. NETT emphasized the importance of addressing nonpulmonary issues such as nutrition, cardiac disease, anxiety, and depression in emphysema. NETT demonstrated that physiological, genomic, and radiographic phenotype can predict patient survival as well as response to treatment. Because the major purpose of NETT was to compare bilateral LVRS with optimal medical treatment in emphysema, patients enrolled into NETT were comprehensively characterized and selected to have a specific window of airflow obstruction and hyperinflation and to lack significant comorbidities. The NETT patient population’s restrictive features offer distinct advantages (well-characterized predominant emphysematous phenotype) and disadvantages (lack of comorbidities and significant chronic bronchitis) that must be considered when interpreting the implications of these results. Herein, we provide a summary of the major NETT findings that provide insight into the evaluation and medical treatment of emphysema.

  10. [Combined pulmonary fibrosis and emphysema syndrome].

    PubMed

    Alilović, Marija; Peroš-Golubićić, Tatjana; Tekavec Trkanjec, Jasna; Hećimović, Ana; Smojver-Ježek, Silvana

    2015-01-01

    CPFE-combined pulmonary fibrosis and emphysema is a new term for a syndrome whose main characteristic is fibrosis in lower pulmonary lobes with simultaneous emphysema in upper pulmonary lobes. CPFE patients have well preserved pulmonary test values for unexpectedly long period, but extremely lowered carbon monoxide diffusion capacity and significant arterial hypertension. All CPFE studies indicate that CPFE occurs predominately in older male population. Smoking is considered main cause in developing CPFE. Reduced survival rate is linked with arterial hypertension extent, and mortality rate is greater than that for patients with isolated pulmonary fibrosis or emphysema. This study is focused on characteristics of twelve CPFE patients. This paper describes cases of 12 patients with the syndrome of pulmonary fibrosis associated with emphysema. All patients were male, mean age of 68 years. At the certain period of life they all were smokers, but most of them were also exposed to air pollution due to their profession. Shortness of breath on exertion was present in all patients. All patients had neat pulmonary function tests with significantly reduced diffusing capacity for carbon mon- oxide (average 39%). Pulmonary arterial hypertension (PAH) averaged 56 mmHg (range 25-75 mmHg) was present in 75% of patients. Four patients died during the period of four months, of which three patients had PAH greater than 70 mmHg. The fourth patient died of lung cancer.

  11. Heterogeneity of pulmonary perfusion as a mechanistic image-based phenotype in emphysema susceptible smokers

    PubMed Central

    Alford, Sara K.; van Beek, Edwin J. R.; McLennan, Geoffrey; Hoffman, Eric A.

    2010-01-01

    Recent evidence suggests that endothelial dysfunction and pathology of pulmonary vascular responses may serve as a precursor to smoking-associated emphysema. Although it is known that emphysematous destruction leads to vasculature changes, less is known about early regional vascular dysfunction which may contribute to and precede emphysematous changes. We sought to test the hypothesis, via multidetector row CT (MDCT) perfusion imaging, that smokers showing early signs of emphysema susceptibility have a greater heterogeneity in regional perfusion parameters than emphysema-free smokers and persons who had never smoked (NS). Assuming that all smokers have a consistent inflammatory response, increased perfusion heterogeneity in emphysema-susceptible smokers would be consistent with the notion that these subjects may have the inability to block hypoxic vasoconstriction in patchy, small regions of inflammation. Dynamic ECG-gated MDCT perfusion scans with a central bolus injection of contrast were acquired in 17 NS, 12 smokers with normal CT imaging studies (SNI), and 12 smokers with subtle CT findings of centrilobular emphysema (SCE). All subjects had normal spirometry. Quantitative image analysis determined regional perfusion parameters, pulmonary blood flow (PBF), and mean transit time (MTT). Mean and coefficient of variation were calculated, and statistical differences were assessed with one-way ANOVA. MDCT-based MTT and PBF measurements demonstrate globally increased heterogeneity in SCE subjects compared with NS and SNI subjects but demonstrate similarity between NS and SNI subjects. These findings demonstrate a functional lung-imaging measure that provides a more mechanistically oriented phenotype that differentiates smokers with and without evidence of emphysema susceptibility. PMID:20368443

  12. Critical role of proteostasis-imbalance in pathogenesis of COPD and severe emphysema

    PubMed Central

    Min, Taehong; Bodas, Manish; Mazur, Steven

    2011-01-01

    The environmental, genetic, and/or age-related changes in proteostasis induce inflammation, oxidative stress, and apoptosis. We quantified the correlation of protein expression of critical proteostasis mediators to severity of chronic lung disease using lung tissue samples from control and chronic obstructive pulmonary disease (COPD) subjects (GOLD stage 0–IV) and cigarette smoke (CS)-induced murine model. The human bronchial epithelial cells, HEK-293, and Beas2B cells were used for in vitro experiments to verify the mechanisms. Our data verifies the correlation of higher expression of valosin-containing protein (VCP) retrograde translocation complex (VCP-Rma1-gp78) with severity of emphysema in COPD lung tissues and over-expression of inflammatory, ER stress and apoptotic mediators like NFκB, GADD-153/CHOP, and p-eIF2α. Moreover, subjects with severe emphysema had a higher accumulation of ubiquitinated proteins and deubiquitinating enzyme, UCHL-1, indicating towards the aggregation of misfolded or damaged proteins. The modulation of both protein degradation and synthesis rates by CS-extract substantiates the pathogenetic role of proteostasis-imbalance in emphysema and COPD. We identified that VCP also mediates proteasomal degradation of HDAC2 and Nrf2, as a potential mechanism for increased oxidative stress and corticosteroid resistance in COPD subjects with emphysema. Next, we confirmed that higher VCP expression associates with increased inflammation and apoptosis using in vitro and murine models. Our data clearly shows aberrant proteostasis in COPD subjects with severe emphysema. In addition, we evaluate therapeutic efficacy of salubrinal (ER stress inhibitor) to correct the proteostasis-imbalance based on its ability to control VCP expression and ubiquitin accumulation. Overall, our data demonstrate for the first time the critical role of proteostasis-imbalance in pathogenesis of severe emphysema. PMID:21318260

  13. Critical modifier role of membrane-CFTR dependent ceramide signaling in lung injury and emphysema

    PubMed Central

    Bodas, Manish; Min, Taehong; Mazur, Steven; Vij, Neeraj

    2010-01-01

    Ceramide accumulation mediates the pathogenesis of chronic obstructive lung diseases. Although, an association between lack of CFTR and ceramide accumulation has been described, it is unclear how membrane-CFTR may modulate ceramide signaling in lung injury and emphysema. The Cftr+/+- and Cftr−/−- mice and cells were used to evaluate the CFTR-dependent ceramide signaling in lung injury. Lung tissue from control and COPD patients was used to verify the role of CFTR-dependent ceramide signaling in pathogenesis of chronic emphysema. Our data reveals a novel finding that CFTR expression inversely correlates with severity of emphysema and ceramide-accumulation in COPD subjects compared to controls. We found that chemical inhibition of de novo- ceramide-synthesis controls Pa-LPS induced lung injury in Cftr+/+-mice, while its efficacy was significantly lower in Cftr−/−-mice indicating that membrane-CFTR is required for controlling lipid-raft ceramide levels. Inhibition of membrane-ceramide release showed enhanced protective effect in controlling Pa-LPS induced lung injury in Cftr−/−- mice as compared to the Cftr+/+, confirming our observation that CFTR regulates lipid-raft ceramide- levels and signaling. Our results indicate that inhibition of de novo- ceramide-synthesis may be effective in disease states with low-CFTR expression like emphysema and chronic lung injury but not in complete absence of lipid-raft CFTR as in ΔF508-CF. In contrast, inhibiting membrane ceramide release has the potential of a more effective drug candidate for ΔF508-CF but may not be effectual in treating lung injury and emphysema. Our data demonstrates the critical role of membrane-localized CFTR in regulating ceramide-accumulation and inflammatory-signaling in lung injury and emphysema. PMID:21135173

  14. Critical role of proteostasis-imbalance in pathogenesis of COPD and severe emphysema.

    PubMed

    Min, Taehong; Bodas, Manish; Mazur, Steven; Vij, Neeraj

    2011-06-01

    The environmental, genetic, and/or age-related changes in proteostasis induce inflammation, oxidative stress, and apoptosis. We quantified the correlation of protein expression of critical proteostasis mediators to severity of chronic lung disease using lung tissue samples from control and chronic obstructive pulmonary disease (COPD) subjects (GOLD stage 0-IV) and cigarette smoke (CS)-induced murine model. The human bronchial epithelial cells, HEK-293, and Beas2B cells were used for in vitro experiments to verify the mechanisms. Our data verifies the correlation of higher expression of valosin-containing protein (VCP) retrograde translocation complex (VCP-Rma1-gp78) with severity of emphysema in COPD lung tissues and over-expression of inflammatory, ER stress and apoptotic mediators like NFκB, GADD-153/CHOP, and p-eIF2α. Moreover, subjects with severe emphysema had a higher accumulation of ubiquitinated proteins and deubiquitinating enzyme, UCHL-1, indicating towards the aggregation of misfolded or damaged proteins. The modulation of both protein degradation and synthesis rates by CS-extract substantiates the pathogenetic role of proteostasis-imbalance in emphysema and COPD. We identified that VCP also mediates proteasomal degradation of HDAC2 and Nrf2, as a potential mechanism for increased oxidative stress and corticosteroid resistance in COPD subjects with emphysema. Next, we confirmed that higher VCP expression associates with increased inflammation and apoptosis using in vitro and murine models. Our data clearly shows aberrant proteostasis in COPD subjects with severe emphysema. In addition, we evaluate therapeutic efficacy of salubrinal (ER stress inhibitor) to correct the proteostasis-imbalance based on its ability to control VCP expression and ubiquitin accumulation. Overall, our data demonstrate for the first time the critical role of proteostasis-imbalance in pathogenesis of severe emphysema.

  15. Oxidative stress and nitrosative stress are involved in different stages of proteolytic pulmonary emphysema.

    PubMed

    Lanzetti, Manuella; da Costa, Cristiane Aguiar; Nesi, Renata Tiscoski; Barroso, Marina Valente; Martins, Vanessa; Victoni, Tatiana; Lagente, Vincent; Pires, Karla Maria Pereira; e Silva, Patrícia Machado Rodrigues; Resende, Angela Castro; Porto, Luis Cristóvão; Benjamim, Cláudia Farias; Valença, Samuel Santos

    2012-12-01

    Our aim was to investigate the role of oxidative stress in elastase-induced pulmonary emphysema. C57BL/6 mice were subjected to pancreatic porcine elastase (PPE) instillation (0.05 or 0.5 U per mouse, i.t.) to induce pulmonary emphysema. Lungs were collected on days 7, 14, and 21 after PPE instillation. The control group was sham injected. Also, mice treated with 1% aminoguanidine (AMG) and inducible NO synthase (iNOS) knockout mice received 0.5 U PPE (i.t.), and lungs were analyzed 21 days after. We performed bronchoalveolar lavage, biochemical analyses of oxidative stress, and lung stereology and morphometry assays. Emphysema was observed histologically at 21 days after 0.5 U PPE treatment; tissues from these mice exhibited increased alveolar linear intercept and air-space volume density in comparison with the control group. TNF-α was elevated at 7 and 14 days after 0.5 U PPE treatment, concomitant with a reduction in the IL-10 levels at the same time points. Myeloperoxidase was elevated in all groups treated with 0.5 U PPE. Oxidative stress was observed during early stages of emphysema, with increased nitrite levels and malondialdehyde and superoxide dismutase activity at 7 days after 0.5 U PPE treatment. Glutathione peroxidase activity was increased in all groups treated with 0.5 U PPE. The emphysema was attenuated when iNOS was inhibited using 1% AMG and in iNOS knockout mice. Furthermore, proteolytic stimulation by PPE enhanced the expression of nitrotyrosine and iNOS, whereas the PPE+AMG group showed low expression of iNOS and nitrotyrosine. PPE stimulus also induced endothelial (e) NOS expression, whereas AMG reduced eNOS. Our results suggest that the oxidative and nitrosative stress pathways are triggered by nitric oxide production via iNOS expression in pulmonary emphysema.

  16. Pulmonary Hypertension and Computed Tomography Measurement of Small Pulmonary Vessels in Severe Emphysema

    PubMed Central

    Matsuoka, Shin; Washko, George R.; Yamashiro, Tsuneo; Estepar, Raul San Jose; Diaz, Alejandro; Silverman, Edwin K.; Hoffman, Eric; Fessler, Henry E.; Criner, Gerard J.; Marchetti, Nathaniel; Scharf, Steven M.; Martinez, Fernando J.; Reilly, John J.; Hatabu, Hiroto

    2010-01-01

    {mathrsfs} \\usepackage{pmc} \\usepackage[Euler]{upgreek} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}\\overline{Ppa}\\end{equation*}\\end{document} (r = −0.512, P < 0.0001), whereas the correlation between %CSA5–10 and \\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{pmc} \\usepackage[Euler]{upgreek} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}\\overline{Ppa}\\end{equation*}\\end{document} did not reach statistical significance (r = −0.196, P = 0.083). Multiple linear regression analysis showed that %CSA<5 and diffusing capacity of carbon monoxide (DlCO) % predicted were independent predictors of \\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{pmc} \\usepackage[Euler]{upgreek} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}\\overline{Ppa}\\end{equation*}\\end{document} (r2 = 0.541): %CSA <5 (P < 0.0001), and DlCO % predicted (P = 0.022). Conclusions: The %CSA<5 measured on CT images is significantly correlated to \\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{pmc} \\usepackage[Euler]{upgreek} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}\\overline{Ppa}\\end{equation*}\\end{document} in severe emphysema and can estimate the degree of pulmonary hypertension. PMID:19875683

  17. Congenital lobar emphysema associated with polysplenia syndrome

    PubMed Central

    Choh, Naseer A.; Choh, Suhil A.; Jehangir, Majid; Naikoo, Bashir A.

    2010-01-01

    Polysplenia, or left isomerism, is a rare heterotaxy syndrome characterized by bilateral bi-lobed lungs, bilateral pulmonary atria, a symmetrical midline liver, and multiple aberrant splenic nodules. We report a case of polysplenia associated with congenital lobar emphysema apart from other typical anomalies. Such an association has not been previously reported. The patient was a young male with progressive exertional breathlessness referred for high resolution CT of the lungs. CT, MRI and echocardiography revealed (in addition to congenital lobar emphysema of right lung) a hemiazygos continuation of the inferior vena cava, a persistent left superior vena cava, multiple splenunculi in the right hypochondrium, midline liver, bilateral bilobed lungs, a large pulmonary artery (suggestive of severe pulmonary artery hypertension) and a large VSD—a typical constellation of findings described in polysplenia syndrome. PMID:20864788

  18. [Normal lung volumes in patients with idiopathic pulmonary fibrosis and emphysema].

    PubMed

    Casas, Juan Pablo; Abbona, Horacio; Robles, Adriana; López, Ana María

    2008-01-01

    Pulmonary function tests in idiopathic pulmonary fibrosis characteristically show a restrictive pattern, resulting from reduction of pulmonary compliance due to diffuse fibrosis. Conversely, an obstructive pattern with hyperinflation results in emphysema by loss of elastic recoil, expiratory collapse of the peripheral airways and air trapping. Previous reports suggest that when both diseases coexist, pulmonary volumes are compensated and a smaller than expected reduction or even normal lung volumes can be found. We report 4 male patients of 64, 60, 73 and 70 years, all with heavy cigarette smoking history and progressive breathlessness. Three of them had severe limitation in their quality of life. All four showed advanced lung interstitial involvement, at high resolution CT scan, fibrotic changes predominantly in the subpleural areas of lower lung fields and concomitant emphysema in the upper lobes. Emphysema and pulmonary fibrosis was confirmed by open lung biopsy in one patient. The four patients showed normal spirometry and lung volumes with severe compromise of gas exchange and poor exercise tolerance evaluated by 6 minute walk test. Severe pulmonary arterial hypertension was also confirmed in three patients. Normal lung volumes does not exclude diagnosis of idiopathic pulmonary fibrosis in patients with concomitant emphysema. The relatively preserved lung volumes may underestimate the severity of idiopathic pulmonary fibrosis and attenuate its effects on lung function parameters.

  19. Hyperpolarized 3He diffusion MRI and histology in pulmonary emphysema.

    PubMed

    Woods, Jason C; Choong, Cliff K; Yablonskiy, Dmitriy A; Bentley, John; Wong, Jonathan; Pierce, John A; Cooper, Joel D; Macklem, Peter T; Conradi, Mark S; Hogg, James C

    2006-12-01

    Diffusion MRI of hyperpolarized (3)He shows that the apparent diffusion coefficient (ADC) of (3)He gas is highly restricted in the normal lung and becomes nearly unrestricted in severe emphysema. The nature of this restricted diffusion provides information about lung structure; however, no direct comparison with histology in human lungs has been reported. The purpose of this study is to provide information about (3)He gas diffusivity in explanted human lungs, and describe the relationship between (3)He diffusivity and the surface area to lung volume ratio (SA/V) and mean linear intercept (L(m)) measurements--the gold standard for diagnosis of emphysema. Explanted lungs from patients who were undergoing lung transplantation for advanced COPD, and donor lungs that were not used for transplantation were imaged via (3)He diffusion MRI. Histological measurements were made on the same specimens after they were frozen in the position of study. There is an inverse correlation between diffusivity and SA/V (and a positive correlation between diffusivity and L(m)). An important result is that restricted (3)He diffusivity separated normal from emphysematous lung tissue more clearly than the morphometric analyses. This effect may be due to the smaller histologic sampling size compared to the MRI voxel sizes.

  20. Panlobular emphysema in young intravenous Ritalin abusers

    SciTech Connect

    Schmidt, R.A.; Glenny, R.W.; Godwin, J.D.; Hampson, N.B.; Cantino, M.E.; Reichenbach, D.D. )

    1991-03-01

    We studied a distinctive group of young intravenous Ritalin abusers with profound obstructive lung disease. Clinically, they seemed to have severe emphysema, but the pathologic basis of their symptoms had not been investigated previously. Seven patients have died and been autopsied: in four, the lungs were fixed, inflated, dried, and examined in detail radiologically, grossly, microscopically, and by electron probe X-ray microanalysis. All seven patients had severe panlobular (panacinar) emphysema that tended to be more severe in the lower lung zones and that was associated with microscopic talc granulomas. Vascular involvement by talc granulomas was variable, but significant interstitial fibrosis was not present. Five patients were tested for alpha-1-antitrypsin deficiency and found to be normal, as were six similar living patients. These findings indicate that some intravenous drug abusers develop emphysema that clinically, radiologically, and pathologically resembles that caused by alpha-1-antitrypsin deficiency but which must have a different pathogenesis. Talc from the Ritalin tablets may be important, but the mechanism remains to be elucidated.

  1. ATP in the pathogenesis of lung emphysema.

    PubMed

    Mortaz, Esmaeil; Braber, Saskia; Nazary, Maiwand; Givi, Masoumh Ezzati; Nijkamp, Frans P; Folkerts, Gert

    2009-10-01

    Extracellular ATP is a signaling molecule that often serves as a danger signal to alert the immune system of tissue damage. This molecule activates P2 nucleotide receptors, that include the ionotropic P2X receptors and metabotropic P2Y receptors. Recently, it has been reported that ATP accumulates in the airways of both asthmatic patients and sensitized mice after allergen challenge. The role and function of ATP in the pathogenesis of chronic obstructive pulmonary diseases (COPD) are not well understood. In this study we investigated the effect of cigarette smoke on purinergic receptors and ATP release by neutrophils. Neutrophils and their mediators are key players in the pathogenesis of lung emphysema. Here we demonstrated that in an in vivo model of cigarette smoke-induced lung emphysema, the amount of ATP was increased in the bronchoalveolar lavage fluid. Moreover, activation of neutrophils with cigarette smoke extract induced ATP release. Treatment of neutrophils with apyrase (catalyses the hydrolysis of ATP to yield AMP) and suramin (P2-receptor antagonist) abrogated the release of CXCL8 and elastase induced by cigarette smoke extract and exogenous ATP. These observations indicate that activation of purinergic signaling by cigarette smoke may take part in the pathogenesis of lung emphysema.

  2. Cervical and mediastinal emphysema associated with an asthma exacerbation.

    PubMed

    Khan, Waseem Asrar; Abbas, Shoneen; Bright, John

    2013-02-18

    Surgical emphysema associated with an acute asthma exacerbation is very rare. This report presents the case of a 19- year-old male patient with a background of asthma who presented with palpable cervical surgical emphysema and CT evidence of mediastinal emphysema. There are only a limited number of case reports associated with surgical emphysema in the absence of pneumothorax in patients with an asthma exacerbation. Evidence with regard to the management of such cases is limited and is largely consensus based. Below we discuss the case in a greater detail.

  3. Elastase-induced pulmonary emphysema: insights from experimental models.

    PubMed

    Antunes, Mariana A; Rocco, Patricia R M

    2011-12-01

    Several distinct stimuli can be used to reproduce histological and functional features of human emphysema, a leading cause of disability and death. Since cigarette smoke is the main cause of emphysema in humans, experimental researches have attempted to reproduce this situation. However, this is an expensive and cumbersome method of emphysema induction, and simpler, more efficacious alternatives have been sought. Among these approaches, elastolytic enzymes have been widely used to reproduce some characteristics of human cigarette smoke-induced disease, such as: augmentation of airspaces, inflammatory cell influx into the lungs, and systemic inflammation. Nevertheless, the use of elastase-induced emphysema models is still controversial, since the disease pathways involved in elastase induction may differ from those occurring in smoke-induced emphysema. This indicates that the choice of an emphysema model may impact the results of new therapies or drugs being tested. The aim of this review is to compare the mechanisms of disease induction in smoke and elastase emphysema models, to describe the differences among various elastase models, and to establish the advantages and disadvantages of elastase-induced emphysema models. More studies are required to shed light on the mechanisms of elastase-induced emphysema.

  4. Cervicofacial subcutaneous emphysema associated with dental laser treatment.

    PubMed

    Mitsunaga, S; Iwai, T; Kitajima, H; Yajima, Y; Ohya, T; Hirota, M; Mitsudo, K; Aoki, N; Yamashita, Y; Omura, S; Tohnai, I

    2013-12-01

    Cervicofacial subcutaneous emphysema is a rare complication of dental procedures. Although most cases of emphysema occur incidentally with the use of a high-speed air turbine handpiece, there have been some reports over the past decade of cases caused by dental laser treatment. Emphysema as a complication caused by the air cooling spray of a dental laser is not well known, even though dental lasers utilize compressed air just as air turbines and syringes do. In this study, we comprehensively reviewed cases of emphysema attributed to dental laser treatment that appeared in the literature between January 2001 and September 2012, and we included three such cases referred to us. Among 13 cases identified in total, nine had cervicofacial subcutaneous and mediastinal emphysema. Compared with past reviews, the incidence of mediastinal emphysema caused by dental laser treatment was higher than emphysema caused by dental procedure without dental laser use. Eight patients underwent CO2 laser treatment and two underwent Er:YAG laser treatment. Nine patients had emphysema following laser irradiation for soft tissue incision. Dentists and oral surgeons should be cognizant of the potential risk for iatrogenic emphysema caused by the air cooling spray during dental laser treatment and ensure proper usage of lasers.

  5. Diffuse persistent interstitial pulmonary emphysema treated by lobectomy.

    PubMed

    Matta, Reva; Matta, Judy; Hage, Pierre; Nassif, Yolla; Mansour, Nabil; Diab, Nabil

    2011-10-01

    Persistent interstitial pulmonary emphysema is a rare condition that occurs in preterm infants on mechanical ventilation, characterized by abnormal accumulation of air in the pulmonary interstitium, due to disruption of the basement membrane. Diffuse persistent interstitial pulmonary emphysema is observed when small cysts are noted in all lobes of the lung. The management of infants suffering from diffuse persistent interstitial pulmonary emphysema varies according to severity and stability of the patient, being either conservative treatment or aggressive surgical treatment by pneumonectomy. We report a case of an unstable patient with diffuse persistent interstitial pulmonary emphysema successfully treated by lobectomy as a form of conservative surgical approach.

  6. Cell therapy with bone marrow mononuclear cells in elastase-induced pulmonary emphysema.

    PubMed

    Longhini-Dos-Santos, Nathalia; Barbosa-de-Oliveira, Valter Abraão; Kozma, Rodrigo Heras; Faria, Carolina Arruda de; Stessuk, Talita; Frei, Fernando; Ribeiro-Paes, João Tadeu

    2013-04-01

    Emphysema is characterized by destruction of alveolar walls with loss of gas exchange surface and consequent progressive dyspnea. This study aimed to evaluate the efficiency of cell therapy with bone marrow mononuclear cells (BMMC) in an animal model of elastase-induced pulmonary emphysema. Emphysema was induced in C57Bl/J6 female mice by intranasal instillation of elastase. After 21 days, the mice received bone marrow mononuclear cells from EGFP male mice with C57Bl/J6 background. The groups were assessed by comparison and statistically significant differences (p < 0.05) were observed among the groups treated with BMMC and evaluated after 7, 14 and 21 days. Analysis of the mean linear intercept (Lm) values for the different groups allowed to observe that the group treated with BMMC and evaluated after 21 days showed the most significant result. The group that received no treatment showed a statistically significant difference when compared to other groups, except the group treated and evaluated after 21 days, evidencing the efficacy of cell therapy with BMMC in pulmonary emphysema.

  7. Increased circulating β2-adrenergic receptor autoantibodies are associated with smoking-related emphysema

    PubMed Central

    Hu, Jia-yi; Liu, Bei-bei; Du, Yi-peng; Zhang, Yuan; Zhang, Yi-wei; Zhang, You-yi; Xu, Ming; He, Bei

    2017-01-01

    Smoking is a dominant risk factor for chronic obstructive pulmonary disease (COPD) and emphysema, but not every smoker develops emphysema. Immune responses in smokers vary. Some autoantibodies have been shown to contribute to the development of emphysema in smokers. β2-adrenergic receptors (β2-ARs) are important targets in COPD therapy. β2-adrenergic receptor autoantibodies (β2-AAbs), which may directly affect β2-ARs, were shown to be increased in rats with passive-smoking-induced emphysema in our current preliminary studies. Using cigarette-smoke exposure (CS-exposure) and active-immune (via injections of β2-AR second extracellular loop peptides) rat models, we found that CS-exposed rats showed higher serum β2-AAb levels than control rats before alveolar airspaces became enlarged. Active-immune rats showed increased serum β2-AAb levels, and exhibited alveolar airspace destruction. CS-exposed-active-immune treated rats showed more extensive alveolar airspace destruction than rats undergoing CS-exposure alone. In our current clinical studies, we showed that plasma β2-AAb levels were positively correlated with the RV/TLC (residual volume/total lung capacity) ratio (r = 0.455, p < 0.001) and RV%pred (residual volume/residual volume predicted percentage, r = 0.454, p < 0.001) in 50 smokers; smokers with higher plasma β2-AAb levels exhibited worse alveolar airspace destruction. We suggest that increased circulating β2-AAbs are associated with smoking-related emphysema. PMID:28262783

  8. Combined Pulmonary Fibrosis and Emphysema Preceding Lupus Pleuritis.

    PubMed

    Kamiya, Yosuke; Toyoshima, Mikio; Akiyama, Norimichi; Suda, Takafumi

    2016-01-01

    An 83-year-old man, who was a former smoker, with anti-ribonucleoprotein (RNP) antibody-positive combined pulmonary fibrosis and emphysema presented with a cough and dyspnea. A chest radiograph showed bilateral pleural effusions. His laboratory data showed proteinuria and elevated levels of anti-nuclear antibodies, anti-double strand DNA antibodies, and CA125, with decreased serum complement levels. Thoracentesis showed an exudative pleural effusion with an increased lymphocyte count and elevated CA125 levels. A thoracoscopic biopsy specimen showed proliferation of CA125-positive mesothelial cells. Systemic lupus erythematosus was diagnosed. His symptoms and pleural effusion resolved after the initiation of systemic corticosteroid therapy. The detection of anti-RNP antibody and CA125 levels are helpful in the diagnosis of lupus pleuritis.

  9. Interventional pulmonology for asthma and emphysema: bronchial thermoplasty and bronchoscopic lung volume reduction.

    PubMed

    Miller, Russell J; Murgu, Septimiu D

    2014-12-01

    Emphysema and asthma are responsible for economic and social burden. Altering the natural course of these diseases is a field of intense research. The National Emphysema Treatment Trial showed that lung volume reduction surgery (LVRS) could significantly reduce both morbidity and mortality in properly selected patients. LVRS is seldom performed, however, due to the high morbidity associated with the surgery. Numerous bronchoscopic interventions have been introduced with the goal of providing the clinical benefits of LVRS without the surgical complications. Thus far, these modalities have not produced the results once hoped. However, through active modification of both technique and patient selection, the role of minimally invasive modalities in the treatment of emphysema continues to evolve. Bronchial thermoplasty (BT) is a method of delivering controlled heat to airway mucosa with the goal of reducing airway smooth muscle mass and hence bronchoconstriction. In patients suffering from asthma who cannot achieve control with standard medical care, BT has been shown to be safe and improves symptoms, with long lasting benefit. BT does not seem to affect traditional markers of asthma severity such as forced expiratory volume in 1 second and questions remain regarding proper patient selection for this therapy and its true physiologic effects. This article is a review of bronchoscopic modalities for emphysema and asthma.

  10. Bone marrow cells repair cigarette smoke-induced emphysema in rats.

    PubMed

    Huh, Jin Won; Kim, Sun-Yong; Lee, Ji Hyun; Lee, Jin-Seok; Van Ta, Quang; Kim, Mijung; Oh, Yeon-Mok; Lee, Yun-Song; Lee, Sang-Do

    2011-09-01

    The therapeutic potential of stem cells in chronic obstructive pulmonary disease is not well known although stem cell therapy is effective in models of other pulmonary diseases. We tested the capacities of bone marrow cells (BMCs), mesenchymal stem cells (MSCs), and conditioned media of MSCs (MSC-CM) to repair cigarette smoke-induced emphysema. Inbred female Lewis rats were exposed to cigarette smoke for 6 mo and then received BMCs, MSCs, or MSC-CM from male Lewis rats. For 2 mo after injection, the BMC treatment gradually alleviated the cigarette smoke-induced emphysema and restored the increased mean linear intercept. The BMC treatment significantly increased cell proliferation and the number of small pulmonary vessels, reduced apoptotic cell death, attenuated the mean pulmonary arterial pressure, and inhibited muscularization in small pulmonary vessels. However, only a few male donor cells were detected from 1 day to 1 mo after BMC administration. The MSCs and cell-free MSC-CM also induced the repair of emphysema and increased the number of small pulmonary vessels. Our data show that BMC, MSCs, and MSC-CM treatment repaired cigarette smoke-induced emphysema. The repair activity of these treatments is consistent with a paracrine effect rather than stem cell engraftment because most of the donor cells disappeared and because cell-free MSC-CM also induced the repair.

  11. Activation of C3a receptor is required in cigarette smoke-mediated emphysema

    PubMed Central

    Yuan, Xiaoyi; Shan, Ming; You, Ran; Frazier, Michael V.; Hong, Monica Jeongsoo; Wetsel, Rick A.; Drouin, Scott; Seryshev, Alexander; MD, Li-zhen Song; Cornwell, Lorraine; Rossen, Roger D; Corry, David B.; Kheradmand, Farrah

    2014-01-01

    Exposure to cigarette smoke can initiate sterile inflammatory responses in the lung and activate myeloid dendritic cells (mDCs) that induce differentiation of T helper type 1 (Th1) and Th17 cells in the emphysematous lungs. Consumption of complement proteins increases in acute inflammation, but the contribution of complement protein 3 (C3) to chronic cigarette smoke-induced immune responses in the lung is not clear. Here we show that following chronic exposure to cigarette smoke, C3 deficient (C3−/−) mice develop less emphysema and have fewer CD11b+CD11c+ mDCs infiltrating the lungs as compared to wild type mice. Proteolytic cleavage of C3 by neutrophil elastase releases C3a, which in turn increases expression of its receptor (C3aR) on lung mDCs. Mice deficient in the C3aR (C3ar−/−) partially phenocopy the attenuated responses to chronic smoke observed in C3−/− mice. Consistent with a role for C3 in emphysema C3 and its active fragments are deposited on the lung tissue of smokers with emphysema, and smoke exposed mice. Together, these findings suggest a critical role for C3a through autocrine/paracrine induction of C3aR in the pathogenesis of cigarette smoke induced sterile inflammation and provide new therapeutic targets for the treatment of emphysema. PMID:25465103

  12. A keratan sulfate disaccharide prevents inflammation and the progression of emphysema in murine models.

    PubMed

    Gao, Congxiao; Fujinawa, Reiko; Yoshida, Takayuki; Ueno, Manabu; Ota, Fumi; Kizuka, Yasuhiko; Hirayama, Tetsuya; Korekane, Hiroaki; Kitazume, Shinobu; Maeno, Toshitaka; Ohtsubo, Kazuaki; Yoshida, Keiichi; Yamaguchi, Yoshiki; Lepenies, Bernd; Aretz, Jonas; Rademacher, Christoph; Kabata, Hiroki; Hegab, Ahmed E; Seeberger, Peter H; Betsuyaku, Tomoko; Kida, Kozui; Taniguchi, Naoyuki

    2017-02-01

    Emphysema is a typical component of chronic obstructive pulmonary disease (COPD), a progressive and inflammatory airway disease. However, no effective treatment currently exists. Here, we show that keratan sulfate (KS), one of the major glycosaminoglycans produced in the small airway, decreased in lungs of cigarette smoke-exposed mice. To confirm the protective effect of KS in the small airway, a disaccharide repeating unit of KS designated L4 ([SO3(-)-6]Galβ1-4[SO3(-)-6]GlcNAc) was administered to two murine models: elastase-induced-emphysema and LPS-induced exacerbation of a cigarette smoke-induced emphysema. Histological and microcomputed tomography analyses revealed that, in the mouse elastase-induced emphysema model, administration of L4 attenuated alveolar destruction. Treatment with L4 significantly reduced neutrophil influx, as well as the levels of inflammatory cytokines, tissue-degrading enzymes (matrix metalloproteinases), and myeloperoxidase in bronchoalveolar lavage fluid, suggesting that L4 suppressed inflammation in the lung. L4 consistently blocked the chemotactic migration of neutrophils in vitro. Moreover, in the case of the exacerbation model, L4 inhibited inflammatory cell accumulation to the same extent as that of dexamethasone. Taken together, L4 represents one of the potential glycan-based drugs for the treatment of COPD through its inhibitory action against inflammation.

  13. Comprehensive analysis of elastase-induced pulmonary emphysema in mice: effects of ambient existing particulate matters.

    PubMed

    Inoue, Ken-ichiro; Koike, Eiko; Takano, Hirohisa

    2010-11-01

    Pulmonary exposure of rodents to porcine pancreatic elastase (PPE) induces lesions that morphologically resemble human panacinar emphysema. However, there has been little work on the comprehensive analysis of this model. The present study was designed to extensively examine the biological effects of PPE on inflammation, cell damage, emphysematous change, and cholinergic reactivity in the lungs of mice. Furthermore, we evaluated the effects of pulmonary exposure to diesel exhaust particles (DEP) on the disease model. Intratracheal administration of PPE induced (1) proinflammatory response in the lungs that was characterized by significant infiltration of leukocytes such as macrophages, eosinophils, and lymphocytes and an increased level of interleukin-1β in lung homogenates, (2) lung cell damage, indicated by higher levels of total protein, lactate dehydrogenase, and alkaline phosphatase in lung homogenates, (3) emphysema-related morphological changes including airspace enlargement and progressive destruction of alveolar wall structures, and (4) airway responsiveness to methacholine in the context of the compliance value of the respiratory system in a dose-dependent manner showing an overall trend. A single intratracheal administration of DEP did not significantly facilitate the hallmark of the disease. This is the first study to extensively analyze PPE-induced lung emphysema in mice with evaluation of the effects of DEP. Furthermore, this bioassay may be applied to future investigations that evaluate new therapeutic agents or risk factors for pulmonary emphysema.

  14. Organometallic cyclic polyphenols derived from 1,2-(alpha-keto tri or tetra methylene) ferrocene show strong antiproliferative activity on hormone-independent breast cancer cells.

    PubMed

    Plazuk, Damian; Top, Siden; Vessières, Anne; Plamont, Marie-Aude; Huché, Michel; Zakrzewski, Janusz; Makal, Anna; Woźniak, Krzysztof; Jaouen, Gérard

    2010-08-28

    We have previously shown that achiral ferrocenyl diphenol butene derivatives are strong antitumor agents against both hormone-dependent and -independent breast cancer cell lines. We report now examples of a new series of two planar chiral diphenol derivatives, namely 1,2-[1-[1,1-bis(4-hydroxyphenyl)methylidene]trimethylene] ferrocene (4), and 1,2-[1-[1,1-bis(4-hydroxyphenyl)methylidene]tetramethylene]ferrocene (5). They were prepared under racemic form from a McMurry coupling reaction with 30% and 16% yields, respectively. Compound 5 gave crystals suitable for X-ray structural analysis. Compounds 4 and 5 were tested for ERalpha and ERbeta affinity, lipophilicity, and proliferative/antiproliferative effects against the hormone-dependent breast cancer cell line MCF-7, and the hormone-independent breast cancer cell line MDA-MB-231. Both compounds exhibit better affinity for ERbeta (16.4 +/- 0.1, and 7.0 +/- 0.4, respectively) than for ERalpha (6.4 +/- 0.2, and 6.6 +/- 0.2). The test on hormone-independent breast cancer cell line MDA-MB-231 showed that 4 with a 5-membered ring gives an IC50 value of 2.7 microM while with 5 in which the ring has 6 carbons, the value is reduced to IC50 = 1.23 microM.

  15. Cement dust exposure-related emphysema in a construction worker

    PubMed Central

    Karkhanis, V.; Joshi, J. M.

    2011-01-01

    Although, smoking is considered the most important predisposing factor in development of emphysema; environmental exposures also play an important role. There have been several studies on work related respiratory symptoms and ventilatory disorders among employees of cement industry. We report a case of cement exposure related emphysema in 75 years old woman construction worker. PMID:22084546

  16. Cathepsin E promotes pulmonary emphysema via mitochondrial fission.

    PubMed

    Zhang, Xuchen; Shan, Peiying; Homer, Robert; Zhang, Yi; Petrache, Irina; Mannam, Praveen; Lee, Patty J

    2014-10-01

    Emphysema is characterized by loss of lung elasticity and irreversible air space enlargement, usually in the later decades of life. The molecular mechanisms of emphysema remain poorly defined. We identified a role for a novel cathepsin, cathepsin E, in promoting emphysema by inducing mitochondrial fission. Unlike previously reported cysteine cathepsins, which have been implicated in cigarette smoke-induced lung disease, cathepsin E is a nonlysosomal intracellular aspartic protease whose function has been described only in antigen processing. We examined lung tissue sections of persons with chronic obstructive pulmonary disease, a clinical entity that includes emphysematous change. Human chronic obstructive pulmonary disease lungs had markedly increased cathepsin E protein in the lung epithelium. We generated lung epithelial-targeted transgenic cathepsin E mice and found that they develop emphysema. Overexpression of cathepsin E resulted in increased E3 ubiquitin ligase parkin, mitochondrial fission protein dynamin-related protein 1, caspase activation/apoptosis, and ultimately loss of lung parenchyma resembling emphysema. Inhibiting dynamin-related protein 1, using a small molecule inhibitor in vitro or in vivo, inhibited cathepsin E-induced apoptosis and emphysema. To the best of our knowledge, our study is the first to identify links between cathepsin E, mitochondrial fission, and caspase activation/apoptosis in the pathogenesis of pulmonary emphysema. Our data expand the current understanding of molecular mechanisms of emphysema development and may provide new therapeutic targets.

  17. A parturient with severe bullous emphysema from intravenous drug abuse.

    PubMed

    Siddiqui, S; Afrangui, B M; Malinow, A M

    2002-04-01

    A parturient with severe talcosis-induced, bullous emphysema presented for urgent cesarean delivery. Respiratory effects of anesthesia, positioning for delivery and residual effects of postoperative analgesics all potentially affect the choice of anesthetic technique and drugs used in a patient with severe emphysema. This parturient was given epidural anesthesia for delivery and postoperative analgesia maintained with epidural infusion of bupivacaine and clonidine.

  18. Determinants of exercise-induced oxygen desaturation including pulmonary emphysema in COPD: Results from the ECLIPSE study.

    PubMed

    Andrianopoulos, Vasileios; Celli, Bartolome R; Franssen, Frits M E; Pinto-Plata, Victor M; Calverley, Peter M A; Vanfleteren, Lowie E G W; Vogiatzis, Ioannis; Vestbo, Jørgen; Agusti, Alvar; Bakke, Per S; Rennard, Stephen I; MacNee, William; Tal-Singer, Ruth; Yates, Julie C; Wouters, Emiel F M; Spruit, Martijn A

    2016-10-01

    Exercise-induced oxygen desaturation (EID) is related to mortality in patients with chronic obstructive pulmonary disease (COPD). We investigated: (1) the prevalence of EID; (2) the relative-weight of several physiological determinants of EID including pulmonary emphysema, and (3) the relationship of EID with certain patients' clinical characteristics. Data from 2050 COPD patients (age: 63.3 ± 7.1years; FEV1: 48.7 ± 15.7%pred.) were analyzed. The occurrence of EID (SpO2post ≤88%) at the six-minute walking test (6MWT) was investigated in association with emphysema quantified by computed-tomography (QCT), and several clinical characteristics. 435 patients (21%) exhibited EID. Subjects with EID had more QCT-emphysema, lower exercise capacity and worse health-status (BODE, ADO indexes) compared to non-EID. Determinant of EID were obesity (BMI≥30 kg/m(2)), impaired FEV1 (≤44%pred.), moderate or worse emphysema, and low SpO2 at rest (≤93%). Linear regression indicated that each 1-point increase on the ADO-score independently elevates odds ratio (≤1.5fold) for EID. About one in five COPD patients in the ECLIPSE cohort present EID. Advanced emphysema is associated with EID. In addition, obesity, severe airflow limitation, and low resting oxygen saturation increase the risk for EID. Patients with EID in GOLD stage II have higher odds to have moderate or worse emphysema compared those with EID in GOLD stage III-IV. Emphysematous patients with high ADO-score should be monitored for EID.

  19. Therapeutic effects of adipose-derived stem cells pretreated with pioglitazone in an emphysema mouse model

    PubMed Central

    Hong, Yoonki; Kim, You-Sun; Hong, Seok-Ho; Oh, Yeon-Mok

    2016-01-01

    There is no therapy currently available that influences the natural history of disease progression in patients with chronic obstructive pulmonary disease (COPD). Although stem cell therapy is considered a potential therapeutic option in COPD, there are no clinical trials proving definitive therapeutic effects in patients with COPD. Recently, it was reported that pioglitazone might potentiate the therapeutic effects of stem cells in patients with heart or liver disease. To test the capacity of pioglitazone pretreatment of stem cells for emphysema repair, we evaluated the therapeutic effects of pioglitazone-pretreated human adipose-derived mesenchymal stem cells (ASCs) on elastase-induced or cigarette smoke-induced emphysema in mice. We also investigated the mechanisms of action of pioglitazone-pretreated ASCs. Pioglitazone-pretreated ASCs had a more potent therapeutic effect than non-pretreated ASCs in the repair of both elastase-induced and smoke-induced emphysema models (mean linear intercept, 78.1±2.5 μm vs 83.2±2.6 μm in elastase models and 75.6±1.4 μm vs 80.5±3.2 μm in smoke models, P<0.05). Furthermore, we showed that pioglitazone-pretreated ASCs increased vascular endothelial growth factor (VEGF) production both in vitro and in mouse lungs in the smoke-induced emphysema model. Pioglitazone-pretreated ASCs may have more potent therapeutic effects than non-pretreated ASCs in emphysema mouse models. PMID:27765950

  20. Therapeutic effects of adipose-derived stem cells pretreated with pioglitazone in an emphysema mouse model.

    PubMed

    Hong, Yoonki; Kim, You-Sun; Hong, Seok-Ho; Oh, Yeon-Mok

    2016-10-21

    There is no therapy currently available that influences the natural history of disease progression in patients with chronic obstructive pulmonary disease (COPD). Although stem cell therapy is considered a potential therapeutic option in COPD, there are no clinical trials proving definitive therapeutic effects in patients with COPD. Recently, it was reported that pioglitazone might potentiate the therapeutic effects of stem cells in patients with heart or liver disease. To test the capacity of pioglitazone pretreatment of stem cells for emphysema repair, we evaluated the therapeutic effects of pioglitazone-pretreated human adipose-derived mesenchymal stem cells (ASCs) on elastase-induced or cigarette smoke-induced emphysema in mice. We also investigated the mechanisms of action of pioglitazone-pretreated ASCs. Pioglitazone-pretreated ASCs had a more potent therapeutic effect than non-pretreated ASCs in the repair of both elastase-induced and smoke-induced emphysema models (mean linear intercept, 78.1±2.5 μm vs 83.2±2.6 μm in elastase models and 75.6±1.4 μm vs 80.5±3.2 μm in smoke models, P<0.05). Furthermore, we showed that pioglitazone-pretreated ASCs increased vascular endothelial growth factor (VEGF) production both in vitro and in mouse lungs in the smoke-induced emphysema model. Pioglitazone-pretreated ASCs may have more potent therapeutic effects than non-pretreated ASCs in emphysema mouse models.

  1. PPARγ in emphysema: blunts the damage and triggers repair?

    PubMed

    Kelly, Neil J; Shapiro, Steven D

    2014-03-01

    Cigarette smoke is the most common cause of pulmonary emphysema, which results in an irreversible loss of lung structure and function. Th1 and Th17 immune responses have been implicated in emphysema pathogenesis; however, the drivers of emphysema-associated immune dysfunction are not fully understood. In this issue of the JCI, Shan and colleagues found that peroxisome proliferator-activated receptor γ (PPARγ) is downregulated in APCs isolated from the lungs of emphysematous chronic smokers and mice exposed to cigarette smoke. Furthermore, treatment with a PPARγ agonist prevented emphysema development and appeared to reduce emphysema-associated lung volume expansion in mice exposed to cigarette smoke. Further work will need to be done to evaluate the potential of PPARγ agonists to restore lung capacity in emphysematous patients.

  2. Lung volume reduction surgery for emphysema.

    PubMed

    Flaherty, K R; Martinez, F J

    2000-12-01

    Over the past decades, extensive literature has been published regarding surgical therapies for advanced COPD. Lung-volume reduction surgery would be an option for a significantly larger number of patients than classic bullectomy or lung transplantation. Unfortunately, the initial enthusiasm has been tempered by major questions regarding the optimal surgical approach, safety, firm selection criteria, and confirmation of long-term benefits. In fact, the long-term follow-up reported in patients undergoing classical bullectomy should serve to caution against unbridled enthusiasm for the indiscriminate application of LVRS. Those with the worst long-term outcome despite favourable short-term improvements after bullectomy have consistently been those with the lowest pulmonary function and significant emphysema in the remaining lung who appear remarkably similar to those being evaluated for LVRS. With this in mind, the National Heart, Lung and Blood Institute partnered with the Health Care Finance Administration to establish a multicenter, prospective, randomized study of intensive medical management, including pulmonary rehabilitation versus the same plus bilateral (by MS or VATS), known as the National Emphysema Treatment Trial. The primary objectives are to determine whether LVRS improves survival and exercise capacity. The secondary objectives will examine effects on pulmonary function and HRQL, compare surgical techniques, examine selection criteria for optimal response, identify criteria to determine those who are at prohibitive surgical risk, and examine long-term cost effectiveness. It is hoped that data collected from this novel, multicenter collaboration will place the role of LVRS in a clearer perspective for the physician caring for patients with advanced emphysema.

  3. [Pulmonary emphysema in klotho mutant mice (deficient in klotho gene expression): klotho gene essential in postnatal pulmonary integrity].

    PubMed

    Suga, Tatsuo

    2002-03-01

    The homozygous mutant klotho (KL-/-) mouse, which is deficient in klotho gene expression, exhibits multiple phenotypes resembling human aging that include a short life span, arteriosclerosis, osteoporosis, skin atrophy, and ectopic calcifications. Histologic examination of KL-/- mice at 4 weeks of age reveals pulmonary emphysema. The emphysematous changes are not caused by a developmental defect or hypoplasia of the lung. The lungs of heterozygous mutant klotho (KL+/-) mice show emphysematous changes and alveolar calcification which are almost identical to those in KL-/- mice. These observations indicate that the klotho gene expression is essential to maintaining normal alveolar architecture in postnatal life. Pulmonary function tests reveal prolonged expiration time in KL-/- mice. The expression of type IV collagen and surfactant protein-A mRNA is markedly upregulated in KL-/- mice, suggesting that a defect in matrix synthesis or in type II pneumocyte function, or both, may be involved in the pathogenesis of pulmonary emphysema in this mutant. Several animal strains have been reported to develop pulmonary emphysema, but the klotho mouse is unique because it simultaneously exhibits various aging phenotypes. Analysis of pulmonary emphysema in klotho mice will provide a unique insight into the relationship between pulmonary emphysema and aging.

  4. Longitudinal follow-up study of smoking-induced emphysema progression in low-dose CT screening of lung cancer

    NASA Astrophysics Data System (ADS)

    Suzuki, H.; Matsuhiro, M.; Kawata, Y.; Niki, N.; Nakano, Y.; Ohmatsu, H.; Kusumoto, M.; Tsuchida, T.; Eguchi, K.; Kaneko, Masahiro; Moriyama, N.

    2014-03-01

    Chronic obstructive pulmonary disease is a major public health problem that is predicted to be third leading cause of death in 2030. Although spirometry is traditionally used to quantify emphysema progression, it is difficult to detect the loss of pulmonary function by emphysema in early stage, and to assess the susceptibility to smoking. This study presents quantification method of smoking-induced emphysema progression based on annual changes of low attenuation volume (LAV) by each lung lobe acquired from low-dose CT images in lung cancer screening. The method consists of three steps. First, lung lobes are segmented using extracted interlobar fissures by enhancement filter based on fourdimensional curvature. Second, LAV of each lung lobe is segmented. Finally, smoking-induced emphysema progression is assessed by statistical analysis of the annual changes represented by linear regression of LAV percentage in each lung lobe. This method was applied to 140 participants in lung cancer CT screening for six years. The results showed that LAV progressions of nonsmokers, past smokers, and current smokers are different in terms of pack-year and smoking cessation duration. This study demonstrates effectiveness in diagnosis and prognosis of early emphysema in lung cancer CT screening.

  5. A size-based emphysema severity index: robust to the breath-hold-level variations and correlated with clinical parameters

    PubMed Central

    Hwang, Jeongeun; Lee, Minho; Lee, Sang Min; Oh, Sang Young; Oh, Yeon-Mok; Kim, Namkug; Seo, Joon Beom

    2016-01-01

    Objective To determine the power-law exponents (D) of emphysema hole-size distributions as a competent emphysema index. Robustness to extreme breath-hold-level variations and correlations with clinical parameters for chronic obstructive pulmonary disease (COPD) were investigated and compared to a conventional emphysema index (EI%). Patients and methods A total of 100 patients with COPD (97 males and three females of mean age 67±7.9 years) underwent multidetector row computed tomography scanning at full inspiration and full expiration. The diameters of the emphysematous holes were estimated and quantified with a fully automated algorithm. Power-law exponents (D) of emphysematous hole-size distribution were evaluated. Results The diameters followed a power-law distribution in all cases, suggesting the scale-free nature of emphysema. D of inspiratory and expiratory computed tomography of patients showed intraclass correlation coefficients >0.8, indicating statistically absolute agreement of different breath-hold levels. By contrast, the EI% failed to agree. Bland–Altman analysis also revealed the superior robustness of D to EI%. D also significantly correlated with clinical parameters such as airflow limitation, diffusion capacity, exercise capacity, and quality of life. Conclusion The D of emphysematous hole-size distribution is robust to breath-hold-level variations and sensitive to the severity of emphysema. This measurement may help rule out the confounding effects of variations in breath-hold levels. PMID:27536095

  6. Proliferative Activity of Liver Growth Factor is Associated with an Improvement of Cigarette Smoke-Induced Emphysema in Mice

    PubMed Central

    Terrón-Expósito, Raúl; Díaz-Gil, Juan José; González-Mangado, Nicolás; Peces-Barba, Germán

    2014-01-01

    Cigarette smoke (CS)-induced emphysema is a major component of chronic obstructive pulmonary disease (COPD). COPD treatment is based on the administration of bronchodilators and corticosteroids to control symptoms and exacerbations, however, to date, there are no effective therapies to reverse disease progression. Liver growth factor (LGF) is an albumin-bilirubin complex with mitogenic properties, whose therapeutic effects have previously been reported in a model of emphysema and several rodent models of human disease. To approach the therapeutic effect of LGF in a model of previously established emphysema, morphometric and lung function parameters, matrix metalloproteinase (MMP) activity and the expression of several markers, such as VEGF, PCNA, 3NT and Nrf2, were assessed in air-exposed and CS-exposed C57BL/6J male mice with and without intraperitoneal (i.p.) injection of LGF. CS-exposed mice presented a significant enlargement of alveolar spaces, higher alveolar internal area and loss of lung function that correlated with higher MMP activity, higher expression of 3NT and lower expression of VEGF. CS-exposed mice injected with LGF, showed an amelioration of emphysema and improved lung function, which correlated with lower MMP activity and 3NT expression and higher levels of VEGF, PCNA and Nrf2. Taken together, this study suggests that LGF administration ameliorates CS-induced emphysema, highlights the ability of LGF to promote alveolar cell proliferation and may be a promising strategy to revert COPD progression. PMID:25401951

  7. Sub-Volumetric Classification and Visualization of Emphysema Using a Multi-Threshold Method and Neural Network

    NASA Astrophysics Data System (ADS)

    Tan, Kok Liang; Tanaka, Toshiyuki; Nakamura, Hidetoshi; Shirahata, Toru; Sugiura, Hiroaki

    distribution of emphysema severity in the lung also plays an important role in the assessment of the overall functionality of the lung. We confirm our hypothesis by showing that the proposed sub-volumetric classification results correlate with the parameters of pulmonary function tests better than classical methods. We also visualize emphysema using a technique called the transparent lung model.

  8. Relationship between plasma matrix metalloproteinase levels, pulmonary function, bronchodilator response, and emphysema severity

    PubMed Central

    Koo, Hyeon-Kyoung; Hong, Yoonki; Lim, Myoung Nam; Yim, Jae-Joon; Kim, Woo Jin

    2016-01-01

    Objective Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation in the airway and lung. A protease–antiprotease imbalance has been suggested as a possible pathogenic mechanism for COPD. We evaluated the relationship between matrix metalloproteinase (MMP) levels and COPD severity. Methods Plasma levels of MMP-1, MMP-8, MMP-9, and MMP-12 were measured in 57 COPD patients and 36 normal controls. The relationship between MMP levels and lung function, emphysema index, bronchial wall thickness, pulmonary artery pressure, and quality of life was examined using general linear regression analyses. Results There were significant associations of MMP-1 with bronchodilator reversibility and of MMP-8 and MMP-9 with lung function. Also, MMP-1, MMP-8, and MMP-9 levels were correlated with the emphysema index, independent of lung function. However, MMP-12 was not associated with lung function or emphysema severity. Associations between MMP levels and bronchial wall thickness, pulmonary artery pressure, and quality of life were not statistically significant. Conclusion Plasma levels of MMP-1, MMP-8, and MMP-9 are associated with COPD severity and can be used as a biomarker to better understand the characteristics of COPD patients. PMID:27313452

  9. Cardiopulmonary exercise testing (CPET) in pulmonary emphysema.

    PubMed

    Paoletti, Patrizia; De Filippis, Francesca; Fraioli, Francesco; Cinquanta, Alessandra; Valli, Gabriele; Laveneziana, Pierantonio; Vaccaro, Francesco; Martolini, Dario; Palange, Paolo

    2011-12-15

    In patients affected by chronic obstructive pulmonary disease (COPD), cardiopulmonary response to exercise was never related to the severity of emphysema (E) measured by high resolution computed tomography (HRCT). Sixteen patients (age=65±8 yrs; FEV(1)=54±18%pred; RV=160±28%pred) with moderate to severe E (quantified by lung HRCT as % voxels <-910 HU) were exercised on a cycle-ergometer to exhaustion. Oxygen uptake (V˙(O2)), carbon dioxide output (V˙(CO2)), ventilation (V˙(E)), tidal volume (V(T)), and end-tidal P(CO2) (PET(CO2)) derived variables were measured breath-by-breath. The % of E correlated with: (1) the ratio V(Tpeak) (r=0.74; p=0.001); (2) the V˙(E)/V˙(CO2) slope (r=-0.77; p=0.0004); (3) PET(CO2) values at peak exercise (r=0.80; p=0.0001). Also, the %E was strongly predicted by the following exercise equation: %E(EST) = 58.1 + 11.9 × ΔV˙(E)/V˙(CO2) (r=0.94; p<0.0001). A V(Tpeak)/FEV1 ratio>1 is typically observed in severe E patients; furthermore, the V˙(E)/V˙(CO2) slope and the PET(CO2peak) values decrease and increase respectively as more as the emphysema is severe.

  10. Mesenchymal cell fate and phenotypes in the pathogenesis of emphysema.

    PubMed

    Horowitz, Jeffrey C; Martinez, Fernando J; Thannickal, Victor J

    2009-06-01

    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.

  11. Towards local progression estimation of pulmonary emphysema using CT

    SciTech Connect

    Staring, M. Bakker, M. E.; Shamonin, D. P.; Reiber, J. H. C.; Stoel, B. C.; Stolk, J.

    2014-02-15

    Purpose: Whole lung densitometry on chest CT images is an accepted method for measuring tissue destruction in patients with pulmonary emphysema in clinical trials. Progression measurement is required for evaluation of change in health condition and the effect of drug treatment. Information about the location of emphysema progression within the lung may be important for the correct interpretation of drug efficacy, or for determining a treatment plan. The purpose of this study is therefore to develop and validate methods that enable the local measurement of lung density changes, which requires proper modeling of the effect of respiration on density. Methods: Four methods, all based on registration of baseline and follow-up chest CT scans, are compared. The first naïve method subtracts registered images. The second employs the so-called dry sponge model, where volume correction is performed using the determinant of the Jacobian of the transformation. The third and the fourth introduce a novel adaptation of the dry sponge model that circumvents its constant-mass assumption, which is shown to be invalid. The latter two methods require a third CT scan at a different inspiration level to estimate the patient-specific density-volume slope, where one method employs a global and the other a local slope. The methods were validated on CT scans of a phantom mimicking the lung, where mass and volume could be controlled. In addition, validation was performed on data of 21 patients with pulmonary emphysema. Results: The image registration method was optimized leaving a registration error below half the slice increment (median 1.0 mm). The phantom study showed that the locally adapted slope model most accurately measured local progression. The systematic error in estimating progression, as measured on the phantom data, was below 2 gr/l for a 70 ml (6%) volume difference, and 5 gr/l for a 210 ml (19%) difference, if volume correction was applied. On the patient data an underlying

  12. Compressed air blast injury with palpebral, orbital, facial, cervical, and mediastinal emphysema through an eyelid laceration: a case report and review of literature

    PubMed Central

    2013-01-01

    Background To the best of our knowledge, only 14 cases of orbital or periorbital compressed air injuries from air guns or hoses have been reported in the literature. Case presentation A 30-year-old man was accidentally injured when a compressed air hose nozzle hit his right eye. The right half of his face was markedly swollen and a skin laceration near the right medial canthus was identified. A computed tomography scan showed subcutaneous and intraorbital emphysema around the right eye as well as cervical and mediastinal emphysema. He was prophylactically treated with systemic and topical antibiotics to prevent infection. All emphysemas had completely resolved 2 weeks after the injury. Conclusions A review of all 15 cases (including ours) showed that all patients were male and that 6 of the 15 (40.0%) cases were related to industrial accidents. Although emphysema was restricted to the subconjunctival space in 2 (13.3%) cases, it spread to the orbit in the remaining 13 (86.7%) cases. Cervical and mediastinal emphysemas were found in 3 (20.0%) cases, and intracranial emphysema was confirmed in 6 (40.0%) cases. Prophylactic antibiotics were used in most cases and the prognosis was generally good in all but one patient, who developed optic atrophy and blindness. PMID:24195485

  13. Toward computer-aided emphysema quantification on ultralow-dose CT: reproducibility of ventrodorsal gravity effect measurement and correction

    NASA Astrophysics Data System (ADS)

    Wiemker, Rafael; Opfer, Roland; Bülow, Thomas; Rogalla, Patrik; Steinberg, Amnon; Dharaiya, Ekta; Subramanyan, Krishna

    2007-03-01

    Computer aided quantification of emphysema in high resolution CT data is based on identifying low attenuation areas below clinically determined Hounsfield thresholds. However, the emphysema quantification is prone to error since a gravity effect can influence the mean attenuation of healthy lung parenchyma up to +/- 50 HU between ventral and dorsal lung areas. Comparing ultra-low-dose (7 mAs) and standard-dose (70 mAs) CT scans of each patient we show that measurement of the ventrodorsal gravity effect is patient specific but reproducible. It can be measured and corrected in an unsupervised way using robust fitting of a linear function.

  14. Functional Benefits of Bilateral Emphysema Reduction Surgery in an Adolescent.

    PubMed

    Julian, Valérie; Moreau de Bellaing, Anne; Filaire, Marc; Richard, Ruddy; Labbé, André

    2016-09-01

    Acquired emphysema is a rare pathology in pediatrics. We report the case of a patient born at term with a neonatal respiratory distress, which had required mechanical ventilation. She developed gradually chronic obstructive pulmonary disease with severe emphysematous lesions, respiratory failure and functional impairments. Bilateral emphysema resection, performed at 16 years old, allowed major functional benefits at rest and during exercise. We present the results of respiratory functional evaluations, walk tests and maximal exercise tests (including measure of dynamic hyperinflation) before and after surgery, which highlights that surgery is a successful option in the treatment of compressive emphysema in childhood.

  15. Thoracic magnetic resonance imaging for the evaluation of pulmonary emphysema.

    PubMed

    Lee, Sang Min; Seo, Joon Beom; Hwang, Hye Jeon; Kim, Eun Young; Oh, Sang Young; Kim, Ji-Eun

    2013-05-01

    Pulmonary emphysema is a pathologic condition characterized by permanently enlarged airspaces distal to the terminal bronchiole with destruction of the alveolar walls. Functional information of the lungs is important to understand the pathophysiology of emphysema and that of chronic obstructive pulmonary disease. With the recent developments in magnetic resonance imaging (MRI) techniques, functional MRI with variable MR sequences can be used for the evaluation of different physiological and anatomic changes seen in cases of pulmonary emphysema. In this review article, we will focus on a brief description of each method, results of some of the most recent work, and the clinical application of such knowledge.

  16. Effect of a cysteinyl leukotriene receptor antagonist on experimental emphysema and asthma combined with emphysema.

    PubMed

    Ikeda, Genyo; Miyahara, Nobuaki; Koga, Hikari; Fuchimoto, Yasuko; Waseda, Koichi; Kurimoto, Etsuko; Taniguchi, Akihiko; Tanimoto, Yasushi; Kataoka, Mikio; Tanimoto, Mitsune; Kanehiro, Arihiko

    2014-01-01

    The incidence of overlapping bronchial asthma and chronic obstructive pulmonary disease has increased in recent years. Cysteinyl leukotrienes (CysLTs) play an important role in asthma, and the type 1 CysLT receptor (CysLT1R) is expressed by many inflammatory cells. We evaluated the effect of montelukast, a CysLT1R antagonist, on mouse models of asthma, porcine pancreatic elastase (PPE)-induced emphysema, and asthma combined with emphysema. Mice were sensitized with ovalbumin (OVA) on Days 0 and 14 and subsequently challenged with OVA on Days 28, 29, and 30. Pulmonary emphysema was induced by intratracheal instillation of PPE on Day 25. Mice were treated subcutaneously with montelukast or vehicle from Day 25 to Day 31. Airway hyperresponsiveness (AHR), static compliance; the number of inflammatory cells, the levels of cytokines, chemokines, LTs, and perforin in the bronchoalveolar lavage fluid, and the quantitative morphometry of lung sections were analyzed on Day 32. Treatment with montelukast significantly attenuated the AHR and eosinophilic airway inflammation in OVA-sensitized and OVA-challenged mice. Administration of montelukast significantly reduced the AHR, static compliance, and neutrophilic airway inflammation, while attenuating emphysematous lung changes, in PPE-treated mice. In PPE-treated mice subjected to allergen sensitization and challenges, montelukast significantly suppressed the AHR, static compliance, and eosinophilic and neutrophilic airway inflammation in addition to the development of experimentally induced emphysema in the lungs. Our data suggest that CysLT1R antagonists may be effective in ameliorating the consequences of PPE-induced lung damage and the changes that follow allergen sensitization and challenges.

  17. Critical modifier role of membrane-cystic fibrosis transmembrane conductance regulator-dependent ceramide signaling in lung injury and emphysema.

    PubMed

    Bodas, Manish; Min, Taehong; Mazur, Steven; Vij, Neeraj

    2011-01-01

    Ceramide accumulation mediates the pathogenesis of chronic obstructive lung diseases. Although an association between lack of cystic fibrosis transmembrane conductance regulator (CFTR) and ceramide accumulation has been described, it is unclear how membrane-CFTR may modulate ceramide signaling in lung injury and emphysema. Cftr(+/+) and Cftr(-/-) mice and cells were used to evaluate the CFTR-dependent ceramide signaling in lung injury. Lung tissue from control and chronic obstructive pulmonary disease patients was used to verify the role of CFTR-dependent ceramide signaling in pathogenesis of chronic emphysema. Our data reveal that CFTR expression inversely correlates with severity of emphysema and ceramide accumulation in chronic obstructive pulmonary disease subjects compared with control subjects. We found that chemical inhibition of de novo ceramide synthesis controls Pseudomonas aeruginosa-LPS-induced lung injury in Cftr(+/+) mice, whereas its efficacy was significantly lower in Cftr(-/-) mice, indicating that membrane-CFTR is required for controlling lipid-raft ceramide levels. Inhibition of membrane-ceramide release showed enhanced protective effect in controlling P. aeruginosa-LPS-induced lung injury in Cftr(-/-) mice compared with that in Cftr(+/+) mice, confirming our observation that CFTR regulates lipid-raft ceramide levels and signaling. Our results indicate that inhibition of de novo ceramide synthesis may be effective in disease states with low CFTR expression like emphysema and chronic lung injury but not in complete absence of lipid-raft CFTR as in ΔF508-cystic fibrosis. In contrast, inhibiting membrane-ceramide release has the potential of a more effective drug candidate for ΔF508-cystic fibrosis but may not be effectual in treating lung injury and emphysema. Our data demonstrate the critical role of membrane-localized CFTR in regulating ceramide accumulation and inflammatory signaling in lung injury and emphysema.

  18. Mitochondrial phylogeny shows multiple independent ecological transitions and northern dispersion despite of Pleistocene glaciations in meadow and steppe vipers (Vipera ursinii and Vipera renardi).

