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Sample records for emphysema show independent

  1. Emphysema

    MedlinePlus

    ... the ages of 40 and 60. Exposure to secondhand smoke. Secondhand smoke, also known as passive or environmental tobacco smoke, ... someone else's cigarette, pipe or cigar. Being around secondhand smoke increases your risk of emphysema. Occupational exposure to ...

  2. 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

  3. [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.

  4. [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.

  5. 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.

  6. Imaging of pulmonary emphysema: A pictorial review

    PubMed Central

    Takahashi, Masashi; Fukuoka, Junya; Nitta, Norihisa; Takazakura, Ryutaro; Nagatani, Yukihiro; Murakami, Yoko; Otani, Hideji; Murata, Kiyoshi

    2008-01-01

    The term ‘emphysema’ is generally used in a morphological sense, and therefore imaging modalities have an important role in diagnosing this disease. In particular, high resolution computed tomography (HRCT) is a reliable tool for demonstrating the pathology of emphysema, even in subtle changes within secondary pulmonary lobules. Generally, pulmonary emphysema is classified into three types related to the lobular anatomy: centrilobular emphysema, panlobular emphysema, and paraseptal emphysema. In this pictorial review, we discuss the radiological – pathological correlation in each type of pulmonary emphysema. HRCT of early centrilobular emphysema shows an evenly distributed centrilobular tiny areas of low attenuation with ill-defined borders. With enlargement of the dilated airspace, the surrounding lung parenchyma is compressed, which enables observation of a clear border between the emphysematous area and the normal lung. Because the disease progresses from the centrilobular portion, normal lung parenchyma in the perilobular portion tends to be preserved, even in a case of far-advanced pulmonary emphysema. In panlobular emphysema, HRCT shows either panlobular low attenuation or ill-defined diffuse low attenuation of the lung. Paraseptal emphysema is characterized by subpleural well-defined cystic spaces. Recent topics related to imaging of pulmonary emphysema will also be discussed, including morphometry of the airway in cases of chronic obstructive pulmonary disease, combined pulmonary fibrosis and pulmonary emphysema, and bronchogenic carcinoma associated with bullous lung disease. PMID:18686729

  7. The Relationship Between Pulmonary Emphysema and Kidney Function in Smokers

    PubMed Central

    Chandra, Divay; Stamm, Jason A.; Palevsky, Paul M.; Leader, Joseph K.; Fuhrman, Carl R.; Zhang, Yingze; Bon, Jessica; Duncan, Steven R.; Branch, Robert A.; Weissfeld, Joel; Gur, David; Gladwin, Mark T.

    2012-01-01

    Background: It has been reported that the prevalence of kidney dysfunction may be increased in patients exposed to tobacco with airflow obstruction. We hypothesized that kidney dysfunction would associate with emphysema rather than with airflow obstruction measured by the FEV1. Methods: Five hundred eight current and former smokers completed a chest CT scan, pulmonary function tests, medical questionnaires, and measurement of serum creatinine. Glomerular filtration rates (eGFRs) were estimated using the method of the Chronic Kidney Disease Epidemiology Collaboration. Quantitative determinants of emphysema and airway dimension were measured from multidetector chest CT scans. Results: The mean age was 66 ± 7 years, and mean eGFR was 101 ± 22 mL/min/1.73 m2. Univariate and multivariate analysis showed a significant association between radiographically measured emphysema and eGFR: Participants with 10% more emphysema had an eGFR that was lower by 4.4 mL/min/1.73 m2 (P = .01), independent of airflow obstruction (FEV1), age, sex, race, height, BMI, diabetes mellitus, hypertension, coronary artery disease, patient-reported dyspnea, pack-years of smoking, and current smoking. There was no association between eGFR and either FEV1 or quantitative CT scan measures of airway dimension. Conclusions: More severe emphysema, rather than airflow obstruction, is associated with kidney dysfunction in tobacco smokers, independent of common risk factors for kidney disease. This finding adds to recent observations of associations between emphysema and comorbidities of COPD, including osteoporosis and lung cancer, which are independent of the traditional measure of reduced FEV1. The mechanisms and clinical implications of kidney dysfunction in patients with emphysema need further investigation. PMID:22459775

  8. The relationship between pulmonary emphysema and kidney function in smokers.

    PubMed

    Chandra, Divay; Stamm, Jason A; Palevsky, Paul M; Leader, Joseph K; Fuhrman, Carl R; Zhang, Yingze; Bon, Jessica; Duncan, Steven R; Branch, Robert A; Weissfeld, Joel; Gur, David; Gladwin, Mark T; Sciurba, Frank C

    2012-09-01

    It has been reported that the prevalence of kidney dysfunction may be increased in patients exposed to tobacco with airflow obstruction. We hypothesized that kidney dysfunction would associate with emphysema rather than with airflow obstruction measured by the FEV₁. Five hundred eight current and former smokers completed a chest CT scan, pulmonary function tests, medical questionnaires, and measurement of serum creatinine. Glomerular filtration rates (eGFRs) were estimated using the method of the Chronic Kidney Disease Epidemiology Collaboration. Quantitative determinants of emphysema and airway dimension were measured from multidetector chest CT scans. The mean age was 66 ± 7 years, and mean eGFR was 101 ± 22 mL/min/1.73 m². Univariate and multivariate analysis showed a significant association between radiographically measured emphysema and eGFR: Participants with 10% more emphysema had an eGFR that was lower by 4.4 mL/min/1.73 m² (P = .01), independent of airflow obstruction (FEV₁), age, sex, race, height, BMI, diabetes mellitus, hypertension, coronary artery disease, patient-reported dyspnea, pack-years of smoking, and current smoking. There was no association between eGFR and either FEV₁ or quantitative CT scan measures of airway dimension. More severe emphysema, rather than airflow obstruction, is associated with kidney dysfunction in tobacco smokers, independent of common risk factors for kidney disease. This finding adds to recent observations of associations between emphysema and comorbidities of COPD, including osteoporosis and lung cancer, which are independent of the traditional measure of reduced FEV₁. The mechanisms and clinical implications of kidney dysfunction in patients with emphysema need further investigation.

  9. 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.

  10. 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

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

    PubMed

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

    2016-12-13

    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 AND METHODS 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.

  12. Pulmonary emphysema subtypes on computed tomography: the MESA COPD study.

    PubMed

    Smith, Benjamin M; Austin, John H M; Newell, John D; D'Souza, Belinda M; Rozenshtein, Anna; Hoffman, Eric A; Ahmed, Firas; Barr, R Graham

    2014-01-01

    Pulmonary emphysema is divided into 3 major subtypes at autopsy: centrilobular, paraseptal, and panlobular emphysema. These subtypes can be defined by visual assessment on computed tomography (CT); however, clinical characteristics of emphysema subtypes on CT are not well defined. We developed a reliable approach to visual assessment of emphysema subtypes on CT and examined if emphysema subtypes have distinct characteristics. The Multi-Ethnic Study of Atherosclerosis COPD Study recruited smokers with chronic obstructive pulmonary disease (COPD) and controls ages 50-79 years with ≥ 10 pack-years. Participants underwent CT following a standardized protocol. Definitions of centrilobular, paraseptal, and panlobular emphysema were obtained by literature review. Six-minute walk distance and pulmonary function were performed following guidelines. Twenty-seven percent of 318 smokers had emphysema on CT. Interrater reliability of emphysema subtype was substantial (K: 0.70). Compared with participants without emphysema, individuals with centrilobular or panlobular emphysema had greater dyspnea, reduced walk distance, greater hyperinflation, and lower diffusing capacity. In contrast, individuals with paraseptal emphysema were similar to controls, except for male predominance. Centrilobular, but not panlobular or paraseptal, emphysema was associated with greater smoking history (+21 pack-years P <.001). Panlobular, but not other types of emphysema, was associated with reduced body mass index (-5 kg/m(2); P = .01). Other than for dyspnea, these findings were independent of the forced expiratory volume in 1 second. Seventeen percent of smokers without COPD on spirometry had emphysema, which was independently associated with reduced walk distance. Emphysema subtypes on CT are common in smokers with and without COPD. Centrilobular and panlobular emphysema, but not paraseptal emphysema, have considerable symptomatic and physiological consequences. Copyright © 2014 Elsevier Inc

  13. 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.

  14. Basal Gene Expression by Lung CD4+ T Cells in Chronic Obstructive Pulmonary Disease Identifies Independent Molecular Correlates of Airflow Obstruction and Emphysema Extent

    PubMed Central

    Freeman, Christine M.; McCubbrey, Alexandra L.; Crudgington, Sean; Nelson, Joshua; Martinez, Fernando J.; Han, MeiLan K.; Washko, George R.; Chensue, Stephen W.; Arenberg, Douglas A.; Meldrum, Catherine A.; McCloskey, Lisa; Curtis, Jeffrey L.

    2014-01-01

    Lung CD4+ T cells accumulate as chronic obstructive pulmonary disease (COPD) progresses, but their role in pathogenesis remains controversial. To address this controversy, we studied lung tissue from 53 subjects undergoing clinically-indicated resections, lung volume reduction, or transplant. Viable single-cell suspensions were analyzed by flow cytometry or underwent CD4+ T cell isolation, followed either by stimulation with anti-CD3 and cytokine/chemokine measurement, or by real-time PCR analysis. In lung CD4+ T cells of most COPD subjects, relative to lung CD4+ T cells in smokers with normal spirometry: (a) stimulation induced minimal IFN-γ or other inflammatory mediators, but many subjects produced more CCL2; (b) the T effector memory subset was less uniformly predominant, without correlation with decreased IFN-γ production. Analysis of unstimulated lung CD4+ T cells of all subjects identified a molecular phenotype, mainly in COPD, characterized by markedly reduced mRNA transcripts for the transcription factors controlling TH1, TH2, TH17 and FOXP3+ T regulatory subsets and their signature cytokines. This mRNA-defined CD4+ T cell phenotype did not result from global inability to elaborate mRNA; increased transcripts for inhibitory CD28 family members or markers of anergy; or reduced telomerase length. As a group, these subjects had significantly worse spirometry, but not DLCO, relative to subjects whose lung CD4+ T cells expressed a variety of transcripts. Analysis of mRNA transcripts of unstimulated lung CD4+ T cell among all subjects identified two distinct molecular correlates of classical COPD clinical phenotypes: basal IL-10 transcripts correlated independently and inversely with emphysema extent (but not spirometry); by contrast, unstimulated IFN-γ transcripts correlated independently and inversely with reduced spirometry (but not reduced DLCO or emphysema extent). Aberrant lung CD4+ T cells polarization appears to be common in advanced COPD, but also

  15. Pulmonary Emphysema Subtypes on Computed Tomography in Smokers

    PubMed Central

    Smith, Benjamin M.; Austin, John H.M.; Newell, John D.; D’Souza, Belinda M.; Rozenshtein, Anna; Hoffman, Eric A.; Ahmed, Firas; Barr, R. Graham

    2013-01-01

    Background Pulmonary emphysema is divided into three major subtypes at autopsy: centrilobular, paraseptal and panlobular emphysema. These subtypes can be defined by visual assessment on computed tomography (CT); however, clinical characteristics of emphysema subtypes on CT are not well-defined. We developed a reliable approach to visual assessment of emphysema subtypes on CT and examined if emphysema subtypes have distinct characteristics. Methods The Multi-Ethnic Study of Atherosclerosis COPD Study recruited smokers with COPD and controls age 50–79 years with ≥10 pack-years. Participants underwent CT following a standardized protocol. Definitions of centrilobular, paraseptal and panlobular emphysema were obtained by literature review. Six-minute walk distance and pulmonary function were performed following guidelines. Results Twenty-seven percent of 318 smokers had emphysema on CT. Inter-rater reliability of emphysema subtype was substantial (K:0.70). Compared to participants without emphysema, individuals with centrilobular or panlobular emphysema had greater dyspnea, reduced walk distance, greater hyperinflation, and lower diffusing capacity. In contrast, individuals with PSE were similar to controls, except for male predominance. Centrilobular but not panlobular or paraseptal emphysema was associated with greater smoking history (+21 pack-years P<0.001). Panlobular but not other types of emphysema was associated with reduced body mass index (−5 kg/m2;P=0.01). Other than for dyspnea, these findings were independent of the forced expiratory volume in one second. Seventeen percent of smokers without COPD on spirometry had emphysema, which was independently associated with reduced walk distance. Conclusions Emphysema subtypes on CT are common in smokers with and without COPD. Centrilobular and panlobular emphysema but not paraseptal emphysema have considerable symptomatic and physiological consequences. PMID:24384106

  16. 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.

  17. 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 ...

  18. 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.

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

    PubMed Central

    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

    2016-01-01

    Abstract 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. PMID:27902611

  20. Visual assessment of early emphysema and interstitial abnormalities on CT is useful in lung cancer risk analysis.

    PubMed

    Wille, Mathilde M W; Thomsen, Laura H; Petersen, Jens; de Bruijne, Marleen; Dirksen, Asger; Pedersen, Jesper H; Shaker, Saher B

    2016-02-01

    Screening for lung cancer should be limited to a high-risk-population, and abnormalities in low-dose computed tomography (CT) screening images may be relevant for predicting the risk of lung cancer. Our aims were to compare the occurrence of visually detected emphysema and interstitial abnormalities in subjects with and without lung cancer in a screening population of smokers. Low-dose chest CT examinations (baseline and latest possible) of 1990 participants from The Danish Lung Cancer Screening Trial were independently evaluated by two observers who scored emphysema and interstitial abnormalities. Emphysema (lung density) was also measured quantitatively. Emphysema was seen more frequently and its extent was greater among participants with lung cancer on baseline (odds ratio (OR), 1.8, p = 0.017 and p = 0.002) and late examinations (OR 2.6, p < 0.001 and p < 0.001). No significant difference was found using quantitative measurements. Interstitial abnormalities were more common findings among participants with lung cancer (OR 5.1, p < 0.001 and OR 4.5, p < 0.001).There was no association between presence of emphysema and presence of interstitial abnormalities (OR 0.75, p = 0.499). Even early signs of emphysema and interstitial abnormalities are associated with lung cancer. Quantitative measurements of emphysema-regardless of type-do not show the same association. • Visually detected emphysema on CT is more frequent in individuals who develop lung cancer. • Emphysema grading is higher in those who develop lung cancer. • Interstitial abnormalities, including discrete changes, are associated with lung cancer. • Quantitative lung density measurements are not useful in lung cancer risk prediction. • Early CT signs of emphysema and interstitial abnormalities can predict future risk.

  1. An animal model of autoimmune emphysema.

    PubMed

    Taraseviciene-Stewart, Laimute; Scerbavicius, Robertas; Choe, Kang-Hyeon; Moore, Melissa; Sullivan, Andrew; Nicolls, Mark R; Fontenot, Andrew P; Tuder, Rubin M; Voelkel, Norbert F

    2005-04-01

    Although cigarette smoking is implicated in the pathogenesis of emphysema, the precise mechanisms of chronic progressive alveolar septal destruction are not well understood. We show, in a novel animal model, that immunocompetent, but not athymic, nude rats injected intraperitoneally with xenogeneic endothelial cells (ECs) produce antibodies against ECs and develop emphysema. Immunization with ECs also leads to alveolar septal cell apoptosis and activation of matrix metalloproteases MMP-9 and MMP-2. Anti-EC antibodies cause EC apoptosis in vitro and emphysema in passively immunized mice. Moreover, immunization also causes accumulation of CD4+ T cells in the lung. Adoptive transfer of pathogenic, spleen-derived CD4+ cells into naive immunocompetent animal also results in emphysema. This study shows for the first time that humoral- and CD4+ cell-dependent mechanisms are sufficient to trigger the development of emphysema, suggesting that alveolar septal cell destruction might result from immune mechanisms.

  2. 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.

  3. Persistent diffuse pulmonary interstitial emphysema mimicking pulmonary emphysema

    PubMed Central

    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. PMID:21686584

  4. 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

  5. Fetal congenital lobar emphysema.

    PubMed

    Chia, Chun-Chieh; Huang, Soon-Cen; Liu, Min-Chang; Se, Tung-Yi

    2007-03-01

    To report a rare fetal congenital lung anomaly characterized by over inflation of a pulmonary lobe. A 28-year-old systemic lupus erythematous mother, gravida 1 para 0, who had normal prenatal care in our department, was admitted for labor pain and an abnormal fetal heart location was noted incidentally during labor. The baby showed rib retraction in room air but no obvious cyanotic change after delivery. Both the fetus chest X-ray and ultrasound showed a hyperechogenic tumor in the left thoracic cavity with a right-side-shifted heart and trachea. Computed tomography showed a hypodense and multiseptal tumor in the left thoracic cavity with right-sided shift of the heart and trachea. It was a soft, solid tumor in the parenchyma of the left lung and the histopathology confirmed it to be benign congenital lobar emphysema. The favorable outcome in both asymptomatic and mildly symptomatic children suggests that a nonsurgical approach should be considered for these patients.

  6. 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

  7. Emphysema Is Common in Lungs of Cystic Fibrosis Lung Transplantation Patients: A Histopathological and Computed Tomography Study.

    PubMed

    Mets, Onno M; Roothaan, Suzan M; Bronsveld, Inez; Luijk, Bart; van de Graaf, Ed A; Vink, Aryan; de Jong, Pim A

    2015-01-01

    Lung disease in cystic fibrosis (CF) involves excessive inflammation, repetitive infections and development of bronchiectasis. Recently, literature on emphysema in CF has emerged, which might become an increasingly important disease component due to the increased life expectancy. The purpose of this study was to assess the presence and extent of emphysema in endstage CF lungs. In explanted lungs of 20 CF patients emphysema was semi-quantitatively assessed on histology specimens. Also, emphysema was automatically quantified on pre-transplantation computed tomography (CT) using the percentage of voxels below -950 Houndfield Units and was visually scored on CT. The relation between emphysema extent, pre-transplantation lung function and age was determined. All CF patients showed emphysema on histological examination: 3/20 (15%) showed mild, 15/20 (75%) moderate and 2/20 (10%) severe emphysema, defined as 0-20% emphysema, 20-50% emphysema and >50% emphysema in residual lung tissue, respectively. Visually upper lobe bullous emphysema was identified in 13/20 and more diffuse non-bullous emphysema in 18/20. Histology showed a significant correlation to quantified CT emphysema (p = 0.03) and visual emphysema score (p = 0.001). CT and visual emphysema extent were positively correlated with age (p = 0.045 and p = 0.04, respectively). In conclusion, this study both pathologically and radiologically confirms that emphysema is common in end-stage CF lungs, and is age related. Emphysema might become an increasingly important disease component in the aging CF population.

  8. Frequency of Epidermal Growth Factor Receptor Mutation in Smokers with Lung Cancer Without Pulmonary Emphysema.

    PubMed

    Takeda, Kenichi; Yamasaki, Akira; Igishi, Tadashi; Kawasaki, Yuji; Ito-Nishii, Shizuka; Izumi, Hiroki; Sakamoto, Tomohiro; Touge, Hirokazu; Kodani, Masahiro; Makino, Haruhiko; Yanai, Masaaki; Tanaka, Natsumi; Matsumoto, Shingo; Araki, Kunio; Nakamura, Hiroshige; Shimizu, Eiji

    2017-02-01

    Chronic obstructive pulmonary disease is a smoking-related disease, and is categorized into the emphysema and airway dominant phenotypes. We examined the relationship between emphysematous changes and epidermal growth factor receptor (EGFR) mutation status in patients with lung adenocarcinoma. The medical records for 250 patients with lung adenocarcinoma were retrospectively reviewed. All patients were categorized into the emphysema or non-emphysema group. Wild-type EGFR was detected in 136 (54%) and mutant EGFR in 48 (19%). Emphysematous changes were observed in 87 (36%) patients. EGFR mutation was highly frequent in the non-emphysema group (p=0.0014). Multivariate logistic regression analysis showed that emphysema was an independent risk factor for reduced frequency of EGFR mutation (Odds Ratio=3.47, p=0.005). Our data showed a relationship between emphysematous changes and EGFR mutation status. There might be mutually exclusive genetic risk factors for carcinogenesis and development of emphysematous changes. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  9. 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.

  10. 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. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. 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

  12. 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.

  13. Quantifying the extent of emphysema: factors associated with radiologists' estimations and quantitative indices of emphysema severity using the ECLIPSE cohort.

    PubMed

    Gietema, Hester A; Müller, Nestor L; Fauerbach, Paola V Nasute; Sharma, Sanjay; Edwards, Lisa D; Camp, Pat G; Coxson, Harvey O

    2011-06-01

    This study investigated what factors radiologists take into account when estimating emphysema severity and assessed quantitative computed tomography (CT) measurements of low attenuation areas. CT scans and spirometry were obtained on 1519 chronic obstructive pulmonary disease (COPD) subjects, 269 smoker controls, and 184 nonsmoker controls from the Evaluation of COPD Longitudinally to Indentify Surrogate Endpoints (ECLIPSE) study. CT scans were analyzed using the threshold technique (%<-950HU) and a low attenuation cluster analysis. Two radiologists scored emphysema severity (0 to 5 scale), described the predominant type and distribution of emphysema, and the presence of suspected small airways disease. The percent low attenuation area (%LAA) and visual scores of emphysema severity correlated well (r = 0.77, P < .001). %LAA, low attenuation cluster analysis, and absence of radiologist described gas trapping, distribution, and predominant type of emphysema were predictors of visual scores of emphysema severity (all P < .001). CT scans scored as showing regions of gas trapping had smaller lesions for a similar %LAA than those without (P < .001). Visual estimates of emphysema are not only determined by the extent of LAA, but also by lesion size, predominant type, and distribution of emphysema and presence/absence of areas of small airways disease. A computer analysis of low attenuation cluster size helps quantitative algorithms discriminate low attenuation areas from gas trapping, image noise, and emphysema. Copyright © 2011 AUR. Published by Elsevier Inc. All rights reserved.

  14. 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.

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

    PubMed Central

    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. PMID:23695700

  16. Tomosynthesis for the early detection of pulmonary emphysema: diagnostic performance compared with chest radiography, using multidetector computed tomography as reference.

    PubMed

    Yamada, Yoshitake; Jinzaki, Masahiro; Hashimoto, Masahiro; Shiomi, Eisuke; Abe, Takayuki; Kuribayashi, Sachio; Ogawa, Kenji

    2013-08-01

    To compare the diagnostic performance of tomosynthesis with that of chest radiography for the detection of pulmonary emphysema, using multidetector computed tomography (MDCT) as reference. Forty-eight patients with and 63 without pulmonary emphysema underwent chest MDCT, tomosynthesis and radiography on the same day. Two blinded radiologists independently evaluated the tomosynthesis images and radiographs for the presence of pulmonary emphysema. Axial and coronal MDCT images served as the reference standard and the percentage lung volume with attenuation values of -950 HU or lower (LAA-950) was evaluated to determine the extent of emphysema. Receiver-operating characteristic (ROC) analysis and generalised estimating equations model were used. ROC analysis revealed significantly better performance (P < 0.0001) of tomosynthesis than radiography for the detection of pulmonary emphysema. The average sensitivity, specificity, positive predictive value and negative predictive value of tomosynthesis were 0.875, 0.968, 0.955 and 0.910, respectively, whereas the values for radiography were 0.479, 0.913, 0.815 and 0.697, respectively. For both tomosynthesis and radiography, the sensitivity increased with increasing LAA-950. The diagnostic performance of tomosynthesis was significantly superior to that of radiography for the detection of pulmonary emphysema. In both tomosynthesis and radiography, the sensitivity was affected by the LAA-950. • Tomosynthesis showed significantly better diagnostic performance for pulmonary emphysema than radiography. • Interobserver agreement for tomosynthesis was significantly higher than that for radiography. • Sensitivity increased with increasing LAA -950 in both tomosynthesis and radiography. • Tomosynthesis imparts a similar radiation dose to two projection chest radiography. • Radiation dose and cost of tomosynthesis are lower than those of MDCT.

  17. GENERATIVE METHOD TO DISCOVER EMPHYSEMA SUBTYPES WITH UNSUPERVISED LEARNING USING LUNG MACROSCOPIC PATTERNS (LMPS): THE MESA COPD STUDY

    PubMed Central

    Song, Jingkuan; Yang, Jie; Smith, Benjamin; Balte, Pallavi; Hoffman, Eric A.; Barr, R. Graham; Laine, Andrew F.; Angelini, Elsa D.

    2017-01-01

    Pulmonary emphysema overlaps considerably with chronic obstructive pulmonary disease (COPD), and is traditionally subcategorized into three subtypes: centrilobular emphysema (CLE), panlobular emphysema (PLE) and paraseptal emphysema (PSE). Automated classification methods based on supervised learning are generally based upon the current definition of emphysema subtypes, while unsupervised learning of texture patterns enables the objective discovery of possible new radiological emphysema subtypes. In this work, we use a variant of the Latent Dirichlet Allocation (LDA) model to discover lung macroscopic patterns (LMPs) in an unsupervised way from lung regions that encode emphysematous areas. We evaluate the possible utility of the LMPs as potential novel emphysema subtypes via measuring their level of reproducibility when varying the learning set and by their ability to predict traditional radiological emphysema subtypes. Experimental results show that our algorithm can discover highly reproducible LMPs, that predict traditional emphysema subtypes.

  18. Lobar emphysema and atelectasis syndrome, a nosological unity.

    PubMed

    Ring-Mrozik, E; Hecker, W C; Nerlich, A

    1995-06-01

    Shrinking and atelectatic pulmonary processes--atelectasis syndrome--and lobar emphysema show morphological similarities: congenital malformations of the bronchial structure, external compression of the bronchi as well as inflammatory processes. Ventilation mechanics determine whether in the described processes an atelectasis or an emphysema manifests itself clinically. Usually, one finds over-expansions in connection with atelectasis syndrome and atelectases together with lobar emphysema. Both processes can be reversible, if we are not dealing with bronchial malformations. Longer lasting processes as well as acute, life threatening forms require operation. The belief that atelectasis syndrome and lobar emphysema constitute a nosological unity is illustrated by our cases of 9 patients with atelectasis syndrome and 16 patients with lobar emphysema.

  19. Extracellular Matrix Defects in Aneurysmal Fibulin-4 Mice Predispose to Lung Emphysema

    PubMed Central

    Ramnath, Natasja W. M.; van de Luijtgaarden, Koen M.; van der Pluijm, Ingrid; van Nimwegen, Menno; van Heijningen, Paula M.; Swagemakers, Sigrid M. A.; van Thiel, Bibi S.; Ridwan, Ruziedi Y.; van Vliet, Nicole; Vermeij, Marcel; Hawinkels, Luuk J. A. C.; de Munck, Anne; Dzyubachyk, Oleh; Meijering, Erik; van der Spek, Peter; Rottier, Robbert; Yanagisawa, Hiromi; Hendriks, Rudi W.; Kanaar, Roland; Rouwet, Ellen V.; Kleinjan, Alex; Essers, Jeroen

    2014-01-01

    Background In this study we set out to investigate the clinically observed relationship between chronic obstructive pulmonary disease (COPD) and aortic aneurysms. We tested the hypothesis that an inherited deficiency of connective tissue might play a role in the combined development of pulmonary emphysema and vascular disease. Methods We first determined the prevalence of chronic obstructive pulmonary disease in a clinical cohort of aortic aneurysms patients and arterial occlusive disease patients. Subsequently, we used a combined approach comprising pathological, functional, molecular imaging, immunological and gene expression analysis to reveal the sequence of events that culminates in pulmonary emphysema in aneurysmal Fibulin-4 deficient (Fibulin-4R) mice. Results Here we show that COPD is significantly more prevalent in aneurysm patients compared to arterial occlusive disease patients, independent of smoking, other clinical risk factors and inflammation. In addition, we demonstrate that aneurysmal Fibulin-4R/R mice display severe developmental lung emphysema, whereas Fibulin-4+/R mice acquire alveolar breakdown with age and upon infectious stress. This vicious circle is further exacerbated by the diminished antiprotease capacity of the lungs and ultimately results in the development of pulmonary emphysema. Conclusions Our experimental data identify genetic susceptibility to extracellular matrix degradation and secondary inflammation as the common mechanisms in both COPD and aneurysm formation. PMID:25255451

  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. Centrilobular emphysema and panlobular emphysema: two different diseases 1

    PubMed Central

    Anderson, A. E.; Foraker, Alvan G.

    1973-01-01

    Anderson, A. E., and Foraker, A. G. (1973).Thorax, 28, 547-550. Centrilobular emphysema and panlobular emphysema: two different diseases. Twenty-one cases of centrilobular emphysema and 19 cases of panlobular emphysema, previously so designated according to recommended criteria, were reassessed for differences in zonal distribution within lungs through systematic sampling and statistical comparisons. Characteristic distribution profiles were defined for the two forms of disease. Centrilobular emphysema appeared to be mainly a disease of the upper lobe and the apices within the upper and lower lobes. In contrast, panlobular emphysema was a more or less diffuse process within lobes and lungs with mild preferential involvement of the lower lobe. These regional trends coupled with the typical appearance of individual lesions within lobules are considered to provide strong support for the contention that centrilobular emphysema and panlobular emphysema are morphologically distinct entities. Probable reasons for difficulties in differentiating some examples of centrilobular and panlobular emphysema are given. The need for further clarification of associated and background factors is stressed. Images PMID:4784376

  2. Alpha-1 Antitrypsin Deficiency (Inherited Emphysema)

    MedlinePlus

    ... general term used to describe diseases such as emphysema and chronic bronchitis. In emphysema there is damage to the walls of the ... alveoli) in the lungs. The earliest symptom of emphysema is shortness of breath during activity. Later the ...

  3. Increased Risk of Radiographic Emphysema in HIV Is Associated With Elevated Soluble CD14 and Nadir CD4

    PubMed Central

    Attia, Engi F.; Akgün, Kathleen M.; Wongtrakool, Cherry; Goetz, Matthew Bidwell; Rodriguez-Barradas, Maria C.; Rimland, David; Brown, Sheldon T.; Soo Hoo, Guy W.; Kim, Joon; Lee, Patty J.; Schnapp, Lynn M.; Sharafkhaneh, Amir; Justice, Amy C.

    2014-01-01

    BACKGROUND: The association between HIV and emphysema remains incompletely understood. We sought to determine whether HIV is an independent risk factor for emphysema severity and whether markers of HIV severity and systemic biomarkers of inflammation (IL-6), altered coagulation (D-dimer), and immune activation (soluble CD14) are associated with emphysema. METHODS: We performed a cross-sectional analysis of 114 participants with HIV infection and 89 participants without HIV infection in the Examinations of HIV-Associated Lung Emphysema (EXHALE) study. Participants underwent chest CT imaging with blinded semiquantitative interpretation of emphysema severity, distribution, and type. We generated multivariable logistic regression models to determine the risk of HIV for radiographic emphysema, defined as > 10% lung involvement. Similar analyses examined associations of plasma biomarkers, HIV RNA, and recent and nadir CD4 cell counts with emphysema among participants with HIV infection. RESULTS: Participants with HIV infection had greater radiographic emphysema severity with increased lower lung zone and diffuse involvement. HIV was associated with significantly increased risk for > 10% emphysema in analyses adjusted for cigarette smoking pack-years (OR, 2.24; 95% CI, 1.12-4.48). In multivariable analyses restricted to participants with HIV infection, nadir CD4 < 200 cells/μL (OR, 2.98; 95% CI, 1.14-7.81), and high soluble CD14 level (upper 25th percentile) (OR, 2.55; 95% CI, 1.04-6.22) were associated with increased risk of > 10% emphysema. IL-6 and D-dimer were not associated with emphysema in HIV. CONCLUSIONS: HIV is an independent risk factor for radiographic emphysema. Emphysema severity was significantly greater among participants with HIV infection. Among those with HIV, nadir CD4 < 200 cells/μL and elevated soluble CD14 level were associated with emphysema, highlighting potential mechanisms linking HIV with emphysema. PMID:25080158

  4. Disproportionate Contribution of Right Middle Lobe to Emphysema and Gas Trapping on Computed Tomography

    PubMed Central

    Bhatt, Surya P.; Sieren, Jessica C.; Newell, John D.; Comellas, Alejandro P.; Hoffman, Eric A.