    PubMed

    Zinenko, Oleksandr; Stümpel, Nikolaus; Mazanaeva, Lyudmila; Bakiev, Andrey; Shiryaev, Konstantin; Pavlov, Aleksey; Kotenko, Tatiana; Kukushkin, Oleg; Chikin, Yury; Duisebayeva, Tatiana; Nilson, Göran; Orlov, Nikolai L; Tuniyev, Sako; Ananjeva, Natalia B; Murphy, Robert W; Joger, Ulrich

    2015-03-01

    The phylogeny and historical demography of small Eurasian vipers of the Vipera ursinii and V. renardi complexes were studied using mitochondrial DNA sequences analysed with Bayesian inference, Maximum Likelihood and Maximum Parsimony approaches, and mismatch distributions. Diversification in the group resulted from an initial dispersion in the later Pliocene - Pleistocene in two directions: north-westwards via the Balkans (V. ursinii complex) and north-eastwards from Asia Minor via the Caucasus (V. renardi complex). An independent, comparatively recent transition occurred from montane habitats to lowland grasslands in different mitochondrial lineages during the Late Pleistocene, when representatives of the both complexes had reached lowland steppes to the north. Effective population size showed clear signs of rapid growth in eastern V. renardi, triggered by colonization of vast lowland steppes, but in western V. ursinii complex grew during the Last Glaciation and experienced stabilization in Holocene. Expansion and population growth in lowland lineages of V. renardi was not strongly affected by Pleistocene climatic oscillations, when cold, dry conditions could have favoured species living in open grasslands. The high diversity of closely related haplotypes in the Caucasus and Tien-Shan could have resulted from repetitive expansion-constriction-isolation events in montane regions during Pleistocene climate fluctuations. The mitochondrial phylogeny pattern conflicts with the current taxonomy.

  19. APG350 induces superior clustering of TRAIL receptors and shows therapeutic antitumor efficacy independent of cross-linking via Fcγ receptors.

    PubMed

    Gieffers, Christian; Kluge, Michael; Merz, Christian; Sykora, Jaromir; Thiemann, Meinolf; Schaal, René; Fischer, Carmen; Branschädel, Marcus; Abhari, Behnaz Ahangarian; Hohenberger, Peter; Fulda, Simone; Fricke, Harald; Hill, Oliver

    2013-12-01

    Cancer cells can be specifically driven into apoptosis by activating Death-receptor-4 (DR4; TRAIL-R1) and/or Death-receptor-5 (DR5; TRAIL-R2). Albeit showing promising preclinical efficacy, first-generation protein therapeutics addressing this pathway, especially agonistic anti-DR4/DR5-monoclonal antibodies, have not been clinically successful to date. Due to their bivalent binding mode, effective apoptosis induction by agonistic TRAIL-R antibodies is achieved only upon additional events leading to antibody-multimer formation. The binding of these multimers to their target subsequently leads to effective receptor-clustering on cancer cells. The research results presented here report on a new class of TRAIL-receptor agonists overcoming this intrinsic limitation observed for antibodies in general. The main feature of these agonists is a TRAIL-mimic consisting of three TRAIL-protomer subsequences combined in one polypeptide chain, termed the single-chain TRAIL-receptor-binding domain (scTRAIL-RBD). In the active compounds, two scTRAIL-RBDs with three receptor binding sites each are brought molecularly in close proximity resulting in a fusion protein with a hexavalent binding mode. In the case of APG350-the prototype of this engineering concept-this is achieved by fusing the Fc-part of a human immunoglobulin G1 (IgG1)-mutein C-terminally to the scTRAIL-RBD polypeptide, thereby creating six receptor binding sites per drug molecule. In vitro, APG350 is a potent inducer of apoptosis on human tumor cell lines and primary tumor cells. In vivo, treatment of mice bearing Colo205-xenograft tumors with APG350 showed a dose-dependent antitumor efficacy. By dedicated muteins, we confirmed that the observed in vivo efficacy of the hexavalent scTRAIL-RBD fusion proteins is-in contrast to agonistic antibodies-independent of FcγR-based cross-linking events.

  20. [The respiratory muscles in emphysema. The effects of thoracic distension].

    PubMed

    Cassart, M; Estenne, M

    2000-04-01

    Besides increasing the work of ventilation, emphysema increases lung volume which in itself has a deleterious effect on the inspiratory muscles. We review here the effects of an acute change in lung volume on the configuration of the rib cage and muscle function. We also discuss the effects of the chronic distension associated with emphysema. The effects produced by changes in muscle length and configuration on the mechanical force and action of inspiratory muscles is detailed with particular focus on the diaphragm and its structural adaptations to experimental emphysema. We also analyze the activation pattern of inspiratory and expiratory muscles during the breathing process in patients with emphysema. Finally, we discuss the effects of single-lung transplantation and reduction surgery on chest distension and improved inspiratory muscle function.

  1. Pathogenesis of emphysema: from the bench to the bedside.

    PubMed

    Sharafkhaneh, Amir; Hanania, Nicola A; Kim, Victor

    2008-05-01

    Chronic obstructive pulmonary disease (COPD) is characterized physiologically by expiratory flow limitation and pathologically by alveolar destruction and enlargement and small and large airway inflammation and remodeling. An imbalance between protease and antiprotease activity in the lung is proposed as the major mechanism resulting in emphysema. The imbalance is mostly due to an increase in the numbers of alveolar macrophages and neutrophils. Emphysema can also develop from increased alveolar wall cell death and/or failure in alveolar wall maintenance. Chronic inflammation and increased oxidative stress contribute to increased destruction and/or impaired lung maintenance and repair. Genetic factors may play an important role in disease susceptibility because only a minority of smokers develops emphysema. Recent literature implicates surfactant instability, malnutrition, and alveolar cell apoptosis as possible etiologies. Identification of cellular and molecular mechanisms of COPD pathogenesis is an area of active, ongoing research that may help to determine therapeutic targets for emphysema.

  2. [Bronchus dystopia with emphysema and solitary lung cyst in children].

    PubMed

    Römer, K H; Thal, W; Motsch, H

    1982-01-01

    Occasionally bronchial dystopia may be the cause of lobular emphysema. Only by bronchoscopy and bronchography exact diagnosis is possible. For therapy in children the methods of lung resection should be taken into consideration.

  3. Subcutaneous emphysema secondary to dental extraction: A case report.

    PubMed

    Tan, S; Nikolarakos, D

    2017-03-01

    Although less frequently encountered in dental practices, subcutaneous emphysema of the face and neck has been reported in patients following dental extractions, particularly when lower molar teeth are extracted with the use of a high-speed air-turbine drill designed for restorative treatment, which forces air into the cervical fascial spaces. As facial swelling and pain are the most common presentations, subcutaneous emphysema can often be misdiagnosed as an allergic reaction or odontogenic infection. While usually a benign and self-limiting condition, subcutaneous emphysema may have life-threatening complications such as tension pneumothorax, cardiac tamponade, air embolism, tracheal compression and mediastinitis, which are important to recognize in an emergency setting. Dentists should be aware of the serious risks of inducing subcutaneous emphysema and avoid performing tooth extractions with high-speed air-turbine drills which are specifically designed for use for restorative treatments only.

  4. Massive spontaneous subcutaneous emphysema. Acute management with infraclavicular "blow holes".

    PubMed

    Herlan, D B; Landreneau, R J; Ferson, P F

    1992-08-01

    Four patients who recently developed massive spontaneous subcutaneous emphysema in our intensive care unit are reported. No obviously remediable intrathoracic process was found in any of these patients. The acute physiologic impairment and grotesque cosmetic deformity were immediately alleviated by making bilateral 3-cm infraclavicular incisions down to the pectoralis fascia. These acutely decompressed the progressive subcutaneous dissection and each patient's subcutaneous emphysema resolved without any additional invasive therapy.

  5. Interleukin-6 promotes pulmonary emphysema associated with apoptosis in mice.

    PubMed

    Ruwanpura, Saleela M; McLeod, Louise; Miller, Alistair; Jones, Jessica; Bozinovski, Steven; Vlahos, Ross; Ernst, Matthias; Armes, Jane; Bardin, Philip G; Anderson, Gary P; Jenkins, Brendan J

    2011-10-01

    The IL-6 cytokine family, which signals via the shared gp130 coreceptor, is linked with the pathogenesis of emphysema. However, the definitive mechanisms by which these cytokines cause emphysema remain ill-defined. We took an in vivo genetic complementation approach to identify the specific IL-6 cytokine family members and gp130-regulated cellular processes that cause emphysema. We used gp130(F/F) mice homozygous for a subtle knock-in mutation in gp130 that deregulates intracellular signaling by the IL-6 cytokine family. The gp130(F/F) mice spontaneously develop emphysema by age 6 months. Within the IL-6 cytokine family, only IL-6 was significantly up-regulated in the lungs of gp130(F/F) mice, and the genetic targeting of IL-6 in gp130(F/F) mice (gp130(F/F):IL-6(-/-)) prevented emphysema. By contrast, the genetic ablation of receptor signaling via IL-11, which like IL-6 signals via a gp130 homodimer and uses the same signaling machinery, failed to ameliorate emphysema in gp130(F/F) mice. Among the disease-associated processes examined, emphysema strongly correlated with elevated alveolar cell apoptosis. Acute (4-day) exposure to cigarette smoke (CS) further augmented the expression of IL-6 in lungs of gp130(F/F) mice, and subchronic (6-week) exposure to CS exacerbated emphysematous and apoptotic changes in the lungs of gp130(F/F) but not gp130(F/F): IL-6(-/-) mice. IL-6 is the main causative agent of IL-6 cytokine family-induced emphysema, and operates to induce apoptosis in the lung. We propose that the discrete targeting of IL-6 signaling may provide an effective therapeutic strategy against human lung disease.

  6. Emphysema and mechanical stress-induced lung remodeling.

    PubMed

    Suki, Béla; Sato, Susumu; Parameswaran, Harikrishnan; Szabari, Margit V; Takahashi, Ayuko; Bartolák-Suki, Erzsébet

    2013-11-01

    Transpulmonary pressure and the mechanical stresses of breathing modulate many essential cell functions in the lung via mechanotransduction. We review how mechanical factors could influence the pathogenesis of emphysema. Although the progression of emphysema has been linked to mechanical rupture, little is known about how these stresses alter lung remodeling. We present possible new directions and an integrated multiscale view that may prove useful in finding solutions for this disease.

  7. Screening for emphysema via exhaled volatile organic compounds.

    PubMed

    Cristescu, S M; Gietema, H A; Blanchet, L; Kruitwagen, C L J J; Munnik, P; van Klaveren, R J; Lammers, J W J; Buydens, L; Harren, F J M; Zanen, P

    2011-12-01

    Chronic obstructive pulmonary disease (COPD)/emphysema risk groups are well defined and screening allows for early identification of disease. The capability of exhaled volatile organic compounds (VOCs) to detect emphysema, as found by computed tomography (CT) in current and former heavy smokers participating in a lung cancer screening trial, was investigated. CT scans, pulmonary function tests and breath sample collections were obtained from 204 subjects. Breath samples were analyzed with a proton-transfer reaction mass spectrometer (PTR-MS) to obtain VOC profiles listed as ions at various mass-to-charge ratios (m/z). Using bootstrapped stepwise forward logistic regression, we identified specific breath profiles as a potential tool for the diagnosis of emphysema, of airflow limitation or gas-exchange impairment. A marker for emphysema was found at m/z 87 (tentatively attributed to 2-methylbutanal). The area under the receiver operating characteristic curve (ROC) of this marker to diagnose emphysema was 0.588 (95% CI 0.453-0.662). Mass-to-charge ratios m/z 52 (most likely chloramine) and m/z 135 (alkyl benzene) were linked to obstructive disease and m/z 122 (most probably alkyl homologs) to an impaired diffusion capacity. ROC areas were 0.646 (95% CI 0.562-0.730) and 0.671 (95% CI 0.524-0.710), respectively. In the screening setting, exhaled VOCs measured by PTR-MS constitute weak markers for emphysema, pulmonary obstruction and impaired diffusion capacity.

  8. Independent evolution of knuckle-walking in African apes shows that humans did not evolve from a knuckle-walking ancestor.

    PubMed

    Kivell, Tracy L; Schmitt, Daniel

    2009-08-25

    Despite decades of debate, it remains unclear whether human bipedalism evolved from a terrestrial knuckle-walking ancestor or from a more generalized, arboreal ape ancestor. Proponents of the knuckle-walking hypothesis focused on the wrist and hand to find morphological evidence of this behavior in the human fossil record. These studies, however, have not examined variation or development of purported knuckle-walking features in apes or other primates, data that are critical to resolution of this long-standing debate. Here we present novel data on the frequency and development of putative knuckle-walking features of the wrist in apes and monkeys. We use these data to test the hypothesis that all knuckle-walking apes share similar anatomical features and that these features can be used to reliably infer locomotor behavior in our extinct ancestors. Contrary to previous expectations, features long-assumed to indicate knuckle-walking behavior are not found in all African apes, show different developmental patterns across species, and are found in nonknuckle-walking primates as well. However, variation among African ape wrist morphology can be clearly explained if we accept the likely independent evolution of 2 fundamentally different biomechanical modes of knuckle-walking: an extended wrist posture in an arboreal environment (Pan) versus a neutral, columnar hand posture in a terrestrial environment (Gorilla). The presence of purported knuckle-walking features in the hominin wrist can thus be viewed as evidence of arboreality, not terrestriality, and provide evidence that human bipedalism evolved from a more arboreal ancestor occupying the ecological niche common to all living apes.

  9. Intravenous and intratracheal mesenchymal stromal cell injection in a mouse model of pulmonary emphysema.

    PubMed

    Tibboel, Jeroen; Keijzer, Richard; Reiss, Irwin; de Jongste, Johan C; Post, Martin

    2014-06-01

    The aim of this study was to characterize the evolution of lung function and -structure in elastase-induced emphysema in adult mice and the effect of mesenchymal stromal cell (MSC) administration on these parameters. Adult mice were treated with intratracheal (4.8 units/100 g bodyweight) elastase to induce emphysema. MSCs were administered intratracheally or intravenously, before or after elastase injection. Lung function measurements, histological and morphometric analysis of lung tissue were performed at 3 weeks, 5 and 10 months after elastase and at 19, 20 and 21 days following MSC administration. Elastase-treated mice showed increased dynamic compliance and total lung capacity, and reduced tissue-specific elastance and forced expiratory flows at 3 weeks after elastase, which persisted during 10 months follow-up. Histology showed heterogeneous alveolar destruction which also persisted during long-term follow-up. Jugular vein injection of MSCs before elastase inhibited deterioration of lung function but had no effects on histology. Intratracheal MSC treatment did not modify lung function or histology. In conclusion, elastase-treated mice displayed persistent characteristics of pulmonary emphysema. Jugular vein injection of MSCs prior to elastase reduced deterioration of lung function. Intratracheal MSC treatment had no effect on lung function or histology.

  10. [Combined pulmonary fibrosis and emphysema (CPFE)--limitation of usual lung function test and challenge at practice].

    PubMed

    Takai, Daiya

    2014-12-01

    Spirometry and the flow-volume curve test are commonly performed lung function tests. However, a unique clinical entity occasionally shows almost normal data in these tests, and is therefore missed on screening tests. The clinical entity of combined pulmonary emphysema and pulmdoary fibrosis was recognized and documented in the 90's in Japan, the USA, and Europe. Typical emphysema shows obstructive disorders, and pulmonary fibrosis shows restrictive disorders. Thus, the combination of both should lead to a combined disorder pattern in lung function tests, but this is not the case. In 2005, Cottin reported and redefined this combination of emphysema and fibrosis of the lung as "Combined Pulmonary Fibrosis and Emphysema" (CPFE). The patients are typically heavily smoking males who show an almost normal lung function. The upper lobe of these patients usually shows severe emphysema, which contributes to a static volume and a late phase in the forced volume test. On the other hand their lower lobe shows fibrotic change. The fibrotic portion contributes to early phase flow in the flow-volume curve. These mechanisms are a reason for the normal pattern appearance in lung function tests in CPFE patients. As a matter of course, these patients have damaged upper and lower lobes: their diffusing capacity of the lung shows a low performance, their saturation of blood hemoglobin decreases soon after light exercise, and their KL-6 (a blood marker of pulmonary fibrosis) usually shows a high value. They are considered a high risk group regarding complications of post-surgical treatment. Thus, when medical technologists identify suspicious cases, they should advise doctors to add diffusing capacity and KL-6 tests. (Review).

  11. Religious and Spiritual Coping and Quality of Life Among Patients With Emphysema in the National Emphysema Treatment Trial

    PubMed Central

    Green, Marquisha R; Emery, Charles F; Kozora, Elizabeth; Diaz, Philip T; Make, Barry J

    2013-01-01

    BACKGROUND Although prior research indicates that religious and spiritual coping is associated with positive health outcomes, few studies have examined religious and spiritual coping among patients with emphysema. OBJECTIVE To describe the utilization of religious and spiritual coping and its relationship to quality of life among patients with emphysema, in a 2-year longitudinal follow-up study. METHODS Forty patients with emphysema (mean age 63.5 ± 6.0 y, 8 women) who participated in the National Emphysema Treatment Trial were matched on age, sex, race, and education with 40 healthy individuals recruited from the community. We conducted baseline assessment of overall coping strategies, psychological functioning, quality of life, pulmonary function, and exercise capacity, and we assessed overall coping strategies and religious and spiritual coping at 2-year follow-up. RESULTS Ninety percent of the patients with emphysema considered themselves at least slightly religious and spiritual. The patients reported using both negative religious coping (eg, questioning God) and positive religious coping (eg, prayer) more than the healthy control subjects at follow-up. However, greater use of religious and spiritual coping was associated with poorer illness-related quality of life. CONCLUSIONS Patients with emphysema appear to use various coping strategies in responding to their illness. Future research should investigate if patients using religious and spiritual coping would benefit from interventions to address emotional distress and reduced quality of life. PMID:21513606

  12. Moderate Aerobic Training Improves Cardiorespiratory Parameters in Elastase-Induced Emphysema

    PubMed Central

    Henriques, Isabela; Lopes-Pacheco, Miquéias; Padilha, Gisele A.; Marques, Patrícia S.; Magalhães, Raquel F.; Antunes, Mariana A.; Morales, Marcelo M.; Rocha, Nazareth N.; Silva, Pedro L.; Xisto, Débora G.; Rocco, Patricia R. M.

    2016-01-01

    Aim: We investigated the therapeutic effects of aerobic training on lung mechanics, inflammation, morphometry and biological markers associated with inflammation, and endothelial cell damage, as well as cardiac function in a model of elastase-induced emphysema. Methods: Eighty-four BALB/c mice were randomly allocated to receive saline (control, C) or 0.1 IU porcine pancreatic elastase (emphysema, ELA) intratracheally once weekly for 4 weeks. After the end of administration period, once cardiorespiratory impairment associated with emphysema was confirmed, each group was further randomized into sedentary (S) and trained (T) subgroups. Trained mice ran on a motorized treadmill, at moderate intensity, 30 min/day, 3 times/week for 4 weeks. Results: Four weeks after the first instillation, ELA animals, compared to C, showed: (1) reduced static lung elastance (Est,L) and levels of vascular endothelial growth factor (VEGF) in lung tissue, (2) increased elastic and collagen fiber content, dynamic elastance (E, in vitro), alveolar hyperinflation, and levels of interleukin-1β and tumor necrosis factor (TNF)-α, and (3) increased right ventricular diastolic area (RVA). Four weeks after aerobic training, ELA-T group, compared to ELA-S, was associated with reduced lung hyperinflation, elastic and collagen fiber content, TNF-α levels, and RVA, as well as increased Est,L, E, and levels of VEGF. Conclusion: Four weeks of regular and moderate intensity aerobic training modulated lung inflammation and remodeling, thus improving pulmonary function, and reduced RVA and pulmonary arterial hypertension in this animal model of elastase-induced emphysema. PMID:27536247

  13. Intranasal HGF administration ameliorates the physiologic and morphologic changes in lung emphysema.

    PubMed

    Hegab, Ahmed E; Kubo, Hiroshi; Yamaya, Mutsuo; Asada, Masanori; He, Mei; Fujino, Naoya; Mizuno, Shinya; Nakamura, Toshikazu

    2008-08-01

    Hepatocyte growth factor (HGF) has multiple biological effects on stem cells, epithelial proliferation, and wound healing. In this study, we investigated a possible therapeutic benefit of intranasal HGF on elastase-induced emphysema, and assessed the role of stem/progenitor cells in this process. HGF was given twice a week for 1-4 weeks after the establishment of emphysema in mice. HGF inhalation significantly ameliorated the enlargement of airspaces and alveolar wall destruction. Also, elevated static lung compliance returned to control levels within 2 weeks of HGF treatment. The expressions of stem-cell markers, c-kit, stem-cell antigen 1 (Sca-1), and CD34 were also significantly influenced by HGF. Most of the c-kit(+) cells were bone marrow derived, while most Sca-1(+) were lung endogenous cells. CD34(+) cells were from both sources, and a portion of the endogenous CD34(+) cells was also Sca-1(+). Further, HGF increased the expression levels of proliferating cell nuclear antigen (PCNA) and cytokeratin-19. Also, their immunohistochemical staining patterns were colocalized, indicative of epithelial multiplication. The results of the study show that intranasal treatment with HGF reverses both the physiological and morphometric changes of lung emphysema, possibly through stem-cell mobilization and alveolar regeneration, providing a nonsurgical treatment and suggesting the possibility of achieving a similar effect in humans.

  14. Comparison of starvation and elastase models of emphysema in the rat

    SciTech Connect

    Harkema, J.R.; Mauderly, J.L.; Gregory, R.E.; Pickrell, J.A.

    1984-01-01

    Starvation and elastase-induced changes in rat lung structure, biochemistry, and function were compared as models of human pulmonary emphysema. Ten-week-old male rats were instilled intratracheally with either porcine pancreatic elastase in saline (E) or with saline alone. A group of the saline-instilled rats were fed one third of their normal food intake until a 45% loss of body weight occurred (S). The remaining saline-instilled rats served as control animals (C). Post-treatment evaluations included in vivo respiratory function, lung histopathologic and morphometric analyses, lung tissue proteinolytic activity, and lung collagen. The E rats had in vivo respiratory function changes more similar to human emphysema than those of S rats. All lung volume subdivisions were decreased in S rats and increased in E rats. The volume-pressure curve of S rats was shifted to the right of the C curve, whereas that of E rats was shifted to the left. Forced expiratory flow rates of E rats were decreased at all lung volumes, but those of S rats were not. Both E and S rats had larger terminal air spaces and less alveolar surface area than did C rats. The S rats had more collagen per gram lung and higher proteinolytic activity than did C or E rats. These results show that, although starvation induces some changes characteristic of human emphysema, elastase-treatment provides a model more similar to the human disease. 44 references, 5 figures, 4 tables.

  15. Effect of low-level NO/sub 2/ chronic exposure on elastase-induced emphysema

    SciTech Connect

    Lafuma, C.; Harf, A.; Lange, F.; Bozzi, L.; Poncy, J.L.; Bignon, J.

    1987-06-01

    The effect of chronic exposure to 2 ppm nitrogen dioxide (NO/sub 2/) for 8 hr a day, 5 days a week, for 8 weeks was assessed in normal and emphysematous hamsters by measuring (1) lung morphometry (mean linear intercept (Lm) and internal surface area (ISA)), (2) lung mechanics (lung volume, compliance and coefficient of static deflation, pressure-volume curve fitted to an exponential equation), and (3) serum elastolytic activity and protease inhibitor capacity. Emphysema was induced by a single intratracheal injection of 6 IU porcine pancreatic elastase. Four groups of animals were used: control, NO/sub 2/-exposed, elastase-treated, and NO/sub 2/-exposed postelastase. Results show that NO/sub 2/ exposure alone induced mild emphysematous lesions whose degree of severity was of the same order as that of the lesions induced by 6 IU elastase. Exposure to 2 ppm NO/sub 2/ enhanced elastase-induced emphysema. By contrast, study of lung mechanics revealed no difference between the control and NO/sub 2/-exposed groups or between the elastase-treated animals exposed to NO/sub 2/ and those not so exposed. Lastly, results suggest that chronic exposure to 2 ppm NO/sub 2/ may cause individuals with inherited or acquired emphysematous lesions to develop more severe emphysema.

  16. Nanoparticulate carbon black in cigarette smoke induces DNA cleavage and Th17-mediated emphysema

    PubMed Central

    You, Ran; Lu, Wen; Shan, Ming; Berlin, Jacob M; Samuel, Errol LG; Marcano, Daniela C; Sun, Zhengzong; Sikkema, William KA; Yuan, Xiaoyi; Song, Lizhen; Hendrix, Amanda Y; Tour, James M; Corry, David B; Kheradmand, Farrah

    2015-01-01

    Chronic inhalation of cigarette smoke is the major cause of sterile inflammation and pulmonary emphysema. The effect of carbon black (CB), a universal constituent of smoke derived from the incomplete combustion of organic material, in smokers and non-smokers is less known. In this study, we show that insoluble nanoparticulate carbon black (nCB) accumulates in human myeloid dendritic cells (mDCs) from emphysematous lung and in CD11c+ lung antigen presenting cells (APC) of mice exposed to smoke. Likewise, nCB intranasal administration induced emphysema in mouse lungs. Delivered by smoking or intranasally, nCB persisted indefinitely in mouse lung, activated lung APCs, and promoted T helper 17 cell differentiation through double-stranded DNA break (DSB) and ASC-mediated inflammasome assembly in phagocytes. Increasing the polarity or size of CB mitigated many adverse effects. Thus, nCB causes sterile inflammation, DSB, and emphysema and explains adverse health outcomes seen in smokers while implicating the dangers of nCB exposure in non-smokers. DOI: http://dx.doi.org/10.7554/eLife.09623.001 PMID:26437452

  17. Deletion of vitamin D receptor leads to premature emphysema/COPD by increased matrix metalloproteinases and lymphoid aggregates formation

    SciTech Connect

    Sundar, Isaac K.; Hwang, Jae-Woong; Wu, Shaoping; Sun, Jun; Rahman, Irfan

    2011-03-04

    Research highlights: {yields} Vitamin D deficiency is linked to accelerated decline in lung function. {yields} Levels of vitamin D receptor (VDR) are decreased in lungs of patients with COPD. {yields} VDR knock-out mouse showed increased lung inflammation and emphysema. {yields} This was associated with decline in lung function and increased MMPs. {yields} VDR knock-out mouse model is useful for studying the mechanisms of lung diseases. -- Abstract: Deficiency of vitamin D is associated with accelerated decline in lung function. Vitamin D is a ligand for nuclear hormone vitamin D receptor (VDR), and upon binding it modulates various cellular functions. The level of VDR is reduced in lungs of patients with chronic obstructive pulmonary disease (COPD) which led us to hypothesize that deficiency of VDR leads to significant alterations in lung phenotype that are characteristics of COPD/emphysema associated with increased inflammatory response. We found that VDR knock-out (VDR{sup -/-}) mice had increased influx of inflammatory cells, phospho-acetylation of nuclear factor-kappaB (NF-{kappa}B) associated with increased proinflammatory mediators, and up-regulation of matrix metalloproteinases (MMPs) MMP-2, MMP-9, and MMP-12 in the lung. This was associated with emphysema and decline in lung function associated with lymphoid aggregates formation compared to WT mice. These findings suggest that deficiency of VDR in mouse lung can lead to an early onset of emphysema/COPD because of chronic inflammation, immune dysregulation, and lung destruction.

  18. Hhip haploinsufficiency sensitizes mice to age-related emphysema.

    PubMed

    Lao, Taotao; Jiang, Zhiqiang; Yun, Jeong; Qiu, Weiliang; Guo, Feng; Huang, Chunfang; Mancini, John Dominic; Gupta, Kushagra; Laucho-Contreras, Maria E; Naing, Zun Zar Chi; Zhang, Li; Perrella, Mark A; Owen, Caroline A; Silverman, Edwin K; Zhou, Xiaobo

    2016-08-09

    Genetic variants in Hedgehog interacting protein (HHIP) have consistently been associated with the susceptibility to develop chronic obstructive pulmonary disease and pulmonary function levels, including the forced expiratory volume in 1 s (FEV1), in general population samples by genome-wide association studies. However, in vivo evidence connecting Hhip to age-related FEV1 decline and emphysema development is lacking. Herein, using Hhip heterozygous mice (Hhip(+/-)), we observed increased lung compliance and spontaneous emphysema in Hhip(+/-) mice starting at 10 mo of age. This increase was preceded by increases in oxidative stress levels in the lungs of Hhip(+/-) vs. Hhip(+/+) mice. To our knowledge, these results provide the first line of evidence that HHIP is involved in maintaining normal lung function and alveolar structures. Interestingly, antioxidant N-acetyl cysteine treatment in mice starting at age of 5 mo improved lung function and prevented emphysema development in Hhip(+/-) mice, suggesting that N-acetyl cysteine treatment limits the progression of age-related emphysema in Hhip(+/-) mice. Therefore, reduced lung function and age-related spontaneous emphysema development in Hhip(+/-) mice may be caused by increased oxidative stress levels in murine lungs as a result of haploinsufficiency of Hhip.

  19. Prevalence and clinical correlates of bronchoreversibility in severe emphysema.

    PubMed

    Han, M K; Wise, R; Mumford, J; Sciurba, F; Criner, G J; Curtis, J L; Murray, S; Sternberg, A; Weinman, G; Kazerooni, E; Fishman, A P; Make, B; Hoffman, E A; Mosenifar, Z; Martinez, F J

    2010-05-01

    Chronic obstructive pulmonary disease (COPD) exhibits airflow obstruction that is not fully reversible. The importance of bronchoreversibility remains controversial. We hypothesised that an emphysematous phenotype of COPD would be associated with decreased bronchoreversibility. 544 patients randomised to the medical arm of the National Emphysema Treatment Trial formed the study group. Participants underwent multiple measurements of bronchoreversibility on a mean of four sessions over 1.91 yrs. They were also characterised by measures of symptoms, quality of life and quantitative measures of emphysema by computed tomography. Mean baseline forced expiratory volume in 1 s (FEV(1)) in this patient population is 24% predicted. 22.2% of patients demonstrated bronchoreversibility on one or more occasions using American Thoracic Society/European Respiratory Society criteria. Few patients (0.37%) had bronchoreversibility on all completed tests. Patients who demonstrated bronchoreversibility were more likely to be male, and have better lung function and less emphysema. 64% of patients demonstrated large (> or =400 mL) changes in forced vital capacity (FVC). In a severe emphysema population, bronchoreversibility as defined by change in FEV(1) is infrequent, varies over time, and is more common in males and those with less severe emphysema. Improvements in FVC, however, were demonstrated in the majority of patients.

  20. Comparison of methods for evaluation of experimentally induced emphysema

    SciTech Connect

    Busch, R.H.; Buschbom, R.L.; Smith, L.G.

    1984-04-01

    Four methods to quantify induced emphysema, in a manner economically applicable to large numbers of animals, are compared by correlation analyses. Lung tissue used was from rats pretreated intratracheally with elastase or saline prior to exposure to air or (NH/sub 4/)/sub 2/SO/sub 4/ or NH/sub 4/NO/sub 3/ aerosols. The most sensitive quantitative evaluation was from mean chord length (MCL) measurements on scanning electron micrographs (SEM). Four-corner and parallel-line grids provided similar results, and reducing sample size to one selected field per lobe yielded a high degree of reliability for MCL measurements. Alveolar-pore perimeter and area (also measured on SEM photographs) were increased by induced emphysema, but were not reliable indicators for degree of pulmonary involvement. Both subjective score (grading the degree of emphysema) and percentage-area-affected determinations indicated the presence of emphysema, but with less sensitivity than MCL measurements. However, these two subgross methods (performed with a dissecting microscope) provided valuable information on the distribution of pulmonary lesions; emphysema was induced in a nonuniform but consistent and progressive pattern in the two lobes of the lung studied. 23 studied.

  1. [Education of patients with asthma, chronic bronchitis and pulmonary emphysema].

    PubMed

    Krstić-Burić, M; Pavicić, F; Rozman, A; Bogić, B; Crc, M; Plesko, N; Sarajlić, N

    1997-02-01

    Patients' education belongs to the most efficient therapeutic measures in the management of asthma, chronic bronchitis and pulmonary emphysema. The following paper reports the experience in the educational programme at the Polyclinic for Respiratory Diseases in Zagreb. Each patient's education lasted 5 days, 3 lessons per day, in groups of 10-15 persons. The education was carried out by a teaching team consisting of pulmonologists, psychosomatologist, pharmacist, physiotherapist and biometeterologist. From March 1995 to February 1996 135 persons completed the educational programme, 65 of whom were asthma patients. Data on cough and dyspnoea, skills in inhaler and breathing technique were collected at the beginning and 3 months after the education in all asthma patients. Three months after the education the asthma patients showed a significant decrease in dyspnoea and a significant improvement in inhaler and breathing technique. A standard questionnaire was given to all patients at the end of the education and in more than 80% the education was well accepted by the patients. Initial results are encouraging and the programme should be expanded to all parts of Croatia.

  2. Spontaneous pulmonary interstitial emphysema in a term unventilated infant.

    PubMed

    Freysdottir, Drifa; Olutoye, Oluyinka; Langston, Claire; Fernandes, Caraciolo J; Tatevian, Nina

    2006-04-01

    Pulmonary interstitial emphysema (PIE) is a form of air block most frequently seen in ventilated preterm infants with severe lung disease; it is rarely reported in spontaneously breathing term infants. We report on an infant previously diagnosed with laryngomalacia and congestive heart failure and with evidence of antenatal stroke before the onset of pulmonary disease. He presented at 6 weeks of age with spontaneous pneumothorax. Focal cystic changes were seen on imaging studies of the lungs. There was no prior history of mechanical ventilation. Prior chest X-rays did not show cystic changes. He subsequently underwent resection of the affected lung areas. Pathologic examination revealed persistent PIE with cystic expansion, pleural blebs, and reactive pleuritis, as well as subpleural air-space enlargement. The patient did well postoperatively and was discharged home without further problems. This case demonstrates that PIE can occur in an infant without any history of mechanical ventilation, suggesting the need for a high index of suspicion for PIE, even in nonventilated and spontaneously breathing term neonates. PIE should be included in the differential diagnosis of cystic lung lesions in all young infants.

  3. Emphysema model in rats treated intratracheally with elastase

    SciTech Connect

    Yokoyama, E.; Nambu, Z.; Uchiyama, I.; Kyono, H.

    1987-04-01

    Pulmonary functions, morphology, and morphometry were examined in rats at 3, 7, and 10 weeks after a single intratracheal administration of 6.5 units of porcine pancreatic elastase in order to obtain a model of pulmonary emphysema which would be suitable for studying the responses of emphysematous lungs to atmospheric pollutants. Functional residual capacity and residual volume of the elastase-treated rats increased at all the times studied, but their total lung capacity increased only at 7 and 10 weeks compared with those of the saline-treated control rats. The increase in static lung compliance and the decrease in peak flow and maximum flow at 50% of total lung capacity during forced expiration were also observed in all except the 3-week elastase animals. The elastase-treated lungs showed morphological changes characteristic of emphysematous lesions. The increase in mean linear intercept length and the decrease in total alveolar surface area were demonstrated by these elastase-treated lungs. Based on these results, they conclude that an adequate and suitable model of pulmonary emphysemia could be obtained in rats 7-10 weeks after treatment with the present dose of elastase.

  4. Tumour necrosis factor receptor I blockade shows that TNF-dependent and TNF-independent mechanisms synergise in TNF receptor associated periodic syndrome.

    PubMed

    Fairclough, Lucy C; Stoop, A Allart; Negm, Ola H; Radford, Paul M; Tighe, Patrick J; Todd, Ian

    2015-10-01

    TNF receptor associated periodic syndrome (TRAPS) is an autoinflammatory disease involving recurrent episodes of fever and inflammation. It is associated with autosomal dominant mutations in TNF receptor superfamily 1A gene localised to exons encoding the ectodomain of the p55 TNF receptor, TNF receptor-1 (TNFR1). The aim of this study was to investigate the role of cell surface TNFR1 in TRAPS, and the contribution of TNF-dependent and TNF-independent mechanisms to the production of cytokines. HEK-293 and SK-HEP-1 cell lines were stably transfected with WT or TRAPS-associated variants of human TNF receptor superfamily 1A gene. An anti-TNFR1 single domain antibody (dAb), and an anti-TNFR1 mAb, bound to cell surface WT and variant TNFR1s. In HEK-293 cells transfected with death domain-inactivated (R347A) TNFR1, and in SK-HEP-1 cells transfected with normal (full-length) TNFR1, cytokine production stimulated in the absence of exogenous TNF by the presence of certain TNFR1 variants was not inhibited by the anti-TNFR1 dAb. In SK-Hep-1 cells, specific TRAPS mutations increased the level of cytokine response to TNF, compared to WT, and this augmented cytokine production was suppressed by the anti-TNFR1 dAb. Thus, TRAPS-associated variants of TNFR1 enhance cytokine production by a TNF-independent mechanism and by sensitising cells to a TNF-dependent stimulation. The TNF-dependent mechanism requires cell surface expression of TNFR1, as this is blocked by TNFR1-specific dAb.

  5. Pathogenesis of pulmonary emphysema - cellular and molecular events.

    PubMed

    Di Petta, Antonio

    2010-06-01

    Pulmonary emphysema is a chronic obstructive disease, resulting from important alterations in the whole distal structure of terminal bronchioles, either by enlargement of air spaces or by destruction of the alveolar wall, leading to loss of respiratory surface, decreased elastic recoil and lung hyperinflation. For many years, the hypothesis of protease-antiprotease unbalance prevailed as the central theme in the pathogenesis of pulmonary emphysema. According to this hypothesis, the release of active proteolytic enzymes, produced mainly by neutrophils and macrophages, degrades the extracellular matrix, affecting the integrity of its components, especially collagen and elastic fibers. However, new concepts involving cellular and molecular events were proposed, including oxidative stress, cell apoptosis, cellular senescence and failed lung tissue repair. The aim of this review paper was to evaluate the cellular and molecular mechanisms seen in the pathogenesis of pulmonary emphysema.

  6. Subcutaneous Emphysema, Pneumomediastinum and Pneumothorax in a Patient with Dermatomyositis

    PubMed Central

    Bakhshaee, Mehdi; Jokar, Mohammad Hassan; Mirfeizi, Zahra; Atabati, Elham; Tarighat, Somayeh

    2017-01-01

    Introduction: Spontaneous pneumomediastinum, pneumothorax, and subcutaneous emphysema are rare, but serious complications of inflammatory myopathies and occur more commonly in DM than PM. complications of dermatomyositis (DM) and polymyositis (PM), both of which can be fatal. Case Report: A 20-year-old woman was admitted with neck pain, dyspnea, cough, and fever. She had been diagnosed with dermatomyositis 21 months prior. A thorax computed tomography (CT) scan revealed ground glass opacities in her lungs, pneumomediastinum, pneumothorax, and subcutaneous emphysema. Despite intensive immunosuppressive therapy, clinical deterioration and radiological progression were observed, ultimately the patient died. Conclusion: During the care for a patient with dermatomyositis, the otorhinolaryngologist should be cautious of rapidly progressive and fatal neck subcutaneous emphysema. For a patient with dermatomyositis and with normal bronchoscopy and esophagoscopy, the main treatment is control of dermatomyositis with medical therapy. Therefore, a tracheostomy and/or mechanical ventilation may not be necessary.

  7. Severe subcutaneous and deep cervicofacial emphysema of unusual etiology.

    PubMed

    Terzic, Andrej; Becker, Minerva; Masterson, Karen; Scolozzi, Paolo

    2012-01-01

    Subcutaneous and deep cervical emphysema (SCE) in the head and neck are found in a wide spectrum of conditions. Most of them are seen in patients with midfacial trauma or oropharyngeal infections. Subcutaneous and deep cervical emphysema can also be a symptom of life-threatening mediastinitis and/or necrotizing fasciitis, both of which need immediate surgery. Rarely however does SCE occur in isolation as a consequence of elevated intraoral pressure in combination with or without visible lacerations of the oral mucosa. As a consequence, air penetrates the mucosal tears and results in subcutaneous emphysema even extending down to the mediastinum in severe cases. This article describes a series of five cases of isolated SCE. It discusses the diagnosis, the pathomechanism, the differential diagnosis and the treatment. It underlines the importance of anamnesis and careful physical and laboratory examinations in order to differentiate isolated SCE from more severe conditions such as necrotizing fasciitis or mediastinitis, which necessitate immediate surgery.

  8. Subcutaneous emphysema and pneumomediastinum complicating a dental procedure.

    PubMed

    Döngel, Isa; Bayram, Mehmet; Uysal, Ismail Onder; Sunam, Güven Sadi

    2012-07-01

    Cervicofacial emphysema and pneumomediastinum are rarely observed complications of dental interventions. The complications are associated with the use of a high-speed air-turbine dental drill. It is a potentially life-threatening condition, but the majority of cases are self-limiting and benign. We describe a patient with remarkable subcutaneous emphysema, pneumomediastinum, and partial pneumothorax after right second mandibular molar extraction. Dentists and physicians more often attribute the rapid onset of dyspnea in patients after a dental procedure to an allergic reaction to the anesthesia used during the procedure. Dentists and physicians should be aware that soft tissue emphysema can cause acute swelling of the cervicofacial region after dental procedures, which may mimic an allergic reaction.

  9. Endothelial progenitor cells in chronic obstructive pulmonary disease and emphysema.

    PubMed

    Doyle, Margaret F; Tracy, Russell P; Parikh, Megha A; Hoffman, Eric A; Shimbo, Daichi; Austin, John H M; Smith, Benjamin M; Hueper, Katja; Vogel-Claussen, Jens; Lima, Joao; Gomes, Antoinette; Watson, Karol; Kawut, Steven; Barr, R Graham

    2017-01-01

    Endothelial injury is implicated in the pathogenesis of COPD and emphysema; however the role of endothelial progenitor cells (EPCs), a marker of endothelial cell repair, and circulating endothelial cells (CECs), a marker of endothelial cell injury, in COPD and its subphenotypes is unresolved. We hypothesized that endothelial progenitor cell populations would be decreased in COPD and emphysema and that circulating endothelial cells would be increased. Associations with other subphenotypes were examined. The Multi-Ethnic Study of Atherosclerosis COPD Study recruited smokers with COPD and controls age 50-79 years without clinical cardiovascular disease. Endothelial progenitor cell populations (CD34+KDR+ and CD34+KDR+CD133+ cells) and circulating endothelial cells (CD45dimCD31+CD146+CD133-) were measured by flow cytometry. COPD was defined by standard spirometric criteria. Emphysema was assessed qualitatively and quantitatively on CT. Full pulmonary function testing and expiratory CTs were measured in a subset. Among 257 participants, both endothelial progenitor cell populations, and particularly CD34+KDR+ endothelial progenitor cells, were reduced in COPD. The CD34+KDR+CD133+ endothelial progenitor cells were associated inversely with emphysema extent. Both endothelial progenitor cell populations were associated inversely with extent of panlobular emphysema and positively with diffusing capacity. Circulating endothelial cells were not significantly altered in COPD but were inversely associated with pulmonary microvascular blood flow on MRI. There was no consistent association of endothelial progenitor cells or circulating endothelial cells with measures of gas trapping. These data provide evidence that endothelial repair is impaired in COPD and suggest that this pathological process is specific to emphysema.

  10. Endothelial progenitor cells in chronic obstructive pulmonary disease and emphysema

    PubMed Central

    Tracy, Russell P.; Parikh, Megha A.; Hoffman, Eric A.; Shimbo, Daichi; Austin, John H. M.; Smith, Benjamin M.; Hueper, Katja; Vogel-Claussen, Jens; Lima, Joao; Gomes, Antoinette; Watson, Karol; Kawut, Steven; Barr, R. Graham

    2017-01-01

    Endothelial injury is implicated in the pathogenesis of COPD and emphysema; however the role of endothelial progenitor cells (EPCs), a marker of endothelial cell repair, and circulating endothelial cells (CECs), a marker of endothelial cell injury, in COPD and its subphenotypes is unresolved. We hypothesized that endothelial progenitor cell populations would be decreased in COPD and emphysema and that circulating endothelial cells would be increased. Associations with other subphenotypes were examined. The Multi-Ethnic Study of Atherosclerosis COPD Study recruited smokers with COPD and controls age 50–79 years without clinical cardiovascular disease. Endothelial progenitor cell populations (CD34+KDR+ and CD34+KDR+CD133+ cells) and circulating endothelial cells (CD45dimCD31+CD146+CD133-) were measured by flow cytometry. COPD was defined by standard spirometric criteria. Emphysema was assessed qualitatively and quantitatively on CT. Full pulmonary function testing and expiratory CTs were measured in a subset. Among 257 participants, both endothelial progenitor cell populations, and particularly CD34+KDR+ endothelial progenitor cells, were reduced in COPD. The CD34+KDR+CD133+ endothelial progenitor cells were associated inversely with emphysema extent. Both endothelial progenitor cell populations were associated inversely with extent of panlobular emphysema and positively with diffusing capacity. Circulating endothelial cells were not significantly altered in COPD but were inversely associated with pulmonary microvascular blood flow on MRI. There was no consistent association of endothelial progenitor cells or circulating endothelial cells with measures of gas trapping. These data provide evidence that endothelial repair is impaired in COPD and suggest that this pathological process is specific to emphysema. PMID:28291826

  11. Emphysema, Airflow Limitation and Early Age-Related Macular Degeneration

    PubMed Central

    Klein, Ronald; Knudtson, Michael D.; Klein, Barbara E. K.; Wong, Tien Y.; Cotch, Mary Frances; Barr, R. Graham

    2009-01-01

    Objective To describe the relationships of lung function and emphysema, measured with spirometry and computed tomography (CT) scan, to early AMD in a multi-ethnic sample of whites, blacks, Hispanics, and Chinese. Methods and Design 3,399 persons aged 45–84 years residing in six United States communities participating in a period cross-sectional study. AMD was measured from digital retinal photographs at the second Multi-Ethnic Study of Atherosclerosis (MESA) examination. Forced expiratory volume in one second (FEV1) and FEV1/forced vital capacity (FVC) ratio were measured at the third or fourth MESA examination. Percent emphysema was measured from cardiac CT scans at baseline. Apical and basilar lung segments were defined as the cephalad or caudal regions of the lung on the cardiac CT scan. Logistic regression models were used to examine the relationship of lung function and structure to AMD controlling for age, gender, and other factors. Results The prevalence of early AMD was 3.7%. Early AMD was not associated with FEV1 (odds ratio [OR], 95% confidence interval [CI], and P value, 0.82, 0.58–1.15, P=0.25), FEV1/ FVC ratio (0.92, 0.76–1.12, 0.43), percent emphysema (1.13, 0.91–1.40, 0.26) and apical-basilar difference in percent emphysema (1.14, 0.95–1.37, 0.17). Associations were stronger in smokers. Apical-basilar difference in percent emphysema was significantly associated with early AMD among ever smokers (1.28, 1.02–1.60, 0.03). Associations were not modified by race/ethnicity. Conclusions Lung function and emphysema on CT scan were not cross-sectionally associated with AMD; this might be explained by the relatively low smoking exposure in this cohort. PMID:20385944

  12. Massive subcutaneous emphysema, pneumomediastinum, and pneumopericardium in children.

    PubMed

    Giuliani, Stefano; Franklin, Ashanti; Pierce, James; Ford, Henri; Grikscheit, Tracy C

    2010-03-01

    Massive subcutaneous emphysema (SE), pneumomediastinum (PM), and pneumopericardium (PP) are rare conditions in the pediatric population. Air leak syndrome is a constellation of disorders that include SE, PM, PP, and pulmonary interstitial emphysema. In children, SE, PM, and PP are associated with obstructive airway disease most often in the case of asthma. Management may be conservative or involve invasive procedures that require surgical intervention. Here, we describe a case of massive SE, PM, and PP in a 10-year-old child after placement of a peripherally inserted central line and review the literature.

  13. Towards local estimation of emphysema progression using image registration

    NASA Astrophysics Data System (ADS)

    Staring, M.; Bakker, M. E.; Shamonin, D. P.; Stolk, J.; Reiber, J. H. C.; Stoel, B. C.

    2009-02-01

    Progression measurement of emphysema is required to evaluate the health condition of a patient and the effect of drugs. To locally estimate progression we use image registration, which allows for volume correction using the determinant of the Jacobian of the transformation. We introduce an adaptation of the so-called sponge model that circumvents its constant-mass assumption. Preliminary results from CT scans of a lung phantom and from CT data sets of three patients suggest that image registration may be a suitable method to locally estimate emphysema progression.

  14. Orthorexia Nervosa with Hyponatremia, Subcutaneous Emphysema, Pneumomediastimum, Pneumothorax, and Pancytopenia

    PubMed Central

    Park, Sang Won; Kim, Jeong Yup; Go, Gang Ji; Jeon, Eun Sil; Pyo, Heui Jung

    2011-01-01

    30-year-old male was admitted with general weakness and drowsy mental status. He had eaten only 3-4 spoons of brown rice and fresh vegetable without salt for 3 months to treat his tic disorder, and he had been in bed-ridden state. He has had weight loss of 14 kg in the last 3 months. We report a patient with orthorexia nervosa who developed hyponatremia, metabolic acidosis, subcutaneous emphysema, mediastinal emphysema, pneumothorax, and pancytopenia and we will review the literature. Also, we mention to prevent refeeding syndrome, and to start and maintain feeding in malnourished patients. PMID:21998605

  15. Orthorexia nervosa with hyponatremia, subcutaneous emphysema, pneumomediastimum, pneumothorax, and pancytopenia.

    PubMed

    Park, Sang Won; Kim, Jeong Yup; Go, Gang Ji; Jeon, Eun Sil; Pyo, Heui Jung; Kwon, Young Joo

    2011-06-01

    30-year-old male was admitted with general weakness and drowsy mental status. He had eaten only 3-4 spoons of brown rice and fresh vegetable without salt for 3 months to treat his tic disorder, and he had been in bed-ridden state. He has had weight loss of 14 kg in the last 3 months. We report a patient with orthorexia nervosa who developed hyponatremia, metabolic acidosis, subcutaneous emphysema, mediastinal emphysema, pneumothorax, and pancytopenia and we will review the literature. Also, we mention to prevent refeeding syndrome, and to start and maintain feeding in malnourished patients.

  16. Lower-zone emphysema in young patients without α1-antitrypsin deficiency

    PubMed Central

    Martelli, Nestor A.; Goldman, Ernesto; Roncoroni, Aquiles J.

    1974-01-01

    Martelli, N. A., Goldman, E., and Roncoroni, A. J. (1974).Thorax, 29, 237-244. Lowerzone emphysema in young patients without α1-antitrypsin deficiency. Three young patients with radiographic pulmonary emphysema predominantly in the lower zones are reported. The clinical and physiological features were those observed in severe pulmonary emphysema. Predominance of the main lesions in the lower zones was confirmed in two cases by selective pulmonary angiography. One of the patients died and extensive panlobular emphysema was found at necropsy. Although the similarities between our patients and those with emphysema and α1-antitrypsin deficiency were remarkable, the latter condition was ruled out. Images PMID:4545502

  17. Impact of COPD and emphysema on survival of patients with lung cancer: A meta-analysis of observational studies.

    PubMed

    Gao, Yong-Hua; Guan, Wei-Jie; Liu, Qi; Wang, Hua-Qi; Zhu, Ya-Nan; Chen, Rong-Chang; Zhang, Guo-Jun

    2016-02-01

    Both COPD and emphysema are associated with an increased incidence of lung cancer, but the impacts of these comorbidities on lung cancer prognosis are still unclear. Herein, we conducted a meta-analysis to clarify whether the presence of these comorbidities indicates poor survival in patients with lung cancer. A comprehensive search was conducted using PubMed, Embase, Web of Science, ASCO Abstracts and Cochrane library for articles published before 1 June 2015. Papers referenced by the obtained articles were also reviewed. Main outcomes were overall survival (OS) and disease-free survival (DFS) in patients with lung cancer. Pooled hazard ratio (HR) and 95% confidence intervals (CIs) were calculated using random-effects models. Subgroup and sensitivity analyses were also conducted. Of 58 full texts reviewed, 26 met our inclusion criteria that were derived from 21 and seven studies examining the impacts of COPD and emphysema on survival of lung cancer, respectively. Meta-analyses revealed that concomitant COPD was associated with poorer OS (HR, 1.17; 95% CI: 1.10-1.25, n = 20), which was independent of tumour staging, diagnostic criteria of COPD or location, and DFS (HR, 1.52; 95% CI: 1.04-2.23, n = 6) with high heterogeneity (I(2) = 78%). The presence of emphysema in patients with lung cancer predicted worse OS (HR, 1.66; 95% CI: 1.25-2.22, n = 7), but not poorer DFS. The presence of COPD and emphysema are robust predictors of poor survival in patients with lung cancer. Early detection of these diseases should be taken into account for lung cancer surveillance and management.

  18. Everything prevents emphysema: are animal models of cigarette smoke-induced chronic obstructive pulmonary disease any use?

    PubMed

    Churg, Andrew; Sin, Don D; Wright, Joanne L

    2011-12-01

    There is a very large number of experimental approaches that prevent cigarette smoke-induced emphysema in laboratory animals, but the few similar treatments that have been tried in humans have had minimal effects, leading to questions of whether animal models of chronic obstructive pulmonary disease (COPD) are of any use in developing treatments for human disease. We review possible reasons for this problem. First, humans usually get treated when they have severe (Global Initiative for Chronic Obstructive Lung Disease III/IV) COPD, but animal models only produce mild (Global Initiative for Chronic Obstructive Lung Disease I/II) disease that never progresses after smoking cessation, and never develops spontaneous exacerbations (i.e., animal models are not models of severe human disease, and probably can't be used to model treatment of severe disease). Second, animal models have concentrated on emphysema and largely ignored small airway remodeling, but small airway remodeling is an equally important cause of airflow obstruction. In addition, small airway remodeling and emphysema are independent responses to smoke, and some experimental animal treatments prevent both lesions, but many do not. Third, animal models are typically Day 1 of smoke exposure "prevention" models, but humans are always treated well along in the course of their disease; thus, any human treatment will be an intervention, and not a prevention. We propose that animal models should examine both emphysema and small airway remodeling, and that experiments should include a relatively late intervention arm. This approach, combined with the realization that human COPD probably needs early rather than late treatment, may make development of treatments based on animal models more relevant.

  19. Pneumoperitoneum with Subcutaneous Emphysema after Percutaneous Endoscopic Gastrostomy

    PubMed Central

    Karip, Bora; Ozcabi, Yetkin; Ağca, Birol; Alahdab, Yesim; Memisoglu, Kemal

    2014-01-01

    Percutaneous endoscopic gastrostomy is a safe way for enteral nutrition in selected patients. Generally, complications of this procedure are very rare but due to patients general health condition, delayed diagnosis and treatment of complications can be life threatening. In this study, we present a PEG-related massive pneumoperitoneum and subcutaneous emphysema in a patient with neuro-Behçet. PMID:25120935

  20. Pneumomediastinum, bilateral pneumothorax and subcutaneous emphysema complicating acute silicosis.

    PubMed

    Dixit, Ramakant; Meena, Manoj; Patil, Chetan B

    2015-01-01

    A case of acute silicosis complicating as spontaneous pneumomediastinum, bilateral pneumothorax and subcutaneous emphysema is described in a 35-year-old male engaged in stone crusher unit. Diagnosis was established on clinical and radiological assessment and supported by occupational history of the patient. This case is unique one as all these 3 complications at the same time are very uncommon in acute silicosis.

  1. Subcutaneous emphysema during third molar surgery: a case report.

    PubMed

    Romeo, Umberto; Galanakis, Alexandros; Lerario, Francesco; Daniele, Gabriele Maria; Tenore, Gianluca; Palaia, Gaspare

    2011-01-01

    Extraction of third molars is the most common surgical procedure performed in oral surgery on a daily basis and, despite surgical skills and expertise, complications may occur. Complications observed during or after third molar removal may include pain, swelling, bleeding, infection, sinus perforation and nerve damage. Fortunately, with a proper management and a good surgical technique, the incidence of such events is low. Subcutaneous emphysema associated with dental extraction occurs when the air from the high-speed dental handpiece is forced into the soft tissue through the reflected flap and invades the adjacent tissues, leading to swelling, crepitus on palpation and occasionally spreading through the tissue spaces of the fascial planes. Although rare, iatrogenic subcutaneous emphysema can have serious and potentially life-threatening consequences. Care should be taken when using air-driven handpieces. The access of air into the facial tissues is not limited to tooth extractions, but may also occur through other portals of entrance, such as endodontically treated teeth, periodontium and lacerations of intraoral soft tissues. When subcutaneous emphysema occurs, it must be quickly diagnosed and properly managed to reduce the risk of further complications. This report presents a case of subcutaneous emphysema occurred during extraction of a mandibular third molar extraction with the use of an air turbine handpiece. Case management is described and issues relative to the diagnosis and prevention of this surgical complication are discussed.

  2. Testing of compounds in models of pulmonary emphysema.

    PubMed

    Gardi, Concetta; Arezzini, Beatrice; Martorana, Piero A

    2008-01-01

    There is a pressing need for the development of new therapies for emphysema, particularly as no existing treatment has been shown to reduce disease progression. Compounds with a potential activity against the pathological mechanisms postulated to play a role in the development and progression of emphysema should be tested in vivo in animal models of this disease. The choice of the model is of capital importance. While models of elastase-induced emphysema are relatively easy to execute, require low personnel capacity and provide fast results, they also have a limited clinical relevance. On the other hand, models of chronic smoke exposure are time-consuming, expensive and require high personnel capacity but have a high clinical relevance. Presently, mainly two pharmacological approaches are being considered and investigated in experimental studies. The first approach consists of pharmacological interventions designed to slow down the rate at which alveolar wall is lost in emphysema. In this approach we find anti-inflammatory agents, protease inhibitors and antioxidants. The attempt to reduce lung inflammatory cell infiltration is most appealing since such an effect would also reduce the lung burden of both proteases and oxidants. The second approach is an attempt to reverse the process of alveolar loss by inducing alveolar growth. To our knowledge here only the effects of retinoids and/or retinoid receptor agonists have been investigated. This report presents a selected review of the literature of animal studies using these pharmacological approaches.

  3. Borrelia miyamotoi infections among wild rodents show age and month independence and correlation with Ixodes persulcatus larval attachment in Hokkaido, Japan.

    PubMed

    Taylor, Kyle R; Takano, Ai; Konnai, Satoru; Shimozuru, Michito; Kawabata, Hiroki; Tsubota, Toshio

    2013-02-01

    To clarify how Borrelia miyamotoi is maintained in the environment in Hokkaido, we examined Ixodes persulcatus for its prevalence among wild rodents and its tick vector by detecting a portion of the borrelial flaB gene in rodent urinary bladder and blood samples, and from whole ticks. We compared B. miyamotoi infection rates to Borrelia garinii and Borrelia afzelii, which are human Lyme disease pathogens also carried by wild rodents, and which are transmitted by the same vector tick. Whereas B. garinii and B. afzelii showed age dependence of infection rates among wild rodents (18.4% and 9.9% among adults and 6.0% and 3.4% among sub-adults, respectively) when looking at urinary bladder samples, B. miyamotoi infection rates were not age dependent for either blood (4.2% among adults, and 7.9% among sub-adults) or urinary bladder samples (1.0% among adults, and 1.7% among sub-adults). Moreover, while B. garinii and B. afzelii infection rates showed increases across months (June, July [p<0.05] and August [p<0.01] had higher rates than in May for adult rodents with B. garinii, and July and August had higher rates than in May [p<0.01] for adult rodents with B. afzelii), B. miyamotoi infection rates did not show significant month dependence. These differences in month and age dependence led us to suspect that B. miyamotoi may not develop persistent infections in wild rodents, as B. garinii and B. afzelii are thought to. Furthermore, we examined the extent of rodent exposure to I. persulcatus nymphs and larvae throughout most of the tick's active season (May through September), and determined that B. miyamotoi infection rates in sub-adult rodents were correlated with larval burden (p<0.01), suggesting that larvae may be very important in transmission of B. miyamotoi to wild rodents.

  4. Quantification of Emphysema: A Bullae Distribution Based Approach

    NASA Astrophysics Data System (ADS)

    Tan, Kok Liang; Tanaka, Toshiyuki; Nakamura, Hidetoshi; Shirahata, Toru; Sugiura, Hiroaki

    Computed tomography (CT)-based quantifications of emphysema encompass, and are not limited to, the ratio of the low-attenuation area, the bullae size, and the distribution of bullae in the lung. The standard CT-based emphysema describing indices include the mean lung density, the percentage of area of low attenuation [the pixel index (PI)] and the bullae index (BI). These standard emphysema describing indices are not expressive for describing the distribution of bullae in the lung. Consequently, the goal of this paper is to present a new emphysema describing index, the bullae congregation index (BCI), that describes whether bullae gather in a specific area of the lung and form a nearly single mass, and if so, how dense the mass of bullae is in the lung. BCI ranges from zero to ten corresponding to sparsely distributed bullae to densely distributed bullae. BCI is calculated based on the relative distance between every pair of bullae in the lung. The bullae pair distances are sorted into 200 distance classes. A smaller distance class corresponds to a closer proximity between the bullae. BCI is derived by calculating the percentage of the area of bullae in the lung that are separated by a certain distance class. Four bullae congregation classes are defined based on BCI. We evaluate BCI using 114 CT images that are hand-annotated by a radiologist into four bullae congregation classes. The average four-class classification accuracy of BCI is 88.21%. BCI correlates better than PI, BI and other standard statistical dispersion based methods with the radiological consensus-classified bullae congregation class.While BCI is not a specific index for indicating emphysema severity, it complements the existing set of emphysema describing indices to facilitate a more thorough knowledge about the emphysematous conditions in the lung. BCI is especially useful when it comes to comparing the distribution of bullae for cases with approximately the same PI, BI or PI and BI. BCI is easy

  5. SerpinB1 deficiency is not associated with increased susceptibility to pulmonary emphysema in mice.

    PubMed

    Cremona, Tiziana P; Tschanz, Stefan A; von Garnier, Christophe; Benarafa, Charaf

    2013-12-01

    Chronic obstructive pulmonary disease (COPD) is characterized by emphysema and chronic bronchitis and is a leading cause of morbidity and mortality worldwide. Tobacco smoke and deficiency in α1-antitrypsin (AAT) are the most prominent environmental and genetic risk factors, respectively. Yet the pathogenesis of COPD is not completely elucidated. Disease progression appears to include a vicious circle driven by self-perpetuating lung inflammation, endothelial and epithelial cell death, and proteolytic degradation of extracellular matrix proteins. Like AAT, serpinB1 is a potent inhibitor of serine proteases including neutrophil elastase and cathepsin G. Because serpinB1 is expressed in myeloid and lung epithelial cells and is protective during lung infections, we investigated the role of serpinB1 in preventing age-related and cigarette smoke-induced emphysema in mice. Fifteen-month-old mice showed increased lung volume and decreased pulmonary function compared with young adult mice (3 mo old), but no differences were observed between serpinB1-deficient (KO) and wild-type (WT) mice. Chronic exposure to secondhand cigarette smoke resulted in structural emphysematous changes compared with respective control mice, but no difference in lung morphometry was observed between genotypes. Of note, the different pattern of stereological changes induced by age and cigarette smoke suggest distinct mechanisms leading to increased airway volume. Finally, expression of intracellular and extracellular protease inhibitors were differently regulated in lungs of WT and KO mice following smoke exposure; however, activity of proteases was not significantly altered. In conclusion, we showed that, although AAT and serpinB1 are similarly potent inhibitors of neutrophil proteases, serpinB1 deficiency is not associated with more severe emphysema.

  6. Retinoid treatment of Emphysema in Patients on the Alpha-1 International Registry. The REPAIR study: study design, methodology and quality control of study assessments.

    PubMed

    Stolk, Jan; Cooper, Brendan G; Stoel, Berend; Rames, Alexis; Rutman, Olga; Soliman, Sherif; Stockley, Robert

    2010-12-01

    Emphysema is characterized by the destruction of alveolar wall and enlargement of alveolar airspaces, resulting in a reduction of the total lung gas exchange area, loss of lung elastic recoil and hyperinflation. The REPAIR study (Retinoid treatment of Emphysema in Patients on the Alpha-1 International Registry) is the first proof-of-concept study of a new potential disease-modifying drug, Palovarotene©, an orally active, gamma selective retinoid agonist in patients with emphysema secondary to alpha-1-antitrypsin deficiency (AATD) as a model population for the general smoke-induced emphysema population. This article describes the study design as well as the effectiveness of the quality control that was implemented on the key efficacy endpoints, based on data derived from the placebo-treated subjects. In this multicentre, multinational study the implementation of standardized procedures included: careful site selection, use of trained staff, regular monitoring and machine calibration, use of biological controls and regular feedback to sites by an independent quality control centre. All of these procedures resulted in high-quality measurements of lung density, spirometry, static lung volumes and gas transfer. It was also confirmed that CT lung density was the most sensitive endpoint followed by TLco, FEV(1) and RV measured by body box.

  7. Smad3 signaling involved in pulmonary fibrosis and emphysema.

    PubMed

    Gauldie, Jack; Kolb, Martin; Ask, Kjetil; Martin, Gail; Bonniaud, Philippe; Warburton, David

    2006-11-01

    The incidence of finding evidence of both emphysema and pulmonary fibrosis in the same patient has received increased attention. Several investigators have found on biopsy the presence of emphysema of the upper zones and diffuse parenchymal disease with fibrosis of the lower zones of the lung, especially associated with current or previous heavy smokers. Believed previously to be two different disease mechanisms, there are now data to implicate some common pathways of cell and molecular activation leading to the different morphologic and physiologic outcomes. According to a current view, emphysema may originate from a protease/antiprotease imbalance, whereas a role for antiproteases has been proposed in the modulation of fibrosis. Overexpression of transforming growth factor beta (TGF-beta) in experimental rodent models leads to progressive pulmonary fibrosis, accompanied with marked up-regulation of protease inhibitors, such as tissue inhibitor of metalloproteinases (TIMP) and plasminogen activator inhibitor-1 (PAI-1) genes, along with excessive matrix accumulation. It may be that a "matrix degrading" pulmonary microenvironment, one in which metalloproteinase activities prevail, favors the development of emphysema, whereas a "matrix nondegrading" microenvironment, with enhanced presence of TIMPs, would lead to matrix accumulation and fibrosis. Surprisingly, although Smad3 null mice, deficient in TGF-beta signal transmission, are resistant to bleomycin- and TGF-beta-mediated fibrosis, they develop spontaneous age-related airspace enlargement, consistent with emphysema, with a lack of ability to repair tissue damage appropriately. A common element is tissue damage and repair, with TGF-beta and the Smad signaling pathway playing prominent molecular roles. Both changes can be followed in experimental models with noninvasive imaging and physiologic measurements.

  8. Therapeutic effect of lecithinized superoxide dismutase on pulmonary emphysema.

    PubMed

    Tanaka, Ken-Ichiro; Tanaka, Yuta; Miyazaki, Yuri; Namba, Takushi; Sato, Keizo; Aoshiba, Kazutetsu; Azuma, Arata; Mizushima, Tohru

    2011-09-01

    No medication exists that clearly improves the mortality of chronic obstructive pulmonary disease (COPD). Oxidative molecules, in particular superoxide anions, play important roles in the COPD-associated abnormal inflammatory response and pulmonary emphysema, which arises because of an imbalance in proteases and antiproteases and increased apoptosis. Superoxide dismutase (SOD) catalyzes the dismutation of superoxide anions. Lecithinized human Cu/Zn- SOD (PC-SOD) has overcome a number of the clinical limitations of SOD, including low tissue affinity and low stability in plasma. In this study, we examine the effect of PC-SOD on elastase-induced pulmonary emphysema, an animal model of COPD. The severity of the pulmonary inflammatory response and emphysema in mice was assessed by various criteria, such as the number of leukocytes in the bronchoalveolar lavage fluid and the enlargement of airspace. Not only intravenous administration but also inhalation of PC-SOD suppressed elastase-induced pulmonary inflammation, emphysema, and dysfunction. Inhalation of PC-SOD suppressed the elastase-induced increase in the pulmonary level of superoxide anions and apoptosis. Inhalation of PC-SOD also suppressed elastase-induced activation of proteases and decreased in the level of antiproteases and expression of proinflammatory cytokines and chemokines. We also found that inhalation of PC-SOD suppressed cigarette smoke-induced pulmonary inflammation. The results suggest that PC-SOD protects against pulmonary emphysema by decreasing the pulmonary level of superoxide anions, resulting in the inhibition of inflammation and apoptosis and amelioration of the protease/antiprotease imbalance. We propose that inhalation of PC-SOD would be therapeutically beneficial for COPD.

  9. Proteasome inhibitor-adapted myeloma cells are largely independent from proteasome activity and show complex proteomic changes, in particular in redox and energy metabolism

    PubMed Central

    Soriano, G P; Besse, L; Li, N; Kraus, M; Besse, A; Meeuwenoord, N; Bader, J; Everts, B; den Dulk, H; Overkleeft, H S; Florea, B I; Driessen, C

    2016-01-01

    Adaptive resistance of myeloma to proteasome inhibition represents a clinical challenge, whose biology is poorly understood. Proteasome mutations were implicated as underlying mechanism, while an alternative hypothesis based on low activation status of the unfolded protein response was recently suggested (IRE1/XBP1-low model). We generated bortezomib- and carfilzomib-adapted, highly resistant multiple myeloma cell clones (AMO-BTZ, AMO-CFZ), which we analyzed in a combined quantitative and functional proteomic approach. We demonstrate that proteasome inhibitor-adapted myeloma cells tolerate subtotal proteasome inhibition, irrespective of a proteasome mutation, and uniformly show an 'IRE1/XBP1-low' signature. Adaptation of myeloma cells to proteasome inhibitors involved quantitative changes in >600 protein species with similar patterns in AMO-BTZ and AMO-CFZ cells: proteins involved in metabolic regulation, redox homeostasis, and protein folding and destruction were upregulated, while apoptosis and transcription/translation were downregulated. The quantitatively most upregulated protein in AMO-CFZ cells was the multidrug resistance protein (MDR1) protein ABCB1, and carfilzomib resistance could be overcome by MDR1 inhibition. We propose a model where proteasome inhibitor-adapted myeloma cells tolerate subtotal proteasome inhibition owing to metabolic adaptations that favor the generation of reducing equivalents, such as NADPH, which is supported by oxidative glycolysis. Proteasome inhibitor resistance may thus be targeted by manipulating the energy and redox metabolism. PMID:27118406

  10. Versatile reporter systems show that transactivation by human T-cell leukemia virus type 1 Tax occurs independently of chromatin remodeling factor BRG1.

    PubMed

    Zhang, Ling; Liu, Meihong; Merling, Randall; Giam, Chou-Zen

    2006-08-01

    Potent activation of human T-cell leukemia virus type 1 (HTLV-1) gene expression is mediated by the virus-encoded transactivator protein Tax and three imperfect 21-bp repeats in the viral long terminal repeats. Each 21-bp repeat contains a cAMP-responsive-element core flanked by 5' G-rich and 3' C-rich sequences. Tax alone does not bind DNA. Rather, it interacts with basic domain-leucine zipper transcription factors CREB and ATF-1 to form ternary complexes with the 21-bp repeats. In the context of the ternary complexes, Tax contacts the G/C-rich sequences and recruits transcriptional coactivators CREB-binding protein (CBP)/p300 to effect potent transcriptional activation. Using an easily transduced and chromosomally integrated reporter system derived from a self-inactivating lentivirus vector, we showed in a BRG1- and BRM1-deficient adrenal carcinoma cell line, SW-13, that Tax- and 21-bp repeat-mediated transactivation does not require BRG1 or BRM1 and is not enhanced by BRG1. With a similar reporter system, we further demonstrated that Tax- and tumor necrosis factor alpha-induced NF-kappaB activation occurs readily in SW-13 cells in the absence of BRG1 and BRM1. These results suggest that the assembly of stable multiprotein complexes containing Tax, CREB/ATF-1, and CBP/p300 on the 21-bp repeats is the principal mechanism employed by Tax to preclude nucleosome formation at the HTLV-1 enhancer/promoter. This most likely bypasses the need for BRG1-containing chromatin-remodeling complexes. Likewise, recruitment of CBP/p300 by NF-kappaB may be sufficient to disrupt histone-DNA interaction for the initiation of transcription.

  11. Successful surgical treatment of impending rupture of thoracoabdominal aortic aneurysm in an elderly patient with severe pulmonary emphysema.

    PubMed

    Uezu, T; Koja, K; Kuniyoshi, Y; Akasaki, M; Miyagi, K; Shimoji, M

    1999-08-01

    In a case of successful surgery for impending thoracoabdominal aortic aneurysmic rupture, an 83-year-old man with severe pulmonary emphysema was transferred to our hospital diagnosed with impending aneurysmic rupture. The aneurysm had been pointed out 2.5 years ago but surgical repair was not undertaken due to the patient's severe pulmonary emphysema. After admission, computed tomography showed an enlarging saccular thoracoabdominal aortic aneurysm. Emergency surgery was conducted because of severe pain below the left costal margin. We resected the wall of the saccular aortic aneurysm and reconstructed the aorta with an on-lay patch under femoro-femoral bypass and selective visceral organ perfusion. Tracheostomy provided respiratory care on the day following surgery. The patient was weaned from respiratory support 6 days after surgery. Postoperative aortography showed that the reconstructed thoracoabdominal aorta functioned satisfactorily. The patient remains in good health 18 months after surgery.

  12. Cutis laxa with pulmonary emphysema, conjunctivochalasis, nasolacrimal duct obstruction, abnormal hair, and a novel FBLN5 mutation.

    PubMed

    Kantaputra, Piranit Nik; Kaewgahya, Massupa; Wiwatwongwana, Atchareeya; Wiwatwongwana, Damrong; Sittiwangkul, Rekwan; Iamaroon, Anak; Dejkhamron, Prapai

    2014-09-01

    We report on a 4-year-old girl with autosomal recessive cutis laxa, type IA, or pulmonary emphysema type (ARCL1A; OMIM #219100), with loose and wrinkled skin, mitral and tricuspid valve prolapse, conjunctivochalasis, obstructed nasolacrimal ducts, hypoplastic maxilla, and early childhood-onset pulmonary emphysema. Mutation analysis of FBLN5 showed a homozygous c.432C>G missense mutation, and heterozygosity in the parents. This is predicted to cause amino acid substitution p.Cys144Trp. Conjunctivochalasis or redundant folds of conjunctiva and obstructed nasolacrimal ducts have not been reported to be associated with FBLN5 mutations. Histopathological study of the conjunctival biopsy showed that most blood vessels had normal elastic fibers. The gingiva appeared normal, but histologically elastic fibers were defective. Scanning electron micrography of scalp hair demonstrated hypoplastic hair follicles. The cuticles appear intact underneath the filamentous meshwork.

  13. Exercise intolerance and systemic manifestations of pulmonary emphysema in a mouse model

    PubMed Central

    Lüthje, Lars; Raupach, Tobias; Michels, Hellmuth; Unsöld, Bernhard; Hasenfuss, Gerd; Kögler, Harald; Andreas, Stefan

    2009-01-01

    Background Systemic effects of chronic obstructive pulmonary disease (COPD) significantly contribute to severity and mortality of the disease. We aimed to develop a COPD/emphysema model exhibiting systemic manifestations of the disease. Methods Female NMRI mice were treated 5 times intratracheally with porcine pancreatic elastase (emphysema) or phosphate-buffered saline (control). Emphysema severity was quantified histologically by mean linear intercept, exercise tolerance by treadmill running distance, diaphragm dysfunction using isolated muscle strips, pulmonary hypertension by measuring right ventricular pressure, and neurohumoral activation by determining urinary norepinephrine concentration. Results Mean linear intercept was higher in emphysema (260.7 ± 26.8 μm) than in control lungs (24.7 ± 1.7 μm). Emphysema mice lost body weight, controls gained weight. Running distance was shorter in emphysema than in controls. Diaphragm muscle length was shorter in controls compared to emphysema. Fatigue tests of muscle strips revealed impaired relaxation in emphysema diaphragms. Maximum right ventricular pressure and norepinephrine were elevated in emphysema compared to controls. Linear correlations were observed between running distance changes and intercept, right ventricular weight, norepinephrine, and diaphragm length. Conclusion The elastase mouse model exhibited severe emphysema with consecutive exercise limitation, and neurohumoral activation. The model may deepen our understanding of systemic aspects of COPD. PMID:19175913

  14. The impact of emphysema on dosimetric parameters for stereotactic body radiotherapy of the lung

    PubMed Central

    Ochiai, Satoru; Nomoto, Yoshihito; Yamashita, Yasufumi; Inoue, Tomoki; Murashima, Shuuichi; Hasegawa, Daisuke; Kurita, Yoshie; Watanabe, Yui; Toyomasu, Yutaka; Kawamura, Tomoko; Takada, Akinori; Noriko; Kobayashi, Shigeki; Sakuma, Hajime

    2016-01-01

    The purpose of this study was to evaluate the impact of emphysematous changes in lung on dosimetric parameters in stereotactic body radiation therapy (SBRT) for lung tumor. A total of 72 treatment plans were reviewed, and dosimetric factors [including homogeneity index (HI) and conformity index (CI)] were evaluated. Emphysematous changes in lung were observed in 43 patients (60%). Patients were divided into three groups according to the severity of emphysema: no emphysema (n = 29), mild emphysema (n = 22) and moderate to severe emphysema groups (n = 21). The HI (P < 0.001) and the CI (P = 0.029) were significantly different in accordance with the severity of emphysema in one-way analysis of variance (ANOVA). The HI value was significantly higher in the moderate to severe emphysema group compared with in the no emphysema (Tukey, P < 0.001) and mild emphysema groups (P = 0.002). The CI value was significantly higher in the moderate to severe emphysema group compared with in the no emphysema group (P = 0.044). In multiple linear regression analysis, the severity of emphysema (P < 0.001) and the mean material density of the lung within the PTV (P < 0.001) were significant factors for HI, and the mean density of the lung within the PTV (P = 0.005) was the only significant factor for CI. The mean density of the lung within the PTV was significantly different in accordance with the severity of emphysema (one-way ANOVA, P = 0.008) and the severity of emphysema (P < 0.001) was one of the significant factors for the density of the lung within the PTV in multiple linear regression analysis. Our results suggest that emphysematous changes in the lung significantly impact on several dosimetric parameters in SBRT, and they should be carefully evaluated before treatment planning. PMID:27380802

  15. High-density lipoproteins potentiate α1-antitrypsin therapy in elastase-induced pulmonary emphysema.

    PubMed

    Moreno, Juan-Antonio; Ortega-Gomez, Almudena; Rubio-Navarro, Alfonso; Louedec, Liliane; Ho-Tin-Noé, Benoit; Caligiuri, Giuseppina; Nicoletti, Antonino; Levoye, Angelique; Plantier, Laurent; Meilhac, Olivier

    2014-10-01

    Several studies report that high-density lipoproteins (HDLs) can carry α1-antitrypsin (AAT; an elastase inhibitor). We aimed to determine whether injection of exogenous HDL, enriched or not in AAT, may have protective effects against pulmonary emphysema. After tracheal instillation of saline or elastase, mice were randomly treated intravenously with saline, human plasma HDL (75 mg apolipoprotein A1/kg), HDL-AAT (75 mg apolipoprotein A1-3.75 mg AAT/kg), or AAT alone (3.75 mg/kg) at 2, 24, 48, and 72 hours. We have shown that HDL-AAT reached the lung and prevented the development of pulmonary emphysema by 59.3% at 3 weeks (alveoli mean chord length, 22.9 ± 2.8 μm versus 30.7 ± 4.5 μm; P < 0.001), whereas injection of HDL or AAT alone only showed a moderate, nonsignificant protective effect (28.2 ± 4.2 μm versus 30.7 ± 5 μm [P = 0.23] and 27.3 ± 5.66 μm versus 30.71 ± 4.96 μm [P = 0.18], respectively). Indeed, protection by HDL-AAT was significantly higher than that observed with HDL or AAT (P = 0.006 and P = 0.048, respectively). This protective effect was associated (at 6, 24, and 72 h) with: (1) a reduction in neutrophil and macrophage number in the bronchoalveolar lavage fluid; (2) decreased concentrations of IL-6, monocyte chemoattractant protein-1, and TNF-α in both bronchoalveolar lavage fluid and plasma; (3) a reduction in matrix metalloproteinase-2 and matrix metalloproteinase-9 activities; and (4) a reduction in the degradation of fibronectin, a marker of tissue damage. In addition, HDL-AAT reduced acute cigarette smoke-induced inflammatory response. Intravenous HDL-AAT treatment afforded a better protection against elastase-induced pulmonary emphysema than AAT alone, and may represent a significant development for the management of emphysema associated with AAT deficiency.

  16. Bax-induced apoptosis shortens the life span of DNA repair defect Ku70-knockout mice by inducing emphysema.

    PubMed

    Matsuyama, Shigemi; Palmer, James; Bates, Adam; Poventud-Fuentes, Izmarie; Wong, Kelvin; Ngo, Justine; Matsuyama, Mieko

    2016-06-01

    Cells with DNA damage undergo apoptosis or cellular senescence if the damage cannot be repaired. Recent studies highlight that cellular senescence plays a major role in aging. However, age-associated diseases, including emphysema and neurodegenerative disorders, are caused by apoptosis of lung alveolar epithelial cells and neurons, respectively. Therefore, enhanced apoptosis also promotes aging and shortens the life span depending on the cell type. Recently, we reported that ku70(-) (/) (-)bax(-) (/) (-) and ku70(-) (/) (-)bax(+/) (-) mice showed significantly extended life span in comparison with ku70(-) (/) (-)bax(+/+) mice. Ku70 is essential for non-homologous end joining pathway for DNA double strand break repair, and Bax plays an important role in apoptosis. Our study suggests that Bax-induced apoptosis has a significant impact on shortening the life span of ku70(-) (/) (-) mice, which are defective in one of DNA repair pathways. The lung alveolar space gradually enlarges during aging, both in mouse and human, and this age-dependent change results in the decrease of respiration capacity during aging that can lead to emphysema in more severe cases. We found that emphysema occurred in ku70(-) (/) (-) mice at the age of three-months old, and that Bax deficiency was able to suppress it. These results suggest that Bax-mediated apoptosis induces emphysema in ku70(-) (/) (-) mice. We also found that the number of cells, including bronchiolar epithelial cells and type 2 alveolar epithelial cells, shows a higher DNA double strand break damage response in ku70 KO mouse lung than in wild type. Recent studies suggest that non-homologous end joining activity decreases with increased age in mouse and rat model. Together, we hypothesize that the decline of Ku70-dependent DNA repair activity in lung alveolar epithelial cells is one of the causes of age-dependent decline of lung function resulting from excess Bax-mediated apoptosis of lung alveolar epithelial cells (and their

  17. Alendronate inhalation ameliorates elastase-induced pulmonary emphysema in mice by induction of apoptosis of alveolar macrophages.

    PubMed

    Ueno, Manabu; Maeno, Toshitaka; Nishimura, Satoshi; Ogata, Fusa; Masubuchi, Hiroaki; Hara, Kenichiro; Yamaguchi, Kouichi; Aoki, Fumiaki; Suga, Tatsuo; Nagai, Ryozo; Kurabayashi, Masahiko

    2015-03-10

    Alveolar macrophages play a crucial role in the pathogenesis of emphysema, for which there is currently no effective treatment. Bisphosphonates are widely used to treat osteoclast-mediated bone diseases. Here we show that delivery of the nitrogen-containing bisphosphonate alendronate via aerosol inhalation ameliorates elastase-induced emphysema in mice. Inhaled, but not orally ingested, alendronate inhibits airspace enlargement after elastase instillation, and induces apoptosis of macrophages in bronchoalveolar fluid via caspase-3- and mevalonate-dependent pathways. Cytometric analysis indicates that the F4/80(+)CD11b(high)CD11c(mild) population characterizing inflammatory macrophages, and the F4/80(+)CD11b(mild)CD11c(high) population defining resident alveolar macrophages take up substantial amounts of the bisphosphonate imaging agent OsteoSense680 after aerosol inhalation. We further show that alendronate inhibits macrophage migratory and phagocytotic activities and blunts the inflammatory response of alveolar macrophages by inhibiting nuclear factor-κB signalling. Given that the alendronate inhalation effectively induces apoptosis in both recruited and resident alveolar macrophages, we suggest this strategy may have therapeutic potential for the treatment of emphysema.

  18. Ventilation asymmetry after transplantation for emphysema: role of chest wall and mediastinum.

    PubMed

    De Groote, Anne; Van Muylem, Alain; Scillia, Pietro; Cheron, Guy; Verleden, Geert; Paiva, Manuel; Estenne, Marc

    2004-12-01

    After single-lung transplantation for emphysema, the hyperinflated native lung and the graft have different extents and rates of inflation and emptying. This requires that breathing produces asymmetrical expansion of the chest wall, displacement of the mediastinum, or both. In a first study in four seated transplant recipients, we measured the volumes of the two hemithoraces with optoelectronic plethysmography. Functional residual capacity and total lung capacity were identical on the native and transplanted sides, and changes in chest wall volume during CO(2)-induced hyperpnea and FVC maneuvers were similar on both sides. Studies with computerized tomography in three of these patients and in four additional patients in supine posture indicated that the mediastinum was shifted toward the graft at functional residual capacity and total lung capacity. The mediastinum moved toward the native lung during tidal and full inspiration and toward the graft during tidal and forced expiration; additional studies with fluoroscopy showed qualitatively similar changes in upright posture. In summary, the two hemithoraces assume identical static volumes and show similar volume changes during CO(2)-induced hyperpnea and FVC maneuvers in patients with single-lung transplantation for emphysema; displacement of the mediastinum accommodates part, if not all, of the unequal lung volumes and asymmetrical ventilation.

  19. Orbital emphysema as a complication of bungee jumping.

    PubMed

    Krott, R; Mietz, H; Krieglstein, G K

    1997-07-01

    Bungee jumping is a dangerous sport with increasing popularity in the western world. We report the case of a 28-yr-old man who sustained an orbital emphysema as a result of bungee jumping. He jumped head first from a 160-ft high bridge over a river. At the end of the jump he dived into the water with his head in a reclined position. The sudden dive into the water caused an increase of the air pressure in the nose and paranasal sinuses, which led to an emphysema of the right orbit resulting from a skull fracture not detectable by x-ray. The patient was treated with oral antibiotics. Five days later, he had no clinical complaints and the ophthalmologic examination was normal. This variation of bungee jumping may bear severe risk factors for health in addition to those known from the classic jumps.

  20. Massive surgical emphysema secondary to iatrogenic tracheal laceration

    PubMed Central

    Chamberlain, Sarah; Rahman, Habib; Frunza, Gabriela; Wickham, Alexander

    2015-01-01

    A 78-year-old woman was admitted for a revision total hip replacement following a failed dynamic hip screw placed emergently 4 months earlier. Anaesthetic management consisted of general anaesthesia with endotracheal intubation and femoral nerve block. The patient's perioperative course was unremarkable except for a promptly recognised and corrected oesophageal intubation and a short period of breathing against a closed adjustable pressure limiting valve. In recovery, following a period of hypotension resistant to fluid therapy, she suddenly desaturated, developed severe facial and upper thoracic subcutaneous emphysema and type 2 respiratory failure. She was diagnosed with bilateral pneumothoraces, pneumomediastinum, pneumopericardium and surgical emphysema. This was treated emergently with supplemental oxygen and bilateral chest drains. A CT scan demonstrated a tracheal laceration, which was managed conservatively in the critical care unit. The patient had a tracheostomy on day 5 to treat an on-going air leak and later made a full recovery. PMID:25750221

  1. Subcutaneous emphysema of periorbital region after stainless steel crown preparation in a young child

    PubMed Central

    Khandelwal, Vishal; Agrawal, Piyush; Agrawal, Deepak; Nayak, Prathibha Anand

    2013-01-01

    Subcutaneous emphysema occurs when air is forced beneath the tissue, leading to swelling, crepitus on palpation and has the potential to spread along the fascial planes. This report describes the youngest case of subcutaneous emphysema related to dental treatment that has been documented to date. In addition to the patient's age, the case is of interest because periorbital subcutaneous emphysema is a rarest complication of stainless steel crown procedure. PMID:23704466

  2. Pneumothorax, Pneumomediastinum, Pneumoperitoneum and Surgical Emphysema in Mechanically Ventilated Patients

    PubMed Central

    Kamha, A; Alzeer, H; Elithy, M

    2008-01-01

    A 29 year old male patient of Indian ancestry was admitted to an outside hospital with rapid deterioration of his level of consciousness. The patient required mechanical ventilation and transfer to MICU at Hamad Medical Corporation. The patient remained hypoxic. Chest X-ray, CT of chest, abdomen, pelvis and proximal areas of both lower limbs were performed. Pneumomediastinum, pneumoperitoneum, and extensive surgical emphysema were the diagnoses. PMID:21516154

  3. Cervicothoracic Subcutaneous Emphysema and Pneumomediastinum After Third Molar Extraction.

    PubMed

    Picard, Maxime; Pham Dang, Nathalie; Mondie, Jean Michel; Barthelemy, Isabelle

    2015-12-01

    Third molar extraction is one of the most common interventions in dental and maxillofacial surgery. Complications are frequent and well documented, with swelling, pain, bleeding, infection, and lingual or alveolar nerve injury being the most common. This report describes a case of subcutaneous extensive emphysema and pneumomediastinum that occurred 4 days after extraction of an impacted right mandibular third molar. The management and etiology of this case and those reported in the literature are discussed.

  4. Cervicofacial and mediastinal emphysema due to a dental procedure

    PubMed Central

    Ramnarine, Mityanand; Dubin, Zvi

    2017-01-01

    Dental procedures, though commonplace and usually very safe, are not without complications. We report on a case of extensive cervicofacial and mediastinal emphysema after a routine dental procedure, initially masquerading as an allergic reaction in an otherwise young and healthy woman. A review of the relevant literature on this clinical entity is presented, which serves to underscore the need for awareness by the treating clinician of this condition and its potential sequela. PMID:28243011

  5. Pneumoperitoneum, Retropneumoperitoneum, Pneumomediastinum, and Diffuse Subcutaneous Emphysema following Diagnostic Colonoscopy

    PubMed Central

    Falidas, Evangelos; Anyfantakis, Georgios; Vlachos, Konstantinos; Goudeli, Christina; Stavros, Boutzouvis; Villias, Constantinos

    2012-01-01

    Colonoscopy is a widely used diagnostic and curative procedure. Extraperitoneal perforation with pneumoretroperitoneum, pneumomediastinum and subcutaneous emphysema combined with intraperitoneal perforation is an extremely rare complication. We report a case of a 78-year-old woman presented to the emergency department with abdominal pain and diffuse abdominal, chest, neck, and facial swelling appeared after a diagnostic colonoscopy. Diagnostic and therapeutic modalities are discussed. PMID:23024878

  6. Inducible targeting of IL-13 to the adult lung causes matrix metalloproteinase- and cathepsin-dependent emphysema.

    PubMed

    Zheng, T; Zhu, Z; Wang, Z; Homer, R J; Ma, B; Riese, R J; Chapman, H A; Shapiro, S D; Elias, J A

    2000-11-01

    Cigarette smoke exposure is the major cause of chronic obstructive pulmonary disease (COPD). However, only a minority of smokers develop significant COPD, and patients with asthma or asthma-like airway hyperresponsiveness or eosinophilia experience accelerated loss of lung function after cigarette smoke exposure. Pulmonary inflammation is a characteristic feature of lungs from patients with COPD. Surprisingly, the mediators of this inflammation and their contributions to the pathogenesis and varied natural history of COPD are not well defined. Here we show that IL-13, a critical cytokine in asthma, causes emphysema with enhanced lung volumes and compliance, mucus metaplasia, and inflammation, when inducibly overexpressed in the adult murine lung. MMP-2, -9, -12, -13, and -14 and cathepsins B, S, L, H, and K were induced by IL-13 in this setting. In addition, treatment with MMP or cysteine proteinase antagonists significantly decreased the emphysema and inflammation, but not the mucus in these animals. These studies demonstrate that IL-13 is a potent stimulator of MMP and cathepsin-based proteolytic pathways in the lung. They also demonstrate that IL-13 causes emphysema via a MMP- and cathepsin-dependent mechanism(s) and highlight common mechanisms that may underlie COPD and asthma.

  7. Improvement of metabolic disorders by an EP(2) receptor agonist via restoration of the subcutaneous adipose tissue in pulmonary emphysema.

    PubMed

    Tsuji, Takao; Yamaguchi, Kazuhiro; Kikuchi, Ryota; Nakamura, Hiroyuki; Misaka, Ryoichi; Nagai, Atsushi; Aoshiba, Kazutetsu

    2017-03-02

    Chronic obstructive pulmonary disease (COPD) is often associated with co-morbidities. Metabolic disorders like hyperlipidemia and diabetes occur also in underweight COPD patients, although the mechanism is uncertain. Subcutaneous adipose tissue (SAT) plays an important role in energy homeostasis, since restricted capacity to increase fat cell number with increase in fat cell size occurring instead, is associated with lipotoxicity and metabolic disorders. The aim of this study is to show the protective role of SAT for the metabolic disorders in pulmonary emphysema of a murine model. We found ectopic fat accumulation and impaired glucose homeostasis with wasting of SAT in a murine model of elastase-induced pulmonary emphysema (EIE mice) reared on a high-fat diet. ONO-AE1-259, a selective E-prostanoid (EP) 2 receptor agonist, improved angiogenesis and subsequently adipogenesis, and finally improved ectopic fat accumulation and glucose homeostasis with restoration of the capacity for storage of surplus energy in SAT. These results suggest that metabolic disorders like hyperlipidemia and diabetes occured in underweight COPD is partially due to the less capacity for storage of surplus energy in SAT, though the precise mechanism is uncertained. Our data pave the way for the development of therapeutic interventions for metabolic disorders in emphysema patients, e.g., use of pro-angiogenic agents targeting the capacity for storage of surplus energy in the subcutaneous adipose tissue.

  8. [Therapeutic application of collateral ventilation in diffuse pulmonary emphysema: study protocol presentation].

    PubMed

    Saad, Roberto; Dorgan Neto, Vicente; Botter, Marcio; Stirbulov, Roberto; Rivaben, Jorge; Gonçalves, Roberto

    2008-06-01

    We present a protocol to test a new surgical procedure for the treatment of patients with diffuse lung emphysema who, after having received the golden standard treatment (pulmonary rehabilitation), continue to present respiratory failure with disabling dyspnea. Ten patients with severe lung hyperinflation will be evaluated. The method proposed is designed to create alternative expiratory passages for air trapped in the emphysematous lung by draining the lung parenchyma, thereby establishing communication between the alveoli and the external environment. The ten patients selected will be required to meet the inclusion criteria and to give written informed consent. Those ten patients will be included in the study pending the approval of the Ethics in Research Committee of the São Paulo Santa Casa School of Medicine, São Paulo, Brazil. The protocol we will employ in order to evaluate the proposed procedure is feasible and will show whether debilitated patients suffering from diffuse pulmonary emphysema can benefit from this procedure, which could represent an alternative to lung transplant or lung volume reduction surgery, the only options currently available.

  9. Complex integration of matrix, oxidative stress, and apoptosis in genetic emphysema.

    PubMed

    Podowski, Megan; Calvi, Carla L; Cheadle, Christopher; Tuder, Rubin M; Biswals, Shyam; Neptune, Enid R

    2009-07-01

    Alveolar enlargement, which is characteristic of bronchopulmonary dysplasia, congenital matrix disorders, and cigarette smoke-induced emphysema, is thought to result from enhanced inflammation and ensuing excessive matrix proteolysis. Although there is recent evidence that cell death and oxidative stress punctuate these diseases, the mechanistic link between abnormal lung extracellular matrix and alveolar enlargement is lacking. We hypothesized that the tight-skin (TSK) mouse, which harbors a spontaneous internal duplication in the microfibrillar glycoprotein fibrillin-1, might show whether matrix alterations are sufficient to promote oxidative stress and cell death, injury cascades central to the development of clinical emphysema. We observed no evidence of increased metalloprotease activation by histochemical and zymographic methods. We did find initial oxidative stress followed by increased apoptosis in the postnatal TSK lung. Both blunted antioxidant production and reduced extracellular superoxide dismutase activity were evident in the neonatal lung. High-dose antioxidant treatment with N-acetylcysteine improved airspace caliber and attenuated oxidative stress and apoptosis in neonatal and adult TSK mice. These data establish that an abnormal extracellular matrix without overt elastolysis is sufficient to confer susceptibility to postnatal normoxia, reminiscent of bronchopulmonary dysplasia. The resultant oxidative stress and apoptosis culminate in profound airspace enlargement. The TSK lung exemplifies the critical interplay between extracellular matrix, oxidative stress, and cell-death cascades that may contribute to genetic and acquired airspace enlargement.

  10. Complex Integration of Matrix, Oxidative Stress, and Apoptosis in Genetic Emphysema

    PubMed Central

    Podowski, Megan; Calvi, Carla L.; Cheadle, Christopher; Tuder, Rubin M.; Biswals, Shyam; Neptune, Enid R.

    2009-01-01

    Alveolar enlargement, which is characteristic of bronchopulmonary dysplasia, congenital matrix disorders, and cigarette smoke-induced emphysema, is thought to result from enhanced inflammation and ensuing excessive matrix proteolysis. Although there is recent evidence that cell death and oxidative stress punctuate these diseases, the mechanistic link between abnormal lung extracellular matrix and alveolar enlargement is lacking. We hypothesized that the tight-skin (TSK) mouse, which harbors a spontaneous internal duplication in the microfibrillar glycoprotein fibrillin-1, might show whether matrix alterations are sufficient to promote oxidative stress and cell death, injury cascades central to the development of clinical emphysema. We observed no evidence of increased metalloprotease activation by histochemical and zymographic methods. We did find initial oxidative stress followed by increased apoptosis in the postnatal TSK lung. Both blunted antioxidant production and reduced extracellular superoxide dismutase activity were evident in the neonatal lung. High-dose antioxidant treatment with N-acetylcysteine improved airspace caliber and attenuated oxidative stress and apoptosis in neonatal and adult TSK mice. These data establish that an abnormal extracellular matrix without overt elastolysis is sufficient to confer susceptibility to postnatal normoxia, reminiscent of bronchopulmonary dysplasia. The resultant oxidative stress and apoptosis culminate in profound airspace enlargement. The TSK lung exemplifies the critical interplay between extracellular matrix, oxidative stress, and cell-death cascades that may contribute to genetic and acquired airspace enlargement. PMID:19541933

  11. Tetomilast attenuates elastase-induced pulmonary emphysema through inhibition of oxidative stress in rabbits.

    PubMed

    Baila, Bulin; Ohno, Yasushi; Nagamoto, Hisashi; Kotosai, Kounori; Yabuuchi, Youichi; Funaguchi, Norihiko; Ito, Fumitaka; Endo, Junki; Mori, Hidenori; Takemura, Genzou; Fujiwara, Takako; Fujiwara, Hisayoshi; Minatoguchi, Shinya

    2012-01-01

    Tetomilast was originally identified as a potent inhibitor of superoxide production in human neutrophils, and is of interest because it may relieve oxidative stress related to chronic obstructive pulmonary disease (COPD). Our objective was to determine whether tetomilast effectively protects against the development of porcine pancreatic elastase (PPE)-induced emphysema in rabbits. Rabbits were divided into three groups (sham n=19, PPE n=19, PPE/Tetomilast n=18). The rabbits were once daily orally administered vehicle solution or tetomilast 5 d/week for 4 weeks before the PPE instillation. We compared pulmonary function, inflammatory cell infiltration, oxidative stress, and the incidences of apoptosis among the three groups. Tetomilast suppressed PPE-induced increases in the incidence of apoptosis and the production of 8-hydroxy-deoxyguanosine (8-OHdG) in lung tissues. PPE-instilled rabbits treated with tetomilast showed significantly less mean linear intercept and significantly better pulmonary function than rabbits administered PPE alone. Tetomilast may inhibit the development of emphysema by attenuating pulmonary inflammation and apoptosis caused by PPE-induced oxidative stress.

  12. Correlation analysis between pulmonary function test parameters and CT image parameters of emphysema

    NASA Astrophysics Data System (ADS)

    Liu, Cheng-Pei; Li, Chia-Chen; Yu, Chong-Jen; Chang, Yeun-Chung; Wang, Cheng-Yi; Yu, Wen-Kuang; Chen, Chung-Ming

    2016-03-01

    Conventionally, diagnosis and severity classification of Chronic Obstructive Pulmonary Disease (COPD) are usually based on the pulmonary function tests (PFTs). To reduce the need of PFT for the diagnosis of COPD, this paper proposes a correlation model between the lung CT images and the crucial index of the PFT, FEV1/FVC, a severity index of COPD distinguishing a normal subject from a COPD patient. A new lung CT image index, Mirage Index (MI), has been developed to describe the severity of COPD primarily with emphysema disease. Unlike conventional Pixel Index (PI) which takes into account all voxels with HU values less than -950, the proposed approach modeled these voxels by different sizes of bullae balls and defines MI as a weighted sum of the percentages of the bullae balls of different size classes and locations in a lung. For evaluation of the efficacy of the proposed model, 45 emphysema subjects of different severity were involved in this study. In comparison with the conventional index, PI, the correlation between MI and FEV1/FVC is -0.75+/-0.08, which substantially outperforms the correlation between PI and FEV1/FVC, i.e., -0.63+/-0.11. Moreover, we have shown that the emphysematous lesion areas constituted by small bullae balls are basically irrelevant to FEV1/FVC. The statistical analysis and special case study results show that MI can offer better assessment in different analyses.

  13. Combined pulmonary fibrosis and emphysema: a distinct underrecognised entity.

    PubMed

    Cottin, V; Nunes, H; Brillet, P-Y; Delaval, P; Devouassoux, G; Tillie-Leblond, I; Israel-Biet, D; Court-Fortune, I; Valeyre, D; Cordier, J-F

    2005-10-01

    The syndrome resulting from combined pulmonary fibrosis and emphysema has not been comprehensively described. The current authors conducted a retrospective study of 61 patients with both emphysema of the upper zones and diffuse parenchymal lung disease with fibrosis of the lower zones of the lungs on chest computed tomography. Patients (all smokers) included 60 males and one female, with a mean age of 65 yrs. Dyspnoea on exertion was present in all patients. Basal crackles were found in 87% and finger clubbing in 43%. Pulmonary function tests were as follows (mean+/-sd): total lung capacity 88%+/-17, forced vital capacity (FVC) 88%+/-18, forced expiratory volume in one second (FEV1) 80%+/-21 (% predicted), FEV1/FVC 69%+/-13, carbon monoxide diffusion capacity of the lung 37%+/-16 (% predicted), carbon monoxide transfer coefficient 46%+/-19. Pulmonary hypertension was present in 47% of patients at diagnosis, and 55% during follow-up. Patients were followed for a mean of 2.1+/-2.8 yrs from diagnosis. Survival was 87.5% at 2 yrs and 54.6% at 5 yrs, with a median of 6.1 yrs. The presence of pulmonary hypertension at diagnosis was a critical determinant of prognosis. The authors hereby individualise the computer tomography-defined syndrome of combined pulmonary fibrosis and emphysema characterised by subnormal spirometry, severe impairment of gas exchange, high prevalence of pulmonary hypertension, and poor survival.

  14. Do endobronchial valves improve outcomes in patients with emphysema?

    PubMed

    Barua, Anupama; Vaughan, Paul; Wotton, Robin; Naidu, Babu

    2012-12-01

    A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether endobronchial valves improve outcomes in patients with severe emphysema. Eighty-seven papers were found using the reported search, of which seven represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Endobronchial Valve for Emphysema Palliation Trial demonstrated that endobronchial valve increased forced expiratory volume in one second by 4.3% (95% confidence interval 1.4-7.2) and decreased by 2.5% in the control group (95% confidence interval -5.4 to 0.4) at a 6-month interval. This benefit is more marked in patients who do not have collateral ventilation into the area of lung being isolated as mapped by bronchoscopic physiological mapping (Chartis) or by computed tomography imaging documenting intact fissures. This evidence is reflected in the Endobronchial Valve for Emphysema Palliation Trial. Patients treated with endobronchial valve with high heterogeneity and complete fissures had greater improvement in forced expiratory volume in one second at 6- and 12-month intervals. We conclude that endobronchial valve placement improves lung function, exercise capacity and quality of life in selected patients with emphysematous diseases.

  15. Health-related quality of life in emphysema.

    PubMed

    Kaplan, Robert M; Ries, Andrew L

    2008-05-01

    Patients with emphysema may experience reduced health-related quality of life (HRQOL). HRQOL measures have evolved from two different measurement traditions: psychometric theory and decision theory. Psychometric methods typically create a profile of outcomes, whereas decision theory methods offer a summary score on a continuum ranging from 0.0 (for death or worst possible health) to 1.0 (for best possible health). Decision theory methods are better suited for cost-effectiveness studies. Generic HRQOL measures can be applied to any disease population, whereas disease-targeted measures are tailored to a specific clinical condition. Disease-targeted measures are typically more sensitive to clinical change, but cannot offer a comparison basis for different clinical conditions. This article reviews the measurement of HRQOL in patients with emphysema. The National Emphysema Treatment Trial (NETT) offers an example of the application of both generic and disease-targeted, as well as profile and decision theory, methods. The NETT illustrates how HRQOL measures can be used to assess outcomes and estimate cost-effectiveness in a major clinical trial.

  16. Estimating pulmonary artery pressures by echocardiography in patients with emphysema.

    PubMed

    Fisher, M R; Criner, G J; Fishman, A P; Hassoun, P M; Minai, O A; Scharf, S M; Fessler, H E

    2007-11-01

    In patients with emphysema being evaluated for lung volume reduction surgery, Doppler echocardiography has been used to screen for pulmonary hypertension as an indicator of increased peri-operative risk. To determine the accuracy of this test, the present authors compared the results of right heart catheterisations and Doppler echocardiograms in 163 patients participating in the cardiovascular substudy of the National Emphysema Treatment Trial. Substudy patients had both catheterisation and Doppler echocardiography performed before and after randomisation. In 74 paired catheterisations and echocardiograms carried out on 63 patients, the mean values of invasively measured pulmonary artery systolic pressures and the estimated right ventricular systolic pressures were similar. However, using the World Health Organization's definitions of pulmonary hypertension, echocardiography had a sensitivity of 60%, specificity of 74%, positive predictive value of 68% and a negative predictive value of 67% compared with the invasive measurement. Bland-Altman analysis revealed a bias of 0.37 kPa with 95% limits of agreement from -2.5-3.2 kPa. In patients with severe emphysema, echocardiographic estimates of pulmonary artery pressures correlate very weakly with right heart catheterisations, and the test characteristics (e.g. sensitivity, specificity, etc.) of echocardiographic assessments are poor.

  17. Emergent bronchofiberoptic bronchial occlusion for intractable pneumothorax with severe emphysema.

    PubMed

    Okada, S; Kano, K; Yamauchi, H; Satoh, S

    1998-11-01

    Emergent bronchofiberoptic bronchial occlusion using fibrin glue and woven polyglycolic acid mesh for persistent pneumothorax with severe emphysema is described. A 74-year-old man who had severe pulmonary dysfunction accompanying chronic emphysema was admitted with a complaint of sudden severe dyspnea. The chest X-ray on admission revealed collapse of the right lung. The patient was placed on a mechanical ventilator because of acute respiratory failure. In spite of continuous suction through a chest drainage tube, air leakage persisted. On the seventh hospital day, subcutaneous emphysema was apparent in the face and scrotum in addition to the chest. First, a double-lumen catheter was inserted into the right B5 bronchus, and fibrin glue was infused into the drainage bronchus via the double-lumen catheter. However, the procedure failed. Next, a combination of fibrin glue and woven polyglycolic acid mesh which had been cut into small pieces was introduced and pushed into the B5 bronchus using forceps. The air leakage stopped immediately after the administration. This procedure is simple and a minimally invasive method for the treatment of intractable pneumothorax in a compromised patient on a mechanical ventilator.

  18. Pneumomediastinum and subcutaneous emphysema after dental extraction detected incidentally by regular medical checkup: a case report.

    PubMed

    Arai, Ikuko; Aoki, Takayuki; Yamazaki, Hiroshi; Ota, Yoshihide; Kaneko, Akihiro

    2009-04-01

    Most cases of pneumomediastinum are caused by iatrogenic injury during surgery on the cervical region and chest or by tracheostomy. It is also well known that emphysema may occur secondary to dental treatment using an air turbine drill, but there have been few cases of emphysema extending to involve the mediastinum. Presented is a rare case in which subcutaneous emphysema and pneumomediastinum developed asymptomatically, probably due to extraction of a mandibular third molar, and were found incidentally on the day after the dental procedure. To avoid subcutaneous emphysema and pneumomediastinum associated with dental treatment and surgical intraoral procedures such as tooth extraction, air turbine drills should be used only when it is essential.

  19. Automated quantification of pulmonary emphysema from computed tomography scans: comparison of variation and correlation of common measures in a large cohort

    NASA Astrophysics Data System (ADS)

    Keller, Brad M.; Reeves, Anthony P.; Yankelevitz, David F.; Henschke, Claudia I.

    2010-03-01

    The purpose of this work was to retrospectively investigate the variation of standard indices of pulmonary emphysema from helical computed tomographic (CT) scans as related to inspiration differences over a 1 year interval and determine the strength of the relationship between these measures in a large cohort. 626 patients that had 2 scans taken at an interval of 9 months to 15 months (μ: 381 days, σ: 31 days) were selected for this work. All scans were acquired at a 1.25mm slice thickness using a low dose protocol. For each scan, the emphysema index (EI), fractal dimension (FD), mean lung density (MLD), and 15th percentile of the histogram (HIST) were computed. The absolute and relative changes for each measure were computed and the empirical 95% confidence interval was reported both in non-normalized and normalized scales. Spearman correlation coefficients are computed between the relative change in each measure and relative change in inspiration between each scan-pair, as well as between each pair-wise combination of the four measures. EI varied on a range of -10.5 to 10.5 on a non-normalized scale and -15 to 15 on a normalized scale, with FD and MLD showing slightly larger but comparable spreads, and HIST having a much larger variation. MLD was found to show the strongest correlation to inspiration change (r=0.85, p<0.001), and EI, FD, and HIST to have moderately strong correlation (r = 0.61-0.74, p<0.001). Finally, HIST showed very strong correlation to EI (r = 0.92, p<0.001), while FD showed the least strong relationship to EI (r = 0.82, p<0.001). This work shows that emphysema index and fractal dimension have the least variability overall of the commonly used measures of emphysema and that they offer the most unique quantification of emphysema relative to each other.

  20. Severity of lung fibrosis affects early surgical outcomes of lung cancer among patients with combined pulmonary fibrosis and emphysema.

    PubMed

    Mimae, Takahiro; Suzuki, Kenji; Tsuboi, Masahiro; Ikeda, Norihiko; Takamochi, Kazuya; Aokage, Keiju; Shimada, Yoshihisa; Miyata, Yoshihiro; Okada, Morihito

    2016-07-01

    Combined pulmonary fibrosis and emphysema (CPFE) is defined as upper lobe emphysema and lower lobe fibrosis, which are representative lung disorders that increase the prevalence of lung cancer. This unique disorder may affect the morbidity and mortality during the early period after surgery. The present study aimed to identify which clinicopathological features significantly affect early surgical outcomes after lung resection in nonsmall cell lung cancer (NSCLC) patients and in those with CPFE.We retrospectively assessed 2295 patients with NSCLC and found that 151 (6.6%) had CPFE. All were surgically treated between January 2008 and December 2010 at 4 institutions.The postoperative complication rates for patients with and without CPFE were 39% and 17%, respectively. The 90-day mortality rates were higher among patients with than without CPFE (7.9% vs 1%). Acute exacerbation of interstitial pneumonia was the main cause of death among 12 patients with CPFE who died within 90 days after surgery. Multivariate logistic regression analysis selected CPFE, gender, age, and clinical stage as independent predictive factors for postoperative complications, and CPFE, clinical stage, and sex for 90-day mortality. The severity of lung fibrosis on preoperative CT images was an independent predictive factor for 90-day mortality among patients with CPFE.The key predictive factor for postoperative mortality and complications of lung resection for NSCLC was CPFE. The severity of lung fibrosis was the principal predictor of early outcomes after lung surgery among patients with CPFE and NSCLC.

  1. Systematic review with meta-analysis of the epidemiological evidence relating smoking to COPD, chronic bronchitis and emphysema

    PubMed Central

    2011-01-01

    Background Smoking is a known cause of the outcomes COPD, chronic bronchitis (CB) and emphysema, but no previous systematic review exists. We summarize evidence for various smoking indices. Methods Based on MEDLINE searches and other sources we obtained papers published to 2006 describing epidemiological studies relating incidence or prevalence of these outcomes to smoking. Studies in children or adolescents, or in populations at high respiratory disease risk or with co-existing diseases were excluded. Study-specific data were extracted on design, exposures and outcomes considered, and confounder adjustment. For each outcome RRs/ORs and 95% CIs were extracted for ever, current and ex smoking and various dose response indices, and meta-analyses and meta-regressions conducted to determine how relationships were modified by various study and RR characteristics. Results Of 218 studies identified, 133 provide data for COPD, 101 for CB and 28 for emphysema. RR estimates are markedly heterogeneous. Based on random-effects meta-analyses of most-adjusted RR/ORs, estimates are elevated for ever smoking (COPD 2.89, CI 2.63-3.17, n = 129 RRs; CB 2.69, 2.50-2.90, n = 114; emphysema 4.51, 3.38-6.02, n = 28), current smoking (COPD 3.51, 3.08-3.99; CB 3.41, 3.13-3.72; emphysema 4.87, 2.83-8.41) and ex smoking (COPD 2.35, 2.11-2.63; CB 1.63, 1.50-1.78; emphysema 3.52, 2.51-4.94). For COPD, RRs are higher for males, for studies conducted in North America, for cigarette smoking rather than any product smoking, and where the unexposed base is never smoking any product, and are markedly lower when asthma is included in the COPD definition. Variations by sex, continent, smoking product and unexposed group are in the same direction for CB, but less clearly demonstrated. For all outcomes RRs are higher when based on mortality, and for COPD are markedly lower when based on lung function. For all outcomes, risk increases with amount smoked and pack-years. Limited data show risk decreases

  2. A Novel Antiapoptotic Role for α1-Antitrypsin in the Prevention of Pulmonary Emphysema

    PubMed Central

    Petrache, Irina; Fijalkowska, Iwona; Zhen, Lijie; Medler, Terry R.; Brown, Emile; Cruz, Pedro; Choe, Kang-Hyeon; Taraseviciene-Stewart, Laimute; Scerbavicius, Robertas; Shapiro, Lee; Zhang, Bing; Song, Sihong; Hicklin, Dan; Voelkel, Norbert F.; Flotte, Terence; Tuder, Rubin M.

    2006-01-01

    Rationale: There is growing evidence that alveolar cell apoptosis plays an important role in emphysema pathogenesis, a chronic inflammatory lung disease characterized by alveolar destruction. The association of α1-antitrypsin deficiency with the development of emphysema has supported the concept that protease/antiprotease imbalance mediates cigarette smoke–induced emphysema. Objectives: We propose that, in addition to its antielastolytic effects, α1-antitrypsin may have broader biological effects in the lung, preventing emphysema through inhibition of alveolar cells apoptosis. Methods, Measurements, and Main Results: Transduction of human α1-antitrypsin via replication-deficient adeno-associated virus attenuated airspace enlargement and emphysema caused by inhibition of vascular endothelial growth factor (VEGF) receptors with SU5416 in mice, a model of apoptosis-dependent emphysema lacking neutrophilic inflammation. The overexpressed human serine protease inhibitor accumulated in lung cells and suppressed caspase-3 activation and oxidative stress in lungs treated with the VEGF blocker or with VEGF receptor-1 and -2 antibodies. Similar results were obtained in SU5416-treated rats given human α1-antitrypsin intravenously. Conclusions: Our findings suggest that inhibition of structural alveolar cell apoptosis by α1-antitrypsin represents a novel protective mechanism of the serpin against emphysema. Further elucidation of this mechanism may extend the therapeutic options for emphysema caused by reduced level or loss of function of α1-antitrypsin. PMID:16514110

  3. Sex-specific features of emphysema among current and former smokers with COPD

    PubMed Central

    Hardin, Megan; Foreman, Marilyn; Dransfield, Mark T.; Hansel, Nadia; Han, MeiLan K; Cho, Michael H; Bhatt, Surya P; Ramsdell, Joe; Lynch, David; Curtis, Jeffrey L.; Silverman, Edwin K.; Washko, George; DeMeo, Dawn

    2017-01-01

    Rationale Recent studies suggest that men with COPD have more emphysema than women. It is not known if these differences persist across degrees of COPD severity. Objectives Our aim was to identify sex-specific differences in quantitative emphysema within COPD subgroups based on COPD severity. Methods We included non-Hispanic white and African American subjects from the COPDGene study with at least ten pack-years of smoking and COPD GOLD spirometry grade II or greater. We examined sex-specific differences in log-transformed emphysema (%LAA) by GOLD spirometry grade, among subjects with early-onset COPD (<55 years old) and advanced emphysema (>25 % emphysema). Measurements and Main Results Compared to women, men had higher log %LAA: overall (1.97 ± 1.4 v 1.69±1.6, ß=0.32(0.04), P=1.34×10-14), among non-Hispanic whites (P=8.37×10-14), and African American subjects (P=0.002). Women with early-onset COPD, severe emphysema, and GOLD grade IV COPD had similar emphysema as men but markedly fewer pack-years smoking (early-onset P=0.01, severe emphysema and GOLD grade IV P<0.001). Conclusions This study identifies subsets of female smokers with COPD who are particularly susceptible to parenchymal destruction. PMID:26541532

  4. Centrilobular emphysema combined with pulmonary fibrosis results in improved survival: a response.

    PubMed

    Cottin, Vincent; Cordier, Jean-François; Wells, Athol U

    2011-07-25

    Better survival in combined pulmonary fibrosis and emphysema than in lone pulmonary fibrosis: bias or reality? A response to Centrilobular emphysema combined with pulmonary fibrosis results in improved survival by Todd et al., Fibrogenesis & Tissue Repair 2011, 4:6.Please see related letter http://fibrogenesis.com/content/4/1/17.

  5. Sex-specific features of emphysema among current and former smokers with COPD.

    PubMed

    Hardin, Megan; Foreman, Marilyn; Dransfield, Mark T; Hansel, Nadia; Han, MeiLan K; Cho, Michael H; Bhatt, Surya P; Ramsdell, Joe; Lynch, David; Curtis, Jeffrey L; Silverman, Edwin K; Washko, George; DeMeo, Dawn

    2016-01-01

    Recent studies suggest that males with chronic obstructive pulmonary disease (COPD) have more emphysema than females. It is not known if these differences persist across degrees of COPD severity. Our aim was to identify sex-specific differences in quantitative emphysema within COPD subgroups based on COPD severity.We included non-Hispanic white and African-American subjects from the COPDGene study with at least 10 pack-years of smoking and COPD Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometry grade II or greater. We examined sex-specific differences in log-transformed emphysema (log per cent low-attenuation area (%LAA)) by GOLD spirometry grade among subjects with early-onset COPD (<55 years old) and advanced emphysema (>25% emphysema).Compared with females, males had higher log %LAA: overall (1.97±1.4 versus 1.69±1.6, β=0.32 (0.04), p=1.34×10(-14)), and among non-Hispanic white (p=8.37×10(-14)) and African-American subjects (p=0.002). Females with early-onset COPD, severe emphysema and GOLD grade IV COPD had similar emphysema as males, but markedly fewer pack-years smoking (early-onset, p=0.01; severe emphysema and GOLD grade IV, p<0.001).This study identifies subsets of female smokers with COPD who are particularly susceptible to parenchymal destruction.

  6. Proteoglycans maintain lung stability in an elastase-treated mouse model of emphysema.

    PubMed

    Takahashi, Ayuko; Majumdar, Arnab; Parameswaran, Harikrishnan; Bartolák-Suki, Erzsébet; Suki, Béla

    2014-07-01

    Extracellular matrix remodeling and tissue rupture contribute to the progression of emphysema. Lung tissue elasticity is governed by the tensile stiffness of fibers and the compressive stiffness of proteoglycans. It is not known how proteoglycan remodeling affects tissue stability and destruction in emphysema. The objective of this study was to characterize the role of remodeled proteoglycans in alveolar stability and tissue destruction in emphysema. At 30 days after treatment with porcine pancreatic elastase, mouse lung tissue stiffness and alveolar deformation were evaluated under varying tonicity conditions that affect the stiffness of proteoglycans. Proteoglycans were stained and measured in the alveolar walls. Computational models of alveolar stability and rupture incorporating the mechanical properties of fibers and proteoglycans were developed. Although absolute tissue stiffness was only 24% of normal, changes in relative stiffness and alveolar shape distortion due to changes in tonicity were increased in emphysema (P < 0.01 and P < 0.001). Glycosaminoglycan amount per unit alveolar wall length, which is responsible for proteoglycan stiffness, was higher in emphysema (P < 0.001). Versican expression increased in the tissue, but decorin decreased. Our network model predicted that the rate of tissue deterioration locally governed by mechanical forces was reduced when proteoglycan stiffness was increased. Consequently, this general network model explains why increasing proteoglycan deposition protects the alveolar walls from rupture in emphysema. Our results suggest that the loss of proteoglycans observed in human emphysema contributes to disease progression, whereas treatments that promote proteoglycan deposition in the extracellular matrix should slow the progression of emphysema.

  7. Emphysema- and airway-dominant COPD phenotypes defined by standardised quantitative computed tomography.

    PubMed

    Subramanian, Deepak R; Gupta, Sumit; Burggraf, Dorothe; Vom Silberberg, Suzan J; Heimbeck, Irene; Heiss-Neumann, Marion S; Haeussinger, Karl; Newby, Chris; Hargadon, Beverley; Raj, Vimal; Singh, Dave; Kolsum, Umme; Hofer, Thomas P; Al-Shair, Khaled; Luetzen, Niklas; Prasse, Antje; Müller-Quernheim, Joachim; Benea, Giorgio; Leprotti, Stefano; Boschetto, Piera; Gorecka, Dorota; Nowinski, Adam; Oniszh, Karina; Castell, Wolfgang Zu; Hagen, Michael; Barta, Imre; Döme, Balázs; Strausz, Janos; Greulich, Timm; Vogelmeier, Claus; Koczulla, Andreas R; Gut, Ivo; Hohlfeld, Jens; Welte, Tobias; Lavae-Mokhtari, Mahyar; Ziegler-Heitbrock, Loems; Brightling, Christopher; Parr, David G

    2016-07-01

    EvA (Emphysema versus Airway disease) is a multicentre project to study mechanisms and identify biomarkers of emphysema and airway disease in chronic obstructive pulmonary disease (COPD). The objective of this study was to delineate objectively imaging-based emphysema-dominant and airway disease-dominant phenotypes using quantitative computed tomography (QCT) indices, standardised with a novel phantom-based approach.441 subjects with COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 1-3) were assessed in terms of clinical and physiological measurements, laboratory testing and standardised QCT indices of emphysema and airway wall geometry.QCT indices were influenced by scanner non-conformity, but standardisation significantly reduced variability (p<0.001) and led to more robust phenotypes. Four imaging-derived phenotypes were identified, reflecting "emphysema-dominant", "airway disease-dominant", "mixed" disease and "mild" disease. The emphysema-dominant group had significantly higher lung volumes, lower gas transfer coefficient, lower oxygen (PO2 ) and carbon dioxide (PCO2 ) tensions, higher haemoglobin and higher blood leukocyte numbers than the airway disease-dominant group.The utility of QCT for phenotyping in the setting of an international multicentre study is improved by standardisation. QCT indices of emphysema and airway disease can delineate within a population of patients with COPD, phenotypic groups that have typical clinical features known to be associated with emphysema-dominant and airway-dominant disease.

  8. Morphologic aspects of airways of patients with pulmonary emphysema followed by bronchial asthma-like attack.

    PubMed

    Haraguchi, M; Shimura, S; Shirato, K

    1996-02-01

    Morphometric analysis of airways was performed in autopsied lungs from four patients with pulmonary emphysema (PE) followed by bronchial-asthma (BA)-like attacks (Group PE+BA) (four males, 72 +/- 9 yr). The results were compared with those from five pulmonary emphysema patients (Group PE) (five males, age 71 +/- 4 hr), three patients with bronchial asthma (Group BA) (one female and two males, age 65 +/- 7 yr), and four control subjects with no pulmonary diseases (Group Cont) (one female, three males, age 64 +/- 4 yr). The proportion of gland area to bronchial wall (gland%), ratio of goblet-cell occupancy to the total epithelial layer (goblet%), thickness of the basement membrane, amount of intraluminal mucus (mucus occupying ratio; MOR%), and number of various cell types per square millimeter in airway walls in a section 4 microns thick were measured in central (3 to 8 mm diameter) and peripheral airways (2 mm or less diameter). Gland% for the PE+BA group was significantly greater than that for the Cont group, whereas it did not differ significantly from that of the PE or BA groups. Goblet% and thickness of the basement membrane in central and/or peripheral airways in Group PE+BA were significantly greater than those in Group Cont, whereas those in Group PE were similar to those in Group Cont. Although not statistically significant, MOR% in central and peripheral airways from Group PE+BA showed a similar value to that in Group BA, whereas MOR% in Group PE was the same as that in Group Cont. The eosinophil number in peripheral airways walls in Group PE+BA showed a similar value to that in Group BA, which was significantly greater than in Group Cont. Other cells (macrophages, lymphocytes, and neutrophils) showed similar values among Groups PE+BA, PE, and BA. The number of eosinophils in central and/or peripheral airways correlated significantly with both goblet% and BMT, whereas other cells did not. These findings indicate that the airways of Group PE+BA are

  9. Mesenchymal stem cell-based HSP70 promoter-driven VEGFA induction by resveratrol alleviates elastase-induced emphysema in a mouse model.

    PubMed

    Chen, Young-Bin; Lan, Ying-Wei; Chen, Lih-Geeng; Huang, Tsung-Teng; Choo, Kong-Bung; Cheng, Winston T K; Lee, Hsuan-Shu; Chong, Kowit-Yu

    2015-11-01

    Chronic obstructive pulmonary disease (COPD) is a sustained blockage of the airways due to lung inflammation occurring with chronic bronchitis and/or emphysema. Progression of emphysema may be slowed by vascular endothelial growth factor A (VEGFA), which reduces apoptotic tissue depletion. Previously, authors of the present report demonstrated that cis-resveratrol (c-RSV)-induced heat-shock protein 70 (HSP70) promoter-regulated VEGFA expression promoted neovascularization of genetically modified mesenchymal stem cells (HSP-VEGFA-MSC) in a mouse model of ischemic disease. Here, this same stem cell line was evaluated for its protective capacity to alleviate elastase-induced pulmonary emphysema in mice. Results of this study showed that c-RSV-treatment of HSP-VEGFA-MSC exhibited synergy between HSP70 transcription activity and induced expression of anti-oxidant-related genes when challenged by cigarette smoke extracts. Eight weeks after jugular vein injection of HSP-VEGFA-MSC into mice with elastase-induced pulmonary emphysema followed by c-RSV treatment to induce transgene expression, significant improvement was observed in respiratory functions. Expression of VEGFA, endogenous nuclear factor erythroid 2-related factor (Nrf 2), and manganese superoxide dismutase (MnSOD) was significantly increased in the lung tissues of the c-RSV-treated mice. Histopathologic examination of treated mice revealed gradual but significant abatement of emphysema and restoration of airspace volume. In conclusion, the present investigation demonstrates that c-RSV-regulated VEGFA expression in HSP-VEGFA-MSC significantly improved the therapeutic effects on the treatment of COPD in the mouse, possibly avoiding side effects associated with constitutive VEGFA expression.

  10. Facial, Cervical, and Mediastinal Emphysema of the Clarinet Player: Case Report

    PubMed Central

    Biçer, Yusuf Özgür; Kesgin, Selcan; Tezcan, Erkan; Köybaşı, Serap

    2014-01-01

    Background: Cervicofacial emphysema may arise due to the leakage of air from a defect in the aerodigestive tract to the fascial layers of neck and face. Rarely, it may be caused by insufflation of air through the Stensen’s duct. Case Report: We present a case with diffuse facial, cervical and mediastinal emphysema due to playing a wind instrument immediately after a facial trauma. There was no mucosal defect or laceration noticed by examination which could explain the origin of the emphysema. Despite the widespread cervicofacial emphysema with mediastinal involvement, the patient significantly improved within 48 hours without any intervention. Conclusion: Even though cervicofacial emphysema ameliorates spontaneously, increased care must be taken, especially when there is pneumomediastinum and/or pneumothorax. PMID:25667794

  11. Biologic lung volume reduction therapy for advanced homogeneous emphysema.

    PubMed

    Refaely, Y; Dransfield, M; Kramer, M R; Gotfried, M; Leeds, W; McLennan, G; Tewari, S; Krasna, M; Criner, G J

    2010-07-01

    This report summarises phase 2 trial results of biologic lung volume reduction (BioLVR) for treatment of advanced homogeneous emphysema. BioLVR therapy was administered bronchoscopically to 25 patients with homogeneous emphysema in an open-labelled study. Eight patients received low dose (LD) treatment with 10 mL per site at eight subsegments; 17 received high dose (HD) treatment with 20 mL per site at eight subsegments. Safety was assessed in terms of medical complications during 6-month follow-up. Efficacy was assessed in terms of change from baseline in gas trapping, spirometry, diffusing capacity, exercise capacity, dyspnoea and health-related quality of life. There were no deaths or serious medical complications during the study. A statistically significant reduction in gas trapping was observed at 3-month follow-up among HD patients, but not LD patients. At 6 months, changes from baseline in forced expiratory volume in 1 s (-8.0+/-13.93% versus +13.8+/-20.26%), forced vital capacity (-3.9+/-9.41% versus +9.0+/-13.01%), residual volume/total lung capacity ratio (-1.4+/-13.82% versus -5.4+/-12.14%), dyspnoea scores (-0.4+/-1.27 versus -0.8+/-0.73 units) and St George's Respiratory Questionnaire total domain scores (-4.9+/-8.3 U versus -12.2+/-12.38 units) were better with HD than with LD therapy. BioLVR therapy with 20 mL per site at eight subsegmental sites may be a safe and effective therapy in patients with advanced homogeneous emphysema.

  12. Nitrogen dioxide exposure and development of pulmonary emphysema

    SciTech Connect

    Stavert, D.M.; Archuleta, D.C.; Holland, L.M.; Lehnert, B.E.

    1986-01-01

    Lungs of adult Fischer-344 rats were evaluated for emphysematous changes after (1) a single intratracheal instillation of elastase (E), (2) a 25-d exposure to 35 ppm nitrogen dioxide (NO/sub 2/), and (3) elastase instillation followed by 25-d exposure to 35 ppm NO/sub 2/ (E + NO/sub 2/). Residual volumes (RV) of the NO/sub 2/ and NS groups were virtually identical, whereas the RV of the E and E + NO/sub 2/ lungs were significantly greater than those of the NS and NO/sub 2/ lungs. Directionally similar changes in the excised lung volumes and total lung capacities were obtained with the E and E + NO/sub 2/ groups; NO/sub 2/ alone, however, did not alter these volumetric parameters. No differences in arterial blood gases and pH values, minute ventilation, or breathing frequencies were found among the experimental groups. The mean linear intercept values (MLI) obtained with the NS and NO/sub 2/ exposed lungs were essentially identical with average values of approx. 62 ..mu..m. This morphometric parameter was substantially increased in the E- and E + NO/sub 2/-exposed lungs; no significant differences, however, were found between the MLI values obtained with the E and E + NO/sub 2/ lungs. From these data as well as histologic examinations of lung sections for evidence of emphysema, it was concluded that (1) a subchronic, moderately high level of NO/sub 2/ exposure does not produce an irreversible emphysematous lesion in the rat model and (2) exposure of rats to 35 ppm for 25 d after elastase instillation into the lungs does not potentiate protease-induced emphysema or bring about a progression in preexisting emphysema.

  13. Scan-rescan reproducibility of CT densitometric measures of emphysema

    NASA Astrophysics Data System (ADS)

    Chong, D.; van Rikxoort, E. M.; Kim, H. J.; Goldin, J. G.; Brown, M. S.

    2011-03-01

    This study investigated the reproducibility of HRCT densitometric measures of emphysema in patients scanned twice one week apart. 24 emphysema patients from a multicenter study were scanned at full inspiration (TLC) and expiration (RV), then again a week later for four scans total. Scans for each patient used the same scanner and protocol, except for tube current in three patients. Lung segmentation with gross airway removal was performed on the scans. Volume, weight, mean lung density (MLD), relative area under -950HU (RA-950), and 15th percentile (PD-15) were calculated for TLC, and volume and an airtrapping mask (RA-air) between -950 and -850HU for RV. For each measure, absolute differences were computed for each scan pair, and linear regression was performed against volume difference in a subgroup with volume difference <500mL. Two TLC scan pairs were excluded due to segmentation failure. The mean lung volumes were 5802 +/- 1420mL for TLC, 3878 +/- 1077mL for RV. The mean absolute differences were 169mL for TLC volume, 316mL for RV volume, 14.5g for weight, 5.0HU for MLD, 0.66p.p. for RA-950, 2.4HU for PD-15, and 3.1p.p. for RA-air. The <500mL subgroup had 20 scan pairs for TLC and RV. The R2 values were 0.8 for weight, 0.60 for MLD, 0.29 for RA-950, 0.31 for PD-15, and 0.64 for RA-air. Our results indicate that considerable variability exists in densitometric measures over one week that cannot be attributed to breathhold or physiology. This has implications for clinical trials relying on these measures to assess emphysema treatment efficacy.