    2014-01-01

    Rationale Given that the diagnosis of chronic obstructive pulmonary disease (COPD) relies on demonstrating airflow limitation by spirometry, which is known to be poorly sensitive to early disease, and to regional differences in emphysema, we sought to evaluate individual lobar contributions to global spirometric measures. Methods Subjects with COPD were compared with smokers without airflow obstruction, and non-smokers. Emphysema (% low attenuation area, LAAinsp<−950 HU, at end-inspiration) and gas trapping (%LAAexp<−856 HU at end-expiration) on CT were quantified using density mask analyses for the whole lung and for individual lobes, and distribution across lobes and strength of correlation with spirometry were compared. Results The right middle lobe had the highest %LAAinsp<−950 HU in smokers and controls, and the highest %LAAexp<−856 HU in all three groups. While RML contributed to emphysema and gas trapping disproportionately to its relatively small size, it also showed the least correlation with spirometry. There was no change in correlation of whole lung CT metrics with spirometry when the middle lobe was excluded from analyses. Similarly, RML had the highest %LAAexp<−856 HU while having the least correlation with spirometry. Conclusions Because of the right middle lobe’s disproportionate contribution to CT-based emphysema measurements, and low contribution to spirometry, longitudinal studies of emphysema progression may benefit from independent analysis of the middle lobe in whole lung quantitative CT assessments. Our findings may also have implications for heterogeneity assessments and target lobe selection for lung volume reduction. Clinical Trial Registration ClinicalTrials.gov NCT00608764 PMID:25054539

  5. 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

  6. 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.

  7. 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}.

  8. 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.

  9. 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

  10. [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.

  11. Serial changes and prognostic implications of CT findings in combined pulmonary fibrosis and emphysema: comparison with fibrotic idiopathic interstitial pneumonias alone.

    PubMed

    Lee, Geewon; Kim, Ki Uk; Lee, Ji Won; Suh, Young Ju; Jeong, Yeon Joo

    2017-05-01

    Background Although fibrotic idiopathic interstitial pneumonias (IIPs) alone and those combined with pulmonary emphysema are naturally progressive diseases, the process of deterioration and outcomes are variable. Purpose To evaluate and compare serial changes of computed tomography (CT) abnormalities and prognostic predictive factors in fibrotic IIPs alone and those combined with pulmonary emphysema. Material and Methods A total of 148 patients with fibrotic IIPs alone (82 patients) and those combined with pulmonary emphysema (66 patients) were enrolled. Semi-quantitative CT analysis was used to assess the extents of CT characteristics which were evaluated on initial and follow-up CT images. Univariate and multivariate analyses were performed to assess the effects of clinical and CT variables on survival. Results Significant differences were noted between fibrotic scores, as determined using initial CT scans, in the fibrotic IIPs alone (21.22 ± 9.83) and those combined with pulmonary emphysema groups (14.70 ± 7.28) ( P < 0.001). At follow-up CT scans, changes in the extent of ground glass opacities (GGO) were greater ( P = 0.031) and lung cancer was more prevalent ( P = 0.001) in the fibrotic IIPs combined with pulmonary emphysema group. Multivariate Cox proportional hazards analysis showed changes in the extent of GGO (hazard ratio, 1.056) and the presence of lung cancer (hazard ratio, 4.631) were predictive factors of poor survivals. Conclusion Although patients with fibrotic IIPs alone and those combined with pulmonary emphysema have similar mortalities, lung cancer was more prevalent in patients with fibrotic IIPs combined with pulmonary emphysema. Furthermore, changes in the extent of GGO and the presence of lung cancer were independent prognostic factors of poor survivals.

  12. 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.

  13. 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.

  14. Showing no spot sign is a strong predictor of independent living after intracerebral haemorrhage.

    PubMed

    Havsteen, Inger; Ovesen, Christian; Christensen, Anders F; Hansen, Christine Krarup; Nielsen, Jens Kellberg; Christensen, Hanne

    2014-01-01

    A spot sign on computed tomography angiography (CTA) is a potentially strong predictor of poor outcome on ultra-early radiological imaging. The aim of this study was to assess the spot sign as a predictor of functional outcome at 3 months as well as long-term mortality, with a focus on the ability to identify patients with a spontaneous, acceptable outcome. In a prospective, consecutive single-centre registry of acute stroke patients, we investigated patients with spontaneous intracerebral haemorrhage (ICH) admitted within 4.5 h after symptom onset from April 2009 to January 2013. The standard work-up in our centre included CTA for spot sign status, unless a contraindication was present. Modified Rankin Scale (mRS) scores were assessed at 3 months in the outpatient clinic or by telephone interviews. Long-term mortality was assessed by electronic chart follow-up for up to 1,500 days. Of the 128 patients, 37 (28.9%) had a spot sign on admission CTA. The presence of a spot sign was associated with larger median admission haematoma volume [38.0 ml (IQR 18.0-78.0) vs. 12.0 ml (5.0-24.0); p<0.0001] and higher median National Institutes of Health Stroke Scale score [19 (IQR 12-23) vs. 12 (6-16); p<0.0001]. Three months after stroke, the median functional outcome was considerably better in patients without spot sign [mRS score 3 (IQR 2-4) vs. 6 (4-6); p<0.0001]. The absence of a spot sign showed a sensitivity and specificity for good outcome (mRS scores 0-2) of 0.91 and 0.36, respectively. The presence of a spot sign was, in multivariate models, an independent inverse predictor of good 3-month outcome (OR 0.17; 95% CI: 0.03-0.88) as well as a prominent independent predictor of poor 3-month outcome (mRS scores 5-6; OR 3.40; 95% CI: 1.10-10.5) and death during follow-up (HR 3.04; 95% CI: 1.45-6.34). Patients with a spot sign surviving the acute phase had long-term survival comparable to patients with no spot sign. The absence or presence of a spot sign is a reliable ultra

  15. 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

  16. 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

  17. Genome-wide Association Study Identifies BICD1 as a Susceptibility Gene for Emphysema

    PubMed Central

    Kong, Xiangyang; Cho, Michael H.; Anderson, Wayne; Coxson, Harvey O.; Muller, Nestor; Washko, George; Hoffman, Eric A.; Bakke, Per; Gulsvik, Amund; Lomas, David A.; Silverman, Edwin K.; Pillai, Sreekumar G.

    2011-01-01

    Rationale: Chronic obstructive pulmonary disease (COPD), characterized by airflow limitation, is a disorder with high phenotypic and genetic heterogeneity. Pulmonary emphysema is a major but variable component of COPD; familial data suggest that different components of COPD, such as emphysema, may be influenced by specific genetic factors. Objectives: To identify genetic determinants of emphysema assessed through high-resolution chest computed tomography in individuals with COPD. Methods: We performed a genome-wide association study (GWAS) of emphysema determined from chest computed tomography scans with a total of 2,380 individuals with COPD in three independent cohorts of white individuals from (1) a cohort from Bergen, Norway, (2) the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Study, and (3) the National Emphysema Treatment Trial (NETT). We tested single-nucleotide polymorphism associations with the presence or absence of emphysema determined by radiologist assessment in two of the three cohorts and a quantitative emphysema trait (percentage of lung voxels less than –950 Hounsfield units) in all three cohorts. Measurements and Main Results: We identified association of a single-nucleotide polymorphism in BICD1 with the presence or absence of emphysema (P = 5.2 × 10−7 with at least mild emphysema vs. control subjects; P = 4.8 × 10−8 with moderate and more severe emphysema vs. control subjects). Conclusions: Our study suggests that genetic variants in BICD1 are associated with qualitative emphysema in COPD. Variants in BICD1 are associated with length of telomeres, which suggests that a mechanism linked to accelerated aging may be involved in the pathogenesis of emphysema. Clinical trial registered with www.clinicaltrials.gov (NCT00292552). PMID:20709820

  18. 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

  19. 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…

  20. [Congenital lobar emphysema].

    PubMed

    Belio-Castillo, C; Prado-Pallares, M; Blanco-Rodríguez, G

    1991-05-01

    This article includes the way cases of congenital lobe emphysema were treated at the Hospital Infantil de México "Federico Gómez" during 1971 to 1989. A total of 17 cases were gathered, 13 were males and 4 were females; admittance age varied from 13 days to 3 years. The children's main symptoms were respiratory failure and cyanosis. The diagnosis was enhanced by a chest X-ray where lobe hyperclarity was detected, as well as a deviation of the mediastinum and a collapsed lung. A lobectomy was performed in all cases. The upper left lobe was seen to be the most affected. Two of the children died. It is important to recognize this disease early on and conduct prompt surgical treatment.

  1. 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.

  2. Spontaneous emphysema of the neck.

    PubMed

    El-Ghazali, A M

    1983-04-01

    A case of spontaneous emphysema in the neck in a 17-year-old male was reported. Pathogenesis and management are discussed. Although it is a benign and self-limiting condition, it may carry a potential for serious complications.

  3. 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

  4. 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.

  5. 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.

  6. Effect of Emphysema Extent on Serial Lung Function in Patients with Idiopathic Pulmonary Fibrosis.

    PubMed

    Cottin, Vincent; Hansell, David M; Sverzellati, Nicola; Weycker, Derek; Antoniou, Katerina M; Atwood, Mark; Oster, Gerry; Kirchgaessler, Klaus-Uwe; Collard, Harold R; Wells, Athol U

    2017-06-28

    Rationale Patients with idiopathic pulmonary fibrosis and emphysema may have artificially preserved lung volumes. Objectives This post-hoc analysis investigated the relationship between baseline emphysema and fibrosis extents, and pulmonary function changes over 48 weeks. Methods Data were pooled from two Phase III, randomized, double-blind, placebo-controlled trials of interferon γ-1b in idiopathic pulmonary fibrosis (GIPF-001 [NCT00047645]; GIPF-007 [NCT00075998]). Patients with Week 48 data, baseline high-resolution computed tomography images and forced expiratory volume in 1 second/forced vital capacity ratios <0.8 or >0.9 (<0.7 or >0.9 in GIPF-007) and randomly selected patients with ratios 0.8-0.9 and 0.7-0.8 were included. Changes from baseline in pulmonary function at Week 48 were analyzed by emphysema extent. The relationship between emphysema and fibrosis extents and pulmonary function changes was assessed using multivariate linear regression. Measurements and Main Results Emphysema was identified in 38% of patients. A negative correlation was observed between fibrosis and emphysema extents (r = -0.232; P < 0.001). In quartile analysis, patients with the greatest emphysema extent (28%-65%) showed the smallest forced vital capacity decline, with a difference of 3.32% at Week 48 versus patients with no emphysema (P = 0.047). In multivariate analyses, emphysema extent ≥15% was associated with significantly reduced forced vital capacity decline over 48 weeks versus no emphysema/emphysema <15%. No such association was observed for carbon monoxide diffusing capacity or composite physiologic index. Conclusions Forced vital capacity measurements may not be appropriate to monitor disease progression in patients with idiopathic pulmonary fibrosis and emphysema extent ≥15%. Clinical trial registration available at www.clinicaltrials.gov, IDs NCT00047645 and NCT00075998.

  7. Analytical estimation show low depth-independent water loss due to vapor flux from deep aquifers

    NASA Astrophysics Data System (ADS)

    Selker, John S.

    2017-06-01

    Recent articles have provided estimates of evaporative flux from water tables in deserts that span 5 orders of magnitude. In this paper, we present an analytical calculation that indicates aquifer vapor flux to be limited to 0.01 mm/yr for sites where there is negligible recharge and the water table is well over 20 m below the surface. This value arises from the geothermal gradient, and therefore, is nearly independent of the actual depth of the aquifer. The value is in agreement with several numerical studies, but is 500 times lower than recently reported experimental values, and 100 times larger than an earlier analytical estimate.

  8. Computed tomography density histogram analysis to evaluate pulmonary emphysema in ex-smokers.

    PubMed

    Owrangi, Amir M; Etemad-Rezai, Roya; McCormack, David G; Cunningham, Ian A; Parraga, Grace

    2013-05-01

    High-resolution computed tomography (CT) measurements of emphysema typically use Hounsfield unit (HU) density histogram thresholds or observer scores based on regions of low x-ray attenuation. Our objective was to develop an automated measurement of emphysema using principal component analysis (PCA) of the CT density histogram. Ninety-seven ex-smokers, including 53 subjects with chronic obstructive pulmonary disease (COPD) and 44 asymptomatic subjects (AEs), provided written informed consent to imaging as well as plethysmography and spirometry. We applied PCA to the CT density histogram to generate whole lung and regional density histogram principal components including the first and second components and the sum of both principal components (density histogram principal component score [DHPCS]). Significant relationships for DHPCS with single HU thresholds, pulmonary function measurements, an expert's emphysema score, and hyperpolarized (3)He magnetic resonance imaging apparent diffusion coefficients (ADCs) were determined using linear regression and Pearson coefficients. Receiver operator characteristics analysis was performed using forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) as the independent diagnostic. There was a significant difference (P < .0001) between AE and COPD subjects for DHPCS; FEV1/FVC; diffusing capacity of lung for carbon monoxide%predicted; attenuation values below -950, -910, and -856 HU; and (3)He ADCs. There were significant correlations for DHPCS with FEV1/FVC (r = -0.85, P < .0001); diffusing capacity of lung for carbon monoxide%predicted (r = -0.67, P < .0001); attenuation values below -950/-910/-856 HU (r = 0.93/0.96/0.76, P < .0001); and (3)He ADCs (r = 0.85, P < .0001). Receiver operator characteristics analysis showed a 91% classification rate for DHPCS. We generated an automated emphysema score using PCA of the CT density histogram with a 91% COPD classification rate that showed strong and significant

  9. Cross-Sectional Analysis of the Utility of Pulmonary Function Tests in Predicting Emphysema in Ever-Smokers

    PubMed Central

    Hesselbacher, Sean E.; Ross, Robert; Schabath, Matthew B.; Smith, E. O’Brian; Perusich, Sarah; Barrow, Nadia; Smithwick, Pamela; Mammen, Manoj J.; Coxson, Harvey; Krowchuk, Natasha; Corry, David B.; Kheradmand, Farrah

    2011-01-01

    Emphysema is largely an under-diagnosed medical condition that can exist in smokers in the absence of airway obstruction. We aimed to determine the sensitivity and specificity of pulmonary function tests (PFTs) in assessing emphysema using quantitative CT scans as the reference standard. We enrolled 224 ever-smokers (current or former) over the age of 40. CT of thorax was used to quantify the low attenuation area (% emphysema), and to measure the standardized airway wall thickness. PFTs were used individually and in combination to predict their ability to discriminate radiographic emphysema. Significant emphysema (>7%) was detected in 122 (54%) subjects. Twenty six (21%) emphysema subjects had no evidence of airflow obstruction (FEV1/FVC ratio <70%), while all subjects with >23% emphysema showed airflow obstruction. The sensitivity and specificity of spirometry for detecting radiographic emphysema were 79% and 75%, respectively. Standardized airway wall thickness was increased in subjects with airflow obstruction, but did not correlate with emphysema severity. In this cohort of lifetime ever-smokers, PFTs alone were inadequate for diagnosing emphysema. Airway wall thickness quantified by CT morphometry was associated with airflow limitation, but not with emphysema indicating that the heterogeneous nature of lung disease in smokers may represent distinct phenotypes. PMID:21655122

  10. Pulmonary hypertension and computed tomography measurement of small pulmonary vessels in severe emphysema.

    PubMed

    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

    2010-02-01

    Vascular alteration of small pulmonary vessels is one of the characteristic features of pulmonary hypertension in chronic obstructive pulmonary disease. The in vivo relationship between pulmonary hypertension and morphological alteration of the small pulmonary vessels has not been assessed in patients with severe emphysema. We evaluated the correlation of total cross-sectional area of small pulmonary vessels (CSA) assessed on computed tomography (CT) scans with the degree of pulmonary hypertension estimated by right heart catheterization. In 79 patients with severe emphysema enrolled in the National Emphysema Treatment Trial (NETT), we measured CSA less than 5 mm(2) (CSA(<5)) and 5 to 10 mm(2) (CSA(5-10)), and calculated the percentage of total CSA for the lung area (%CSA(<5) and %CSA(5-10), respectively). The correlations of %CSA(<5) and %CSA(5-10) with pulmonary arterial mean pressure (Ppa) obtained by right heart catheterization were evaluated. Multiple linear regression analysis using Ppa as the dependent outcome was also performed. The %CSA(<5) had a significant negative correlation with Ppa (r = -0.512, P < 0.0001), whereas the correlation between %CSA(5-10) and Ppa 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 (DL(CO)) % predicted were independent predictors of Ppa (r(2) = 0.541): %CSA (<5) (P < 0.0001), and DL(CO) % predicted (P = 0.022). The %CSA(<5) measured on CT images is significantly correlated to Ppa in severe emphysema and can estimate the degree of pulmonary hypertension.

  11. 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

  12. 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

  13. [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.

  14. Polygenic Scores Predict Alcohol Problems in an Independent Sample and Show Moderation by the Environment

    PubMed Central

    Salvatore, Jessica E.; Aliev, Fazil; Edwards, Alexis C.; Evans, David M.; Macleod, John; Hickman, Matthew; Lewis, Glyn; Kendler, Kenneth S.; Loukola, Anu; Korhonen, Tellervo; Latvala, Antti; Rose, Richard J.; Kaprio, Jaakko; Dick, Danielle M.

    2014-01-01

    Alcohol problems represent a classic example of a complex behavioral outcome that is likely influenced by many genes of small effect. A polygenic approach, which examines aggregate measured genetic effects, can have predictive power in cases where individual genes or genetic variants do not. In the current study, we first tested whether polygenic risk for alcohol problems—derived from genome-wide association estimates of an alcohol problems factor score from the age 18 assessment of the Avon Longitudinal Study of Parents and Children (ALSPAC; n = 4304 individuals of European descent; 57% female)—predicted alcohol problems earlier in development (age 14) in an independent sample (FinnTwin12; n = 1162; 53% female). We then tested whether environmental factors (parental knowledge and peer deviance) moderated polygenic risk to predict alcohol problems in the FinnTwin12 sample. We found evidence for both polygenic association and for additive polygene-environment interaction. Higher polygenic scores predicted a greater number of alcohol problems (range of Pearson partial correlations 0.07–0.08, all p-values ≤ 0.01). Moreover, genetic influences were significantly more pronounced under conditions of low parental knowledge or high peer deviance (unstandardized regression coefficients (b), p-values (p), and percent of variance (R2) accounted for by interaction terms: b = 1.54, p = 0.02, R2 = 0.33%; b = 0.94, p = 0.04, R2 = 0.30%, respectively). Supplementary set-based analyses indicated that the individual top single nucleotide polymorphisms (SNPs) contributing to the polygenic scores were not individually enriched for gene-environment interaction. Although the magnitude of the observed effects are small, this study illustrates the usefulness of polygenic approaches for understanding the pathways by which measured genetic predispositions come together with environmental factors to predict complex behavioral outcomes. PMID:24727307

  15. Polygenic scores predict alcohol problems in an independent sample and show moderation by the environment.

    PubMed

    Salvatore, Jessica E; Aliev, Fazil; Edwards, Alexis C; Evans, David M; Macleod, John; Hickman, Matthew; Lewis, Glyn; Kendler, Kenneth S; Loukola, Anu; Korhonen, Tellervo; Latvala, Antti; Rose, Richard J; Kaprio, Jaakko; Dick, Danielle M

    2014-04-10

    Alcohol problems represent a classic example of a complex behavioral outcome that is likely influenced by many genes of small effect. A polygenic approach, which examines aggregate measured genetic effects, can have predictive power in cases where individual genes or genetic variants do not. In the current study, we first tested whether polygenic risk for alcohol problems-derived from genome-wide association estimates of an alcohol problems factor score from the age 18 assessment of the Avon Longitudinal Study of Parents and Children (ALSPAC; n = 4304 individuals of European descent; 57% female)-predicted alcohol problems earlier in development (age 14) in an independent sample (FinnTwin12; n = 1162; 53% female). We then tested whether environmental factors (parental knowledge and peer deviance) moderated polygenic risk to predict alcohol problems in the FinnTwin12 sample. We found evidence for both polygenic association and for additive polygene-environment interaction. Higher polygenic scores predicted a greater number of alcohol problems (range of Pearson partial correlations 0.07-0.08, all p-values ≤ 0.01). Moreover, genetic influences were significantly more pronounced under conditions of low parental knowledge or high peer deviance (unstandardized regression coefficients (b), p-values (p), and percent of variance (R2) accounted for by interaction terms: b = 1.54, p = 0.02, R2 = 0.33%; b = 0.94, p = 0.04, R2 = 0.30%, respectively). Supplementary set-based analyses indicated that the individual top single nucleotide polymorphisms (SNPs) contributing to the polygenic scores were not individually enriched for gene-environment interaction. Although the magnitude of the observed effects are small, this study illustrates the usefulness of polygenic approaches for understanding the pathways by which measured genetic predispositions come together with environmental factors to predict complex behavioral outcomes.

  16. 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

  17. 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

  18. Improved neurobehavioral functioning in emphysema patients following medical therapy.

    PubMed

    Kozora, Elizabeth; Emery, Charles F; Zhang, Lening; Make, Barry

    2010-01-01

    To evaluate the neuropsychological and psychological functioning of emphysema patients following 10 weeks of multidisciplinary medical therapy (MT). Patients with moderate to severe emphysema (n = 56) enrolled in the National Emphysema Treatment Trial at 2 sites (National Jewish Health and Ohio State University) completed cognitive, psychological, and quality-of-life (QOL) tests at baseline and 6 to 10 weeks following participation in pulmonary rehabilitation. Healthy control subjects (matched on age, sex, race, and education, n = 54) completed the same tests at baseline and 6 to 10 weeks later. Controlling for practice effects and educational level, emphysema patients in the MT group demonstrated significant improvement compared with controls on a global index of cognition, and in measures of visuomotor sequential skills and visual memory. The MT group showed significant reductions in several measures of depression and anxiety, and the control group showed a significant reduction in total depression, but acute anxiety scores were worse 6 to 10 weeks later. The MT group showed significant improvement on 6 of 9 QOL variables and no change was detected in the control group. Improvement on the cognitive index score in the mt group was related to decline in depression and increased workload. emphysema patients who received MT demonstrated improvement in specific neuropsychological functions, depression, anxiety, and QOL scores compared with control subjects during the same interval (with no treatment). Mechanisms for these neurobehavioral changes include greater exercise endurance and decreased depression.

  19. Lung cancer, pulmonary emphysema and pleural effusion: An autopsy study.

    PubMed

    Marel, Miloslav; Koubkova, Leona; Kovarikova, Zuzana; Grandcourtova, Alzbeta; Petrik, Frantisek; Hroudova, Hana; Capkova, Linda; Kodet, Roman; Fila, Libor

    2015-12-01

    To determine the exact incidence of lung cancer, pulmonary emphysema and pleural effusion we decided to carry out an autopsy study. In this autopsy study carried out over two years, we compared the results of autopsy findings with the clinical data in accompanying records of the deceased. Among the 708 deceased subjects, there were 398 males and 310 females with a median age of 71 years. At autopsy, 55 cases of lung carcinoma (BCA) were found, of which 24 have not been identified during life (44%). Among the deceased with BCA, emphysema was also observed at autopsy in 40% of the cases. Pulmonary emphysema was described macroscopically in 28% of the full set of 708 deceased, whereas the accompanying records of the deceased described this condition in only 12% of the cases. Microscopic changes compatible with emphysema were identified in 54% of the examined lungs. Pleural effusions were described in the accompanying records of 13% of the deceased, while the autopsies showed this condition in 33% of the deceased. BCA was accompanied by effusion in 25% of the cases. The obtained results show that the studied conditions are present in more cases than are reported by clinicians. The study confirms the commonly accepted association between lung cancer and emphysema.

  20. 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.

  1. 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

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

    PubMed

    Triplette, Matthew; 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

    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. 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. 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). 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.

  3. Novel therapeutic approach for pulmonary emphysema using gelatin microspheres releasing basic fibroblast growth factor in a canine model.

    PubMed

    Chang, Sung Soo; Yokomise, Hiroyasu; Matsuura, Natsumi; Gotoh, Masashi; Tabata, Yasuhiko

    2014-08-01

    The prognosis of patients with emphysema is poor as there is no truly effective treatment. Our previous study showed that the alveolar space was smaller and the microvessel density was higher in a canine emphysema model after the intrapulmonary arterial administration of gelatin microspheres slowly releasing basic fibroblast growth factor (bFGF-GMS). In the present study, we evaluated the functional effect of injecting bFGF-GMS via the pulmonary artery in this canine pulmonary emphysema model. Using the porcine pancreatic elastase (PPE)-induced total emphysema model, we approximated the value of lung compliance with a Power Lab System, and performed blood gas analysis in a control group, a total emphysema group, and a bFGF group in which bFGF-GMS were injected toward the whole pulmonary artery via the femoral vein. Each group comprised five dogs. Lung compliance was higher in the total emphysema group than in the control group (p = 0.031), and the bFGF group showed no significant improvement of lung compliance vs. the total emphysema group (p = 0.112). PaO2 (partial pressure of oxygen in arterial blood) was improved by administering bFGF-GMS in the total emphysema model (p = 0.027). In the canine total emphysema model, blood gas parameters were improved by the whole pulmonary arterial administration of bFGF-GMS. This method has the potential to be an effective novel therapy for pulmonary emphysema.

  4. 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.

  5. 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

  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. Centrilobular emphysema combined with pulmonary fibrosis results in improved survival

    PubMed Central

    2011-01-01

    Background We hypothesized that, in patients with pulmonary fibrosis combined with emphysema, clinical characteristics and outcomes may differ from patients with pulmonary fibrosis without emphysema. We identified 102 patients who met established criteria for pulmonary fibrosis. The amount of emphysema (numerical score) and type of emphysema (centrilobular, paraseptal, or mixed) were characterized in each patient. Clinical characteristics, pulmonary function tests and patient survival were analysed. Results Based on the numerical emphysema score, patients were classified into those having no emphysema (n = 48), trivial emphysema (n = 26) or advanced emphysema (n = 28). Patients with advanced emphysema had a significantly higher amount of smoking in pack/years than patients with no emphysema or trivial emphysema (P < 0.0001). Median survival [1st, 3rd quartiles] of patients with advanced emphysema was 63 [36, 82] months compared to 29 [18, 49] months in patients without emphysema and 32 [19, 48] months in patients with trivial emphysema (P < 0.001). Median forced vital capacity (FVC) and total lung capacity (TLC) were higher in the advanced emphysema group compared to patients with no emphysema (P < 0.01 and P < 0.001, respectively), whereas median DLCO did not differ among groups and was overall low. Within the advanced emphysema group (n = 28), further characterization of the type of emphysema was performed and, within these subgroups of patients, survival was 75 [58, 85] months for patients with centrilobular emphysema, 75 [48, 85] months for patients with mixed centrilobular/paraseptal emphysema, and 24 [22, 35] months for patients with paraseptal emphysema (P < 0.01). Patients with advanced paraseptal emphysema had similar survival times to patients without emphysema. Conclusions Patients with pulmonary fibrosis combined with advanced centrilobular or mixed emphysema have an improved survival compared with patients with pulmonary fibrosis without emphysema

  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. 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

  11. Emphysema and chronic obstructive pulmonary disease in coal miners.

    PubMed

    Santo Tomas, Linus H

    2011-03-01

    Coal mining remains a major industry that has workers at risk for developing chronic lung disease. Aside from simple coal workers' pneumoconiosis and progressive massive fibrosis, the development of emphysema and obstructive lung disease independent of smoking may be underappreciated. This article reviews more recent studies that may help rectify this faulty view. Cumulative exposure to coal dust is a significant risk factor for the development of emphysema and has an additive effect to smoking. Increased coal dust exposure is associated with increased risk of death from chronic obstructive pulmonary disease (COPD). In newly employed coal miners, bronchitic symptoms are associated with a rapid decline in lung function within 2 years after starting work. In evaluating impairment, the chest radiograph may be helpful as a marker of exposure but the diffusing capacity is most correlated with dyspnea, whereas the emphysema computed tomography score has good association with expiratory flow limitation. Latest studies further support the association of emphysema and COPD with coal dust exposure. Increased cumulative exposure may also increase risk of death from these diseases.

  12. 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.

  13. Independence.

    ERIC Educational Resources Information Center

    Stephenson, Margaret E.

    2000-01-01

    Discusses the four planes of development and the periods of creation and crystallization within each plane. Identifies the type of independence that should be achieved by the end of the first two planes of development. Maintains that it is through individual work on the environment that one achieves independence. (KB)

  14. Spontaneous subcutaneous emphysema associated with mephedrone usage

    PubMed Central

    Maan, ZN; D’Souza, AR

    2012-01-01

    Subcutaneous emphysema in the head and neck is a rare condition, normally caused by major underlying injury to the airway or gastrointestinal tract. We report a non-traumatic occurrence of spontaneous cervical subcutaneous emphysema in a 30-year-old man who had been snorting mephedrone. The patient made an uneventful recovery, being managed conservatively, and did not require airway support. The occurrence of spontaneous cervical emphysema associated with snorting mephedrone has not been previously described in the literature. PMID:22524925

  15. 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

  16. 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.

  17. Combined pulmonary fibrosis and emphysema in a welder.

    PubMed

    Roshan, R; Guptal, M; Kulshrestha, R; Menon, B; Chhabra, S K

    2012-03-01

    Combined pulmonary fibrosis and emphysema (CPFE) syndrome is an uncommon entity characterised by emphysema of the upper lobes and diffuse fibrosis of the lower lobes and carries a bad prognosis with the onset of pulmonary hypertension. Lung involvement due to exposures suffered by welders is generally considered benign though, rarely, a diffuse interstitial fibrotic disease has been reported. CPFE syndrome has however never been reported in welders. A 65-year-old man, welder by occupation and an ex-smoker, presented with progressive exertional dyspnoea associated with dry cough noticed for the last four months. On examination, there was mild tachypnea, clubbing and bilateral basal velcro crepitations on chest auscultation. Lung function test revealed mild mixed ventilatory impairment with severe diffusion defect. HRCT chest showed bilateral upper lobe emphysema and diffuse interstitial fibrosis in the lower lobes. Transbronchial lung biopsy revealed interstitial fibrosis, chronic inflammation and iron deposits. A diagnosis of combined pulmonary fibrosis with emphysema (CPFE) with interstitial pulmonary siderofibrosis (IPS) was established. A review of literature did not show any other report of a similar nature.

  18. 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

  19. 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.

  20. 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

  1. Polymorphism of SERPINE2 gene is associated with pulmonary emphysema in consecutive autopsy cases

    PubMed Central

    2010-01-01

    Background The SERPINA1, SERPINA3, and SERPINE2 genes, which encode antiproteases, have been proposed to be susceptible genes for of chronic obstructive pulmonary disease (COPD) and related phenotypes. Whether they are associated with emphysema is not known. Methods Twelve previously reported single nucleotide polymorphisms (SNPs) in SERPINA1 (rs8004738, rs17751769, rs709932, rs11832, rs1303, rs28929474, and rs17580), SERPINA3 (rs4934, rs17473, and rs1800463), and SERPINE2 (rs840088 and rs975278) were genotyped in samples obtained from 1,335 consecutive autopsies of elderly Japanese people. The association between these SNPs and the severity of emphysema, as assessed using macroscopic scores, was determined. Results Emphysema of more than moderate degree was detected in 189 subjects (14.1%) and showed a significant gender difference (males, 20.5% and females, 7.0%; p < 0.0001). Among the 12 examined SNPs, only rs975278 in the SERPINE2 gene was positively associated with emphysema. Unlike the major alleles, homozygous minor alleles of rs975278 were associated with emphysema (odds ratio (OR) = 1.54; 95% confidence interval (CI) = 1.02-2.30; p = 0.037) and the association was very prominent in smokers (OR = 2.02; 95% CI = 1.29-3.15; p = 0.002). Conclusions SERPINE2 may be a risk factor for the development of emphysema and its association with emphysema may be stronger in smokers. PMID:21067581

  2. 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

  3. 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

  4. Emphysema and airway disease affect within-breath changes in respiratory resistance in COPD patients.

    PubMed

    Hasegawa, Koichi; Sato, Susumu; Tanimura, Kazuya; Fuseya, Yoshinori; Uemasu, Kiyoshi; Sato, Atsuyasu; Hirai, Toyohiro; Mishima, Michiaki; Muro, Shigeo

    2015-07-01

    Chronic obstructive pulmonary disease (COPD) is characterized by a mixture of emphysema and airway disease. The forced oscillation technique (FOT) has been applied to COPD patients to clarify changes in respiratory mechanics; dynamic changes in respiratory resistance (Rrs) during breathing (within-breath changes in Rrs, ΔRrs) are characteristic of COPD. However, the pathophysiological significance of these changes is unknown. The aim of this study was to assess how emphysema and airway disease influence ΔRrs in COPD patients. In this cross-sectional study, stable COPD patients were recruited and underwent respiratory impedance measurements with a commercially available FOT device. Rrs was recorded during tidal breathing and then analyzed as whole-breath Rrs (Rrs at 5 Hz, R5; Rrs at 20 Hz, R20; and their difference, R5-R20) or as ΔRrs, the difference between the expiratory and inspiratory Rrs (ΔR5, ΔR20 and ΔR5-R20). The percentage of the low attenuation area (LAA%) and airway wall area (WA%) was quantified by computed tomography analysis, and their contributions to ΔRrs were examined. Seventy-five COPD patients were recruited. LAA% was negatively correlated with ΔR5 and ΔR5-R20 (P = 0.0002 and P = 0.0033, respectively); meanwhile, WA% in B(10) was positively correlated with ΔR5 and ΔR5-R20 (P = 0.0057 and P < 0.0001, respectively). Multivariate analysis revealed that the contribution of both LAA% and WA% in B(10) to ΔRrs was independent of the severity of airflow limitations. This study shows that emphysema suppresses ΔRrs in COPD patients, while airway disease increases ΔRrs in these patients. © 2015 Asian Pacific Society of Respirology.