  14. Xenon-Enhanced Dual-Energy CT Imaging in Combined Pulmonary Fibrosis and Emphysema

    PubMed Central

    Kobayashi, Masahiro; Nakamura, Yasuhiko; Gocho, Kyoko; Ishida, Fumiaki; Isobe, Kazutoshi; Shiraga, Nobuyuki; Homma, Sakae

    2017-01-01

    Background Little has been reported on the feasibility of xenon-enhanced dual-energy computed tomography (Xe-DECT) in the visual and quantitative analysis of combined pulmonary fibrosis and emphysema (CPFE). Objectives We compared CPFE with idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD), as well as correlation with parameters of pulmonary function tests (PFTs). Methods Studied in 3 groups were 25 patients with CPFE, 25 with IPF without emphysema (IPF alone), 30 with COPD. Xe-DECT of the patients’ entire thorax was taken from apex to base after a patient’s single deep inspiration of 35% stable nonradioactive xenon. The differences in several parameters of PFTs and percentage of areas enhanced by xenon between 3 groups were compared and analyzed retrospectively. Results The percentage of areas enhanced by xenon in both lungs were calculated as CPFE/IPF alone/COPD = 72.2 ± 15.1% / 82.2 ± 14.7% /45.2 ± 23.2%, respectively. In the entire patients, the percentage of areas enhanced by xenon showed significantly a positive correlation with FEV1/FVC (R = 0.558, P < 0.0001) and %FEV1, (R = 0.528, P < 0.0001) and a negative correlation with %RV (R = -0.594, P < 0.0001) and RV/TLC (R = -0.579, P < 0.0001). The percentage of areas enhanced by xenon in patients with CPFE showed significantly a negative correlation with RV/TLC (R = -0.529, P = 0.007). Xenon enhancement of CPFE indicated 3 different patterns such as upper predominant, diffuse, and multifocal defect. The percentage of areas enhanced by xenon in upper predominant defect pattern was significantly higher than that in diffuse defect and multifocal defect pattern among these 3 different patterns in CPFE. Conclusion The percentage of areas enhanced by xenon demonstrated strong correlations with obstructive ventilation impairment. Therefore, we conclude that Xe-DECT may be useful for distinguishing emphysema lesion from fibrotic lesion in CPFE. PMID:28107411

  15. Subcutaneous Emphysema in Acute Asthma: A Cause for Concern?

    PubMed

    Mitchell, Patrick D; King, Thomas J; O'Shea, Donal B

    2015-08-01

    Pneumomediastinum has been described in patients with asthma. In this case report, we describe a young patient who presented to our medical assessment unit with an asthma exacerbation and progressive dyspnea. The patient developed pneumomediastinum, a rare complication of an asthma exacerbation. Pneumomediastinum is usually characterized by chest pain, dyspnea, and neck swelling caused by subcutaneous emphysema. Although the condition is usually benign and treatment is primarily supportive, surgical intervention may be needed if the patient develops hemodynamic compromise or respiratory failure through mechanisms similar to those seen in a tension pneumothorax.

  16. Native lung-sparing lobar transplantation for pulmonary emphysema.

    PubMed

    Yamane, Masaomi; Okutani, Daisuke; Sugimoto, Seiichiro; Toyooka, Shinichi; Aoe, Motoi; Okazaki, Megumi; Sano, Yoshifumi; Date, Hiroshi

    2008-09-01

    The living-donor lobar lung transplantation procedure has been developed clinically as an alternative approach for patients considered too ill to await cadaveric transplantation. With this procedure, 2 lobes are implanted in the recipient in place of whole right and left lungs, respectively. However, the shortage of graft volume can be a problem when compared with full-sized cadaveric grafts. In an attempt to solve this problem, we have developed a native lobe-preserving lobar transplant technique using a large animal model. We report a first successful case of a patient undergoing native lobe-preserving lobar lung transplantation for severe pulmonary emphysema.

  17. Emphysema mimicking interstitial lung disease: Two case reports

    PubMed Central

    Juhl, Kasper S.; Bendstrup, Elisabeth; Rasmussen, Finn; Hilberg, Ole

    2014-01-01

    Honeycombing in general is a sign of severe end-stage fibrosis. Here we present two cases, where the combination of emphysema, acute inflammation and pulmonary embolism gave an appearance of honeycombing seen in pulmonary fibrosis. HRCT interpretation in the evaluation of acutely ill patients with pulmonary infection is a challenge. Our case reports emphasize the importance of a multidisciplinary approach, when it comes to patients with suspected complicated pulmonary diseases. At the same time they give very realistic examples of the challenges found in diagnosing patients with simultaneous acute and chronic pulmonary diseases. PMID:26236586

  18. Occult lung cancer in patients with bullous emphysema

    PubMed Central

    Venuta, F.; Rendina, E. A.; Pescarmona, E. O.; De Giacomo, T.; Vizza, D.; Flaishman, I.; Ricci, C.

    1997-01-01

    BACKGROUND: The incidence of lung cancer is increased in patients with bullous emphysema. METHODS: A series of 95 patients undergoing excision of bullous lung tissue was reviewed to determine the incidence and long term outcome of occult carcinoma present in the resected material. RESULTS: Four patients (4.2%) had peripheral foci of large cell carcinoma in the resection specimen (three bullectomies and one lobectomy). CONCLUSIONS: Resected bullous lung tissue should be carefully examined for areas of bronchogenic carcinoma. The results of incidental complete excision are favourable. 




 PMID:9093350

  19. [Functional respiratory evolution in two patients with emphysema and pulmonary fibrosis].

    PubMed

    Arce, Santiago C; Molinari, Luciana; De Vito, Eduardo L

    2009-01-01

    Combined pulmonary fibrosis and emphysema (CPFE) is a frequently under-diagnosed condition. Isolated pulmonary function tests (PFT) can give rise to misinterpretations. We have found no reports on these patients' spirometric progression. We describe two cases of CPFE, showing long-term functional evolution to have a more accurate understanding of current spirometric values. The most relevant findings are: 1) spirometry with discrete functional alterations in the presence of a marked dyspnea and the need, in one patient, for chronic oxygen therapy; and 2) functional evolution reflecting "pseudonormalisation" of the initial obstructive spirometric pattern, possibly as a result of fibrosis development. A mild obstructive defect in a patient with chronic airflow limitation and marked impairment of his/her clinical status and functional class should alert on the possibility of associated pulmonary fibrosis. A computed tomography (CT) and previous PFTs will allow a better understanding of this condition.

  20. Skeletal muscle oxidative metabolism in an animal model of pulmonary emphysema: formoterol and skeletal muscle dysfunction.

    PubMed

    Sullo, Nikol; Roviezzo, Fiorentina; Matteis, Maria; Spaziano, Giuseppe; Del Gaudio, Stefania; Lombardi, Assunta; Lucattelli, Monica; Polverino, Francesca; Lungarella, Giuseppe; Cirino, Giuseppe; Rossi, Francesco; D'Agostino, Bruno

    2013-02-01

    Skeletal muscle dysfunction is a significant contributor to exercise limitation in pulmonary emphysema. This study investigated skeletal muscle oxidative metabolism before and after aerosol exposure to a long-acting β-agonist (LABA), such as formoterol, in the pallid mouse (B6.Cg-Pldnpa/J), which has a deficiency in serum α(1)-antitrypsin (α(1)-PI) and develops spontaneous pulmonary emphysema. C57 BL/6J and its congener pallid mice of 8-12 and 16 months of age were treated with vehicle or formoterol aerosol challenge for 120 seconds. Morphological and morphometric studies and evaluations of mitochondrial adenosine diphosphate-stimulated respiration and of cytochrome oxidase activity on skeletal muscle were performed. Moreover, the mtDNA content in skeletal muscle and the mediators linked to muscle mitochondrial function and biogenesis, as well as TNF-α and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), were also evaluated. The lungs of pallid mice at 12 and 16 months of age showed patchy areas of airspace enlargements, with the destruction of alveolar septa. No significant differences were observed in basal values of mitochondrial skeletal muscle oxidative processes between C57 BL/6J and pallid mice. Exposure to LABA significantly improved mitochondrial skeletal muscle oxidative processes in emphysematous mice, where the mtDNA content was significantly higher with respect to 8-month-old pallid mice. This effect was compared with a significant increase of PGC-1α in skeletal muscles of 16-month-old pallid mice, with no significant changes in TNF-α concentrations. In conclusion, in emphysematous mice that showed an increased mtDNA content, exposure to inhaled LABA can improve mitochondrial skeletal muscle oxidative processes. PGC-1α may serve as a possible mediator of this effect.

  1. Light cigarette smoke-induced emphysema and NFκB activation in mouse lung

    PubMed Central

    Santos Valenca, Samuel; Castro, Paulo; Alves Pimenta, Wagner; Lanzetti, Manuella; Vargas Silva, Simone; Barja-Fidalgo, Cristina; Gonçalves Koatz, Vera Lúcia; Porto, Luís Cristóvão

    2006-01-01

    Light cigarette (LC) exposure is supposed to be less hazardous with a decreased incidence of cancer and tobacco-associated diseases. C57BL/6 mouse groups were subjected to smoke from 3, 6 or 12 LC for 60 days and compared with mice exposed to ambient air (EAA) in order to study lung injury by morphometrical and biochemical methods. Bronchoalveolar lavage (BAL) analysis and histology and stereology were performed. Tissue from the right lung was used for measuring thiobarbituric acid reactive substances (TBARS) and Western blot analysis. One way anova was performed followed by the Student–Newman Keuls post-test (P < 0.05). The cellular content of BAL was 95% alveolar macrophages in all groups except in mice exposed to 3 LC, where 23% neutrophils were observed. Emphysema was not observed in three and 6 LC, but it was found in 12 LC parallel to increased volume density (Vv) of airspaces from 61.0 ± 0.6 (EAA) to 80.9 ± 1.0 (12 LC) and decreased Vv of elastic fibres from 17.8 ± 0.9 (EAA) to 11.8 ± 0.6 (12 LC). All exposed groups to LC showed low TBARS levels compared with mice EAA. Lung tissue from animals exposed to 12 LC showed decreased tissue inhibitor of metalloprotease-2 and increased matrix metalloprotease-12 detection, which suggests an imbalance in extracellular matrix (ECM). Increased tumour necrosis factor-α and nuclear factor-κB detection were observed in exposed groups to LC when compared with mice EAA. The data suggest that LC is so dangerous to lungs as full-flavour cigarettes inducing ECM imbalance and emphysema. PMID:16965565

  2. Decreased proteasomal function accelerates cigarette smoke-induced pulmonary emphysema in mice.

    PubMed

    Yamada, Yosuke; Tomaru, Utano; Ishizu, Akihiro; Ito, Tomoki; Kiuchi, Takayuki; Ono, Ayako; Miyajima, Syota; Nagai, Katsura; Higashi, Tsunehito; Matsuno, Yoshihiro; Dosaka-Akita, Hirotoshi; Nishimura, Masaharu; Miwa, Soichi; Kasahara, Masanori

    2015-06-01

    Chronic obstructive pulmonary disease (COPD) is a disease common in elderly people, characterized by progressive destruction of lung parenchyma and chronic inflammation of the airways. The pathogenesis of COPD remains unclear, but recent studies suggest that oxidative stress-induced apoptosis in alveolar cells contributes to emphysematous lung destruction. The proteasome is a multicatalytic enzyme complex that plays a critical role in proteostasis by rapidly destroying misfolded and modified proteins generated by oxidative and other stresses. Proteasome activity decreases with aging in many organs including lungs, and an age-related decline in proteasomal function has been implicated in various age-related pathologies. However, the role of the proteasome system in the pathogenesis of COPD has not been investigated. Recently, we have established a transgenic (Tg) mouse model with decreased proteasomal chymotrypsin-like activity, showing age-related phenotypes. Using this model, we demonstrate here that decreased proteasomal function accelerates cigarette smoke (CS)-induced pulmonary emphysema. CS-exposed Tg mice showed remarkable airspace enlargement and increased foci of inflammation compared with wild-type controls. Importantly, apoptotic cells were found in the alveolar walls of the affected lungs. Impaired proteasomal activity also enhanced apoptosis in cigarette smoke extract (CSE)-exposed fibroblastic cells derived from mice and humans in vitro. Notably, aggresome formation and prominent nuclear translocation of apoptosis-inducing factor were observed in CSE-exposed fibroblastic cells isolated from Tg mice. Collective evidence suggests that CS exposure and impaired proteasomal activity coordinately enhance apoptotic cell death in the alveolar walls that may be involved in the development and progression of emphysema in susceptible individuals such as the elderly.

  3. Resolvin D1 Reduces Emphysema and Chronic Inflammation

    PubMed Central

    Hsiao, Hsi-Min; Thatcher, Thomas H.; Colas, Romain A.; Serhan, Charles N.; Phipps, Richard P.; Sime, Patricia J.

    2016-01-01

    Chronic obstructive pulmonary disease is characterized, in part, by chronic inflammation that persists even after smoking cessation, suggesting that a failure to resolve inflammation plays an important role in the pathogenesis of the disease. It is widely recognized that the resolution of inflammation is an active process, governed by specialized proresolving lipid mediators, including lipoxins, resolvins, maresins, and protectins. Here, we report that proresolving signaling and metabolic pathways are disrupted in lung tissue from patients with chronic obstructive pulmonary disease, suggesting that supplementation with proresolving lipid mediators might reduce the development of emphysema by controlling chronic inflammation. Groups of mice were exposed long-term to cigarette smoke and treated with the proresolving mediator resolvin D1. Resolvin D1 was associated with a reduced development of cigarette smoke–induced emphysema and airspace enlargement, with concurrent reductions in inflammation, oxidative stress, and cell death. Interestingly, resolvin D1 did not promote the differentiation of M2 macrophages and did not promote tissue fibrosis. Taken together, our results suggest that cigarette smoking disrupts endogenous proresolving pathways and that supplementation with specialized proresolving lipid mediators is an important therapeutic strategy in chronic lung disease, especially if endogenous specialized proresolving lipid mediator signaling is impaired. PMID:26468975

  4. Correlation of regional breath sound with regional ventilation in emphysema

    SciTech Connect

    Ploysongsang, Y.; Pare, J.A.; Macklem, P.T.

    1982-09-01

    We measured regional breath sound intensities (Ib) by a microphone amplifier system in 8 subjects with emphysema. We also measured regional white noise transmissions (Tn) from the same areas in all subjects. The recorded areas were 5, 10, 15, and 20 cm from the apex of the lung just lateral to the right anterior midclavicular line. Xenon ventilation indexes (xenon tidal raw counts, an index of total regional ventilation; xenon equilibration raw counts, an index of ventilating lung volume; xenon ventilation per unit volume (Vr), an index of ventilation per unit volume) were also recorded from the same areas. The Ib, Tn, Ib/Tn (an index of sound generation), and xenon ventilation indexes were all expressed as a fraction of the mean value of all four recorded areas. The Ib and Ib/Tn correlated best with the xenon tidal raw counts, correlated well with the xenon equilibration raw counts, and correlated poorly with Vr. We conclude that Ib and Ib/Tn can be used to quantify regional ventilation in subjects with emphysema.

  5. Combined pulmonary fibrosis and emphysema (CPFE): what radiologist should know.

    PubMed

    Ciccarese, Federica; Attinà, Domenico; Zompatori, Maurizio

    2016-07-01

    Combined pulmonary fibrosis and emphysema is a relatively newly defined entity, which has been deeply studied in the recent years. Despite the wide numbers of papers on this topic, there are still several open questions about pathogenesis, epidemiology, natural history and prognosis. The diagnosis could be assessed only after HRCT scan as functional tests often result in an underestimation of this syndrome. What radiologists need to know about this syndrome consists in the heterogeneity of appearances: emphysema is mainly paraseptal and fibrotic pattern could be variable, including the variant of airspace enlargement with fibrosis which needs to be differentiated from honeycombing. A special attention must be paid on complications which could worsen the prognosis, such as pulmonary hypertension and lung cancer. Further studies are needed to address if the type of fibrotic pattern as well as fibrosis CT index could be considered as prognostic factors. Thus, the role of radiologists in the management of these patients is crucial as it involves diagnosis, detection of complications and could possible concerns the identification of patients at higher risk.

  6. Basic mechanisms leading to focal emphysema in coal workers' pneumoconiosis

    SciTech Connect

    Rom, W.N. )

    1990-10-01

    Coal miners develop focal emphysema characterized by dilatation of second- and third-order respiratory bronchioles with coal mine dust-laden macrophages infiltrating the wall. A reticulin network with small amounts of collagen and atrophy of smooth muscle occurs. To evaluate the mechanisms of lung injury associated with this lesion, 17 long-term non- or ex-smoking West Virginia underground coal miners underwent bronchoalveolar lavage (BAL) and were compared to healthy nonsmoker and smoker controls. The coal miners had evidence of an alveolar macrophage-neutrophil alveolitis with a significant increase in neutrophils/microliter of epithelial lining fluid and an increased gallium lung scan index (206 +/- 26 units). Alveolar macrophages lavaged from coal miners spontaneously released exaggerated amounts of superoxide anion and hydrogen peroxide in vitro compared to nonsmoking controls. Coal workers had significantly elevated levels of neutrophil elastase in BAL fluid complexed with alpha 1-antitrypsin (P less than 0.01) and normal levels of alpha 1-antitrypsin. An accumulation of activated, dust-laden inflammatory cells with increased release of oxidants and elastase may contribute to the development of focal emphysema identified at postmortem in miners with coal workers' pneumoconiosis.

  7. Emergent structure-function relations in emphysema and asthma.

    PubMed

    Winkler, Tilo; Suki, Béla

    2011-01-01

    Structure-function relationships in the respiratory system are often a result of the emergence of self-organized patterns or behaviors that are characteristic of certain respiratory diseases. Proper description of such self-organized behavior requires network models that include nonlinear interactions among different parts of the system. This review focuses on 2 models that exhibit self-organized behavior: a network model of the lung parenchyma during the progression of emphysema that is driven by mechanical force-induced breakdown, and an integrative model of bronchoconstriction in asthma that describes interactions among airways within the bronchial tree. Both models suggest that the transition from normal to pathologic states is a nonlinear process that includes a tipping point beyond which interactions among the system components are reinforced by positive feedback, further promoting the progression of pathologic changes. In emphysema, the progressive destruction of tissue is irreversible, while in asthma, it is possible to recover from a severe bronchoconstriction. These concepts may have implications for pulmonary medicine. Specifically, we suggest that structure-function relationships emerging from network behavior across multiple scales should be taken into account when the efficacy of novel treatments or drug therapy is evaluated. Multiscale, computational, network models will play a major role in this endeavor.

  8. Different modulation of decorin production by lung fibroblasts from patients with mild and severe emphysema.

    PubMed

    Noordhoek, Jacobien A; Postma, Dirkje S; Chong, Luis L; Menkema, Lorian; Kauffman, Henk F; Timens, Wim; van Straaten, Jeanette F M; van der Geld, Ymke M

    2005-03-01

    We have previously reported diminished immunohistochemical staining of decorin in lung tissue from patients with severe emphysema. The aim of this study is to investigate whether this diminished staining is due to a quantitative abnormal production of decorin by pulmonary fibroblasts in vitro. Therefore, we measured decorin (Western blot), collagen type I (ELISA), and fibronectin (ELISA) production by fibroblasts obtained from lung tissue of patients with severe and mild emphysema at basal culture conditions and after modulation with transforming growth factor-beta1, basic fibroblast growth factor, and interferon-gamma. Decorin production at basal culture conditions was significantly higher in fibroblast cultures from patients with severe emphysema compared to fibroblasts from mild emphysema. After stimulation with transforming growth factor-beta1 and basic fibroblast growth factor, decorin production was significantly more reduced in fibroblast cultures from patients with severe emphysema whereas collagen type I and fibronectin production were not affected. We conclude that decorin production by lung fibroblasts of patients with severe emphysema is dysregulated after modulation with cytokines known to be important in smoking associated inflammation. This dysregulation of decorin production may contribute to the impaired lung tissue repair, present in patients with emphysema, since these alterations in the extracellular matrix may cause diminished cytokine binding and neutralization.

  9. Critical role of tumor necrosis factor receptor 1 in the pathogenesis of pulmonary emphysema in mice.

    PubMed

    Fujita, Masaki; Ouchi, Hiroshi; Ikegame, Satoshi; Harada, Eiji; Matsumoto, Takemasa; Uchino, Junji; Nakanishi, Yoichi; Watanabe, Kentaro

    2016-01-01

    COPD is a major cause of chronic morbidity and mortality throughout the world. Although tumor necrosis factor-α (TNF-α) has a critical role in the development of COPD, the role of different TNF receptors (TNFRs) in pulmonary emphysema has not been resolved. We aimed to clarify the role of TNFRs in the development of pulmonary emphysema. TNF-α transgenic mice, a murine model of COPD in which the mice spontaneously develop emphysema with a large increase in lung volume and pulmonary hypertension, were crossed with either TNFR1-deficient mice or TNFR2-deficient mice. After 6 months, the gross appearance of the lung, lung histology, and pulmonary and cardiac physiology were determined. In addition, the relationship between apoptosis and emphysema was investigated. Pulmonary emphysema-like changes disappeared with deletion of TNFR1. However, slight improvements were attained with deletion of TNFR2. Apoptotic cells in the interstitium of the lung were observed in TNF-α transgenic mice. The apoptotic signals through TNFR1 appear critical for the pathogenesis of pulmonary emphysema. In contrast, the inflammatory process has a less important role for the development of emphysema.

  10. Normalization of CT scans reconstructed with different kernels to reduce variability in emphysema measurements

    NASA Astrophysics Data System (ADS)

    Gallardo Estrella, L.; van Ginneken, B.; van Rikxoort, E. M.

    2013-03-01

    Chronic Obstructive Pulmonary Disease (COPD) is a lung disease characterized by progressive air flow limitation caused by emphysema and chronic bronchitis. Emphysema is quantified from chest computed tomography (CT) scans as the percentage of attentuation values below a fixed threshold. The emphysema quantification varies substantially between scans reconstructed with different kernels, limiting the possibilities to compare emphysema quantifications obtained from scans with different reconstruction parameters. In this paper we propose a method to normalize scans reconstructed with different kernels to have the same characteristics as scans reconstructed with a reference kernel and investigate if this normalization reduces the variability in emphysema quantification. The proposed normalization splits a CT scan into different frequency bands based on hierarchical unsharp masking. Normalization is performed by changing the energy in each frequency band to the average energy in each band in the reference kernel. A database of 15 subjects with COPD was constructed for this study. All subjects were scanned at total lung capacity and the scans were reconstructed with four different reconstruction kernels. The normalization was applied to all scans. Emphysema quantification was performed before and after normalization. It is shown that the emphysema score varies substantially before normalization but the variation diminishes after normalization.

  11. Unicentric study of cell therapy in chronic obstructive pulmonary disease/pulmonary emphysema

    PubMed Central

    Ribeiro-Paes, João Tadeu; Bilaqui, Aldemir; Greco, Oswaldo T; Ruiz, Milton Artur; Marcelino, Monica Y; Stessuk, Talita; de Faria, Carolina A; Lago, Mario R

    2011-01-01

    Within the chronic obstructive pulmonary disease (COPD) spectrum, lung emphysema presents, as a primarily histopathologic feature, the destruction of pulmonary parenchyma and, accordingly, an increase in the airflow obstruction distal to the terminal bronchiole. Notwithstanding the significant advances in prevention and treatment of symptoms, no effective or curative therapy has been accomplished. In this context, cellular therapy with stem cells (SCs) arises as a new therapeutic approach, with a wide application potential. The purpose of this study is to evaluate the safety of SCs infusion procedure in patients with advanced COPD (stage IV dyspnea). After selection, patients underwent clinical examination and received granulocyte colony-stimulating factor, immediately prior to the bone marrow harvest. The bone marrow mononuclear cells (BMMC) were isolated and infused into a peripheral vein. The 12-month follow-up showed a significant improvement in the quality of life, as well as a clinical stable condition, which suggest a change in the natural process of the disease. Therefore, the proposed methodology in this study for BMMC cell therapy in sufferers of advanced COPD was demonstrated to be free of significant adverse effects. Although a larger sample and a greater follow-up period are needed, it is possible to infer that BMMC cell therapy introduces an unprecedented change in the course or in the natural history of emphysema, inhibiting or slowing the progression of disease. This clinical trial was registered with ClinicalTrials.gov (NCT01110252) and was approved by the Brazilian National Committee of Ethics in Research (registration no. 14764, CONEP report 233/2009). PMID:21311694

  12. Insulin modulates inflammatory and repair responses to elastase-induced emphysema in diabetic rats.

    PubMed

    Di Petta, Antonio; Greco, Karin V; Castro, Eveline O; Lopes, Fernanda D T Q S; Martins, Milton A; Capelozzi, Vera L; Moreira, Luiz F P; Sannomiya, Paulina

    2011-12-01

    As pulmonary emphysema and diabetes mellitus are common diseases, concomitance of both is correspondingly expected to occur frequently. To examine whether insulin influences the development of inflammation in the alveolar septa, diabetic male Wistar rats (alloxan, 42 mg/kg, i.v., n = 37) and matching controls (n = 31) were used. Ten days after alloxan injection, diabetic and control rats were instilled with physiologic saline solution containing porcine pancreatic elastase (PPE, 0.25 IU/0.2 ml, right lung) or saline only (left lung). The following analyses were performed: (i) number of leucocytes in the bronchoalveolar lavage (BAL) fluid of the animals, 6 h after PPE/saline instillation (early time point); and (ii) mean alveolar diameter (μm) and quantification of elastic and collagen fibres (%) 50 days after PPE/saline instillation (late time point). Relative to controls, alloxan-induced diabetic rats showed a 42% reduction in the number of neutrophils in BAL fluid, a 20% increase in the mean alveolar diameter and a 33% decrease in elastic fibre density in the alveolar septa. Treatment of diabetic rats with 4 IU neutral protamine Hagedorn (NPH) insulin, 2 h before elastase instillation, restored the number of neutrophils in the BAL fluid. The mean alveolar diameter and elastic fibre content in alveolar septa matched the values observed in control rats if diabetic rats were treated with 4 IU NPH insulin 2 h before instillation followed by 2 IU/day for the next 50 days. Density of collagen fibres did not differ between the various groups. Thus, the data presented suggest that insulin modulates the inflammatory and repair responses in elastase-induced emphysema, and assures normal repair and tissue remodelling.

  13. Unicentric study of cell therapy in chronic obstructive pulmonary disease/pulmonary emphysema.

    PubMed

    Ribeiro-Paes, João Tadeu; Bilaqui, Aldemir; Greco, Oswaldo T; Ruiz, Milton Artur; Marcelino, Monica Y; Stessuk, Talita; de Faria, Carolina A; Lago, Mario R

    2011-01-01

    Within the chronic obstructive pulmonary disease (COPD) spectrum, lung emphysema presents, as a primarily histopathologic feature, the destruction of pulmonary parenchyma and, accordingly, an increase in the airflow obstruction distal to the terminal bronchiole. Notwithstanding the significant advances in prevention and treatment of symptoms, no effective or curative therapy has been accomplished. In this context, cellular therapy with stem cells (SCs) arises as a new therapeutic approach, with a wide application potential. The purpose of this study is to evaluate the safety of SCs infusion procedure in patients with advanced COPD (stage IV dyspnea). After selection, patients underwent clinical examination and received granulocyte colony-stimulating factor, immediately prior to the bone marrow harvest. The bone marrow mononuclear cells (BMMC) were isolated and infused into a peripheral vein. The 12-month follow-up showed a significant improvement in the quality of life, as well as a clinical stable condition, which suggest a change in the natural process of the disease. Therefore, the proposed methodology in this study for BMMC cell therapy in sufferers of advanced COPD was demonstrated to be free of significant adverse effects. Although a larger sample and a greater follow-up period are needed, it is possible to infer that BMMC cell therapy introduces an unprecedented change in the course or in the natural history of emphysema, inhibiting or slowing the progression of disease. This clinical trial was registered with ClinicalTrials.gov (NCT01110252) and was approved by the Brazilian National Committee of Ethics in Research (registration no. 14764, CONEP report 233/2009).

  14. TLR4 deficiency promotes autophagy during cigarette smoke-induced pulmonary emphysema.

    PubMed

    An, Chang Hyeok; Wang, Xiao Mei; Lam, Hilaire C; Ifedigbo, Emeka; Washko, George R; Ryter, Stefan W; Choi, Augustine M K

    2012-11-01

    Toll-like receptors (TLRs) exert important nonimmune functions in lung homeostasis. TLR4 deficiency promotes pulmonary emphysema. We examined the role of TLR4 in regulating cigarette smoke (CS)-induced autophagy, apoptosis, and emphysema. Lung tissue was obtained from chronic obstructive lung disease (COPD) patients. C3H/HeJ (Tlr4-mutated) mice and C57BL/10ScNJ (Tlr4-deficient) mice and their respective control strains were exposed to chronic CS or air. Human or mouse epithelial cells (wild-type, Tlr4-knockdown, and Tlr4-deficient) were exposed to CS-extract (CSE). Samples were analyzed for TLR4 expression, and for autophagic or apoptotic proteins by Western blot analysis or confocal imaging. Chronic obstructive lung disease lung tissues and human pulmonary epithelial cells exposed to CSE displayed increased TLR4 expression, and increased autophagic [microtubule-associated protein-1 light-chain-3B (LC3B)] and apoptotic (cleaved caspase-3) markers. Beas-2B cells transfected with TLR4 siRNA displayed increased expression of LC3B relative to control cells, basally and after exposure to CSE. The basal and CSE-inducible expression of LC3B and cleaved caspase-3 were elevated in pulmonary alveolar type II cells from Tlr4-deficient mice. Wild-type mice subjected to chronic CS-exposure displayed airspace enlargement;, however, the Tlr4-mutated or Tlr4-deficient mice exhibited a marked increase in airspace relative to wild-type mice after CS-exposure. The Tlr4-mutated or Tlr4-deficient mice showed higher levels of LC3B under basal conditions and after CS exposure. The expression of cleaved caspase-3 was markedly increased in Tlr4-deficient mice exposed to CS. We describe a protective regulatory function of TLR4 against emphysematous changes of the lung in response to CS.

  15. Lung cancer risk among patients with combined pulmonary fibrosis and emphysema.

    PubMed

    Kwak, Nakwon; Park, Chang-Min; Lee, Jinwoo; Park, Young Sik; Lee, Sang-Min; Yim, Jae-Joon; Yoo, Chul-Gyu; Kim, Young Whan; Han, Sung Koo; Lee, Chang-Hoon

    2014-03-01

    Although combined pulmonary fibrosis and emphysema (CPFE) might be relevant to lung cancer, no comparison studies have been done. We evaluated the risk of lung cancer among CPFE patients compared to IPF and emphysema patients. We retrospectively reviewed the medical records of patients who were diagnosed as CPFE, IPF and emphysema using chest CT scans at Seoul National University Hospital from Jan 2000 to Dec 2011. Patients with CPFE were enrolled and matched (1:1:2) with IPF and emphysema patients based on the radiological criteria. The main outcome was time to diagnosis of lung cancer and evaluated with Cox-proportional hazard regression. Forty-eight CPFE, 48 IPF, and 96 emphysema patients were included in this study. Twenty-five cases of lung cancer occurred. The CPFE group had a higher risk of lung cancer (adjusted HR 4.62, 95% CI 1.58-13.55) than that of the emphysema group. Also, IPF group had a higher risk of lung cancer (adjusted HR 4.15, 95% CI 1.03-16.78) than that of emphysema group. However, there was no statistically significant difference in lung cancer risk between the CPFE and IPF group. Additionally, the CPFE group had a higher risk of lung cancer or death (adjusted HR 4.62, 95% CI 2.25-9.47) than that of the emphysema group. In conclusion, patients with CPFE and IPF had a higher risk of lung cancer than those with emphysema, although lung cancer risk was similar between CPFE and IPF.

  16. Mediastinal emphysema after head-banging in a rock artist: pseudo shaken-baby syndrome in adulthood.

    PubMed

    Matsuzaki, Saeko; Tsunoda, Koichi; Chong, Tonghyo; Hamaguchi, Reo

    2012-12-01

    A 34-year-old man was seen because of severe right neck pain. He was a guitarist in a special type of heavy metal rock (so-called visual-kei, a subgenre related to glam-rock) band and habitually shook his head violently throughout concert performances. He regularly experienced neck and chest pain after a concert, which persisted for some time. Computed tomography scanning of the neck showed mediastinal emphysema. We surmise that head-banging resemble those of shaken-baby syndrome.

  17. Mediastinal emphysema in mountain climbers: report of two cases and review.

    PubMed

    Vosk, A; Houston, C S

    1977-01-01

    Two cases of mediastinal emphysema occurring in healthy individuals climbing to the summit of Mount Rainier (4,393 m.) are described. In both, the condition was probably attributable to a voluntary, forced pressure breathing technique--a modified Valsalva maneuver. The various circumstances in which mediastinal emphysema may occur are discussed, along with its possible serious complication of cardiorespiratory compromise. The means of diagnosis are presented, emphasizing that cases in which the important finding of subcutaneous emphysema is absent may be those in which the danger is greatest. Therapeutic measures that occasionally may be necessary are outlined, though the condition is usually a benign one that subsides without specific treatment.

  18. Subcutaneous emphysema of the scrotum (pneumoscrotum) due to traumatic pneumothorax: a case report

    PubMed Central

    Simaioforidis, Vasileios; Kontos, Stylianos; Fokitis, Ioannis; Lefakis, Georgios; Koritsiadis, Sotirios

    2008-01-01

    Introduction Subcutaneous emphysema of the scrotum due to traumatic pneumothorax is a rare medical situation and only a few cases are reported in the literature. Case report We present the case of a 22 year old man who was admitted to the emergency department after a motorcycle accident having a painless crepitant scrotum and chest excoriations. Further evaluation revealed subcutaneous emphysema of the scrotum caused by left pneumothorax. Conclusion In conclusion, subcutaneous emphysema of the scrotum (or pneumoscrotum) due to traumatic pneumothorax is not an urgent condition and assessment should be supportive with intervention directed at the etiology, e.g. the pneumothorax. PMID:18976497

  19. Algorithm of pulmonary emphysema extraction using thoracic 3D CT images

    NASA Astrophysics Data System (ADS)

    Saita, Shinsuke; Kubo, Mitsuru; Kawata, Yoshiki; Niki, Noboru; Nakano, Yasutaka; Ohmatsu, Hironobu; Tominaga, Keigo; Eguchi, Kenji; Moriyama, Noriyuki

    2007-03-01

    Recently, due to aging and smoking, emphysema patients are increasing. The restoration of alveolus which was destroyed by emphysema is not possible, thus early detection of emphysema is desired. We describe a quantitative algorithm for extracting emphysematous lesions and quantitatively evaluate their distribution patterns using low dose thoracic 3-D CT images. The algorithm identified lung anatomies, and extracted low attenuation area (LAA) as emphysematous lesion candidates. Applying the algorithm to thoracic 3-D CT images and then by follow-up 3-D CT images, we demonstrate its potential effectiveness to assist radiologists and physicians to quantitatively evaluate the emphysematous lesions distribution and their evolution in time interval changes.

  20. Anxiety is associated with diminished exercise performance and quality of life in severe emphysema: a cross-sectional study

    PubMed Central

    2010-01-01

    Background Anxiety in patients with chronic obstructive pulmonary disease (COPD) is associated with self-reported disability. The purpose of this study is to determine whether there is an association between anxiety and functional measures, quality of life and dyspnea. Methods Data from 1828 patients with moderate to severe emphysema enrolled in the National Emphysema Treatment Trial (NETT), collected prior to rehabilitation and randomization, were used in linear regression models to test the association between anxiety symptoms, measured by the Spielberger State Trait Anxiety Inventory (STAI) and: (a) six-minute walk distance test (6 MWD), (b) cycle ergometry peak workload, (c) St. Georges Respiratory Questionnaire (SRGQ), and (d) UCSD Shortness of Breath Questionnaire (SOBQ), after controlling for potential confounders including age, gender, FEV1 (% predicted), DLCO (% predicted), and the Beck Depression Inventory (BDI). Results Anxiety was significantly associated with worse functional capacity [6 MWD (B = -0.944, p < .001), ergometry peak workload (B = -.087, p = .04)], quality of life (B = .172, p < .001) and shortness of breath (B = .180, p < .001). Regression coefficients show that a 10 point increase in anxiety score is associated with a mean decrease in 6 MWD of 9 meters, a 1 Watt decrease in peak exercise workload, and an increase of almost 2 points on both the SGRQ and SOBQ. Conclusion In clinically stable patients with moderate to severe emphysema, anxiety is associated with worse exercise performance, quality of life and shortness of breath, after accounting for the influence of demographic and physiologic factors known to affect these outcomes. Trail Registration ClinicalTrials.gov NCT00000606 PMID:20214820

  1. Long-term follow-up after bronchoscopic lung volume reduction treatment with coils in patients with severe emphysema

    PubMed Central

    Hartman, Jorine E; Klooster, Karin; Gortzak, Kiki; ten Hacken, Nick HT; Slebos, Dirk-Jan

    2015-01-01

    Background and objective Bronchoscopic lung volume reduction coil (LVR-coil) treatment has been shown to be safe and clinically effective in patients with severe emphysema in the short term; however, long-term safety and effectiveness has not been evaluated. The aim of this study was to investigate the long-term safety and effectiveness of LVR-coil treatment in patients with severe emphysema. Methods Thirty-eight patients with severe emphysema (median age is 59 years, forced expiratory volume in 1 s is 27% predicted) who were treated in LVR-coil clinical trials were invited for a voluntary annual visit. Safety was evaluated by chest X-ray and recording of adverse events and by efficacy by pulmonary function testing, 6-min walk distance (6MWD) and questionnaires. Results Thirty-five patients visited the hospital 1 year, 27 patients 2 years and 22 patients 3 years following coil placement. No coil migrations were observed on X-rays. At 1-year follow-up, all clinical outcomes significantly improved compared with baseline. At 2 years, residual volume % pred, modified Medical Research Council (mMRC) and the SGRQ score were still significantly improved. At 3 years, a significant improvement in mMRC score remained, with 40% of the patients reaching the 6MWD minimal important difference, and 59% for the St George's Respiratory Questionnaire (SGRQ) minimal important difference. Conclusions Follow-up of the patients treated with LVR-coils in our pilot studies showed that the coil treatment is safe with no late pneumothoraces, coil migrations or unexpected adverse events. Clinical benefit gradually declines over time; at 3 years post-treatment, around 50% of the patients maintained improvement in 6MWD, SGRQ and mMRC. PMID:25418910

  2. Endobronchial valves for advanced emphysema: an endobronchial follow-up.

    PubMed

    Salcedo, Pablo S; Seijo, Luis M; Zulueta, Javier J

    2014-01-01

    Lung volume reduction surgery is a therapeutic option for selected patients with advanced emphysema. However, it is an invasive procedure benefitting only a selected group of patients with heterogeneous upper lobe predominant disease and limited exercise capacity. The most widely studied alternatives are endobronchial valves. Hundreds of patients worldwide have undergone endobronchial valve placement. Although short-term outcomes have been described, little is known about the long-term side effects following this treatment, and endoscopic follow-up is virtually nonexistent. The images, biopsies, and microbiologic evidence accrued from this patient are witnesses to the natural evolution of endobronchial valves in the airways and should offer a word of caution with regard to valve placement in patients with life expectancies exceeding those typical of severe chronic obstructive lung disease.

  3. The Receptor for Advanced Glycation End Products (RAGE) Contributes to the Progression of Emphysema in Mice

    PubMed Central

    Sambamurthy, Nisha; Leme, Adriana S.; Oury, Tim D.; Shapiro, Steven D.

    2015-01-01

    Several recent clinical studies have implied a role for the receptor for advanced glycation end products (RAGE) and its variants in chronic obstructive pulmonary disease (COPD). In this study we have defined a role for RAGE in the pathogenesis of emphysema in mice. RAGE deficient mice (RAGE-/-) exposed to chronic cigarette smoke were significantly protected from smoke induced emphysema as determined by airspace enlargement and had no significant reduction in lung tissue elastance when compared to their air exposed controls contrary to their wild type littermates. The progression of emphysema has been largely attributed to an increased inflammatory cell-mediated elastolysis. Acute cigarette smoke exposure in RAGE-/- mice revealed an impaired early recruitment of neutrophils, approximately a 6-fold decrease compared to wild type mice. Hence, impaired neutrophil recruitment with continued cigarette smoke exposure reduces elastolysis and consequent emphysema. PMID:25781626

  4. [Subcutaneous emphysema, pneumomediastinum, pneumoperitoneum and retropneumoperitoneum following a colonoscopy with mucosectomy].

    PubMed

    Cirt, Nadia; de Lajarte-Thirouard, Anne-Sophie; Olivié, Damien; Pagenault, Mael; Bretagne, Jean-François

    2006-05-01

    The occurrence of associated intraperitoneal and retroperitoneal colonic perforation is uncommon after colonoscopy. We report a case of this complication revealed by subcutaneous emphysema, pneumomediastinum, pneumoperitoneum and retro-pneumoperitoneum after colonic mucosectomy.

  5. Variation compensation and analysis on diaphragm curvature analysis for emphysema quantification on whole lung CT scans

    NASA Astrophysics Data System (ADS)

    Keller, Brad M.; Reeves, Anthony P.; Barr, R. Graham; Yankelevitz, David F.; Henschke, Claudia I.

    2010-03-01

    CT scans allow for the quantitative evaluation of the anatomical bases of emphysema. Recently, a non-density based geometric measurement of lung diagphragm curvature has been proposed as a method for the quantification of emphysema from CT. This work analyzes variability of diaphragm curvature and evaluates the effectiveness of a compensation methodology for the reduction of this variability as compared to emphysema index. Using a dataset of 43 scan-pairs with less than a 100 day time-interval between scans, we find that the diaphragm curvature had a trend towards lower overall variability over emphysema index (95% CI:-9.7 to + 14.7 vs. -15.8 to +12.0), and that the variation of both measures was reduced after compensation. We conclude that the variation of the new measure can be considered comparable to the established measure and the compensation can reduce the apparent variation of quantitative measures successfully.

  6. Experimental pulmonary emphysema induced in the rat by intratracheally administered elastase: morphogenesis

    SciTech Connect

    Busch, R.H.; Lauhala, K.E.; Loscutoff, S.M.; McDonald, K.E.

    1984-01-01

    Emphysema was produced experimentally in rats by administration of porcine pancreatic elastase at dose levels of 75, 100, 125, and 150 units elastase activity/100 g body wt. All doses studied were equally effective in producing emphysema. Dose levels of over 75 units activity/100 g offered no advantage in terms of degree or severity of emphysema produced; however, such doses exacerbated hemorrhage and edema, resulting in relatively high postinstillation mortality. Lesion morphogenesis at all doses tested paralleled those described in this and in other species by other investigators. The 75-unit activity produced a quantifiable degree of emphysema which was relatively constant among animals. Results suggest that because of group differences in susceptibility to elastase (or variations in batches of elastase), dose-range studies should be performed on each new group of animals. 5 references, 8 figures.

  7. Normal expiratory flow rate and lung volumes in patients with combined emphysema and interstitial lung disease: a case series and literature review.

    PubMed

    Heathcote, Karen L; Cockcroft, Donald W; Fladeland, Derek A; Fenton, Mark E

    2011-01-01

    Pulmonary function tests in patients with idiopathic pulmonary fibrosis characteristically show a restrictive pattern including small lung volumes and increased expiratory flow rates resulting from a reduction in pulmonary compliance due to diffuse fibrosis. Conversely, an obstructive pattern with hyperinflation results in emphysema by loss of elastic recoil, expiratory collapse of the peripheral airways and air trapping. When the diseases coexist, pulmonary volumes are compensated, and a smaller than expected reduction or even normal lung volumes can be found. The present report describes 10 patients with progressive breathlessness, three of whom experienced severe limitation in their quality of life. All patients showed lung interstitial involvement and emphysema on computed tomography scan of the chest. The 10 patients showed normal spirometry and lung volumes with severe compromise of gas exchange. Normal lung volumes do not exclude diagnosis of idiopathic pulmonary fibrosis in patients with concomitant emphysema. The relatively preserved lung volumes may underestimate the severity of idiopathic pulmonary fibrosis and attenuate its effects on lung function parameters.

  8. Is lung volume reduction surgery effective in the treatment of advanced emphysema?

    PubMed

    Zahid, Imran; Sharif, Sumera; Routledge, Tom; Scarci, Marco

    2011-03-01

    A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether lung volume reduction surgery (LVRS) might be superior to medical treatment in the management of patients with severe emphysema. Overall 497 papers were found using the reported search, of which 12 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results are tabulated. We conclude that LVRS produces superior patient outcomes compared to medical treatment in terms of exercise capacity, lung function, quality of life and long-term (>1 year postoperative) survival. A large proportion of the best evidence on this topic is based on analysis of the National Emphysema Treatment Trial (NETT). Seven studies compared LVRS to medical treatment alone (MTA) using data generated by the NETT trial. They found higher quality of life scores (45.3 vs. 27.5, P<0.001), improved maximum ventilation (32.8 vs. 29.6 l/min, P=0.001) and lower exacerbation rate per person-year (0.27 vs. 0.37%, P=0.0005) with LVRS than MTA. Mortality rates for LVRS were greater up to one year (P=0.01), equivalent by three years (P=0.15) and lower after four years (P=0.06) postoperative compared to MTA. Patients with upper-lobe-predominant disease and low exercise capacity (0.36 vs. 0.54, P=0.003) benefited the most from undergoing LVRS rather than MTA in terms of probability of death at five years compared to patients with non-upper-lobe disease (0.38 vs. 0.45, P=0.03) or upper-lobe-disease with high exercise capacity (0.33 vs. 0.38, P=0.32). Five studies compared LVRS to MTA using data independent from the NETT trial. They found greater six-minute walking distances (433 vs. 300 m, P<0.002), improved total lung capacity (18.8 vs. 7.9% predicted, P<0.02) and quality of life scores (47 vs. 23.2, P<0.05) with LVRS compared to MTA. Even though LVRS has a much

  9. Pulmonary stem cells and the induction of tissue regeneration in the treatment of emphysema.

    PubMed

    Lenssen, Josephine; Stolk, Jan

    2007-01-01

    A common feature of lung disorders with poor treatment options, including emphysema, is a failure to initiate a repair process of the alveolar epithelium. Several putative stem cell niches in the lung thought to be involved in lung homeostasis have been described. Apparently, under pathophysiological conditions these resident progenitor cells are unable to recover damaged alveolar epithelium, in particular in emphysema. The potential therapeutic effect of retinoic acid receptor agonists on various resident lung progenitor cells is reviewed.

  10. Association between markers of emphysema and more severe chronic obstructive pulmonary disease

    PubMed Central

    Boschetto, P; Quintavalle, S; Zeni, E; Leprotti, S; Potena, A; Ballerin, L; Papi, A; Palladini, G; Luisetti, M; Annovazzi, L; Iadarola, P; De Rosa, E; Fabbri, L M; Mapp, C E

    2006-01-01

    Background The predominant emphysema phenotype is associated with more severe airflow limitation in patients with chronic obstructive pulmonary disease (COPD). A study was undertaken to investigate whether COPD patients, with or without emphysema quantitatively confirmed by high resolution computed tomography (HRCT), have different COPD severity as assessed by the BODE index (body mass index, airflow obstruction, dyspnoea, exercise performance) and inspiratory capacity to total lung capacity ratio (IC/TLC), and by different biological markers of lung parenchymal destruction. Methods Twenty six outpatients with COPD and eight healthy non‐smokers were examined. Each subject underwent HRCT scanning, pulmonary function tests, cell counts, and measurements of neutrophil elastase, matrix metalloproteinase (MMP)‐9 and tissue inhibitor of metalloproteinase (TIMP)‐1 in induced sputum, as well as measurement of desmosine, a marker of elastin degradation in urine, plasma and sputum. Results Patients with HRCT confirmed emphysema had a higher BODE index and lower IC/TLC ratio than subjects without HRCT confirmed emphysema and controls. Forced expiratory volume in 1 second (FEV1), FEV1/forced vital capacity ratio, and carbon monoxide transfer coefficient were lower, whereas the number of eosinophils, MMP‐9, and the MMP‐9/TIMP‐1 ratio in sputum were higher in patients with emphysema. In COPD patients the number of sputum eosinophils was the biological variable that correlated positively with the HRCT score of emphysema (p = 0.04). Conclusions These results suggest that COPD associated with HRCT confirmed emphysema is characterised by more severe lung function impairment, more intense airway inflammation and, possibly, more serious systemic dysfunction than COPD not associated with HRCT confirmed emphysema. PMID:16769715

  11. Myosin heavy chain and physiological adaptation of the rat diaphragm in elastase-induced emphysema

    PubMed Central

    Kim, Dong Kwan; Zhu, Jianliang; Kozyak, Benjamin W; Burkman, James M; Rubinstein, Neal A; Lankford, Edward B; Stedman, Hansell H; Nguyen, Taitan; Levine, Sanford; Shrager, Joseph B

    2003-01-01

    Background Several physiological adaptations occur in the respiratory muscles in rodent models of elastase-induced emphysema. Although the contractile properties of the diaphragm are altered in a way that suggests expression of slower isoforms of myosin heavy chain (MHC), it has been difficult to demonstrate a shift in MHCs in an animal model that corresponds to the shift toward slower MHCs seen in human emphysema. Methods We sought to identify MHC and corresponding physiological changes in the diaphragms of rats with elastase-induced emphysema. Nine rats with emphysema and 11 control rats were studied 10 months after instillation with elastase. MHC isoform composition was determined by both reverse transcriptase polymerase chain reaction (RT-PCR) and immunocytochemistry by using specific probes able to identify all known adult isoforms. Physiological adaptation was studied on diaphragm strips stimulated in vitro. Results In addition to confirming that emphysematous diaphragm has a decreased fatigability, we identified a significantly longer time-to-peak-tension (63.9 ± 2.7 ms versus 53.9 ± 2.4 ms). At both the RNA (RT-PCR) and protein (immunocytochemistry) levels, we found a significant decrease in the fastest, MHC isoform (IIb) in emphysema. Conclusion This is the first demonstration of MHC shifts and corresponding physiological changes in the diaphragm in an animal model of emphysema. It is established that rodent emphysema, like human emphysema, does result in a physiologically significant shift toward slower diaphragmatic MHC isoforms. In the rat, this occurs at the faster end of the MHC spectrum than in humans. PMID:12617755

  12. Severe cellulitis and abdominal wall emphysema following laparoscopic colonic surgery: A case report.

    PubMed

    Tanaka, Ryo; Kameyama, Hitoshi; Chida, Tadasu; Kanda, Tatsuo; Kano, Yosuke; Ichikawa, Hiroshi; Hanyu, Takaaki; Ishikawa, Takashi; Kosugi, Shin-Ichi; Wakai, Toshifumi

    2015-05-01

    Abdominal wall emphysema is a common complication of laparoscopic surgery. This condition is usually harmless; however, if an infection occurs, it can develop into a serious condition such as necrotizing fasciitis. We report a case of a 51-year-old woman suffering from severe cellulitis that spread from an area of abdominal wall emphysema after laparoscopic surgery for sigmoid colon cancer. Recognizing this complication, early diagnosis, and prompt treatment are cornerstones for successful management of this potentially fatal disease.

  13. Texture-based segmentation and analysis of emphysema depicted on CT images

    NASA Astrophysics Data System (ADS)

    Tan, Jun; Zheng, Bin; Wang, Xingwei; Lederman, Dror; Pu, Jiantao; Sciurba, Frank C.; Gur, David; Leader, J. Ken

    2011-03-01

    In this study we present a texture-based method of emphysema segmentation depicted on CT examination consisting of two steps. Step 1, a fractal dimension based texture feature extraction is used to initially detect base regions of emphysema. A threshold is applied to the texture result image to obtain initial base regions. Step 2, the base regions are evaluated pixel-by-pixel using a method that considers the variance change incurred by adding a pixel to the base in an effort to refine the boundary of the base regions. Visual inspection revealed a reasonable segmentation of the emphysema regions. There was a strong correlation between lung function (FEV1%, FEV1/FVC, and DLCO%) and fraction of emphysema computed using the texture based method, which were -0.433, -.629, and -0.527, respectively. The texture-based method produced more homogeneous emphysematous regions compared to simple thresholding, especially for large bulla, which can appear as speckled regions in the threshold approach. In the texture-based method, single isolated pixels may be considered as emphysema only if neighboring pixels meet certain criteria, which support the idea that single isolated pixels may not be sufficient evidence that emphysema is present. One of the strength of our complex texture-based approach to emphysema segmentation is that it goes beyond existing approaches that typically extract a single or groups texture features and individually analyze the features. We focus on first identifying potential regions of emphysema and then refining the boundary of the detected regions based on texture patterns.

  14. Proteoglycans Maintain Lung Stability in an Elastase-Treated Mouse Model of Emphysema

    PubMed Central

    Takahashi, Ayuko; Majumdar, Arnab; Parameswaran, Harikrishnan; Bartolák-Suki, Erzsébet

    2014-01-01

    Extracellular matrix remodeling and tissue rupture contribute to the progression of emphysema. Lung tissue elasticity is governed by the tensile stiffness of fibers and the compressive stiffness of proteoglycans. It is not known how proteoglycan remodeling affects tissue stability and destruction in emphysema. The objective of this study was to characterize the role of remodeled proteoglycans in alveolar stability and tissue destruction in emphysema. At 30 days after treatment with porcine pancreatic elastase, mouse lung tissue stiffness and alveolar deformation were evaluated under varying tonicity conditions that affect the stiffness of proteoglycans. Proteoglycans were stained and measured in the alveolar walls. Computational models of alveolar stability and rupture incorporating the mechanical properties of fibers and proteoglycans were developed. Although absolute tissue stiffness was only 24% of normal, changes in relative stiffness and alveolar shape distortion due to changes in tonicity were increased in emphysema (P < 0.01 and P < 0.001). Glycosaminoglycan amount per unit alveolar wall length, which is responsible for proteoglycan stiffness, was higher in emphysema (P < 0.001). Versican expression increased in the tissue, but decorin decreased. Our network model predicted that the rate of tissue deterioration locally governed by mechanical forces was reduced when proteoglycan stiffness was increased. Consequently, this general network model explains why increasing proteoglycan deposition protects the alveolar walls from rupture in emphysema. Our results suggest that the loss of proteoglycans observed in human emphysema contributes to disease progression, whereas treatments that promote proteoglycan deposition in the extracellular matrix should slow the progression of emphysema. PMID:24450478

  15. A subset of high-grade pulmonary neuroendocrine carcinomas shows up-regulation of matrix metalloproteinase-7 associated with nuclear beta-catenin immunoreactivity, independent of EGFR and HER-2 gene amplification or expression.

    PubMed

    Pelosi, Giuseppe; Scarpa, Aldo; Veronesi, Giulia; Spaggiari, Lorenzo; Del Curto, Barbara; Moore, Patrick S; Maisonneuve, Patrick; Sonzogni, Angelica; Masullo, Michele; Viale, Giuseppe

    2005-12-01

    Nuclear translocation of beta-catenin has been correlated with epidermal growth factor receptor (EGFR) overexpression/activation in non-small cell lung cancer. Less is known on beta-catenin transactivation in high-grade pulmonary neuroendocrine tumors and on the status of beta-catenin activating EGFR and human epidermal growth factor receptor 2 (HER-2) or beta-catenin target genes cyclin D1 and matrix metalloproteinase-7 (MMP-7). beta-catenin immunoreactivity was evaluated in 51 large-cell neuroendocrine carcinomas (LCNEC) and 45 small-cell lung carcinomas (SCLC). Nineteen cases were assessed for beta-catenin gene exon 3 mutations, expression of MMP-7, and expression/gene amplification of EGFR, HER-2, and cyclin D1. beta-catenin was expressed in all 96 high-grade neuroendocrine tumors, the vast majority (94%) showing >50% immunopositive cells. A disarrayed immunoreactivity, however, was commonly encountered consisting in variably altered membrane-associated patterns of staining along with progressive accumulation of cytoplasmic immunoreactivity. In LCNEC, but not in SCLC, the disarrayed patterns correlated with EGFR and HER-2 protein expression. beta-catenin nuclear accumulation was found in nine tumors, including seven LCNEC and two SCLC, and was always associated with disarrayed immunoreactivity and increased MMP-7, but not cyclin D1 expression. These cases, however, did not show beta-catenin gene mutations or EGFR and HER-2 gene amplification or expression. No association was found between nuclear beta-catenin and any clinicopathological variable including patients' survival. The subcellular compartmentalization of beta-catenin is profoundly altered in high-grade pulmonary neuroendocrine tumors. A minor subset of these tumors shows beta-catenin nuclear accumulation in association with increased expression of MMP-7, but not of cyclin D1, independent of EGFR and HER-2 gene amplification or expression.

  16. Size-based emphysema cluster analysis on low attenuation area in 3D volumetric CT: comparison with pulmonary functional test

    NASA Astrophysics Data System (ADS)

    Lee, Minho; Kim, Namkug; Lee, Sang Min; Seo, Joon Beom; Oh, Sang Young

    2015-03-01

    To quantify low attenuation area (LAA) of emphysematous regions according to cluster size in 3D volumetric CT data of chronic obstructive pulmonary disease (COPD) patients and to compare these indices with their pulmonary functional test (PFT). Sixty patients with COPD were scanned by a more than 16-multi detector row CT scanner (Siemens Sensation 16 and 64) within 0.75mm collimation. Based on these LAA masks, a length scale analysis to estimate each emphysema LAA's size was performed as follows. At first, Gaussian low pass filter from 30mm to 1mm kernel size with 1mm interval on the mask was performed from large to small size, iteratively. Centroid voxels resistant to the each filter were selected and dilated by the size of the kernel, which was regarded as the specific size emphysema mask. The slopes of area and number of size based LAA (slope of semi-log plot) were analyzed and compared with PFT. PFT parameters including DLco, FEV1, and FEV1/FVC were significantly (all p-value< 0.002) correlated with the slopes (r-values; -0.73, 0.54, 0.69, respectively) and EI (r-values; -0.84, -0.60, -0.68, respectively). In addition, the D independently contributed regression for FEV1 and FEV1/FVC (adjust R sq. of regression study: EI only, 0.70, 0.45; EI and D, 0.71, 0.51, respectively). By the size based LAA segmentation and analysis, we evaluated the Ds of area, number, and distribution of size based LAA, which would be independent factors for predictor of PFT parameters.

  17. Different proliferative capacity of lung fibroblasts obtained from control subjects and patients with emphysema.

    PubMed

    Noordhoek, Jacobien A; Postma, Dirkje S; Chong, Luis L; Vos, Johannes T W M; Kauffman, Henk F; Timens, Wim; van Straaten, Jeannette F M

    2003-07-01

    To characterize the possible role of a dysregulated proliferative capacity of pulmonary fibroblasts in insufficient tissue repair in lungs from patients with pulmonary emphysema, the authors undertook in vitro proliferative studies with pulmonary fibroblasts obtained from lung tissue of patients with emphysema. A comparison was made with fibroblasts from control subjects. The authors determined the in vitro proliferative capacity of fibroblasts at basal culture conditions and after modulation with interleukin-1beta, interferon-gamma, transforming growth factor-beta(1), and basic fibroblast growth factor. Proliferative capacity was determined by measurement of 5-bromo-2-deoxyuridine (BrdU) incorporation. BrdU incorporation by fibroblast cultures from both groups was very similar. Fibroblast cultures from control subjects, however, incorporated more BrdU after incubation with interleukin-1beta than cultures from patients with emphysema (P<.05). On the other hand, transforming growth factor-beta(1) decreased incorporation of BrdU stronger in fibroblast cultures from control subjects than from patients with emphysema (P<.05). Thus, the proliferative capacity of fibroblast cultures isolated from lung tissue of patients with pulmonary emphysema is different from that of control subjects. Although the difference is small, it may be an essential contribution to the development of pulmonary emphysema that only occurs after repeated smoke-induced injury over many years of an individual's life.

  18. Systemic and airway inflammation and the presence of emphysema in patients with COPD.

    PubMed

    Papaioannou, Andriana I; Mazioti, Argyro; Kiropoulos, Theodoros; Tsilioni, Irini; Koutsokera, Angela; Tanou, Kalliopi; Nikoulis, Dimitrios J; Georgoulias, Panagiotis; Zakynthinos, Epameinondas; Gourgoulianis, Konstantinos I; Kostikas, Konstantinos

    2010-02-01

    The aim of this study was to determine the impact of HRCT-confirmed emphysema on biomarkers evaluating airway and systemic inflammation in COPD patients. Forty-nine consecutive male COPD outpatients with stable COPD were divided in two groups according to the presence or absence of emphysema on HRCT. Patients underwent pulmonary function tests, plus assessment of exercise capacity, body composition and quality of life. Biomarkers were measured in serum (CRP, interleukin-6, TNF-alpha, leptin, adiponectin, osteocalcin, insulin growth factor-1, and systemic oxidative stress), in plasma (fibrinogen and VEGF) and in whole blood (B-type natriuretic peptide). TNF-alpha, 8-isoprostane and pH were additionally measured in exhaled breath condensate. Patients with emphysema had more severe lung function impairment, lower body-mass index and fat-free mass index, and poorer quality of life. Additionally, they presented increased systemic oxidative stress and plasma fibrinogen and lower BNP compared to patients without emphysema. After proper adjustment for disease severity, all differences remained with the exceptions of body-mass index, fat-free mass index and BNP. COPD patients with HRCT-confirmed emphysema present increased systemic oxidative stress and fibrinogen, suggesting that they may be more prone to the systemic consequences of COPD compared to patients without emphysema.

  19. Quantitative computed tomography assessment of lung structure and function in pulmonary emphysema.

    PubMed

    Madani, A; Keyzer, C; Gevenois, P A

    2001-10-01

    Accurate diagnosis and quantification of pulmonary emphysema during life is important to understand the natural history of the disease, to assess the extent of the disease, and to evaluate and follow-up therapeutic interventions. Since pulmonary emphysema is defined through pathological criteria, new methods of diagnosis and quantification should be validated by comparisons against histological references. Recent studies have addressed the capability of computed tomography (CT) to quantify pulmonary emphysema accurately. The studies reviewed in this article have been based on CT scans obtained after deep inspiration or expiration, on subjective visual grading and on objective measurements of attenuation values. Especially dedicated software was used for this purpose, which provided numerical data, on both two- and three-dimensional approaches, and compared CT data with pulmonary function tests. More recently, fractal and textural analyses were applied to computed tomography scans to assess the presence, the extent, and the types of emphysema. Quantitative computed tomography has already been used in patient selection for surgical treatment of pulmonary emphysema and in pharmacotherapeutical trials. However, despite numerous and extensive studies, this technique has not yet been standardized and important questions about how best to use computed tomography for the quantification of pulmonary emphysema are still unsolved.

  20. Emphysema and pulmonary impairment in coal miners: Quantitative relationship with dust exposure and cigarette smoking

    NASA Astrophysics Data System (ADS)

    Kuempel, E. D.; Vallyathan, V.; Green, F. H. Y.

    2009-02-01

    Coal miners have been shown to be at increased risk of developing chronic obstructive pulmonary diseases including emphysema. The objective of this study was to determine whether lifetime cumulative exposure to respirable coal mine dust is a significant predictor of developing emphysema at a clinically-relevant level of severity by the end of life, after controlling for cigarette smoking and other covariates. Clinically-relevant emphysema severity was determined from the association between individuals' lung function during life (forced expiratory volume in one second, FEV1, as a percentage of predicted normal values) and emphysema severity at autopsy (as the proportion of lung tissue affected). In a logistic regression model, cumulative exposure to respirable coal mine dust was a statistically significant predictor of developing clinically-relevant emphysema severity, among both ever-smokers and never-smokers. The odds ratio for developing emphysema associated with FEV1 <80% at the cohort mean cumulative coal dust exposure (87 mg/m3 x yr) was 2.30 (1.46-3.64, 95% confidence limits), and at the cohort mean cigarette smoking (among smokers: 42 pack-years) was 1.95 (1.39-2.79).

  1. Adaptive quantification and longitudinal analysis of pulmonary emphysema with a hidden Markov measure field model.

    PubMed

    Hame, Yrjo; Angelini, Elsa D; Hoffman, Eric A; Barr, R Graham; Laine, Andrew F

    2014-07-01

    The extent of pulmonary emphysema is commonly estimated from CT scans by computing the proportional area of voxels below a predefined attenuation threshold. However, the reliability of this approach is limited by several factors that affect the CT intensity distributions in the lung. This work presents a novel method for emphysema quantification, based on parametric modeling of intensity distributions and a hidden Markov measure field model to segment emphysematous regions. The framework adapts to the characteristics of an image to ensure a robust quantification of emphysema under varying CT imaging protocols, and differences in parenchymal intensity distributions due to factors such as inspiration level. Compared to standard approaches, the presented model involves a larger number of parameters, most of which can be estimated from data, to handle the variability encountered in lung CT scans. The method was applied on a longitudinal data set with 87 subjects and a total of 365 scans acquired with varying imaging protocols. The resulting emphysema estimates had very high intra-subject correlation values. By reducing sensitivity to changes in imaging protocol, the method provides a more robust estimate than standard approaches. The generated emphysema delineations promise advantages for regional analysis of emphysema extent and progression.

  2. Therapeutic effects of LASSBio-596 in an elastase-induced mouse model of emphysema

    PubMed Central

    Padilha, Gisele A.; Henriques, Isabela; Lopes-Pacheco, Miquéias; Abreu, Soraia C.; Oliveira, Milena V.; Morales, Marcelo M.; Lima, Lidia M.; Barreiro, Eliezer J.; Silva, Pedro L.; Xisto, Debora G.; Rocco, Patricia R. M.

    2015-01-01

    Emphysema is an intractable pulmonary disease characterized by an inflammatory process of the airways and lung parenchyma and ongoing remodeling process in an attempt to restore lung structure. There is no effective drug therapy that regenerates lung tissue or prevents the progression of emphysema; current treatment is aimed at symptomatic relief. We hypothesized that LASSBio-596, a molecule with potent anti-inflammatory and immunomodulatory effects, might reduce pulmonary inflammation and remodeling and thus improve lung function in experimental emphysema. Emphysema was induced in BALB/c mice by intratracheal administration of porcine pancreatic elastase (0.1 IU) once weekly during 4 weeks. A control group received saline using the same protocol. After the last instillation of saline or elastase, dimethyl sulfoxide, or LASSBio-596 were administered intraperitoneally, once daily for 8 days. After 24 h, in elastase-induced emphysema animals, LASSBio-596 yielded: (1) decreased mean linear intercept, hyperinflation and collagen fiber content, (2) increased elastic fiber content, (3) reduced number of M1 macrophages, (4) decreased tumor necrosis factor-α, interleukin-1β, interleukin-6, and transforming growth factor-β protein levels in lung tissue, and increased vascular endothelial growth factor. These changes resulted in increased static lung elastance. In conclusion, LASSBio-596 therapy reduced lung inflammation, airspace enlargement, and small airway wall remodeling, thus improving lung function, in this animal model of elastase-induced emphysema. PMID:26483698

  3. "The Show"

    ERIC Educational Resources Information Center

    Gehring, John

    2004-01-01

    For the past 16 years, the blue-collar city of Huntington, West Virginia, has rolled out the red carpet to welcome young wrestlers and their families as old friends. They have come to town chasing the same dream for a spot in what many of them call "The Show". For three days, under the lights of an arena packed with 5,000 fans, the…

  4. Oxidative and proteolysis-related parameters of skeletal muscle from hamsters with experimental pulmonary emphysema: a comparison between papain and elastase induction.

    PubMed

    Brunnquell, Cláudia R; Vieira, Nichelle A; Sábio, Laís R; Sczepanski, Felipe; Cecchini, Alessandra L; Cecchini, Rubens; Guarnier, Flávia A

    2015-06-01

    The objective of this study was to investigate whether emphysema induced by elastase or papain triggers the same effects on skeletal muscle, related to oxidative stress and proteolysis, in hamsters. For this purpose, we evaluated pulmonary lesions, body weight, muscle loss, oxidative stress (thiobarbituric acid-reactive substances, total and oxidized glutathiones, chemiluminescence stimulated by tert-butyl hydroperoxide and carbonyl proteins), chymotrypsin-like and calpain-like proteolytic activities and muscle fibre cross-sectional area in the gastrocnemius muscles of emphysemic hamsters. Two groups of animals received different intratracheal inductions of experimental emphysema: by 40 mg/ml papain (EP) or 5.2 IU/100 g animal (EE) elastase (n = 10 animals/group). The control group received intratracheal instillation of 300 μl sterile NaCl 0.9%. Compared with the control group, the EP group had reduced muscle weight (18.34%) and the EE group had increased muscle weight (8.37%). Additionally, tert-butyl hydroperoxide-initiated chemiluminescence, carbonylated proteins and chymotrypsin-like proteolytic activity were all elevated in the EP group compared to the CS group, while total glutathione was decreased compared to the EE group. The EE group showed more fibres with increased cross-sectional areas and increased calpain-like activity. Together, these data show that elastase and papain, when used to induce experimental models of emphysema, lead to different speeds and types of adaptation. These findings provide more information on choosing a suitable experimental model for studying skeletal muscle adaptations in emphysema.

  5. Oxidative and proteolysis-related parameters of skeletal muscle from hamsters with experimental pulmonary emphysema: a comparison between papain and elastase induction

    PubMed Central

    Brunnquell, Cláudia R; Vieira, Nichelle A; Sábio, Laís R; Sczepanski, Felipe; Cecchini, Alessandra L; Cecchini, Rubens; Guarnier, Flávia A

    2015-01-01

    The objective of this study was to investigate whether emphysema induced by elastase or papain triggers the same effects on skeletal muscle, related to oxidative stress and proteolysis, in hamsters. For this purpose, we evaluated pulmonary lesions, body weight, muscle loss, oxidative stress (thiobarbituric acid-reactive substances, total and oxidized glutathiones, chemiluminescence stimulated by tert-butyl hydroperoxide and carbonyl proteins), chymotrypsin-like and calpain-like proteolytic activities and muscle fibre cross-sectional area in the gastrocnemius muscles of emphysemic hamsters. Two groups of animals received different intratracheal inductions of experimental emphysema: by 40 mg/ml papain (EP) or 5.2 IU/100 g animal (EE) elastase (n = 10 animals/group). The control group received intratracheal instillation of 300 μl sterile NaCl 0.9%. Compared with the control group, the EP group had reduced muscle weight (18.34%) and the EE group had increased muscle weight (8.37%). Additionally, tert-butyl hydroperoxide-initiated chemiluminescence, carbonylated proteins and chymotrypsin-like proteolytic activity were all elevated in the EP group compared to the CS group, while total glutathione was decreased compared to the EE group. The EE group showed more fibres with increased cross-sectional areas and increased calpain-like activity. Together, these data show that elastase and papain, when used to induce experimental models of emphysema, lead to different speeds and types of adaptation. These findings provide more information on choosing a suitable experimental model for studying skeletal muscle adaptations in emphysema. PMID:26102076

  6. Pathogenesis and management of virus infection-induced exacerbation of senile bronchial asthma and chronic pulmonary emphysema.

    PubMed

    Yamaya, Metstuo

    2002-06-01

    The number of senile patients with therapy resistant bronchial asthma, chronic pulmonary emphysema increases due to the habit of smoking and increased number of older people, and these inflammatory pulmonary diseases are the leading causes of death worldwide. Rhinoviruses cause the majority of common colds, and provoke exacerbations of bronchial asthma and chronic pulmonary emphysema. Here, I review the pathogenesis and management of rhinovirus infection-induced exacerbation of senile bronchial asthma and chronic pulmonary emphysema.

  7. Extracellular vesicles derived from Gram-negative bacteria, such as Escherichia coli, induce emphysema mainly via IL-17A-mediated neutrophilic inflammation.

    PubMed

    Kim, You-Sun; Lee, Won-Hee; Choi, Eun-Jeong; Choi, Jun-Pyo; Heo, Young Joo; Gho, Yong Song; Jee, Young-Koo; Oh, Yeon-Mok; Kim, Yoon-Keun

    2015-04-01

    Recent evidence indicates that Gram-negative bacteria-derived extracellular vesicles (EVs) in indoor dust can evoke neutrophilic pulmonary inflammation, which is a key pathology of chronic obstructive pulmonary disease (COPD). Escherichia coli is a ubiquitous bacterium present in indoor dust and secretes nanometer-sized vesicles into the extracellular milieu. In the current study, we evaluated the role of E. coli-derived EVs on the development of COPD, such as emphysema. E. coli EVs were prepared by sequential ultrafiltration and ultracentrifugation. COPD phenotypes and immune responses were evaluated in C57BL/6 wild-type (WT), IFN-γ-deficient, or IL-17A-deficient mice after airway exposure to E. coli EVs. The present study showed that indoor dust from a bed mattress harbors E. coli EVs. Airway exposure to E. coli EVs increased the production of proinflammatory cytokines, such as TNF-α and IL-6. In addition, the repeated inhalation of E. coli EVs for 4 wk induced neutrophilic inflammation and emphysema, which are associated with enhanced elastase activity. Emphysema and elastase activity enhanced by E. coli EVs were reversed by the absence of IFN-γ or IL-17A genes. In addition, during the early period, lung inflammation is dependent on IL-17A and TNF-α, but not on IFN-γ, and also on TLR4. Moreover, the production of IFN-γ is eliminated by the absence of IL-17A, whereas IL-17A production is not abolished by IFN-γ absence. Taken together, the present data suggest that E. coli-derived EVs induce IL-17A-dependent neutrophilic inflammation and thereby emphysema, possibly via upregulation of elastase activity.

  8. IL-21 is increased in peripheral blood of emphysema mice and promotes Th1/Tc1 cell generation in vitro.

    PubMed

    Duan, Minchao; Huang, Ying; Zhong, Xiaoning; Tang, Haijuan

    2014-06-01

    Interleukin-21 (IL-21) has been reported to be involved in many Th1-associated diseases. However, the alteration and immune regulation of IL-21 in emphysema remains unknown. In this study, we tested the levels of IFN-γ and IL-21 and the frequencies of Th1 and Tc1 in peripheral blood from cigarette smoke (CS)-exposed mice and air-exposed mice and explored the effect of IL-21 on generation of Th1 and Tc1 cells in vitro. It was found that the levels of IFN-γ and IL-21 and the frequencies of Th1, Tc1, CD4(+) IL-21(+), CD4(+) IL-21R(+), and CD8(+) IL-21R(+) T cells were much higher in CS-exposed mice. Moreover, the levels of IL-21 were correlated positively with Th1 cells and with Tc1 cells. Finally, the in vitro experiments showed that IL-21 could promote Th1/Tc1 cell generation in CS-exposed mice. These results indirectly provide evidence that IL-21 produced by CD4(+) T cells could promote Th1/Tc1 response, leading to systemic inflammation in emphysema.

  9. Addition of açaí (Euterpe oleracea) to cigarettes has a protective effect against emphysema in mice.

    PubMed

    de Moura, Roberto Soares; Pires, Karla Maria Pereira; Santos Ferreira, Thiago; Lopes, Alan Aguiar; Nesi, Renata Tiscoski; Resende, Angela Castro; Sousa, Pergentino Jose Cunha; da Silva, Antonio Jorge Ribeiro; Porto, Luis Cristóvão; Valenca, Samuel Santos

    2011-04-01

    Chronic inhalation of cigarette smoke (CS) induces emphysema by the damage contributed by oxidative stress during inhalation of CS. Ingestion of açai fruits (Euterpe oleracea) in animals has both antioxidant and anti-inflammatory effects. This study compared lung damage in mice induced by chronic (60-day) inhalation of regular CS and smoke from cigarettes containing 100mg of hydroalcoholic extract of açai berry stone (CS + A). Sham smoke-exposed mice served as the control group. Mice were sacrificed on day 60, bronchoalveolar lavage was performed, and the lungs were removed for histological and biochemical analyses. Histopathological investigation showed enlargement of alveolar space in CS mice compared to CS + A and control mice. The increase in leukocytes in the CS group was higher than the increase observed in the CS + A group. Oxidative stress, as evaluated by antioxidant enzyme activities, mieloperoxidase, glutathione, and 4-hydroxynonenal, was reduced in mice exposed to CS+A versus CS. Macrophage and neutrophil elastase levels were reduced in mice exposed to CS + A versus CS. Thus, the presence of açai extract in cigarettes had a protective effect against emphysema in mice, probably by reducing oxidative and inflammatory reactions. These results raise the possibility that addition of açaí extract to normal cigarettes could reduce their harmful effects.

  10. Understanding independence

    NASA Astrophysics Data System (ADS)

    Annan, James; Hargreaves, Julia

    2016-04-01

    In order to perform any Bayesian processing of a model ensemble, we need a prior over the ensemble members. In the case of multimodel ensembles such as CMIP, the historical approach of ``model democracy'' (i.e. equal weight for all models in the sample) is no longer credible (if it ever was) due to model duplication and inbreeding. The question of ``model independence'' is central to the question of prior weights. However, although this question has been repeatedly raised, it has not yet been satisfactorily addressed. Here I will discuss the issue of independence and present a theoretical foundation for understanding and analysing the ensemble in this context. I will also present some simple examples showing how these ideas may be applied and developed.

  11. Predictors of Mortality in Patients with Emphysema and Severe Airflow Obstruction

    PubMed Central

    Martinez, Fernando J.; Foster, Gregory; Curtis, Jeffrey L.; Criner, Gerard; Weinmann, Gail; Fishman, Alfred; DeCamp, Malcolm M.; Benditt, Joshua; Sciurba, Frank; Make, Barry; Mohsenifar, Zab; Diaz, Philip; Hoffman, Eric; Wise, Robert

    2006-01-01

    Purpose: Limited data exist describing risk factors for mortality in patients having predominantly emphysema. Subjects and Methods: A total of 609 patients with severe emphysema (ages 40–83 yr; 64.2% male) randomized to the medical therapy arm of the National Emphysema Treatment Trial formed the study group. Cox proportional hazards regression analysis was used to investigate risk factors for all-cause mortality. Risk factors examined included demographics, body mass index, physiologic data, quality of life, dyspnea, oxygen utilization, hemoglobin, smoking history, quantitative emphysema markers on computed tomography, and a modification of a recently described multifunctional index (modified BODE). Results: Overall, high mortality was seen in this cohort (12.7 deaths per 100 person-years; 292 total deaths). In multivariate analyses, increasing age (p = 0.001), oxygen utilization (p = 0.04), lower total lung capacity % predicted (p = 0.05), higher residual volume % predicted (p = 0.04), lower maximal cardiopulmonary exercise testing workload (p = 0.002), greater proportion of emphysema in the lower lung zone versus the upper lung zone (p = 0.005), and lower upper-to-lower-lung perfusion ratio (p = 0.007), and modified BODE (p = 0.02) were predictive of mortality. FEV1 was a significant predictor of mortality in univariate analysis (p = 0.005), but not in multivariate analysis (p = 0.21). Conclusion: Although patients with advanced emphysema experience significant mortality, subgroups based on age, oxygen utilization, physiologic measures, exercise capacity, and emphysema distribution identify those at increased risk of death. PMID:16543549

  12. Coactivator-Associated Arginine Methyltransferase-1 Function in Alveolar Epithelial Senescence and Elastase-Induced Emphysema Susceptibility.

    PubMed

    Sarker, Rim S J; John-Schuster, Gerrit; Bohla, Alexander; Mutze, Kathrin; Burgstaller, Gerald; Bedford, Mark T; Königshoff, Melanie; Eickelberg, Oliver; Yildirim, Ali Ö

    2015-12-01

    Chronic obstructive pulmonary disease (COPD) is characterized by an irreversible loss of lung function and is one of the most prevalent and severe diseases worldwide. A major feature of COPD is emphysema, which is the progressive loss of alveolar tissue. Coactivator-associated arginine methyltransferase-1 (CARM1) regulates histone methylation and the transcription of genes involved in senescence, proliferation, and differentiation. Complete loss of CARM1 leads to disrupted differentiation and maturation of alveolar epithelial type II (ATII) cells. We thus hypothesized that CARM1 regulates the development and progression of emphysema. To address this, we investigated the contribution of CARM1 to alveolar rarefication using the mouse model of elastase-induced emphysema in vivo and small interfering (si)RNA-mediated knockdown in ATII-like LA4 cells in vitro. We demonstrate that emphysema progression in vivo is associated with a time-dependent down-regulation of CARM1. Importantly, elastase-treated CARM1 haploinsufficient mice show significantly increased airspace enlargement (52.5 ± 9.6 μm versus 38.8 ± 5.5 μm; P < 0.01) and lung compliance (2.8 ± 0.32 μl/cm H2O versus 2.4 ± 0.4 μl/cm H2O; P < 0.04) compared with controls. The knockdown of CARM1 in LA4 cells led to decreased sirtuin 1 expression (0.034 ± 0.003 versus 0.022 ± 0.001; P < 0.05) but increased expression of p16 (0.27 ± 0.013 versus 0.31 ± 0.010; P < 0.5) and p21 (0.81 ± 0.088 versus 1.28 ± 0.063; P < 0.01) and higher β-galactosidase-positive senescent cells (50.57 ± 7.36% versus 2.21 ± 0.34%; P < 0.001) compared with scrambled siRNA. We further demonstrated that CARM1 haploinsufficiency impairs transdifferentiation and wound healing (32.18 ± 0.9512% versus 8.769 ± 1.967%; P < 0.001) of alveolar epithelial cells. Overall, these results reveal a novel function of CARM1 in regulating emphysema development

  13. Low cost biological lung volume reduction therapy for advanced emphysema

    PubMed Central

    Bakeer, Mostafa; Abdelgawad, Taha Taha; El-Metwaly, Raed; El-Morsi, Ahmed; El-Badrawy, Mohammad Khairy; El-Sharawy, Solafa

    2016-01-01

    Background Bronchoscopic lung volume reduction (BLVR), using biological agents, is one of the new alternatives to lung volume reduction surgery. Objectives To evaluate efficacy and safety of biological BLVR using low cost agents including autologous blood and fibrin glue. Methods Enrolled patients were divided into two groups: group A (seven patients) in which autologous blood was used and group B (eight patients) in which fibrin glue was used. The agents were injected through a triple lumen balloon catheter via fiberoptic bronchoscope. Changes in high resolution computerized tomography (HRCT) volumetry, pulmonary function tests, symptoms, and exercise capacity were evaluated at 12 weeks postprocedure as well as for complications. Results In group A, at 12 weeks postprocedure, there was significant improvement in the mean value of HRCT volumetry and residual volume/total lung capacity (% predicted) (P-value: <0.001 and 0.038, respectively). In group B, there was significant improvement in the mean value of HRCT volumetry and (residual volume/total lung capacity % predicted) (P-value: 0.005 and 0.004, respectively). All patients tolerated the procedure with no mortality. Conclusion BLVR using autologous blood and locally prepared fibrin glue is a promising method for therapy of advanced emphysema in term of efficacy, safety as well as cost effectiveness. PMID:27536091

  14. [Lung transplantation for pulmonary emphysema--who, when, how?].

    PubMed

    Schreder, T; Gottlieb, J

    2010-10-01

    End stage pulmonary emphysema is the most common indication for lung transplantation worldwide. The shortness of donor organs and the better natural prognosis compared to other diseases leading to transplantation such as pulmonary fibrosis and cystic fibrosis demands careful patient selection.Lung transplantation is considered in patients with declining lung function after receiving all conservative treatment options including smoking cessation and rehabilitation programmes. Preoperative evaluation using consensus criteria needs to be performed by a multidisciplinary team in specialized centres. Assessment of co-morbidities is crucial, as they may significantly increase transplant-related mortality. The largest survival advantage from lung transplantation has been shown for the subgroup of patients below 60 years of age presenting with end-stage obstructive lung disease (FEV1 < 20% predicted) and respiratory failure. Similarly, high risk patients with secondary pulmonary hypertension or cachexia (BMI < 20) will likely benefit from transplantation.The 5-year-survival rate averages 60 percent, with superior outcome following double versus single lung transplantation. A clear survival benefit can only be achieved in a subgroup of patients, whereas the impact on quality of life seems to be even more important in patients suffering from chronic obstructive pulmonary disease.

  15. Active relearning for robust supervised classification of pulmonary emphysema

    NASA Astrophysics Data System (ADS)

    Raghunath, Sushravya; Rajagopalan, Srinivasan; Karwoski, Ronald A.; Bartholmai, Brian J.; Robb, Richard A.

    2012-03-01

    Radiologists are adept at recognizing the appearance of lung parenchymal abnormalities in CT scans. However, the inconsistent differential diagnosis, due to subjective aggregation, mandates supervised classification. Towards optimizing Emphysema classification, we introduce a physician-in-the-loop feedback approach in order to minimize uncertainty in the selected training samples. Using multi-view inductive learning with the training samples, an ensemble of Support Vector Machine (SVM) models, each based on a specific pair-wise dissimilarity metric, was constructed in less than six seconds. In the active relearning phase, the ensemble-expert label conflicts were resolved by an expert. This just-in-time feedback with unoptimized SVMs yielded 15% increase in classification accuracy and 25% reduction in the number of support vectors. The generality of relearning was assessed in the optimized parameter space of six different classifiers across seven dissimilarity metrics. The resultant average accuracy improved to 21%. The co-operative feedback method proposed here could enhance both diagnostic and staging throughput efficiency in chest radiology practice.

  16. Comparison of changes in hemodynamics between unilateral and bilateral lung volume reduction for pulmonary emphysema.

    PubMed

    Koizumi, K; Haraguchi, S; Akiyama, H; Hirata, T; Hirai, K; Mikami, I; Tanaka, S

    2001-10-01

    This study was aimed to compare changes in hemodynamics between unilateral (UL) or simultaneous bilateral (BL) lung volume reduction surgery (LVRS) for chronic obstructive lung disease. Sixteen patients underwent LVRS by stapler resection with neodymium: yttrium-alminum-garnet (Nd: YAG) laser ablation; five underwent BL-LVRS (four by median sternotomy and one by thoracoscopy) and 11 underwent UL-LVRS by thoracoscopy. Four patients had multiple bullae within pulmonary emphysema. At preoperation and 6, 12, 24, and 48 hours postoperatively, hemodynamics and right ventricular performance were evaluated. UL- and BL-LVRS reduced afterload of the right and left ventricle postoperatively. Although the pulmonary arterial resistance increased after surgery, the total pulmonary resistance decreased (p=0.001) in association with the reduced systemic vascular resistance (p=0.001). These reductions improved cardiopulmonary circulation, resulting in increased stroke volume and cardiac output (p=0.003). The right ventricular ejection fraction showed minimal change 48 hours postoperation. Two patients died of pneumonia caused by persistent air leakage. In conclusion, both the UL- and BL-LVRS showed similar effectiveness in terms of improvement in the systemic and cardiopulmonary circulation after LVRS, if there were no postoperative complications. We concluded that we had to reduce and repair the persistent air leakage after LVRS.

  17. Effects of Diffusion Time on Short-Range Hyperpolarized 3He Diffusivity Measurements in Emphysema

    PubMed Central

    Gierada, David S.; Woods, Jason C.; Bierhals, Andrew J.; Bartel, Seth T.; Ritter, Jon H.; Choong, Cliff K.; Das, Nitin A.; Hong, Cheng; Pilgram, Thomas K.; Chang, Yulin V.; Jacob, Richard E.; Hogg, James C.; Battafarano, Richard J.; Cooper, Joel D.; Meyers, Bryan F.; Patterson, G. Alexander; Yablonskiy, Dmitriy A.; Conradi, Mark S.

    2010-01-01

    Purpose To characterize the effect of diffusion time on short-range hyperpolarized 3He MR diffusion measurements across a wide range of emphysema severity. Materials and Methods 3He diffusion MR imaging was performed on 19 lungs or lobes resected from 18 subjects with varying degrees of emphysema using 3 diffusion times (1.6 msec, 5 msec, and 10 msec) at constant b value. Emphysema severity was quantified as the mean apparent diffusion coefficient (ADC) and as the percentage of pixels with ADC higher than multiple thresholds from 0.30–0.55 cm2/sec (ADC index). Quantitative histology (mean linear intercept) was obtained in 10 of the lung specimens from 10 of the subjects. Results The mean ADCs with diffusion times of 1.6, 5.0, and 10.0 msec were 0.46, 0.40, and 0.37 cm2/sec, respectively (P <0.0001, ANOVA). There was no relationship between the ADC magnitude and the effect of diffusion time on ADC values. Mean linear intercept correlated with ADC (r=0.91–0.94, P<0.001) and ADC index (r=0.78–0.92, P<0.01) at all diffusion times. Conclusion Decreases in ADC with longer diffusion time were unrelated to emphysema severity. The strong correlations between the ADC at all diffusion times tested and quantitative histology demonstrate that the ADC is a robust measure of emphysema. PMID:19787725

  18. Keratinocyte growth factor protects against elastase-induced pulmonary emphysema in mice.

    PubMed

    Plantier, Laurent; Marchand-Adam, Sylvain; Antico Arciuch, Valeria G; Antico, Valeria G; Boyer, Laurent; De Coster, Cécile; Marchal, Joëlle; Bachoual, Rafik; Mailleux, Arnaud; Boczkowski, Jorge; Crestani, Bruno

    2007-11-01

    Pulmonary emphysema is characterized by persistent inflammation and progressive alveolar destruction. The keratinocyte growth factor (KGF) favorably influences alveolar maintenance and repair and possesses anti-inflammatory properties. We aimed to determine whether exogenous KGF prevented or corrected elastase-induced pulmonary emphysema in vivo. Treatment with 5 mg x kg(-1) x day(-1) KGF before elastase instillation prevented pulmonary emphysema. This effect was associated with 1) a sharp reduction in bronchoalveolar lavage fluid total protein and inflammatory cell recruitment, 2) a reduction in the pulmonary expression of the chemokines CCL2 (or monocyte chemoattractant protein-1) and CXCL2 (or macrophage inflammatory protein-2alpha) and of the adhesion molecules ICAM-1 and VCAM-1, 3) a reduction in matrix metalloproteinase (MMP)-2 and MMP-9 activity at day 3, and 4) a major reduction in DNA damage detected by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) in alveolar cells at day 7. Treatment with KGF after elastase instillation had no effect on elastase-induced emphysema despite the conserved expression of the KGF receptor in the lungs of elastase-instilled animals as determined by immunohistochemistry. In vitro, KGF abolished the elastase-induced increase in CCL2, CXCL2, and ICAM-1 mRNA in the MLE-12 murine alveolar epithelial cell line. We conclude that KGF pretreatment protected against elastase-induced pulmonary inflammation, activation of MMPs, alveolar cell DNA damage, and subsequent emphysema in mice.

  19. Influence of preexisting pulmonary emphysema on susceptibility of rats to inhaled diesel exhaust

    SciTech Connect

    Mauderly, J.L.; Bice, D.E.; Cheng, Y.S.; Gillett, N.A.; Griffith, W.C.; Henderson, R.F.; Pickrell, J.A.; Wolff, R.K. )

    1990-05-01

    The susceptibilities of normal rats and rats with preexisting pulmonary emphysema to chronically inhaled diesel exhaust were compared. Rats were exposed 7 h/day, 5 days/wk for 24 months to diesel exhaust at 3.5 mg soot/m3, or to clean air as controls. Emphysema was induced in one-half of the rats by intratracheal instillation of elastase 6 wk before exhaust exposure. Measurements included lung burdens of diesel soot, respiratory function, bronchoalveolar lavage, clearance of radiolabeled particles, pulmonary immune responses, lung collagen, excised lung weight and volume, histopathology, and mean linear intercept of terminal air spaces. Parameters indicated by analysis of variance to exhibit significant interactions between the influences of emphysema and exhaust were examined to determine if the effects were more than additive (indicating increased susceptibility). Although 14 of 63 parameters demonstrated emphysema-exhaust interactions, none indicated increased susceptibility. Less soot accumulated in lungs of emphysematous rats than in those of nonemphysematous rats, and the reduced accumulation had a sparing effect in the emphysematous rats. The results did not support the hypothesis that emphysematous lungs are more susceptible than are normal lungs to chronic exposure to high levels of diesel exhaust. The superimposition of effects of emphysema and exhaust, however, might still warrant special concern for heavy exposures of emphysematous subjects.

  20. Pulmonary emphysema classification based on an improved texton learning model by sparse representation

    NASA Astrophysics Data System (ADS)

    Zhang, Min; Zhou, Xiangrong; Goshima, Satoshi; Chen, Huayue; Muramatsu, Chisako; Hara, Takeshi; Yokoyama, Ryujiro; Kanematsu, Masayuki; Fujita, Hiroshi

    2013-03-01

    In this paper, we present a texture classification method based on texton learned via sparse representation (SR) with new feature histogram maps in the classification of emphysema. First, an overcomplete dictionary of textons is learned via KSVD learning on every class image patches in the training dataset. In this stage, high-pass filter is introduced to exclude patches in smooth area to speed up the dictionary learning process. Second, 3D joint-SR coefficients and intensity histograms of the test images are used for characterizing regions of interest (ROIs) instead of conventional feature histograms constructed from SR coefficients of the test images over the dictionary. Classification is then performed using a classifier with distance as a histogram dissimilarity measure. Four hundreds and seventy annotated ROIs extracted from 14 test subjects, including 6 paraseptal emphysema (PSE) subjects, 5 centrilobular emphysema (CLE) subjects and 3 panlobular emphysema (PLE) subjects, are used to evaluate the effectiveness and robustness of the proposed method. The proposed method is tested on 167 PSE, 240 CLE and 63 PLE ROIs consisting of mild, moderate and severe pulmonary emphysema. The accuracy of the proposed system is around 74%, 88% and 89% for PSE, CLE and PLE, respectively.

  1. Segmental bronchi collapsibility: computed tomography-based quantification in patients with chronic obstructive pulmonary disease and correlation with emphysema phenotype, corresponding lung volume changes and clinical parameters

    PubMed Central

    Thaiss, Wolfgang Maximilian; Ditt, Hendrik; Hetzel, Jürgen; Schülen, Eva; Nikolaou, Konstantin; Horger, Marius

    2016-01-01

    Background Global pulmonary function tests lack region specific differentiation that might influence therapy in severe chronic obstructive pulmonary disease (COPD) patients. Therefore, the aim of this work was to assess the degree of expiratory 3rd generation bronchial lumen collapsibility in patients with severe COPD using chest-computed tomography (CT), to evaluate emphysema-phenotype, lobar volumes and correlate results with pulmonary function tests. Methods Thin-slice chest-CTs acquired at end-inspiration & end-expiration in 42 COPD GOLD IV patients (19 females, median-age: 65.9 y) from November 2011 to July 2014 were re-evaluated. The cross-sectional area of all segmental bronchi was measured 5 mm below the bronchial origin in both examinations. Lung lobes were semi-automatically segmented, volumes calculated at end-inspiratory and end-expiratory phase and visually defined emphysema-phenotypes defined. Results of CT densitometry were compared with lung functional tests including forced expiratory volume at 1 s (FEV1), total lung capacity (TLC), vital capacity (VC), residual volume (RV), diffusion capacity parameters and the maximal expiratory flow rates (MEFs). Results Mean expiratory bronchial collapse was 31%, stronger in lobes with homogenous (38.5%) vs. heterogeneous emphysema-phenotype (27.8%, P=0.014). The mean lobar expiratory volume reduction was comparable in both emphysema-phenotypes (volume reduction 18.6%±8.3% in homogenous vs. 17.6%±16.5% in heterogeneous phenotype). The degree of bronchial lumen collapsibility, did not correlate with expiratory volume reduction. MEF25 correlated weakly with 3rd generation airway collapsibility (r=0.339, P=0.03). All patients showed a concentric expiratory reduction of bronchial cross-sectional area. Conclusions Changes in collapsibility of 3rd generation bronchi in COPD grade IV patients is significantly lower than that in the trachea and the main bronchi. Collapsibility did not correlate with the reduction in

  2. Perforation of an Occult Carcinoma of the Prostate as a Rare Differential Diagnosis of Subcutaneous Emphysema of the Leg

    PubMed Central

    Hockertz, Thomas

    2016-01-01

    We report a case of subcutaneous emphysema caused by perforation of the rectum due to a carcinoma of the prostate. Although rare, an abdominal cause must always be considered as a rare differential diagnosis of subcutaneous emphysema. As a matter of fact adequate diagnostic with rapid treatment is essential for the outcome. PMID:27597913

  3. Contributions of dust exposure and cigarette smoking to emphysema severity in coal miners in the United States

    SciTech Connect

    Kuempel, E.D.; Wheeler, M.W.; Smith, R.J.; Vallyathan, V.; Green, F.H.Y.

    2009-08-15

    Previous studies have shown associations between dust exposure or lung burden and emphysema in coal miners, although the separate contributions of various predictors have not been clearly demonstrated. The objective was to quantitatively evaluate the relationship between cumulative exposure to respirable coal mine dust, cigarette smoking, and other factors on emphysema severity. The study group included 722 autopsied coal miners and nonminers in the United States. Data on work history, smoking, race, and age at death were obtained from medical records and questionnaire completed by next-of-kin. Emphysema was classified and graded using a standardized schema. Job-specific mean concentrations of respirable coal mine dust were matched with work histories to estimate cumulative exposure. Relationships between various metrics of dust exposure (including cumulative exposure and lung dust burden) and emphysema severity were investigated in weighted least squares regression models. Emphysema severity was significantly elevated in coal miners compared with nonminers among ever- and never-smokers (P < 0.0001). Cumulative exposure to respirable coal mine dust or coal dust retained in the lungs were significant predictors of emphysema severity (P < 0.0001) after accounting for cigarette smoking, age at death, and race. The contributions of coal mine dust exposure and cigarette smoking were similar in predicting emphysema severity averaged over this cohort. Coal dust exposure, cigarette smoking, age, and race are significant and additive predictors of emphysema severity in this study.

  4. Activated charcoal filter effectively reduces p-benzosemiquinone from the mainstream cigarette smoke and prevents emphysema.

    PubMed

    Dey, Neekkan; Das, Archita; Ghosh, Arunava; Chatterjee, Indu B

    2010-06-01

    In this paper, we have made a comparative evaluation of the cytotoxicity and pathophysiological effects of mainstream smoke from cellulose acetate (CA)-filtered cigarettes with that of charcoal-filtered cigarettes developed in our laboratory. Previously, we had demonstrated that the mainstream smoke from an Indian CA-filtered commercial cigarette contains p-benzosemiquinone (p-BSQ), a major, highly toxic, long-lived water-soluble radical. Here, we have examined 16 brands of different CA-filtered cigarettes including Kentucky research cigarettes, and observed that mainstream smoke from all the cigarettes contains substantial amounts of p-BSQ (100-200 μg/cigarette). We also show that when the CA filter is replaced by a charcoal filter, the amount of p-BSQ in the mainstream smoke is reduced by 73-80%, which is accompanied by a reduction of carbonyl formation in bovine serum albumin to the extent of 70- 90%. The charcoal filter also prevented cytotoxicity in A549 cells as evidenced by MTT assay, apoptosis as evidenced by FACS analysis, TUNEL assay, overexpression of Bax, activation of p53 and caspase 3, as well as emphysematous lung damage in a guinea pig model as seen by histology and morphometric analysis. The results indicate that the charcoal filter developed in our laboratory may protect smokers from cigarette smoke-induced cytotoxity, protein modification, apoptosis and emphysema.

  5. A randomised trial of lung sealant versus medical therapy for advanced emphysema.

    PubMed

    Come, Carolyn E; Kramer, Mordechai R; Dransfield, Mark T; Abu-Hijleh, Muhanned; Berkowitz, David; Bezzi, Michela; Bhatt, Surya P; Boyd, Michael B; Cases, Enrique; Chen, Alexander C; Cooper, Christopher B; Flandes, Javier; Gildea, Thomas; Gotfried, Mark; Hogarth, D Kyle; Kolandaivelu, Kumaran; Leeds, William; Liesching, Timothy; Marchetti, Nathaniel; Marquette, Charles; Mularski, Richard A; Pinto-Plata, Victor M; Pritchett, Michael A; Rafeq, Samaan; Rubio, Edmundo R; Slebos, Dirk-Jan; Stratakos, Grigoris; Sy, Alexander; Tsai, Larry W; Wahidi, Momen; Walsh, John; Wells, J Michael; Whitten, Patrick E; Yusen, Roger; Zulueta, Javier J; Criner, Gerard J; Washko, George R

    2015-09-01

    Uncontrolled pilot studies demonstrated promising results of endoscopic lung volume reduction using emphysematous lung sealant (ELS) in patients with advanced, upper lobe predominant emphysema. We aimed to evaluate the safety and efficacy of ELS in a randomised controlled setting.Patients were randomised to ELS plus medical treatment or medical treatment alone. Despite early termination for business reasons and inability to assess the primary 12-month end-point, 95 out of 300 patients were successfully randomised, providing sufficient data for 3- and 6-month analysis.57 patients (34 treatment and 23 control) had efficacy results at 3 months; 34 (21 treatment and 13 control) at 6 months. In the treatment group, 3-month lung function, dyspnoea, and quality of life improved significantly from baseline when compared to control. Improvements persisted at 6 months with >50% of treated patients experiencing clinically important improvements, including some whose lung function improved by >100%. 44% of treated patients experienced adverse events requiring hospitalisation (2.5-fold more than control, p=0.01), with two deaths in the treated cohort. Treatment responders tended to be those experiencing respiratory adverse events.Despite early termination, results show that minimally invasive ELS may be efficacious, yet significant risks (probably inflammatory) limit its current utility.

  6. Papain-induced experimental pulmonary emphysema in male and female mice.

    PubMed

    Machado, Mariana Nascimento; Figueirôa, Silviane Fernandes da Silva; Mazzoli-Rocha, Flavia; Valença, Samuel dos Santos; Zin, Walter Araújo

    2014-08-15

    In papain-induced models of emphysema, despite the existing extensive description of the cellular and molecular aspects therein involved, sexual hormones may play a complex and still not fully understood role. Hence, we aimed at exploring the putative gender-related differences in lung mechanics, histology and oxidative stress in papain-exposed mice. Thirty adult BALB/c mice received intratracheally either saline (50 μL) or papain (10 U/50 μL saline) once a week for 2 weeks. In males papain increased lung resistive and viscoelastic/inhomogeneous pressures, static elastance, and viscoelastic component of elastance, while females showed higher static elastance and resistive pressure only. Both genders presented similar higher parenchymal cellularity and mean alveolar diameter, and less collagen-elastic fiber content and body weight gain than their respective controls. Increased functional residual capacity was more prominent in males. Female papain-treated mice were more susceptible to oxidative stress. Thus, male and female papain-exposed mice respond differently, which should be carefully considered to avoid confounding results.

  7. Simultaneous surgical treatment of chronic post-traumatic aneurysm of the thoracic aorta, diaphragmatic hernia and giant emphysema bulla.

    PubMed

    Luciani, N; Lapenna, E; De Bonis, M; Pirronti, T; Possati, G F

    2002-10-01

    Thoraco-abdominal blunt trauma can lead to multiple injuries of several organs. We report a case of a patient in whom, 10 years after a trauma, a chest X-ray showed visceral herniation into the left thorax. Angio computed tomographic scan (CTS) and magnetic resonance imaging (MRI) confirmed these lesions and also showed a saccular thoracic aortic aneurysm. During the surgical procedure a giant post-traumatic emphysema bulla of the left lower pulmonary lobe was discovered and repaired. In the presence of diaphragmatic injuries, CTS and MRI are mandatory for excluding other organ involvement, and during the surgical procedure, careful inspection of left thorax and abdomen should always be done to repair other possible injuries not seen before.

  8. Cotinine Concentration in Serum Correlates with Tobacco Smoke-Induced Emphysema in Mice

    PubMed Central

    Xu, Xin; Su, Yunchao; Fan, Z. Hugh

    2014-01-01

    Secondhand smoke (SHS) has been associated with a variety of adverse health outcomes in nonsmokers, including emphysema (a chronic obstructive pulmonary disease). One way to detect SHS exposure is to measure the concentration of cotinine, the primary metabolite of nicotine, in bodily fluids. We have developed a method for cotinine analysis by combining micellar electrokinetic chromatography with enrichment techniques. We employed the method to measure cotinine concentrations in serum samples of mice exposed to tobacco smoke for 12 or 24 weeks and found that it was 3.1-fold or 4.8-fold higher than those exposed to room air for the same period. Further, we investigated the morphological changes in lungs of mice and observed tobacco smoke induced emphysema. Our results indicate that the method can be used to measure cotinine and there is an association between the serum cotinine concentration and tobacco smoke-induced emphysema in mice. PMID:24463700

  9. The lung volume reduction coil for the treatment of emphysema: a new therapy in development.

    PubMed

    Klooster, Karin; Ten Hacken, Nick H T; Slebos, Dirk-Jan

    2014-09-01

    Lung volume reduction (LVR) coil treatment is a novel therapy for patients with severe emphysema. In this bilateral bronchoscopic treatment, approximately 10 LVR coils per lobe are delivered under fluoroscopic guidance in two sequential procedures. The LVR coil reduces lung volume by compressing the most destructed areas of the lung parenchyma and restores the lung elastic recoil. Both patients with upper- and lower-lobe predominant emphysema as well as a homogeneous emphysema distribution can be treated. LVR coil treatment results in an improvement of pulmonary function, exercise tolerance and quality of life. The LVR-coil treatment has been evaluated in several European clinical trials since 2008 and received CE mark approval in 2010. Currently, two large multicenter randomized controlled trials are underway in Europe and North America to assess the efficacy and safety of the LVR-coil treatment at 12 months compared with usual care. In this review, we share our experience with the LVR-coil treatment.

  10. Cotinine Concentration in Serum Correlates with Tobacco Smoke-Induced Emphysema in Mice

    NASA Astrophysics Data System (ADS)

    Xu, Xin; Su, Yunchao; Fan, Z. Hugh

    2014-01-01

    Secondhand smoke (SHS) has been associated with a variety of adverse health outcomes in nonsmokers, including emphysema (a chronic obstructive pulmonary disease). One way to detect SHS exposure is to measure the concentration of cotinine, the primary metabolite of nicotine, in bodily fluids. We have developed a method for cotinine analysis by combining micellar electrokinetic chromatography with enrichment techniques. We employed the method to measure cotinine concentrations in serum samples of mice exposed to tobacco smoke for 12 or 24 weeks and found that it was 3.1-fold or 4.8-fold higher than those exposed to room air for the same period. Further, we investigated the morphological changes in lungs of mice and observed tobacco smoke induced emphysema. Our results indicate that the method can be used to measure cotinine and there is an association between the serum cotinine concentration and tobacco smoke-induced emphysema in mice.

  11. Respiratory function responses of animals and man to oxidant gases and to pulmonary emphysema

    SciTech Connect

    Mauderly, J.L.

    1984-01-01

    Data on the respiratory functional responses of animals and humans to inhaled oxidant gases and to pulmonary emphysema were reviewed and compared. Comparisons included responses to short-term inhalation of ozone, nitrogen dioxide, and oxygen and the functional manifestations of chronic emphysema. The comparisons illustrated that animals and humans have qualitatively similar functional responses to the irritant, bronchoconstrictive, and sensitizing effects of acutely inhaled ozone and nitrogen dioxide. Animals and humans responded similarly to the inflammatory and edematous effects of inhaled oxygen. Similar changes in maximal expiratory flow-volume curves, pressure-volume curves, lung volumes, and alveolar-capillary gas exchange occurred in animals and humans with emphysema. These results suggest that similar respiratory functional changes occur in both animals and humans when similar morphological changes result from lung injury. This observation lends confidence to the use of laboratory animals in studies to predict the effects of long-term exposure of humans to inhaled oxidant gases. 42 references.

  12. Hyperpolarized 83Kr magnetic resonance imaging of alveolar degradation in a rat model of emphysema.

    PubMed

    Lilburn, David M L; Lesbats, Clémentine; Six, Joseph S; Dubuis, Eric; Yew-Booth, Liang; Shaw, Dominick E; Belvisi, Maria G; Birrell, Mark A; Pavlovskaya, Galina E; Meersmann, Thomas

    2015-06-06

    Hyperpolarized (83)Kr surface quadrupolar relaxation (SQUARE) generates MRI contrast that was previously shown to correlate with surface-to-volume ratios in porous model surface systems. The underlying physics of SQUARE contrast is conceptually different from any other current MRI methodology as the method uses the nuclear electric properties of the spin I = 9/2 isotope (83)Kr. To explore the usage of this non-radioactive isotope for pulmonary pathophysiology, MRI SQUARE contrast was acquired in excised rat lungs obtained from an elastase-induced model of emphysema. A significant (83)Kr T1 relaxation time increase in the SQUARE contrast was found in the elastase-treated lungs compared with the baseline data from control lungs. The SQUARE contrast suggests a reduction in pulmonary surface-to-volume ratio in the emphysema model that was validated by histology. The finding supports usage of (83)Kr SQUARE as a new biomarker for surface-to-volume ratio changes in emphysema.

  13. Pneumothorax caused by aggressive use of an incentive spirometer in a patient with emphysema.

    PubMed

    Kenny, Jon-Emile S; Kuschner, Ware G

    2013-07-01

    A 68-year-old man presented to the emergency department with a small pneumothorax following aggressive use of an incentive spirometer. The patient had a baseline chest radiograph consistent with emphysema. He was initially treated with oxygen in the emergency department, with resolution of his symptoms. The pneumothorax resolved spontaneously over a period of 3 days. The development of the pneumothorax was likely due to the patient's repeated forceful inspiratory maneuvers in the setting of emphysema and lung hyperinflation. Inspiratory resistive breathing can cause large negative swings in intrathoracic pressure, which may result in mechanical stress of lung tissue. This is the first report of a secondary pneumothorax associated with use of an incentive spirometer. Patients with bullous emphysema should be counseled to avoid frequent high intensity maneuvers with an incentive spirometer if the potential benefits of the procedure are marginal.

  14. Incidental lung volume reduction following fulminant pulmonary hemorrhage in a patient with severe emphysema.

    PubMed

    Hetzel, Juergen; Spengler, Werner; Horger, Marius; Boeckeler, Michael

    2015-06-01

    Endoscopic lung volume reduction is an emerging technique meant to improve lung function parameters, quality of life, and exercise tolerance in patients with severe lung emphysema. This is the first report of lung volume reduction by autologous blood in a patient with non-bullous lung emphysema. A 74-year-old woman with heterogeneous lung emphysema developed accidentally diffuse lobar bleeding immediately after valve placement. Due to persistent hemorrhage, the valves had to be removed shortly thereafter. Despite extraction of the valves, respiratory function of the patient improved rapidly indicated also by a drop in the COPD assessment test questionnaire, 3 months later. This was consistent with both improvement of lung function tests and six-minute walking test.

  15. Elastase induced lung epithelial cell apoptosis and emphysema through placenta growth factor

    PubMed Central

    Hou, H-H; Cheng, S-L; Liu, H-T; Yang, F-Z; Wang, H-C; Yu, C-J

    2013-01-01

    Chronic pulmonary obstructive disease (COPD) is the fourth leading cause of death worldwide, however, the pathogenic factors and mechanisms are not fully understood. Pulmonary emphysema is one of the major components of COPD and is thought to result from oxidative stress, chronic inflammation, protease–antiprotease imbalance and lung epithelial (LE) cell apoptosis. In our previous studies, COPD patients were noted to have higher levels of placenta growth factor (PlGF) in serum and bronchoalveolar lavage fluid than controls. In addition, transgenic mice overexpressing PlGF developed pulmonary emphysema and exposure to PlGF in LE cells induced apoptosis. Furthermore, intratracheal instillation of porcine pancreatic elastase (PPE) on to PlGF wild type mice induced emphysema, but not in PlGF knockout mice. Therefore, we hypothesized that PPE generates pulmonary emphysema through the upregulation of PlGF expression in LE cells. The elevation of PlGF then leads to LE cell apoptosis. In the present study, we investigated whether PPE induces PlGF expression, whether PlGF induces apoptosis and whether the downstream mechanisms of PlGF are related to LE cell apoptosis. We found that PPE increased PlGF secretion and expression both in vivo and in vitro. Moreover, PlGF-induced LE cell apoptosis and PPE-induced emphysema in the mice were mediated by c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK) pathways. Given these findings, we suggest that the increase in PlGF and PlGF-induced JNK and p38 MAPK pathways contribute to PPE-induced LE cell apoptosis and emphysema. Regulatory control of PlGF and agents against its downstream signals may be potential therapeutic targets for COPD. PMID:24008737

  16. Defect of hepatocyte growth factor production by fibroblasts in human pulmonary emphysema.

    PubMed

    Plantier, Laurent; Marchand-Adam, Sylvain; Marchal-Sommé, Joëlle; Lesèche, Guy; Fournier, Michel; Dehoux, Monique; Aubier, Michel; Crestani, Bruno

    2005-04-01

    Pulmonary emphysema results from an excessive degradation of lung parenchyma associated with a failure of alveolar repair. Secretion by pulmonary fibroblasts of hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF) is crucial to an effective epithelial repair after lung injury. We hypothesized that abnormal HGF or KGF secretion by pulmonary fibroblasts could play a role in the development of emphysema. We measured in vitro production of HGF and KGF by human fibroblasts cultured from emphysematous and normal lung samples. HGF and KGF production was quantified at basal state and after stimulation. Intracellular content of HGF was lower in emphysema (1.52 pg/mug, range of 0.15-7.40 pg/mug) than in control fibroblasts (14.16 pg/mug, range of 2.50-47.62 pg/mug; P = 0.047). HGF production by emphysema fibroblasts (19.3 pg/mug protein, range of 10.4-39.2 pg/mug) was lower than that of controls at baseline (57.5 pg/mug, range of 20.4-116 pg/mug; P = 0.019) and after stimulation with interleukin-1beta or prostaglandin E(2). Neither retinoic acids (all-trans and 9-cis) nor N-acetylcysteine could reverse this abnormality. KGF production by emphysema fibroblasts (5.3 pg/mug, range of 2.2-9.3 pg/mug) was similar to that of controls at baseline (2.6 pg/mug, range of 1-6.1 pg/mug; P = 0.14) but could not be stimulated with interleukin-1beta. A decreased secretion of HGF by pulmonary fibroblasts could contribute to the insufficient alveolar repair in pulmonary emphysema.

  17. Distinct Quantitative Computed Tomography Emphysema Patterns Are Associated with Physiology and Function in Smokers

    PubMed Central

    San José Estépar, Raúl; Mendoza, Carlos S.; Hersh, Craig P.; Laird, Nan; Crapo, James D.; Lynch, David A.; Silverman, Edwin K.; Washko, George R.

    2013-01-01

    Rationale: Emphysema occurs in distinct pathologic patterns, but little is known about the epidemiologic associations of these patterns. Standard quantitative measures of emphysema from computed tomography (CT) do not distinguish between distinct patterns of parenchymal destruction. Objectives: To study the epidemiologic associations of distinct emphysema patterns with measures of lung-related physiology, function, and health care use in smokers. Methods: Using a local histogram-based assessment of lung density, we quantified distinct patterns of low attenuation in 9,313 smokers in the COPDGene Study. To determine if such patterns provide novel insights into chronic obstructive pulmonary disease epidemiology, we tested for their association with measures of physiology, function, and health care use. Measurements and Main Results: Compared with percentage of low-attenuation area less than −950 Hounsfield units (%LAA-950), local histogram-based measures of distinct CT low-attenuation patterns are more predictive of measures of lung function, dyspnea, quality of life, and health care use. These patterns are strongly associated with a wide array of measures of respiratory physiology and function, and most of these associations remain highly significant (P < 0.005) after adjusting for %LAA-950. In smokers without evidence of chronic obstructive pulmonary disease, the mild centrilobular disease pattern is associated with lower FEV1 and worse functional status (P < 0.005). Conclusions: Measures of distinct CT emphysema patterns provide novel information about the relationship between emphysema and key measures of physiology, physical function, and health care use. Measures of mild emphysema in smokers with preserved lung function can be extracted from CT scans and are significantly associated with functional measures. PMID:23980521

  18. Vitamin C prevents cigarette smoke-induced pulmonary emphysema in mice and provides pulmonary restoration.

    PubMed

    Koike, Kengo; Ishigami, Akihito; Sato, Yasunori; Hirai, Toyohiro; Yuan, Yiming; Kobayashi, Etsuko; Tobino, Kazunori; Sato, Tadashi; Sekiya, Mitsuaki; Takahashi, Kazuhisa; Fukuchi, Yoshinosuke; Maruyama, Naoki; Seyama, Kuniaki

    2014-02-01

    Vitamin C (VC) is a potent antioxidant and is essential for collagen synthesis. We investigated whether VC treatment prevents and cures smoke-induced emphysema in senescence marker protein-30 knockout (SMP30-KO) mice, which cannot synthesize VC. Two smoke-exposure experiments using SMP30-KO mice were conducted. In the first one (a preventive study), 4-month-old mice received minimal VC (0.0375 g/l) [VC(L)] or physiologically sufficient VC (1.5 g/l) [VC(S)] and exposed to cigarette smoke or smoke-free air for 2 months. Pulmonary evaluations followed when the mice were 6 months of age. The second study began after the establishment of smoke-induced emphysema (a treatment study). These mice no longer underwent smoke exposure but received VC(S) or VC(L) treatment for 2 months. Morphometric analysis was performed, and measurements of oxidative stress, collagen synthesis, and vascular endothelial growth factor in the lungs were evaluated. Chronic smoke exposure caused emphysema (29.6% increases of mean linear intercepts [MLI] and 106.5% increases of destructive index compared with the air-only group) in 6-month-old SMP30-KO mice, and this emphysema closely resembled human chronic obstructive pulmonary disease. Smoke-induced emphysema persisted in the VC(L) group after smoking cessation, whereas VC treatment provided pulmonary restoration (18.5% decrease of MLI and 41.3% decrease of destructive index compared with VC(L) group). VC treatment diminished oxidative stress, increased collagen synthesis, and improved vascular endothelial growth factor levels in the lungs. Our results suggest that VC not only prevents smoke-induced emphysema in SMP30-KO mice but also restores emphysematous lungs. Therefore, VC may provide a new therapeutic strategy for treating chronic obstructive pulmonary disease in humans.

  19. Metabolomics screening identifies reduced L-carnitine to be associated with progressive emphysema.

    PubMed

    Conlon, Thomas M; Bartel, Jörg; Ballweg, Korbinian; Günter, Stefanie; Prehn, Cornelia; Krumsiek, Jan; Meiners, Silke; Theis, Fabian J; Adamski, Jerzy; Eickelberg, Oliver; Yildirim, Ali Önder

    2016-02-01

    Chronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitis, small airway remodelling and emphysema. Emphysema is the destruction of alveolar structures, leading to enlarged airspaces and reduced surface area impairing the ability for gaseous exchange. To further understand the pathological mechanisms underlying progressive emphysema, we used MS-based approaches to quantify the lung, bronchoalveolar lavage fluid (BALF) and serum metabolome during emphysema progression in the established murine porcine pancreatic elastase (PPE) model on days 28, 56 and 161, compared with PBS controls. Partial least squares (PLS) analysis revealed greater changes in the metabolome of lung followed by BALF rather than serum during emphysema progression. Furthermore, we demonstrate for the first time that emphysema progression is associated with a reduction in lung-specific L-carnitine, a metabolite critical for transporting long-chain fatty acids into the mitochondria for their subsequent β-oxidation. In vitro, stimulation of the alveolar epithelial type II (ATII)-like LA4 cell line with L-carnitine diminished apoptosis induced by both PPE and H2O2. Moreover, PPE-treated mice demonstrated impaired lung function compared with PBS-treated controls (lung compliance; 0.067±0.008 ml/cmH20 compared with 0.035±0.005 ml/cmH20, P<0.0001), which improved following supplementation with L-carnitine (0.051±0.006, P<0.01) and was associated with a reduction in apoptosis. In summary, our results provide a new insight into the role of L-carnitine and, importantly, suggest therapeutic avenues for COPD.

  20. Protective effects of basic fibroblast growth factor in the development of emphysema induced by interferon-γ.

    PubMed

    Lee, Byung-Jae; Moon, Hyung-Geun; Shin, Tae-Seop; Jeon, Seong Gyu; Lee, Eun-Young; Gho, Yong Song; Lee, Chun Geun; Zhu, Zhou; Elias, Jack A; Kim, Yoon-Keun

    2011-04-30

    Recent clinical evidence indicates that the non-eosinophilic subtype of severe asthma is characterized by fixed airway obstruction, which may be related to emphysema. Transgenic studies have demonstrated that high levels of IFN-γ in the airways induce emphysema. Fibroblast growth factor 2 (FGF2), which is the downstream mediator of TGF-β, is important in wound healing. We investigated the role of FGF2 in IFN-γ-induced emphysema and the therapeutic effects of recombinant FGF2 in the prevention of emphysema in a severe non-eosinophilic asthma model. To evaluate the role of FGF2 in IFN-γ-induced emphysema, lung targeted IFN-γ transgenic mice were cross-bred with FGF2-deficient mice. A severe non-eosinophilic asthma model was generated by airway application of LPS-containing allergens twice a week for 4 weeks. To evaluate protective effects of FGF2, recombinant FGF2 (10 μg) was injected subcutaneously during allergen challenge in the severe asthma model. We found that non-eosinophilic inflammation and emphysema induced by transgenic overexpression of IFN-γ in the airways were aggravated by the absence of FGF2. Airway challenge with LPS-containing allergens induced more inflammation in mice sensitized with LPS-containing allergens compared to challenge with allergens alone. In addition, LPS-induced lung inflammation and emphysema depended on IFN-γ but not on IL-13. Interestingly, emphysema in the severe asthma model was significantly inhibited by treatment with recombinant FGF2 during allergen challenge, whereas lung inflammation was unaffected. Therefore, our present data suggest that FGF2 may help protect against IFN-γ-induced emphysema, and that recombinant FGF2 may help lessen the severity of emphysema.

  1. Lactosylceramide-accumulation in lipid-rafts mediate aberrant-autophagy, inflammation and apoptosis in cigarette smoke induced emphysema.

    PubMed

    Bodas, Manish; Min, Taehong; Vij, Neeraj

    2015-05-01

    Ceramide-accumulation is known to be involved in the pathogenesis of chronic inflammatory lung diseases including cigarette smoke-induced emphysema (CS-emphysema) but the exact sphingolipid metabolite that initiates emphysema progression remains ambiguous. We evaluated here a novel role for the sphingolipid, lactosylceramide (LacCer), as a potential mechanism for pathogenesis of CS-emphysema. We assessed the expression of LacCer, and LacCer-dependent inflammatory, apoptosis and autophagy responses in lungs of mice exposed to CS, as well as peripheral lung tissues from COPD subjects followed by experimental analysis to verify the role of LacCer in CS-emphysema. We observed significantly elevated LacCer-accumulation in human COPD lungs with increasing severity of emphysema over non-emphysema controls. Moreover, increased expression of defective-autophagy marker, p62, in lung tissues of severe COPD subjects suggest that LacCer induced aberrant-autophagy may contribute to the pathogenesis of CS-emphysema. We verified that CS-extract treatment significantly induces LacCer-accumulation in both bronchial-epithelial cells (BEAS2B) and macrophages (Raw264.7) as a mechanism to initiate aberrant-autophagy (p62-accumulation) and apoptosis that was rescued by pharmacological inhibitor of LacCer-synthase. Further, we corroborated that CS exposure induces LacCer-accumulation in murine lungs that can be controlled by LacCer-synthase inhibitor. We propose LacCer-accumulation as a novel prognosticator of COPD-emphysema severity, and provide evidence on the therapeutic efficacy of LacCer-synthase inhibitor in CS induced COPD-emphysema.

  2. Endoscopic lung volume reduction effectively treats acute respiratory failure secondary to bullous emphysema.

    PubMed

    Sexton, Paul; Garrett, Jeffrey E; Rankin, Nigel; Anderson, Graeme

    2010-10-01

    Emphysema often affects the lungs in a heterogeneous fashion, and collapse or removal of severely hyperinflated portions of lung can improve overall lung function and symptoms. The role of lung volume reduction (LVR) surgery in selected patients is well established, but that of non-surgical LVR is still being defined. In particular, use of endobronchial LVR is still under development. This case report describes a 48-year-old non-smoker with severe bullous emphysema complicated by acute hypercapnic respiratory failure, who was successfully treated by endobronchial valve placement while intubated in an intensive care unit.

  3. Iatrogenic subcutaneous emphysema of endodontic origin - case report with literature review.

    PubMed

    Mishra, Lora; Patnaik, Swarnav; Patro, Sangram; Debnath, Nitai; Mishra, Satyaranjan

    2014-01-01

    Surgical emphysema is well known and many case reports have been published on this. Many authors have reported this as a complication post dentoalveolar treatment. Diffusion of air into facial planes and periorbital area during endodontic procedures has been rarely reported. The use of three way air syringe and forceful irrigation of root canal can lead to surgical emphysema of subcutaneous tissue planes in and around the teeth which are involved. This case report highlights one such complication seen during endodontic treatment, discusses aetiology, complications and conservative management of this dental office emergency.

  4. Abdominal and scrotal wall emphysema in a patient with severe ulcerative colitis.

    PubMed

    Sharma, Manik; Thandassery, Ragesh Babu; Hilli, Shatha Al; Kaabi, Saad Al

    2014-07-01

    Severe ulcerative colitis can be associated with bowel perforation. Bowel perforation rarely leads on to abdominal wall and scrotal wall emphysema. Bowel perforation in such cases can be spontaneous or iatrogenic (colonoscopy-related). We report a rare scenario where a patient presented with abdominal wall and scrotal emphysema after topical corticosteroid enema-induced traumatic rectal perforation. Topical corticosteroids were stopped immediately after identification of rectal perforation. The patient was managed conservatively with intravenous antibiotics. With this report we intend to sensitise clinicians and topical enema manufacturers regarding this rare complication.

  5. Assessment of multislice CT to quantify pulmonary emphysema function and physiology in a rat model

    NASA Astrophysics Data System (ADS)

    Cao, Minsong; Stantz, Keith M.; Liang, Yun; Krishnamurthi, Ganapathy; Presson, Robert G., Jr.

    2005-04-01

    Purpose: The purpose of this study is to evaluate multi-slice computed tomography technology to quantify functional and physiologic changes in rats with pulmonary emphysema. Method: Seven rats were scanned using a 16-slice CT (Philips MX8000 IDT) before and after artificial inducement of emphysema. Functional parameters i.e. lung volumes were measured by non-contrast spiral scan during forced breath-hold at inspiration and expiration followed by image segmentation based on attenuation threshold. Dynamic CT imaging was performed immediately following the contrast injection to estimate physiology changes. Pulmonary perfusion, fractional blood volume, and mean transit times (MTTs) were estimated by fitting the time-density curves of contrast material using a compartmental model. Results: The preliminary results indicated that the lung volumes of emphysema rats increased by 3.52+/-1.70mL (p<0.002) at expiration and 4.77+/-3.34mL (p<0.03) at inspiration. The mean lung densities of emphysema rats decreased by 91.76+/-68.11HU (p<0.01) at expiration and low attenuation areas increased by 5.21+/-3.88% (p<0.04) at inspiration compared with normal rats. The perfusion for normal and emphysema rats were 0.25+/-0.04ml/s/ml and 0.32+/-0.09ml/s/ml respectively. The fractional blood volumes for normal and emphysema rats were 0.21+/-0.04 and 0.15+/-0.02. There was a trend toward faster MTTs for emphysema rats (0.42+/-0.08s) than normal rats (0.89+/-0.19s) with p<0.006, suggesting that blood flow crossing the capillaries increases as the capillary volume decreases and which may cause the red blood cells to leave the capillaries incompletely saturated with oxygen if the MTTs become too short. Conclusion: Quantitative measurement using CT of structural and functional changes in pulmonary emphysema appears promising for small animals.

  6. Computational modeling helps uncover mechanisms related to the progression of emphysema

    PubMed Central

    Suki, Béla; Parameswaran, Harikrishnan

    2014-01-01

    Emphysema is a progressive disease characterized by deterioration of alveolar structure and decline in lung function. While morphometric and molecular biology studies have not fully uncovered the underlying mechanisms, they have produced data to advance computational modeling. In this review, we discuss examples in which modeling has led to novel insight into mechanisms related to disease progression. Finally, we propose a general scheme of multiscale modeling approach that could help unravel the progressive nature of emphysema and provide patient specific mechanisms perhaps suitable for use in treatment therapies. PMID:24904681

  7. Computational modeling helps uncover mechanisms related to the progression of emphysema.

    PubMed

    Suki, Béla; Parameswaran, Harikrishnan

    2014-07-08

    Emphysema is a progressive disease characterized by deterioration of alveolar structure and decline in lung function. While morphometric and molecular biology studies have not fully uncovered the underlying mechanisms, they have produced data to advance computational modeling. In this review, we discuss examples in which modeling has led to novel insight into mechanisms related to disease progression. Finally, we propose a general scheme of multiscale modeling approach that could help unravel the progressive nature of emphysema and provide patient specific mechanisms perhaps suitable for use in treatment therapies.

  8. Noninvasive assessment of pulmonary emphysema using dynamic contrast-enhanced magnetic resonance imaging.

    PubMed

    Morino, Shigeyuki; Toba, Toshinari; Araki, Masato; Azuma, Takashi; Tsutsumi, Sadami; Tao, Hiroyuki; Nakamura, Tatsuo; Nagayasu, Takeshi; Tagawa, Tsutomu

    2006-01-01

    Emphysema tends to be complicated by diffuse abnormalities in the pulmonary peripheral microvasculature. The aim of this study was to evaluate whether dynamic contrast-enhanced magnetic resonance imaging (MRI) could provide a valid assessment of pulmonary blood flow as an indicator of the severity of emphysema. To do this, the authors compared MRI data with the pathological findings in lung tissue. Dynamic contrast-enhanced MRI is a noninvasive method and can be used to repeatedly monitor clinicopathological severity. Using MRI clear pulmonary vascular information can be obtained easily, and the relative pulmonary blood flow in the lung parenchyma can be quantified.

  9. A Case of Pulmonary Interstitial Emphysema Treated by Percutaneous Catheter Insertion in Extremely Low Birth Weight Infant

    PubMed Central

    Kim, Changsin; Shin, Jeong Eun; Eun, Ho Seon; Park, Min Soo; Park, Kook In; Namgung, Ran; Lee, Sungsoo; Yoon, Choon Sik

    2016-01-01

    The pulmonary interstitial emphysema (PIE) is a life-threatening illness in premature infants with mechanical ventilation. While most are managed conservatively, decompression would be necessary. Here, we report the first case of PIE treated by percutaneous catheter insertion in an extremely low birth weight (ELBW) infant in Korea. The patient, born with 660 g in 23+2 weeks of gestation, showed PIE in left lower lung on postnatal day 12. Percutaneous catheter insertion was performed on postnatal day 25. The size of PIE decreased, but didn't disappear completely. On postnatal day 42, we exchanged catheter and inserted additional catheter in pleural space. However, sudden desaturation and pneumothorax occurred on postnatal day 44. We changed catheter in pleural space, and pneumothorax and PIE improved. Finally, we successfully removed catheters, and weaned patient out. As in our case, percutaneous catheter insertion would be a useful option for ELBW infants with PIE. PMID:27593885

  10. Are Independent Probes Truly Independent?

    ERIC Educational Resources Information Center

    Camp, Gino; Pecher, Diane; Schmidt, Henk G.; Zeelenberg, Rene

    2009-01-01

    The independent cue technique has been developed to test traditional interference theories against inhibition theories of forgetting. In the present study, the authors tested the critical criterion for the independence of independent cues: Studied cues not presented during test (and unrelated to test cues) should not contribute to the retrieval…

  11. Widespread subcutaneous emphysema and barotrauma resulting from high pressure gas injection.

    PubMed

    Smith, Barnaby; Brown, Troy

    2012-09-21

    Widespread subcutaneous emphysema is an unusual emergency presentation. We present a case of accidental high pressure insufflation, the pathophysiology and subsequent medical management in the acute setting. Such presentations are rare but dramatic and can have important life-threatening consequences that require immediate treatment.

  12. Atorvastatin and Simvastatin Promoted Mouse Lung Repair After Cigarette Smoke-Induced Emphysema.

    PubMed

    Pinho-Ribeiro, Vanessa; Melo, Adriana Correa; Kennedy-Feitosa, Emanuel; Graca-Reis, Adriane; Barroso, Marina Valente; Cattani-Cavalieri, Isabella; Carvalho, Giovanna Marcella Cavalcante; Zin, Walter Araújo; Porto, Luis Cristóvão; Gitirana, Lycia Brito; Lanzetti, Manuella; Valença, Samuel Santos

    2017-03-01

    Cigarette smoke (CS) induces pulmonary emphysema by inflammation, oxidative stress, and metalloproteinase (MMP) activation. Pharmacological research studies have not focused on tissue repair after the establishment of emphysema but have instead focused on inflammatory stimulation. The aim of our study was to analyze the effects of atorvastatin and simvastatin on mouse lung repair after emphysema caused by CS. Male mice (C57BL/6, n = 45) were divided into the following groups: control (sham-exposed), CSr (mice exposed to 12 cigarettes a day for 60 days and then treated for another 60 days with the vehicle), CSr+A (CSr mice treated with atorvastatin for 60 days), and CSr+S (CSr mice treated with simvastatin for 60 days). The treatment with atorvastatin and simvastatin was administered via inhalation (15 min with 1 mg/mL once a day). Mice were sacrificed 24 h after the completion of the 120-day experimental procedure. We performed biochemical, morphological, and physiological analyses. We observed decreased levels of leukocytes and cytokines in statin-treated mice, accompanied by a reduction in oxidative stress markers. We also observed a morphological improvement confirmed by a mean linear intercept counting in statin-treated mice. Finally, statins also ameliorated lung function. We conclude that inhaled atorvastatin and simvastatin improved lung repair after cigarette smoke-induced emphysema in mice.