  5. 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%.

  6. [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.

  7. 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

  8. Planarized and Twisted Intramolecular Charge Transfer: A Concept for Fluorophores Showing Two Independent Rotations in Excited State.

    PubMed

    Haberhauer, Gebhard

    2017-07-12

    TICT (twisted intramolecular charge transfer) compounds are characterized by showing a rotation around a single bond in the excited state: starting from an almost planar geometry in the ground state, a twisted system is formed in the electronic excited state. The previously reported PLICT (planarized intramolecular charge transfer) compounds show inverse behavior: starting from a twisted geometry in the electronic ground state, a planarized system is formed in the excited state by rotation around a single bond. Here, a concept for planarized and twisted intramolecular charge transfer (PLATICT) states is presented which amalgamates both (TICT and PLICT) effects. Due to an intramolecular charge transfer, both a twisting around one single bond and a planarization around another one occurs. In sum, the PLATICT system shows two independent rotations around different axes in the excited state. By means of quantum chemical calculations (TD-cam-B3LYP and CC2) and experimental studies, it is demonstrated that N-aryl-substituted 1-aminoindoles are able to form photoinduced PLATICT states. In the fluorescence spectra of N-aryl-substituted 1-aminoindoles with a methoxycarbonyl or a cyano group as substituent in the aryl ring, very large Stokes shifts (ca. 18 000 cm(-1) ; >250 nm) are observed. The two independent rotations in the excited state, the very large Stokes shifts and their easy availability starting from indoline, make them very attractive for use as optical switches and motors in various fields of chemistry. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. 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.

  10. 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.

  11. Spontaneous Retropharyngeal and Mediastinal Emphysema.

    PubMed

    Cho, Do-Yeon; Aaron, Geoffrey P; Shepard, Kimberly G

    2016-06-01

    A 14-year-old girl with no significant medical history presented at Emergency Department with sore throat and odynophagia after one episode of nonviolent coughing. She denied any respiratory distress, voice change, foreign body ingestion, retching, substance abuse, dental procedures, or trauma. She was afebrile with normal oxygen saturation and physical examination including the head and neck was unremarkable with the exception of bilateral neck crepitus without tenderness on palpation. Fiberoptic laryngoscopy revealed a patent laryngeal airway with normal vocal fold movement. Lateral neck X-ray demonstrated a linear air-column in the retropharyngeal space and computed tomography confirmed emphysema involving the retropharyngeal space and mediastinum with no evidence of fluid collection or abscess formation. Spontaneous retropharyngeal and mediastinal emphysema are clinical entities where free air is present within the confines of retropharyngeal space and mediastinum without obvious cause. It is benign and self-limited in nature and allows for conservative management. This case is presented with a review of literature.

  12. [Prediction of the efficiency of endoscopic lung volume reduction by valves in severe emphysema].

    PubMed

    Bocquillon, V; Briault, A; Reymond, E; Arbib, F; Jankowski, A; Ferretti, G; Pison, C

    2016-11-01

    In severe emphysema, endoscopic lung volume reduction with valves is an alternative to surgery with less morbidity and mortality. In 2015, selection of patients who will respond to this technique is based on emphysema heterogeneity, a complete fissure visible on the CT-scan and absence of collateral ventilation between lobes. Our case report highlights that individualized prediction is possible. A 58-year-old woman had severe, disabling pulmonary emphysema. A high resolution thoracic computed tomography scan showed that the emphysema was heterogeneous, predominantly in the upper lobes, integrity of the left greater fissure and no collateral ventilation with the left lower lobe. A valve was inserted in the left upper lobe bronchus. At one year, clinical and functional benefits were significant with complete atelectasis of the treated lobe. The success of endoscopic lung volume reduction with a valve can be predicted, an example of personalized medicine. Copyright © 2016 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  13. Necropsy incidence of emphysema in Uganda

    PubMed Central

    Jones, Aled W.; Madda, P. J.

    1974-01-01

    Jones, A. W. and Madda, P. J. (1974).Thorax, 29, 195-198. Necropsy incidence of emphysema in Uganda. The incidence and types of pulmonary emphysema and the degree of dust pigmentation of the lungs were investigated in a series of 183 necropsies in Uganda. Emphysema was present in 43 (23·5%) lungs. Panlobular or centrilobular emphysema was found in 17 cases, an overall incidence of 9·3% (10·4% of the 135 males and 6·3% of the 48 females). It was generally of mild degree and the mean lung involvement, as assessed by a point counting method, was 9·2% in the 17 cases described above. Panlobular and centrilobular emphysema occurred in the older age groups; 13 of the 17 cases were 50 years old or more. The remaining 26 cases consisted of irregular (scar) emphysema which occurred in trace amounts (less than 1%). Dust pigmentation was present in all 17 cases of emphysematous lungs and was generally more severe than in the non-emphysematous lungs. The incidence of emphysema in this predominantly rural population is low and is similar to that found in Ibadan, Nigeria. PMID:4831525

  14. 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.

  15. The role of oxidative processes in emphysema.

    PubMed

    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.

  16. Emphysema induced by elastase enhances acute inflammatory pulmonary response to intraperitoneal LPS in rats.

    PubMed

    da Fonseca, Lídia Maria Carneiro; Reboredo, Maycon Moura; Lucinda, Leda Marília Fonseca; Fazza, Thaís Fernanda; Rabelo, Maria Aparecida Esteves; Fonseca, Adenilson Souza; de Paoli, Flavia; Pinheiro, Bruno Valle

    2016-12-01

    Abnormalities in lungs caused by emphysema might alter their response to sepsis and the occurrence of acute lung injury (ALI). This study compared the extension of ALI in response to intraperitoneal lipopolysaccharide (LPS) injection in Wistar rats with and without emphysema induced by elastase. Adult male Wistar rats were randomized into four groups: control, emphysema without sepsis, normal lung with sepsis and emphysema with sepsis. Sepsis was induced, and 24 h later the rats were euthanised. The following analysis was performed: blood gas measurements, bronchoalveolar lavage (BAL), lung permeability and histology. Animals that received LPS showed significant increase in a lung injury scoring system, inflammatory cells in bronchoalveolar lavage (BAL) and IL-6, TNF-α and CXCL2 mRNA expression in lung tissue. Animals with emphysema and sepsis showed increased alveolocapillary membrane permeability, demonstrated by higher BAL/serum albumin ratio. In conclusion, the presence of emphysema induced by elastase increases the inflammatory response in the lungs to a systemic stimulus, represented in this model by the intraperitoneal injection of LPS. © 2016 The Authors. International Journal of Experimental Pathology © 2016 International Journal of Experimental Pathology.

  17. [Orbital emphysema: radiologic and ophthalmologic findings].

    PubMed

    Solanas-Álava, Susana; Rodríguez-Marco, Nelson Arturo; Artigas-Martín, José María; Fernández-Larripa, Sonia

    2017-01-01

    Orbital emphysema, or the presence of air in orbital tissues, is normally associated with an injury although it can arise when a Valsalva maneuver causes an increase in upper airway pressure. This potential complication of an orbital wall fracture, usually in the ethmoid bone, occurs in 50% of such cases. On fracture, air passes from the nasal fossa, sinuses, or subcutaneous tissue. The condition is benign and transient in most cases, and loss of vision is rare. No protocol for treating orbital emphysema with serious complications in which vision is affected has been established. We report 9 cases of orbital emphysema, describing events leading to the fractures, radiologic findings, and treatments.

  18. 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

  19. 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.

  20. Paratracheal air cysts on thoracic multidetector CT: incidence, morphological characteristics and relevance to pulmonary emphysema.

    PubMed

    Bae, H-J; Kang, E-Y; Yong, H S; Kim, Y K; Woo, O H; Oh, Y-W; Doo, K W

    2013-01-01

    To determine the incidence, morphological characteristics and relevance of paratracheal air cysts (PTACs) with pulmonary emphysema, as seen on thoracic multidetector CT (MDCT). The CT images of 854 consecutive patients who underwent thoracic MDCT during a period of 2 months at our institution were reviewed. 538 of the patients were male and 316 were female. The incidence, size and shape of the PTACs and their relation to pulmonary emphysema were retrospectively analysed. Among the 854 patients, 69 (8.1%) had PTACs. 37 (6.9%) of the 538 male patients and 32 (10.1%) of the 316 female patients had PTACs. The highest prevalence of PTACs (25 patients, 11.2%) was found in those who were in the sixth decade of life. 48 (69.6%) PTACs measured 3-10 mm at the longest diameter and 33 (47.8%) were elongated on the coronal section images. 12 (17.4%) patients with PTACs had underlying gross morphological emphysema. The relationship between the presence of PTACs and the presence of emphysema and the relationship between the presence of PTACs and the severity of emphysema were not statistically significant. The size of PTACs showed an inverse relation to the severity of emphysema. The incidence of PTACs was estimated to be much higher than that of previous studies. There was a slight female predilection for PTACs, most commonly found in the sixth decade of life; PTACs mostly measured 3-10 mm and were elongated in shape. The relation of PTACs to gross morphological emphysema was low. PTACs are not correlated with the presence of emphysema on MDCT.

  1. 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.

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

    PubMed

    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; Barr, R Graham

    2015-09-01

    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. To investigate whether PMBF is reduced in mild as well as more severe chronic obstructive pulmonary disease (COPD) and emphysema. 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. 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. 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.

  3. Congenital Lobar Emphysema with Pulmonary Extramedullary Hematopoiesis.

    PubMed

    Suryawanshi, Kishor; Nikumbh, Dhiraj; Singhavi, Sudhir; Damle, Rajshri; Dravid, Nandkumar

    2017-01-01

    Congenital lobar emphysema is a one of the rare variety of congenital abnormality of the lung causing respiratory distress in newborns and infants. Herein, we report a case of congenital lobar emphysema in a 3-week-old female admitted to the pediatric intensive care unit with severe respiratory distress. CT scan revealed a hyperinflated, hyperlucent left upper lobe, collapse of the ipsilateral lung and marked mediastinal shift to the right. The patient underwent emergency left upper lobectomy with improvement of her condition in the postoperative period. Histopathological findings confirmed the clinical diagnosis of congenital lobar emphysema with an unusual finding of pulmonary extramedullary hematopoiesis. Congenital lobar emphysema often presents a diagnostic and therapeutic dilemma and therefore requires a high index of suspicion in neonates presenting with respiratory distress to avoid morbidity and mortality.

  4. Large subconjunctival emphysema causing diplopia and lagophthalmos.

    PubMed

    Kaiserman, I

    2003-01-01

    To describe a patient who developed diplopia, lagophthalmos and exposure keratopathy due to a large subconjunctival emphysema. A 24-year-old man sustained an injury in his left eye from a compressed air hose. The patient complained of pain and diplopia. He underwent slit-lamp examination, funduscopy and computed tomography. Ophthalmic examination revealed a decrease in vision in the left eye to 0.5, a conjunctival laceration adjacent to the medial limbus, subconjunctival hemorrhage, a large subconjunctival emphysema, lagophthalmos, hypertropia and superficial punctate keratopathy. The posterior pole was intact as were the orbital bones. Two weeks after the injury the conjunctival emphysema, diplopia, lagophthalmos and superficial keratopathy resolved, and visual acuity improved to 1. Large subconjunctival emphysema can result in diplopia, lagophthalmos and exposure keratopathy.

  5. 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

  6. Congenital lobar emphysema in a kitten.

    PubMed

    Blonk, M; Van de Maele, I; Combes, A; Stablay, B; De Cock, H; Polis, I; Rybachuk, G; de Rooster, H

    2017-03-28

    A five-month-old ragdoll cat presented with severe respiratory signs, unresponsive to medical therapy. Hyperinflation of the right middle lung lobe was diagnosed with radiography and computed tomography. Lung lobectomy following a median sternotomy led to full recovery. Histopathological analysis revealed lobar emphysema and, based on the animal's age, congenital lobar emphysema was considered the most likely diagnosis. © 2017 British Small Animal Veterinary Association.

  7. 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.

  8. 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

  9. Cognitive and psychological issues in emphysema.

    PubMed

    Kozora, Elizabeth; Emery, Charles; Kaplan, Robert M; Wamboldt, Fredrick S; Zhang, Lening; Make, Barry J

    2008-05-01

    Various psychological and cognitive difficulties have been documented in patients with emphysema. The aim of this article is to review prior literature on the prevalence of these difficulties in emphysema, as well as identify specific studies demonstrating improvement in these areas after therapy. Traditional therapies such as continuous and intermittent oxygen therapy and comprehensive pulmonary rehabilitation are reviewed. In general, these studies demonstrate reductions in symptoms of depression and anxiety as well as specific improvements in complex attention and verbal fluency. In a more recent study, patients with emphysema who underwent lung volume reduction surgery (LVRS) demonstrated improved psychomotor speed, verbal memory, and naming skills at 6 months compared with patients with emphysema who were in comprehensive rehabilitation only. The patients with emphysema who had LVRS also demonstrated greater decline in depressive symptoms compared with the rehabilitation patients at 6 months. There were no associations between improved neuropsychological tests and changes in depression, exercise tests, pulmonary function, oxygenation, or quality of life scores, and thus the mechanism of behavioral improvement identified in the patients who underwent LVRS remained unclear. Overall, studies suggest that psychological and cognitive improvements occur subsequent to a variety of medical and behavioral treatment therapeutic approaches, and that LVRS appears to have an advantage for some patients with emphysema.

  10. Sex differences in severe pulmonary emphysema.

    PubMed

    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

    2007-08-01

    Limited data on sex differences in advanced COPD are available. To compare male and female emphysema patients with severe disease. One thousand fifty-three patients (38.8% female) evaluated for lung volume reduction surgery as part of the National Emphysema Treatment Trial were analyzed. 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 Dl(co) and arterial Po(2), higher arterial Pco(2), shorter six-minute walk distance, and lower maximal wattage during oxygen-supplemented cycle ergometry. For a given FEV(1)% 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. 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.

  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. Experimental progressive emphysema in BALB/cJ mice as a model for chronic alveolar destruction in humans.

    PubMed

    Limjunyawong, Nathachit; Craig, John M; Lagassé, H A Daniel; Scott, Alan L; Mitzner, Wayne

    2015-10-01

    Emphysema, one of the major components of chronic obstructive pulmonary disease (COPD), is characterized by the progressive and irreversible loss of alveolar lung tissue. Even though >80% of COPD cases are associated with cigarette smoking, only a relatively small proportion of smokers develop emphysema, suggesting a potential role for genetic factors in determining individual susceptibility to emphysema. Although strain-dependent effects have been shown in animal models of emphysema, the molecular basis underlying this intrinsic susceptibility is not fully understood. In this present study, we investigated emphysema development using the elastase-induced experimental emphysema model in two commonly used mouse strains, C57BL/6J and BALB/cJ. The results demonstrate that mice with different genetic backgrounds show disparate susceptibility to the development of emphysema. BALB/cJ mice were found to be much more sensitive than C57BL/6J to elastase injury in both a dose-dependent and time-dependent manner, as measured by significantly higher mortality, greater body weight loss, greater decline in lung function, and a greater loss of alveolar tissue. The more susceptible BALB/cJ strain also showed the persistence of inflammatory cells in the lung, especially macrophages and lymphocytes. A comparative gene expression analysis following elastase-induced injury showed BALB/cJ mice had elevated levels of il17A mRNA and a number of classically (M1) and alternatively (M2) activated macrophage genes, whereas the C57BL/6J mice demonstrated augmented levels of interferon-γ. These findings suggest a possible role for these cellular and molecular mediators in modulating the severity of emphysema and highlight the possibility that they might contribute to the heterogeneity observed in clinical emphysema outcomes. Copyright © 2015 the American Physiological Society.

  14. Experimental progressive emphysema in BALB/cJ mice as a model for chronic alveolar destruction in humans

    PubMed Central

    Limjunyawong, Nathachit; Craig, John M.; Lagassé, H. A. Daniel; Scott, Alan L.

    2015-01-01

    Emphysema, one of the major components of chronic obstructive pulmonary disease (COPD), is characterized by the progressive and irreversible loss of alveolar lung tissue. Even though >80% of COPD cases are associated with cigarette smoking, only a relatively small proportion of smokers develop emphysema, suggesting a potential role for genetic factors in determining individual susceptibility to emphysema. Although strain-dependent effects have been shown in animal models of emphysema, the molecular basis underlying this intrinsic susceptibility is not fully understood. In this present study, we investigated emphysema development using the elastase-induced experimental emphysema model in two commonly used mouse strains, C57BL/6J and BALB/cJ. The results demonstrate that mice with different genetic backgrounds show disparate susceptibility to the development of emphysema. BALB/cJ mice were found to be much more sensitive than C57BL/6J to elastase injury in both a dose-dependent and time-dependent manner, as measured by significantly higher mortality, greater body weight loss, greater decline in lung function, and a greater loss of alveolar tissue. The more susceptible BALB/cJ strain also showed the persistence of inflammatory cells in the lung, especially macrophages and lymphocytes. A comparative gene expression analysis following elastase-induced injury showed BALB/cJ mice had elevated levels of il17A mRNA and a number of classically (M1) and alternatively (M2) activated macrophage genes, whereas the C57BL/6J mice demonstrated augmented levels of interferon-γ. These findings suggest a possible role for these cellular and molecular mediators in modulating the severity of emphysema and highlight the possibility that they might contribute to the heterogeneity observed in clinical emphysema outcomes. PMID:26232300

  15. 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.

  16. 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.

  17. Pulmonary emphysema in cystic fibrosis detected by densitometry on chest multidetector computed tomography.

    PubMed

    Wielpütz, Mark O; Weinheimer, Oliver; Eichinger, Monika; Wiebel, Matthias; Biederer, Jürgen; Kauczor, Hans-Ulrich; Heußel, Claus P; Mall, Marcus A; Puderbach, Michael

    2013-01-01

    Histopathological studies on lung specimens from patients with cystic fibrosis (CF) and recent results from a mouse model indicate that emphysema may contribute to CF lung disease. However, little is known about the relevance of emphysema in patients with CF. In the present study, we used computationally generated density masks based on multidetector computed tomography (MDCT) of the chest for non-invasive characterization and quantification of emphysema in CF. Volumetric MDCT scans were acquired in parallel to pulmonary function testing in 41 patients with CF (median age 20.1 years; range 7-66 years) and 21 non-CF controls (median age 30.4 years; range 4-68 years), and subjected to dedicated software. The lung was segmented, low attenuation volumes below a threshold of -950 Hounsfield units were assigned to emphysema volume (EV), and the emphysema index was computed (EI). Results were correlated with forced expiratory volume in 1 s percent predicted (FEV1%), residual volume (RV), and RV/total lung capacity (RV/TLC). We show that EV was increased in CF (457±530 ml) compared to non-CF controls (78±90 ml) (P<0.01). EI was also increased in CF (7.7±7.5%) compared to the control group (1.2±1.4%) (P<0.05). EI correlated inversely with FEV1% (rs=-0.66), and directly with RV (rs=0.69) and RV/TLC (rs=0.47) in patients with CF (P<0.007), but not in non-CF controls. Emphysema in CF was detected from early adolescence (~13 years) and increased with age (rs=0.67, P<0.001). Our results indicate that early onset emphysema detected by densitometry on chest MDCT is a characteristic pathology that contributes to airflow limitation and may serve as a novel endpoint for monitoring lung disease in CF.

  18. Pulmonary Emphysema in Cystic Fibrosis Detected by Densitometry on Chest Multidetector Computed Tomography

    PubMed Central

    Wielpütz, Mark O.; Weinheimer, Oliver; Eichinger, Monika; Wiebel, Matthias; Biederer, Jürgen; Kauczor, Hans-Ulrich; Heußel, Claus P.

    2013-01-01

    Background Histopathological studies on lung specimens from patients with cystic fibrosis (CF) and recent results from a mouse model indicate that emphysema may contribute to CF lung disease. However, little is known about the relevance of emphysema in patients with CF. In the present study, we used computationally generated density masks based on multidetector computed tomography (MDCT) of the chest for non-invasive characterization and quantification of emphysema in CF. Methods Volumetric MDCT scans were acquired in parallel to pulmonary function testing in 41 patients with CF (median age 20.1 years; range 7-66 years) and 21 non-CF controls (median age 30.4 years; range 4-68 years), and subjected to dedicated software. The lung was segmented, low attenuation volumes below a threshold of -950 Hounsfield units were assigned to emphysema volume (EV), and the emphysema index was computed (EI). Results were correlated with forced expiratory volume in 1 s percent predicted (FEV1%), residual volume (RV), and RV/total lung capacity (RV/TLC). Results We show that EV was increased in CF (457±530 ml) compared to non-CF controls (78±90 ml) (P<0.01). EI was also increased in CF (7.7±7.5%) compared to the control group (1.2±1.4%) (P<0.05). EI correlated inversely with FEV1% (rs=-0.66), and directly with RV (rs=0.69) and RV/TLC (rs=0.47) in patients with CF (P<0.007), but not in non-CF controls. Emphysema in CF was detected from early adolescence (~13 years) and increased with age (rs=0.67, P<0.001). Conclusions Our results indicate that early onset emphysema detected by densitometry on chest MDCT is a characteristic pathology that contributes to airflow limitation and may serve as a novel endpoint for monitoring lung disease in CF. PMID:23991177

  19. Genome-Wide Association Identifies Regulatory Loci Associated with Distinct Local Histogram Emphysema Patterns

    PubMed Central

    Cho, Michael H.; San José Estépar, Raúl; McDonald, Merry-Lynn N.; Laird, Nan; Beaty, Terri H.; Washko, George; Crapo, James D.; Silverman, Edwin K.

    2014-01-01

    Rationale: Emphysema is a heritable trait that occurs in smokers with and without chronic obstructive pulmonary disease. Emphysema occurs in distinct pathologic patterns, but the genetic determinants of these patterns are unknown. Objectives: To identify genetic loci associated with distinct patterns of emphysema in smokers and investigate the regulatory function of these loci. Methods: Quantitative measures of distinct emphysema patterns were generated from computed tomography scans from smokers in the COPDGene Study using the local histogram emphysema quantification method. Genome-wide association studies (GWAS) were performed in 9,614 subjects for five emphysema patterns, and the results were referenced against enhancer and DNase I hypersensitive regions from ENCODE and Roadmap Epigenomics cell lines. Measurements and Main Results: Genome-wide significant associations were identified for seven loci. Two are novel associations (top single-nucleotide polymorphism rs379123 in MYO1D and rs9590614 in VMA8) located within genes that function in cell-cell signaling and cell migration, and five are in loci previously associated with chronic obstructive pulmonary disease susceptibility (HHIP, IREB2/CHRNA3, CYP2A6/ADCK, TGFB2, and MMP12). Five of these seven loci lay within enhancer or DNase I hypersensitivity regions in lung fibroblasts or small airway epithelial cells, respectively. Enhancer enrichment analysis for top GWAS associations (single-nucleotide polymorphisms associated at P < 5 × 10−6) identified multiple cell lines with significant enhancer enrichment among top GWAS loci, including lung fibroblasts. Conclusions: This study demonstrates for the first time genetic associations with distinct patterns of pulmonary emphysema quantified by computed tomography scan. Enhancer regions are significantly enriched among these GWAS results, with pulmonary fibroblasts among the cell types showing the strongest enrichment. PMID:25006744

  20. 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.

  1. The burden of image based emphysema and bronchiolitis in HIV-infected individuals on antiretroviral therapy.

    PubMed

    Guaraldi, Giovanni; Besutti, Giulia; Scaglioni, Riccardo; Santoro, Antonella; Zona, Stefano; Guido, Ligabue; Marchioni, Alessandro; Orlando, Gabriella; Carli, Federica; Beghe, Bianca; Fabbri, Leonardo; Leipsic, Jonathon; Sin, Don D; Man, S F Paul

    2014-01-01

    With the widespread use of anti-retroviral therapy (ART), individuals infected with human immune deficiency virus (HIV) are increasingly experiencing morbidity and mortality from respiratory disorders. However, the prevalence or the risk factors associated with emphysema and bronchiolitis are largely unknown. Thoracic computed tomography (CT) scans were performed in 1,446 patients infected with HIV who were on ART and who attended a tertiary care metabolic clinic (average age 48 years and 29% females). Detailed history and physical examination including anthropometric measurements were performed. Complete pulmonary function tests were performed in a subset of these patients (n = 364). No subjects were acutely ill with a respiratory condition at the time of CT scanning. Nearly 50% of the subjects had CT evidence for emphysema, bronchiolitis or both with 13% (n = 195) showing bronchiolitis, 19% (n = 274) showing emphysema and 16% (n = 238) revealing both. These phenotypes were synergistically associated with reduced regular physical activity (p for interaction <.0001). The most significant risk factors for both phenotypes were cigarette smoking, intravenous drug use and peripheral leucocytosis. Together, the area-under-the curve statistics was 0.713 (p = 0.0037) for discriminating those with and without these phenotypes. There were no significant changes in lung volumes or flow rates related to these phenotypes, though the carbon monoxide diffusion capacity was reduced for the emphysema phenotype. Emphysema and bronchiolitis are extremely common in HIV-infected patients who are treated with ART and can be identified by use of thoracic CT scanning.

  2. Clarithromycin prevents smoke-induced emphysema in mice.

    PubMed

    Nakanishi, Yutaka; Kobayashi, Dale; Asano, Yasuo; Sakurai, Takanobu; Kashimura, Masato; Okuyama, Shigeru; Yoneda, Yukio; Shapiro, Steven D; Takayama, Kiyoshi

    2009-02-15

    Modulating the low-grade chronic inflammation in chronic obstructive pulmonary disease remains challenging. Clarithromycin (CAM), a macrolide antibiotic, reportedly ameliorates chronic inflammation via mechanisms independent of its antibacterial activity. The aim of this study was to examine whether CAM can prevent or reduce emphysema induced by chronic cigarette smoke exposure. Mice were exposed to cigarette smoke daily for 6 months and treated with orally administered CAM at doses of 25 to 100 mg/kg twice a day throughout the course of the experiment to test the preventive effects. The administration of CAM at 50 or 100 mg/kg was performed during the second half of a 6-month exposure period to assess the therapeutic effects. Histologic analysis was performed to evaluate the effect of CAM. CAM treatment for 6 months decreased airspace enlargement and the destruction of the alveolar walls and impaired the accumulation of macrophages in bronchoalveolar lavage fluid in a dose-related fashion. The administration of clarithromycin at 100 mg/kg in the therapeutic protocol reduced emphysema compared with the smoke-exposed group without treatment. An immunohistologic analysis revealed that CAM reduced the number of F4/80-positive macrophages in the lung parenchyma. In an in vitro test, CAM at 5 to 20 microM directly suppressed the activation of macrophages stimulated with tumor necrosis factor-alpha. Our data demonstrated that CAM at a clinically achievable dose prevented cigarette smoke-induced emphysema by modulating lung inflammation. This study supports the possibility that low-dose CAM treatment might provide a new therapeutic strategy for chronic obstructive pulmonary diseases.

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. New-born females show higher stress- and genotype-independent methylation of SLC6A4 than males.

    PubMed

    Dukal, Helene; Frank, Josef; Lang, Maren; Treutlein, Jens; Gilles, Maria; Wolf, Isabell Ac; Krumm, Bertram; Massart, Renaud; Szyf, Moshe; Laucht, Manfred; Deuschle, Michael; Rietschel, Marcella; Witt, Stephanie H

    2015-01-01

    Research has demonstrated an association between exposure to early life stress and an increased risk of psychiatric disorders in later life, in particular depression. However, the mechanism through which early life stress contributes to disease development remains unclear. Previous studies have reported an association between early life stress and altered methylation of the serotonin transporter gene (SLC6A4), a key candidate gene for several psychiatric disorders. These differences in methylation are influenced by sex and genetic variation in the SLC6A4-linked polymorphic region (5-HTTLPR). Furthermore, one study indicated that stress during pregnancy may induce methylation changes in SLC6A4 in the newborn. The present study is the first to investigate whether early life stress during pregnancy impacts on SLC6A4 methylation in newborns, taking into account the influence of genetic variation and sex. Cord blood was obtained from newborns with high (n = 45) or low (n = 45) early life stress, defined as maternal stress during pregnancy. The effect on methylation of early life stress, 5-HTTLPR genotype, and sex was assessed at four cytosin-phosphate-guanine dinucleotide (CpG) sites in the promoter associated CpG island north shore (CpG 1 to 4). The epigenetic analyses focused on these CpG sites, since research has shown that CpG island shore methylation has functional consequences. Significant sex-specific methylation was observed, with females displaying higher methylation levels than males (p < 0.001). Importantly, this effect was influenced by neither early life stress nor genotype. The present data suggest that sex-specific methylation of SLC6A4 is present at birth, and is independent of early life stress and 5-HTTLPR genotype. This may contribute to the sex-specific prevalence of depression.

  8. Validation of RNAi Silencing Efficiency Using Gene Array Data shows 18.5% Failure Rate across 429 Independent Experiments.

    PubMed

    Munkácsy, Gyöngyi; Sztupinszki, Zsófia; Herman, Péter; Bán, Bence; Pénzváltó, Zsófia; Szarvas, Nóra; Győrffy, Balázs

    2016-09-27

    No independent cross-validation of success rate for studies utilizing small interfering RNA (siRNA) for gene silencing has been completed before. To assess the influence of experimental parameters like cell line, transfection technique, validation method, and type of control, we have to validate these in a large set of studies. We utilized gene chip data published for siRNA experiments to assess success rate and to compare methods used in these experiments. We searched NCBI GEO for samples with whole transcriptome analysis before and after gene silencing and evaluated the efficiency for the target and off-target genes using the array-based expression data. Wilcoxon signed-rank test was used to assess silencing efficacy and Kruskal-Wallis tests and Spearman rank correlation were used to evaluate study parameters. All together 1,643 samples representing 429 experiments published in 207 studies were evaluated. The fold change (FC) of down-regulation of the target gene was above 0.7 in 18.5% and was above 0.5 in 38.7% of experiments. Silencing efficiency was lowest in MCF7 and highest in SW480 cells (FC = 0.59 and FC = 0.30, respectively, P = 9.3E-06). Studies utilizing Western blot for validation performed better than those with quantitative polymerase chain reaction (qPCR) or microarray (FC = 0.43, FC = 0.47, and FC = 0.55, respectively, P = 2.8E-04). There was no correlation between type of control, transfection method, publication year, and silencing efficiency. Although gene silencing is a robust feature successfully cross-validated in the majority of experiments, efficiency remained insufficient in a significant proportion of studies. Selection of cell line model and validation method had the highest influence on silencing proficiency.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Implications of Emphysema and Lung Function for the Development of Pneumonia in Patients with Chronic Obstructive Pulmonary Disease.

    PubMed

    Hong, Yoonki; Lee, Jae Seung; Yoo, Kwang Ha; Lee, Ji-Hyun; Kim, Woo Jin; Lim, Seong Yong; Rhee, Chin Kook; Lee, Sang-Do; Oh, Yeon-Mok

    2016-04-01

    Chronic obstructive pulmonary disease (COPD) is sometimes complicated with pneumonia, but little is known about the risk factors that promote the development of pneumonia in COPD. These risk factors were evaluated in the present study. The data of 324 patients with COPD from a prospective multi-center observational cohort with obstructive lung disease were evaluated retrospectively. To identify risk factors for the development of pneumonia in COPD, the clinical and radiological data at enrollment and the time to the first episode of pneumonia were analyzed by Cox proportional hazard analysis. The median follow-up time was 1,099 days and 28 patients (8.6%) developed pneumonia. The Cox analysis showed that post-bronchodilator forced expiratory volume in one second (FEV1, % of predicted) and the computed tomography (CT) emphysema extent (inspiratory V950) were independent risk factors for the development of pneumonia (post-bronchodilator FEV1: hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.94-1.00; p=0.048 and inspiratory V950: HR, 1.04; 95% CI, 1.01-1.07; p=0.01). Emphysema severity measured by CT and post-bronchodilator FEV1 are important risk factors for the development of pneumonia in COPD.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. Structural studies show energy transfer within stabilized phycobilisomes independent of the mode of rod-core assembly.