  13. Autologous transplantation of adipose tissue-derived stromal cells ameliorates pulmonary emphysema.

    PubMed

    Shigemura, N; Okumura, M; Mizuno, S; Imanishi, Y; Nakamura, T; Sawa, Y

    2006-11-01

    Adipose tissue is a useful tool for management of most complex cardiothoracic problems, including the reinforcement of damaged lungs, and adipose tissue-derived stromal cells (ASCs) have been suggested to secrete hepatocyte growth factor (HGF), a multipotent regenerative factor that contributes to the repair process after lung injury. The goal of this study was to demonstrate the therapeutic impact of autologous transplantation of ASCs through HGF supplementation for the enhancement of alveolar repair in a rat model of emphysema. ASCs were isolated from inguinal subcutaneous fat pads and characterized by flow cytometry. Cultured ASC were found to secrete significantly larger amounts of HGF (15 112 +/- 1628 pg per 10(6) cells) than other angiogenic factors. Transplantation of ASCs into elastase-treated emphysema models induced a significant increase in endogenous HGF expression in lung tissues with a small amount of increase in other organs, with the high levels lasting for up to 4 weeks after transplantation. Further, alveolar and vascular regeneration were significantly enhanced via inhibition of alveolar cell apoptosis, enhancement of epithelial cell proliferation and promotion of angiogenesis in pulmonary vasculature, leading to restoration of pulmonary function affected by emphysema. These data suggest that autologous ASC cell therapy may have a therapeutic potential for pulmonary emphysema, through inducing HGF expression selectively in injured lung tissues.

  14. Surgical Approaches to Treating Emphysema: Lung Volume Reduction Surgery, Bullectomy, and Lung Transplantation.

    PubMed

    Marchetti, Nathaniel; Criner, Gerard J

    2015-08-01

    Chronic obstructive pulmonary disease (COPD) is a common and morbid progressive disease where treatment is focused on improving dyspnea, reducing exacerbations, attenuating comorbidities, and improving quality of life. Surgical therapy can be beneficial to a carefully selected subset of individuals and is the subject of this review. The National Emphysema Treatment Trial (NETT) has not only demonstrated the efficacy of lung volume reduction surgery (LVRS) but has also provided many lessons regarding advanced emphysema. NETT demonstrated that LVRS improves exercise performance, quality of life, and pulmonary function in those with upper lobe predominant emphysema in the setting of advanced disease. Those with upper lobe predominant emphysema and low exercise tolerance also had a survival advantage compared with maximal medical therapy. Careful patient selection is paramount to success, as there clearly are patients in whom LVRS increases mortality. Giant bullae are rare, but bullectomy has been demonstrated to improve dyspnea and lung function in cases where the bulla occupies at least one-third of the hemithorax and compresses some adjacent lung tissue. For patients with chronic respiratory failure due to COPD who have not improved despite maximal surgical and medical therapy, lung transplantation remains an option in those without significant comorbid conditions.

  15. Development and analysis of a finite element model to simulate pulmonary emphysema in CT imaging.

    PubMed

    Diciotti, Stefano; Nobis, Alessandro; Ciulli, Stefano; Landini, Nicholas; Mascalchi, Mario; Sverzellati, Nicola; Innocenti, Bernardo

    2015-01-01

    In CT imaging, pulmonary emphysema appears as lung regions with Low-Attenuation Areas (LAA). In this study we propose a finite element (FE) model of lung parenchyma, based on a 2-D grid of beam elements, which simulates pulmonary emphysema related to smoking in CT imaging. Simulated LAA images were generated through space sampling of the model output. We employed two measurements of emphysema extent: Relative Area (RA) and the exponent D of the cumulative distribution function of LAA clusters size. The model has been used to compare RA and D computed on the simulated LAA images with those computed on the models output. Different mesh element sizes and various model parameters, simulating different physiological/pathological conditions, have been considered and analyzed. A proper mesh element size has been determined as the best trade-off between reliable results and reasonable computational cost. Both RA and D computed on simulated LAA images were underestimated with respect to those calculated on the models output. Such underestimations were larger for RA (≈ -44 ÷ -26%) as compared to those for D (≈ -16 ÷ -2%). Our FE model could be useful to generate standard test images and to design realistic physical phantoms of LAA images for the assessment of the accuracy of descriptors for quantifying emphysema in CT imaging.

  16. Three-dimensional analysis of alveolar wall destruction in the early stage of pulmonary emphysema.

    PubMed

    Kobayashi, Yukihiro; Uehara, Takeshi; Kawasaki, Kenji; Sugano, Mitsutoshi; Matsumoto, Takehisa; Matsumoto, Gou; Honda, Takayuki

    2015-03-01

    The morphological mechanism of alveolar wall destruction during pulmonary emphysema has not been clarified. The aim of this study was to elucidate this process three-dimensionally. Lung specimens from five patients with pulmonary emphysema were used, and five controls with normal alveolar structure were also examined. Sections 150 μm thick were stained with hematoxylin and eosin, elastica, and silver impregnation, and immunostained with selected antibodies. We examined these sections three-dimensionally using a laser confocal microscope and a light microscope. There were only a few Kohn's pores and no fenestrae in the normal alveoli from the controls. In the lungs of the emphysema patients a small rupture appeared in the extremely thin alveolar wall among the alveolar capillaries. This rupture enlarged to form a circle surrounded by the capillaries, which was called an alveolar fenestra. Two neighboring fenestrae fused by breakdown of the collapsed or cord-like capillary between them to form a large fenestra. The large fenestrae fused repeatedly to become larger, and these were bordered by thick elastic fibers constructing an alveolar framework. Alveolar wall destruction during emphysema could start from small ruptures of the alveolar wall that become fenestrae surrounded by capillaries, which fuse repeatedly to become larger fenestrae rimmed with elastic fibers. The alveolar capillary network could initially prevent enlargement of the fenestrae, and the thick elastic fibers constituting the alveolar framework could secondarily prevent destruction of the alveolar wall structure.

  17. Tension pneumothorax and subcutaneous emphysema during retrieval of an ingested lithium button battery.

    PubMed

    Parray, Tariq; Siddiqui, Saif M; Hughes, Melissa; Shah, Shailesh

    2010-06-01

    We present a case of a child with an ingested lithium battery causing esophageal perforation with mediastinal injury extending to the pleural cavity. During the endoscopic retrieval of the battery, the child developed the rare complication of subcutaneous emphysema, tension pneumothorax, and pneumomediastinum from excessive iatrogenic air insufflation. The patient developed mediastinitis and had a complicated postoperative course.

  18. A human surfactant peptide-elastase inhibitor construct as a treatment for emphysema

    PubMed Central

    Guarnieri, Frank; Spencer, Jean L.; Lucey, Edgar C.; Nugent, Matthew A.; Stone, Phillip J.

    2010-01-01

    Two million Americans suffer from pulmonary emphysema, costing $2.5 billion/year and contributing to 100,000 deaths/year. Emphysema is thought to result from an imbalance between elastase and endogenous inhibitors of elastase, leading to tissue destruction and a loss of alveoli. Decades of research have still not resulted in an effective treatment other than stopping cigarette smoking, a highly addictive behavior. On the basis of our previous work, we hypothesize that small molecule inhibitors of human neutrophil elastase are ineffective because of rapid clearance from the lungs. To develop a long-acting elastase inhibitor with a lung pharmacodynamic profile that has minimal immunogenicity, we covalently linked an elastase inhibitor, similar to a trifluoro inhibitor that was used in clinical trials, to a 25-amino-acid fragment of human surfactant peptide B. We used this construct to prevent human neutrophil elastase-induced emphysema in a rodent model. The elastase inhibitor alone, although in a 70-fold molar excess to elastase in a mixture with <0.6% residual elastase activity, provided no protection from elastase-induced emphysema. Covalently combining an endogenous peptide from the target organ with a synthetic small molecule inhibitor is a unique way of endowing an active compound with the pharmacodynamic profile needed to create in vivo efficacy. PMID:20534582

  19. Delayed detection of subcutaneous emphysema following routine endotracheal intubation -A case report-

    PubMed Central

    Jo, Youn Yi; Park, Woo Young; Choi, Eunkyeong; Koo, Bon Nyeo

    2010-01-01

    A tracheal intubation-related tracheobronchial rupture is a relatively rare complication. We report a case of tracheobronchial rupture after single lumen endotracheal intubation. Twenty four hours after extubation of an endotracheal tube, subcutaneous emphysema developed on the patient's neck. A pneumomediastinum was also detected by computerized tomography (CT). The patient recovered uneventfully after conservative management. PMID:20877710

  20. TGF-β-Smad3 signaling in emphysema and pulmonary fibrosis: an epigenetic aberration of normal development?

    PubMed

    Warburton, David; Shi, Wei; Xu, Bing

    2013-01-15

    It is well accepted that TGF-β signaling has critical functional roles in lung development, injury, and repair. We showed previously that null mutation of Smad3, a critical node in the TGF-β pathway, protects mice against fibrosis induced by bleomycin. However, more recently we noticed that abnormal alveolarization also occurs in Smad3-deficient mice and that this is followed by progressive emphysema-like alveolar wall destruction mediated by MMP9. We now know that Smad3 cooperates with c-Jun to synergistically regulate a protein deacetylase SIRT1, by binding to an AP-1 site in the SIRT1 promoter. Consistently, Smad3 knockout lung at postnatal day 28 had reduced SIRT1 expression, which in turn resulted in increased histone acetylation at the binding sites of the transcription factors AP-1, NF-κB, and Pea3 on the MMP9 promoter, as well as increased acetylation of NF-κB. Thus, upon TGF-β activation, phosphorylated Smad3 can be translocated into the nucleus with Smad4, whereat Smad3 in turn collaborates with c-Jun to activate SIRT1 transcription. SIRT1 can deacetylate NF-κB at lysine 30, as well as histones adjacent to the transcription factor AP-1, NF-κB, and Pea3 binding sites of the MMP9 promoter, thereby suppressing MMP9 transcription, hence fixing MMP9 in the OFF mode. Conversely, when Smad3 is missing, this regulatory pathway is inactivated so that MMP9 is epigenetically turned ON. We postulate that these developmental epigenetic mechanisms by which Smad3 regulates MMP9 transcription cell autonomously may be important in modulating both emphysema and pulmonary fibrosis and that this could explain why both pathologies can appear within the same lung specimen.

  1. Ascorbate attenuates pulmonary emphysema by inhibiting tobacco smoke and Rtp801-triggered lung protein modification and proteolysis.

    PubMed

    Gupta, Indranil; Ganguly, Souradipta; Rozanas, Christine R; Stuehr, Dennis J; Panda, Koustubh

    2016-07-19

    Cigarette smoking causes emphysema, a fatal disease involving extensive structural and functional damage of the lung. Using a guinea pig model and human lung cells, we show that oxidant(s) present in tobacco smoke not only cause direct oxidative damage of lung proteins, contributing to the major share of lung injury, but also activate Rtp801, a key proinflammatory cellular factor involved in tobacco smoke-induced lung damage. Rtp801 triggers nuclear factor κB and consequent inducible NOS (iNOS)-mediated overproduction of NO, which in combination with excess superoxide produced during Rtp801 activation, contribute to increased oxido-nitrosative stress and lung protein nitration. However, lung-specific inhibition of iNOS with a iNOS-specific inhibitor, N6-(1-iminoethyl)-L-lysine, dihydrochloride (L-NIL) solely restricts lung protein nitration but fails to prevent or reverse the major tobacco smoke-induced oxidative lung injury. In comparison, the dietary antioxidant, ascorbate or vitamin C, can substantially prevent such damage by inhibiting both tobacco smoke-induced lung protein oxidation as well as activation of pulmonary Rtp801 and consequent iNOS/NO-induced nitration of lung proteins, that otherwise lead to increased proteolysis of such oxidized or nitrated proteins by endogenous lung proteases, resulting in emphysematous lung damage. Vitamin C also restricts the up-regulation of matrix-metalloproteinase-9, the major lung protease involved in the proteolysis of such modified lung proteins during tobacco smoke-induced emphysema. Overall, our findings implicate tobacco-smoke oxidant(s) as the primary etiopathogenic factor behind both the noncellular and cellular damage mechanisms governing emphysematous lung injury and demonstrate the potential of vitamin C to accomplish holistic prevention of such damage.

  2. Ascorbate attenuates pulmonary emphysema by inhibiting tobacco smoke and Rtp801-triggered lung protein modification and proteolysis

    PubMed Central

    Gupta, Indranil; Ganguly, Souradipta; Rozanas, Christine R.; Stuehr, Dennis J.

    2016-01-01

    Cigarette smoking causes emphysema, a fatal disease involving extensive structural and functional damage of the lung. Using a guinea pig model and human lung cells, we show that oxidant(s) present in tobacco smoke not only cause direct oxidative damage of lung proteins, contributing to the major share of lung injury, but also activate Rtp801, a key proinflammatory cellular factor involved in tobacco smoke-induced lung damage. Rtp801 triggers nuclear factor κB and consequent inducible NOS (iNOS)-mediated overproduction of NO, which in combination with excess superoxide produced during Rtp801 activation, contribute to increased oxido-nitrosative stress and lung protein nitration. However, lung-specific inhibition of iNOS with a iNOS-specific inhibitor, N6-(1-iminoethyl)-L-lysine, dihydrochloride (L-NIL) solely restricts lung protein nitration but fails to prevent or reverse the major tobacco smoke-induced oxidative lung injury. In comparison, the dietary antioxidant, ascorbate or vitamin C, can substantially prevent such damage by inhibiting both tobacco smoke-induced lung protein oxidation as well as activation of pulmonary Rtp801 and consequent iNOS/NO-induced nitration of lung proteins, that otherwise lead to increased proteolysis of such oxidized or nitrated proteins by endogenous lung proteases, resulting in emphysematous lung damage. Vitamin C also restricts the up-regulation of matrix-metalloproteinase-9, the major lung protease involved in the proteolysis of such modified lung proteins during tobacco smoke-induced emphysema. Overall, our findings implicate tobacco-smoke oxidant(s) as the primary etiopathogenic factor behind both the noncellular and cellular damage mechanisms governing emphysematous lung injury and demonstrate the potential of vitamin C to accomplish holistic prevention of such damage. PMID:27382160

  3. NOS2 Is Critical to the Development of Emphysema in Sftpd Deficient Mice but Does Not Affect Surfactant Homeostasis

    PubMed Central

    Guo, Chang-Jiang; Scott, Pamela A.; Haenni, Beat; Beers, Michael F.; Ochs, Matthias; Gow, Andrew J.

    2014-01-01

    Rationale Surfactant protein D (SP-D) has important immuno-modulatory properties. The absence of SP-D results in an inducible NO synthase (iNOS, coded by NOS2 gene) related chronic inflammation, development of emphysema-like pathophysiology and alterations of surfactant homeostasis. Objective In order to test the hypothesis that SP-D deficiency related abnormalities in pulmonary structure and function are a consequence of iNOS induced inflammation, we generated SP-D and iNOS double knockout mice (DiNOS). Methods Structural data obtained by design-based stereology to quantify the emphysema-like phenotype and disturbances of the intracellular surfactant were correlated to invasive pulmonary function tests and inflammatory markers including activation markers of alveolar macrophages and compared to SP-D (Sftpd−/−) and iNOS single knockout mice (NOS2−/−) as well as wild type (WT) littermates. Measurements and Results DiNOS mice had reduced inflammatory cells in BAL and BAL-derived alveolar macrophages showed an increased expression of markers of an alternative activation as well as reduced inflammation. As evidenced by increased alveolar numbers and surface area, emphysematous changes were attenuated in DiNOS while disturbances of the surfactant system remained virtually unchanged. Sftpd−/− demonstrated alterations of intrinsic mechanical properties of lung parenchyma as shown by reduced stiffness and resistance at its static limits, which could be corrected by additional ablation of NOS2 gene in DiNOS. Conclusion iNOS related inflammation in the absence of SP-D is involved in the emphysematous remodeling leading to a loss of alveoli and associated alterations of elastic properties of lung parenchyma while disturbances of surfactant homeostasis are mediated by different mechanisms. PMID:24465666

  4. Annexin V decreases PS-mediated macrophage efferocytosis and deteriorates elastase-induced pulmonary emphysema in mice.

    PubMed

    Yoshida, S; Minematsu, N; Chubachi, S; Nakamura, H; Miyazaki, M; Tsuduki, K; Takahashi, S; Miyasho, T; Iwabuchi, T; Takamiya, R; Tateno, H; Mouded, M; Shapiro, S D; Asano, K; Betsuyaku, T

    2012-11-15

    Efferocytosis is believed to be a key regulator for lung inflammation in chronic obstructive pulmonary disease. In this study we pharmacologically inhibited efferocytosis with annexin V and attempted to determine its impact on the progression of pulmonary emphysema in mouse. We first demonstrated in vitro and in vivo efferocytosis experiments using annexin V, an inhibitor for phosphatidylserine-mediated efferocytosis. We then inhibited efferocytosis in porcine pancreatic elastase (PPE)-treated mice. PPE-treated mice were instilled annexin V intranasally starting from day 8 until day 20. Mean linear intercept (Lm) was measured, and cell apoptosis was assessed in lung specimen obtained on day 21. Cell profile, apoptosis, and mRNA expression of matrix metalloproteinases (MMPs) and growth factors were evaluated in bronchoalveolar lavage (BAL) cells on day 15. Annexin V attenuated macrophage efferocytosis both in vitro and in vivo. PPE-treated mice had a significant higher Lm, and annexin V further increased that by 32%. More number of macrophages was found in BAL fluid in this group. Interestingly, cell apoptosis was not increased by annexin V treatment both in lung specimens and BAL fluid, but macrophages from mice treated with both PPE and annexin V expressed higher MMP-2 mRNA levels and had a trend for higher MMP-12 mRNA expression. mRNA expression of keratinocyte growth factor tended to be downregulated. We showed that inhibited efferocytosis with annexin V worsened elastase-induced pulmonary emphysema in mice, which was, at least partly, attributed to a lack of phenotypic change in macrophages toward anti-inflammatory one.

  5. Quantitative computed tomography of lung parenchyma in patients with emphysema: analysis of higher-density lung regions

    NASA Astrophysics Data System (ADS)

    Lederman, Dror; Leader, Joseph K.; Zheng, Bin; Sciurba, Frank C.; Tan, Jun; Gur, David

    2011-03-01

    Quantitative computed tomography (CT) has been widely used to detect and evaluate the presence (or absence) of emphysema applying the density masks at specific thresholds, e.g., -910 or -950 Hounsfield Unit (HU). However, it has also been observed that subjects with similar density-mask based emphysema scores could have varying lung function, possibly indicating differences of disease severity. To assess this possible discrepancy, we investigated whether density distribution of "viable" lung parenchyma regions with pixel values > -910 HU correlates with lung function. A dataset of 38 subjects, who underwent both pulmonary function testing and CT examinations in a COPD SCCOR study, was assembled. After the lung regions depicted on CT images were automatically segmented by a computerized scheme, we systematically divided the lung parenchyma into different density groups (bins) and computed a number of statistical features (i.e., mean, standard deviation (STD), skewness of the pixel value distributions) in these density bins. We then analyzed the correlations between each feature and lung function. The correlation between diffusion lung capacity (DLCO) and STD of pixel values in the bin of -910HU <= PV < -750HU was -0.43, as compared with a correlation of -0.49 obtained between the post-bronchodilator ratio (FEV1/FVC) measured by the forced expiratory volume in 1 second (FEV1) dividing the forced vital capacity (FVC) and the STD of pixel values in the bin of -1024HU <= PV < -910HU. The results showed an association between the distribution of pixel values in "viable" lung parenchyma and lung function, which indicates that similar to the conventional density mask method, the pixel value distribution features in "viable" lung parenchyma areas may also provide clinically useful information to improve assessments of lung disease severity as measured by lung functional tests.

  6. Comparison of biophysical factors influencing on emphysema quantification with low-dose CT

    NASA Astrophysics Data System (ADS)

    Heo, Chang Yong; Kim, Jong Hyo

    2014-03-01

    Emphysema Index(EI) measurements in MDCT is known to be influenced by various biophysical factors such as total lung volume, and body size. We investigated the association of the four biophysical factors with emphysema index in low-dose MDCT. In particular, we attempted to identify a potentially stronger biophysical factor than total lung volume. A total of 400 low-dose MDCT volumes taken at 120kVp, 40mAs, 1mm thickness, and B30f reconstruction kernel were used. The lungs, airways, and pulmonary vessels were automatically segmented, and two Emphysema Indices, relative area below -950HU(RA950) and 15th percentile(Perc15), were extracted from the segmented lungs. The biophysical factors such as total lung volume(TLV), mode of lung attenuation(ModLA), effective body diameter(EBD), and the water equivalent body diameter(WBD) were estimated from the segmented lung and body area. The association of biophysical factors with emphysema indices were evaluated by correlation coefficients. The mean emphysema indices were 8.3±5.5(%) in RA950, and -930±18(HU) in Perc15. The estimates of biophysical factors were 4.7±1.0(L) in TLV, -901±21(HU) in ModLA, 26.9±2.2(cm) in EBD, and 25.9±2.6(cm) in WBD. The correlation coefficients of biophysical factors with RA950 were 0.73 in TLV, 0.94 in ModLA, 0.31 in EBD, and 0.18 WBD, the ones with Perc15 were 0.74 in TLV, 0.98 in ModLA, 0.29 in EBD, and 0.15 WBD. Study results revealed that two biophysical factors, TLV and ModLA, mostly affects the emphysema indices. In particular, the ModLA exhibited strongest correlation of 0.98 with Perc15, which indicating the ModLA is the most significant confounding biophysical factor in emphysema indices measurement.

  7. Role of LTB₄ in the pathogenesis of elastase-induced murine pulmonary emphysema.

    PubMed

    Shim, Y Michael; Paige, Mikell; Hanna, Halim; Kim, Su H; Burdick, Marie D; Strieter, Robert M

    2010-12-01

    Exaggerated levels of the leukotriene B₄ (LTB₄) frequently coexist at sites of inflammation and tissue remodeling. Therefore, we hypothesize that the LTB₄ pathway plays an important role in the pathogenesis of neutrophilic inflammation that contributes to pulmonary emphysema. In this study, significant levels of LTB₄ were detected in human lung tissues with emphysema compared with lungs without emphysema (9,497 ± 2,839 vs. 4,142 ± 1,173 pg/ml, n = 9 vs. 10, P = 0.04). To further determine the biological role of LTB₄ in the pathogenesis of emphysema, we compared the lungs of wild-type (WT) and LTA₄ hydrolase-/- mice (LTB₄ deficient, LTA₄H-/-) exposed to intranasal elastase or vehicle control. We found that intranasal elastase induced accumulation of LTB₄ in the lungs and caused progressively worsening emphysema between 14 and 28 days after elastase exposure in WT mice but not in LTA₄H-/- mice. Premortem physiology documented increased lung compliance in elastase-exposed WT mice compared with elastase-exposed LTA₄H-/- mice as measured by Flexivent (0.058 ± 0.005 vs. 0.041 ± 0.002 ml/cmH₂O pressure). Postmortem morphometry documented increased total lung volume and alveolar sizes in elastase-exposed WT mice compared with elastase-exposed LTA₄H-/- mice as measured by volume displacement and alveolar chord length assessment. Furthermore, elastase-exposed LTA₄H-/- mice were found to have significantly delayed influx of the CD45(high)CD11b(high)Ly6G(high) leukocytes compatible with neutrophils compared with elastase-exposed WT mice. Mechanistic insights to these phenotypes were provided by demonstrating protection from elastase-induced murine emphysema with neutrophil depletion in the elastase-exposed WT mice and by demonstrating time-dependent modulation of cysteinyl leukotriene biosynthesis in the elastase-exposed LTA₄H-/- mice compared with elastase-exposed WT mice. Together, these findings demonstrated that LTB₄ played an important

  8. Bilateral periorbital and cervicofacial emphysema following retinal surgery and fluid gas exchange in a case of inadvertent globe perforation.

    PubMed

    Asnani, Haresh T; Mehta, Vinod C; Nair, Akshay Gopinathan; Jain, Vandana

    2015-06-01

    Surgical emphysema is defined as gas or air trapped in the subcutaneous tissue plane. Here, we report a rare case of bilateral periorbital and cervicofacial subcutaneous emphysema following a vitreoretinal surgery for inadvertent globe perforation during the administration of peribulbar anesthesia. This condition, although self-resolving when restricted to the subcutaneous plane has the potential to spread into deeper tissue planes such as the retropharyngeal space. The presence of crepitus helps to distinguish it from angioneurotic edema. Ophthalmologists must be sensitive to the fact that surgical emphysema can be a very rare, but possible complication of an intraocular surgery following globe perforation.

  9. Clinical significance of serum concentration of interleukin 8 in patients with bronchial asthma or chronic pulmonary emphysema.

    PubMed

    Kanazawa, H; Kurihara, N; Otsuka, T; Fujii, T; Tanaka, S; Kudoh, S; Hirata, K; Takeda, T

    1996-01-01

    Interleukin-8 (IL-8) belongs to the family of chemotactic cytokines and has been shown to activate neutrophils in vitro and in vivo. In this study, we measured IL-8 concentration in the serum of patients with pulmonary emphysema or bronchial asthma. IL-8 concentration in serum of emphysema patients was significantly higher than in asthmatics; in emphysema patients it was significantly correlated with the smoking index and the annual decrease of FEV1.0. In asthmatics IL-8 concentration was below the level of detection, but was markedly increased during exacerbation of asthma. Our findings suggest that IL-8 may be one of the causal factors in these diseases.

  10. Increased levels of interleukin-8 in BAL fluid from smokers susceptible to pulmonary emphysema

    PubMed Central

    Tanino, M; Betsuyaku, T; Takeyabu, K; Tanino, Y; Yamaguchi, E; Miyamoto, K; Nishimura, M

    2002-01-01

    Background: It has previously been shown that smokers with computed tomographic (CT) evidence of subclinical emphysema have signs of neutrophil activation, despite having no appreciable increase in the number of neutrophils in their bronchoalveolar lavage (BAL) fluid. Methods: The levels of the following chemoattractants in BAL fluid from 61 community based older volunteers classified into four groups according to current smoking status and the presence or absence of emphysema were determined: interleukin 8 (IL-8), epithelial neutrophil activating protein 78 (ENA-78) and leukotriene B4 (LTB4) which are primarily chemotactic for neutrophils; monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein-1α (MIP-1α) which are predominantly chemotactic for mononuclear leucocytes. Results: Of the five chemoattractants studied, only the level of IL-8 in BAL fluid clearly distinguished between subjects with and without emphysema among current smokers (median values 34.7 and 12.2 pg/ml, respectively, p<0.01). In addition, the levels of IL-8 and neutrophil elastase-α1 protease inhibitor complex in BAL fluid were significantly correlated (r=0.65, p<0.01). There was no difference in either the release of IL-8 from cultured alveolar macrophages at 24 hours or the expression of IL-8 messenger RNA of alveolar macrophages in the two groups of current smokers with and without emphysema. Conclusion: An accelerated response of IL-8 to chronic smoking is a factor that characterises those smokers who are susceptible to pulmonary emphysema, although the cellular source of IL-8 remains to be determined. PMID:11978916

  11. Lung sound intensity in patients with emphysema and in normal subjects at standardised airflows.

    PubMed Central

    Schreur, H J; Sterk, P J; Vanderschoot, J; van Klink, H C; van Vollenhoven, E; Dijkman, J H

    1992-01-01

    BACKGROUND: A common auscultatory finding in pulmonary emphysema is a reduction of lung sounds. This might be due to a reduction in the generation of sounds due to the accompanying airflow limitation or to poor transmission of sounds due to destruction of parenchyma. Lung sound intensity was investigated in normal and emphysematous subjects in relation to airflow. METHODS: Eight normal men (45-63 years, FEV1 79-126% predicted) and nine men with severe emphysema (50-70 years, FEV1 14-63% predicted) participated in the study. Emphysema was diagnosed according to pulmonary history, results of lung function tests, and radiographic criteria. All subjects underwent phonopneumography during standardised breathing manoeuvres between 0.5 and 2 1 below total lung capacity with inspiratory and expiratory target airflows of 2 and 1 l/s respectively during 50 seconds. The synchronous measurements included airflow at the mouth and lung volume changes, and lung sounds at four locations on the right chest wall. For each microphone airflow dependent power spectra were computed by using fast Fourier transformation. Lung sound intensity was expressed as log power (in dB) at 200 Hz at inspiratory flow rates of 1 and 2 l/s and at an expiratory flow rate of 1 l/s. RESULTS: Lung sound intensity was well repeatable on two separate days, the intraclass correlation coefficient ranging from 0.77 to 0.94 between the four microphones. The intensity was strongly influenced by microphone location and airflow. There was, however, no significant difference in lung sound intensity at any flow rate between the normal and the emphysema group. CONCLUSION: Airflow standardised lung sound intensity does not differ between normal and emphysematous subjects. This suggests that the auscultatory finding of diminished breath sounds during the regular physical examination in patients with emphysema is due predominantly to airflow limitation. Images PMID:1440459

  12. Efficacy of alpha1-antitrypsin augmentation therapy in conditions other than pulmonary emphysema.

    PubMed

    Blanco, Ignacio; Lara, Beatriz; de Serres, Frederick

    2011-04-12

    Up to now alpha 1-antitrypsin (AAT) augmentation therapy has been approved only for commercial use in selected adults with severe AAT deficiency-related pulmonary emphysema (i.e. PI*ZZ genotypes as well as combinations of Z, rare and null alleles expressing AAT serum concentrations <11 μmol/L). However, the compassionate use of augmentation therapy in recent years has proven outstanding efficacy in small cohorts of patients suffering from uncommon AAT deficiency-related diseases other than pulmonary emphysema, such as fibromyalgia, systemic vasculitis, relapsing panniculitis and bronchial asthma. Moreover, a series of preclinical studies provide evidence of the efficacy of AAT augmentation therapy in several infectious diseases, diabetes mellitus and organ transplant rejection. These facts have generated an expanding number of medical applications and patents with claims for other indications of AAT besides pulmonary emphysema. The aim of the present study is to compile and analyze both clinical and histological features of the aforementioned published case studies and reports where AAT augmentation therapy was used for conditions other than pulmonary emphysema. Particularly, our research refers to ten case reports and two clinical trials on AAT augmentation therapy in patients with both AAT deficiency and, at least, one of the following diseases: fibromyalgia, vasculitis, panniculitis and bronchial asthma. In all the cases, AAT was successfully applied whereas previous maximal conventional therapies had failed. In conclusion, laboratory studies in animals and humans as well as larger clinical trials should be, thus, performed in order to determine both the strong clinical efficacy and security of AAT in the treatment of conditions other than pulmonary emphysema.

  13. Characterization of a Mouse Model of Emphysema Induced by Multiple Instillations of Low-Dose Elastase

    PubMed Central

    Oliveira, Milena V.; Abreu, Soraia C.; Padilha, Gisele A.; Rocha, Nazareth N.; Maia, Lígia A.; Takiya, Christina M.; Xisto, Debora G.; Suki, Bela; Silva, Pedro L.; Rocco, Patricia R. M.

    2016-01-01

    Many experimental models have been proposed to study the pathophysiological features of emphysema, as well as to search for new therapeutic approaches for acute or chronically injured lung parenchyma. We aimed to characterize an emphysema model induced by multiple instillations of elastase by tracking changes in inflammation, remodeling, and cardiac function after each instillation. Forty-eight C57BL/6 mice were randomly assigned across two groups. Emphysema (ELA) animals received 1, 2, 3, or 4 intratracheal instillations of pancreatic porcine elastase (PPE, 0.2 IU) with a 1-week interval between them. Controls (C) received saline following the same protocol. Before and after implementation of the protocol, animals underwent echocardiographic analysis. After the first instillation of PPE, the percentage of mononuclear cells in the lung parenchyma increased compared to C (p = 0.0001). The second instillation resulted in hyperinflated alveoli, increased mean linear intercept, and reduced elastic fiber content in lung parenchyma compared to C (p = 0.0197). Following the third instillation, neutrophils and collagen fiber content in alveolar septa and airways increased, whereas static lung elastance was reduced compared to C (p = 0.0094). After the fourth instillation, the percentage of M1 macrophages in lungs; levels of interleukin-1β (IL-1β), keratinocyte-derived chemokine, hepatocyte growth factor (HGF), and vascular endothelial growth factor (VEGF); and collagen fiber content in the pulmonary vessel wall were increased compared to C (p = 0.0096). At this time point, pulmonary arterial hypertension was apparent, with increased diastolic right ventricular wall thickness. In conclusion, the initial phase of emphysema was characterized by lung inflammation with predominance of mononuclear cells, whereas at the late stage, impairment of pulmonary and cardiovascular functions was observed. This model enables analysis of therapies at different time points during

  14. Characterization of a Mouse Model of Emphysema Induced by Multiple Instillations of Low-Dose Elastase.

    PubMed

    Oliveira, Milena V; Abreu, Soraia C; Padilha, Gisele A; Rocha, Nazareth N; Maia, Lígia A; Takiya, Christina M; Xisto, Debora G; Suki, Bela; Silva, Pedro L; Rocco, Patricia R M

    2016-01-01

    Many experimental models have been proposed to study the pathophysiological features of emphysema, as well as to search for new therapeutic approaches for acute or chronically injured lung parenchyma. We aimed to characterize an emphysema model induced by multiple instillations of elastase by tracking changes in inflammation, remodeling, and cardiac function after each instillation. Forty-eight C57BL/6 mice were randomly assigned across two groups. Emphysema (ELA) animals received 1, 2, 3, or 4 intratracheal instillations of pancreatic porcine elastase (PPE, 0.2 IU) with a 1-week interval between them. Controls (C) received saline following the same protocol. Before and after implementation of the protocol, animals underwent echocardiographic analysis. After the first instillation of PPE, the percentage of mononuclear cells in the lung parenchyma increased compared to C (p = 0.0001). The second instillation resulted in hyperinflated alveoli, increased mean linear intercept, and reduced elastic fiber content in lung parenchyma compared to C (p = 0.0197). Following the third instillation, neutrophils and collagen fiber content in alveolar septa and airways increased, whereas static lung elastance was reduced compared to C (p = 0.0094). After the fourth instillation, the percentage of M1 macrophages in lungs; levels of interleukin-1β (IL-1β), keratinocyte-derived chemokine, hepatocyte growth factor (HGF), and vascular endothelial growth factor (VEGF); and collagen fiber content in the pulmonary vessel wall were increased compared to C (p = 0.0096). At this time point, pulmonary arterial hypertension was apparent, with increased diastolic right ventricular wall thickness. In conclusion, the initial phase of emphysema was characterized by lung inflammation with predominance of mononuclear cells, whereas at the late stage, impairment of pulmonary and cardiovascular functions was observed. This model enables analysis of therapies at different time points during

  15. Effect of Elastase-induced Emphysema on the Force-generating Ability of the Diaphragm

    PubMed Central

    Supinski, Gerald S.; Kelsen, Steven G.

    1982-01-01

    The effect of emphysema on the ability of the diaphragm to generate force was examined in costal diaphragm muscle strips from 10 Golden hamsters killed 18 mo after intratracheal injection of pancreatic elastase in a dose producing hyperinflation (mean total lung capacity [TLC] = 163% of control) and generalized panacinar emphysema. 13 saline-injected normal animals served as controls. The time course of isometric tension and the effect of alterations in muscle fiber and sarcomere length on the isometric tension (T) generated in response to tetanizing electrical stimuli (length-tension [L-T] relationship) were examined. Elastase administration caused an increase in diaphragm muscle thickness and reduction in the length of costal diaphragm muscle fibers measured in situ. Emphysema significantly increased the maximum tetanic tension as a result of hypertrophy. Maximal tension corrected for increases in muscle cross-sectional area (T/cm2), however, was the same in emphysematous (E) and control (C) animals. Emphysema also shifted the muscle fiber L-T curve of the diaphragm but not of a control muscle, the soleus, toward shorter lengths. In contrast to the effects of E on the diaphragm muscle fiber L-T curve, the sarcomere L-T curve was the same in E and C. Since the length at which tension was maximal correlated closely with sarcomere number (r = 0.94; P < 0.001) reduction in the number of sarcomeres in series in muscles from emphysematous animals appeared to explain the shift in the muscle fiber L-T curve. We conclude that in elastase-induced emphysema adaptive changes both in diaphragm cross-sectional area and sarcomere number augment the force-generating ability of the diaphragm. We speculate that changes in sarcomere number compensate for alterations in muscle fiber length resulting from chronic hyperinflation of the thorax, while diaphragmatic muscle hypertrophy represents a response to changes in respiratory load and/or diaphragm configuration (La

  16. A low vitamin A status increases the susceptibility to cigarette smoke-induced lung emphysema in C57BL/6J mice.

    PubMed

    van Eijl, S; Mortaz, E; Versluis, C; Nijkamp, F P; Folkerts, G; Bloksma, N

    2011-04-01

    Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation. Cigarette smoke has been considered a major player in the pathogenesis of COPD. The inflamed airways of COPD patients contain several inflammatory cells. Vitamin A metabolites have been implicated in the repair of lung damage. Exposure to cigarette smoke has been shown to depress levels of retinol in lungs of rats. The purpose of this study was to investigate if a low, but not deficient, vitamin A status potentiated susceptibility to the development of cigarette smoke-induced lung emphysema in mice. Mice were bred that were the offspring's of 3 generations of mice that were fed a purified diet containing low levels of vitamin A and exposed to cigarette smoke for 3 months, every weekday. Then, levels of 9-cis, 13-cis, and all-trans retinoic acid, retinol and retinyl palmitate were measured in plasma, liver and right lung lobe. The left lung lobe was used to assess mean linear intercept (Lm), as a measure of smoke-induced lung damage. Average feed intakes were not different between treatment groups. We show that both retinol and retinyl palmitate levels were dramatically decreased in the storage organs of mice on the low vitamin A diet (retinol 2-fold in both lung and liver, and retinyl palmitate 5- fold in lung) which shows that the depletion was successful. However, this treatment did not result in the development of lung emphysema. However, smoke exposure led to a significant increase in Lm in mice with a low vitamin A status compared to the room air-breathing controls. Lung levels of acid retinoids were similar in all mice, irrespective of diet or smoke exposure. Concluding, a low vitamin A status increases the susceptibility to the development of cigarette smoke-induced lung emphysema, possibly because of decreased anti-oxidant capacity in the lungs due to locally reduced retinol and retinyl palmitate levels. These observations indicate that human populations with a low

  17. In patients with extensive subcutaneous emphysema, which technique achieves maximal clinical resolution: infraclavicular incisions, subcutaneous drain insertion or suction on in situ chest drain?

    PubMed

    Johnson, Charles H N; Lang, Sommer A; Bilal, Haris; Rammohan, Kandadai S

    2014-06-01

    A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: 'In patients with extensive subcutaneous emphysema, which technique achieves maximal clinical resolution: infraclavicular incisions, subcutaneous drain insertion or suction on in situ chest drain?'. Altogether more than 200 papers were found using the reported search, of which 14 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Subcutaneous emphysema is usually a benign, self-limiting condition only requiring conservative management. Interventions are useful in the context of severe patient discomfort, respiratory distress or persistent air leak. In the absence of any comparative study, it is not possible to choose definitively between infraclavicular incisions, drain insertion and increasing suction on an in situ drain as the best method for managing severe subcutaneous emphysema. All the three techniques described have been shown to provide effective relief. Increasing suction on a chest tube already in situ provided rapid relief in patients developing SE following pulmonary resection. A retrospective study showed resolution in 66%, increasing to 98% in those who underwent video-assisted thoracic surgery with identification and closure of the leak. Insertion of a drain into the subcutaneous tissue also provided rapid sustained relief. Several studies aided drainage by using regular compressive massage. Infraclavicular incisions were also shown to provide rapid relief, but were noted to be more invasive and carried the potential for cosmetic defect. No major complications were illustrated.

  18. Lung perfusion and emphysema distribution affect the outcome of endobronchial valve therapy

    PubMed Central

    Thomsen, Christian; Theilig, Dorothea; Herzog, Dominik; Poellinger, Alexander; Doellinger, Felix; Schreiter, Nils; Schreiter, Vera; Schürmann, Dirk; Temmesfeld-Wollbrueck, Bettina; Hippenstiel, Stefan; Suttorp, Norbert; Hubner, Ralf-Harto

    2016-01-01

    The exclusion of collateral ventilation (CV) and other factors affect the clinical success of endoscopic lung volume reduction (ELVR). However, despite its benefits, the outcome of ELVR remains difficult to predict. We investigated whether clinical success could be predicted by emphysema distribution assessed by computed tomography scan and baseline perfusion assessed by perfusion scintigraphy. Data from 57 patients with no CV in the target lobe (TL) were retrospectively analyzed after ELVR with valves. Pulmonary function tests (PFT), St George’s Respiratory Questionnaire (SGRQ), and 6-minute walk tests (6MWT) were performed on patients at baseline. The sample was grouped into high and low levels at the median of TL perfusion, ipsilateral nontarget lobe (INL) perfusion, and heterogeneity index (HI). These groups were analyzed for association with changes in outcome parameters from baseline to 3 months follow-up. Compared to baseline, patients showed significant improvements in PFT, SGRQ, and 6MWT (all P≤0.001). TL perfusion was not associated with changes in the outcome. High INL perfusion was significantly associated with increases in 6MWT (P=0.014), and high HI was associated with increases in forced expiratory volume in 1 second (FEV1), (P=0.012). Likewise, there were significant correlations for INL perfusion and improvement of 6MWT (r=0.35, P=0.03) and for HI and improvement in FEV1 (r=0.45, P=0.001). This study reveals new attributes that associate with positive outcomes for patient selection prior to ELVR. Patients with high perfusions in INL demonstrated greater improvements in 6MWT, while patients with high HI were more likely to respond in FEV1. PMID:27354783

  19. Liver growth factor treatment reverses emphysema previously established in a cigarette smoke exposure mouse model.

    PubMed

    Pérez-Rial, Sandra; Del Puerto-Nevado, Laura; Girón-Martínez, Alvaro; Terrón-Expósito, Raúl; Díaz-Gil, Juan J; González-Mangado, Nicolás; Peces-Barba, Germán

    2014-11-01

    Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease largely associated with cigarette smoke exposure (CSE) and characterized by pulmonary and extrapulmonary manifestations, including systemic inflammation. Liver growth factor (LGF) is an albumin-bilirubin complex with demonstrated antifibrotic, antioxidant, and antihypertensive actions even at extrahepatic sites. We aimed to determine whether short LGF treatment (1.7 μg/mouse ip; 2 times, 2 wk), once the lung damage was established through the chronic CSE, contributes to improvement of the regeneration of damaged lung tissue, reducing systemic inflammation. We studied AKR/J mice, divided into three groups: control (air-exposed), CSE (chronic CSE), and CSE + LGF (LGF-treated CSE mice). We assessed pulmonary function, morphometric data, and levels of various systemic inflammatory markers to test the LGF regenerative capacity in this system. Our results revealed that the lungs of the CSE animals showed pulmonary emphysema and inflammation, characterized by increased lung compliance, enlargement of alveolar airspaces, systemic inflammation (circulating leukocytes and serum TNF-α level), and in vivo lung matrix metalloproteinase activity. LGF treatment was able to reverse all these parameters, decreasing total cell count in bronchoalveolar lavage fluid and T-lymphocyte infiltration in peripheral blood observed in emphysematous mice and reversing the decrease in monocytes observed in chronic CSE mice, and tends to reduce the neutrophil population and serum TNF-α level. In conclusion, LGF treatment normalizes the physiological and morphological parameters and levels of various systemic inflammatory biomarkers in a chronic CSE AKR/J model, which may have important pathophysiological and therapeutic implications for subjects with stable COPD.

  20. Distinct subcutaneous emphysema following surgical wisdom tooth extraction in a patient suffering from ‘Gilles de la Tourette syndrome’

    PubMed Central

    Tomasetti, Patrick; Kuttenberger, Johannes; Bassetti, Renzo

    2015-01-01

    Subcutaneous emphysema is a rare complication in oral surgery. In most cases, it resolves spontaneously. However, air might disperse into deeper facial spaces causing life-threatening complications such as compression of the tracheobronchial tree or the development of pneumomediastinum. Moreover, microorganisms might spread from the oral cavity into deeper spaces. Hence, rapid diagnosis of subcutaneous emphysema is important. Characteristic signs are both a shiftable swelling and crepitation. In this case report, a 30-year-old man, suffering from the Gilles de la Tourette Syndrome, with a distinct subcutaneous emphysema after bilateral surgical wisdom tooth extraction is presented. Induced by a specific motor tic, air accumulated from the periorbital through to the parapharyngeal region. Applying a 10-cm-long Redon drainage tube as air valve, 10 days after wisdom teeth extraction, the patient was asymptomatic with complete resolution of the emphysema. PMID:26077530

  1. Salam's independence

    NASA Astrophysics Data System (ADS)

    Fraser, Gordon

    2009-01-01

    In his kind review of my biography of the Nobel laureate Abdus Salam (December 2008 pp45-46), John W Moffat wrongly claims that Salam had "independently thought of the idea of parity violation in weak interactions".

  2. Subcutaneous Facial and Neck Emphysema as First Sign of Intestinal Perforation in a Female Patient After a Routine Colonoscopy

    PubMed Central

    Anyfantakis, Dimitrios; Kastanakis, Miltiades; Karona, Paraskevi; Papadomichelakis, Alexandros; Bobolakis, Emmanouil

    2016-01-01

    Colonoscopy is a safe procedure for the diagnosis and management of colorectal diseases. Colonic perforation due to colonoscopy represents an uncommon complication. Here we present an unusual case of iatrogenic bowel perforation resulting in subcutaneous facial and neck emphysema, pneumomediastinum and pneumoretroperitoneum. Taking a detailed recent medical history information is always required when encountering patients with subcutaneous emphysema after invasive examination procedures. Alertness on iatrogenic complication eventualities may improve prognosis and avoid life-threatening conditions. PMID:28149153

  3. Emphysema on Thoracic CT and Exercise Ventilatory Inefficiency in Mild-to-Moderate COPD.

    PubMed

    Jones, Joshua H; Zelt, Joel T; Hirai, Daniel M; Diniz, Camilla V; Zaza, Aida; O'Donnell, Denis E; Neder, J Alberto

    2017-04-01

    There is growing evidence that emphysema on thoracic computed tomography (CT) is associated with poor exercise tolerance in COPD patients with only mild-to-moderate airflow obstruction. We hypothesized that an excessive ventilatory response to exercise (ventilatory inefficiency) would underlie these abnormalities. In a prospective study, 19 patients (FEV1 = 82 ± 13%, 12 Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 1) and 26 controls underwent an incremental exercise test. Ventilatory inefficiency was assessed by the ventilation ([Formula: see text]E)/CO2 output ([Formula: see text]CO2) nadir. Pulmonary blood flow (PBF) in a submaximal test was calculated by inert gas rebreathing. Emphysema was quantified as % of attenuation areas below 950 HU. Patients typically presented with centrilobular emphysema (76.8 ± 10.1% of total emphysema) in the upper lobes (upper/total lung ratio = 0.82 ± 0.04). They had lower peak oxygen uptake ([Formula: see text]O2), higher [Formula: see text]E/[Formula: see text]CO2 nadir, and greater dyspnea scores than controls (p < 0.05). Lower peak [Formula: see text]O2 and worse dyspnea were found in patients with higher [Formula: see text]E/[Formula: see text]CO2 nadirs (≥30). Patients had blunted increases in PBF from rest to iso-[Formula: see text]O2 exercise (p < 0.05). Higher [Formula: see text]E/[Formula: see text]CO2 nadir in COPD was associated with emphysema severity (r = 0.63) which, in turn, was related to reduced lung diffusing capacity (r = -0.72) and blunted changes in PBF from rest to exercise (r = -0.69) (p < 0.01). Ventilation "wasted" in emphysematous areas is associated with impaired exercise ventilatory efficiency in mild-to-moderate COPD. Exercise ventilatory inefficiency links structure (emphysema) and function (DLCO) to a key clinical outcome (poor exercise tolerance) in COPD patients with only modest spirometric abnormalities.

  4. Influence of emphysema distribution on pulmonary function parameters in COPD patients

    PubMed Central

    Bastos, Helder Novais e; Neves, Inês; Redondo, Margarida; Cunha, Rui; Pereira, José Miguel; Magalhães, Adriana; Fernandes, Gabriela

    2015-01-01

    ABSTRACT OBJECTIVE: To evaluate the impact that the distribution of emphysema has on clinical and functional severity in patients with COPD. METHODS: The distribution of the emphysema was analyzed in COPD patients, who were classified according to a 5-point visual classification system of lung CT findings. We assessed the influence of emphysema distribution type on the clinical and functional presentation of COPD. We also evaluated hypoxemia after the six-minute walk test (6MWT) and determined the six-minute walk distance (6MWD). RESULTS: Eighty-six patients were included. The mean age was 65.2 ± 12.2 years, 91.9% were male, and all but one were smokers (mean smoking history, 62.7 ± 38.4 pack-years). The emphysema distribution was categorized as obviously upper lung-predominant (type 1), in 36.0% of the patients; slightly upper lung-predominant (type 2), in 25.6%; homogeneous between the upper and lower lung (type 3), in 16.3%; and slightly lower lung-predominant (type 4), in 22.1%. Type 2 emphysema distribution was associated with lower FEV1, FVC, FEV1/FVC ratio, and DLCO. In comparison with the type 1 patients, the type 4 patients were more likely to have an FEV1 < 65% of the predicted value (OR = 6.91, 95% CI: 1.43-33.45; p = 0.016), a 6MWD < 350 m (OR = 6.36, 95% CI: 1.26-32.18; p = 0.025), and post-6MWT hypoxemia (OR = 32.66, 95% CI: 3.26-326.84; p = 0.003). The type 3 patients had a higher RV/TLC ratio, although the difference was not significant. CONCLUSIONS: The severity of COPD appears to be greater in type 4 patients, and type 3 patients tend to have greater hyperinflation. The distribution of emphysema could have a major impact on functional parameters and should be considered in the evaluation of COPD patients. PMID:26785956

  5. The role of persisting infections in the pathogenesis of pulmonary emphysema. Electron microscopy reveals a probable bacterial colonization of the alveolar space and the bronchioles.

    PubMed

    Theegarten, D; Stamatis, G; Morgenroth, K

    1999-01-01

    Lung volume reduction surgery (LVRS) yields resection specimens from patients with advanced pulmonary emphysema. Regarding the development of lung function parameters, recent results obtained by light microscopy revealed an unfavorable prognosis in patients with remarkable inflammation, particularly in the bronchioli. Tissue from ten patients (alpha1-antitrypsin level in the normal range) was furthermore investigated by electron microscopy. Scanning electron microscopy shows 0.4-0.6 micron spherical bodies variably densely arranged in the whole alveolar space and in the bronchioles of all patients. These bodies are mostly seen on the microvilli of type II pneumocytes. An immunological reaction with activation of macrophages and granulocytes occurs simultaneously. Macrophages show cytoplasmic extensions to the spherical bodies, which exhibit a cellular membrane but no cellular wall. This favors the diagnosis of bacterial colonization of the alveolar space and the bronchioles by mycoplasmas or L-forms of other bacteria. As patients undergoing lung volume reduction surgery are under optimal medical treatment and without any infection clinically, these findings appear to be relevant for the pathogenesis and/or progression of pulmonary emphysema.

  6. Phenotypic and genetic characterization of a novel phenotype in pigs characterized by juvenile hairlessness and age dependent emphysema

    PubMed Central

    Bruun, Camilla S; Jørgensen, Claus B; Bay, Lene; Cirera, Susanna; Jensen, Henrik E; Leifsson, Páll S; Nielsen, Jens; Christensen, Knud; Fredholm, Merete

    2008-01-01

    Background A pig phenotype characterized by juvenile hairlessness, thin skin and age dependent lung emphysema has been discovered in a Danish pig herd. The trait shows autosomal co-dominant inheritance with all three genotypes distinguishable. Since the phenotype shows resemblance to the integrin β6 -/- knockout phenotype seen in mice, the two genes encoding the two subunits of integrin αvβ6, i.e. ITGB6 and ITGAV, were considered candidate genes for this trait. Results The mutated pig phenotype is characterized by hairlessness until puberty, thin skin with few hair follicles and absence of musculi arrectores pili, and at puberty or later localized areas of emphysema are seen in the lungs. Comparative mapping predicted that the porcine ITGB6 andITGAV orthologs map to SSC15. In an experimental family (n = 113), showing segregation of the trait, the candidate region was confirmed by linkage analysis with four microsatellite markers. Mapping of the porcine ITGB6 and ITGAV in the IMpRH radiation hybrid panel confirmed the comparative mapping information. Sequencing of the ITGB6 and ITGAV coding sequences from affected and normal pigs revealed no evidence of a causative mutation, but alternative splicing of the ITGB6 pre-mRNA was detected. For both ITGB6 and ITGAV quantitative PCR revealed no significant difference in the expression levels in normal and affected animals. In a western blot, ITGB6 was detected in lung protein samples of all three genotypes. This result was supported by flow cytometric analyses which showed comparable reactions of kidney cells from affected and normal pigs with an integrin αvβ6 monoclonal antibody. Also, immunohistochemical staining of lung tissue with an integrin β6 antibody showed immunoreaction in both normal and affected pigs. Conclusion A phenotype resembling the integrin β6 -/- knockout phenotype seen in mice has been characterized in the pig. The candidate region on SSC15 has been confirmed by linkage analysis but molecular

  7. Orbital emphysema following nose blowing as a sequel of a snowboard related head injury.

    PubMed

    Taguchi, Y; Sakakibara, Y; Uchida, K; Kishi, H

    2004-10-01

    A case of orbital emphysema as a sequel of a snowboard related head injury is reported. It is believed that a fracture of the medial orbital wall was caused by the increased intraorbital pressure when the patient hit his forehead on the snowy ground, allowing air to enter the orbit when he blew his nose. Wearing goggles may prevent this type of sports related injury.

  8. Smokers with emphysema and small airway disease on computed tomography have lower bone density.

    PubMed

    Pompe, Esther; de Jong, Pim A; van Rikxoort, Eva M; Gallardo Estrella, Leticia; de Jong, Werner U; Vliegenthart, Rozemarijn; Oudkerk, Matthijs; van der Aalst, Carlijn M; van Ginneken, Bram; Lammers, Jan-Willem J; Mohamed Hoesein, Firdaus Aa

    2016-01-01

    Osteoporosis is more common in patients with COPD and in smokers. The aim of this study was to assess whether measures of emphysema and airway disease on computed tomography (CT) were associated with lower bone density or vertebral fractures in smokers with and without COPD. For this purpose, we included participants from the NELSON lung cancer screening trial. Bone density was measured as Hounsfield Units in the first lumbar vertebra, and vertebral fractures were assessed semiquantitatively. The 15th percentile method (Perc15) was used to assess emphysema, and the airway lumen perimeter (Pi10) was used for airway wall thickness. Expiratory/inspiratory-ratiomean lung density (E/I-ratioMLD) was used as a measure for air trapping and tracheal index to assess tracheal deformity. Linear regression models and logistic regression models were used to assess associations between CT biomarkers, bone density, and presence of fractures. Exactly 1,093 male participants were eligible for analysis. Lower Perc15 and higher E/I-ratioMLD were significantly associated with lower bone density (b=-1.27, P=0.02 and b=-0.37, P=0.02, respectively). Pi10 and tracheal index were not associated with bone density changes. CT-derived biomarkers were not associated with fracture prevalence. Bone density is lower with increasing extent of emphysema and small airway disease but is not associated with large airway disease and tracheal deformity. This may indicate the necessity to measure bone density early in smokers with emphysema and air trapping to prevent vertebral fractures.

  9. Bronchoscopic thermal vapour ablation therapy in the management of heterogeneous emphysema.

    PubMed

    Snell, Gregory; Herth, Felix J F; Hopkins, Peter; Baker, Kimberley M; Witt, Christian; Gotfried, Mark H; Valipour, Arschang; Wagner, Manfred; Stanzel, Franz; Egan, Jim J; Kesten, Steven; Ernst, Armin

    2012-06-01

    The need for a less invasive procedure than surgical lung volume reduction that can produce consistent improvements with reduced morbidity remains a medical goal in patients with emphysema. We sought to determine the effect of bronchoscopic thermal vapour ablation (BTVA) on lung volumes and outcomes in patients with emphysema. 44 patients with upper lobe-predominant emphysema were treated unilaterally with BTVA. Entry criteria included: age 40-75 yrs, forced expiratory volume in 1 s (FEV(1)) 15-45% predicted, previous pulmonary rehabilitation and a heterogeneity index (tissue/air ratio of lower lobe/upper lobe) from high-resolution computed tomography (HRCT) ≥ 1.2. Changes in FEV(1), St George's Respiratory Questionnaire (SGRQ), 6-min walk distance (6 MWD), modified Medical Research Council (mMRC) dyspnoea score, and hyperinflation were measured at baseline, and 3 and 6 months post-BTVA. At 6 months, mean ± SE FEV(1) improved by 141 ± 26 mL (p<0.001) and residual volume was reduced by 406 ± 113 mL (p<0.0001). SGRQ total score improved by 14.0 ± 2.4 points (p<0.001), with 73% improving by ≥ 4 points. Improvements were observed in 6 MWD (46.5 ± 10.6 m) and mMRC dyspnoea score (0.9 ± 0.2) (p<0.001 for both). Lower respiratory events (n=11) were the most common adverse event and occurred most often during the initial 30 days. BTVA therapy results in clinically relevant improvements in lung function, quality of life and exercise tolerance in upper lobe predominant emphysema.

  10. A comparison of fixation methods on lung morphology in a murine model of emphysema.

    PubMed

    Braber, S; Verheijden, K A T; Henricks, P A J; Kraneveld, A D; Folkerts, G

    2010-12-01

    Emphysema is characterized by enlargement of the alveoli, which is the most important parameter to assess the presence and severity of this disease. Alveolar enlargement is primarily defined on morphological criteria; therefore, characterization of this disease with morphological parameters is a prerequisite to study the pathogenesis. For this purpose, different methods of lung fixation were evaluated in a murine model of LPS-induced lung emphysema. Five different methods of lung fixation were evaluated: intratracheal instillation of fixatives, in situ fixation, fixed-volume fixation, vascular whole body perfusion, and vacuum inflation. In addition, the effects of three different fixatives (10% formalin, Carnoy's, and agarose/10% formalin solution) and two embedding methods (paraffin and plastic) were investigated on the murine lung morphology. Mice received intranasal administration of LPS to induce alveolar wall destruction. Quantification of air space enlargement was determined by mean linear intercept analysis, and the histological sections were analyzed for the most optimal fixation method. Additionally, routine immunohistological staining was performed on lung tissue of PBS-treated mice. Intratracheal instillation of formalin or agarose/formalin solution, in situ fixation, and fixed-volume fixation provided a normal lung architecture, in contrast to the lungs fixed via whole body perfusion and vacuum inflation. Formalin-fixed lungs resulted in the most optimal lung morphology for lung emphysema analysis when embedded in paraffin, while for Carnoy's fixed lungs, plastic embedding was preferred. The histological findings, the mean linear intercept measurement, and the immunohistochemistry data demonstrated that fixation by intratracheal instillation of 10% formalin or in situ fixation with 10% formalin are the two most optimal methods to fix lungs for alveolar enlargement analysis to study lung emphysema.

  11. Left Upper Lobectomy for Congenital Lobar Emphysema in a Low Weight Infant

    PubMed Central

    Petsios, Konstantinos; Bobos, Dimitrios; Sarafidis, Kosmas; Nikopoulos, Stefanos; Kyriakoulis, Konstantinos; Lioulias, Achilleas; Giannopoulos, Nicholas

    2016-01-01

    Congenital lobar emphysema (CLE) is a rare lung congenital malformation. Differential diagnosis of the disease remains challenging in an infant with acute respiratory distress. We report a case of a 3-week-old female infant with a weight of 2.1 kg who presented respiratory distress related to CLE. Left upper lobectomy was performed and she had an uneventful recovery. PMID:27597924

  12. Small-animal dark-field radiography for pulmonary emphysema evaluation

    NASA Astrophysics Data System (ADS)

    Yaroshenko, Andre; Meinel, Felix G.; Hellbach, Katharina; Bech, Martin; Velroyen, Astrid; Müller, Mark; Bamberg, Fabian; Nikolaou, Konstantin; Reiser, Maximilian F.; Yildirim, Ali Ã.-.; Eickelberg, Oliver; Pfeiffer, Franz

    2014-03-01

    Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality worldwide and emphysema is one of its main components. The disorder is characterized by irreversible destruction of the alveolar walls and enlargement of distal airspaces. Despite the severe changes in the lung tissue morphology, conventional chest radiographs have only a limited sensitivity for the detection of mild to moderate emphysema. X-ray dark-field is an imaging modality that can significantly increase the visibility of lung tissue on radiographic images. The dark-field signal is generated by coherent, small-angle scattering of x-rays on the air-tissue interfaces in the lung. Therefore, morphological changes in the lung can be clearly visualized on dark-field images. This is demonstrated by a preclinical study with a small-animal emphysema model. To generate a murine model of pulmonary emphysema, a female C57BL/6N mouse was treated with a single orotracheal application of porcine pancreatic elastase (80 U/kg body weight) dissolved in phosphate-buffered saline (PBS). Control mouse received PBS. The mice were imaged using a small-animal dark-field scanner. While conventional x-ray transmission radiography images revealed only subtle indirect signs of the pulmonary disorder, the difference between healthy and emphysematous lungs could be clearly directly visualized on the dark-field images. The dose applied to the animals is compatible with longitudinal studies. The imaging results correlate well with histology. The results of this study reveal the high potential of dark-field radiography for clinical lung imaging.

  13. Exercise testing in severe emphysema: association with quality of life and lung function.

    PubMed

    Brown, Cynthia D; Benditt, Joshua O; Sciurba, Frank C; Lee, Shing M; Criner, Gerard J; Mosenifar, Zab; Shade, David M; Slivka, William A; Wise, Robert A

    2008-04-01

    Six-minute walk testing (6MWT) and cardiopulmonary exercise testing (CPX) are used to evaluate impairment in emphysema. However, the extent of impairment in these tests as well as the correlation of these tests with each other and lung function in advanced emphysema is not well characterized. During screening for the National Emphysema Treatment Trial, maximum ergometer CPX and 6MWT were performed in 1,218 individuals with severe COPD with an average FEV(1) of 26.9 +/- 7.1 % predicted. Predicted values for 6MWT and CPX were calculated from reference equations. Correlation coefficients and multivariable regression models were used to determine the association between lung function, quality of life (QOL) scores, and exercise measures. The two forms of exercise testing were correlated with each other (r = 0.57, p < 0.0001). However, the impairment of performance on CPX was greater than on the 6MWT (27.6 +/- 16.8 vs. 67.9 +/- 18.9 % predicted). Both exercise tests had similar correlation with measures of QOL, but maximum exercise capacity was better correlated with lung function measures than 6-minute walk distance. After adjustment, 6MWD had a slightly greater association with total SGRQ score than maximal exercise (effect size 0.37 +/- 0.04 vs. 0.25 +/- 0.03 %predicted/unit). Despite advanced emphysema, patients are able to maintain 6MWD to a greater degree than maximum exercise capacity. Moreover, the 6MWT may be a better test of functional capacity given its greater association with QOL measures whereas CPX is a better test of physiologic impairment.

  14. Quantitative assessment of emphysema from whole lung CT scans: comparison with visual grading

    NASA Astrophysics Data System (ADS)

    Keller, Brad M.; Reeves, Anthony P.; Apanosovich, Tatiyana V.; Wang, Jianwei; Yankelevitz, David F.; Henschke, Claudia I.

    2009-02-01

    Emphysema is a disease of the lungs that destroys the alveolar air sacs and induces long-term respiratory dysfunction. CT scans allow for imaging of the anatomical basis of emphysema and for visual assessment by radiologists of the extent present in the lungs. Several measures have been introduced for the quantification of the extent of disease directly from CT data in order to add to the qualitative assessments made by radiologists. In this paper we compare emphysema index, mean lung density, histogram percentiles, and the fractal dimension to visual grade in order to evaluate the predictability of radiologist visual scoring of emphysema from low-dose CT scans through quantitative scores, in order to determine which measures can be useful as surrogates for visual assessment. All measures were computed over nine divisions of the lung field (whole lung, individual lungs, and upper/middle/lower thirds of each lung) for each of 148 low-dose, whole lung scans. In addition, a visual grade of each section was also given by an expert radiologist. One-way ANOVA and multinomial logistic regression were used to determine the ability of the measures to predict visual grade from quantitative score. We found that all measures were able to distinguish between normal and severe grades (p<0.01), and between mild/moderate and all other grades (p<0.05). However, no measure was able to distinguish between mild and moderate cases. Approximately 65% prediction accuracy was achieved from using quantitative score to predict visual grade, with 73% if mild and moderate cases are considered as a single class.

  15. Curcumin attenuates elastase- and cigarette smoke-induced pulmonary emphysema in mice.

    PubMed

    Suzuki, Masaru; Betsuyaku, Tomoko; Ito, Yoko; Nagai, Katsura; Odajima, Nao; Moriyama, Chinatsu; Nasuhara, Yasuyuki; Nishimura, Masaharu

    2009-04-01

    Curcumin, a yellow pigment obtained from turmeric (Curcumina longa), is a dietary polyphenol that has been reported to possess anti-inflammatory and antioxidant properties. The effect of curcumin against the development of pulmonary emphysema in animal models is unknown. The aim of this study was to determine whether curcumin is able to attenuate the development of pulmonary emphysema in mice. Nine-week-old male C57BL/6J mice were treated with intratracheal porcine pancreatic elastase (PPE) or exposed to mainstream cigarette smoke (CS) (60 min/day for 10 consecutive days or 5 days/wk for 12 wk) to induce pulmonary inflammation and emphysema. Curcumin (100 mg/kg) or vehicle was administrated daily by oral gavage 1 h and 24 h before intratracheal PPE treatment and daily thereafter throughout a 21-day period in PPE-exposed mice and 1 h before each CS exposure in CS-exposed mice. As a result, curcumin treatment significantly inhibited PPE-induced increase of neutrophils in bronchoalveolar lavage fluid at 6 h and on day 1 after PPE administration, with an increase in antioxidant gene expression at 6 h and significantly attenuated PPE-induced air space enlargement on day 21. It was also found that curcumin treatment significantly inhibited CS-induced increase of neutrophils and macrophages in bronchoalveolar lavage fluid after 10 consecutive days of CS exposure and significantly attenuated CS-induced air space enlargement after 12 wk of CS exposure. In conclusion, oral curcumin administration attenuated PPE- and CS-induced pulmonary inflammation and emphysema in mice.

  16. Influence of experimental pulmonary emphysema on the toxicological effects from inhaled nitrogen dioxide and diesel exhaust

    SciTech Connect

    Mauderly, J.L.; Bice, D.E.; Cheng, Y.S.; Gillett, N.A.; Henderson, R.F.; Pickrell, J.A.; Wolff, R.K. )

    1989-10-01

    This project examined the influence of preexisting, experimentally induced pulmonary emphysema on the adverse health effects in rats of chronic inhalation exposure to either nitrogen dioxide or automotive diesel-engine exhaust. Previous reports indicated that humans with chronic lung disease were among those most severely affected by episodic exposures to high concentrations of airborne toxicants. There were no previous reports comparing the effects of chronic inhalation exposure to components of automotive emissions in emphysematous and normal animals. The hypothesis tested in this project was that rats with preexisting pulmonary emphysema were more susceptible than rats with normal lungs to the adverse effects of the toxicant exposures. Young adult rats were housed continuously in inhalation exposure chambers and exposed seven hours per day, five days per week, for 24 months to nitrogen dioxide at 9.5 parts per million (ppm)2, or to diesel exhaust at 3.5 mg soot/m3, or to clean air as control animals. These concentrations were selected to produce mild, but distinct, effects in rats with normal lungs. Pulmonary emphysema was induced in one-half of the rats by intratracheal instillation of the proteolytic enzyme elastase six weeks before the toxicant exposures began. Health effects were evaluated after 12, 18, and 24 months of exposure. The measurements included respiratory function, clearance of inhaled radiolabeled particles, pulmonary immune responses to instilled antigen, biochemistry and cytology of airway fluid, total lung collagen, histopathology, lung morphometry, and lung burdens of diesel soot. The significance of influences of emphysema and toxicant exposure, and interactions between influences of the two treatments, were evaluated by analysis of variance.