    PubMed

    David, Liron; Prado, Mindy; Arteni, Ana A; Elmlund, Dominika A; Blankenship, Robert E; Adir, Noam

    2014-03-01

    The major light harvesting complex in cyanobacteria and red algae is the phycobilisome (PBS), comprised of hundreds of seemingly similar chromophores, which are protein bound and assembled in a fashion that enables highly efficient uni-directional energy transfer to reaction centers. The PBS is comprised of a core containing 2-5 cylinders surrounded by 6-8 rods, and a number of models have been proposed describing the PBS structure. One of the most critical steps in the functionality of the PBS is energy transfer from the rod substructures to the core substructure. In this study we compare the structural and functional characteristics of high-phosphate stabilized PBS (the standard fashion of stabilization of isolated complexes) with cross-linked PBS in low ionic strength buffer from two cyanobacterial species, Thermosynechococcus vulcanus and Acaryochloris marina. We show that chemical cross-linking preserves efficient energy transfer from the phycocyanin containing rods to the allophycocyanin containing cores with fluorescent emission from the terminal emitters. However, this energy transfer is shown to exist in PBS complexes of different structures as characterized by determination of a 2.4Å structure by X-ray crystallography, single crystal confocal microscopy, mass spectrometry and transmission electron microscopy of negatively stained and cryogenically preserved complexes. We conclude that the PBS has intrinsic structural properties that enable efficient energy transfer from rod substructures to the core substructures without requiring a single unique structure. We discuss the significance of our observations on the functionality of the PBS in vivo. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. 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.

  1. Cigarette smoke induced autophagy-impairment accelerates lung aging, COPD-emphysema exacerbations and pathogenesis.

    PubMed

    Vij, Neeraj; Chandramani, Prashanth; Westphal, Colin Van; Hole, Rachel; Bodas, Manish

    2016-07-13

    Cigarette-smoke (CS) exposure and aging are the leading causes of chronic obstructive pulmonary disease (COPD)-emphysema development, although the molecular mechanism that mediates disease pathogenesis remains poorly understood. To investigate the impact of CS-exposure and aging on autophagy, and pathophysiological changes associated with lung aging (senescence) and emphysema progression. Beas2b cells, C57BL/6 mice and human (GOLD 0-IV) lung tissues were used to determine the central mechanism involved in CS/age-related COPD-emphysema pathogenesis. Beas2b cells and murine lungs exposed to CSE/CS showed a significant (p<0.05) accumulation of poly-ubiquitinated proteins and impaired-autophagy marker, p62, in aggresome-bodies. Moreover, treatment with autophagy-inducing antioxidant drug, cysteamine significantly (p<0.001) decreased CSE/CS-induced aggresome-bodies. We also found a significant (p<0.001) increase in levels of aggresome-bodies in the lungs of smokers and COPD-subjects in comparison to non-smoker controls. Furthermore, the presence and levels of aggresome-bodies statistically correlated with severity of emphysema and alveolar senescence. In addition to CS exposure, lungs from old mice also showed accumulation of aggresome-bodies, suggesting this as a common mechanism to initiate cellular senescence and emphysema. Additionally, Beas2b cells and murine lungs exposed to CSE/CS showed cellular apoptosis and senescence, which were both controlled by cysteamine treatment. In parallel, we evaluated the impact of CS on pulmonary exacerbation, using mice exposed to CS and/or infected with Pseudomonas aeruginosa (Pa), and confirmed cysteamine's potential as an autophagy-inducing antibacterial drug, based on its ability to control CS-induced pulmonary exacerbation (Pa-bacterial counts) and resulting inflammation. CS induced autophagy-impairment accelerates lung aging, COPD-emphysema exacerbations and pathogenesis. Copyright © 2016, American Journal of Physiology

  2. Acute exacerbation of combined pulmonary fibrosis and emphysema associated with Hermansky-Pudlak syndrome.

    PubMed

    Sugino, Keishi; Gocho, Kyoko; Kikuchi, Naoshi; Shibuya, Kazutoshi; Uekusa, Toshimasa; Homma, Sakae

    2016-03-01

    A 30-year-old male smoker with congenital amblyopia and oculocutaneous albinism was admitted to our hospital complaining of progressive dyspnea on exertion. Chest computed tomography images revealed diffuse reticular opacities and honeycombing in the bilateral lower lobes with sparing of the subpleural region along with emphysema predominantly in the upper lobes. Lung biopsy specimens showed a mixture of usual interstitial pneumonia and a non-specific interstitial pneumonia pattern with emphysema. Of note, cuboidal epithelial cells with foamy cytoplasm on the alveolar walls and phagocytic macrophages with ceroid pigments in the fibrotic lesions were observed. The patient was diagnosed with Hermansky-Pudlak syndrome (HPS) associated with combined pulmonary fibrosis and emphysema (CPFE). Six years following the patient's initial admission to our hospital, he died from acute exacerbation (AE) of CPFE associated with HPS. This is one of only few reports available on the clinicopathological characteristics of AE in CPFE associated with HPS.

  3. [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.

  4. [Hyoid fracture and traumatic subcutaneous cervical emphysema from an attempted hanging. Apropos a case].

    PubMed

    Cañizares, M A; Arnau, A; Fortea, A; Zarzuela, V; Martínez-Vallina, P; Cantó, A

    2000-01-01

    We describe a patient with a history of psychiatric disorder who was brought to our hospital after attempted suicide by hanging. Severe subcutaneous facial, palpebral and cervical emphysema was present, with dysphonia, dysphagia and slight respiratory difficulty. Fiberoptic bronchoscopy revealed upper airway obstruction due to edema in an intact airway. Successive CAT scans gave evidence of hyoid fracture and laryngocele, in addition to the corresponding emphysema of the subcutaneous area and pneumomediastinum. Given the persistence of dysphagia, we ordered esophageal tests, which showed functional alteration of the upper esophageal sphincter. Suprasternal cervicotomy to drain the pneumomediastinum and laryngeal microsurgery to treat the laryngocele resolved the problem.

  5. 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.

  6. A stripe sign on 99mTc-Technegas SPECT in pulmonary emphysema.

    PubMed

    Suga, Kazuyoshi; Kawakami, Yasuhiko; Iwanaga, Hideyuki; Tokuda, Osamu; Matsunaga, Naofumi

    2008-06-01

    By focusing on a stripe sign (interposed preserved radioactivity between central defects and pleural surface of the lung), the cross-sectional ventilation difference between the central and peripheral lung in pulmonary emphysema was evaluated on Tc-Technegas SPECT, and compared with other forms of chronic obstructive pulmonary disease (COPD). Technegas and perfusion SPECT were performed in 47 patients with relatively advanced emphysema, 15 patients with other forms of COPD without alveolar destruction and six controls. The presence or absence of a stripe sign was evaluated at upper, middle and lower lung zones on both SPECT. At stripe sign-positive lung zones on Technegas SPECT in pulmonary emphysema, the pattern of low attenuation areas (LAAs) distribution on X-ray CT was also evaluated. Of the total of 282 lung zones in patients with emphysema, a stripe sign was positive on Technegas SPECT at 153 (54.2%) zones in 27 (57.4%) patients, although less frequently positive on perfusion SPECT at 166 (58.8%) zones in 30 (63.8%) patients. This sign was negative on Technegas SPECT throughout the stripe sign-negative zones on perfusion SPECT. Throughout the lung zones in controls and patients with other forms of COPD, this sign was negative both on Technegas and perfusion SPECT. On X-ray CT, 124 (81%) of 153 stripe-positive lung zones on Technegas SPECT in pulmonary emphysema showed central lung-dominant LAA. In contrast to other forms of COPD, a stripe sign was frequently positive on Technegas SPECT in relatively advanced emphysema, with central-lung dominant LAA on X-ray CT. Relative preservation of peripheral lung ventilation seems to be a characteristic feature of this disease, indicating a lower susceptibility of the peripheral lung for alveolar destruction.

  7. Low agreement of visual rating for detailed quantification of pulmonary emphysema in whole-lung CT.

    PubMed

    Mascalchi, Mario; Diciotti, Stefano; Sverzellati, Nicola; Camiciottoli, Gianna; Ciccotosto, Cesareo; Falaschi, Fabio; Zompatori, Maurizio

    2012-02-01

    Multidetector spiral computed tomography (CT) has opened the possibility of quantitative evaluation of emphysema extent in the whole lung. Visual assessment can be used for such a purpose, but its reproducibility has not been established. To assess agreement of detailed assessment of pulmonary emphysema on whole-lung CT using a visual scale. Thirty patients with chronic obstructive pulmonary disease underwent whole-lung inspiratory CT. Four chest radiologists rated the same 22 ± 2 thin sections using a visual scale which defines a range of emphysema extent between 0 and 100. Two of them repeated the rating two months later. Inter- and intra-operator agreement was evaluated with the Bland and Altman method. In addition, the percentage of emphysema at -950 Hounsfield units in the whole lung was determined using fully automated commercially available software for 3D densitometry. In three of six operator pairs and in one of two intra-operator pairs the Kendall τ test showed a significant correlation between the difference and the average magnitude of visual scores. Among different operators the half-width of 95% limits of agreement (95% LoA) was wide ranging between a score of 14.2-27.7 for an average visual score of 20 and between 18.5-36.8 for an average visual score of 80. Within the same operator the half-width of 95% LoA ranged between a score of 10.9-21.0 for an average visual score of 20 and between 25.1-30.1 for an average visual score of 80. The visual scores of the four radiologists were correlated with the results of densitometry (P < 0.001; r = 0.65-0.81). The inter- and intra-operator agreement of detailed assessment of emphysema in the whole lung using a visual scale is low and decreases with increasing emphysema extent.

  8. 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

  9. Cigarette Smoke Induction of Osteopontin (SPP1) Mediates TH17 Inflammation in Human and Experimental Emphysema

    PubMed Central

    Shan, Ming; Yuan, Xiaoyi; Song, Li-zhen; Roberts, Luz; Zarinkamar, Nazanin; Seryshev, Alexander; Zhang, Yiqun; Hilsenbeck, Susan; Chang, Seon-Hee; Dong, Chen; Corry, David B.; Kheradmand, Farrah

    2014-01-01

    Smoking-related lung diseases are among the leading causes of death worldwide, underscoring the need to understand their pathogenesis and develop new effective therapies. We have shown that CD1a+ antigen-presenting cells (APCs) from lungs of patients with emphysema can induce autoreactive T helper 1 (TH1) and TH17 cells. Similarly, the canonical cytokines interferon-γ (IFN-γ) and interleukin-17A (IL-17A) are specifically linked to lung destruction in smokers, but how smoke activates APCs to mediate emphysema remains unknown. Here, we show that, in addition to increasing IFN-γ expression, cigarette smoke increased the expression of IL-17A in both CD4+ and γδ T cells from mouse lung. IL-17A deficiency resulted in attenuation of, whereas lack of γδ T cells exacerbated, smoke-induced emphysema in mice. Adoptive transfer of lung APCs isolated from mice with emphysema revealed that this cell population was capable of transferring disease even in the absence of active smoke exposure, a process that was dependent on IL-17A expression. Spp1 (the gene for osteopontin) was highly expressed in the pathogenic lung APCs of smoke-exposed mice and was required for the TH17 responses and emphysema in vivo, in part through its inhibition of the expression of the transcription factor Irf7. Thus, the Spp1-Irf7 axis is critical for induction of pathological TH17 responses, revealing a major mechanism by which smoke activates lung APCs to induce emphysema and identifying a pathway that could be targeted for therapeutic purposes. PMID:22261033

  10. 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

  11. 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.

  12. 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

  13. Decreased expression of interleukin 13 in human lung emphysema

    PubMed Central

    Boutten, A; Bonay, M; Laribe, S; Leseche, G; Castier, Y; Lecon-Malas, V; Fournier, M; Durand, G; Aubier, M; Dehoux, M; Crestani, B

    2004-01-01

    Background: The overexpression of interferon (IFN)γ or interleukin (IL)-13 in the adult murine lung induces the development of changes that mirror human lung emphysema. Methods: IL-13 and IFNγ expression was determined in lung samples from five groups of patients: severe emphysema without α1-antitrypsin deficiency (SE+, n = 10); severe emphysema with α1-antitrypsin deficiency (SE–, n = 5); mild localised emphysema (ME, n = 8); non-emphysema smokers (NE-S, n = 9), and non-emphysema non-smokers (NE-NS, n = 11). Lung IL-13 and IFNγ mRNA were analysed by RT-PCR. Lung concentrations of IL-13 protein were assessed by ELISA. Results: The expression of IFNγ mRNA was similar in patients with or without emphysema. IL-13 mRNA was markedly decreased in the SE+ group compared with the SE– (p = 0.04), ME (p = 0.02), and non-emphysema groups (p = 0.01). IL-13 mRNA correlated with forced expiratory volume in 1 second (r = 0.5, p = 0.04) and arterial oxygen tension (r = 0.45, p = 0.03) in emphysema patients. In contrast to the non-emphysematous lung, IL-13 protein was below the detection limit of the assay in most emphysematous lung homogenates. Conclusion: The lung IL-13 content is reduced in patients with severe emphysema without α1-antitrypsin deficiency. PMID:15454650

  14. Percent Emphysema and Daily Motor Activity Levels in the General Population: Multi-Ethnic Study of Atherosclerosis.

    PubMed

    Lo Cascio, Christian M; Quante, Mirja; Hoffman, Eric A; Bertoni, Alain G; Aaron, Carrie P; Schwartz, Joseph E; Avdalovic, Mark V; Fan, Vincent S; Lovasi, Gina S; Kawut, Steven M; Austin, John H M; Redline, Susan; Barr, R Graham

    2017-05-01

    COPD is associated with reduced physical capacity. However, it is unclear whether pulmonary emphysema, which can occur without COPD, is associated with reduced physical activity in daily life, particularly among people without COPD and never smokers. We hypothesized that greater percentage of emphysema-like lung on CT scan is associated with reduced physical activity assessed by actigraphy and self-report. The Multi-Ethnic Study of Atherosclerosis (MESA) enrolled participants free of clinical cardiovascular disease from the general population. Percent emphysema was defined as percentage of voxels < -950 Hounsfield units on full-lung CT scans. Physical activity was measured by wrist actigraphy over 7 days and a questionnaire. Multivariable linear regression was used to adjust for age, sex, race/ethnicity, height, weight, education, smoking, pack-years, and lung function. Among 1,435 participants with actigraphy and lung measures, 47% had never smoked, and 8% had COPD. Percent emphysema was associated with lower activity levels on actigraphy (P = .001), corresponding to 1.5 hour less per week of moderately paced walking for the average participant in quintile 2 vs 4 of percent emphysema. This association was significant among participants without COPD (P = .004) and among ever (P = .01) and never smokers (P = .03). It was also independent of coronary artery calcium and left ventricular ejection fraction. There was no evidence that percent emphysema was associated with self-reported activity levels. Percent emphysema was associated with decreased physical activity in daily life objectively assessed by actigraphy in the general population, among participants without COPD, and nonsmokers. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  15. Towards local progression estimation of pulmonary emphysema using CT.

    PubMed

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

    2014-02-01

    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. 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. 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 linearity assumption

  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. Combined Pulmonary Fibrosis and Emphysema Alters Physiology but Has Similar Mortality to Pulmonary Fibrosis Without Emphysema

    PubMed Central

    Rounds, Sharon

    2010-01-01

    Studies have described individuals with combined pulmonary fibrosis and emphysema (CPFE), with preserved lung volumes, significant reductions in gas exchange, and high prevalence of pulmonary hypertension. While physiologic changes in CPFE are well documented, there is little mortality data in the CPFE population compared to appropriate controls. A study was performed to determine the features and outcomes of a group of individuals with imaging and/or pathologic evidence of CPFE to determine if individuals with combined pulmonary fibrosis and emphysema have different features and survival than individuals with pulmonary fibrosis alone. We conducted a retrospective study at a Veterans Affairs Medical Center. Included in the study were individuals hospitalized over a 5-year period who were given a clinical diagnosis of pulmonary fibrosis. Individuals with confirmed imaging or pathologic evidence of pulmonary fibrosis were divided into a study group with concomitant emphysema (CPFE group, n = 20) and a control group without emphysema (isolated pulmonary fibrosis (PF) group, n = 24). The CPFE group, all current or former cigarette smokers, had significantly larger lung volumes, more expiratory airflow obstruction, and worse gas exchange than the isolated pulmonary fibrosis group. Mortality did not differ between the groups. Combined pulmonary fibrosis and emphysema results in unique physiologic features but no difference in survival compared with a group with pulmonary fibrosis alone. PMID:20614219

  18. Baseline regional perfusion impacts exercise response to endobronchial valve therapy in advanced pulmonary emphysema.

    PubMed

    Argula, Rahul G; Strange, Charlie; Ramakrishnan, Viswanathan; Goldin, Jonathan

    2013-11-01

    Advanced heterogeneous emphysema with hyperinflation impacts exercise tolerance in COPD. Bronchoscopic lung volume reduction using Zephyr endobronchial valves (EBVs) has been shown to improve lung function in patients with heterogeneous emphysema. It is unclear whether the target lobe perfusion of patients receiving EBV therapy impacts exercise tolerance as measured by the 6-min walk test distance (6MWTD). We performed a retrospective analysis on the treatment group of the Endobronchial Valve for Emphysema Palliation Trial (VENT) to evaluate the impact of perfusion, measured by 99mTc-MAA-perfusion scintigraphy, on the 6-month improvement in 6MWTD. A mixed-model analysis was performed for the treatment outcome, adjusting for other variables such as age, target lobe position, fissure integrity, BMI, sex, destruction score, and lobar exclusion. Dichotomized at the median, of the 169 patients who received EBV therapy, 88 had a low target lobe regional perfusion and 81 had high target lobe regional perfusion at baseline. Patients with a low target lobe regional perfusion had a significant improvement in 6MWTD when compared with those with a high baseline target lobe regional perfusion (30.24 m vs 3.72 m, P = .03). Shifts in perfusion after EBV therapy occurred only in patients with high baseline perfusion and did not correlate with improved 6MWTD. Patients having heterogeneous emphysema with a low baseline target lobe regional perfusion benefit from EBV therapy, independent of the degree of target lobe destruction. This effect is attenuated if the EBV therapy is not occlusive. Characterization of baseline perfusion may enhance clinical results of patients with emphysema undergoing EBV therapy. ClinicalTrials.gov; No.: NCT00000606; URL: www.clincialtrials.gov.

  19. 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

  20. [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.

  1. [Combined pulmonary fibrosis and emphysema associated with microscopic polyangiitis].

    PubMed

    M'Saad, S; Kammoun, K; Yangui, I; Fourati, H; Feki, W; Marouen, F; Daoud, E; Kammoun, S

    2016-05-01

    Combined pulmonary fibrosis and emphysema (CPFE) is a rare entity of unknown etiology. It usually occurs in the context of smoking and, less commonly, connective tissue disease. However, it has been rarely previously described in the context of vasculitis. We report a case of CPFE occurring in a 44-year-old man, who was a light smoker without any previous medical history. He presented with fever, chronic cough and breathlessness that progressively evolved to acute respiratory failure. At the initial evaluation, CT scan showed emphysema and patchy bilateral areas of ground-glass opacity. Three years later, the patient simultaneously developed a honeycomb fibrosis and a microscopic polyangiitis with renal involvement justifying the introduction of an immunosuppressive treatment in combination with high dose of systemic corticosteroids. After a stabilization period of 6years, the patient gradually developed chronic respiratory failure with moderate pulmonary hypertension requiring long-term oxygen therapy and nocturnal non-invasive ventilation. The association of microscopic polyangiitis to CFPE suggests that autoimmune diseases may have a common pathogenic role in the development of emphysematous and fibrotic lesions in CPFE. Copyright © 2015 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  2. 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.

  3. 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.

  4. Pulmonary emphysema induced by methylphenidate: experimental study.

    PubMed

    Rapello, Gabriel Victor Guimarães; Antoniolli, Andréia; Pereira, Daniel Martins; Facco, Gilberto; Pêgo-Fernandes, Paulo Manuel; Pazetti, Rogério

    2015-01-01

    Methylphenidate is the most widely used drug for treating attention deficit hyperactivity disorder. However, it has important side effects, such as abdominal pain, insomnia, anorexia and loss of appetite, and also some cases of early severe emphysema after drug abuse have been reported. Our aim was to investigate the development of pulmonary emphysema in rats that were subjected to different doses of methylphenidate. Experimental study carried out at the laboratory of a public university. Eighteen male Wistar rats were divided into three groups: control (0.9% saline solution); MP 0.8 (methylphenidate, 0.8 mg/kg); MP 1.2 (methylphenidate, 1.2 mg/kg). After 90 days of daily gavage, the animals were sacrificed and lung tissue samples were prepared for analysis on the mean alveolar diameter (Lm). The Lm was greater in MP 0.8 (47.91 ± 3.13; P < 0.01) and MP 1.2 (46.36 ± 4.39; P < 0.05) than in the control group (40.00 ± 3.48). Methylphenidate caused an increase in the alveolar diameter of rats, which was compatible with human pulmonary emphysema.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

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

    PubMed

    Hu, Jia-Yi; Liu, Bei-Bei; Du, Yi-Peng; Zhang, Yuan; Zhang, Yi-Wei; Zhang, You-Yi; Xu, Ming; He, Bei

    2017-03-06

    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.

  12. 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

  13. 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.

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

    PubMed

    Yuan, X; Shan, M; You, R; Frazier, M V; Hong, M J; Wetsel, R A; Drouin, S; Seryshev, A; Song, L-Z; Cornwell, L; Rossen, R D; Corry, D B; Kheradmand, F

    2015-07-01

    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 with wild-type mice. Proteolytic cleavage of C3 by neutrophil elastase releases C3a, which in turn increases the 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.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. Targeting Nrf2 with the triterpenoid CDDO-imidazolide attenuates cigarette smoke-induced emphysema and cardiac dysfunction in mice.

    PubMed

    Sussan, Thomas E; Rangasamy, Tirumalai; Blake, David J; Malhotra, Deepti; El-Haddad, Hazim; Bedja, Djahida; Yates, Melinda S; Kombairaju, Ponvijay; Yamamoto, Masayuki; Liby, Karen T; Sporn, Michael B; Gabrielson, Kathleen L; Champion, Hunter C; Tuder, Rubin M; Kensler, Thomas W; Biswal, Shyam

    2009-01-06

    Chronic obstructive pulmonary disease (COPD), which comprises emphysema and chronic bronchitis resulting from prolonged exposure to cigarette smoke (CS), is a major public health burden with no effective treatment. Emphysema is also associated with pulmonary hypertension, which can progress to right ventricular failure, an important cause of morbidity and mortality among patients with COPD. Nuclear erythroid 2 p45 related factor-2 (Nrf2) is a redox-sensitive transcription factor that up-regulates a battery of antioxidative genes and cytoprotective enzymes that constitute the defense against oxidative stress. Recently, it has been shown that patients with advanced COPD have a decline in expression of the Nrf2 pathway in lungs, suggesting that loss of this antioxidative protective response is a key factor in the pathophysiological progression of emphysema. Furthermore, genetic disruption of Nrf2 in mice causes early-onset and severe emphysema. The present study evaluated whether the strategy of activation of Nrf2 and its downstream network of cytoprotective genes with a small molecule would attenuate CS-induced oxidative stress and emphysema. Nrf2(+/+) and Nrf2(-/-) mice were fed a diet containing the potent Nrf2 activator, 1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Im), while being exposed to CS for 6 months. CDDO-Im significantly reduced lung oxidative stress, alveolar cell apoptosis, alveolar destruction, and pulmonary hypertension in Nrf2(+/+) mice caused by chronic exposure to CS. This protection from CS-induced emphysema depended on Nrf2, as Nrf2(-/-) mice failed to show significant reduction in alveolar cell apoptosis and alveolar destruction after treatment with CDDO-Im. These results suggest that targeting the Nrf2 pathway during the etiopathogenesis of emphysema may represent an important approach for prophylaxis against COPD.

  1. Rate of progression of CT-quantified emphysema in male current and ex-smokers: a follow-up study

    PubMed Central

    2013-01-01

    Background Little is known about the factors associated with CT-quantified emphysema progression in heavy smokers. The objective of this study was to investigate the effect of length of smoking cessation and clinical / demographical factors on the rate of emphysema progression and FEV1-decline in male heavy smokers. Methods 3,670 male smokers with mean (SD) 40.8 (17.9) packyears underwent chest CT scans and pulmonary function tests at baseline and after 1 and 3 years follow-up. Smoking status (quitted ≥5, ≥1-<5, <1 years or current smoker) was noted. Rate of progression of emphysema and FEV1-decline after follow-up were assessed by analysis of variance adjusting for age, height, baseline pulmonary function and emphysema severity, packyears, years in study and respiratory symptoms. The quitted ≥5 group was used as reference. Results Median (Q1-Q3) emphysema severity,<-950 HU, was 8.8 (5.1 – 14.1) and mean (SD) FEV1 was 3.4 (0.73) L or 98.5 (18.5) % of predicted. The group quitted ‘>5 years’ showed significantly lower rates of progression of emphysema compared to current smokers, 1.07% and 1.12% per year, respectively (p<0.001). Current smokers had a yearly FEV1-decline of 69 ml, while subjects quit smoking >5 years had a yearly decline of 57.5 ml (p<0.001). Conclusion Quit smoking >5 years significantly slows the rate of emphysema progression and lung function decline. Trial registration Registered at http://www.trialregister.nl with trial number ISRCTN63545820. PMID:23688060

  2. The Burden of Image Based Emphysema and Bronchiolitis in HIV-Infected Individuals on Antiretroviral Therapy

    PubMed Central

    Guaraldi, Giovanni; Besutti, Giulia; Scaglioni, Riccardo; Santoro, Antonella; Zona, Stefano; Guido, Ligabue; Marchioni, Alessandro; Orlando, Gabriella; Carli, Federica; Beghe, Bianca; Fabbri, Leonardo; Leipsic, Jonathon; Sin, Don D.; Man, S. F. Paul

    2014-01-01

    Background With the widespread use of anti-retroviral therapy (ART), individuals infected with human immune deficiency virus (HIV) are increasingly experiencing morbidity and mortality from respiratory disorders. However, the prevalence or the risk factors associated with emphysema and bronchiolitis are largely unknown. Methods Thoracic computed tomography (CT) scans were performed in 1,446 patients infected with HIV who were on ART and who attended a tertiary care metabolic clinic (average age 48 years and 29% females). Detailed history and physical examination including anthropometric measurements were performed. Complete pulmonary function tests were performed in a subset of these patients (n = 364). No subjects were acutely ill with a respiratory condition at the time of CT scanning. Findings Nearly 50% of the subjects had CT evidence for emphysema, bronchiolitis or both with 13% (n = 195) showing bronchiolitis, 19% (n = 274) showing emphysema and 16% (n = 238) revealing both. These phenotypes were synergistically associated with reduced regular physical activity (p for interaction <.0001). The most significant risk factors for both phenotypes were cigarette smoking, intravenous drug use and peripheral leucocytosis. Together, the area-under-the curve statistics was 0.713 (p = 0.0037) for discriminating those with and without these phenotypes. There were no significant changes in lung volumes or flow rates related to these phenotypes, though the carbon monoxide diffusion capacity was reduced for the emphysema phenotype. Interpretation Emphysema and bronchiolitis are extremely common in HIV-infected patients who are treated with ART and can be identified by use of thoracic CT scanning. PMID:25354261

  3. Severe pulmonary hypertension due to combined pulmonary fibrosis and emphysema: another cause of death among smokers

    PubMed Central

    Hirano, André Carramenha de Góes; Targueta, Eduardo Pelegrineti; Martines, João Augusto dos Santos; Andrade, Dafne; Lovisolo, Silvana Maria; Felipe-Silva, Aloisio

    2017-01-01

    In 2005, the combined pulmonary fibrosis and emphysema (CPFE) was first defined as a distinct entity, which comprised centrilobular or paraseptal emphysema in the upper pulmonary lobes, and fibrosis in the lower lobes accompanied by reduced diffused capacity of the lungs for carbon monoxide (DLCO). Recently, the fibrosis associated with the connective tissue disease was also included in the diagnosis of CPFE, although the exposure to tobacco, coal, welding, agrochemical compounds, and tire manufacturing are the most frequent causative agents. This entity characteristically presents reduced DLCO with preserved lung volumes and severe pulmonary hypertension, which is not observed in emphysema and fibrosis alone. We present the case of a 63-year-old woman with a history of heavy tobacco smoking abuse, who developed progressive dyspnea, severe pulmonary hypertension, and cor pulmonale over a 2-year period. She attended the emergency facility several times complaining of worsening dyspnea that was treated as decompensate chronic obstructive pulmonary disease (COPD). The imaging examination showed paraseptal emphysema in the upper pulmonary lobes and fibrosis in the middle and lower lobes. The echo Doppler cardiogram revealed the dilation of the right cardiac chambers and pulmonary hypertension, which was confirmed by pulmonary trunk artery pressure measurement by catheterization. During this period, she was progressively restricted to the minimal activities of daily life and dependent on caregivers. She was brought to the hospital neurologically obtunded, presenting anasarca, and respiratory failure, which led her to death. The autopsy showed signs of pulmonary hypertension and findings of fibrosis and emphysema in the histological examination of the lungs. The authors highlight the importance of the recognition of this entity in case of COPD associated with severe pulmonary hypertension of unknown cause. PMID:28740835

  4. 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.

  5. Combined pulmonary fibrosis and emphysema (CPFE): an entity different from emphysema or pulmonary fibrosis alone

    PubMed Central

    Lin, Huijin

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) and idiopathic interstitial pneumonias (IIP), with different radiological, pathological, functional and prognostic characteristics, have been regarded as separate entities for a long time. However, there is an increasing recognition of the coexistence of emphysema and pulmonary fibrosis in individuals. The association was first described as a syndrome by Cottin in 2005, named “combined pulmonary fibrosis and emphysema (CPFE)”, which is characterized by exertional dyspnea, upper-lobe emphysema and lower-lobe fibrosis, preserved lung volume and severely diminished capacity of gas exchange. CPFE is frequently complicated by pulmonary hypertension, acute lung injury and lung cancer and prognosis of it is poor. Treatments for CPFE patients with severe pulmonary hypertension are less effective other than lung transplantation. However, CPFE has not yet attracted wide attention of clinicians and there is no research systematically contrasting the differences among CPFE, emphysema/COPD and IIP at the same time. The authors will review the existing knowledge of CPFE and compare them to either entity alone for the first time, with the purpose of improving the awareness of this syndrome and exploring novel effective therapeutic strategies in clinical practice. PMID:25973246

  6. 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

  7. 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.

  8. 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.

  9. Cathepsin E Promotes Pulmonary Emphysema via Mitochondrial Fission

    PubMed Central

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

    2015-01-01

    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. PMID:25239563

  10. Emphysema in active farmer’s lung disease

    PubMed Central

    Chardon, Marie-Laure; Dournes, Gaël; Laurent, Lucie; Degano, Bruno; Laurent, François; Dalphin, Jean Charles

    2017-01-01

    Background Farmer’s lung (FL) is a common type of hypersensitivity pneumonitis. It is often considered that fibrosis is the most frequent finding in chronic FL. Nevertheless, three cohort studies have suggested that some patients with chronic FL may develop emphysema. We aimed to evaluate the current prevalence of emphysema in active FL, to describe the radiological and functional features of emphysema in active FL, and to identify risk factors associated with emphysema in this population. Methods Patients aged over 18 years with active FL were prospectively recruited through the SOPHIA study (CPP Est; P-2009-521), between 2007 and 2015. Each patient had complete medical history screening, clinical examination, high resolution computed tomodensitometry, bronchoalveolar lavage, pulmonary function tests and serum precipitins. Results Among 33 patients with active FL, the prevalence of emphysema in this series of incident active FL cases was higher (48.5%) than that of fibrosis (12%) and was not dependent on smoking habits. Most patients with emphysema did not have lung hyperinflation. The possible risk factors for emphysema in active FL were a longer duration of exposure to organic dusts, and at a higher level. Conclusion Emphysema is found in half of patients with active FL and may be influenced by exposure patterns. PMID:28614400

  11. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Association of the transfer coefficient of the lung for carbon monoxide with emphysema progression in male smokers.

    PubMed

    Mohamed Hoesein, F A A; Zanen, P; van Ginneken, B; van Klaveren, R J; Lammers, J-W J

    2011-11-01

    A decreased transfer coefficient of the lung for carbon monoxide (K(CO)) is associated with emphysema. We evaluated whether in heavy smokers, baseline K(CO) was associated with the progression of computed tomography (CT)-detected emphysema, and the progression of airflow limitation. Heavy smokers, mean ± sd 41.3 ± 18.7 pack-yrs, participating in a lung cancer screening trial underwent diffusion testing and CT scanning of the lungs. CT scanning was repeated after median (25th-75th percentile) 2.8 (2.7-3.0) yrs and emphysema was assessed by lung densitometry using the 15th percentile. The association between K(CO) at baseline with progression of emphysema and lung function decline was assessed by multiple linear regression, correcting for baseline CT-quantified emphysema severity and forced expiratory volume in 1 s (FEV₁/forced vital capacity (FVC), age, height, body mass index, pack-yrs and smoking status (current or former smoker). 522 participants aged 60.1 ± 5.4 yrs were included. Mean ± sd 15th percentile was -938 ± 19, absolute FEV₁/FVC was 71.6 ± 9% and K(CO) was 1.23 ± 0.25, which is 81.8 ± 16.5% of predicted. By interpolation, a one sd (0.25) lower K(CO) value at baseline predicted a 1.6 HU lower 15th percentile and a 0.78% lower FEV₁/FVC after follow-up (p < 0.001). A lower baseline K(CO) value is independently associated with a more rapid progression of emphysema and airflow limitation in heavy smokers.

  13. 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

  14. 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.

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

    PubMed Central

    Kelly, Neil J.; Shapiro, Steven D.

    2014-01-01

    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. PMID:24569365

  16. 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.

  17. 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.

  18. Surgical Outcomes of Lung Cancer Patients with Combined Pulmonary Fibrosis and Emphysema and Those with Idiopathic Pulmonary Fibrosis without Emphysema.

    PubMed

    Sato, Seijiro; Koike, Terumoto; Hashimoto, Takehisa; Ishikawa, Hiroyuki; Okada, Akira; Watanabe, Takehiro; Tsuchida, Masanori

    2016-08-23

    Combined pulmonary fibrosis and emphysema (CPFE) is a unique disorder. The aim of this study was to compare the surgical outcomes of lung cancer patients with CPFE and those with idiopathic pulmonary fibrosis (IPF) without emphysema. A total of 1548 patients who underwent surgery for primary lung cancer between January 2001 and December 2012 were retrospectively reviewed. Of the 1548 patients, 55 (3.6%) had CPFE on computed tomography (CT), and 45 (2.9%) had IPF without emphysema. The overall and disease-free 5-year survival rates for patients with CPFE were not significantly worse than those for patients with IPF without emphysema (24.9% vs. 36.8%, p = 0.814; 39.8% vs. 39.3%, p = 0.653, respectively). Overall, 21 (38.1%) patients with CPFE and nine patients (20.0%) with IPF without emphysema developed postoperative cardiopulmonary complications. Patients with CPFE had significantly more postoperative cardiopulmonary complications involving pulmonary air leakage for >6 days, hypoxemia, and arrhythmia than patients with IPF without emphysema (p = 0.048). There was no significant difference in survival after surgical treatment between CPFE patients and IPF patients without emphysema, but CPFE patients had significantly higher morbidity than IPF patients without emphysema.

  19. 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.

  20. [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.

  1. 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

  2. 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

  3. 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.

  4. Posttraumatic orbital emphysema: a numerical model.

    PubMed

    Skorek, Andrzej; Kłosowski, Paweł; Plichta, Lukasz; Raczyńska, Dorota; Zmuda Trzebiatowski, Marcin; Lemski, Paweł

    2014-01-01

    Orbital emphysema is a common symptom accompanying orbital fracture. The pathomechanism is still not recognized and the usually assumed cause, elevated pressure in the upper airways connected with sneezing or coughing, does not always contribute to the occurrence of this type of fracture. Observations based on the finite model (simulating blowout type fracture) of the deformations of the inferior orbital wall after a strike in its lower rim. Authors created a computer numeric model of the orbit with specified features-thickness and resilience modulus. During simulation an evenly spread 14400 N force was applied to the nodular points in the inferior rim (the maximal value not causing cracking of the outer rim, but only ruptures in the inferior wall). The observation was made from 1 · 10(-3) to 1 · 10(-2) second after a strike. Right after a strike dislocations of the inferior orbital wall toward the maxillary sinus were observed. Afterwards a retrograde wave of the dislocation of the inferior wall toward the orbit was noticed. Overall dislocation amplitude reached about 6 mm. Based on a numeric model of the orbit submitted to a strike in the inferior wall an existence of a retrograde shock wave causing orbital emphysema has been found.

  5. Posttraumatic Orbital Emphysema: A Numerical Model

    PubMed Central

    Skorek, Andrzej; Kłosowski, Paweł; Plichta, Łukasz; Zmuda Trzebiatowski, Marcin; Lemski, Paweł

    2014-01-01

    Orbital emphysema is a common symptom accompanying orbital fracture. The pathomechanism is still not recognized and the usually assumed cause, elevated pressure in the upper airways connected with sneezing or coughing, does not always contribute to the occurrence of this type of fracture. Observations based on the finite model (simulating blowout type fracture) of the deformations of the inferior orbital wall after a strike in its lower rim. Authors created a computer numeric model of the orbit with specified features—thickness and resilience modulus. During simulation an evenly spread 14400 N force was applied to the nodular points in the inferior rim (the maximal value not causing cracking of the outer rim, but only ruptures in the inferior wall). The observation was made from 1 · 10−3 to 1 · 10−2 second after a strike. Right after a strike dislocations of the inferior orbital wall toward the maxillary sinus were observed. Afterwards a retrograde wave of the dislocation of the inferior wall toward the orbit was noticed. Overall dislocation amplitude reached about 6 mm. Based on a numeric model of the orbit submitted to a strike in the inferior wall an existence of a retrograde shock wave causing orbital emphysema has been found. PMID:25309749

  6. 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.

  7. Paratracheal air cysts: prevalence and relevance to pulmonary emphysema and bronchiectasis using thoracic multidetector CT.

    PubMed

    Boyaci, Nurefsan; Sen Dokumaci, Dilek; Karakas, Ekrem; Yalcin, Funda; Oney Kurnaz, Ayse Gul

    2015-01-01

    We aimed to determine the prevalence of paratracheal air cysts (PTACs) and the relationship of PTACs with emphysema and bronchiectasis through retrospective analysis of multidetector computed tomography (MDCT) findings. MDCT findings of 1027 consecutive patients who underwent routine thorax examination between January 2012 and January 2013 were evaluated retrospectively for the presence of PTACs. Localization of the PTACs, as well as their size, shape, and relationship with the trachea were examined. Presence of emphysema and bronchiectasis was recorded, and bronchiectasis severity index was calculated when present. We randomly selected 80 patients who had no visible PTACs as the control group. The findings of patients with and without PTACs were compared. PTACs were determined in 82 of 1027 patients (8%), in 8.8% of females and 7.3% of males. The presence of PTACs was determined to be independent of gender (P = 0.361). Eighty-one PTACs (98.8%) were located in the right side of the trachea and 56.1% had a tracheal connection. The presence of PTACs significantly correlated with the presence and severity of bronchiectasis (P = 0.001 and P = 0.005 respectively). There was no significant relationship between the presence of PTACs and the presence of emphysema on CT images (P = 0.125). The prevalence of PTACs was determined as 8% in this study. There was significant association between PTACs and bronchiectasis.

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

    PubMed

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

    2016-01-01

    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. 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. 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. 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.

  9. 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

  10. Role of computed tomography in quantitative assessment of emphysema

    PubMed Central

    Choromańska, Agnieszka; Macura, Katarzyna J.

    2012-01-01

    Summary Pulmonary emphysema, together with chronic bronchitis is a part of chronic obstructive pulmonary disease (COPD), which is one of the leading causes of death in the United States and worldwide. There are many methods to diagnose emphysema. Unfortunately many of them, for example pulmonary function tests (PFTs), clinical signs and conventional radiology are able to detect emphysema usually in its late stages when a great portion of lung parenchyma has been already destroyed by the disease. Computed tomography (CT) allows for early detection of emphysema. CT also makes it possible to quantify the total amount of emphysema in the lungs which is important in order to precisely estimate the severity of the disease. Those abilities of CT are important in monitoring the course of the disease and in attempts to prevent its further progression. In this review we discuss currently available methods for imaging emphysema with emphasis on the quantitative assessment of emphysema. To date, quantitative methods have not been widely used clinically, however, the initial results of several research studies regarding this subject are very encouraging. PMID:22802863

  11. 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.

  12. Lung Volume Reduction in Pulmonary Emphysema from the Radiologist's Perspective.

    PubMed

    Doellinger, F; Huebner, R H; Kuhnigk, J M; Poellinger, A

    2015-08-01

    Pulmonary emphysema causes decrease in lung function due to irreversible dilatation of intrapulmonary air spaces, which is linked to high morbidity and mortality. Lung volume reduction (LVR) is an invasive therapeutical option for pulmonary emphysema in order to improve ventilation mechanics. LVR can be carried out by lung resection surgery or different minimally invasive endoscopical procedures. All LVR-options require mandatory preinterventional evaluation to detect hyperinflated dysfunctional lung areas as target structures for treatment. Quantitative computed tomography can determine the volume percentage of emphysematous lung and its topographical distribution based on the lung's radiodensity. Modern techniques allow for lobebased quantification that facilitates treatment planning. Clinical tests still play the most important role in post-interventional therapy monitoring, but CT is crucial in the detection of postoperative complications and foreshadows the method's high potential in sophisticated experimental studies. Within the last ten years, LVR with endobronchial valves has become an extensively researched minimally-invasive treatment option. However, this therapy is considerably complicated by the frequent occurrence of functional interlobar shunts. The presence of "collateral ventilation" has to be ruled out prior to valve implantations, as the presence of these extraanatomical connections between different lobes may jeopardize the success of therapy. Recent experimental studies evaluated the automatic detection of incomplete lobar fissures from CT scans, because they are considered to be a predictor for the existence of shunts. To date, these methods are yet to show acceptable results. Today, surgical and various minimal invasive methods of lung volume reduction are in use. Radiological and nuclear medical examinations are helpful in the evaluation of an appropriate lung area. Imaging can detect periinterventional complications. Reduction of lung

  13. Increased collagen deposition correlated with lung destruction in human emphysema.

    PubMed

    Martin-Mosquero, C; Peces-Barba, G; Rubio, M L; Ortega, M; Rodriguez-Nieto, M J; Martinez Galan, L; Gonzalez-Mangado, N

    2006-08-01

    To study the relationship between collagen amount and degree of emphysema as assessed by mean linear intercept (Lm) and correlating these with lung function test workup in patients with and without COPD. Lung function tests were assessed in 16 smokers or ex-smokers and 1 non-smoker in order to separate them into two groups: COPD (FEV1/FVC lower than 70%) and non-COPD. A piece of lung tissue was used to analyse the collagen amount (HYP) by means of a colorimetric method. Morphometry was assessed to divide patients into two groups according to Lm: Lm > 260 micrometers was considered non-emphysema and Lm < 260 mm mild-emphysema. The non-emphysema group had a mean Lm value of 246.08+/-3.12 micrometers and the mild-emphysema group of 276.29+/-4.26 micrometers. The amount of hydroxyproline was significantly higher in the mild-emphysema group than in the non-emphysema group (7.82+/-0.67 vs. 5.50+/-0.54 microgram/g tissue). There was a clear positive correlation between Lm and HYP (r=0.55) and a negative correlation between Lm and DlCO (R=-0.5092). No correlation was found between the functional test and HYP, nor were there significant differences between COPD and non-COPD patients for Lm and HYP. Emphysema is associated with collagen deposition in the lungs, and air space size correlates with the amount of lung collagen even when there is no emphysema.

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. The use of subcutaneous drains to manage subcutaneous emphysema.

    PubMed

    Sherif, H M; Ott, D A

    1999-01-01

    Subcutaneous emphysema is a frequent complication of thoracic and cardiac surgical procedures, and emergency tracheostomy is often advocated as the treatment for this complication. However, we report the case of a patient in whom massive subcutaneous emphysema, which had developed after emergent replacement of the aortic root, was relieved using subcutaneous drains and suction, instead of a tracheostomy. We found that the subcutaneous drains provided effective decompression of the head and neck areas, and markedly reduced airway pressure and subcutaneous air. We recommend subcutaneous drains for safe, effective, and inexpensive management of massive subcutaneous emphysema.

  20. Fourteen-year-old girl with endobronchial carcinoid tumour presenting with asthma and lobar emphysema.

    PubMed

    Andersen, Julie Bjerglund; Mortensen, Jann; Damgaard, Karen; Skov, Marianne; Sparup, Jørgen; Petersen, Bodil Laub; Rechnitzer, Catherine; Borgwardt, Lise

    2010-04-01

    Bronchial carcinoid tumours seldom occur in children, and represent a rare cause of pulmonary obstruction. Because of low clinical suspicion and the variable ways of presentation, diagnosis may be delayed. We report on a patient with this tumour. It is hoped that increased awareness of the tumour can lead to earlier diagnosis. Report of a case. This case describes a 14-year-old previously healthy girl, presenting with asthma-like symptoms throughout 2 years, decreased lung function and emphysema in left lower lobe on chest x-ray. Computerized tomography (CT) showed an intraluminal process in the left main bronchus and emphysema in both the upper and lower left lobe and showed no signs of metastasis or spread to lung tissue. Bronchoscopy showed an inflammatory polyp. Surgical resection demonstrated a typical carcinoid tumour. Later control biopsy revealed no persisting malignant tissue. The asthma symptoms returned and a new bronchoscopy showed scarring and narrowing of the left bronchus. Treatment comprised of dilatation by bronchoscopy plus daily combination corticosteroids and beta-2-agonist inhalation and the symptoms improved. No signs of relapse 16 months postdiagnosis. The case clearly shows the delay, which is common in the diagnosis of children with bronchial carcinoid tumours. Symptoms of the obstructive nature of the tumour are variable and might present as emphysema seen on x-ray and CT. Carcinoid tumour should be considered in children with longstanding pulmonary symptoms with no response to conventional treatment. Prognosis is good but long-term follow up is needed.

  1. 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.

  2. Size variation and collapse of emphysema holes at inspiration and expiration CT scan: evaluation with modified length scale method and image co-registration

    PubMed Central

    Oh, Sang Young; Lee, Minho; Seo, Joon Beom; Kim, Namkug; Lee, Sang Min; Lee, Jae Seung; Oh, Yeon Mok

    2017-01-01

    A novel approach of size-based emphysema clustering has been developed, and the size variation and collapse of holes in emphysema clusters are evaluated at inspiratory and expiratory computed tomography (CT). Thirty patients were visually evaluated for the size-based emphysema clustering technique and a total of 72 patients were evaluated for analyzing collapse of the emphysema hole in this study. A new approach for the size differentiation of emphysema holes was developed using the length scale, Gaussian low-pass filtering, and iteration approach. Then, the volumetric CT results of the emphysema patients were analyzed using the new method, and deformable registration was carried out between inspiratory and expiratory CT. Blind visual evaluations of EI by two readers had significant correlations with the classification using the size-based emphysema clustering method (r-values of reader 1: 0.186, 0.890, 0.915, and 0.941; reader 2: 0.540, 0.667, 0.919, and 0.942). The results of collapse of emphysema holes using deformable registration were compared with the pulmonary function test (PFT) parameters using the Pearson’s correlation test. The mean extents of low-attenuation area (LAA), E1 (<1.5 mm), E2 (<7 mm), E3 (<15 mm), and E4 (≥15 mm) were 25.9%, 3.0%, 11.4%, 7.6%, and 3.9%, respectively, at the inspiratory CT, and 15.3%, 1.4%, 6.9%, 4.3%, and 2.6%, respectively at the expiratory CT. The extents of LAA, E2, E3, and E4 were found to be significantly correlated with the PFT parameters (r=−0.53, −0.43, −0.48, and −0.25), with forced expiratory volume in 1 second (FEV1; −0.81, −0.62, −0.75, and −0.40), and with diffusing capacity of the lungs for carbon monoxide (cDLco), respectively. The fraction of emphysema that shifted to the smaller subgroup showed a significant correlation with FEV1, cDLco, forced expiratory flow at 25%–75% of forced vital capacity, and residual volume (RV)/total lung capacity (r=0.56, 0.73, 0.40, and −0.58). A detailed

  3. Size variation and collapse of emphysema holes at inspiration and expiration CT scan: evaluation with modified length scale method and image co-registration.

    PubMed

    Oh, Sang Young; Lee, Minho; Seo, Joon Beom; Kim, Namkug; Lee, Sang Min; Lee, Jae Seung; Oh, Yeon Mok

    2017-01-01

    A novel approach of size-based emphysema clustering has been developed, and the size variation and collapse of holes in emphysema clusters are evaluated at inspiratory and expiratory computed tomography (CT). Thirty patients were visually evaluated for the size-based emphysema clustering technique and a total of 72 patients were evaluated for analyzing collapse of the emphysema hole in this study. A new approach for the size differentiation of emphysema holes was developed using the length scale, Gaussian low-pass filtering, and iteration approach. Then, the volumetric CT results of the emphysema patients were analyzed using the new method, and deformable registration was carried out between inspiratory and expiratory CT. Blind visual evaluations of EI by two readers had significant correlations with the classification using the size-based emphysema clustering method (r-values of reader 1: 0.186, 0.890, 0.915, and 0.941; reader 2: 0.540, 0.667, 0.919, and 0.942). The results of collapse of emphysema holes using deformable registration were compared with the pulmonary function test (PFT) parameters using the Pearson's correlation test. The mean extents of low-attenuation area (LAA), E1 (<1.5 mm), E2 (<7 mm), E3 (<15 mm), and E4 (≥15 mm) were 25.9%, 3.0%, 11.4%, 7.6%, and 3.9%, respectively, at the inspiratory CT, and 15.3%, 1.4%, 6.9%, 4.3%, and 2.6%, respectively at the expiratory CT. The extents of LAA, E2, E3, and E4 were found to be significantly correlated with the PFT parameters (r=-0.53, -0.43, -0.48, and -0.25), with forced expiratory volume in 1 second (FEV1; -0.81, -0.62, -0.75, and -0.40), and with diffusing capacity of the lungs for carbon monoxide (cDLco), respectively. The fraction of emphysema that shifted to the smaller subgroup showed a significant correlation with FEV1, cDLco, forced expiratory flow at 25%-75% of forced vital capacity, and residual volume (RV)/total lung capacity (r=0.56, 0.73, 0.40, and -0.58). A detailed assessment of the size

  4. Genetic polymorphism in matrix metalloproteinase-9 and transforming growth factor-β1 and susceptibility to combined pulmonary fibrosis and emphysema in a Chinese population.

    PubMed

    Xu, Ling; Bian, Wei; Gu, Xiao-Hua; Shen, Ce

    2017-03-01

    In this study, we aimed to explore the association of genetic polymorphism in matrix metalloproteinase-9 (MMP-9) and transforming growth factor-β1 (TGF-β1) and the susceptibility to combined pulmonary fibrosis and emphysema (CPFE). We examined the polymorphisms of the MMP-9 C-1562T and TGF-β1 T869C in 38 CPFE patients, 50 pulmonary emphysema patients, and 34 idiopathic pulmonary fibrosis (IPF) patients. The frequencies of polymorphic genotypes in MMP-9 were 78.95% CC and 21.05% CT in CPFE group, 76.0% CC and 24.0% CT in emphysema group, and 100.0% CC in IPF group. There were highly statistically significant increased frequencies of the CT genotype and T allele in CPFE and emphysema groups compared with IPF group (p < 0.05). The frequencies of polymorphic genotypes in TGF-β1 were 2.63% CC, 28.95% CT, 68.42% TT in CPFE group, 4.00% CC, 16.00% CT, 80.00% TT in emphysema group, and 5.88% CC, 41.18% CT, 52.94% TT in IPF group. Significant increases in the TT genotype and T allele frequencies were observed in emphysema group compared with IPF group (p < 0.05). Our study has showed that T allele in MMP-9 (C-1562T) and T allele in TGF-β1 (T869C) are risk factors of pulmonary emphysema. The T allele in MMP-9 (C-1562T) possibly predisposes patients with pulmonary fibrosis to develop emphysema. Copyright © 2017. Published by Elsevier Taiwan.

  5. 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.

  6. Impact of combined pulmonary fibrosis and emphysema on surgical complications and long-term survival in patients undergoing surgery for non-small-cell lung cancer.

    PubMed

    Hata, Atsushi; Sekine, Yasuo; Kota, Ohashi; Koh, Eitetsu; Yoshino, Ichiro

    2016-01-01

    The outcome of radical surgery for lung cancer was investigated in patients with combined pulmonary fibrosis and emphysema (CPFE). A retrospective chart review involved 250 patients with lung cancer who underwent pulmonary resection at Tokyo Women's Medical University Yachiyo Medical Center between 2008 and 2012. Based on the status of nontumor-bearing lung evaluated by preoperative computed tomography (CT), the patients were divided into normal, emphysema, interstitial pneumonia (IP), and CPFE groups, and their clinical characteristics and surgical outcome were analyzed. The normal, emphysema, IP, and CPFE groups comprised 124 (49.6%), 108 (43.2%), seven (2.8%), and eleven (4.4%) patients, respectively. The 5-year survival rate of the CPFE group (18.7%) was significantly lower than that of the normal (77.5%) and emphysema groups (67.1%) (P<0.0001 and P=0.0027, respectively) but equivalent to that of the IP group (44.4%) (P=0.2928). In a subset analysis of cancer stage, the 5-year overall survival rate of the CPFE group in stage I (n=8, 21.4%) was also lower than that of the normal group and emphysema group in stage I (n=91, 84.9% and n=70, 81.1%; P<0.0001 and P<0.0001, respectively). During entire observation period, the CPFE group was more likely to die of respiratory failure (27.2%) compared with the normal and emphysema groups (P<0.0001). Multivariate analysis of prognostic factors using Cox proportional hazard model identified CPFE as an independent risk factor (P=0.009). CPFE patients have a poorer prognosis than those with emphysema alone or with normal lung on CT finding. The intensive evaluation of preoperative CT images is important, and radical surgery for lung cancer should be decided carefully when patients concomitantly harbor CPFE, because of unfavorable prognosis.

  7. 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. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Granulomatosis with polyangiitis and associated pulmonary emphysema: Breathtaking vasculitis.

    PubMed

    Gadre, Shruti K; Stoller, James K; Mehta, Atul C

    2015-01-01

    Pulmonary emphysema occasionally occurs in the absence of smoking or noxious exposures. Other than through a known association with alpha-1 antitryspin deficiency, to our knowledge, no reports implicate granulomatosis with polyangiitis (GPA) in causing airflow obstruction with small airway involvement and severe air trapping. To extend available experience, we report a 51-year-old male with biopsy-proven cytoplasmic-antineutrophilic cytoplasmic antibody proteinase 3 (ANCA PR3)-positive GPA who developed centrilobular emphysema and airflow obstruction during a phase of active vasculitis. He was a lifelong non-smoker and had a normal alpha-1 antitrypsin level and a PI*MM phenotype. Treatment with corticosteroids and cyclophosphamide caused clinical remission of his vasculitis which was associated with improvement in his respiratory symptoms. However, to date, structural changes of emphysema have persisted for over 9 years of follow-up. Clinicians should remain vigilant to the possibility of emphysema in patients with pulmonary vasculitis.

  9. Granulomatosis with polyangiitis and associated pulmonary emphysema: Breathtaking vasculitis

    PubMed Central

    Gadre, Shruti K.; Stoller, James K.; Mehta, Atul C.

    2015-01-01

    Pulmonary emphysema occasionally occurs in the absence of smoking or noxious exposures. Other than through a known association with alpha-1 antitryspin deficiency, to our knowledge, no reports implicate granulomatosis with polyangiitis (GPA) in causing airflow obstruction with small airway involvement and severe air trapping. To extend available experience, we report a 51-year-old male with biopsy-proven cytoplasmic–antineutrophilic cytoplasmic antibody proteinase 3 (ANCA PR3)-positive GPA who developed centrilobular emphysema and airflow obstruction during a phase of active vasculitis. He was a lifelong non-smoker and had a normal alpha-1 antitrypsin level and a PI*MM phenotype. Treatment with corticosteroids and cyclophosphamide caused clinical remission of his vasculitis which was associated with improvement in his respiratory symptoms. However, to date, structural changes of emphysema have persisted for over 9 years of follow-up. Clinicians should remain vigilant to the possibility of emphysema in patients with pulmonary vasculitis. PMID:26180387

  10. 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.

  11. 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.

  12. [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.

  13. 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.

  14. 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.

  15. 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.

  16. Genome-Wide Study of Percent Emphysema on Computed Tomography in the General Population. The Multi-Ethnic Study of Atherosclerosis Lung/SNP Health Association Resource Study

    PubMed Central

    Manichaikul, Ani; Hoffman, Eric A.; Smolonska, Joanna; Gao, Wei; Cho, Michael H.; Baumhauer, Heather; Budoff, Matthew; Austin, John H. M.; Washko, George R.; Carr, J. Jeffrey; Kaufman, Joel D.; Pottinger, Tess; Powell, Charles A.; Wijmenga, Cisca; Zanen, Pieter; Groen, Harry J. M.; Postma, Dirkje S.; Wanner, Adam; Rouhani, Farshid N.; Brantly, Mark L.; Powell, Rhea; Smith, Benjamin M.; Rabinowitz, Dan; Raffel, Leslie J.; Hinckley Stukovsky, Karen D.; Crapo, James D.; Beaty, Terri H.; Hokanson, John E.; Silverman, Edwin K.; Dupuis, Josée; O’Connor, George T.; Boezen, H. Marike; Rich, Stephen S.

    2014-01-01

    Rationale: Pulmonary emphysema overlaps partially with spirometrically defined chronic obstructive pulmonary disease and is heritable, with moderately high familial clustering. Objectives: To complete a genome-wide association study (GWAS) for the percentage of emphysema-like lung on computed tomography in the Multi-Ethnic Study of Atherosclerosis (MESA) Lung/SNP Health Association Resource (SHARe) Study, a large, population-based cohort in the United States. Methods: We determined percent emphysema and upper-lower lobe ratio in emphysema defined by lung regions less than −950 HU on cardiac scans. Genetic analyses were reported combined across four race/ethnic groups: non-Hispanic white (n = 2,587), African American (n = 2,510), Hispanic (n = 2,113), and Chinese (n = 704) and stratified by race and ethnicity. Measurements and Main Results: Among 7,914 participants, we identified regions at genome-wide significance for percent emphysema in or near SNRPF (rs7957346; P = 2.2 × 10−8) and PPT2 (rs10947233; P = 3.2 × 10−8), both of which replicated in an additional 6,023 individuals of European ancestry. Both single-nucleotide polymorphisms were previously implicated as genes influencing lung function, and analyses including lung function revealed independent associations for percent emphysema. Among Hispanics, we identified a genetic locus for upper-lower lobe ratio near the α-mannosidase–related gene MAN2B1 (rs10411619; P = 1.1 × 10−9; minor allele frequency [MAF], 4.4%). Among Chinese, we identified single-nucleotide polymorphisms associated with upper-lower lobe ratio near DHX15 (rs7698250; P = 1.8 × 10−10; MAF, 2.7%) and MGAT5B (rs7221059; P = 2.7 × 10−8; MAF, 2.6%), which acts on α-linked mannose. Among African Americans, a locus near a third α-mannosidase–related gene, MAN1C1 (rs12130495; P = 9.9 × 10−6; MAF, 13.3%) was associated with percent emphysema. Conclusions: Our results suggest that some genes previously identified as

  17. Pulmonary function and emphysema in Williams-Beuren syndrome.

    PubMed

    Wan, Emily S; Pober, Barbara R; Washko, George R; Raby, Benjamin A; Silverman, Edwin K

    2010-03-01

    Williams-Beuren syndrome (WBS) is caused by a submicroscopic deletion on chromosome 7q11.23 that encompasses the entire elastin (ELN) gene. Elastin, a key component of elastic fibers within the lung, is progressively destroyed in emphysema. Defects in the elastin gene have been associated with increased susceptibility towards developing chronic obstructive pulmonary disease (COPD) and emphysema in both humans and mice. We postulate that hemizygosity at the elastin gene locus may increase susceptibility towards the development of COPD and emphysema in subjects with WBS. We describe an adult subject with WBS who was a lifelong non-smoker and was found to have moderate emphysema. We also examined the pulmonary function of a separate cohort of adolescents and young adults with WBS. Although no significant spirometric abnormalities were identified, a significant proportion of subjects reported respiratory symptoms. Thus, while significant obstructive disease does not appear to be common in relatively young adults with WBS, subclinical emphysema and lung disease may exist which possibly could worsen with advancing age. Further investigation may elucidate the pathogenesis of non-smoking-related emphysema. (c) 2010 Wiley-Liss, Inc.

  18. 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.

  19. Improved diagnosis of pulmonary emphysema using in vivo dark-field radiography.

    PubMed

    Meinel, Felix G; Yaroshenko, Andre; Hellbach, Katharina; Bech, Martin; Müller, Mark; Velroyen, Astrid; Bamberg, Fabian; Eickelberg, Oliver; Nikolaou, Konstantin; Reiser, Maximilian F; Pfeiffer, Franz; Yildirim, Ali Ö

    2014-10-01

    The purpose of this study was to assess whether the recently developed method of grating-based x-ray dark-field radiography can improve the diagnosis of pulmonary emphysema in vivo. Pulmonary emphysema was induced in female C57BL/6N mice using endotracheal instillation of porcine pancreatic elastase and confirmed by in vivo pulmonary function tests, histopathology, and quantitative morphometry. The mice were anesthetized but breathing freely during imaging. Experiments were performed using a prototype small-animal x-ray dark-field scanner that was operated at 35 kilovolt (peak) with an exposure time of 5 seconds for each of the 10 grating steps. Images were compared visually. For quantitative comparison of signal characteristics, regions of interest were placed in the upper, middle, and lower zones of each lung. Receiver-operating-characteristic statistics were performed to compare the effectiveness of transmission and dark-field signal intensities and the combined parameter "normalized scatter" to differentiate between healthy and emphysematous lungs. A clear visual difference between healthy and emphysematous mice was found for the dark-field images. Quantitative measurements of x-ray dark-field signal and normalized scatter were significantly different between the mice with pulmonary emphysema and the control mice and showed good agreement with pulmonary function tests and quantitative histology. The normalized scatter showed a significantly higher discriminatory power (area under the receiver-operating-characteristic curve [AUC], 0.99) than dark-field (AUC, 0.90; P = 0.01) or transmission signal (AUC, 0.69; P < 0.001) alone did, allowing for an excellent discrimination of healthy and emphysematous lung regions. In a murine model, x-ray dark-field radiography is technically feasible in vivo and represents a substantial improvement over conventional transmission-based x-ray imaging for the diagnosis of pulmonary emphysema.

  20. Pulmonary capillaritis and its relationship to development of emphysema in hypocomplementaemic urticarial vasculitis syndrome.

    PubMed

    Hunt, David P J; Weil, Rimona; Nicholson, Andrew G; Burke, Margaret M; Du Bois, Ron M; Wells, Athol U

    2006-03-01

    Hypocomplementaemic urticarial vasculitis syndrome (HUVS) is a rare disorder characterised by complement activation and the presence of C1q precipitins together with a syndrome of urticarial vasculitis, angioedema, arthralgia, ocular inflammation, glomerulonephritis and obstructive lung disease. The pathophysiology of the obstructive airways disease is poorly understood. We report a 46 year-old woman with HUVS who developed progressive obstructive airways disease. Lung biopsy early in the course of her disease revealed pulmonary capillaritis. The disease progressed despite treatment with steroids and cyclosporin and the patient eventually underwent successful double lung transplantation. The explanted lung showed the coexistence of a patchy active vasculitis with severe panacinar emphysema. This is the first description of the histopathological process of HUVS in an explanted lung. Through analysis of serial histopathological specimens and clinical data we show the evolution of pulmonary capillaritis to emphysema, and demonstrate that active vasculitis can coexist with emphysema in patients with HUVS and obstructive airways disease. We suggest that there is a role for ongoing immunosuppressive therapy in these patients.

  1. 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.