  17. Lung Volume Reduction Coils as a Novel Bronchoscopic Treatment for Emphysema

    PubMed Central

    Connolly, Timothy A.

    2016-01-01

    Chronic obstructive pulmonary disease remains a major cause of morbidity and mortality worldwide. Despite regular advances in pharmacology, there remains great potential for addressing structural deficiencies, especially in emphysema. The loss of alveolar attachments to small bronchial tubes results in diffuse loss of elastic recoil and airway collapse during exhalation. This appears physiologically as hyperinflation of lung volumes with flattened diaphragms and significantly elevated residual volumes (RV) on pulmonary function testing (predicted RV > 175%). PMID:28298960

  18. Emphysema as a result of involuntary exposure to tobacco smoke: morphometrical study of the rat.

    PubMed

    Escolar, J D; Martínez, M N; Rodríguez, F J; Gonzalo, C; Escolar, M A; Roche, P A

    1995-01-01

    Several attempts have been made to describe the relation that exists between tobacco smoke and emphysema, through different experimental models of the active smoker. Despite the negative effects that involuntarily inhaled tobacco smoke can have on the lung, no experimental model of the passive smoker has been proposed. In this study, an experimental model of the involuntary smoker is described and the following hypothesis proposed: Passive exposure to tobacco smoke produces morphological alterations in the rat lung, which are compatible with emphysema. Emphysema will be considered to have been caused when enlargement of the distal airspaces of the lung and lung tissue destruction are demonstrated. Sixty Wistar rats were used, divided into two groups: a control group and a group that was passively exposed to tobacco smoke for a period of 3 months. A morphometrical study of the lung was performed using a computerized system. To demonstrate enlargement of the distal airspaces of the lung, the following variables were quantified: alveolar chord and mean linear intercept index (Lm); tissue loss was demonstrated by means of the quantification of the variables: tissue density, internal alveolar perimeter (IAP), and wall thickness (WT). The elastic fiber was also quantified. The animals that were exposed to tobacco smoke displayed the following significant alterations (p < .05): an increase of the alveolar chord and of the Lm, a decrease of the IAP, WT, and tissue density, and a loss of the elastic component of the lung. On the basis of these findings, it is concluded that the rats that were exposed in a passive way to tobacco smoke display morphological pulmonary alterations that are compatible with the definition of emphysema.

  19. Sensitivity of heterozygous α1,6-fucosyltransferase knock-out mice to cigarette smoke-induced emphysema: implication of aberrant transforming growth factor-β signaling and matrix metalloproteinase gene expression.

    PubMed

    Gao, Congxiao; Maeno, Toshitaka; Ota, Fumi; Ueno, Manabu; Korekane, Hiroaki; Takamatsu, Shinji; Shirato, Ken; Matsumoto, Akio; Kobayashi, Satoshi; Yoshida, Keiichi; Kitazume, Shinobu; Ohtsubo, Kazuaki; Betsuyaku, Tomoko; Taniguchi, Naoyuki

    2012-05-11

    We previously demonstrated that a deficiency in core fucosylation caused by the genetic disruption of α1,6-fucosyltransferase (Fut8) leads to lethal abnormalities and the development of emphysematous lesions in the lung by attenuation of TGF-β1 receptor signaling. Herein, we investigated the physiological relevance of core fucosylation in the pathogenesis of emphysema using viable heterozygous knock-out mice (Fut8(+/-)) that were exposed to cigarette smoke (CS). The Fut8(+/-) mice exhibited a marked decrease in FUT8 activity, and matrix metalloproteinase (MMP)-9 activities were elevated in the lung at an early stage of exposure. Emphysema developed after a 3-month CS exposure, accompanied by the recruitment of large numbers of macrophages to the lung. CS exposure substantially and persistently elevated the expression level of Smad7, resulting in a significant reduction of Smad2 phosphorylation (which controls MMP-9 expression) in Fut8(+/-) mice and Fut8-deficient embryonic fibroblast cells. These in vivo and in vitro studies show that impaired core fucosylation enhances the susceptibility to CS and constitutes at least part of the disease process of emphysema, in which TGF-β-Smad signaling is impaired and the MMP-mediated destruction of lung parenchyma is up-regulated.

  20. A new experimental model of cigarette smoke-induced emphysema in Wistar rats*, **

    PubMed Central

    Kozma, Rodrigo de las Heras; Alves, Edson Marcelino; Barbosa-de-Oliveira, Valter Abraão; Lopes, Fernanda Degobbi Tenorio Quirino dos Santos; Guardia, Renan Cenize; Buzo, Henrique Vivi; de Faria, Carolina Arruda; Yamashita, Camila; Cavazzana, Manzelio; Frei, Fernando; Ribeiro-Paes, Maria José de Oliveira; Ribeiro-Paes, João Tadeu

    2014-01-01

    OBJECTIVE: To describe a new murine model of cigarette smoke-induced emphysema. METHODS: Twenty-four male Wistar rats were divided into two groups: the cigarette smoke group, comprising 12 rats exposed to smoke from 12 commercial filter cigarettes three times a day (a total of 36 cigarettes per day) every day for 30 weeks; and the control group, comprising 12 rats exposed to room air three times a day every day for 30 weeks. Lung function was assessed by mechanical ventilation, and emphysema was morphometrically assessed by measurement of the mean linear intercept (Lm). RESULTS: The mean weight gain was significantly (approximately ten times) lower in the cigarette smoke group than in the control group. The Lm was 25.0% higher in the cigarette smoke group. There was a trend toward worsening of lung function parameters in the cigarette smoke group. CONCLUSIONS: The new murine model of cigarette smoke-induced emphysema and the methodology employed in the present study are effective and reproducible, representing a promising and economically viable option for use in studies investigating the pathophysiology of and therapeutic approaches to COPD. PMID:24626269

  1. Hyperpolarized 83Kr magnetic resonance imaging of alveolar degradation in a rat model of emphysema

    PubMed Central

    Lilburn, David M. L.; Lesbats, Clémentine; Six, Joseph S.; Dubuis, Eric; Yew-Booth, Liang; Shaw, Dominick E.; Belvisi, Maria G.; Birrell, Mark A.; Pavlovskaya, Galina E.; Meersmann, Thomas

    2015-01-01

    Hyperpolarized 83Kr surface quadrupolar relaxation (SQUARE) generates MRI contrast that was previously shown to correlate with surface-to-volume ratios in porous model surface systems. The underlying physics of SQUARE contrast is conceptually different from any other current MRI methodology as the method uses the nuclear electric properties of the spin I = 9/2 isotope 83Kr. To explore the usage of this non-radioactive isotope for pulmonary pathophysiology, MRI SQUARE contrast was acquired in excised rat lungs obtained from an elastase-induced model of emphysema. A significant 83Kr T1 relaxation time increase in the SQUARE contrast was found in the elastase-treated lungs compared with the baseline data from control lungs. The SQUARE contrast suggests a reduction in pulmonary surface-to-volume ratio in the emphysema model that was validated by histology. The finding supports usage of 83Kr SQUARE as a new biomarker for surface-to-volume ratio changes in emphysema. PMID:25994296

  2. Status of and prospects for bronchoscopic lung volume reduction for patients with severe emphysema.

    PubMed

    Yu, Hang; Wang, Lijie; Wu, Zhen; Yang, Zhen

    2016-11-15

    Bronchoscopic lung volume reduction (BLVR) is a minimally invasive treatment for severe emphysema, providing treatment options for patients who are unable to undergo lung volume reduction surgery (LVRS) or lung transplantation. Current BLVR techniques include bronchoscopic volume reduction with valve implants, use of a lung volume reduction coil (LVRC), bronchoscopic thermal vapor ablation (BTVA), biological lung volume reduction (BioLVR), and use of airway bypass stents (ABS). To date, several randomized controlled trials of these bronchoscopic therapies have been conducted in patients with emphysema, and bronchoscopic volume reduction with valve implants remains the best approach thus far. Recent studies indicate that BLVR may be of great value in improving lung function, exercise capacity, and quality of life and that BLVR has the potential to replace conventional surgery for patients with severe emphysema. Optimal patient selection and the proper selection of the BLVR technique in accordance with patient characteristics are crucial to the success of BLVR. More multicenter, prospective, randomized controlled trials need to be conducted in the future to optimize the current selection strategy and evaluate the safety, efficiency, and long-term benefit of BLVR techniques.

  3. Titanium dioxide nanoparticles induce emphysema-like lung injury in mice.

    PubMed

    Chen, Huei-Wen; Su, Sheng-Fang; Chien, Chiang-Ting; Lin, Wei-Hsiang; Yu, Sung-Liang; Chou, Cheng-Chung; Chen, Jeremy J W; Yang, Pan-Chyr

    2006-11-01

    Titanium dioxide nanoparticles (nanoTiO2) have been widely used as a photocatalyst in air and water cleaning. However, these nanoparticles inhalation can induce pulmonary toxicity and its mechanism is not fully understood. In this study we investigated the pulmonary toxicity of nanoTiO2 and its molecular pathogenesis. The adult male ICR mice were exposed to intratracheal single dose of 0.1 or 0.5 mg nanoTiO2 (19-21 nm) and lung tissues were collected at 3rd day, 1st wk, and 2nd wk for morphometric, microarray gene expression, and pathway analyses. NanoTiO2 can induce pulmonary emphysema, macrophages accumulation, extensive disruption of alveolar septa, type II pneumocyte hyperplasia, and epithelial cell apoptosis. NanoTiO2 induced differential expression of hundreds of genes include activation of pathways involved in cell cycle, apoptosis, chemokines, and complement cascades. In particular, nanoTiO2 up-regulates placenta growth factor (PlGF) and other chemokines (CXCL1, CXCL5, and CCL3) expressions that may cause pulmonary emphysema and alveolar epithelial cell apoptosis. Cultured human THP-1 cell-derived macrophages treated with nanoTiO2 in vitro also resulted in up-regulations of PlGF, CXCL1, CXCL5, and CCL3. These results indicated that nanoTiO2 can induce severe pulmonary emphysema, which may be caused by activation of PlGF and related inflammatory pathways.

  4. Promotion of adipogenesis by an EP2 receptor agonist via stimulation of angiogenesis in pulmonary emphysema.

    PubMed

    Tsuji, Takao; Yamaguchi, Kazuhiro; Kikuchi, Ryota; Itoh, Masayuki; Nakamura, Hiroyuki; Nagai, Atsushi; Aoshiba, Kazutetsu

    2014-08-01

    Body weight loss is a common manifestation in patients with chronic obstructive pulmonary disease (COPD), particularly those with severe emphysema. Adipose angiogenesis is a key mediator of adipogenesis and use of pro-angiogenic agents may serve as a therapeutic option for lean COPD patients. Since angiogenesis is stimulated by PGE2, we examined whether ONO-AE1-259, a selective E-prostanoid (EP) 2 receptor agonist, might promote adipose angiogenesis and adipogenesis in a murine model of elastase-induced pulmonary emphysema (EIE mice). Mice were intratracheally instilled with elastase or saline, followed after 4 weeks by intraperitoneal administration of ONO-AE1-259 for 4 weeks. The subcutaneous adipose tissue (SAT) weight decreased in the EIE mice, whereas in the EIE mice treated with ONO-AE1-259, the SAT weight was largely restored, which was associated with significant increases in SAT adipogenesis, angiogenesis, and VEGF protein production. In contrast, ONO-AE1-259 administration induced no alteration in the weight of the visceral adipose tissue. These results suggest that in EIE mice, ONO-AE1-259 stimulated adipose angiogenesis possibly via VEGF production, and thence, adipogenesis. Our data pave the way for the development of therapeutic interventions for weight loss in emphysema patients, e.g., use of pro-angiogenic agents targeting the adipose tissue vascular component.

  5. Effects of Diffusion Time on Short-Range Hyperpolarized 3He Diffusivity Measurements in Emphysema

    SciTech Connect

    Gierada, David S.; Woods, Jason C.; Bierhals, Andrew J.; Bartel, Seth T.; Ritter, Jon H.; Choong, Cliff K.; Das, Nitin A.; Hong, Cheng; Pilgram, Thomas K.; Chang, Yulin V.; Jacob, Rick E.; Hogg, James C.; Battafarano, Richard J.; Cooper, Joel D.; Meyers, Bryan F.; Patterson, G Alexander; Yablonskiy, Dmitriy A.; Conradi, Mark S.

    2009-09-28

    Purpose: To characterize the effect of diffusion time on short-range hyperpolarized 3He MR diffusion measurements across a wide range of emphysema severity. Materials and Methods: 3He diffusion MR imaging was performed on 19 lungs or lobes resected from 18 subjects with varying degrees of emphysema using 3 diffusion times (1.6 msec, 5 msec, and 10 msec) at constant b value. Emphysema severity was quantified as the mean apparent diffusion coefficient (ADC) and as the percentage of pixels with ADC higher than multiple thresholds from 0.30-0.55 cm2/sec (ADC index). Quantitative histology (mean linear intercept) was obtained in 10 of the lung specimens from 10 of the subjects. Results: The mean ADCs with diffusion times of 1.6, 5.0, and 10.0 msec were 0.46, 0.40, and 0.37 cm2/sec, respectively (P <0.0001, ANOVA). There was no relationship between the ADC magnitude and the effect of diffusion time on ADC values. Mean linear intercept correlated with ADC (r=0.91-0.94, P<0.001) and ADC index (r=0.78-0.92, P<0.01) at all diffusion times.

  6. Quantifying lung morphology with respiratory-gated micro-CT in a murine model of emphysema

    NASA Astrophysics Data System (ADS)

    Ford, N. L.; Martin, E. L.; Lewis, J. F.; Veldhuizen, R. A. W.; Holdsworth, D. W.; Drangova, M.

    2009-04-01

    Non-invasive micro-CT imaging techniques have been developed to investigate lung structure in free-breathing rodents. In this study, we investigate the utility of retrospectively respiratory-gated micro-CT imaging in an emphysema model to determine if anatomical changes could be observed in the image-derived quantitative analysis at two respiratory phases. The emphysema model chosen was a well-characterized, genetically altered model (TIMP-3 knockout mice) that exhibits a homogeneous phenotype. Micro-CT scans of the free-breathing, anaesthetized mice were obtained in 50 s and retrospectively respiratory sorted and reconstructed, providing 3D images representing peak inspiration and end expiration with 0.15 mm isotropic voxel spacing. Anatomical measurements included the volume and CT density of the lungs and the volume of the major airways, along with the diameters of the trachea, left bronchus and right bronchus. From these measurements, functional parameters such as functional residual capacity and tidal volume were calculated. Significant differences between the wild-type and TIMP-3 knockout groups were observed for measurements of CT density over the entire lung, indicating increased air content in the lungs of TIMP-3 knockout mice. These results demonstrate retrospective respiratory-gated micro-CT, providing images at multiple respiratory phases that can be analyzed quantitatively to investigate anatomical changes in murine models of emphysema.

  7. Identification of Clinical Phenotypes in Idiopathic Interstitial Pneumonia with Pulmonary Emphysema.

    PubMed

    Sato, Suguru; Tanino, Yoshinori; Misa, Kenichi; Fukuhara, Naoko; Nikaido, Takefumi; Uematsu, Manabu; Fukuhara, Atsuro; Wang, Xintao; Ishida, Takashi; Munakata, Mitsuru

    2016-01-01

    Objective Since the term "combined pulmonary fibrosis and emphysema" (CPFE) was first proposed, the co-existence of pulmonary fibrosis and pulmonary emphysema (PE) has drawn considerable attention. However, conflicting results on the clinical characteristics of patients with both pulmonary fibrosis and PE have been published because of the lack of an exact definition of CPFE. The goal of this study was thus to clarify the clinical characteristics and phenotypes of idiopathic interstitial pneumonia (IIP) with PE. Methods We retrospectively analyzed IIP patients who had been admitted to our hospital. Their chest high-resolution computed tomography images were classified into two groups according to the presence of PE. We then performed a cluster analysis to identify the phenotypes of IIP patients with PE. Results Forty-four (53.7%) out of 82 patients had at least mild emphysema in their bilateral lungs. The cluster analysis separated the IIP patients with PE into three clusters. The overall survival rate of one cluster that consisted of mainly idiopathic pulmonary fibrosis (IPF) patients was significantly worse than those of the other clusters. Conclusion Three different phenotypes can be identified in IIP patients with PE, and IPF with PE is a distinct clinical phenotype with a poor prognosis.

  8. An application to pulmonary emphysema classification based on model of texton learning by sparse representation

    NASA Astrophysics Data System (ADS)

    Zhang, Min; Zhou, Xiangrong; Goshima, Satoshi; Chen, Huayue; Muramatsu, Chisako; Hara, Takeshi; Yokoyama, Ryojiro; Kanematsu, Masayuki; Fujita, Hiroshi

    2012-03-01

    We aim at using a new texton based texture classification method in the classification of pulmonary emphysema in computed tomography (CT) images of the lungs. Different from conventional computer-aided diagnosis (CAD) pulmonary emphysema classification methods, in this paper, firstly, the dictionary of texton is learned via applying sparse representation(SR) to image patches in the training dataset. Then the SR coefficients of the test images over the dictionary are used to construct the histograms for texture presentations. Finally, classification is performed by using a nearest neighbor classifier with a histogram dissimilarity measure as distance. The proposed approach is tested on 3840 annotated regions of interest consisting of normal tissue and mild, moderate and severe pulmonary emphysema of three subtypes. The performance of the proposed system, with an accuracy of about 88%, is comparably higher than state of the art method based on the basic rotation invariant local binary pattern histograms and the texture classification method based on texton learning by k-means, which performs almost the best among other approaches in the literature.

  9. Inhibition of elastase-pulmonary emphysema in dominant-negative MafB transgenic mice.

    PubMed

    Aida, Yasuko; Shibata, Yoko; Abe, Shuichi; Inoue, Sumito; Kimura, Tomomi; Igarashi, Akira; Yamauchi, Keiko; Nunomiya, Keiko; Kishi, Hiroyuki; Nemoto, Takako; Sato, Masamichi; Sato-Nishiwaki, Michiko; Nakano, Hiroshi; Sato, Kento; Kubota, Isao

    2014-01-01

    Alveolar macrophages (AMs) play important roles in the pathogenesis of chronic obstructive pulmonary disease (COPD). We previously demonstrated upregulation of the transcription factor MafB in AMs of mice exposed to cigarette smoke. The aim of this study was to elucidate the roles of MafB in the development of pulmonary emphysema. Porcine pancreatic elastase was administered to wild-type (WT) and dominant-negative (DN)-MafB transgenic (Tg) mice in which MafB activity was suppressed only in macrophages. We measured the mean linear intercept and conducted cell differential analysis of bronchoalveolar lavage (BAL) cells, surface marker analysis using flow cytometry, and immunohistochemical staining using antibodies to matrix metalloproteinase (MMP)-9 and MMP-12. Airspace enlargement of the lungs was suppressed significantly in elastase-treated DN-MafB Tg mice compared with treated WT mice. AMs with projected pseudopods were decreased in DN-MafB Tg mice. The number of cells intermediately positive for F4/80 and weakly or intermediately positive for CD11b, which are considered cell subsets of matured AMs, decreased in the BAL of DN-MafB Tg mice. Furthermore, MMP-9 and -12 were significantly downregulated in BAL cells of DN-MafB Tg mice. Because MMPs exacerbate emphysema, MafB may be involved in pulmonary emphysema development through altered maturation of macrophages and MMP expression.

  10. Independent Living.

    ERIC Educational Resources Information Center

    Nathanson, Jeanne H., Ed.

    1994-01-01

    This issue of "OSERS" addresses the subject of independent living of individuals with disabilities. The issue includes a message from Judith E. Heumann, the Assistant Secretary of the Office of Special Education and Rehabilitative Services (OSERS), and 10 papers. Papers have the following titles and authors: "Changes in the…

  11. Three-dimensional accurate detection of lung emphysema in rats using ultra-short and zero echo time MRI.

    PubMed

    Bianchi, Andrea; Tibiletti, Marta; Kjørstad, Åsmund; Birk, Gerald; Schad, Lothar R; Stierstorfer, Birgit; Rasche, Volker; Stiller, Detlef

    2015-11-01

    Emphysema is a life-threatening pathology that causes irreversible destruction of alveolar walls. In vivo imaging techniques play a fundamental role in the early non-invasive pre-clinical and clinical detection and longitudinal follow-up of this pathology. In the present study, we aimed to evaluate the feasibility of using high resolution radial three-dimensional (3D) zero echo time (ZTE) and 3D ultra-short echo time (UTE) MRI to accurately detect lung pathomorphological changes in a rodent model of emphysema.Porcine pancreas elastase (PPE) was intratracheally administered to the rats to produce the emphysematous changes. 3D ZTE MRI, low and high definition 3D UTE MRI and micro-computed tomography images were acquired 4 weeks after the PPE challenge. Signal-to-noise ratios (SNRs) were measured in PPE-treated and control rats. T2* values were computed from low definition 3D UTE MRI. Histomorphometric measurements were made after euthanizing the animals. Both ZTE and UTE MR images showed a significant decrease in the SNR measured in PPE-treated lungs compared with controls, due to the pathomorphological changes taking place in the challenged lungs. A significant decrease in T2* values in PPE-challenged animals compared with controls was measured using UTE MRI. Histomorphometric measurements showed a significant increase in the mean linear intercept in PPE-treated lungs. UTE yielded significantly higher SNR compared with ZTE (14% and 30% higher in PPE-treated and non-PPE-treated lungs, respectively).This study showed that optimized 3D radial UTE and ZTE MRI can provide lung images of excellent quality, with high isotropic spatial resolution (400 µm) and SNR in parenchymal tissue (>25) and negligible motion artifacts in freely breathing animals. These techniques were shown to be useful non-invasive instruments to accurately and reliably detect the pathomorphological alterations taking place in emphysematous lungs, without incurring the risks of cumulative radiation

  12. The Impact of Homogeneous Versus Heterogeneous Emphysema on Dynamic Hyperinflation in Patients With Severe COPD Assessed for Lung Volume Reduction

    PubMed Central

    Boutou, Afroditi K.; Zoumot, Zaid; Nair, Arjun; Davey, Claire; Hansell, David M.; Jamurtas, Athanasios; Polkey, Michael I.; Hopkinson, Nicholas S.

    2015-01-01

    Abstract Dynamic hyperinflation (DH) is a pathophysiologic hallmark of Chronic Obstructive Pulmonary Disease (COPD). The aim of this study was to investigate the impact of emphysema distribution on DH during a maximal cardiopulmonary exercise test (CPET) in patients with severe COPD. This was a retrospective analysis of prospectively collected data among severe COPD patients who underwent thoracic high-resolution computed tomography, full lung function measurements and maximal CPET with inspiratory manouvers as assessment for a lung volume reduction procedure. ΔIC was calculated by subtracting the end-exercise inspiratory capacity (eIC) from resting IC (rIC) and expressed as a percentage of rIC (ΔIC %). Emphysema quantification was conducted at 3 predefined levels using the syngo PULMO-CT (Siemens AG); a difference >25% between best and worse slice was defined as heterogeneous emphysema. Fifty patients with heterogeneous (62.7% male; 60.9 ± 7.5 years old; FEV1% = 32.4 ± 11.4) and 14 with homogeneous emphysema (61.5% male; 62.5 ± 5.9 years old; FEV1% = 28.1 ± 10.3) fulfilled the enrolment criteria. The groups were matched for all baseline variables. ΔIC% was significantly higher in homogeneous emphysema (39.8% ± 9.8% vs.31.2% ± 13%, p = 0.031), while no other CPET parameter differed between the groups. Upper lobe predominance of emphysema correlated positively with peak oxygen pulse, peak oxygen uptake and peak respiratory rate, and negatively with ΔIC%. Homogeneous emphysema is associated with more DH during maximum exercise in COPD patients. PMID:26398112

  13. Heme oxygenase-1-mediated autophagy protects against pulmonary endothelial cell death and development of emphysema in cadmium-treated mice.

    PubMed

    Surolia, Ranu; Karki, Suman; Kim, Hyunki; Yu, Zhihong; Kulkarni, Tejaswini; Mirov, Sergey B; Carter, A Brent; Rowe, Steven M; Matalon, Sadis; Thannickal, Victor J; Agarwal, Anupam; Antony, Veena B

    2015-08-01

    Pulmonary exposure to cadmium, a major component of cigarette smoke, has a dramatic impact on lung function and the development of emphysema. Cigarette smoke exposure induces heme oxygenase-1 (HO-1), a cytoprotective enzyme. In this study, we employed a truncated mouse model of emphysema by intratracheal instillation of cadmium (CdCl2) solution (0.025% per 1 mg/kg body wt) in HO-1(+/+), HO-1(-/-), and overexpressing humanized HO-1 bacterial artificial chromosome (hHO-1BAC) mice. We evaluated the role of HO-1 in cadmium-induced emphysema in mice by analyzing histopathology, micro-computed tomography scans, and lung function tests. CdCl2-exposed HO-1(-/-) mice exhibited more severe emphysema compared with HO-1(+/+) or hHO-1BAC mice. Loss of pulmonary endothelial cells (PECs) from the alveolar capillary membrane is recognized to be a target in emphysema. PECs from HO-1(+/+), HO-1(-/-), and hHO-1BAC were employed to define the underlying molecular mechanism for the protection from emphysema by HO-1. Electron microscopy, expression of autophagic markers (microtubule-associated protein 1B-light chain 3 II, autophagy protein 5, and Beclin1) and apoptotic marker (cleaved caspase 3) suggested induction of autophagy and apoptosis in PECs after CdCl2 treatment. CdCl2-treated HO-1(-/-) PECs exhibited downregulation of autophagic markers and significantly increased cleaved caspase 3 expression and activity (∼4-fold higher). Moreover, hHO-1BAC PECs demonstrated upregulated autophagy and absence of cleaved caspase 3 expression or activity. Pretreatment of HO-1(+/+) PECs with rapamycin induced autophagy and resulted in reduced cell death upon cadmium treatment. Induction of autophagy following CdCl2 treatment was found to be protective from apoptotic cell death. HO-1 induced protective autophagy in PECs and mitigated cadmium-induced emphysema.

  14. Intratracheally administered titanium dioxide or carbon black nanoparticles do not aggravate elastase-induced pulmonary emphysema in rats

    PubMed Central

    2012-01-01

    Background Titanium dioxide (TiO2) and carbon black (CB) nanoparticles (NPs) have biological effects that could aggravate pulmonary emphysema. The aim of this study was to evaluate whether pulmonary administration of TiO2 or CB NPs in rats could induce and/or aggravate elastase-induced emphysema, and to investigate the underlying molecular mechanisms. Methods On day 1, Sprague-Dawley rats were intratracheally instilled with 25 U kg−1 pancreatic porcine elastase or saline. On day 7, they received an intratracheal instillation of TiO2 or CB (at 100 and 500 μg) dispersed in bovine serum albumin or bovine serum albumin alone. Animals were sacrificed at days 8 or 21, and bronchoalveolar lavage (BAL) cellularity, histological analysis of inflammation and emphysema, and lung mRNA expression of heme oxygenase-1 (HO-1), interleukin-1β (IL-1β), macrophage inflammatory protein-2, monocyte chemotactic protein-1, and matrix metalloprotease (MMP)-1, and -12 were measured. In addition, pulmonary MMP-12 expression was also analyzed at the protein level by immunohistochemistry. Results TiO2 NPs per se did not modify the parameters investigated, but CB NPs increased perivascular/peribronchial infiltration, and macrophage MMP-12 expression, without inducing emphysema. Elastase administration increased BAL cellularity, histological inflammation, HO-1, IL-1β and macrophage MMP-12 expression and induced emphysema. Exposure to TiO2 NPs did not modify pulmonary responses to elastase, but exposure to CB NPs aggravated elastase-induced histological inflammation without aggravating emphysema. Conclusions TiO2 and CB NPs did not aggravate elastase-induced emphysema. However, CB NPs induced histological inflammation and MMP-12 mRNA and protein expression in macrophages. PMID:22849372

  15. Comparison between Variable and Conventional Volume-Controlled Ventilation on Cardiorespiratory Parameters in Experimental Emphysema.

    PubMed

    Henriques, Isabela; Padilha, Gisele A; Huhle, Robert; Wierzchon, Caio; Miranda, Paulo J B; Ramos, Isalira P; Rocha, Nazareth; Cruz, Fernanda F; Santos, Raquel S; de Oliveira, Milena V; Souza, Sergio A; Goldenberg, Regina C; Luiz, Ronir R; Pelosi, Paolo; de Abreu, Marcelo G; Silva, Pedro L; Rocco, Patricia R M

    2016-01-01

    Emphysema is characterized by loss of lung tissue elasticity and destruction of structures supporting alveoli and capillaries. The impact of mechanical ventilation strategies on ventilator-induced lung injury (VILI) in emphysema is poorly defined. New ventilator strategies should be developed to minimize VILI in emphysema. The present study was divided into two protocols: (1) characterization of an elastase-induced emphysema model in rats and identification of the time point of greatest cardiorespiratory impairment, defined as a high specific lung elastance associated with large right ventricular end-diastolic area; and (2) comparison between variable (VV) and conventional volume-controlled ventilation (VCV) on lung mechanics and morphometry, biological markers, and cardiac function at that time point. In the first protocol, Wistar rats (n = 62) received saline (SAL) or porcine pancreatic elastase (ELA) intratracheally once weekly for 4 weeks, respectively. Evaluations were performed 1, 3, 5, or 8 weeks after the last intratracheal instillation of saline or elastase. After identifying the time point of greatest cardiorespiratory impairment, an additional 32 Wistar rats were randomized into the SAL and ELA groups and then ventilated with VV or VCV (n = 8/group) [tidal volume (VT) = 6 mL/kg, positive end-expiratory pressure (PEEP) = 3 cmH2O, fraction of inspired oxygen (FiO2) = 0.4] for 2 h. VV was applied on a breath-to-breath basis as a sequence of randomly generated VT values (mean VT = 6 mL/kg), with a 30% coefficient of variation. Non-ventilated (NV) SAL and ELA animals were used for molecular biology analysis. The time point of greatest cardiorespiratory impairment, was observed 5 weeks after the last elastase instillation. At this time point, interleukin (IL)-6, cytokine-induced neutrophil chemoattractant (CINC)-1, amphiregulin, angiopoietin (Ang)-2, and vascular endothelial growth factor (VEGF) mRNA levels were higher in ELA compared to SAL. In ELA animals

  16. Comparison between Variable and Conventional Volume-Controlled Ventilation on Cardiorespiratory Parameters in Experimental Emphysema

    PubMed Central

    Henriques, Isabela; Padilha, Gisele A.; Huhle, Robert; Wierzchon, Caio; Miranda, Paulo J. B.; Ramos, Isalira P.; Rocha, Nazareth; Cruz, Fernanda F.; Santos, Raquel S.; de Oliveira, Milena V.; Souza, Sergio A.; Goldenberg, Regina C.; Luiz, Ronir R.; Pelosi, Paolo; de Abreu, Marcelo G.; Silva, Pedro L.; Rocco, Patricia R. M.

    2016-01-01

    Emphysema is characterized by loss of lung tissue elasticity and destruction of structures supporting alveoli and capillaries. The impact of mechanical ventilation strategies on ventilator-induced lung injury (VILI) in emphysema is poorly defined. New ventilator strategies should be developed to minimize VILI in emphysema. The present study was divided into two protocols: (1) characterization of an elastase-induced emphysema model in rats and identification of the time point of greatest cardiorespiratory impairment, defined as a high specific lung elastance associated with large right ventricular end-diastolic area; and (2) comparison between variable (VV) and conventional volume-controlled ventilation (VCV) on lung mechanics and morphometry, biological markers, and cardiac function at that time point. In the first protocol, Wistar rats (n = 62) received saline (SAL) or porcine pancreatic elastase (ELA) intratracheally once weekly for 4 weeks, respectively. Evaluations were performed 1, 3, 5, or 8 weeks after the last intratracheal instillation of saline or elastase. After identifying the time point of greatest cardiorespiratory impairment, an additional 32 Wistar rats were randomized into the SAL and ELA groups and then ventilated with VV or VCV (n = 8/group) [tidal volume (VT) = 6 mL/kg, positive end-expiratory pressure (PEEP) = 3 cmH2O, fraction of inspired oxygen (FiO2) = 0.4] for 2 h. VV was applied on a breath-to-breath basis as a sequence of randomly generated VT values (mean VT = 6 mL/kg), with a 30% coefficient of variation. Non-ventilated (NV) SAL and ELA animals were used for molecular biology analysis. The time point of greatest cardiorespiratory impairment, was observed 5 weeks after the last elastase instillation. At this time point, interleukin (IL)-6, cytokine-induced neutrophil chemoattractant (CINC)-1, amphiregulin, angiopoietin (Ang)-2, and vascular endothelial growth factor (VEGF) mRNA levels were higher in ELA compared to SAL. In ELA animals

  17. A 15-year-old boy with anterior chest pain, progressive dyspnea, and subcutaneous emphysema of the neck.

    PubMed

    Scichilone, Nicola; Buttacavoli, Maria; Camarda, Gaetana; Marchese, Margherita; Bellia, Maria; Spatafora, Mario

    2009-01-01

    We describe the case of an adolescent who was admitted to the hospital because of sudden occurrence of chest pain, dyspnea and subcutaneous emphysema. On admission, physical examination revealed subcutaneous crepitations in the superior part of the rib cage, and auscultation of the chest showed widespread wheezing. The radiological assessment confirmed the diagnosis of pneumomediastinum and pneumothorax. A follow-up CT scan performed one week after the admission showed almost complete resolution of the radiological alterations. At the following visits, the patient was asymptomatic, but reported to have suffered from frequent episodes of rhinorrea, sneezing, nasal blockage, and sometimes, chest tightness, especially during exposure to pets and/or windy weather. Skin prick testing showed sensitivities to dermatophagoides pteronyssinus and farinae, grass pollen and dog dander. Spirometry documented significant improvement in lung function after short-acting bronchodilator, allowing for the diagnosis of asthma to be made. Although pneumomediastinum may be a complication of various respiratory diseases, including asthma, it has never been reported as the first presentation of underlying bronchial asthma. Herein, the physiopathological mechanisms, the diagnostic procedures and treatment of pneumomediastinum in asthma are discussed. We suggest that the diagnosis of asthma should be considered in the differential diagnosis of pneumomediastinum in adolescence.

  18. Myeloid-Specific Fos-Related Antigen-1 Regulates Cigarette Smoke–Induced Lung Inflammation, Not Emphysema, in Mice

    PubMed Central

    Vaz, Michelle; Rajasekaran, Subbiah; Potteti, Haranatha R.

    2015-01-01

    Heightened lung inflammation is a cardinal feature of chronic obstructive pulmonary disease (COPD). Cigarette smoke (CS)-induced macrophage recruitment and activation, accompanied by abnormal secretion of a number of inflammatory cytokines and matrix metalloproteinases, play a major role in the pathophysiology of COPD. The Fos-related antigen-1 (Fra-1) transcription factor differentially regulates several cellular processes that are implicated in COPD, such as inflammation and immune responses, cell proliferation and death, and extracellular remodeling. Although CS stimulates Fra-1 expression in the lung, the precise role of this transcription factor in the regulation of CS-induced lung inflammation in vivo is poorly understood. Here, we report that myeloid-specific Fra-1 signaling is important for CS-induced lung macrophagic inflammatory response. In response to chronic CS exposure, mice with Fra-1 specifically deleted in myeloid cells showed reduced levels of CS-induced lung macrophagic inflammation, accompanied by decreased expression levels of proinflammatory cytokines compared with their wild-type counterparts. Consistent with this result, bone marrow–derived Fra-1–null macrophages treated with CS showed decreased levels of proinflammatory mediators and matrix metalloproteinases. Interestingly, deletion of Fra-1 in myeloid cells did not affect the severity of emphysema. We propose that Fra-1 plays a key role in promoting chronic CS-induced lung macrophagic inflammation in vivo, and that targeting this transcription factor may be useful in dampening persistent lung inflammation in patients with COPD. PMID:25489966

  19. 'Independence' Panorama

    NASA Technical Reports Server (NTRS)

    2005-01-01

    [figure removed for brevity, see original site] Click on the image for 'Independence' Panorama (QTVR)

    This is the Spirit 'Independence' panorama, acquired on martian days, or sols, 536 to 543 (July 6 to 13, 2005), from a position in the 'Columbia Hills' near the summit of 'Husband Hill.' The summit of 'Husband Hill' is the peak near the right side of this panorama and is about 100 meters (328 feet) away from the rover and about 30 meters (98 feet) higher in elevation. The rocky outcrops downhill and on the left side of this mosaic include 'Larry's Lookout' and 'Cumberland Ridge,' which Spirit explored in April, May, and June of 2005.

    The panorama spans 360 degrees and consists of 108 individual images, each acquired with five filters of the rover's panoramic camera. The approximate true color of the mosaic was generated using the camera's 750-, 530-, and 480-nanometer filters. During the 8 martian days, or sols, that it took to acquire this image, the lighting varied considerably, partly because of imaging at different times of sol, and partly because of small sol-to-sol variations in the dustiness of the atmosphere. These slight changes produced some image seams and rock shadows. These seams have been eliminated from the sky portion of the mosaic to better simulate the vista a person standing on Mars would see. However, it is often not possible or practical to smooth out such seams for regions of rock, soil, rover tracks or solar panels. Such is the nature of acquiring and assembling large panoramas from the rovers.

  20. Splicing mutation in the fibrillin-1 gene associated with neonatal Marfan syndrome and severe pulmonary emphysema with tracheobronchomalacia.

    PubMed

    Shinawi, Marwan; Boileau, Catherine; Brik, Riva; Mandel, Hanna; Bentur, Lea

    2005-04-01

    Neonatal Marfan syndrome is an autosomal-dominant connective tissue disease with unique clinical manifestations and mutations. We describe the clinical course of an infant with neonatal Marfan syndrome that had the novel IVS31-2A > G splice site mutation in fibrillin-1. This mutation affects the second base of the acceptor consensus splice site of intron 31, and probably leads to abnormal splicing events. The patient presented with respiratory distress and heart murmur in early neonatal life. Cardiac evaluation revealed pulmonic stenosis, atrioventricular regurgitation, and a dilated aortic root that were controlled by balloon dilatation of the pulmonic stenosis and medications for congestive heart failure. At age 3 months, he presented with severe respiratory distress caused by upper and lower airway obstruction. Imaging studies showed severe pulmonary emphysema, and a bronchoscopy demonstrated megatracheobronchomalacia, an unusual finding in this syndrome. Subsequently, the patient developed recurrent hyperinflation of the right and left lungs, with emphysematous changes and mediastinal shift. After discussing with his parents the grave prognosis for neonatal Marfan syndrome, he was discharged home with oxygen treatment and died at home at age 4.5 months. This case report demonstrates and discusses pulmonary involvement in neonatal Marfan syndrome and the difficult therapeutic challenges created by the severe cardiopulmonary abnormalities in this invariably fatal condition.

  1. Predicting Structure-Function Relations and Survival following Surgical and Bronchoscopic Lung Volume Reduction Treatment of Emphysema

    PubMed Central

    Mondoñedo, Jarred R.

    2017-01-01

    Lung volume reduction surgery (LVRS) and bronchoscopic lung volume reduction (bLVR) are palliative treatments aimed at reducing hyperinflation in advanced emphysema. Previous work has evaluated functional improvements and survival advantage for these techniques, although their effects on the micromechanical environment in the lung have yet to be determined. Here, we introduce a computational model to simulate a force-based destruction of elastic networks representing emphysema progression, which we use to track the response to lung volume reduction via LVRS and bLVR. We find that (1) LVRS efficacy can be predicted based on pre-surgical network structure; (2) macroscopic functional improvements following bLVR are related to microscopic changes in mechanical force heterogeneity; and (3) both techniques improve aspects of survival and quality of life influenced by lung compliance, albeit while accelerating disease progression. Our model predictions yield unique insights into the microscopic origins underlying emphysema progression before and after lung volume reduction. PMID:28182686

  2. Predicting Structure-Function Relations and Survival following Surgical and Bronchoscopic Lung Volume Reduction Treatment of Emphysema.

    PubMed

    Mondoñedo, Jarred R; Suki, Béla

    2017-02-01

    Lung volume reduction surgery (LVRS) and bronchoscopic lung volume reduction (bLVR) are palliative treatments aimed at reducing hyperinflation in advanced emphysema. Previous work has evaluated functional improvements and survival advantage for these techniques, although their effects on the micromechanical environment in the lung have yet to be determined. Here, we introduce a computational model to simulate a force-based destruction of elastic networks representing emphysema progression, which we use to track the response to lung volume reduction via LVRS and bLVR. We find that (1) LVRS efficacy can be predicted based on pre-surgical network structure; (2) macroscopic functional improvements following bLVR are related to microscopic changes in mechanical force heterogeneity; and (3) both techniques improve aspects of survival and quality of life influenced by lung compliance, albeit while accelerating disease progression. Our model predictions yield unique insights into the microscopic origins underlying emphysema progression before and after lung volume reduction.

  3. Opposing effects of emphysema, hay fever, and select genetic variants on lung cancer risk.

    PubMed

    Schabath, Matthew B; Delclos, George L; Martynowicz, Marek M; Greisinger, Anthony J; Lu, Charles; Wu, Xifeng; Spitz, Margaret R

    2005-03-01

    The authors compared histories of nonmalignant respiratory diseases (asthma, bronchitis, emphysema, hay fever, and pneumonia) in 1,553 lung cancer patients and 1,375 healthy controls enrolled in a Texas case-control study from 1995 to 2003. They incorporated data on two biologically relevant polymorphic genes, matrix metalloproteinase-1 and myeloperoxidase. Emphysema was associated with a statistically significant increased lung cancer risk (odds ratio (OR) = 2.87, 95% confidence interval (CI): 2.20, 3.76), while hay fever had a significant protective effect (OR = 0.58, 95% CI: 0.48, 0.70). Odds ratios were consistent after exclusion of respiratory disease diagnoses made up to 10 years before interview. There was little association between other respiratory diseases and lung cancer risk. Among carriers of "protective" genotypes, emphysema was associated with a 1.7-fold increased risk (95% CI: 0.84, 3.50), as compared with the substantially higher risk for persons possessing one (OR = 4.98, 95% CI: 2.94, 8.44) or two (OR = 4.23, 95% CI: 1.84, 9.73) "adverse" genotypes. For hay fever, significantly decreased risks were evident with one (OR = 0.32, 95% CI: 0.21, 0.50) or two (OR = 0.35, 95% CI: 0.19, 0.66) protective genotypes as compared with none (OR = 0.69, 95% CI: 0.30, 1.59). The biologic role of respiratory disease in lung cancer is unclear. Further study may yield new insights for identification of susceptible subgroups.

  4. Modeling the influence of vitamin D deficiency on cigarette smoke-induced emphysema

    PubMed Central

    Crane-Godreau, Mardi A.; Black, Candice C.; Giustini, Andrew J.; Dechen, Tenzin; Ryu, Jihan; Jukosky, James A.; Lee, Hong-Kee; Bessette, Katherine; Ratcliffe, Nora R.; Hoopes, P. Jack; Fiering, Steven; Kelly, John A.; Leiter, J. C.

    2013-01-01

    Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. While the primary risk factor for COPD is cigarette smoke exposure, vitamin D deficiency has been epidemiologically implicated as a factor in the progressive development of COPD-associated emphysema. Because of difficulties inherent to studies involving multiple risk factors in the progression of COPD in humans, we developed a murine model in which to study the separate and combined effects of vitamin D deficiency and cigarette smoke exposure. During a 16-week period, mice were exposed to one of four conditions, control diet breathing room air (CD-NS), control diet with cigarette smoke exposure (CD-CSE), vitamin D deficient diet breathing room air (VDD-NS) or vitamin D deficient diet with cigarette smoke exposure (VDD-CSE). At the end of the exposure period, the lungs were examined by a pathologist and separately by morphometric analysis. In parallel experiments, mice were anesthetized for pulmonary function testing followed by sacrifice and analysis. Emphysema (determined by an increase in alveolar mean linear intercept length) was more severe in the VDD-CSE mice compared to control animals and animals exposed to VDD or CSE alone. The VDD-CSE and the CD-CSE mice had increased total lung capacity and increased static lung compliance. There was also a significant increase in the matrix metalloproteinase-9: tissue inhibitor of metalloproteinases-1 (TIMP-1) ratio in VDD-CSE mice compared with all controls. Alpha-1 antitrypsin (A1AT) expression was reduced in VDD-CSE mice as well. In summary, vitamin D deficiency, when combined with cigarette smoke exposure, seemed to accelerate the appearance of emphysemas, perhaps by virtue of an increased protease-antiprotease ratio in the combined VDD-CSE animals. These results support the value of our mouse model in the study of COPD. PMID:23781205

  5. Automated measurement of pulmonary emphysema and small airway remodeling in cigarette smoke-exposed mice.

    PubMed

    Laucho-Contreras, Maria E; Taylor, Katherine L; Mahadeva, Ravi; Boukedes, Steve S; Owen, Caroline A

    2015-01-16

    COPD is projected to be the third most common cause of mortality world-wide by 2020((1)). Animal models of COPD are used to identify molecules that contribute to the disease process and to test the efficacy of novel therapies for COPD. Researchers use a number of models of COPD employing different species including rodents, guinea-pigs, rabbits, and dogs((2)). However, the most widely-used model is that in which mice are exposed to cigarette smoke. Mice are an especially useful species in which to model COPD because their genome can readily be manipulated to generate animals that are either deficient in, or over-express individual proteins. Studies of gene-targeted mice that have been exposed to cigarette smoke have provided valuable information about the contributions of individual molecules to different lung pathologies in COPD((3-5)). Most studies have focused on pathways involved in emphysema development which contributes to the airflow obstruction that is characteristic of COPD. However, small airway fibrosis also contributes significantly to airflow obstruction in human COPD patients((6)), but much less is known about the pathogenesis of this lesion in smoke-exposed animals. To address this knowledge gap, this protocol quantifies both emphysema development and small airway fibrosis in smoke-exposed mice. This protocol exposes mice to CS using a whole-body exposure technique, then measures respiratory mechanics in the mice, inflates the lungs of mice to a standard pressure, and fixes the lungs in formalin. The researcher then stains the lung sections with either Gill's stain to measure the mean alveolar chord length (as a readout of emphysema severity) or Masson's trichrome stain to measure deposition of extracellular matrix (ECM) proteins around small airways (as a readout of small airway fibrosis). Studies of the effects of molecular pathways on both of these lung pathologies will lead to a better understanding of the pathogenesis of COPD.

  6. Effects of the association of diabetes and pulmonary emphysema on cardiac structure and function in rats.

    PubMed

    Di Petta, Antonio; Simas, Rafael; Ferreira, Clebson L; Capelozzi, Vera L; Salemi, Vera M C; Moreira, Luiz F P; Sannomiya, Paulina

    2015-10-01

    Chronic obstructive pulmonary disease is often associated with chronic comorbid conditions of cardiovascular disease, diabetes mellitus and hypertension. This study aimed to investigate the effects of the association of diabetes and pulmonary emphysema on cardiac structure and function in rats. Wistar rats were divided into control non-diabetic instilled with saline (CS) or elastase (CE), diabetic instilled with saline (DS) or elastase (DE), DE treated with insulin (DEI) groups and echocardiographic measurements, morphometric analyses of the heart and lungs, and survival analysis conducted 50 days after instillation. Diabetes mellitus was induced [alloxan, 42 mg/kg, intravenously (iv)] 10 days before the induction of emphysema (elastase, 0.25 IU/100 g). Rats were treated with NPH insulin (4 IU before elastase plus 2 IU/day, 50 days). Both CE and DE exhibited similar increases in mean alveolar diameter, which are positively correlated with increases in right ventricular (RV) wall thickness (P = 0.0022), cavity area (P = 0.0001) and cardiomyocyte thickness (P = 0.0001). Diabetic saline group demonstrated a reduction in left ventricular (LV) wall, interventricular (IV) septum, cardiomyocyte thickness and an increase in cavity area, associated with a reduction in LV fractional shortening (P < 0.05), and an increase in LViv relaxation time (P < 0.05). Survival rate decreased from 80% in DS group to 40% in DE group. In conclusion, alloxan diabetes did not affect RV hypertrophy secondary to chronic emphysema, even in the presence of insulin. Diabetes per se induced left ventricular dysfunction, which was less evident in the presence of RV hypertrophy. Survival rate was substantially reduced as a consequence, at least in part, of the coexistence of RV hypertrophy and diabetic cardiomyopathy.

  7. Quantitative CT Measurement of Cross-sectional Area of Small Pulmonary Vessel in COPD: Correlations with Emphysema and Airflow Limitation

    PubMed Central

    Matsuoka, Shin; Washko, George R.; Dransfield, Mark T.; Yamashiro, Tsuneo; Estepar, Raul San Jose; Diaz, Alejandro; Silverman, Edwin K.; Patz, Samuel; Hatabu, Hiroto

    2009-01-01

    Rationale and Objectives Pulmonary vascular alteration is one of the characteristic features of COPD. Recent studies suggest that vascular alteration is closely related to endothelial dysfunction, and may be further influenced by emphysema. However, the relationship between morphological alteration of small pulmonary vessels and the extent of emphysema has not been assessed in vivo. The objectives of this study are: 1) to evaluate the correlation of total cross-sectional area (CSA) of small pulmonary vessels with the extent of emphysema and airflow obstruction using CT scans, and 2) to assess the difference of total CSA between COPD phenotypes. Materials and Methods We measured CSA less than 5mm2 and 5–10 mm2, and calculated the percentage of the total CSA for the lung area (%CSA<5, and %CSA5-10, respectively) using CT scans in 191 subjects. The extent of emphysema (%LAA-950) was calculated, and the correlations of %CSA<5 and %CSA5-10 with %LAA-950 and results of pulmonary function tests (PFTs) were evaluated. The differences in %CSA between COPD phenotypes were also assessed. Results %CSA<5 had significant negative correlations with %LAA-950 (r=−0.83, p<0.0001). There was a weak but statistically significant correlation of %CSA<5 with FEV1% predicted (r=0.29, p<0.0001) and FEV1/FVC (r=0.45, p<0.0001). %CSA5-10 had weak correlations with %LAA-950 and results of PFTs. %CSA<5 was significantly higher in bronchitis phenotype than emphysema phenotype (p<0.0001). Conclusions Total cross sectional area of small pulmonary vessels at sub-subsegmental levels strongly correlates with the extent of emphysema (%LAA-950), and reflects differences between COPD phenotypes. PMID:19796970

  8. Subcutaneous Emphysema Induced by Cryotherapy: A Complication due to Previous Punctures

    PubMed Central

    Martínez-Coronado, Jared; Torres-Álvarez, Bertha; Castanedo-Cázares, Juan Pablo

    2015-01-01

    Cryosurgery is a common therapeutic modality used in dermatology; therefore we must be aware of its possible adverse effects. We report a case of a patient with subcutaneous emphysema which occurred following the application of cryotherapy after multiple punctures of local anesthetic and intralesional steroids in a chest keloid scar. Despite the fact that this condition was gradually resolved after expectant observation, we warn about this complication when sprayed cryotherapy is preceded by multiple punctures on cutaneous lesions above bony surfaces. In similar settings, cryotherapy must be first administered or a cotton-tip applicator should be used. PMID:26171258

  9. Aquaporin 5 regulates cigarette smoke induced emphysema by modulating barrier and immune properties of the epithelium.

    PubMed

    Aggarwal, Neil R; Chau, Eric; Garibaldi, Brian T; Mock, Jason R; Sussan, Thomas; Rao, Keshav; Rao, Kaavya; Menon, Anil G; D'Alessio, Franco R; Damarla, Mahendra; Biswal, Shyam; King, Landon S; Sidhaye, Venkataramana K

    2013-10-01

    Chronic obstructive pulmonary disease (COPD) causes significant morbidity and mortality. Cigarette smoke, the most common risk factor for COPD, induces airway and alveolar epithelial barrier permeability and initiates an innate immune response. Changes in abundance of aquaporin 5 (AQP5), a water channel, can affect epithelial permeability and immune response after cigarette smoke exposure. To determine how AQP5-derived epithelial barrier modulation affects epithelial immune response to cigarette smoke and development of emphysema, WT and AQP5(-/-) mice were exposed to cigarette smoke (CS). We measured alveolar cell counts and differentials, and assessed histology, mean-linear intercept (MLI), and surface-to-volume ratio (S/V) to determine severity of emphysema. We quantified epithelial-derived signaling proteins for neutrophil trafficking, and manipulated AQP5 levels in an alveolar epithelial cell line to determine specific effects on neutrophil transmigration after CS exposure. We assessed paracellular permeability and epithelial turnover in response to CS. In contrast to WT mice, AQP5(-/-) mice exposed to 6 months of CS did not demonstrate a significant increase in MLI or a significant decrease in S/V compared with air-exposed mice, conferring protection against emphysema. After sub-acute (4 weeks) and chronic (6 mo) CS exposure, AQP5(-/-) mice had fewer alveolar neutrophil but similar lung neutrophil numbers as WT mice. The presence of AQP5 in A549 cells, an alveolar epithelial cell line, was associated with increase neutrophil migration after CS exposure. Compared with CS-exposed WT mice, neutrophil ligand (CD11b) and epithelial receptor (ICAM-1) expression were reduced in CS-exposed AQP5(-/-) mice, as was secreted LPS-induced chemokine (LIX), an epithelial-derived neutrophil chemoattractant. CS-exposed AQP5(-/-) mice demonstrated decreased type I pneumocytes and increased type II pneumocytes compared with CS-exposed WT mice suggestive of enhanced epithelial

  10. Lung Volume Reduction After Stereotactic Ablative Radiation Therapy of Lung Tumors: Potential Application to Emphysema

    SciTech Connect

    Binkley, Michael S.; Shrager, Joseph B.; Leung, Ann N.; Popat, Rita; Trakul, Nicholas; Atwood, Todd F.; Chaudhuri, Aadel; Maxim, Peter G.; Diehn, Maximilian; Loo, Billy W.

    2014-09-01

    Purpose: Lung volume reduction surgery (LVRS) improves dyspnea and other outcomes in selected patients with severe emphysema, but many have excessive surgical risk for LVRS. We analyzed the dose-volume relationship for lobar volume reduction after stereotactic ablative radiation therapy (SABR) of lung tumors, hypothesizing that SABR could achieve therapeutic volume reduction if applied in emphysema. Methods and Materials: We retrospectively identified patients treated from 2007 to 2011 who had SABR for 1 lung tumor, pre-SABR pulmonary function testing, and ≥6 months computed tomographic (CT) imaging follow-up. We contoured the treated lobe and untreated adjacent lobe(s) on CT before and after SABR and calculated their volume changes relative to the contoured total (bilateral) lung volume (TLV). We correlated lobar volume reduction with the volume receiving high biologically effective doses (BED, α/β = 3). Results: 27 patients met the inclusion criteria, with a median CT follow-up time of 14 months. There was no grade ≥3 toxicity. The median volume reduction of the treated lobe was 4.4% of TLV (range, −0.4%-10.8%); the median expansion of the untreated adjacent lobe was 2.6% of TLV (range, −3.9%-11.6%). The volume reduction of the treated lobe was positively correlated with the volume receiving BED ≥60 Gy (r{sup 2}=0.45, P=.0001). This persisted in subgroups determined by high versus low pre-SABR forced expiratory volume in 1 second, treated lobe CT emphysema score, number of fractions, follow-up CT time, central versus peripheral location, and upper versus lower lobe location, with no significant differences in effect size between subgroups. Volume expansion of the untreated adjacent lobe(s) was positively correlated with volume reduction of the treated lobe (r{sup 2}=0.47, P<.0001). Conclusions: We identified a dose-volume response for treated lobe volume reduction and adjacent lobe compensatory expansion after lung tumor SABR, consistent across

  11. Transthoracic Biopsy Causes Massive Subcutaneous Emphysema in a Low Risk Patient

    PubMed Central

    Dag, Yusuf

    2016-01-01

    Subcutaneous Emphysema (SE) can be defined as air leakage under skin from the respiratory or gastrointestinal system. It is frequently accompanied by pneumomediastinum. Thoracentesis, image-guided lung biopsies, pulmonary diseases and therapies resulting in necrosis can cause this pathology. The risk of pneumothorax and SE increased with the distance of the lesion to the pleura, and small size of the lesion. Although, our patient had low risk for SE, there were minimal pneumothoraces and massive SE. We consider that tumour necrosis and subcutaneous tissue may be related via transthoracic biopsy and this leads to massive SE. PMID:28050477

  12. [Neumopericardium and spontaneous post partum subcutaneus emphysema. A case report and literature review].

    PubMed

    Velasco Alva, S M; Pliego Pérez, A R; Espínola Zetina, C

    2001-05-01

    The barotrauma cases related to childbirth are an uncommon event, especially the neumopericardium. This entity must be suspected in a patient with subcutaneuos emphysema and confirmed by chest X-ray. The management is based on closed observation, support measures and antibiotic to prevent infection. The radiological follow up is important to evaluate the resolution of this problem. The patient must be followed with caution if the neumopericardium increases because this could lead to a cardiac tamponade with fatal consequences. The description of a case diagnosed and managed in our hospital is done herein which evolution was satisfactory towards resolution of the pneumopericardium without the need of further intervention.

  13. Nitrogenous subcutaneous emphysema caused by spray application of fibrin glue during retroperitoneal laparoscopic surgery.

    PubMed

    Matsuse, Shinji; Maruyama, Atsushi; Hara, Yoshiki

    2011-06-01

    We report a case of a patient treated by retroperitoneoscopic partial nephrectomy who developed nitrogenous subcutaneous emphysema (SCE) as a complication. The use of a nitrogen gas-pressured fibrin tissue adhesive applied as a spray caused excessively increased pressure in the closed retroperitoneal space and resulted in widespread SCE with protracted clinical course. To the best of our knowledge, this is the first report of nitrogenous SCE associated with pneumoperitoneum. The clinical significance of nitrogenous SCE is emphasized, and the risks associated with the use of fibrin glue as a spray during laparoscopic surgery are discussed.

  14. Single-lung transplantation in emphysema: Retrospective study analyzing survival and waiting list mortality

    PubMed Central

    Borro, José M; Delgado, María; Coll, Elisabeth; Pita, Salvador

    2016-01-01

    AIM: To performed remains a subject of debate and is the principal aim of the study. METHODS: This retrospective analysis included 73 patients with emphysema (2000-2012). The outcomes of patients undergoing single-lung transplantation (SL) (n = 40) or double-lung transplant (DL) (n = 33) were compared in a Cox multivariate analysis to study the impact of the technique, postoperative complications and acute and chronic rejection on survival rates. Patients were selected for inclusion in the waiting list according to the International Society of Heart Lung Transplantation criteria. Pre and postoperative rehabilitation and prophylaxis, surgical technique and immunosuppressive treatment were similar in every patients. Lung transplantation waiting list information on a national level and retrospective data on emphysema patient survival transplanted in Spain during the study period, was obtained from the lung transplantation registry managed by the National Transplant Organization (ONT). RESULTS: Both groups were comparable in terms of gender and clinical characteristics. We found significant differences in the mean age between the groups, the DL patients being younger as expected from the inclusion criteria. Perioperative complications occurred in 27.6% SL vs 54% DL (P = 0.032). Excluding perioperative mortality, median survival was 65.3 mo for SL and 59.4 mo for DL (P = 0.96). Bronchiolitis obliterans and overall 5-year survival were similar in both groups. Bacterial respiratory infection, cytomegalovirus and fungal infection rates were higher but not significant in SL. No differences were found between type of transplant and survival (P = 0.48). To support our results, national data on all patients with emphysema in waiting list were obtained (n = 1001). Mortality on the waiting list was 2.4% for SL vs 6.2% for DL. There was no difference in 5 year survival between 235 SL and 430 DL patients transplanted (P = 0.875). CONCLUSION: Our results suggest that SL

  15. Subcutaneous emphysema, pneumo-orbita and pneumomediastinum following a facial trauma caused by a high-pressure car washer.

    PubMed

    Yılmaz, Fevzi; Çiftçi, Orçun; Özlem, Miray; Komut, Erdal; Altunbilek, Ertuğrul

    2014-03-01

    Pneumomediastinum is air leakage to mediastinal space from various potential sites, including lung, esophagus, trachea, and neck. It is a rare condition that develops either spontaneously with increased intraalveolar or intrabronchial pressure, or due to trauma. Although cases where face or neck trauma with subcutaneous emphysema that extended to mediastinal cavity via anatomical connections in face and neck have been reported, orbital traumas leading to pneumomediastinum are very rare occurrences that have seldom been reported. This paper documents a 17-year-old male who presented with diffuse subcutaneous emphysema involving paraorbital facial areas, which extended to neck and mediastinal cavity.

  16. Orbital emphysema after a protracted episode of sneezing in a patient with no history of trauma or sinus surgery.

    PubMed

    Khader, Qasim A; Abdul-Baqi, Khader J

    2010-11-01

    Orbital emphysema is a benign self-limiting condition. It can occur directly (as a result of trauma to the face) or indirectly (secondary to a blowout fracture). We report a case of orbital emphysema in a 38-year-old man who presented with ecchymosis of the right eye, pressure within the right orbit, and periorbital swelling following a protracted episode of vigorous sneezing. The diagnosis was confirmed by computed tomography. Systemic antibiotics were given, and the patient was cautioned to avoid blowing his nose. His signs and symptoms resolved within 1 week.

  17. Heme oxygenase-1 attenuates inflammation and oxidative damage in a rat model of smoke-induced emphysema.

    PubMed

    Wei, Jingjing; Fan, Guoquan; Zhao, Hui; Li, Jianqiang

    2015-11-01

    Emphysema is a serious disease of the respiratory system and is associated with inflammation and oxidative stress. Heme oxygenase-1 (HO-1), a rate-limiting enzyme involved in heme biosynthesis, exerts potent anti-inflammatory, antioxidant, anti-apoptotic and anti‑proliferative effects in various diseases. In the present study, we examined the effects of HO-1 on smoke‑induced emphysema, as well as the underlying mechanisms in a rat model of smoke-induced emphysema. Rats were either exposed to cigarette smoke or sham‑exposed for 20 weeks to establish the model of smoke-induced emphysema. The rats were subcutaneously injected with protoporphyrin IX [tin-protoporphyrin IX (SnPP) or ferriprotoporphyrin IX chloride (hemin)] during this period to examine the protective effects of HO-1. Subsequently, the development of emphysema, inflammatory cells, the levels of inflammatory mediators, particularly interleukin (IL)-17, tumor necrosis factor (TNF)‑α, monocyte chemotactic protein‑1 [MCP‑1, also known as chemokine (C-C motif) ligand 2 (CCL2)], IL-8 [also known as chemokine (C-X-C motif) ligand 8 (CXCL8)], macrophage inflammatory protein‑2α [MIP-2α, also known as chemokine (C-X-C motif) ligand 2 (CXCL2)] and IL-10, as well as the malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) content were determined. Exposure to smoke increased the total cell, neutrophil and macrophage counts in the bronchoalveolar lavage fluid (BALF). It also increased the levels of the inflammatory mediators, IL-17, TNF-α, MCP-1, IL-8 and MIP-2α, as well as the MDA content and induced emphysema. Treatment with hemin upregulated HO-1 expression and attenuated the development of smoke-induced emphysema by reducing inflammatory cell infiltration, decreasing the levels of inflammatory mediators and attenuating oxidative damage, to a certain extent. In conclusion, our findings demonstrate that HO-1 exerts anti-inflammatory and antioxidant effects, thus attenuating the

  18. The fissure: interlobar collateral ventilation and implications for endoscopic therapy in emphysema.

    PubMed

    Koster, Theodoor David; Slebos, Dirk-Jan

    2016-01-01

    In patients with severe emphysema, bronchoscopic lung volume reduction using one-way valves is a promising therapeutic option to improve lung function and quality of life. The goal of this treatment is to achieve a complete lobar atelectasis. In a significant proportion of patients, this atelectasis cannot be achieved due to interlobar collateral ventilation. This collateral ventilation is generated through incomplete lobar fissures. Therefore, only patients with complete fissures and no collateral ventilation can be selected for endobronchial therapy with one-way valves. Incomplete fissures are very common and exhibit a great variation in anatomy. The reported prevalence is 17%-85% for the right major fissure, 19%-74% for the left major fissure, and 20%-90% for the minor fissure. There are several methods of measuring or predicting the presence of collateral ventilation, with computed tomography (CT)-fissure analysis and the Chartis measurement being the most important. CT-fissure analysis is an indirect method to measure the completeness of fissures as a surrogate for collateral ventilation. The Chartis system is an endobronchial method to directly measure the presence of collateral ventilation. Both methods have unique value, and the combination of both can accurately predict the treatment response to the bronchoscopic placement of endobronchial valves. This review provides an in-depth view of lung fissure and collateral ventilation to help understand its importance in selecting the appropriate patients for new emphysema treatments and thus avoid useless treatment in unsuitable patients.

  19. Two-year follow-up in patients treated with emphysematous lung sealant for advanced emphysema.

    PubMed

    Kramer, Mordechai R; Refaely, Yael; Maimon, Nimrod; Rosengarten, Dror; Fruchter, Oren

    2013-11-01

    Endoscopic lung volume-reduction therapy for emphysema has been associated with therapeutic responses smaller in magnitude and less durable than surgical volume reduction (LVRS). Bronchoscopic emphysematous lung sealant (ELS) therapy has been shown to produce improvements in pulmonary function similar to surgery at 1 year. This case series summarizes safety and efficacy data of all patients from the initial ELS study out to 2 years. Between 1 and 2 years, there were three all-cause adverse events requiring hospitalization. One patient went on to successful lung transplant. Improvements relative to baseline in spirometry (change in FEV1: + 14.3 ± 33.1%; change in FVC: + 5.8 ± 23.2%) and diffusing capacity (change in diffusing capacity of the lung for carbon monoxide: + 10.6 ± 20.6%) were observed at 2 years. An exponential model fit to FEV₁ data at 6, 12, 18, and 24 months predicted improvements from a baseline of > 5% out to 4.1 years, similar to what has been reported following surgery. This report confirms long-term safety and efficacy following ELS therapy in advanced emphysema. Studies in a larger cohort are needed to define the role of ELS therapy in the treatment algorithm of patients with this condition.

  20. Estimating structural alterations in animal models of lung emphysema. Is there a gold standard?

    PubMed

    Ochs, Matthias

    2014-01-01

    Chronic obstructive pulmonary disease (COPD) is one of the most common lung diseases. The major component of COPD, which affects the gas-exchanging parenchyma of the lung, emphysema, is characterized by destruction of alveolar septae leading to loss of functional surface, loss of alveoli and enlargement of remaining distal airspaces. These microstructural alterations can be modeled in animals and can be measured using stereological methods applied to imaging datasets. Many animal models of emphysema exist, but most of them are insufficiently characterized with respect to the underlying nature (e.g. destructive or developmental) and the degree of the structural alterations. The most popular parameter for assessment of emphysematous alterations, mean linear intercept length, has severe limitations. It can, therefore, not be recommended. Better design-based stereological alternatives exist but are less often applied, such as total volumes of parenchymal compartments (alveolar airspace, alveolar duct airspace, alveolar septum), total alveolar surface area, total alveolar number and mean alveolar size and its size variation. A prerequisite is the use of appropriate fixation, sampling, and specimen processing protocols. This article reviews the challenges of stereologic assessment of emphysematous alterations in the lung and illustrates possible strategies.

  1. Costs of pulmonary rehabilitation and predictors of adherence in the National Emphysema Treatment Trial.

    PubMed

    Fan, Vincent S; Giardino, Nicholas D; Blough, David K; Kaplan, Robert M; Ramsey, Scott D

    2008-04-01

    This study reports the costs associated with rehabilitation among participants in the National Emphysema Treatment Trial (NETT), and evaluates factors associated with adherence to rehabilitation. Pulmonary rehabilitation is recommended for moderate-to-severe COPD and required by the Centers for Medicare and Medicaid Services (CMS) prior to lung volume reduction surgery (LVRS). Between January 1998 and July 2002, 1,218 subjects with emphysema and severe airflow limitation (FEV(1) < or = 45% predicted) were randomized. Primary outcome measures were designated as mortality and maximal exercise capacity 2 years after randomization. Pre-randomization, estimated mean total cost per patient of rehabilitation was $2,218 (SD $314; 2006 dollars) for the medical group and $2,187 (SD $304) for the surgical group. Post-randomization, mean cost per patient in the medical and surgical groups was $766 and $962 respectively. Among patients who attended > or = 1 post-randomization rehabilitation session, LVRS patients, patients with an FEV(1) > or = 20% predicted, and higher education were significantly more likely to complete rehabilitation. Patients with depressive and anxiety symptoms, and those who live > 36 miles compared to < 6 miles away were less likely to be adherent. Patients who underwent LVRS completed more exercise sessions than those in the medical group and were more likely to be adherent with post-randomization rehabilitation. A better understanding of patient factors such as socioeconomic status, depression, anxiety and transportation issues may improve adherence to pulmonary rehabilitation.

  2. Idiopathic interstitial pneumonias and emphysema: detection and classification using a texture-discriminative approach

    NASA Astrophysics Data System (ADS)

    Fetita, C.; Chang-Chien, K. C.; Brillet, P. Y.; Pr"teux, F.; Chang, R. F.

    2012-03-01

    Our study aims at developing a computer-aided diagnosis (CAD) system for fully automatic detection and classification of pathological lung parenchyma patterns in idiopathic interstitial pneumonias (IIP) and emphysema using multi-detector computed tomography (MDCT). The proposed CAD system is based on three-dimensional (3-D) mathematical morphology, texture and fuzzy logic analysis, and can be divided into four stages: (1) a multi-resolution decomposition scheme based on a 3-D morphological filter was exploited to discriminate the lung region patterns at different analysis scales. (2) An additional spatial lung partitioning based on the lung tissue texture was introduced to reinforce the spatial separation between patterns extracted at the same resolution level in the decomposition pyramid. Then, (3) a hierarchic tree structure was exploited to describe the relationship between patterns at different resolution levels, and for each pattern, six fuzzy membership functions were established for assigning a probability of association with a normal tissue or a pathological target. Finally, (4) a decision step exploiting the fuzzy-logic assignments selects the target class of each lung pattern among the following categories: normal (N), emphysema (EM), fibrosis/honeycombing (FHC), and ground glass (GDG). According to a preliminary evaluation on an extended database, the proposed method can overcome the drawbacks of a previously developed approach and achieve higher sensitivity and specificity.

  3. Detection and classification of interstitial lung diseases and emphysema using a joint morphological-fuzzy approach

    NASA Astrophysics Data System (ADS)

    Chang Chien, Kuang-Che; Fetita, Catalin; Brillet, Pierre-Yves; Prêteux, Françoise; Chang, Ruey-Feng

    2009-02-01

    Multi-detector computed tomography (MDCT) has high accuracy and specificity on volumetrically capturing serial images of the lung. It increases the capability of computerized classification for lung tissue in medical research. This paper proposes a three-dimensional (3D) automated approach based on mathematical morphology and fuzzy logic for quantifying and classifying interstitial lung diseases (ILDs) and emphysema. The proposed methodology is composed of several stages: (1) an image multi-resolution decomposition scheme based on a 3D morphological filter is used to detect and analyze the different density patterns of the lung texture. Then, (2) for each pattern in the multi-resolution decomposition, six features are computed, for which fuzzy membership functions define a probability of association with a pathology class. Finally, (3) for each pathology class, the probabilities are combined up according to the weight assigned to each membership function and two threshold values are used to decide the final class of the pattern. The proposed approach was tested on 10 MDCT cases and the classification accuracy was: emphysema: 95%, fibrosis/honeycombing: 84% and ground glass: 97%.

  4. Correlation of emphysema score with perceived malignancy of pulmonary nodules: a multi-observer study using the LIDC-IDRI CT lung database

    NASA Astrophysics Data System (ADS)

    Wiemker, Rafael; Bülow, Thomas; Blaffert, Thomas; Dharaiya, Ekta

    2009-02-01

    Presence of emphysema is recognized to be one of the single most significant risk factors in risk models for the prediction of lung cancer. Therefore, an automatically computed emphysema score would be a prime candidate as an additional numerical feature for computer aided diagnosis (CADx) for indeterminate pulmonary nodules. We have applied several histogram-based emphysema scores to 460 thoracic CT scans from the IDRI CT lung image database, and analyzed the emphysema scores in conjunction with 3000 nodule malignancy ratings of 1232 pulmonary nodules made by expert observers. Despite the emphysema being a known risk factor, we have not found any impact on the readers' malignancy rating of nodules found in a patient with higher emphysema score. We have also not found any correlation between the number of expert-detected nodules in a patient and his emphysema score, or the relative craniocaudal location of the nodules and their malignancy rating. The inter-observer agreement of the expert ratings was excellent on nodule diameter (as derived from manual delineations), good for calcification, and only modest for malignancy and shape descriptions such as spiculation, lobulation, margin, etc.

  5. Emphysema and fibrosis: risk factors in responsiveness to air pollution

    SciTech Connect

    Costa, D.L.; Lehmann, J.R.

    1984-01-01

    Episodic and epidemiologic data appear to support the belief that chronic non-specific lung disease imposes an additional risk to affected individuals when challenged by air pollution. While this concept has been implicitly enacted into law, little knowledge or understanding of the tenets of disease-based hyper-susceptibility exists. The clinical and animal experimental data show trends, but in general, have provided little substance to defend or challenge the legitimacy of the margins of safety incorporated into the standards of the EPA regulated pollutants. As more data on so-called normal individuals are being collected, many of these safety margins appear to be eroding, thus offering little encouragement that susceptible subgroups of the population are actually being protected. 39 references, 8 tables.

  6. Sirtuin 1 Activator SRT1720 Protects Against Lung Injury via Reduction of Type II Alveolar Epithelial Cells Apoptosis in Emphysema.

    PubMed

    Gu, Chao; Li, Yaqing; Xu, Wu-Lin; Yan, Jian-Ping; Xia, Ying-jie; Ma, Ying-Yu; Chen, Chun; Wang, Hui-Ju; Tao, Hou-quan

    2015-08-01

    In chronic obstructive pulmonary disease (COPD), two major pathological changes that occur are the loss of alveolar structure and airspace enlargement. Type II alveolar epithelial cells (AECII) play a vital role in maintaining alveolar homeostasis and lung tissue repair. Sirtuin 1 (SIRT1), a NAD(+)-dependent histone deacetylase, regulates many pathophysiological processes including inflammation, apoptosis, cellular senescence and stress resistance. The main aim of this study was to investigate whether SRT1720, a pharmacological SIRT1 activator, could protect against AECII apoptosis in rats with emphysema caused by cigarette smoke exposure and intratracheal lipopolysaccharide instillation in vivo. During the induction of emphysema in rats, administration of SRT1720 improved lung function including airway resistance and pulmonary dynamic compliance. SRT1720 treatment up-regulated the levels of surfactant protein (SP)A, SPC, SIRT1 and forkhead box O 3, increased SIRT1 activity, down-regulated the level of p53 and inhibited AECII apoptosis. Lung injury caused by emphysema was alleviated after SRT1720 treatment. SRT1720 could protect against AECII apoptosis in rats with emphysema and thus could be used in COPD treatment.

  7. Association of environmental tobacco smoke exposure in childhood with early emphysema in adulthood among nonsmokers: the MESA-lung study.

    PubMed

    Lovasi, Gina S; Diez Roux, Ana V; Hoffman, Eric A; Kawut, Steven M; Jacobs, David R; Barr, R Graham

    2010-01-01

    Mechanical stress to alveolar walls may cause progressive damage after an early-life insult such as exposure to environmental tobacco smoke (ETS). This hypothesis was examined by using data from the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based cohort aged 45-84 years, free of clinical cardiovascular disease, recruited from 6 US sites in 2000-2002. The MESA-Lung Study assessed a fractal, structural measure of early emphysema ("alpha," lower values indicate more emphysema) and a standard quantitative measure ("percent emphysema") from cardiac computed tomography scans. Childhood ETS exposure was assessed retrospectively as a report of living with one or more regular indoor smokers. Analyses included 1,781 nonsmokers (<100 cigarettes, 20 cigars, or 20 pipefulls in their lifetime and urinary cotinine levels <100 ng/mL); mean age was 61 years (standard deviation, 10), and 65% were women. Childhood ETS exposure from 2 or more smokers (17%) compared with none (52%) was associated with 0.05 lower alpha and 2.8 higher percent emphysema (P for trend = 0.04 and 0.01, respectively) after adjustment for demographic, anthropometric, parental, and participant characteristics, as well as adult exposures (e.g., cumulative residential air pollution exposure, exposure to ETS as an adult). Childhood ETS exposure was associated with detectable differences on computed tomography scans of adult lungs of nonsmokers.

  8. Emphysema Quantification in Inflation-Fixed Lungs Using Low-Dose Computed Tomography and 3He Magnetic Resonance Imaging

    SciTech Connect

    Gierada, David S.; Woods, Jason C.; Jacob, Rick E.; Bierhals, Andrew J.; Choong, Cliff K.; Bartel, Seth T.; Chang, Yulin V.; Das, Nitin A.; Hong, Cheng; Lutey, Barbara; Ritter, Jon H.; Pilgram, Thomas K.; Cooper, Joel D.; Patterson, G Alexander; Battafarano, Richard J.; Meyers, Bryan F.; Yablonskiy, Dmitriy A.; Conradi, Mark S.

    2010-09-02

    Abstract: Objective: To evaluate the use of inflation-fixed lung tissue for emphysema quantification with CT and 3He MR diffusion imaging. Methods: Fourteen subjects representing a range of chronic obstructive pulmonary disease severity who underwent complete or lobar lung resection were studied. CT measurements of lung attenuation and MR measurements of the hyperpolarized 3He apparent diffusion coefficient (ADC) in resected specimens fixed in inflation with heated formalin vapor were compared with measurements obtained before fixation. Results: The mean CT emphysema index was 56% ± 17% before and 58% ± 19% after fixation (P=0.77;R=0.76). Index differences correlated with differences in lung volume (R2=0.47). The mean 3He ADC was 0.40 ± 0.15 cm2/sec before and 0.39 ± 0.14 cm2/sec after fixation (P=0.03, R=0.98). The CT emphysema index and the 3He ADC were correlated before (R=0.89) and after fixation (R=0.79). Conclusion: Concordance of CT and 3He MR imaging measurements in unfixed and inflation-fixed lungs supports the use of inflation-fixed lungs for quantitative imaging studies in emphysema.

  9. Mechanical failure, stress redistribution, elastase activity and binding site availability on elastin during the progression of emphysema.

    PubMed

    Suki, Béla; Jesudason, Rajiv; Sato, Susumu; Parameswaran, Harikrishnan; Araujo, Ascanio D; Majumdar, Arnab; Allen, Philip G; Bartolák-Suki, Erzsébet

    2012-08-01

    Emphysema is a disease of the lung parenchyma with progressive alveolar tissue destruction that leads to peripheral airspace enlargement. In this review, we discuss how mechanical forces can contribute to disease progression at various length scales. Airspace enlargement requires mechanical failure of alveolar walls. Because the lung tissue is under a pre-existing tensile stress, called prestress, the failure of a single wall results in a redistribution of the local prestress. During this process, the prestress increases on neighboring alveolar walls which in turn increases the probability that these walls also undergo mechanical failure. There are several mechanisms that can contribute to this increased probability: exceeding the failure threshold of the ECM, triggering local mechanotransduction to release enzymes, altering enzymatic reactions on ECM molecules. Next, we specifically discuss recent findings that stretching of elastin induces an increase in the binding off rate of elastase to elastin as well as unfolds hidden binding sites along the fiber. We argue that these events can initiate a positive feedback loop which generates slow avalanches of breakdown that eventually give rise to the relentless progression of emphysema. We propose that combining modeling at various length scales with corresponding biological assays, imaging and mechanics data will provide new insight into the progressive nature of emphysema. Such approaches will have the potential to contribute to resolving many of the outstanding issues which in turn may lead to the amelioration or perhaps the treatment of emphysema in the future.

  10. Several clinical interests regarding lung volume reduction surgery for severe emphysema: meta-analysis and systematic review of randomized controlled trials

    PubMed Central

    2011-01-01

    Objectives We aim to address several clinical interests regarding lung volume reduction surgery (LVRS) for severe emphysema using meta-analysis and systematic review of randomized controlled trials (RCTs). Methods Eight RCTs published from 1999 to 2010 were identified and synthesized to compare the efficacy and safety of LVRS vs conservative medical therapy. One RCT was obtained regarding comparison of median sternotomy (MS) and video-assisted thoracoscopic surgery (VATS). And three RCTs were available evaluating clinical efficacy of using bovine pericardium for buttressing, autologous fibrin sealant and BioGlue, respectively. Results Odds ratio (95%CI), expressed as the mortality of group A (the group underwent LVRS) versus group B (conservative medical therapies), was 5.16(2.84, 9.35) in 3 months, 3(0.94, 9.57) in 6 months, 1.05(0.82, 1.33) in 12 months, respectively. On the 3rd, 6th and 12th month, all lung function indices of group A were improved more significantly as compared with group B. PaO2 and PaCO2 on the 6th and 12th month showed the same trend. 6MWD of group A on the 6th month and 12th month were improved significantly than of group B, despite no difference on the 3rd month. Quality of life (QOL) of group A was better than of group B in 6 and 12 months. VATS is preferred to MS, due to the earlier recovery and lower cost. And autologous fibrin sealant and BioGlue seems to be the efficacious methods to reduce air leak following LVRS. Conclusions LVRS offers the more benefits regarding survival, lung function, gas exchange, exercise capacity and QOL, despite the higher mortality in initial three postoperative months. LVRS, with the optimization of surgical approach and material for reinforcement of the staple lines, should be recommended to patients suffering from severe heterogeneous emphysema. PMID:22074613

  11. Postcard from Independence, Mo.

    ERIC Educational Resources Information Center

    Archer, Jeff

    2004-01-01

    This article reports results showing that the Independence, Missori school district failed to meet almost every one of its improvement goals under the No Child Left Behind Act. The state accreditation system stresses improvement over past scores, while the federal law demands specified amounts of annual progress toward the ultimate goal of 100…

  12. Subcutaneous emphysema

    MedlinePlus

    ... catheter into a vein close to the heart), endotracheal intubation (tube into the throat and trachea through the ... The person may receive: Breathing support, including oxygen, endotracheal intubation (tube through the nose or mouth into the ...

  13. Effects of formoterol and ipratropium bromide on repeated cadmium inhalation-induced pulmonary inflammation and emphysema in rats.

    PubMed

    Zhang, WenHui; Fievez, Laurence; Zhang, Fan; Cheu, Esteban; Antoine, Nadine; Delguste, Catherine; Zhang, Yong; Rong, WeiFang; Bureau, Fabrice; Advenier, Charles; Gustin, Pascal

    2010-11-25

    The anti-inflammatory properties of inhaled formoterol and ipratropium bromide, alone or in combination, were investigated in a rat model of chronic pulmonary inflammation with airspace enlargement induced by cadmium inhalation. At the end of the protocol, cadmium-induced increase of airway resistance was prevented by formoterol (4 mg/30 ml) or ipratropium (0.20 mg/20 ml). Formoterol elicited a significant decrease in total cell and neutrophil counts in bronchoalveolar lavage fluid as well as on the activity of gelatinase B (MMP-9), an enzyme strongly expressed in alveolar macrophages and epithelial cells. Additionally, a significant attenuation of the lung lesions characterized by inflammatory cell infiltration within the alveoli and the interstitium and a decrease in mean linear intercept were observed. Although ipratropium alone had no effects on the cadmium-induced pulmonary inflammation and emphysema, its combination with an inefficient concentration of formoterol (1 mg/30 ml) showed a synergistic inhibitory effect on neutrophil and total cell counts as well as on the mean linear intercept associated with a synergistic inhibition on the MMP-9 activity. Gelatinase A (MMP-2) activity was not influenced by drug pretreatments. Neither macrophage metalloelastase (MMP-12) activity nor levels of cytokines IL-1β, TNF-α and GM-CSF in bronchoalveolar lavage fluid were modified in rats chronically exposed to cadmium. No desensitization of β(2)-adrenoceptors or cholinergic receptors on airway smooth muscles and inflammatory cells during the protocol was observed. In conclusion, formoterol alone or combined with ipratropium bromide partially protects the lungs against the chronic inflammation and airspace enlargement by reducing neutrophilic infiltration possibly via the inhibition of MMP-9 activity.

  14. Diffuse Subcutaneous Emphysema and Pneumomediastinum Secondary to a Minor Blunt Chest Trauma

    PubMed Central

    Heymann, Eric P.; Exadaktylos, Aristomenis K.

    2017-01-01

    Full medical evaluation is paramount for all trauma patients. Minor traumas are often overlooked, as they are thought to bear low injury potential. In this case report, we describe the case of a 48-year-old man presenting to our Emergency Department with mild to moderate right-sided shoulder and scapular pain following a fall from his own height ten days previously. Clinical and paraclinical investigations (CT) revealed diffuse right shoulder pain, with crepitations on palpation of the neck, right shoulder, and right lateral chest wall. Computed tomography (CT) demonstrated right-sided costal fractures (ribs 7 to 9), with diffuse subcutaneous emphysema and pneumomediastinum due to laceration of the visceral and parietal pleura and the adjacent lung parenchyma. In addition, a small ipsilateral pneumothorax was found. Surprisingly, the clinical status was only minimally affected by mild to moderate pain and minor functional impairment. PMID:28392950

  15. Spontaneous Pneumothorax With Subcutaneous Emphysema: A Rare Complication of Respiratory Syncytial Virus Infection

    PubMed Central

    Silva, Carmen; Almeida, Ana Filipe; Ferraz, Catarina; Nunes, Teresa; Guedes Vaz, Luisa

    2016-01-01

    Viral bronchiolitis is the most common lower respiratory tract infection in infants and children under the age of 2. Respiratory syncytial virus (RSV) is the infecting agent in more than 50% of the cases. Usually the clinical course is uneventful and complications are uncommon. Secondary air leaks are a recognized rare complication of bronchiolitis, although the real incidence remains unknown. We report a case of a 21-month-old female that developed a spontaneous pneumothorax (PNO) with subcutaneous emphysema (SE) late in the course of RSV acute bronchiolitis. Additional investigation ruled out any underlying disease predisposing to spontaneous PNO. Physicians, especially those who work with small children, must be aware of this uncommon complication of bronchiolitis that may appear late in the course of the disease despite an initial clinical improvement. PMID:26858803

  16. Spontaneous Pneumothorax With Subcutaneous Emphysema: A Rare Complication of Respiratory Syncytial Virus Infection.

    PubMed

    Silva, Carmen; Almeida, Ana Filipe; Ferraz, Catarina; Nunes, Teresa; Guedes Vaz, Luisa

    2016-03-01

    Viral bronchiolitis is the most common lower respiratory tract infection in infants and children under the age of 2. Respiratory syncytial virus (RSV) is the infecting agent in more than 50% of the cases. Usually the clinical course is uneventful and complications are uncommon. Secondary air leaks are a recognized rare complication of bronchiolitis, although the real incidence remains unknown. We report a case of a 21-month-old female that developed a spontaneous pneumothorax (PNO) with subcutaneous emphysema (SE) late in the course of RSV acute bronchiolitis. Additional investigation ruled out any underlying disease predisposing to spontaneous PNO. Physicians, especially those who work with small children, must be aware of this uncommon complication of bronchiolitis that may appear late in the course of the disease despite an initial clinical improvement.

  17. Algorithm of pulmonary emphysema extraction using thoracic 3-D CT images

    NASA Astrophysics Data System (ADS)

    Saita, Shinsuke; Kubo, Mitsuru; Kawata, Yoshiki; Niki, Noboru; Nakano, Yasutaka; Ohmatsu, Hironobu; Tominaga, Keigo; Eguchi, Kenji; Moriyama, Noriyuki

    2008-03-01

    Emphysema patients have the tendency to increase due to aging and smoking. Emphysematous disease destroys alveolus and to repair is impossible, thus early detection is essential. CT value of lung tissue decreases due to the destruction of lung structure. This CT value becomes lower than the normal lung- low density absorption region or referred to as Low Attenuation Area (LAA). So far, the conventional way of extracting LAA by simple thresholding has been proposed. However, the CT value of CT image fluctuates due to the measurement conditions, with various bias components such as inspiration, expiration and congestion. It is therefore necessary to consider these bias components in the extraction of LAA. We removed these bias components and we proposed LAA extraction algorithm. This algorithm has been applied to the phantom image. Then, by using the low dose CT(normal: 30 cases, obstructive lung disease: 26 cases), we extracted early stage LAA and quantitatively analyzed lung lobes using lung structure.

  18. Spontaneous pneumomediastinum, pneumoretroperitoneum, and cervicofacial subcutaneous emphysema after repeatedly and forcefully blowing into a bottle

    PubMed Central

    Swe, Thein; Naing, Akari Thein; Lixon, Antony; Quist, Joseph

    2016-01-01

    Spontaneous pneumomediastinum (SPM) is an uncommon, self-limiting condition associated with increased intra-thoracic pressure resulting in alveolar rupture. Search of the literature revealed no detailed case report about a 26-year-old psychiatric patient who repeatedly and forcefully blew air into a bottle for 5 days resulting in a combined condition of spontaneous pneumoretroperitoneum, pneumomediastinum, and cervicofacial subcutaneous emphysema. It is crucial to find a primary source and treat appropriately. Psychiatric patients may have psychotic behaviors mimicking Valsalva's maneuver that increases intra-thoracic pressure and causing SPM. Optimal medications should be given to control psychotic behaviors. Family members and caregivers should be explained about this unusual behavior so that they can prevent this rare condition. PMID:27987288

  19. Molecular basis of alpha 1-antitrypsin deficiency and emphysema associated with the alpha 1-antitrypsin Mmineral springs allele.

    PubMed Central

    Curiel, D T; Vogelmeier, C; Hubbard, R C; Stier, L E; Crystal, R G

    1990-01-01

    The Mmineral springs alpha 1-antitrypsin (alpha 1AT) allele, causing alpha 1AT deficiency and emphysema, is unique among the alpha 1AT-deficiency alleles in that it was observed in a black family, whereas most mutations causing alpha 1AT deficiency are confined to Caucasian populations of European descent. Immobilized pH gradient analysis of serum demonstrated that alpha 1AT Mmineral springs migrated cathodal to the normal M2 allele. Evaluation of Mmineral springs alpha 1AT as an inhibitor of neutrophil elastase, its natural substrate, demonstrated markedly lower than normal function. Characterization of the alpha 1AT Mmineral springs gene demonstrated that it differed from the common normal M1(Ala213) allele by a single-base substitution causing the amino acid substitution Gly-67 (GGG)----Glu-67 (GAG). Capitalizing on the fact that this mutation creates a polymorphism for the restriction endonuclease AvaII, family analysis demonstrated that the Mmineral springs alpha 1AT allele was transmitted in an autosomal-codominant fashion. Evaluation of genomic DNA showed that the index case was homozygous for the alpha 1AT Mmineral springs allele. Cytoplasmic blot analysis of blood monocytes of the Mmineral springs homozygote demonstrated levels of alpha 1AT mRNA transcripts comparable to those in cells of a normal M1 (Val213) homozygote control. Evaluation of in vitro translation of Mmineral springs alpha 1AT mRNA transcripts demonstrated a normal capacity to direct the translation of alpha 1AT. Evaluation of secretion of alpha 1AT by the blood monocytes by pulse-chase labeling with [35S]methionine, however, demonstrated less secretion by the Mmineral springs cells than normal cells. To characterize the posttranslational events causing the alpha 1AT-secretory defect associated with the alpha 1AT Mmineral springs gene, retroviral gene transfer was used to establish polyclonal populations of murine fibroblasts containing either a normal human M1 alpha 1AT cDNA or an Mmineral

  20. Elastase induces lung epithelial cell autophagy through placental growth factor: a new insight of emphysema pathogenesis.

    PubMed

    Hou, Hsin-Han; Cheng, Shih-Lung; Chung, Kuei-Pin; Kuo, Mark Yen-Ping; Yeh, Cheng-Chang; Chang, Bei-En; Lu, Hsuan-Hsuan; Wang, Hao-Chien; Yu, Chong-Jen

    2014-09-01

    Chronic obstructive pulmonary disease (COPD) is a devastating disease, which is associated with increasing mortality and morbidity. Therefore, there is a need to clearly define the COPD pathogenic mechanism and to explore effective therapies. Previous studies indicated that cigarette smoke (CS) induces autophagy and apoptosis in lung epithelial (LE) cells. Excessive ELANE/HNE (elastase, neutrophil elastase), a factor involved in protease-antiprotease imbalance and the pathogenesis of COPD, causes LE cell apoptosis and upregulates the expression of several stimulus-responsive genes. However, whether or not elastase induces autophagy in LE cell remains unknown. The level of PGF (placental growth factor) is higher in COPD patients than non-COPD controls. We hypothesize that elastase induces PGF expression and causes autophagy in LE cells. In this study, we demonstrated that porcine pancreatic elastase (PPE) induced PGF expression and secretion in LE cells in vitro and in vivo. The activation of MAPK8/JNK1 (mitogen-activated protein kinase 8) and MAPK14/p38alpha MAPK signaling pathways was involved in the PGF mediated regulation of the TSC (tuberous sclerosis complex) pathway and autophagy in LE cells. Notably, PGF-induced MAPK8 and MAPK14 signaling pathways mediated the inactivation of MTOR (mechanistic target of rapamycin), the upregulation of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3 β) and the increase of autophagosome formation in mice. Furthermore, the PPE-induced autophagy promotes further apoptosis in vitro and in vivo. In summary, elastase-induced autophagy promotes LE cell apoptosis and pulmonary emphysema through the upregulation of PGF. PGF and its downstream MAPK8 and MAPK14 signaling pathways are potential therapeutic targets for the treatment of emphysema and COPD.

  1. Bronchoscopic lung volume reduction by endobronchial valve in advanced emphysema: the first Asian report

    PubMed Central

    Park, Tai Sun; Hong, Yoonki; Lee, Jae Seung; Oh, Sang Young; Lee, Sang Min; Kim, Namkug; Seo, Joon Beom; Oh, Yeon-Mok; Lee, Sang-Do; Lee, Sei Won

    2015-01-01

    Purpose Endobronchial valve (EBV) therapy is increasingly being seen as a therapeutic option for advanced emphysema, but its clinical utility in Asian populations, who may have different phenotypes to other ethnic populations, has not been assessed. Patients and methods This prospective open-label single-arm clinical trial examined the clinical efficacy and the safety of EBV in 43 consecutive patients (mean age 68.4±7.5, forced expiratory volume in 1 second [FEV1] 24.5%±10.7% predicted, residual volume 208.7%±47.9% predicted) with severe emphysema with complete fissure and no collateral ventilation in a tertiary referral hospital in Korea. Results Compared to baseline, the patients exhibited significant improvements 6 months after EBV therapy in terms of FEV1 (from 0.68±0.26 L to 0.92±0.40 L; P<0.001), 6-minute walk distance (from 233.5±114.8 m to 299.6±87.5 m; P=0.012), modified Medical Research Council dyspnea scale (from 3.7±0.6 to 2.4±1.2; P<0.001), and St George’s Respiratory Questionnaire (from 65.59±13.07 to 53.76±11.40; P=0.028). Nine patients (20.9%) had a tuberculosis scar, but these scars did not affect target lobe volume reduction or pneumothorax frequency. Thirteen patients had adverse events, ten (23.3%) developed pneumothorax, which included one death due to tension pneumothorax. Conclusion EBV therapy was as effective and safe in Korean patients as it has been shown to be in Western countries. (Trial registration: ClinicalTrials.gov: NCT01869205). PMID:26251590

  2. Automated diagnosis of interstitial lung diseases and emphysema in MDCT imaging

    NASA Astrophysics Data System (ADS)

    Fetita, Catalin; Chang Chien, Kuang-Che; Brillet, Pierre-Yves; Prêteux, Françoise

    2007-09-01

    Diffuse lung diseases (DLD) include a heterogeneous group of non-neoplasic disease resulting from damage to the lung parenchyma by varying patterns of inflammation. Characterization and quantification of DLD severity using MDCT, mainly in interstitial lung diseases and emphysema, is an important issue in clinical research for the evaluation of new therapies. This paper develops a 3D automated approach for detection and diagnosis of diffuse lung diseases such as fibrosis/honeycombing, ground glass and emphysema. The proposed methodology combines multi-resolution 3D morphological filtering (exploiting the sup-constrained connection cost operator) and graph-based classification for a full characterization of the parenchymal tissue. The morphological filtering performs a multi-level segmentation of the low- and medium-attenuated lung regions as well as their classification with respect to a granularity criterion (multi-resolution analysis). The original intensity range of the CT data volume is thus reduced in the segmented data to a number of levels equal to the resolution depth used (generally ten levels). The specificity of such morphological filtering is to extract tissue patterns locally contrasting with their neighborhood and of size inferior to the resolution depth, while preserving their original shape. A multi-valued hierarchical graph describing the segmentation result is built-up according to the resolution level and the adjacency of the different segmented components. The graph nodes are then enriched with the textural information carried out by their associated components. A graph analysis-reorganization based on the nodes attributes delivers the final classification of the lung parenchyma in normal and ILD/emphysematous regions. It also makes possible to discriminate between different types, or development stages, among the same class of diseases.

  3. Structure-function relations in an elastase-induced mouse model of emphysema.

    PubMed

    Hamakawa, Hiroshi; Bartolák-Suki, Erzsébet; Parameswaran, Harikrishnan; Majumdar, Arnab; Lutchen, Kenneth R; Suki, Béla

    2011-09-01

    Emphysema is a progressive disease characterized by the destruction of peripheral airspaces and subsequent decline in lung function. However, the relation between structure and function during disease progression is not well understood. The objective of this study was to assess the time course of the structural, mechanical, and remodeling properties of the lung in mice after elastolytic injury. At 2, 7, and 21 days after treatment with porcine pancreatic elastase, respiratory impedance, the constituents of lung extracellular matrix, and histological sections of the lung were evaluated. In the control group, no changes were observed in the structural or functional properties, whereas, in the treatment group, the respiratory compliance and its variability significantly increased by Day 21 (P < 0.001), and the difference in parameters decreased with increasing positive end-expiratory pressure. The heterogeneity of airspace structure gradually increased over time. Conversely, the relative amounts of elastin and type I collagen exhibited a peak (P < 0.01) at Day 2, but returned to baseline levels by Day 21. Structure-function relations manifested themselves in strong correlations between compliance parameters and both mean size and heterogeneity of airspace structure (r(2) > 0.9). Similar relations were also obtained in a network model of the parenchyma in which destruction was based on the notion that mechanical forces contribute to alveolar wall rupture. We conclude that, in a mouse model of emphysema, progressive decline in lung function is sensitive to the development of airspace heterogeneity governed by local, mechanical, force-induced failure of remodeled collagen.

  4. IL-17A Modulates Oxidant Stress-Induced Airway Hyperresponsiveness but Not Emphysema

    PubMed Central

    Pinart, Mariona; Zhang, Min; Li, Feng; Hussain, Farhana; Zhu, Jie; Wiegman, Coen; Ryffel, Bernard; Chung, Kian Fan

    2013-01-01

    IL-17A induces the release of pro-inflammatory cytokines and of reactive oxygen species which could lead to neutrophilic inflammation. We determined the role of IL-17 receptor (IL-17R) signalling in oxidant-induced lung emphysema and airway hyperresponsiveness. IL-17R−/− and wild-type C57/BL6 mice were exposed to ozone (3 ppm; 3 hours) for 12 times over 6 weeks. Bronchial responsiveness to acetylcholine was measured, and lungs were retrieved. Mean linear intercept (Lm) and isometric contractile responses of intrapulmonary airways to acetylcholine were determined. In wild-type mice but not in IL-17R−/−, chronic ozone exposure caused airway hyperresponsiveness. The increase in Lm after chronic ozone exposure of wild-type mice was also observed in IL-17R−/− mice. The increased maximal contractile response to acetylcholine seen in airways of wild-type mice exposed to ozone was abolished in IL-17R−/− mice. p38-mitogen-activated protein kinase (MAPK) and dexamethasone-dependent increase in contractile response was reduced in airways from IL-17R−/− ozone-exposed mice. Lung inflammation scores were not altered in IL-17R−/− mice exposed to ozone compared to wild-type mice. The increased release of IL-17 and IL-1β, and the activation of p38 MAPK in the lungs of ozone-exposed mice was reduced in IL-17R−/− mice. IL-17R signalling underlies the increase in airway hyperresponsiveness seen after ozone exposure, mediated by the increased contractility of airway smooth muscle. The emphysema and lung inflammation induced by ozone is not dependent on IL-17. PMID:23505509

  5. IL-17A modulates oxidant stress-induced airway hyperresponsiveness but not emphysema.

    PubMed

    Pinart, Mariona; Zhang, Min; Li, Feng; Hussain, Farhana; Zhu, Jie; Wiegman, Coen; Ryffel, Bernard; Chung, Kian Fan

    2013-01-01

    IL-17A induces the release of pro-inflammatory cytokines and of reactive oxygen species which could lead to neutrophilic inflammation. We determined the role of IL-17 receptor (IL-17R) signalling in oxidant-induced lung emphysema and airway hyperresponsiveness. IL-17R(-/-) and wild-type C57/BL6 mice were exposed to ozone (3 ppm; 3 hours) for 12 times over 6 weeks. Bronchial responsiveness to acetylcholine was measured, and lungs were retrieved. Mean linear intercept (Lm) and isometric contractile responses of intrapulmonary airways to acetylcholine were determined. In wild-type mice but not in IL-17R(-/-), chronic ozone exposure caused airway hyperresponsiveness. The increase in Lm after chronic ozone exposure of wild-type mice was also observed in IL-17R(-/-) mice. The increased maximal contractile response to acetylcholine seen in airways of wild-type mice exposed to ozone was abolished in IL-17R(-/-) mice. p38-mitogen-activated protein kinase (MAPK) and dexamethasone-dependent increase in contractile response was reduced in airways from IL-17R(-/-) ozone-exposed mice. Lung inflammation scores were not altered in IL-17R(-/-) mice exposed to ozone compared to wild-type mice. The increased release of IL-17 and IL-1β, and the activation of p38 MAPK in the lungs of ozone-exposed mice was reduced in IL-17R(-/-) mice. IL-17R signalling underlies the increase in airway hyperresponsiveness seen after ozone exposure, mediated by the increased contractility of airway smooth muscle. The emphysema and lung inflammation induced by ozone is not dependent on IL-17.

  6. [The clinical importance of determining fibronectin and the activity of proteolysis inhibitors in patients with bronchial asthma complicated by pulmonary emphysema].

    PubMed

    Okopnaia, L M; Glazatova, T M; Zorin, V N; Vassim, K; Padalka, I M

    1995-01-01

    Examinations of 27 inpatients with infection-dependent bronchial asthma complicated by pulmonary emphysema revealed low levels of fibronectin and alpha proteinase inhibitor, which were in a positive correlation. The said deficiency was stable in asthmatics and was virtually unchanged as remission was attained. Hence, we may propose that the said changes may underlie not only the development, but stabilization and progress of pulmonary emphysema in patients with the infection-dependent variant of bronchial asthma.

  7. "Punk" rock can be bad for you: a case of surgical emphysema from a "punk" rocker's leather jacket.

    PubMed

    Lane, N; Graudins, A

    2006-06-01

    Stab wounds to the thorax are seen in the emergency department (ED) and can be caused by a variety of mechanisms. This case highlights an unusual cause of injury: a leather jacket with spikes on the back of it. This type of jacket is often worn by "punks" as a fashion statement. We report that falling onto such a jacket may result in accidental thoracic injury leading to subcutaneous emphysema. A thorough clinical assessment is mandatory to exclude underlying lung injury or pneumothorax. In patients with subcutaneous emphysema and an otherwise normal chest radiograph, an in hospital observation period of 24 hours to check for any delayed complications is adequate if the patient remains clinically stable.

  8. Television Quiz Show Simulation

    ERIC Educational Resources Information Center

    Hill, Jonnie Lynn

    2007-01-01

    This article explores the simulation of four television quiz shows for students in China studying English as a foreign language (EFL). It discusses the adaptation and implementation of television quiz shows and how the students reacted to them.

  9. Early emphysema in the tight skin and pallid mice: roles of microfibril-associated glycoproteins, collagen, and mechanical forces.

    PubMed

    Ito, Satoru; Bartolák-Suki, Erzsébet; Shipley, J Michael; Parameswaran, Harikrishnan; Majumdar, Arnab; Suki, Bélâ

    2006-06-01

    The nature of the development of emphysema in the tight skin (Tsk) and the pallid (Pa) mice are not well understood. We assessed the mechanical and nonlinear properties of the respiratory system, the alveolar structure, and the levels of microfibril-associated glycoproteins (MAGP) 1 and 2 in Tsk mice with developmental emphysema; in Pa mice, which are thought to develop adult onset emphysema; and their background, the C57BL/6 mice, at an age of 7 wk. Minor differences between collagen-related elastic properties of the lungs of the Pa and C57BL/6 mice were seen at this early age. The lungs of the Tsk mice were significantly softer yet more nonlinear than those of the Pa and C57BL/6 mice. The MAGP-1 levels were similar in all three groups. However, the level of MAGP-2, which is associated with both fibrillin-1 and collagen, was higher in the Tsk than in the Pa mice, which also had more MAGP-2 than the C57BL/6. Both the mean and the variance of alveolar diameters were larger in the Tsk than in the other two groups, while the variance in the Pa was larger than in the C57BL/6 mice, implying early development of heterogeneity. Using a network model of the parenchyma, we linked the pathophysiologic changes in the Tsk mice to mechanical forces and failure of the alveolar walls. Our findings suggest the possibility that MAGP-2-related abnormal collagen assembly, combined with mechanical forces, is involved in the progression of emphysema in the Tsk mice.

  10. The ratio of the alveolar ventilations of SF6 and He in patients with lung emphysema and in healthy subjects.

    PubMed

    Luijendijk, S C M; van der Grinten, C P M

    2002-03-01

    This study assess the possible impact of changes in the morphometry of acinar airways and air spaces on the efficacy of intrapulmonary gas mixing for sulphur hexafluoride (SF6) relative to that for helium (He). To that end the alveolar ventilations of He and SF6 were determined in patients with macroscopic lung emphysema and in healthy subjects. He-SF6 washout tests were performed in 17 patients (15 emphysema, 2 chronic bronchitis) and 21 healthy subjects. Using a three-compartment model, the data obtained were used to estimate the overall, effective, alveolar ventilations of SF6 and He, and their ratio VAASF6/VAHe. Mean VAASF6/VAHe (+/- S.D.) for patients (0.80 +/- 0.06) was significantly smaller (P < 0.001) than the value for the group of age-matched healthy subjects (0.90 +/- 0.05) which was non-significantly smaller than the result for the group of young, healthy subjects (0.93 +/- 0.03). In our patients, we also determined a score for emphysema using high resolution computed tomography, and this score correlated inversely with VAASF6/VAHe (r = -0.56, P = 0.018). We have interpreted our observations to mean that in patients with lung emphysema, the efficacy of intrapulmonary gas mixing for SF6 as compared with that for He reflected by VAASF6/VAHe is diminished due to increased diffusive path-lengths within the enlarged air spaces of their lungs which impair diffusive gas mixing for SF6 more than for He.

  11. Decitabine enhances stem cell antigen-1 expression in cigarette smoke extract-induced emphysema in animal model.

    PubMed

    He, Zhi-Hui; Chen, Yan; Chen, Ping; He, Sheng-Dong; Ye, Ji-Ru; Liu, Da

    2016-01-01

    Stem cell antigen-1 (Sca-1) is a mouse glycosyl phosphatidylinositol-anchored protein and a cell surface marker found on hematopoietic stem cells (HSCs). Despite decades of study, its biological functions remain little known. Sca-1 is a typical marker of bone marrow-derived HSCs, it is also expressed by a mixture of tissue-resident stem, progenitor cells in nonhematopoietic organs. Endothelial progenitor cell (EPC) is a subtype of HSC and contributes to endothelial repair by homing in on locations of injury. Abnormal genetic methylation has been detected in smoking-related diseases. The present study aimed to investigate the lung function and histomorphology, the expression of Sca-1 gene in lung tissues, and bone marrow-derived EPCs in cigarette smoke extract (CSE)-induced emphysema mice, and to further determine whether Decitabine (Dec), the most widely used inhibitor of DNA methylation, could protect against the damages caused by CSE. The results of the present study demonstrated that Dec could partly protect against CSE-induced emphysema in mice, enhance Sca-1 expression in lung tissue, and bone marrow-derived EPCs. The results suggested that the depletion of the progenitor cell pool and DNA methylation of Sca-1 gene may be involved in the progression of emphysema in mice.

  12. Inactivation of alpha 1-antitrypsin by aqueous coal solutions: Possible relation to the emphysema of coal workers

    SciTech Connect

    Huang, X.; Laurent, P.A.; Zalma, R.; Pezerat, H. )

    1993-07-01

    Increasing evidence demonstrates that emphysema in coal workers may be related to their exposure to coal dusts. The hypothesis that emphysema could be related to the production of reactive oxygen species (ROS) generated by inhaled coal dusts was examined in the present study. Using ESR, we investigated whether the interaction of different coals with dissolved oxygen in aqueous medium could generate ROS. Indeed, we found that one of the five examined French coal samples, Vouters coal, was effective in oxidizing formate anions or ethanol by a radical pathway. Inactivation of alpha 1-antitrypsin (alpha 1-AT) in vitro was then examined for all five coal filtrates. The Vouters coal filtrate, which exhibits oxidative activity, can also inactivate alpha 1-AT. When this coal filtrate was crystallized and redissolved, its oxidative activity was found to be conserved. By use of various analytical techniques, the active component of this coal filtrate was identified to be primarily ferrous sulfate. We confirmed that pure ferrous sulfate can effectively reduce oxygen to produce ROS in aqueous medium in vitro and can also inactivate alpha 1-AT. In this report, the nature of the coal-generated oxidative species, the origin of ferrous sulfate, and the stability of ferrous sulfate in the different coal samples are discussed. These results offer evidence that some inhaled coal dusts are capable of producing ROS, which may play an important role in the development of coal workers' emphysema.

  13. Mechanics, nonlinearity, and failure strength of lung tissue in a mouse model of emphysema: possible role of collagen remodeling.

    PubMed

    Ito, Satoru; Ingenito, Edward P; Brewer, Kelly K; Black, Lauren D; Parameswaran, Harikrishnan; Lutchen, Kenneth R; Suki, Béla

    2005-02-01

    Enlargement of the respiratory air spaces is associated with the breakdown and reorganization of the connective tissue fiber network during the development of pulmonary emphysema. In this study, a mouse (C57BL/6) model of emphysema was developed by direct instillation of 1.2 IU of porcine pancreatic elastase (PPE) and compared with control mice treated with saline. The PPE treatment caused 95% alveolar enlargement (P = 0.001) associated with a 29% lower elastance along the quasi-static pressure-volume curves (P < 0.001). Respiratory mechanics were measured at several positive end-expiratory pressures in the closed-chest condition. The dynamic tissue elastance was 19% lower (P < 0.001), hysteresivity was 9% higher (P < 0.05), and harmonic distortion, a measure of collagen-related dynamic nonlinearity, was 33% higher in the PPE-treated group (P < 0.001). Whole lung hydroxyproline content, which represents the total collagen content, was 48% higher (P < 0.01), and alpha-elastin content was 13% lower (P = 0.16) in the PPE-treated group. There was no significant difference in airway resistance (P = 0.7). The failure stress at which isolated parenchymal tissues break during stretching was 40% lower in the PPE-treated mice (P = 0.002). These findings suggest that, after elastolytic injury, abnormal collagen remodeling may play a significant role in all aspects of lung functional changes and mechanical forces, leading to progressive emphysema.

  14. Assessment of Independent Risk Factors of Developing Pneumothorax During Percutaneous Core Needle Lung Biopsy: Focus on Lesion Depth

    PubMed Central

    Lee, Ha-Yeon; Lee, In Jae

    2016-01-01

    Background Previous studies identifying risk factors for pneumothorax in percutaneous core needle lung biopsies reported inconsistent and contradictory results. Objectives We aimed to identify independent risk factors for pneumothorax associated with computed tomography (CT)-guided percutaneous core needle lung biopsy (PCNB). Patients and Methods We retrospectively reviewed 591 biopsy procedures for focal lung lesions. Risk factors for pneumothorax as a complication after lung biopsy were determined by univariate and multivariate analyses of variables including the patient’s age, gender, lesion depth from the pleural surface, lesion size, lesion location, presence or absence of fissure crossing by the needle, emphysema in the same lobe where the biopsy was performed, and the final diagnosis of the biopsy lesion. Results Pneumothorax occurred in 100 (16.9%) of 591 procedures. Based on univariate analyses, significant risk factors affecting the incidence of pneumothorax were patient gender (P = 0.039), lesion depth from the pleural surface (P < 0.001), fissure crossing by the needle (P = 0.002), and the presence of emphysema (P = 0.009). From the multivariate analysis, an increased rate of pneumothorax was strongly correlated with lesion depth from the pleural surface (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.50 - 1.96; P < 0.001) and the presence of emphysema (OR, 2.95; 95% CI, 1.73 - 5.04; P < 0.001). Conclusion Lesion depth from the pleural surface and the presence of emphysema were strongly correlated with the increasing incidence of pneumothorax after CT-guided PCNB. Our results may be applicable for the risk management of PCNBs to reduce pneumothorax as a complication. PMID:27895865

  15. Hydrogen Sulfide Ameliorates Tobacco Smoke-Induced Oxidative Stress and Emphysema in Mice

    PubMed Central

    Han, Weihong; Dong, Zheng; Dimitropoulou, Christiana

    2011-01-01

    Abstract Aims The mutual interactions between reactive oxygen species, airway inflammation, and alveolar cell death play crucial role in the pathogenesis of chronic obstructive pulmonary disease (COPD). In the present study, we investigated the possibility that hydrogen sulfide (H2S) donor sodium hydrosulfide (NaHS) might be a novel option for intervention in COPD. Results We used a mouse model of tobacco smoke (TS)-induced emphysema. Mice were injected with H2S donor NaHS (50 μmol/kg in 0.25 ml phosphate buffer saline, intraperitoneally) or vehicle daily before exposed to TS for 1 h/day, 5 days/week for 12 and 24 weeks. We found that NaHS ameliorated TS-induced increase in mean linear intercepts, the thickness of bronchial walls, and the numbers of total cell counts as well as neutrophils, monocytes, and tumor necrosis factor α in bronchial alveolar lavage. Moreover, NaHS reduced increases in right ventricular systolic pressure, the thickness of pulmonary vascular walls, and the ratio of RV/LV+S in TS-exposed mice. Further, TS exposure for 12 and 24 weeks reduced the protein contents of cystathionine γ-lyase (CGL), cystathionine β-synthetase (CBS), nuclear erythroid-related factor 2 (Nrf2), Pser473-Akt, as well as glutathione/oxidized glutathione ratio in the lungs. TS-exposed lungs exhibited large amounts of 8-hydroxyguanine-positive and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells. Treatment with NaHS increased Pser473-Akt and attenuated TS-induced reduction of CGL, CBS, and Nrf2 as well as glutathione/oxidized glutathione ratio in the lungs. NaHS also reduced amounts of 8-hydroxyguanine-positive, terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells and active caspase-3 in TS-exposed lungs. Additionally, knocking-down Akt protein abolished the protective effects of NaHS against TS-induced apoptosis and downregulation of Nrf2, CGL, and CBS in pulmonary artery endothelial cells. Conclusion These

  16. Diffusion capacity and CT measures of emphysema and airway wall thickness – relation to arterial oxygen tension in COPD patients

    PubMed Central

    Saure, Eirunn Waatevik; Bakke, Per Sigvald; Eagan, Tomas Mikal Lind; Aanerud, Marianne; Jensen, Robert Leroy; Grydeland, Thomas Blix; Johannessen, Ane; Nilsen, Roy Miodini; Thorsen, Einar; Hardie, Jon Andrew

    2016-01-01

    Background Decreased diffusing capacity of the lung for carbon monoxide (DLCO) is associated with emphysema. DLCO is also related to decreased arterial oxygen tension (PaO2), but there are limited data on associations between PaO2 and computed tomography (CT) derived measures of emphysema and airway wall thickness. Objective To examine whether CT measures of emphysema and airway wall thickness are associated with level of arterial oxygen tension beyond that provided by measurements of diffusion capacity and spirometry. Methods The study sample consisted of 271 smoking or ex-smoking COPD patients from the Bergen COPD Cohort Study examined in 2007–2008. Emphysema was assessed as percent of low-attenuation areas<−950 Hounsfield units (%LAA), and airway wall thickness as standardised measure at an internal perimeter of 10 mm (AWT-Pi10). Multiple linear regression models were fitted with PaO2 as the outcome variable, and %LAA, AWT-Pi10, DLCO and carbon monoxide transfer coefficient (KCO) as main explanatory variables. The models were adjusted for sex, age, smoking status, and haemoglobin concentration, as well as forced expiratory volume in one second (FEV1). Results Sixty two per cent of the subjects were men, mean (SD) age was 64 (7) years, mean (SD) FEV1 in percent predicted was 50 (15)%, and mean PaO2 (SD) was 9.3 (1.1) kPa. The adjusted regression coefficient (CI) for PaO2 was –0.32 (−0.04–(−0.019)) per 10% increase in %LAA (p<0.01). When diffusion capacity and FEV1 were added to the model, respectively, the association lost its statistical significance. No relationship between airway wall thickness and PaO2 was found. Conclusion CT assessment of airway wall thickness is not associated with arterial oxygen tension in COPD patients. Emphysema score measured by chest CT, is related to decreased PaO2, but cannot replace measurements of diffusion capacity in the clinical evaluation of hypoxaemia. PMID:27178139

  17. Lung injury-dependent oxidative status and chymotrypsin-like activity of skeletal muscles in hamsters with experimental emphysema

    PubMed Central

    2013-01-01

    Background Peripheral skeletal muscle is altered in patients suffering from emphysema and chronic obstructive pulmonary disease (COPD). Oxidative stress have been demonstrated to participate on skeletal muscle loss of several states, including disuse atrophy, mechanical ventilation, and chronic diseases. No evidences have demonstrated the occurance in a severity manner. Methods We evaluated body weight, muscle loss, oxidative stress, and chymotrypsin-like proteolytic activity in the gastrocnemius muscle of emphysemic hamsters. The experimental animals had 2 different severities of lung damage from experimental emphysema induced by 20 mg/mL (E20) and 40 mg/mL (E40) papain. Results The severity of emphysema increased significantly in E20 (60.52 ± 2.8, p < 0.05) and E40 (52.27 ± 4.7; crossed the alveolar intercepts) groups. As compared to the control group, there was a reduction on body (171.6 ± 15.9 g) and muscle weight (251.87 ± 24.87 mg) in the E20 group (157.5 ± 10.3 mg and 230.12 ± 23.52 mg, for body and muscle weight, respectively), which was accentuated in the E40 group (137.4 ± 7.2 g and 197.87 ± 10.49 mg, for body and muscle weight, respectively). Additionally, the thiobarbituric acid reactive substances (TBARS), tert-butyl hydroperoxide-initiated chemiluminescence (CL), carbonylated proteins, and chymotrypsin-like proteolytic activity were elevated in the E40 group as compared to the E20 group (p < 0.05 for all comparisons). The severity of emphysema significantly correlated with the progressive increase in CL (r = −0.95), TBARS (r = −0.98), carbonyl proteins (r = −0.99), and chymotrypsin-like proteolytic activity (r = −0.90). Furthermore, augmentation of proteolytic activity correlated significantly with CL (r = 0.97), TBARS (r = 0.96), and carbonyl proteins (r = 0.91). Conclusions Taken together, the results of the present study suggest that muscle atrophy observed in this model of emphysema is mediated by increased muscle chymotrypsin

  18. Involvement of B-cell CLL/lymphoma 2 promoter methylation in cigarette smoke extract-induced emphysema

    PubMed Central

    Zeng, Huihui; Shi, Zhihui; Kong, Xianglong; Chen, Yan; Zhang, Hongliang; Peng, Hong; Luo, Hong

    2016-01-01

    Abnormal apoptotic events play an important role in the pathogenesis of emphysema. The B-cell CLL/lymphoma 2 (Bcl-2) family proteins are essential and critical regulators of apoptosis. We determined whether the anti-apoptotic Bcl-2 play a role in the cigarette smoke extract (CSE)-induced emphysema. Furthermore, given the involvement of epigenetics in chronic obstructive pulmonary disease, we hypothesized that the deregulation of Bcl-2 might be caused by gene methylation. The emphysema in BALB/C mice was established by intraperitoneally injection of CSE. 5-aza-2′-deoxycytidine (AZA; a demethylation reagent) and phosphate-buffered saline were also administered intraperitoneally as CSE. TUNEL assay was used to assess apoptotic index of pulmonary cells. The methylation status of CpG dinucleotides within the Bcl-2 promoter was observed in all groups by bisulfite sequencing PCR. Pulmonary expression of Bcl-2, Bax, and cytochrome C were measured after four weeks of treatment. The apoptotic index of pulmonary cells in CSE injection group was much higher than control ((25.88 ± 7.55)% vs. (6.28 ± 2.96)%). Compared to control mice, decreased expression of Bcl-2 and high methylation of Bcl-2 promoter was observed in CSE injected mice (0.88 ± 0.08 vs. 0.49 ± 0.11, (3.82 ± 1.34)% vs. (35.68 ± 5.99)%, P < 0.01).CSE treatment induced lung cell apoptosis and decreased lung function. AZA treatment increased Bcl-2 expression with Bcl-2 promoter demethylation. AZA also alleviated the lung cell apoptosis and function failure caused by CSE treatment. The decreased expression of anti-apoptotic Bcl-2 might account for the increased apoptosis in CSE induced-emphysema. Apparently, epigenetic alternation played a role in this deregulation of Bcl-2 expression, and it might support the involvement of epigenetic events in the pathogenesis of emphysema. PMID:26924842

  19. Independent Peer Reviews

    SciTech Connect

    2012-03-16

    Independent Assessments: DOE's Systems Integrator convenes independent technical reviews to gauge progress toward meeting specific technical targets and to provide technical information necessary for key decisions.

  20. Interleukin-1beta causes pulmonary inflammation, emphysema, and airway remodeling in the adult murine lung.

    PubMed

    Lappalainen, Urpo; Whitsett, Jeffrey A; Wert, Susan E; Tichelaar, Jay W; Bry, Kristina

    2005-04-01

    The production of the inflammatory cytokine interleukin (IL)-1 is increased in lungs of patients with chronic obstructive pulmonary disease (COPD) or asthma. To characterize the in vivo actions of IL-1 in the lung, transgenic mice were generated in which human IL-1beta was expressed in the lung epithelium with a doxycycline-inducible system controlled by the rat Clara cell secretory protein (CCSP) promoter. Induction of IL-1beta expression in the lungs of adult mice caused pulmonary inflammation characterized by neutrophil and macrophage infiltrates. IL-1beta caused distal airspace enlargement, consistent with emphysema. IL-1beta caused disruption of elastin fibers in alveolar septa and fibrosis in airway walls and in the pleura. IL-1beta increased the thickness of conducting airways, enhanced mucin production, and caused lymphocytic aggregates in the airways. Decreased immunostaining for the winged helix transcription factor FOXA2 was associated with goblet cell hyperplasia in IL-1beta-expressing mice. The production of the neutrophil attractant CXC chemokines KC (CXCL1) and MIP-2 (CXCL2), and of matrix metalloproteases MMP-9 and MMP-12, was increased by IL-1beta. Chronic production of IL-1beta in respiratory epithelial cells of adult mice causes lung inflammation, enlargement of distal airspaces, mucus metaplasia, and airway fibrosis in the adult mouse.

  1. Kinetics of in vitro bronchoconstriction in an elastolytic mouse model of emphysema.

    PubMed

    Khan, M A; Kianpour, S; Stämpfli, M R; Janssen, L J

    2007-10-01

    Thin-slice videomicroscopy was used to examine the kinetics of constriction in small airways in situ. Balb/C mice inhaled elastase (0-20 IU), and were then left to recover for 14 days before euthanisation and lung removal. Cholinergic responsiveness was assessed in thin lung slices. Magnitude and velocity of narrowing in response to 10(-5) M acetylcholine (ACh), as well as the full concentration-response relationship for ACh (10(-8)-10(-5) M) were assessed. In vivo exposure to elastase was accompanied by statistically significantly decreased magnitudes and velocities of contraction, but no change in the ACh concentration-response relationship. Conversely, overnight, in vitro exposure of slices from control animals to elastase (2.5 microg.mL(-1)) resulted in increased magnitudes and velocities of airway narrowing, with impaired relaxation, as well as marked tearing of the airways from the surrounding parenchyma. These changes are characteristic of decreased tethering forces on the airway wall. Thus, the lung slice technique coupled with videomicroscopic analysis of airway contraction velocities provides a powerful tool to study airway-parenchymal interactions. The elastolytic model of emphysema, which manifests with airspace enlargement and loss of parenchymal attachments, is accompanied by decreased airway contraction kinetics. The mechanism(s) underlying this loss of function remain to be elucidated.

  2. The Role of Interleukin-23 in the Early Development of Emphysema in HIV1+ Smokers

    PubMed Central

    Barjaktarevic, Igor Z.; Crystal, Ronald G.

    2016-01-01

    Rationale. Matrix metalloproteinase-9 (MMP-9) expression is upregulated in alveolar macrophages (AM) of HIV1+ smokers who develop emphysema. Knowing that lung epithelial lining fluid (ELF) of HIV1+ smokers contains increased levels of inflammatory cytokines compared to HIV1− smokers, we hypothesized that upregulation of lung cytokines in HIV1+ smokers may be functionally related to increased MMP-9 expression. Methods. Cytokine arrays evaluated cytokine protein levels in ELF obtained from 5 groups of individuals: HIV1− healthy nonsmokers, HIV1− healthy smokers, HIV1− smokers with low diffusing capacity (DLCO), HIV1+ nonsmokers, and HIV1+ smokers with low DLCO. Results. Increased levels of the Th17 related cytokine IL-23 were found in HIV1− smokers with low DLCO and HIV1+ smokers and nonsmokers. Relative IL-23 gene expression was increased in AM of HIV1+ individuals, with greater expression in AM of HIV1+ smokers with low DLCO. Infection with HIV1 in vitro induced IL-23 expression in normal AM. IL-23 stimulation of AM/lymphocyte cocultures in vitro induced upregulation of MMP-9. Lung T lymphocytes express receptor IL-23R and interact with AM in order to upregulate MMP-9. Conclusion. This mechanism may contribute to the increased tissue destruction in the lungs of HIV1+ smokers and suggests that Th17 related inflammation may play a role. PMID:27446965

  3. Cigarette smoke inhibits alveolar repair: a mechanism for the development of emphysema.

    PubMed

    Rennard, Stephen I; Togo, Shinsaku; Holz, Olaf

    2006-11-01

    Classically, emphysema has been believed to develop when mediators of tissue injury exceed protective mechanisms within the lung. Evidence also supports the concept that tissue destruction represents a balance between tissue injury and tissue repair. In this context, cigarette smoke is directly toxic to cells within the lung and can impair the repair functions of fibroblasts, epithelial cells, and mesenchymal cells. This may occur in the absence of overt cytotoxicity and may result from alteration of selected biochemical pathways. A variety of repair functions can be affected, including chemotaxis, proliferation, production of extracellular matrix, and remodeling of extracellular matrix. Finally, cigarette smoke can damage DNA but can also compromise apoptosis. As a result, DNA repair mechanisms can be initiated, leading to recovery of cells that potentially contain somatic cell mutations. This pathway may contribute not only to the development of cancer but to the persistent abnormalities in tissue structure that characterize chronic obstructive pulmonary disease. Understanding the mechanisms that mediate normal tissue repair and understanding the bases for altered tissue repair in the face of cigarette smoking offer new opportunities designed to address the structural alterations that characterize chronic obstructive pulmonary disease.

  4. Adipose stem cell-derived nanovesicles inhibit emphysema primarily via an FGF2-dependent pathway

    PubMed Central

    Kim, You-Sun; Kim, Ji-Young; Cho, RyeonJin; Shin, Dong-Myung; Lee, Sei Won; Oh, Yeon-Mok

    2017-01-01

    Cell therapy using stem cells has produced therapeutic benefits in animal models of COPD. Secretory mediators are proposed as one mechanism for stem cell effects because very few stem cells engraft after injection into recipient animals. Recently, nanovesicles that overcome the disadvantages of natural exosomes have been generated artificially from cells. We generated artificial nanovesicles from adipose-derived stem cells (ASCs) using sequential penetration through polycarbonate membranes. ASC-derived artificial nanovesicles displayed a 100 nm-sized spherical shape similar to ASC-derived natural exosomes and expressed both exosomal and stem cell markers. The proliferation rate of lung epithelial cells was increased in cells treated with ASC-derived artificial nanovesicles compared with cells treated with ASC-derived natural exosomes. The lower dose of ASC-derived artificial nanovesicles had similar regenerative capacity compared with a higher dose of ASCs and ASC-derived natural exosomes. In addition, FGF2 levels in the lungs of mice treated with ASC-derived artificial nanovesicles were increased. The uptake of ASC-derived artificial nanovesicles was inhibited by heparin, which is a competitive inhibitor of heparan sulfate proteoglycan that is associated with FGF2 signaling. Taken together, the data indicate that lower doses of ASC-derived artificial nanovesicles may have beneficial effects similar to higher doses of ASCs or ASC-derived natural exosomes in an animal model with emphysema, suggesting that artificial nanovesicles may have economic advantages that warrant future clinical studies. PMID:28082743

  5. Lung regeneration by fetal lung tissue implantation in a mouse pulmonary emphysema model.

    PubMed

    Uyama, Koh; Sakiyama, Shoji; Yoshida, Mitsuteru; Kenzaki, Koichiro; Toba, Hiroaki; Kawakami, Yukikiyo; Okumura, Kazumasa; Takizawa, Hiromitsu; Kondo, Kazuya; Tangoku, Akira

    2016-01-01

    The mortality and morbidity of chronic obstructive pulmonary disease are high. However, no radical therapy has been developed to date. The purpose of this study was to evaluate whether fetal mouse lung tissue can grow and differentiate in the emphysematous lung. Fetal lung tissue from green fluorescent protein C57BL/6 mice at 16 days' gestation was used as donor material. Twelve-month-old pallid mice were used as recipients. Donor lungs were cut into small pieces and implanted into the recipient left lung by performing thoracotomy under anesthesia. The recipient mice were sacrificed at day 7, 14, and 28 after implantation and used for histological examination. Well-developed spontaneous pulmonary emphysema was seen in 12-month-old pallid mice. Smooth and continuous connection between implanted fetal lung tissue and recipient lung was recognized. Air space expansion and donor tissue differentiation were observed over time. We could clearly distinguish the border zones between injected tissue and native tissue by the green fluorescence of grafts. Fetal mouse lung fragments survived and differentiated in the emphysematous lung of pallid mice. Implantation of fetal lung tissue in pallid mice might lead to further lung regeneration research from the perspective of respiratory and exercise function. J. Med. Invest. 63: 182-186, August, 2016.

  6. Adipose stem cell-derived nanovesicles inhibit emphysema primarily via an FGF2-dependent pathway.

    PubMed

    Kim, You-Sun; Kim, Ji-Young; Cho, RyeonJin; Shin, Dong-Myung; Lee, Sei Won; Oh, Yeon-Mok

    2017-01-13

    Cell therapy using stem cells has produced therapeutic benefits in animal models of COPD. Secretory mediators are proposed as one mechanism for stem cell effects because very few stem cells engraft after injection into recipient animals. Recently, nanovesicles that overcome the disadvantages of natural exosomes have been generated artificially from cells. We generated artificial nanovesicles from adipose-derived stem cells (ASCs) using sequential penetration through polycarbonate membranes. ASC-derived artificial nanovesicles displayed a 100 nm-sized spherical shape similar to ASC-derived natural exosomes and expressed both exosomal and stem cell markers. The proliferation rate of lung epithelial cells was increased in cells treated with ASC-derived artificial nanovesicles compared with cells treated with ASC-derived natural exosomes. The lower dose of ASC-derived artificial nanovesicles had similar regenerative capacity compared with a higher dose of ASCs and ASC-derived natural exosomes. In addition, FGF2 levels in the lungs of mice treated with ASC-derived artificial nanovesicles were increased. The uptake of ASC-derived artificial nanovesicles was inhibited by heparin, which is a competitive inhibitor of heparan sulfate proteoglycan that is associated with FGF2 signaling. Taken together, the data indicate that lower doses of ASC-derived artificial nanovesicles may have beneficial effects similar to higher doses of ASCs or ASC-derived natural exosomes in an animal model with emphysema, suggesting that artificial nanovesicles may have economic advantages that warrant future clinical studies.

  7. Elastase-induced emphysema: retention of instilled proteinase in the rat

    SciTech Connect

    Sandhaus, R.A.; Janoff, A.

    1982-11-01

    Airway instillation of proteinases with the ability to degrade elastin has been used to produce disease in the rat analogous to human pulmonary emphysema. This study examined the retention, localization, and fate of endotracheally instilled elastase using /sup 125/I labeled enzyme and immunoperoxidase histochemistry. Porcine pancreatic elastase labeled with /sup 125/I was detected in rat lungs through 96 h after instillation; over half of the label was still present after 7 h. Similar results were obtained when elastase was reacted with a specific, catalytic site inactivator prior to instillation. Trypsin and denatured elastase, however, were cleared much more rapidly from the lung (less than half of the label present after 30 min). When lungs were homogenized after instillation of active elastas