  2. Purinergic receptor inhibition prevents the development of smoke-induced lung injury and emphysema.

    PubMed

    Cicko, Sanja; Lucattelli, Monica; Müller, Tobias; Lommatzsch, Marek; De Cunto, Giovanna; Cardini, Silvia; Sundas, William; Grimm, Melanine; Zeiser, Robert; Dürk, Thorsten; Zissel, Gernot; Boeynaems, Jean-Marie; Sorichter, Stephan; Ferrari, Davide; Di Virgilio, Francesco; Virchow, J Christian; Lungarella, Giuseppe; Idzko, Marco

    2010-07-01

    Extracellular ATP acts as a "danger signal" and can induce inflammation by binding to purinergic receptors. Chronic obstructive pulmonary disease is one of the most common inflammatory diseases associated with cigarette smoke inhalation, but the underlying mechanisms are incompletely understood. In this study, we show that endogenous pulmonary ATP levels are increased in a mouse model of smoke-induced acute lung inflammation and emphysema. ATP neutralization or nonspecific P2R-blockade markedly reduced smoke-induced lung inflammation and emphysema. We detected an upregulation the purinergic receptors subtypes on neutrophils (e.g., P2Y2R), macrophages, and lung tissue from animals with smoke-induced lung inflammation. By using P2Y(2)R deficient ((-/-)) animals, we show that ATP induces the recruitment of blood neutrophils to the lungs via P2Y(2)R. Moreover, P2Y(2)R deficient animals had a reduced pulmonary inflammation following acute smoke-exposure. A series of experiments with P2Y(2)R(-/-) and wild type chimera animals revealed that P2Y(2)R expression on hematopoietic cell plays the pivotal role in the observed effect. We demonstrate, for the first time, that endogenous ATP contributes to smoke-induced lung inflammation and then development of emphysema via activation of the purinergic receptor subtypes, such as P2Y(2)R.

  3. [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).

  4. Association Between Airway Caliber Changes With Lung Inflation and Emphysema Assessed by Volumetric CT Scan in Subjects With COPD

    PubMed Central

    Come, Carolyn E.; Ross, James C.; San José Estépar, Raúl; Han, MeiLan K.; Loring, Stephen H.; Silverman, Edwin K.; Washko, George R.

    2012-01-01

    Background: An increase in airway caliber (airway distensibility) with lung inflation is attenuated in COPD. Furthermore, some subjects have a decrease in airway caliber with lung inflation. We aimed to test the hypothesis that airway caliber increases are lower in subjects with emphysema-predominant (EP) compared with airway-predominant (AP) CT scan subtypes. Additionally, we compared clinical and CT scan features of subjects with (airway constrictors) and without a decrease in airway caliber. Methods: Based on GOLD (Global Initiative for Chronic Obstructive Lung Disease) stages and CT scan subtypes, we created a control group (n = 46) and the following matched COPD groups (n = 23 each): GOLD-2-AP, GOLD-2-EP, GOLD-4-AP, and GOLD-4-EP. From the CT scans of all 138 subjects, we measured emphysema, lung volumes, and caliber changes in the third and fourth airway generations of two bronchi. We expressed airway distensibility (ratio of airway lumen diameter change to lung volume change from end tidal breathing to full inspiration) as a global or lobar measure based on normalization by whole-lung or lobar volume changes. Results: Global distensibility in the third and fourth airway generations was significantly lower in the GOLD-2-EP and GOLD-4-EP groups than in control subjects. In GOLD-2 subjects, lobar distensibility of the right-upper-lobe fourth airway generation was significantly lower in those with EP than in those with AP. In multivariate analysis, emphysema was an independent determinant of global and lobar airway distensibility. Compared with nonconstrictors, airway constrictors experienced more dyspnea, were more hyperinflated, and had a higher percentage of emphysema. Conclusions: Distensibility of large- to medium-sized airways is reduced in subjects with an EP CT scan subtype. Emphysema seems to alter airway-parenchyma interdependence. Trial registry: ClinicalTrials.gov; No.: NCT00608764; URL: www.clinicaltrials.gov PMID:21940776

  5. 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.

  6. 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

  7. Religious and spiritual coping and quality of life among patients with emphysema in the National Emphysema Treatment Trial.

    PubMed

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

    2011-10-01

    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. 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. 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. 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. 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.

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. Contrasting geographical distribution of mortality from pneumoconiosis and chronic bronchitis and emphysema in British coal miners.

    PubMed Central

    Coggon, D; Inskip, H; Winter, P; Pannett, B

    1995-01-01

    To explore whether the characteristics of coal mine dust that predispose to chronic airways obstruction are the same as those associated with pneumoconiosis, mortality from the two disease was compared in coal miners in 22 counties of England and Wales during 1979-80 and 1982-90. The proportional mortality ratios (PMRs) for coal workers' pneumoconiosis varied from 135 (95% confidence interval (95% CI) 16-488) in Leicestershire to 3825 (95% CI 1538-7881) in South Glamorgan. The PMRs for chronic bronchitis and emphysema were consistently higher than those in other occupations, but showed much less geographical variation and did not correlate geographically with those for pneumoconiosis. These findings indicate that the pathogenetic mechanisms by which coal mine dust causes chronic bronchitis and emphysema depend on different features of the dust from those producing pneumoconiosis. Also, they suggest that current social security regulations in Britain, which require evidence of pneumoconiosis as a condition of compensation for chronic bronchitis and emphysema in coal miners, may discriminate unfairly against claimants from some regions. PMID:7663643

  13. Severe Emphysema Treated by Endoscopic Bronchial Volume Reduction with Lung Sealant (AeriSeal)

    PubMed Central

    Falkenstern-Ge, R. F.; Ingerl, H.; Kohlhäufl, M.

    2013-01-01

    Endoscopic lung volume reduction using lung sealant is a very new and innovative treatment option for patients with severe progressive and irreversible lung emphysema. A 55-year-old ex-smoker (60 pack years) referred to our center because of severe lung emphysema with progressive worsening of the obstructive ventilator pattern and clinical condition. We detected collateral channels of this patient by using the Chartis system. Therefore, we decided to treat the advanced emphysema of our patient with endoscopic volume reduction using lung sealant (AeriSeal). The foam of lung sealant AeriSeal is instilled into the peripheral airways and alveoli where it polymerizes and functions as tissue glue on the lung surface in order to seal the target region to cause durable irreversible absorption atelectasis. The follow-up evaluation 12 weeks later showed improved lung function (increased FEV 1/partial oxygen pressure/peripheral oxygen saturation and a reduction of TLC and RV) with improved quality of life. Correlation between changes in primary and secondary outcome measures in the lung function parameters and 6-minute-walking test before and 12 weeks after the application of lung sealant revealed significant reduction of hyperinflation and improvement both in the flow rates and in the physical capability of this patient. PMID:23710404

  14. 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.

  15. Bacteriological incidence in pneumonia patients with pulmonary emphysema: a bacterial floral analysis using the 16S ribosomal RNA gene in bronchoalveolar lavage fluid

    PubMed Central

    Naito, Keisuke; Yamasaki, Kei; Yatera, Kazuhiro; Akata, Kentaro; Noguchi, Shingo; Kawanami, Toshinori; Fukuda, Kazumasa; Kido, Takashi; Ishimoto, Hiroshi; Mukae, Hiroshi

    2017-01-01

    Pulmonary emphysema is an important radiological finding in chronic obstructive pulmonary disease patients, but bacteriological differences in pneumonia patients according to the severity of emphysematous changes have not been reported. Therefore, we evaluated the bacteriological incidence in the bronchoalveolar lavage fluid (BALF) of pneumonia patients using cultivation and a culture-independent molecular method. Japanese patients with community-acquired pneumonia (83) and healthcare-associated pneumonia (94) between April 2010 and February 2014 were evaluated. The BALF obtained from pneumonia lesions was evaluated by both cultivation and a molecular method. In the molecular method, ~600 base pairs of bacterial 16S ribosomal RNA genes in the BALF were amplified by polymerase chain reaction, and clone libraries were constructed. The nucleotide sequences of 96 randomly selected colonies were determined, and a homology search was performed to identify the bacterial species. A qualitative radiological evaluation of pulmonary emphysema based on chest computed tomography (CT) images was performed using the Goddard classification. The severity of pulmonary emphysema based on the Goddard classification was none in 47.4% (84/177), mild in 36.2% (64/177), moderate in 10.2% (18/177), and severe in 6.2% (11/177). Using the culture-independent molecular method, Moraxella catarrhalis was significantly more frequently detected in moderate or severe emphysema patients than in patients with no or mild emphysematous changes. The detection rates of Haemophilus influenzae and Pseudomonas aeruginosa were unrelated to the severity of pulmonary emphysematous changes, and Streptococcus species – except for the S. anginosus group and S. pneumoniae – were detected more frequently using the molecular method we used for the BALF of patients with pneumonia than using culture methods. Our findings suggest that M. catarrhalis is more frequently detected in pneumonia patients with moderate

  16. Bacteriological incidence in pneumonia patients with pulmonary emphysema: a bacterial floral analysis using the 16S ribosomal RNA gene in bronchoalveolar lavage fluid.

    PubMed

    Naito, Keisuke; Yamasaki, Kei; Yatera, Kazuhiro; Akata, Kentaro; Noguchi, Shingo; Kawanami, Toshinori; Fukuda, Kazumasa; Kido, Takashi; Ishimoto, Hiroshi; Mukae, Hiroshi

    2017-01-01

    Pulmonary emphysema is an important radiological finding in chronic obstructive pulmonary disease patients, but bacteriological differences in pneumonia patients according to the severity of emphysematous changes have not been reported. Therefore, we evaluated the bacteriological incidence in the bronchoalveolar lavage fluid (BALF) of pneumonia patients using cultivation and a culture-independent molecular method. Japanese patients with community-acquired pneumonia (83) and healthcare-associated pneumonia (94) between April 2010 and February 2014 were evaluated. The BALF obtained from pneumonia lesions was evaluated by both cultivation and a molecular method. In the molecular method, ~600 base pairs of bacterial 16S ribosomal RNA genes in the BALF were amplified by polymerase chain reaction, and clone libraries were constructed. The nucleotide sequences of 96 randomly selected colonies were determined, and a homology search was performed to identify the bacterial species. A qualitative radiological evaluation of pulmonary emphysema based on chest computed tomography (CT) images was performed using the Goddard classification. The severity of pulmonary emphysema based on the Goddard classification was none in 47.4% (84/177), mild in 36.2% (64/177), moderate in 10.2% (18/177), and severe in 6.2% (11/177). Using the culture-independent molecular method, Moraxella catarrhalis was significantly more frequently detected in moderate or severe emphysema patients than in patients with no or mild emphysematous changes. The detection rates of Haemophilus influenzae and Pseudomonas aeruginosa were unrelated to the severity of pulmonary emphysematous changes, and Streptococcus species - except for the S. anginosus group and S. pneumoniae - were detected more frequently using the molecular method we used for the BALF of patients with pneumonia than using culture methods. Our findings suggest that M. catarrhalis is more frequently detected in pneumonia patients with moderate or

  17. Computed Tomography Measurement of Rib Cage Morphometry in Emphysema

    PubMed Central

    Sverzellati, Nicola; Colombi, Davide; Randi, Giorgia; Pavarani, Antonio; Silva, Mario; Walsh, Simon L.; Pistolesi, Massimo; Alfieri, Veronica; Chetta, Alfredo; Vaccarezza, Mauro; Vitale, Marco; Pastorino, Ugo

    2013-01-01

    Background Factors determining the shape of the human rib cage are not completely understood. We aimed to quantify the contribution of anthropometric and COPD-related changes to rib cage variability in adult cigarette smokers. Methods Rib cage diameters and areas (calculated from the inner surface of the rib cage) in 816 smokers with or without COPD, were evaluated at three anatomical levels using computed tomography (CT). CTs were analyzed with software, which allows quantification of total emphysema (emphysema%). The relationship between rib cage measurements and anthropometric factors, lung function indices, and %emphysema were tested using linear regression models. Results A model that included gender, age, BMI, emphysema%, forced expiratory volume in one second (FEV1)%, and forced vital capacity (FVC)% fit best with the rib cage measurements (R2 = 64% for the rib cage area variation at the lower anatomical level). Gender had the biggest impact on rib cage diameter and area (105.3 cm2; 95% CI: 111.7 to 98.8 for male lower area). Emphysema% was responsible for an increase in size of upper and middle CT areas (up to 5.4 cm2; 95% CI: 3.0 to 7.8 for an emphysema increase of 5%). Lower rib cage areas decreased as FVC% decreased (5.1 cm2; 95% CI: 2.5 to 7.6 for 10 percentage points of FVC variation). Conclusions This study demonstrates that simple CT measurements can predict rib cage morphometric variability and also highlight relationships between rib cage morphometry and emphysema. PMID:23935872

  18. 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.

  19. Retinoic acid-related orphan receptor-α is induced in the setting of DNA damage and promotes pulmonary emphysema.

    PubMed

    Shi, Ying; Cao, Jiaofei; Gao, Jane; Zheng, Liang; Goodwin, Andrew; An, Chang Hyoek; Patel, Avignat; Lee, Janet S; Duncan, Steven R; Kaminski, Naftali; Pandit, Kusum V; Rosas, Ivan O; Choi, Augustine M K; Morse, Danielle

    2012-09-01

    The discovery that retinoic acid-related orphan receptor (Rora)-α is highly expressed in lungs of patients with COPD led us to hypothesize that Rora may contribute to the pathogenesis of emphysema. To determine the role of Rora in smoke-induced emphysema. Cigarette smoke extract in vitro and elastase or cigarette smoke exposure in vivo were used to model smoke-related cell stress and airspace enlargement. Lung tissue from patients undergoing lung transplantation was examined for markers of DNA damage and Rora expression. Rora expression was induced by cigarette smoke in mice and in cell culture. Gene expression profiling of Rora-null mice exposed to cigarette smoke demonstrated enrichment for genes involved in DNA repair. Rora expression increased and Rora translocated to the nucleus after DNA damage. Inhibition of ataxia telangiectasia mutated decreased the induction of Rora. Gene silencing of Rora attenuated apoptotic cell death in response to cigarette smoke extract, whereas overexpression of Rora enhanced apoptosis. Rora-deficient mice were protected from elastase and cigarette smoke induced airspace enlargement. Finally, lungs of patients with COPD showed evidence of increased DNA damage even in the absence of active smoking. Taken together, these findings suggest that DNA damage may contribute to the pathogenesis of emphysema, and that Rora has a previously unrecognized role in cellular responses to genotoxicity. These findings provide a potential link between emphysema and features of premature ageing, including enhanced susceptibility to lung cancer.

  20. The Effect of PPE-Induced Emphysema and Chronic LPS-Induced Pulmonary Inflammation on Atherosclerosis Development in APOE*3-LEIDEN Mice

    PubMed Central

    Wagenaar, Gerry T. M.; Plomp, Jaap J.; van Eck, Miranda; Havekes, Louis M.; Rensen, Patrick C. N.; Hiemstra, Pieter S.; Berbée, Jimmy F. P.

    2013-01-01

    Background Chronic obstructive pulmonary disease (COPD) is characterized by pulmonary inflammation, airways obstruction and emphysema, and is a risk factor for cardiovascular disease (CVD). However, the contribution of these individual COPD components to this increased risk is unknown. Therefore, the aim of this study was to determine the contribution of emphysema in the presence or absence of pulmonary inflammation to the increased risk of CVD, using a mouse model for atherosclerosis. Because smoke is a known risk factor for both COPD and CVD, emphysema was induced by intratracheal instillation of porcine pancreatic elastase (PPE). Methods Hyperlipidemic APOE*3-Leiden mice were intratracheally instilled with vehicle, 15 or 30 µg PPE and after 4 weeks, mice received a Western-type diet (WTD). To study the effect of emphysema combined with pulmonary inflammation on atherosclerosis, mice received 30 µg PPE and during WTD feeding, mice were intranasally instilled with vehicle or low-dose lipopolysaccharide (LPS; 1 µg/mouse, twice weekly). After 20 weeks WTD, mice were sacrificed and emphysema, pulmonary inflammation and atherosclerosis were analysed. Results Intratracheal PPE administration resulted in a dose-dependent increase in emphysema, whereas atherosclerotic lesion area was not affected by PPE treatment. Additional low-dose intranasal LPS administration induced a low-grade systemic IL-6 response, as compared to vehicle. Combining intratracheal PPE with intranasal LPS instillation significantly increased the number of pulmonary macrophages and neutrophils. Plasma lipids during the study were not different. LPS instillation caused a limited, but significant increase in the atherosclerotic lesion area. This increase was not further enhanced by PPE. Conclusion This study shows for the first time that PPE-induced emphysema both in the presence and absence of pulmonary inflammation does not affect atherosclerotic lesion development. PMID:24303000

  1. Histologically proven extrinsic allergic alveolitis with severe obstructive pulmonary emphysema

    PubMed

    Bickhardt; Kunze; Rolle; Matthiessen

    2000-03-27

    Anamnesis: 61-year old man with progressive shortness of breath on exercise. Cough and expectoration during the last 6 years. - Exposure: Driver of cereals, massive exposure to mouldy and pest contaminated grains. Gave up his profession in 1979 due to dyspnea with short (2-3 h) latency after exposure. Since 1980 intermittent exposure during occasional jobs; renewed symptomatology. Aspergillus fumigatus detected on agar plates inoculated with material from wet areas in bathroom and kitchen. - Clinical symptoms: Barely audible vesicular breathing, barrel-shaped thorax, inspiratory-intercostal retraction. - Bodyplethysmography: Obstructive pulmonary emphysema with FEV1 0.8 l, TLC 7.8 l, RV/TLC relation 67%. - Precipitin-detection: Significantly increased IgG against Fusarium. Other moulds including Aspergillus: negative; thermophilic actinomycetes: negative; pigeon and chicken: negative; Ouchterlony with native material from patients flat: negative. - CT including HR-CT: Bilateral-substantial emphysema, no bullae, no ground glass-opacity, no signs for interstitial lung diseases, no mediastinal enlargement of lymph nodes. - Alpha-1-Antitrypsin: 1.67 to 2.3 g/l (normal range), phenotype M1. - Histology: In resected material from right-side lung-volume-resection detection of pulmonary emphysema as well as lymphocyte infiltration and numerous epitheloid cell granulomas with Langhans'giant cells without caseation assessed as residues of an exogenous allergic alveolitis. - Conclusion: In a patient with lung volume reduction surgery due to severe emphysema histologically a persistent exogenous allergic alveolitis was detected, which might have caused the emphysema.

  2. 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.

  3. The Association Between Heroin Inhalation and Early Onset Emphysema.

    PubMed

    Walker, Paul P; Thwaite, Erica; Amin, Suzanne; Curtis, John M; Calverley, Peter M A

    2015-11-01

    Inhalation/smoking has become the most common method of recreational opiate consumption in the United Kingdom and other countries. Although some heroin smokers appear to develop COPD, little is known about the association. We present data from a cohort of 73 heroin smokers with clinician-diagnosed and spirometrically confirmed COPD, seen within our clinical service, where symptoms developed before the age of 40 years. The whole group mean age at diagnosis was 41 years, subjects had smoked heroin for 14 years, and mean FEV1 was 1.08 L (31.5% predicted), with mean FEV1/FVC of 0.4. No subject was found to have severe α1-antitrypsin deficiency. Forty-four subjects had either a high-resolution CT (HRCT) scan (32) or measurement of lung diffusion (12). Overall HRCT scan emphysema score averaged across the upper, middle, and lower part of the lung was 2.3 (5%-25% emphysema), with 47% subjects having an upper lobe emphysema score ≥ 3 (25%-50% emphysema). Median diffusing capacity of the lung for carbon monoxide was 48% of predicted value. Recreational smoking of heroin appears to lead to early onset COPD with a predominant emphysema phenotype. This message is important to both clinicians and the public, and targeted screening and education of this high-risk population may be justified.

  4. 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.

  5. 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.

  6. Pulmonary emphysema diagnosis with a preclinical small-animal X-ray dark-field scatter-contrast scanner.

    PubMed

    Yaroshenko, Andre; Meinel, Felix G; Bech, Martin; Tapfer, Arne; Velroyen, Astrid; Schleede, Simone; Auweter, Sigrid; Bohla, Alexander; Yildirim, Ali Ö; Nikolaou, Konstantin; Bamberg, Fabian; Eickelberg, Oliver; Reiser, Maximilian F; Pfeiffer, Franz

    2013-11-01

    To test the hypothesis that the joint distribution of x-ray transmission and dark-field signals obtained with a compact cone-beam preclinical scanner with a polychromatic source can be used to diagnose pulmonary emphysema in ex vivo murine lungs. The animal care committee approved this study. Three excised murine lungs with pulmonary emphysema and three excised murine control lungs were imaged ex vivo by using a grating-based micro-computed tomographic (CT) scanner. To evaluate the diagnostic value, the natural logarithm of relative transmission and the natural logarithm of dark-field scatter signal were plotted on a per-pixel basis on a scatterplot. Probability density function was fit to the joint distribution by using principle component analysis. An emphysema map was calculated based on the fitted probability density function. The two-dimensional scatterplot showed a characteristic difference between control and emphysematous lungs. Control lungs had lower average median logarithmic transmission (-0.29 vs -0.18, P = .1) and lower average dark-field signal (-0.54 vs -0.37, P = .1) than emphysematous lungs. The angle to the vertical axis of the fitted regions also varied significantly (7.8° for control lungs vs 15.9° for emphysematous lungs). The calculated emphysema distribution map showed good agreement with histologic findings. X-ray dark-field scatter images of murine lungs obtained with a preclinical scanner can be used in the diagnosis of pulmonary emphysema. http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13122413/-/DC1. RSNA, 2013

  7. Histological analysis of vasculopathy associated with pulmonary hypertension in combined pulmonary fibrosis and emphysema: comparison with idiopathic pulmonary fibrosis or emphysema alone.

    PubMed

    Awano, Nobuyasu; Inomata, Minoru; Ikushima, Soichiro; Yamada, Daisuke; Hotta, Masatoshi; Tsukuda, Shunji; Kumasaka, Toshio; Takemura, Tamiko; Eishi, Yoshinobu

    2017-05-01

    To evaluate pulmonary vasculopathy in an autopsy series of patients with combined pulmonary fibrosis and emphysema (CPFE), and compare these findings with those of patients with idiopathic pulmonary fibrosis (IPF) alone and emphysema alone. We retrospectively analysed the clinical, radiological and pathological features of 26 patients with CPFE, 11 with IPF, and 23 with emphysema. We evaluated pulmonary vascular, venous-venular and arteriolar tissue changes in the fibrotic, emphysematous and relatively unaffected (preserved) areas by using the Heath-Edwards scoring system. We found moderate-to-severe vasculopathy in the CPFE group, but no significant differences in the fibrotic and emphysematous areas among the three groups. However, in the preserved area, the grading was significantly different among the three groups (P < 0.001), and vasculopathy in the CPFE group was the most severe. Although venous-venular and arteriolar changes in almost all fibrotic and emphysematous areas in the three groups showed no significant differences, there were significant differences in venous-venular (P = 0.004) and arteriolar (P < 0.001) changes in the preserved area among the three groups, which were most prevalent in the CPFE group. In the CPFE group, venous-venular changes and vasculopathy by Heath-Edwards grading were highest in the fibrotic area and lowest in the preserved area. These results imply that pulmonary vasculopathy in patients with CPFE could occur in the whole lung tissue. This may explain the tendency for it to lead to the development of pulmonary hypertension in CPFE cases. © 2016 John Wiley & Sons Ltd.

  8. Past smoking and current dopamine agonist use show an independent and dose-dependent association with impulse control disorders in Parkinson's disease.

    PubMed

    Valença, Guilherme T; Glass, Philip G; Negreiros, Nadja N; Duarte, Meirelayne B; Ventura, Lais M G B; Mueller, Mila; Oliveira-Filho, Jamary

    2013-07-01

    Previous studies have described the association between dopamine replacement therapy in Parkinson's disease and impulse control disorders. A case-control study was performed to establish the prevalence of four of these behaviors in Brazilian patients with Parkinson's disease on stable dopamine replacement therapy and the possible associated risk factors. We investigated 152 patients and 212 healthy controls for pathological gambling, compulsive sexual behavior and compulsive buying and eating. Overall, patients had more impulsive control disorders than controls (18.4% vs. 4.2%, P < 0.001). Impulse control disorders were more common in younger patients (P = 0.008) and in those taking dopamine agonist (P < 0.001) and levodopa (P = 0.02). Higher Unified Parkinson's Disease Rating Scale motor score (P = 0.03) and past smoking (P = 0.02) were also associated in the univariate analysis. Variables independently associated with impulse control disorders were history of smoking (odds ratio = 1.059 for each year of smoking, P = 0.010) and current use of pramipexole (odds ratio = 2.551 for each increase in 1 mg, P < 0.001). Dopaminergic stimulation and previous exposure to smoking are independently associated with impulse control disorders in a dose-dependent manner. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. 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.

  10. 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.

  11. [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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Cluster Analysis in the COPDGene Study Identifies Subtypes of Smokers with Distinct Patterns of Airway Disease and Emphysema

    PubMed Central

    Castaldi, Peter J; Dy, Jennifer; Ross, James; Chang, Yale; Washko, George R; Curran-Everett, Douglas; Williams, Andre; Lynch, David A; Make, Barry J; Crapo, James D; Bowler, Russ P; Regan, Elizabeth A; Hokanson, John E; Kinney, Greg L; Han, Meilan K; Soler, Xavier; Ramsdell, Joseph W; Barr, R Graham; Foreman, Marilyn; van Beek, Edwin; Casaburi, Richard; Criner, Gerald J; Lutz, Sharon M; Rennard, Steven I; Santorico, Stephanie; Sciurba, Frank C; DeMeo, Dawn L; Hersh, Craig P; Silverman, Edwin K; Cho, Michael H

    2014-01-01

    Background There is notable heterogeneity in the clinical presentation of patients with COPD. To characterize this heterogeneity, we sought to identify subgroups of smokers by applying cluster analysis to data from the COPDGene Study. Methods We applied a clustering method, k-means, to data from 10,192 smokers in the COPDGene Study. After splitting the sample into a training and validation set, we evaluated three sets of input features across a range of k (user-specified number of clusters). Stable solutions were tested for association with four COPD-related measures and five genetic variants previously associated with COPD at genome-wide significance. The results were confirmed in the validation set. Findings We identified four clusters that can be characterized as 1) relatively resistant smokers (i.e. no/mild obstruction and minimal emphysema despite heavy smoking), 2) mild upper zone emphysema predominant, 3) airway disease predominant, and 4) severe emphysema. All clusters are strongly associated with COPD-related clinical characteristics, including exacerbations and dyspnea (p<0.001). We found strong genetic associations between the mild upper zone emphysema group and rs1980057 near HHIP, and between the severe emphysema group and rs8034191 in the chromosome 15q region (p<0.001). All significant associations were replicated at p<0.05 in the validation sample (12/12 associations with clinical measures and 2/2 genetic associations). Interpretation Cluster analysis identifies four subgroups of smokers that show robust associations with clinical characteristics of COPD and known COPD-associated genetic variants. PMID:24563194

  17. Cluster analysis in the COPDGene study identifies subtypes of smokers with distinct patterns of airway disease and emphysema.

    PubMed

    Castaldi, Peter J; Dy, Jennifer; Ross, James; Chang, Yale; Washko, George R; Curran-Everett, Douglas; Williams, Andre; Lynch, David A; Make, Barry J; Crapo, James D; Bowler, Russ P; Regan, Elizabeth A; Hokanson, John E; Kinney, Greg L; Han, Meilan K; Soler, Xavier; Ramsdell, Joseph W; Barr, R Graham; Foreman, Marilyn; van Beek, Edwin; Casaburi, Richard; Criner, Gerald J; Lutz, Sharon M; Rennard, Steven I; Santorico, Stephanie; Sciurba, Frank C; DeMeo, Dawn L; Hersh, Craig P; Silverman, Edwin K; Cho, Michael H

    2014-05-01

    There is notable heterogeneity in the clinical presentation of patients with COPD. To characterise this heterogeneity, we sought to identify subgroups of smokers by applying cluster analysis to data from the COPDGene study. We applied a clustering method, k-means, to data from 10 192 smokers in the COPDGene study. After splitting the sample into a training and validation set, we evaluated three sets of input features across a range of k (user-specified number of clusters). Stable solutions were tested for association with four COPD-related measures and five genetic variants previously associated with COPD at genome-wide significance. The results were confirmed in the validation set. We identified four clusters that can be characterised as (1) relatively resistant smokers (ie, no/mild obstruction and minimal emphysema despite heavy smoking), (2) mild upper zone emphysema-predominant, (3) airway disease-predominant and (4) severe emphysema. All clusters are strongly associated with COPD-related clinical characteristics, including exacerbations and dyspnoea (p<0.001). We found strong genetic associations between the mild upper zone emphysema group and rs1980057 near HHIP, and between the severe emphysema group and rs8034191 in the chromosome 15q region (p<0.001). All significant associations were replicated at p<0.05 in the validation sample (12/12 associations with clinical measures and 2/2 genetic associations). Cluster analysis identifies four subgroups of smokers that show robust associations with clinical characteristics of COPD and known COPD-associated genetic variants.

  18. Acute and chronic effects of treatment with mesenchymal stromal cells on LPS-induced pulmonary inflammation, emphysema and atherosclerosis development

    PubMed Central

    Khedoe, P. Padmini S. J.; de Kleijn, Stan; van Oeveren-Rietdijk, Annemarie M.; Plomp, Jaap J.; de Boer, Hetty C.; van Pel, Melissa; Rensen, Patrick C. N.

    2017-01-01

    Background COPD is a pulmonary disorder often accompanied by cardiovascular disease (CVD), and current treatment of this comorbidity is suboptimal. Systemic inflammation in COPD triggered by smoke and microbial exposure is suggested to link COPD and CVD. Mesenchymal stromal cells (MSC) possess anti-inflammatory capacities and MSC treatment is considered an attractive treatment option for various chronic inflammatory diseases. Therefore, we investigated the immunomodulatory properties of MSC in an acute and chronic model of lipopolysaccharide (LPS)-induced inflammation, emphysema and atherosclerosis development in APOE*3-Leiden (E3L) mice. Methods Hyperlipidemic E3L mice were intranasally instilled with 10 μg LPS or vehicle twice in an acute 4-day study, or twice weekly during 20 weeks Western-type diet feeding in a chronic study. Mice received 0.5x106 MSC or vehicle intravenously twice after the first LPS instillation (acute study) or in week 14, 16, 18 and 20 (chronic study). Inflammatory parameters were measured in bronchoalveolar lavage (BAL) and lung tissue. Emphysema, pulmonary inflammation and atherosclerosis were assessed in the chronic study. Results In the acute study, intranasal LPS administration induced a marked systemic IL-6 response on day 3, which was inhibited after MSC treatment. Furthermore, MSC treatment reduced LPS-induced total cell count in BAL due to reduced neutrophil numbers. In the chronic study, LPS increased emphysema but did not aggravate atherosclerosis. Emphysema and atherosclerosis development were unaffected after MSC treatment. Conclusion These data show that MSC inhibit LPS-induced pulmonary and systemic inflammation in the acute study, whereas MSC treatment had no effect on inflammation, emphysema and atherosclerosis development in the chronic study. PMID:28910300

  19. 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.

  20. 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

  1. 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

  2. Emphysema, airflow limitation, and early age-related macular degeneration.

    PubMed

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

    2010-04-01

    To describe the associations of lung function and emphysema, measured with spirometry and computed tomography (CT), with early age-related macular degeneration (AMD) in a sample of white, black, Hispanic, and Chinese subjects. Three thousand three hundred ninety-nine persons aged 45 to 84 years residing in 6 US communities participated in a period cross-sectional study. Age-related macular degeneration was measured from digital retinal photographs at the second Multi-Ethnic Study of Atherosclerosis (MESA) examination. Forced expiratory volume in 1 second (FEV(1)) and FEV(1) to 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 association of lung function and structure with AMD, controlling for age, sex, and other factors. The prevalence of early AMD was 3.7%. Early AMD was not associated with FEV(1) (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.58-1.15; P = .25), FEV(1):FVC ratio (OR, 0.92; 95% CI, 0.76-1.12; P = .43), percent emphysema (OR, 1.13; 95% CI, 0.91-1.40; P = .26), and apical-basilar difference in percent emphysema (OR, 1.14; 95% CI, 0.95-1.37; P = .17). Associations were stronger in smokers. Apical-basilar difference in percent emphysema was significantly associated with early AMD among those who ever smoked (OR, 1.28; 95% CI, 1.02-1.60; P = .03). Associations were not modified by race/ethnicity. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. Bullous emphysema – Not always nicotine-related!

    PubMed Central

    Lüttecke-Hecht, Camilla; Hirche, Tim O.

    2014-01-01

    In a patient admitted for further investigation of haemoptysis and dyspnoea and known emphysema of the lung, a remarkable distribution of emphysematous bullae could be detected on CT-imaging. Further history, besides smoking, revealed apnoea diving-activity during younger adult age. The distinct appearance of partially septated pleura-based bullae lead to the suspicion of a positive-pressure barotrauma of the lungs in the past, now complicated by infection and bleeding. This case highlights the importance of thorough questioning of the patient and underlines the consideration of differential diagnoses of emphysema. PMID:26029539

  9. Paraseptal Emphysema: Prevalence and Distribution on CT and Association with Interstitial Lung Abnormalities

    PubMed Central

    Araki, Tetsuro; Nishino, Mizuki; Zazueta, Oscar E.; Gao, Wei; Dupuis, Josée; Okajima, Yuka; Latourelle, Jeanne C.; Rosas, Ivan O.; Murakami, Takamichi; O’Connor, George T.; Washko, George R.; Hunninghake, Gary M.; Hatabu, Hiroto

    2015-01-01

    Objective To investigate the prevalence and distribution of paraseptal emphysema on chest CT images in the Framingham Heart Study (FHS) population, and assess its impact on pulmonary function. Also pursued was the association with interstitial lung abnormalities. Materials and Methods We assessed 2633 participants in the FHS for paraseptal emphysema on chest CT. Characteristics of participants, including age, sex, smoking status, clinical symptoms, and results of pulmonary function tests, were compared between those with and without paraseptal emphysema. The association between paraseptal emphysema and interstitial lung abnormalities was investigated. Results Of the 2633 participants, 86 (3%) had pure paraseptal emphysema (defined as paraseptal emphysema with no other subtypes of emphysema other than paraseptal emphysema or a very few centrilobular emphysema involved) in at least one lung zone. The upper zone of the lungs was almost always involved. Compared to the participants without paraseptal emphysema, those with pure paraseptal emphysema were significantly older, and were more frequently male and smokers (mean 64 years, 71% male, mean 36 pack-years, p<0.001) and had significantly decreased FEV1/FVC% (p=0.002), and diffusion capacity of carbon monoxide (DLCO) (p=0.002). There was a significant association between pure paraseptal emphysema and interstitial lung abnormalities (p<0.001). Conclusions The prevalence of pure paraseptal emphysema was 3% in the FHS population, predominantly affects the upper lung zone, and contributes to decreased pulmonary function. Cigarette smoking, aging, and male gender were the factors associated with the presence of paraseptal emphysema. Significant association between paraseptal emphysema and interstitial lung abnormalities was observed. PMID:25868675

  10. Morita-Baylis-Hillman adduct shows in vitro activity against Leishmania (Viannia) braziliensis associated with a reduction in IL-6 and IL-10 but independent of nitric oxide.

    PubMed

    Amorim, F M; Rodrigues, Y K S; Barbosa, T P; Néris, P L N; Caldas, J P A; Sousa, S C O; Leite, J A; Rodrigues-Mascarenhas, S; Vasconcellos, M L A A; Oliveira, M R

    2013-01-01

    Current treatments for different clinical forms of leishmaniasis are unsatisfactory, highly toxic and associated with increasing failure rates resulting from the emergence of resistant parasites. Leishmania (Viannia) braziliensis is the main aetiological agent of different clinical forms of American tegumentary leishmaniasis, including the mucosal form for which treatment has high failure rates. The aim of this work was to investigate the activity of the Morita-Baylis-Hillman adduct, methyl 2-{2-[hydroxy(2-nitrophenyl)methyl])acryloyloxy} benzoate in vitro against isolates of L. (V.) braziliensis obtained from patients with different clinical manifestations of tegumentary leishmaniasis: localized cutaneous leishmaniasis, mucosal leishmaniasis and disseminated cutaneous leishmaniasis. The adduct effectively inhibited the growth of promastigotes of the different isolates of L. (V.) braziliensis (IC(50) ≤ 7·77 μg/ml), as well as reduced the infection rate of macrophages infected with these parasites (EC(50) ≤ 1·37 μg/ml). It is remarkable to state that the adduct was more effective against intracellular amastigotes (P ≤ 0·0045). The anti-amastigote activity correlated with an immunomodulatory effect, since the adduct was able to decrease the production of IL-6 and IL-10 by the infected macrophages. However, its effect was independent of nitric oxide production. This work demonstrates the anti-leishmanial activity of methyl 2-{2-[hydroxy(2-nitrophenyl)methyl])acryloyloxy} benzoate and suggests its potential in the treatment of human infections caused by L. (V.) braziliensis.

  11. 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

  12. Craniocervical hyperpneumatization with concurrent pneumorrhachis, pneumomediastinum, and subcutaneous emphysema in a weightlifter.

    PubMed

    Germino, Jessica C; Medverd, Jonathan R; Nguyen, Vicky T; Favinger, Jennifer L; Marder, Carrie P

    2013-10-01

    , and C1 and C2 vertebral bodies. There was also pneumorrhachis extending throughout the entire cervical and thoracic spine, which caused moderate dural compression. Pneumomediastinum and subcutaneous emphysema were present. Maxillofacial CT showed dehiscent bone involving the dens, atlas, and occipital bone, with adjacent soft-tissue gas and pneumorrhachis. He was managed conservatively and advised to stop performing the Valsalva maneuver during weightlifting. His symptoms resolved, and follow-up imaging showed complete resolution of pneumorrhachis and partial reversal of hyperpneumatization. Craniocervical hyperpneumatization is a rare complication of the Valsalva maneuver. Most reported cases have involved only the skull base, or the skull base and C1, and many have been further complicated by microfractures leading to pneumocephalus or extracranial pneumatoceles. We present a unique case of extensive craniocervical hyperpneumatization that extended to the level of C2 and was complicated by microfractures causing severe pneumorrhachis. Concurrent pneumomediastinum in this case may have been an independent complication of the Valsalva maneuver, which could have contributed to pneumorrhachis. Alternatively, pneumomediastinum may have been caused by migration of gas through the neural foramen from the epidural space, driven by positive pressure generated by the one-way valve effect of the Eustachian tube during periods of exertion. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Visually stratified CT honeycombing as a survival predictor in combined pulmonary fibrosis and emphysema.

    PubMed

    Kim, Yong Seek; Jin, Gong Yong; Chae, Kum Ju; Han, Young Min; Chon, Su Bin; Lee, Young Sun; Kwon, Keun Sang; Choi, Hye Mi

    2015-01-01

    To determine whether visually stratified CT findings and pulmonary function variables are helpful in predicting mortality in patients with combined pulmonary fibrosis and emphysema (CPFE). We retrospectively identified 113 patients with CPFE who underwent high-resolution CT between January 2004 and December 2009. The extent of emphysema and fibrosis on CT was visually assessed using a 6- or 5-point scale, respectively. Univariate and multivariate Cox proportional regression analyses were performed to determine the prognostic value of visually stratified CT findings and pulmonary function variables in patients with CPFE. Differences in 5-year survival rates in patients with CPFE according to the extent of honeycombing were calculated using Kaplan-Meier analysis. An increase in the extent of visually stratified honeycombing on CT [hazard ratio (HR), 1.95; p = 0.018; 95% confidence interval (CI), 1.12-3.39] and reduced diffusing capacity of lung for carbon monoxide (DLCO) (HR, 0.97; p = 0.017; 95% CI, 0.94-0.99) were independently associated with increased mortality. In patients with CPFE, the 5-year survival rate was 78.5% for <5% honeycombing, 55.7% for 5-25% honeycombing, 32% for 26-50% honeycombing and 33.3% for >50% honeycombing on CT. The >50% honeycombing on CT and reduced DLCO are important prognostic factors in CPFE. Visual estimation of honeycombing extent on CT can help in the prediction of prognosis in CPFE.

  14. Mice Lacking Ras-GRF1 Show Contextual Fear Conditioning but not Spatial Memory Impairments: Convergent Evidence from Two Independently Generated Mouse Mutant Lines

    PubMed Central

    d’Isa, Raffaele; Clapcote, Steven J.; Voikar, Vootele; Wolfer, David P.; Giese, Karl Peter; Brambilla, Riccardo; Fasano, Stefania

    2011-01-01

    Ras-GRF1 is a neuronal specific guanine exchange factor that, once activated by both ionotropic and metabotropic neurotransmitter receptors, can stimulate Ras proteins, leading to long-term phosphorylation of downstream signaling. The two available reports on the behavior of two independently generated Ras-GRF1 deficient mouse lines provide contrasting evidence on the role of Ras-GRF1 in spatial memory and contextual fear conditioning. These discrepancies may be due to the distinct alterations introduced in the mouse genome by gene targeting in the two lines that could differentially affect expression of nearby genes located in the imprinted region containing the Ras-grf1 locus. In order to determine the real contribution of Ras-GRF1 to spatial memory we compared in Morris Water Maze learning Brambilla’s mice with a third mouse line (GENA53) in which a non-sense mutation was introduced in the Ras-GRF1 coding region without additional changes in the genome and we found that memory in this task is normal. Also, we measured both contextual and cued fear conditioning, which were previously reported to be affected in Brambilla’s mice, and we confirmed that contextual learning but not cued conditioning is impaired in both mouse lines. In addition, we also tested both lines for the first time in conditioned place aversion in the Intellicage, an ecological and remotely controlled behavioral test, and we observed normal learning. Finally, based on previous reports of other mutant lines suggesting that Ras-GRF1 may control body weight, we also measured this non-cognitive phenotype and we confirmed that both Ras-GRF1 deficient mutants are smaller than their control littermates. In conclusion, we demonstrate that Ras-GRF1 has no unique role in spatial memory while its function in contextual fear conditioning is likely to be due not only to its involvement in amygdala functions but possibly to some distinct hippocampal connections specific to contextual learning. PMID

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. [Rectal ozone therapy for patients with pulmonary emphysema].

    PubMed

    Calunga, José Luis; Paz, Yuleidys; Menéndez, Silvia; Martínez, Alfredo; Hernández, Aparicio

    2011-04-01

    Ozone therapy may stimulate antioxidant systems and protect against free radicals. It has not been used formerly in patients with pulmonary emphysema. To assess the effects of rectal ozone therapy in patients with pulmonary emphysema. Sixty four patients with pulmonary emphysema, aged between 40 and 69 years, were randomly assigned to receive rectal ozone in 20 daily sessions, rectal medicinal oxygen or no treatment. Treatments were repeated three months later in the first two groups. At baseline and at the end of the study, spirometry and a clinical assessment were performed. fifty patients completed the protocol, 20 receiving ozone therapy, 20 receiving rectal oxygen and 10 not receiving any therapy. At baseline, patients on ozone therapy had significantly lower values of forced expiratory volume in the first second (fEV1) and fEV1/forced vital capacity. At the end of the treatment period, these parameters were similar in the three treatment groups, therefore they only improved significantly in the group on ozone therapy. No differences were observed in other spirometric parameters. Rectal ozone therapy may be useful in patients with pulmonary emphysema.

  1. [The Proteus syndrome: a rare cause of pulmonary emphysema].

    PubMed

    Launois, C; Vallerand, H; Perotin, J-M; Nardi, J; Dury, S; Toubas, O; Lebargy, F; Deslée, G

    2013-11-01

    The Proteus syndrome is a rare genetic disease which is characterized by the overgrowth of tissues, especially bone, connective and adipose tissue. This condition is related to a somatic mosaic activating mutation in the AKT1 oncogene. We report the case of a 25-year-old man, diagnosed with the Proteus syndrome at the age of 6 months. He exhibited an asymmetric overgrowth of the extremities leading to bilateral amputation of the legs at the age of 10 years. He was hospitalized for acute respiratory failure due to a bronchopulmonary infection. Severe bullous pulmonary emphysema, predominantly on the left, with mediastinal deviation, was diagnosed. The patient recovered with antibiotics. An assessment 2 months later revealed mild hypoxaemia (PaO2=75 mmHg) and severe airflow limitation (FEV1=1260 mL [28% th.], FEV1/V C=69%) with hyperinflation (TLC=7840 mL [107% th.], RV=6010 mL [253% th.]). The Proteus syndrome is a very rare cause of pulmonary emphysema. The pathophysiology of emphysema in this syndrome is unknown. It can be hypothesized that the development of pulmonary cysts leading to emphysema may share the same AKT1 activation pathway with lymphangioleiomyomatosis. Copyright © 2013 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  2. Pulmonary emphysema and tumor microenvironment in primary lung cancer.

    PubMed

    Murakami, Junichi; Ueda, Kazuhiro; Sano, Fumiho; Hayashi, Masataro; Nishimoto, Arata; Hamano, Kimikazu

    2016-02-01

    To clarify the relationship between the presence of pulmonary emphysema and tumor microenvironment and their significance for the clinicopathologic aggressiveness of non-small cell lung cancer. The subjects included 48 patients with completely resected and pathologically confirmed stage I non-small cell lung cancer. Quantitative computed tomography was used to diagnose pulmonary emphysema, and immunohistochemical staining was performed to evaluate the matrix metalloproteinase (MMP) expression status in the intratumoral stromal cells as well as the microvessel density (MVD). Positive MMP-9 staining in the intratumoral stromal cells was confirmed in 17 (35%) of the 48 tumors. These 17 tumors were associated with a high MVD, frequent lymphovascular invasion, a high proliferative activity, and high postoperative recurrence rate (all, P < 0.05). The majority of the tumors (13 of 17) arose in patients with pulmonary emphysema (P = 0.02). Lung cancers arising from pulmonary emphysema were also associated with a high MVD, proliferative activity, and postoperative recurrence rate (all, P < 0.05). The MMP-9 expression in intratumoral stromal cells is associated with the clinicopathologic aggressiveness of lung cancer and is predominantly identified in tumors arising in emphysematous lungs. Further studies regarding the biological links between the intratumoral and extratumoral microenvironment will help to explain why lung cancers originating in emphysematous lung tissues are associated with a poor prognosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. 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.

  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. 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.

  6. Increase of matrix metalloproteinases in woodsmoke-induced lung emphysema in guinea pigs.

    PubMed

    Ramos, Carlos; Cisneros, Jose; Gonzalez-Avila, Georgina; Becerril, Carina; Ruiz, Víctor; Montaño, Martha

    2009-02-01

    Elastolysis, collagenolysis and gelatinolysis are essential in the pathogenesis of tobacco smoke-induced emphysema; however, these activities have been scantily studied in emphysema secondary to woodsmoke. The aim of this study was to analyze elastolysis, collagenolysis and gelatinolysis, MMP-1, MMP-2, and MMP-9 expression, and apoptosis in guinea pigs exposed to smoke produced by 60 g/day of pine wood, 5 days/week, from 1 to 7 months. Histological analysis after 4 to 7 months in smoke exposed guinea pigs showed alveolar mononuclear phagocyte and lymphocytic peribronchiolar inflammation, epithelial and smooth muscle hyperplasia, and pulmonary arterial hypertension. Mild to moderate emphysematous lesions were observed in woodsmoke-exposed animals at 4 to 7 months by increase of mean linear intercepts. A higher percentage of whole blood carboxyhemoglobin (COHb) and elastolytic activity in bronchoalveolar lavage macrophages and lung tissue homogenates was observed at all times. Collagenolysis was increased after 4 to 7 months in woodsmoke-exposed animals, although collagen concentration did not change. Zymography revealed increase in lysis bands of the active MMP-2 and MMP-9 at 4 and 7 months in bronchoalveolar lavage fluid and lung tissue homogenate. Positive immunostaining for MMP-1 and MMP-9 was observed in epithelial cells and macrophages in wood exposed animals at 4 to 7 months. Real-time PCR showed MMP-2 and MMP-9 expression at 3 to 7 months in exposed animals. Furthermore, apoptosis was increased at all times in bronchoalveolar lavage macrophages and lung tissue from exposed animals. Results support a role of metalloproteinases and apoptosis in emphysema secondary to woodsmoke exposure.

  7. 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.

  8. The influence of 5-lipoxygenase on cigarette smoke-induced emphysema in mice.

    PubMed

    Kennedy-Feitosa, Emanuel; Pinto, Rômulo Fonseca Santos; Pires, Karla Maria Pereira; Monteiro, Ana Paula Teixeira; Machado, Mariana Nascimento; Santos, Juliana Carvalho; Ribeiro, Marcelo Lima; Zin, Walter Araújo; Canetti, Cláudio Azevedo; Romana-Souza, Bruna; Porto, Luís Cristóvão; Valenca, Samuel Santos

    2014-01-01

    Pulmonary emphysema is characterized by the loss of lung architecture. Our hypothesis is that the inhibition of 5-lipoxygenase (5-LO) production may be an important strategy to reduce inflammation, oxidative stress, and metalloproteinases in lung tissue resulting from cigarette smoke (CS)-induced emphysema. 5-LO knockout (129S2-Alox5(tm1Fun)/J) and wild-type (WT) mice (129S2/SvPas) were exposed to CS for 60days. Mice exposed to ambient air were used as Controls. Oxidative, inflammatory, and proteolytic markers were analyzed. The alveolar diameter was decreased in CS 5-LO(-/-) mice when compared with the WT CS group. The CS exposure resulted in less pronounced pulmonary inflammation in the CS 5-LO(-/-) group. The CS 5-LO(-/-) group showed leukotriene B4 values comparable to those of the Control group. The expression of MMP-9 was decreased in the CS 5-LO(-/-) group when compared with the CS WT group. The expression of superoxide dismutase, catalase, and glutathione peroxidase were decreased in the CS 5-LO(-/-) group when compared with the Control group. The protein expression of nuclear factor (erythroid-derived 2)-like 2 was reduced in the CS 5-LO(-/-) group when compared to the CS WT group. In conclusion, we show for the first time that 5-LO deficiency protects 129S2 mice against emphysema caused by CS. We suggest that the main mechanism of pathogenesis in this model involves the imbalance between proteases and antiproteases, particularly the association between MMP-9 and TIMP-1. General significance This study demonstrates the influence of 5-LO mediated oxidative stress, inflammation, and proteolytic markers in CS exposed mice. © 2013.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Identification of Novel Saccharomyces cerevisiae Proteins with Nuclear Export Activity: Cell Cycle-Regulated Transcription Factor Ace2p Shows Cell Cycle-Independent Nucleocytoplasmic Shuttling

    PubMed Central

    Jensen, Torben Heick; Neville, Megan; Rain, Jean Christophe; McCarthy, Terri; Legrain, Pierre; Rosbash, Michael

    2000-01-01

    Nuclear export of proteins containing leucine-rich nuclear export signals (NESs) is mediated by the NES receptor CRM1/Crm1p. We have carried out a yeast two-hybrid screen with Crm1p as a bait. The Crm1p-interacting clones were subscreened for nuclear export activity in a visual assay utilizing the Crm1p-inhibitor leptomycin B (LMB). This approach identified three Saccharomyces cerevisiae proteins not previously known to have nuclear export activity. These proteins are the 5′ RNA triphosphatase Ctl1p, the cell cycle-regulated transcription factor Ace2p, and a protein encoded by the previously uncharacterized open reading frame YDR499W. Mutagenesis analysis show that YDR499Wp contains an NES that conforms to the consensus sequence for leucine-rich NESs. Mutagenesis of Ctl1p and Ace2p were unable to identify specific NES residues. However, a 29-amino-acid region of Ace2p, rich in hydrophobic residues, contains nuclear export activity. Ace2p accumulates in the nucleus at the end of mitosis and activates early-G1-specific genes. We now provide evidence that Ace2p is nuclear not only in late M-early G1 but also during other stages of the cell cycle. This feature of Ace2p localization explains its ability to activate genes such as CUP1, which are not expressed in a cell cycle-dependent manner. PMID:11027275

  15. 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

  16. Afatinib, an Irreversible EGFR Family Inhibitor, Shows Activity Toward Pancreatic Cancer Cells, Alone and in Combination with Radiotherapy, Independent of KRAS Status.

    PubMed

    Huguet, Florence; Fernet, Marie; Giocanti, Nicole; Favaudon, Vincent; Larsen, Annette K

    2016-06-01

    Pancreatic adenocarcinoma is characterized by a high frequency of KRAS mutations and frequent deregulation of the epidermal growth factor receptor (EGFR) and other EGFR family members such as HER2/ErbB2. The EGFR inhibitor erlotinib is approved for treatment of pancreatic cancer, but has shown modest activity in most patients. Here we investigated the activity of afatinib, a second-generation irreversible pan-EGFR family kinase inhibitor, alone or in combination with ionizing radiation, toward pancreatic cancer cells. The influence of afatinib on cell proliferation, cell cycle distribution, clonogenic survival, nuclear fragmentation, ploidy, and centrosome amplification following irradiation was determined. Expression and phosphorylation of HER receptors, Akt, DNA-PKcs, and ERK1/2 was characterized by Western blot analysis. Afatinib was growth-inhibitory for all three cell lines but cytotoxic only toward BxPC3 (KRAS (wt)) and Capan-2 (KRAS (mut)) cells, both of which express high levels of EGFR, HER2, and HER3 receptors. Afatinib increased the radiosensitivity of BxPC3 and Capan-2 cells, prevented the radio-induced phosphorylation of Akt, and induced mitotic catastrophe following irradiation. In comparison, Panc-1 cells (KRAS (mut)) expressing low levels of EGFR family receptors were resistant to afatinib-induced radiosensitization. These results must be confirmed in vivo. Afatinib showed cytotoxic and radiosensitizing effects toward a subset of pancreatic cancer cells which was closely correlated with expression of EGFR, HER2, and HER3 receptors, but not with KRAS status.

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

    PubMed

    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

    2016-11-01

    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.

  18. 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.

  19. Design of the exhale airway stents for emphysema (EASE) trial: an endoscopic procedure for reducing hyperinflation.

    PubMed

    Shah, Pallav L; Slebos, Dirk-Jan; Cardoso, Paulo F G; Cetti, Edward J; Sybrecht, Gerhard W; Cooper, Joel D

    2011-01-07

    Airway Bypass is a catheter-based, bronchoscopic procedure in which new passageways are created that bypass the collapsed airways, enabling trapped air to exit the lungs. The Exhale Airway Stents for Emphysema (EASE) Trial was designed to investigate whether Exhale® Drug-Eluting Stents, placed in new passageways in the lungs, can improve pulmonary function and reduce breathlessness in severely hyperinflated, homogeneous emphysema patients (NCT00391612). The multi-center, randomized, double-blind, sham-controlled trial design was posted on http://www.clinicaltrials.gov in October 2006. Because Bayesian statistics are used for the analysis, the proposed enrollment ranged from 225 up to 450 subjects at up to 45 institutions. Inclusion criteria are: high resolution CT scan with evidence of homogeneous emphysema, post-bronchodilator pulmonary function tests showing: a ratio of FEV1/FVC < 70%, FEV1 ≤ 50% of predicted or FEV1 < 1 liter, RV/TLC ≥ 0.65 at screening, marked dyspnea score ≥ 2 on the modified Medical Research Council scale of 0-4, a smoking history of at least 20 pack years and stopped smoking for at least 8 weeks prior to enrollment. Following 16 to 20 supervised pulmonary rehabilitation sessions, subjects were randomized 2:1 to receive either a treatment (Exhale® Drug-Eluting Stent) or a sham bronchoscopy. A responder analysis will evaluate the co-primary endpoints of an FVC improvement ≥ 12% of the patient baseline value and modified Medical Research Council dyspnea scale improvement (reduction) ≥ 1 point at the 6-month follow-up visit. If through the EASE Trial, Airway Bypass is shown to improve pulmonary function and reduce dyspnea while demonstrating an acceptable safety profile, then homogeneous patients will have a minimally invasive treatment option with meaningful clinical benefit. ClinicalTrials.gov: NCT00391612.

  20. Design of the exhale airway stents for emphysema (EASE) trial: an endoscopic procedure for reducing hyperinflation

    PubMed Central

    2011-01-01

    Background Airway Bypass is a catheter-based, bronchoscopic procedure in which new passageways are created that bypass the collapsed airways, enabling trapped air to exit the lungs. The Exhale Airway Stents for Emphysema (EASE) Trial was designed to investigate whether Exhale® Drug-Eluting Stents, placed in new passageways in the lungs, can improve pulmonary function and reduce breathlessness in severely hyperinflated, homogeneous emphysema patients (NCT00391612). Methods/Design The multi-center, randomized, double-blind, sham-controlled trial design was posted on http://www.clinicaltrials.gov in October 2006. Because Bayesian statistics are used for the analysis, the proposed enrollment ranged from 225 up to 450 subjects at up to 45 institutions. Inclusion criteria are: high resolution CT scan with evidence of homogeneous emphysema, post-bronchodilator pulmonary function tests showing: a ratio of FEV1/FVC < 70%, FEV1≤50% of predicted or FEV1 < 1 liter, RV/TLC≥0.65 at screening, marked dyspnea score ≥2 on the modified Medical Research Council scale of 0-4, a smoking history of at least 20 pack years and stopped smoking for at least 8 weeks prior to enrollment. Following 16 to 20 supervised pulmonary rehabilitation sessions, subjects were randomized 2:1 to receive either a treatment (Exhale® Drug-Eluting Stent) or a sham bronchoscopy. A responder analysis will evaluate the co-primary endpoints of an FVC improvement ≥12% of the patient baseline value and modified Medical Research Council dyspnea scale improvement (reduction) ≥1 point at the 6-month follow-up visit. Discussion If through the EASE Trial, Airway Bypass is shown to improve pulmonary function and reduce dyspnea while demonstrating an acceptable safety profile, then homogeneous patients will have a minimally invasive treatment option with meaningful clinical benefit. Trial Registration ClinicalTrials.gov: NCT00391612 PMID:21214899

  1. Improved neurobehavioral functioning in emphysema patients following lung volume reduction surgery compared with medical therapy.

    PubMed

    Kozora, Elizabeth; Emery, Charles F; Ellison, Misoo C; Wamboldt, Frederick S; Diaz, Philip T; Make, Barry

    2005-10-01

    The goal of this study was to evaluate the neuropsychological and psychological functioning of emphysema patients following lung volume reduction surgery (LVRS) compared with patients receiving only medical therapy (MT). Patients with moderate-to-severe emphysema who were enrolled in the National Emphysema Treatment Trial at two sites (National Jewish Medical and Research Center and Ohio State University) were given a neuropsychological battery at baseline, 6 to 10 weeks later (following participation in pulmonary rehabilitation), and at 6 months following randomization to either LVRS or MT treatment. Twenty patients randomized to MT, 19 patients randomized to LVRS, and 39 matched, healthy control subjects completed a battery of tests that measured cognitive functioning, depression, anxiety, and quality of life (QoL). Controlling for practice, patients in the LVRS treatment arm at the 6-month follow-up demonstrated significant improvement compared with MT patients in cognitive tasks involving sequential skills and verbal memory. The LVRS patients also showed significant reductions in depression compared with the MT patients, as well as improved physical and psychosocial QoL. Correlational analysis indicated that improved immediate verbal memory in the LVRS group was related to improved QoL. No associations were found between changes in cognitive function and changes in depression, exercise performance, or pulmonary functioning. Patients who received LVRS demonstrated improvement in specific neuropsychological functions, depression, anxiety, and QoL scores compared with patients with continued MT treatment 6 months following randomization. However, mechanisms for these neurobehavioral changes are unclear. Improved verbal memory and sequential skills following LVRS were not directly associated with depression or exercise capacity. Nonetheless, LVRS led to a strong and likely clinically significant improvement in neuropsychological functioning over and above that

  2. A peculiar blow-out fracture of the inferior orbital wall complicated by extensive subcutaneous emphysema: A case report and review of the literature.

    PubMed

    Rzymska-Grala, Iwona; Palczewski, Piotr; Błaż, Marcin; Zmorzyński, Michał; Gołębiowski, Marek; Wanyura, Hubert

    2012-04-01

    Blow-out fracture of the orbit is a common injury. However, not many cases are associated with massive subcutaneous emphysema. Even fewer cases are caused by minor trauma or are associated with barotrauma to the orbit due to sneezing, coughing, or vomiting. The authors present a case of blow-out fracture complicated by extensive subcutaneous and mediastinal emphysema that occurred without any obvious traumatic event. A 43-year-old man presented to the Emergency Department with a painful right-sided exophthalmos that he had noticed in the morning immediately after waking up. The patient also complained of diplopia. Physical examination revealed exophthalmos and crepitations suggestive of subcutaneous emphysema. The eye movements, especially upward gaze, were impaired. CT showed blow-out fracture of the inferior orbital wall with a herniation of the orbital soft tissues into the maxillary sinus. There was an extensive subcutaneous emphysema in the head and neck going down to the mediastinum. The patient did not remember any significant trauma to the head that could explain the above mentioned findings. At surgery, an inferior orbital wall fracture with a bony defect of 3×2 centimeter was found and repaired. Blow-out fractures of the orbit are usually a result of a direct trauma caused by an object with a diameter exceeding the bony margins of the orbit. In 50% of cases, they are complicated by orbital emphysema and in 4% of cases by herniation of orbital soft tissues into paranasal sinuses. The occurrence of orbital emphysema without trauma is unusual. In some cases it seems to be related to barotrauma due to a rapid increase in pressure in the upper airways during sneezing, coughing, or vomiting, which very rarely leads to orbital wall fracture. Computed tomography is the most accurate method in detecting and assessing the extent of orbital wall fractures.

  3. 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

  4. 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

  5. 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.

  6. Lung Volumes and Emphysema in Smokers with Interstitial Lung Abnormalities

    PubMed Central

    Washko, George R.; Hunninghake, Gary M.; Fernandez, Isis E.; Nishino, Mizuki; Okajima, Yuka; Yamashiro, Tsuneo; Ross, James C.; Estépar, Raúl San José; Lynch, David A.; Brehm, John M.; Andriole, Katherine P.; Diaz, Alejandro A.; Khorasani, Ramin; D’Aco, Katherine; Sciurba, Frank C.; Silverman, Edwin K.; Hatabu, Hiroto; Rosas, Ivan O.

    2011-01-01

    BACKGROUND Cigarette smoking is associated with emphysema and radiographic interstitial lung abnormalities. The degree to which interstitial lung abnormalities are associated with reduced total lung capacity and the extent of emphysema is not known. METHODS We looked for interstitial lung abnormalities in 2416 (96%) of 2508 high-resolution computed tomographic (HRCT) scans of the lung obtained from a cohort of smokers. We used linear and logistic regression to evaluate the associations between interstitial lung abnormalities and HRCT measurements of total lung capacity and emphysema. RESULTS Interstitial lung abnormalities were present in 194 (8%) of the 2416 HRCT scans evaluated. In statistical models adjusting for relevant covariates, interstitial lung abnormalities were associated with reduced total lung capacity (−0.444 liters; 95% confidence interval [CI], −0.596 to −0.292; P<0.001) and a lower percentage of emphysema defined by lung-attenuation thresholds of −950 Hounsfield units (−3%; 95% CI, −4 to −2; P<0.001) and −910 Hounsfield units (−10%; 95% CI, −12 to −8; P<0.001). As compared with participants without interstitial lung abnormalities, those with abnormalities were more likely to have a restrictive lung deficit (total lung capacity <80% of the predicted value; odds ratio, 2.3; 95% CI, 1.4 to 3.7; P<0.001) and were less likely to meet the diagnostic criteria for chronic obstructive pulmonary disease (COPD) (odds ratio, 0.53; 95% CI, 0.37 to 0.76; P<0.001). The effect of interstitial lung abnormalities on total lung capacity and emphysema was dependent on COPD status (P<0.02 for the interactions). Interstitial lung abnormalities were positively associated with both greater exposure to tobacco smoke and current smoking. CONCLUSIONS In smokers, interstitial lung abnormalities — which were present on about 1 of every 12 HRCT scans — were associated with reduced total lung capacity and a lesser amount of emphysema. (Funded by the

  7. Fenretinide causes emphysema, which is prevented by sphingosine 1-phoshate.

    PubMed

    Yasuo, Masanori; Mizuno, Shiro; Allegood, Jeremy; Kraskauskas, Donatas; Bogaard, Harm J; Spiegel, Sarah; Voelkel, Norbert F

    2013-01-01

    Sphingolipids play a role in the development of emphysema and ceramide levels are increased in experimental models of emphysema; however, the mechanisms of ceramide-related pulmonary emphysema are not fully understood. Here we examine mechanisms of ceramide-induced pulmonary emphysema. Male Sprague-Dawley rats were treated with fenretinide (20 mg/kg BW), a synthetic derivative of retinoic acid that causes the formation of ceramide, and we postulated that the effects of fenretinide could be offset by administering sphingosine 1-phosphate (S1P) (100 µg/kg BW). Lung tissues were analyzed and mean alveolar airspace area, total length of the alveolar perimeter and the number of caspase-3 positive cells were measured. Hypoxia-inducible factor alpha (HIF-1α), vascular endothelial growth factor (VEGF) and other related proteins were analyzed by Western blot analysis. Immunohistochemical analysis of HIF-1α was also performed. Ceramide, dihydroceramide, S1P, and dihydro-S1P were measured by mass spectrometer. Chronic intraperitoneal injection of fenretinide increased the alveolar airspace surface area and increased the number of caspase-3 positive cells in rat lungs. Fenretinide also suppressed HIF-1α and VEGF protein expression in rat lungs. Concomitant injection of S1P prevented the decrease in the expression of HIF-1α, VEGF, histone deacetylase 2 (HDAC2), and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) protein expression in the lungs. S1P injection also increased phosphorylated sphingosine kinase 1. Dihydroceramide was significantly increased by fenretinide injection and S1P treatment prevented the increase in dihydroceramide levels in rat lungs. These data support the concept that increased de novo ceramide production causes alveolar septal cell apoptosis and causes emphysema via suppressing HIF-1α. Concomitant treatment with S1P normalizes the ceramide-S1P balance in the rat lungs and increases HIF-1α protein expression via activation of sphingosine kinase

  8. Fenretinide Causes Emphysema, Which Is Prevented by Sphingosine 1-Phoshate

    PubMed Central

    Yasuo, Masanori; Mizuno, Shiro; Allegood, Jeremy; Kraskauskas, Donatas; Bogaard, Harm J.; Spiegel, Sarah; Voelkel, Norbert F.

    2013-01-01

    Sphingolipids play a role in the development of emphysema and ceramide levels are increased in experimental models of emphysema; however, the mechanisms of ceramide-related pulmonary emphysema are not fully understood. Here we examine mechanisms of ceramide-induced pulmonary emphysema. Male Sprague-Dawley rats were treated with fenretinide (20 mg/kg BW), a synthetic derivative of retinoic acid that causes the formation of ceramide, and we postulated that the effects of fenretinide could be offset by administering sphingosine 1-phosphate (S1P) (100 µg/kg BW). Lung tissues were analyzed and mean alveolar airspace area, total length of the alveolar perimeter and the number of caspase-3 positive cells were measured. Hypoxia-inducible factor alpha (HIF-1α), vascular endothelial growth factor (VEGF) and other related proteins were analyzed by Western blot analysis. Immunohistochemical analysis of HIF-1α was also performed. Ceramide, dihydroceramide, S1P, and dihydro-S1P were measured by mass spectrometer. Chronic intraperitoneal injection of fenretinide increased the alveolar airspace surface area and increased the number of caspase-3 positive cells in rat lungs. Fenretinide also suppressed HIF-1α and VEGF protein expression in rat lungs. Concomitant injection of S1P prevented the decrease in the expression of HIF-1α, VEGF, histone deacetylase 2 (HDAC2), and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) protein expression in the lungs. S1P injection also increased phosphorylated sphingosine kinase 1. Dihydroceramide was significantly increased by fenretinide injection and S1P treatment prevented the increase in dihydroceramide levels in rat lungs. These data support the concept that increased de novo ceramide production causes alveolar septal cell apoptosis and causes emphysema via suppressing HIF-1α. Concomitant treatment with S1P normalizes the ceramide-S1P balance in the rat lungs and increases HIF-1α protein expression via activation of sphingosine kinase

  9. 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

  10. 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.

  11. 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.

  12. Investigations into the biochemical mechanisms of pulmonary emphysema: effects of cigarette smoke on enzymes and anti-enzymes in the lung.

    PubMed

    Janoff, A

    1986-01-01

    The mechanism(s) causing emphysema in the cigarette smoker are still poorly understood. However, circumstantial evidence is beginning to provide a tenuous link between smoking and the protease-antiprotease imbalance hypothesis. Independent effects on elastin synthesis may also be important. This triad of chemical and cellular events (leukocyte recruitment, inhibitor inactivation, depressed tissue repair) constitutes a reasonable first approximation from which to approach this complex question.

  13. Macroscopic assessment of pulmonary emphysema by image analysis.

    PubMed Central

    Gevenois, P A; Zanen, J; de Maertelaer, V; De Vuyst, P; Dumortier, P; Yernault, J C

    1995-01-01

    AIMS--To propose a computerised image analysis based method for measuring, on paper mounted lung sections, the area macroscopically occupied by emphysema. METHODS--The study was based on the assessment of 69 lung sections prepared following a modified Gough-Wentworth technique. The results obtained from image analysis, point counting, and panel grading methods were compared, as was the repeatability of image analysis and panel grading. RESULTS--The results from image analysis and from point counting were not significantly different (p = 0.609) and significant quadratic regressions (r = 0.96, p < 0.001) were found between measurements from image analysis and from panel grading, the computerised technique being shown to be the most reproducible. CONCLUSIONS--Image analysis is a valuable and reproducible method to measure the area of lung macroscopically involved by emphysema. PMID:7615849

  14. 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.

  15. 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

  16. [Effect of shenmai injection and aminophylline on small airway smooth muscle cell apoptosis and related gene expression in rats with emphysema].

    PubMed

    Niu, Ru-ji; Fu, Juan; Liu, Hui-guo

    2002-01-01

    To investigate the effect of Shenmai Injection (SMI) and aminophylline on small airway smooth muscle cell (SASMC) apoptosis and the Fas/FasL expression in the papain induced emphysema model rats. Emphysema model in rat was established by a single intratracheal instillation of papain. Apoptosis and Fas/FasL expression of SASMC were examined by immunohistochemical SABC and TUNEL assay at 1, 3, 5, 7, 15 and 30 days after modelling, and the effect of SMI and aminophylline on them were observed. Fas, FasL expressions in normal SASMC were very low with a positive rate of (2.31 +/- 0.05)% and (1.28 +/- 0.47)% respectively. After papain instillation, the positive rates increased along with the prolonging of instillation time. SMI showed an inhibition on SASMC Fas and FasL expression but aminophylline didn't show. SASMC apoptosis was very low in normal rats with a rate of (0.87 +/- 0.32)%, it also raised after papain instillation and increased progressively along with the instillation time. SMI treatment could lower the apoptosis rate but aminophylline couldn't. Fas and FasL participated the SASMC apoptosis modulation in emphysema formation. SMI shows a definite treatment effect on emphysema by influencing the Fas and FasL protein expression and reducing SASMC apoptosis through inhibiting the release of inflammatory mediator.

  17. 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

  18. Massive Cervicothoracic Subcutaneous Emphysema and Pneumomediastinum Developing during a Dental Hygiene Procedure.

    PubMed

    Bocchialini, Gabriele; Ambrosi, Serena; Castellani, Andrea

    2017-01-01

    Subcutaneous emphysema is rare during or after dental procedures (usually extractions). Here, we describe the case of a 65-year-old woman who developed massive cervicothoracic subcutaneous emphysema and pneumomediastinum during a dental hygiene procedure employing an artificial airflow. She was diagnosed based on clinical manifestations and computed tomography (CT). CT revealed massive subcutaneous emphysema extending from the superior left eyelid to the diaphragm. We describe the clinical and radiological characteristics of this rare case.

  19. 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

  20. 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

  1. 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

  2. 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.

  3. Cervicofacial and mediastinal emphysema due to a dental procedure.

    PubMed

    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.

  4. 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.

  5. Ventilation/perfusion SPECT or SPECT/CT for lung function imaging in patients with pulmonary emphysema?

    PubMed

    Froeling, Vera; Heimann, Uwe; Huebner, Ralf-Harto; Kroencke, Thomas J; Maurer, Martin H; Doellinger, Felix; Geisel, Dominik; Hamm, Bernd; Brenner, Winfried; Schreiter, Nils F

    2015-07-01

    To evaluate the utility of attenuation correction (AC) of V/P SPECT images for patients with pulmonary emphysema. Twenty-one patients (mean age 67.6 years) with pulmonary emphysema who underwent V/P SPECT/CT were included. AC/non-AC V/P SPECT images were compared visually and semiquantitatively. Visual comparison of AC/non-AC images was based on a 5-point likert scale. Semiquantitative comparison assessed absolute counts per lung (aCpLu) and lung lobe (aCpLo) for AC/non-AC images using software-based analysis; percentage counts (PC = (aCpLo/aCpLu) × 100) were calculated. Correlation between AC/non-AC V/P SPECT images was analyzed using Spearman's rho correlation coefficient; differences were tested for significance with the Wilcoxon rank sum test. Visual analysis revealed high conformity for AC and non-AC V/P SPECT images. Semiquantitative analysis of PC in AC/non-AC images had an excellent correlation and showed no significant differences in perfusion (ρ = 0.986) or ventilation (ρ = 0.979, p = 0.809) SPECT/CT images. AC of V/P SPECT images for lung lobe-based function imaging in patients with pulmonary emphysema do not improve visual or semiquantitative image analysis.

  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. 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.

  8. 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.

  9. 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.

  10. Sequential cognitive skills in emphysema patients following lung volume reduction surgery: a 2-year longitudinal study.

    PubMed

    Kozora, Elizabeth; Emery, Charles F; Zhang, Lening; Hoth, Karin F; Murphy, James; Make, Barry

    2011-01-01

    This study compared visuomotor speed and cognitive flexibility in emphysema patients treated with either standard multidisciplinary medical therapy (MT) or lung volume reduction surgery (LVRS), followed over a 2-year period. MT patients (n = 544) and 542 LVRS patients completed the Trail Making Test (TMT) Parts A and B prior to randomization (baseline). Testing was repeated at 1 and 2 years. There were no differences on scores for TMT Parts A and B between the LVRS and MT groups at baseline or at years 1 and 2. No significant difference between MT and LVRS was noted in terms of overall change in TMT Parts A and B over 2 years. The MT group had a significant improvement on TMT Part A at each followup time compared with baseline (P < .03) but the LVRS group did not. Both the MT and LVRS groups had a significant decline in performance (increase in time to completion) on TMT Part B when comparing year 1 with baseline (P < .0001). Emphysema patients who received LVRS or MT as treatment performed similarly on measures of visuomotor speed and flexibility at baseline and 1- and 2-year followup. Both groups showed improvement on visuomotor speed during the first year yet overall cognitive flexibility declined. By the second year neither group had any significant change from baseline. These findings suggest that improvement on visuomotor speed and flexibility, observed in a previous 6-month study of LVRS subjects, was not sustained at 1- and 2-year followup.

  11. Sequential Cognitive Skills in Emphysema Patients Following Lung Volume Reduction Surgery: A Two Year Longitudinal Study

    PubMed Central

    Kozora, Elizabeth; Emery, Charles F.; Zhang, Lening; Hoth, Karin F.; Murphy, James; Make, Barry

    2011-01-01

    PURPOSE This study compared visuomotor speed and cognitive flexibility in emphysema patients treated either with standard multidisciplinary medical therapy (MT) or lung volume reduction surgery (LVRS), followed over a 2-year period. METHODS MT patients (n=544) and 542 LVRS patients completed the Trail Making Test (TMT) Parts A and B prior to randomization (baseline). Testing was repeated at 1 and 2 years. RESULTS There were no differences on scores for TMT Part A and B between the LVRS and MT groups at baseline or at years 1 and 2. No significant difference between MT and LVRS was noted in terms of overall change in TMT Part A and B over 2 years. The MT group had a significant improvement on TMT-Part A at each followup time compared to baseline (P<.03) but the LVRS group did not. Both the MT and LVRS groups had a significant decline in performance (increase in time to completion) on TMT-Part B when comparing year 1 to baseline (P<.0001). CONCLUSION Emphysema patients who received LVRS or MT as treatment performed similarly on measures of visuomotor speed and flexibility at baseline and 1 and 2 year followup. Both groups showed improvement on visuomotor speed during the first year yet overall cognitive flexibility declined. By the second year neither group had any significant change from baseline. These findings suggest that improvement on visuomotor speed and flexibility, observed in a previous 6-month study of LVRS subjects, was not sustained at 1 and 2 year followup. PMID:22089885

  12. 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

  13. [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.

  14. Lung volume reduction of pulmonary emphysema: the radiologist task.

    PubMed

    Milanese, Gianluca; Silva, Mario; Sverzellati, Nicola

    2016-03-01

    Several lung volume reduction (LVR) techniques have been increasingly evaluated in patients with advanced pulmonary emphysema, especially in the last decade. Radiologist plays a pivotal role in the characterization of parenchymal damage and, thus, assessment of eligibility criteria. This review aims to discuss the most common LVR techniques, namely LVR surgery, endobronchial valves, and coils LVR, with emphasis on the role of computed tomography (CT). Several trials have recently highlighted the importance of regional quantification of emphysema by computerized CT-based segmentation of hyperlucent parenchyma, which is strongly recommended for candidates to any LVR treatment. In particular, emphysema distribution pattern and fissures integrity are evaluated to tailor the choice of the most appropriate LVR technique. Furthermore, a number of CT measures have been tested for the personalization of treatment, according to imaging detected heterogeneity of parenchymal disease. CT characterization of heterogeneous parenchymal abnormalities provides criteria for selection of the preferable treatment in each patient and improves outcome of LVR as reflected by better quality of life, higher exercise tolerance, and lower mortality.

  15. Pulmonary emphysema associated with the FZ alpha 1-antitrypsin phenotype.

    PubMed

    Cockcroft, D W; Tennent, R K; Horne, S L

    1981-03-15

    In one family three brothers were found to have a moderate deficiency of alpha 1-antitrypsin associated with the unusual Pi (protease inhibitor) phenotype FZ. The Pi phenotypes of their six living siblings were found to be FM (in three), M (in two) and MZ (in one). The three FZ brothers all had moderate to severe obstructive airways disease, and two had at least moderately severe pulmonary emphysema. Additional risk factors included moderate cigarette smoking in two and prolonged exposure to grain dust in all three. The same risk factors applied to the six non-FZ siblings, but they had only mild symptoms and pulmonary dysfunction or no lung problems at all; one, a female smoker with the MZ phenotype, had probable early emphysema demonstrated radiologically. The three FZ men may have had reduced fertility, as they produced only 1 child among them, as compared with 39 among the other eight siblings. This family study thus suggests that individuals with the FZ phenotype are at risk for pulmonary emphysema and chronic obstructive airways disease, particularly in the presence of other risk factors, such as cigarette smoking and grain dust exposure.

  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. Augmentation therapy of alpha-1 antitrypsin deficiency associated emphysema.

    PubMed

    Traclet, J; Delaval, P; Terrioux, P; Mornex, J-F

    2015-04-01

    Alpha-1 antitrypsin, secreted by the liver, inhibits neutrophil elastase. Its deficiency favours the development of emphysema. Restoring a "protective" serum level in deficient patients should make it possible to inhibit the development of emphysema. Human plasma-derived alpha-1 antitrypsin is a blood-derived drug sold in France under the name Alfalastin(®). The recommended posology is an I.V. administration of 60 mg/kg once a week. Human plasma-derived alpha-1 antitrypsin restores anti-elastase protection in the lower lung and prevents experimental emphysema induced by the elastasis of human neutrophils in hamster. The low number of patients with alpha-1 antitrypsin deficiency is one of the difficulties to perform sufficiently powerful randomised studies. However, randomised studies have reported the efficacy of human plasma-derived alpha-1 antitrypsin perfusions on mortality, FEV1 decline and the frequency of exacerbations. Randomised control trials have demonstrated the efficacy of human plasma-derived alpha-1 antitrypsin perfusions on the loss of lung density assessed by CT scan. Augmentation therapy is simple in its conception and implementation, but it is expensive. However, there are currently no other solutions. Copyright © 2014 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. Treatment of recalcitrant subcutaneous emphysema using negative pressure wound therapy dressings

    PubMed Central

    Towe, Christopher; Solomon, Brian; Donington, Jessica S; Pass, Harvey I

    2014-01-01

    Subcutaneous emphysema frequently occurs after pulmonary resection, but is usually mild and self-limiting. Patients can, however, develop severe symptomatic subcutaneous emphysema despite adequate thoracic drainage. There is a paucity of efficacious treatments for subcutaneous emphysema that does not respond to chest tube drainage. Previous reports have suggested that thoracoscopy may be an efficacious treatment, but is unfavourable due to the risks associated with reoperation. We present a case of a patient who developed severe subcutaneous emphysema after pulmonary lobectomy that was quickly and effectively treated using a commercially available negative pressure wound therapy dressing. PMID:25385560

  3. 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.

  4. 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.

  5. Advanced emphysema in African-American and white patients: do differences exist?

    PubMed

    Chatila, Wissam M; Hoffman, Eric A; Gaughan, John; Robinswood, G Blake; Criner, Gerard J

    2006-07-01

    Emphysema is the only smoking-related disease in which white patients have higher prevalence and higher attributable mortality rates than African-American patients. Epidemiologic studies have not addressed, nor explained, the observed racial differences in emphysema. To determine whether white and African-American patients differ with respect to the magnitude, anatomic distribution, and physiologic impairments of emphysema. Characteristics of patients with severe and very severe emphysema enrolled in the National Emphysema Treatment Trial were examined and compared. Patient demographics, cardiopulmonary function, quality of life, and severity/distribution of the emphysema by quantitative CT were analyzed. Of the 1,218 patients enrolled in the trial, 42 were African American (3.4%) and 1,156 were white (95%). African Americans were younger (mean age +/- SD, 63 +/- 7 years vs 67 +/- 6 years) and smoked less (26 +/- 14 cigarettes per day vs 32 +/- 14 cigarettes per day) than white patients (p = 0.01). There was no difference between the two racial groups in pulmonary function (FEV1, 27 +/- 6% predicted vs 27 +/- 7% predicted), gas exchange (Pa(O2), 66 +/- 11 mm Hg vs 65 +/- 10 mm Hg), and exercise (33 +/- 14 W vs 36 +/- 21 W), respectively. Quality of life measures were similar between the groups, but African Americans had a lower socioeconomic status, lower education level, and fewer were married. Radiographic analysis of the extent of emphysema in African Americans, who were matched with selected white patients, revealed significantly less emphysema in the former group and different distribution of severe emphysema. African Americans with emphysema were younger and had a similar degree of lung impairment as the white study population despite smoking less. In a subgroup of matched patients, the severity and distribution of emphysema by quantitative radiographic analysis were different.

  6. Diagnosing and Mapping Pulmonary Emphysema on X-Ray Projection Images: Incremental Value of Grating-Based X-Ray Dark-Field Imaging

    PubMed Central

    Meinel, Felix G.; Schwab, Felix; Schleede, Simone; Bech, Martin; Herzen, Julia; Achterhold, Klaus; Auweter, Sigrid; Bamberg, Fabian; Yildirim, Ali Ö.; Bohla, Alexander; Eickelberg, Oliver; Loewen, Rod; Gifford, Martin; Ruth, Ronald; Reiser, Maximilian F.; Pfeiffer, Franz; Nikolaou, Konstantin

    2013-01-01

    Purpose To assess whether grating-based X-ray dark-field imaging can increase the sensitivity of X-ray projection images in the diagnosis of pulmonary emphysema and allow for a more accurate assessment of emphysema distribution. Materials and Methods Lungs from three mice with pulmonary emphysema and three healthy mice were imaged ex vivo using a laser-driven compact synchrotron X-ray source. Median signal intensities of transmission (T), dark-field (V) and a combined parameter (normalized scatter) were compared between emphysema and control group. To determine the diagnostic value of each parameter in differentiating between healthy and emphysematous lung tissue, a receiver-operating-characteristic (ROC) curve analysis was performed both on a per-pixel and a per-individual basis. Parametric maps of emphysema distribution were generated using transmission, dark-field and normalized scatter signal and correlated with histopathology. Results Transmission values relative to water were higher for emphysematous lungs than for control lungs (1.11 vs. 1.06, p<0.001). There was no difference in median dark-field signal intensities between both groups (0.66 vs. 0.66). Median normalized scatter was significantly lower in the emphysematous lungs compared to controls (4.9 vs. 10.8, p<0.001), and was the best parameter for differentiation of healthy vs. emphysematous lung tissue. In a per-pixel analysis, the area under the ROC curve (AUC) for the normalized scatter value was significantly higher than for transmission (0.86 vs. 0.78, p<0.001) and dark-field value (0.86 vs. 0.52, p<0.001) alone. Normalized scatter showed very high sensitivity for a wide range of specificity values (94% sensitivity at 75% specificity). Using the normalized scatter signal to display the regional distribution of emphysema provides color-coded parametric maps, which show the best correlation with histopathology. Conclusion In a murine model, the complementary information provided by X

  7. Diagnosing and mapping pulmonary emphysema on X-ray projection images: incremental value of grating-based X-ray dark-field imaging.

    PubMed

    Meinel, Felix G; Schwab, Felix; Schleede, Simone; Bech, Martin; Herzen, Julia; Achterhold, Klaus; Auweter, Sigrid; Bamberg, Fabian; Yildirim, Ali Ö; Bohla, Alexander; Eickelberg, Oliver; Loewen, Rod; Gifford, Martin; Ruth, Ronald; Reiser, Maximilian F; Pfeiffer, Franz; Nikolaou, Konstantin

    2013-01-01

    To assess whether grating-based X-ray dark-field imaging can increase the sensitivity of X-ray projection images in the diagnosis of pulmonary emphysema and allow for a more accurate assessment of emphysema distribution. Lungs from three mice with pulmonary emphysema and three healthy mice were imaged ex vivo using a laser-driven compact synchrotron X-ray source. Median signal intensities of transmission (T), dark-field (V) and a combined parameter (normalized scatter) were compared between emphysema and control group. To determine the diagnostic value of each parameter in differentiating between healthy and emphysematous lung tissue, a receiver-operating-characteristic (ROC) curve analysis was performed both on a per-pixel and a per-individual basis. Parametric maps of emphysema distribution were generated using transmission, dark-field and normalized scatter signal and correlated with histopathology. Transmission values relative to water were higher for emphysematous lungs than for control lungs (1.11 vs. 1.06, p<0.001). There was no difference in median dark-field signal intensities between both groups (0.66 vs. 0.66). Median normalized scatter was significantly lower in the emphysematous lungs compared to controls (4.9 vs. 10.8, p<0.001), and was the best parameter for differentiation of healthy vs. emphysematous lung tissue. In a per-pixel analysis, the area under the ROC curve (AUC) for the normalized scatter value was significantly higher than for transmission (0.86 vs. 0.78, p<0.001) and dark-field value (0.86 vs. 0.52, p<0.001) alone. Normalized scatter showed very high sensitivity for a wide range of specificity values (94% sensitivity at 75% specificity). Using the normalized scatter signal to display the regional distribution of emphysema provides color-coded parametric maps, which show the best correlation with histopathology. In a murine model, the complementary information provided by X-ray transmission and dark-field images adds incremental

  8. Clinical features, anti-cancer treatments and outcomes of lung cancer patients with combined pulmonary fibrosis and emphysema.

    PubMed

    Minegishi, Yuji; Kokuho, Nariaki; Miura, Yukiko; Matsumoto, Masaru; Miyanaga, Akihiko; Noro, Rintaro; Saito, Yoshinobu; Seike, Masahiro; Kubota, Kaoru; Azuma, Arata; Kida, Kouzui; Gemma, Akihiko

    2014-08-01

    Combined pulmonary fibrosis and emphysema (CPFE) patients may be at significantly increased risk of lung cancer compared with either isolated emphysema or pulmonary fibrosis patients. Acute exacerbation (AE) of interstitial lung disease caused by anticancer treatment is the most common lethal complication in Japanese lung cancer patients. Nevertheless, the clinical significance of CPFE compared with isolated idiopathic interstitial pneumonias (IIPs) in patients with lung cancer is not well understood. A total of 1536 patients with lung cancer at Nippon Medical School Hospital between March 1998 and October 2011 were retrospectively reviewed. Patients with IIPs were categorized into two groups: (i) CPFE; IIP patients with definite emphysema and (ii) non-CPFE; isolated IIP patients without definite emphysema. The clinical features, anti-cancer treatments and outcomes of the CPFE group were compared with those of the non-CPFE group. CPFE and isolated IIPs were identified in 88 (5.7%) and 63 (4.1%) patients respectively, with lung cancer. AE associated with initial treatment occurred in 22 (25.0%) patients in the CPFE group and in 8 (12.7%) patients in the non-CPFE group, irrespective of treatment modality. Median overall survival (OS) of the CPFE group was 23.7 months and that of the non-CPFE group was 20.3 months (P=0.627). Chemotherapy was performed in a total of 83 patients. AE associated with chemotherapy for advanced lung cancer occurred in 6 (13.6%) patients in the CPFE group and 5 (12.8%) patients in the non-CPFE group. Median OS of the CPFE group was 14.9 months and that of the non-CPFE group was 21.6 months (P=0.679). CPFE was not an independent risk factor for AE and was not an independent prognosis factor in lung cancer patients with IIPs. Therefore, great care must be exercised with CPFE as well as IIP patients when performing anticancer treatment for patients with lung cancer. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. 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.

  10. 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

  11. Master Autophagy Regulator Transcription Factor EB Regulates Cigarette Smoke-Induced Autophagy Impairment and Chronic Obstructive Pulmonary Disease-Emphysema Pathogenesis.

    PubMed

    Bodas, Manish; Patel, Neel; Silverberg, David; Walworth, Kyla; Vij, Neeraj

    2017-07-20

    Recent studies have shown that cigarette smoke (CS)-induced oxidative stress impairs autophagy, resulting in aggresome-formation that correlates with severity of chronic obstructive pulmonary disease (COPD)-emphysema, although the specific step in autophagy pathway that is impaired is unknown. Hence, in this study, we aimed to evaluate the role of master autophagy transcription factor EB (TFEB) in CS-induced COPD-emphysema pathogenesis. We first observed that TFEB accumulates in perinuclear spaces as aggresome-bodies in COPD lung tissues of tobacco smokers and severe emphysema subjects, compared with non-emphysema or nonsmoker controls. Next, Beas2b cells and C57BL/6 mice were exposed to either cigarette smoke extract (CSE) or subchronic-CS (sc-CS), followed by treatment with potent TFEB-inducing drug, gemfibrozil (GEM, or fisetin as an alternate), to experimentally verify the role of TFEB in COPD. Our in vitro results indicate that GEM/fisetin-mediated TFEB induction significantly (p < 0.05) decreases CSE-induced autophagy-impairment (Ub/LC3B reporter and autophagy flux assay) and resulting aggresome-formation (Ub/p62 coexpression/accumulation; immunoblotting and staining) by controlling reactive oxygen species (ROS) activity. Intriguingly, we observed that CS induces TFEB accumulation in the insoluble protein fractions of Beas2b cells, which shows a partial rescue with GEM treatment. Moreover, TFEB knockdown induces oxidative stress, autophagy-impairment, and senescence, which can all be mitigated by GEM-mediated TFEB induction. Finally, in vivo studies were used to verify that CS-induced autophagy-impairment (increased Ub, p62, and valosin-containing protein in the insoluble protein fractions of lung/cell lysates), inflammation (interleukin-6 [IL-6] levels in bronchoalveolar lavage fluid and iNOS expression in lung sections), apoptosis (caspase-3/7), and resulting emphysema (hematoxylin and eosin [H&E]) can be controlled by GEM-mediated TFEB induction (p

  12. Pneumomediastinum, bilateral pneumothorax, pleural effusion, and surgical emphysema after routine apicectomy caused by vomiting.

    PubMed

    Gulati, Archita; Baldwin, Andrew; Intosh, Ian Mc; Krishnan, A

    2008-03-01

    Mediastinal and subcutaneous emphysema may occur after dental and oral surgery as a result of iatrogenic introduction of air or injury to the tracheobronchial tree. We report a patient who developed emphysema and pneumothorax after dentoalveolar surgery, which made diagnosis and management difficult. We suggest that persistent postoperative vomiting caused inhalation of mediastinal and intrathoracic air.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. Periorbital emphysema during endodontic retreatment of an upper central incisor: a case report.

    PubMed

    Al-Qudah, A; Amin, F; Hassona, Y

    2013-11-08

    Subcutaneous emphysema is rarely encountered in endodontic practice and consequently there is a dearth of information in the dental literature about this complication. The following report presents an interesting case of periorbital emphysema encountered during endodontic therapy. Attention is drawn to the presentation and management of this mostly preventable complication.

  19. 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

  20. Ventilation/perfusion SPECT/CT in patients with pulmonary emphysema. Evaluation of software-based analysing.

    PubMed

    Schreiter, V; Steffen, I; Huebner, H; Bredow, J; Heimann, U; Kroencke, T J; Poellinger, A; Doellinger, F; Buchert, R; Hamm, B; Brenner, W; Schreiter, N F

    2015-01-01

    The purpose of this study was to evaluate the reproducibility of a new software based analysing system for ventilation/perfusion single-photon emission computed tomography/computed tomography (V/P SPECT/CT) in patients with pulmonary emphysema and to compare it to the visual interpretation. 19 patients (mean age: 68.1 years) with pulmonary emphysema who underwent V/P SPECT/CT were included. Data were analysed by two independent observers in visual interpretation (VI) and by software based analysis system (SBAS). SBAS PMOD version 3.4 (Technologies Ltd, Zurich, Switzerland) was used to assess counts and volume per lung lobe/per lung and to calculate the count density per lung, lobe ratio of counts and ratio of count density. VI was performed using a visual scale to assess the mean counts per lung lobe. Interobserver variability and association for SBAS and VI were analysed using Spearman's rho correlation coefficient. Interobserver agreement correlated highly in perfusion (rho: 0.982, 0.957, 0.90, 0.979) and ventilation (rho: 0.972, 0.924, 0.941, 0.936) for count/count density per lobe and ratio of counts/count density in SBAS. Interobserver agreement correlated clearly for perfusion (rho: 0.655) and weakly for ventilation (rho: 0.458) in VI. SBAS provides more reproducible measures than VI for the relative tracer uptake in V/P SPECT/CTs in patients with pulmonary emphysema. However, SBAS has to be improved for routine clinical use.

  1. Interactions of regional respiratory mechanics and pulmonary ventilatory impairment in pulmonary emphysema: assessment with dynamic MRI and xenon-133 single-photon emission CT.

    PubMed

    Suga, K; Tsukuda, T; Awaya, H; Matsunaga, N; Sugi, K; Esato, K

    2000-06-01

    Dynamic MRI and (133)Xe single-photon emission CT (SPECT) were used to directly evaluate the interaction of regional respiratory mechanics and lung ventilatory function in pulmonary emphysema. Respiratory diaphragmatic and chest wall (D/CW) motions were analyzed by sequential MRI of fast-gradient echo pulse sequences during two to three respiratory cycles in 28 patients with pulmonary emphysema, including 9 patients undergoing lung volume reduction surgery (LVRS). The extent of air trapping in the regional lung was quantified by the (133)Xe retention index (RI) on three-dimensional (133)Xe SPECT displays. By contrast to healthy subjects (n = 6) with regular, synchronous D/CW motions, pulmonary emphysema patients showed reduced, irregular, or asynchronous motions in the hemithorax or location with greater (133)Xe retention, with significant decreases in the maximal amplitude of D/CW motions (MADM and MACWM; p < 0.0001 and p < 0.05, respectively). The removal of (133)Xe retention sites by LVRS effectively and regionally improved D/CW motions in nine patients, with significant increases in MADM and MACWM (p < 0.01 and p < 0.001, respectively). In a total of 40 studies of the 28 patients including post-LVRS studies, normalized MADM and MACWM correlated with percent predicted FEV(1) (r = 0.881, p < 0.0001; and r = 0.906, p < 0.0001, respectively), and also with (133)Xe RI in each hemithorax (r = -0.871, p < 0 0.0001; and r = -0.901, p < 0 0.0001, respectively.) This direct comparison of regional respiratory mechanics with lung ventilation demonstrated a close interaction between these impairments in pulmonary emphysema. The present techniques provide additional sensitivity for evaluating pathophysiologic compromises in pulmonary emphysema, and may also be useful for selecting resection targets for LVRS and for monitoring the effects.

  2. 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.

  3. 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

  4. Transconjunctival orbital emphysema caused by compressed air injury: A case report

    PubMed Central

    Vasu, Usha; Francis, Febson; Nazareth, Colin

    2008-01-01

    Orbital emphysema following conjunctival tear in the absence of orbital wall fracture, caused by air under pressure is rare. Usually orbital emphysema is seen in facial trauma associated with damage to the adjacent paranasal sinuses or facial bones. To the best of our knowledge, there have been only eight reports of orbital emphysema following use of compressed air during industrial work. The air under pressure is pushed through the subconjunctival space into the subcutaneous and retrobulbar spaces. We present here a rare cause of orbital emphysema in a young man working with compressed air gun. Although the emphysema was severe, there were no orbital bone fracture and the visual recovery of the patient was complete without attendant complications. PMID:18417833

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. Tension Pneumothorax and Subcutaneous Emphysema Complicating Insertion of Nasogastric Tube

    PubMed Central

    AL Saif, Narjis; Al-Azem, M. Ali; Al-Hubail, Rasheed

    2015-01-01

    Nasogastric tube has a key role in the management of substantial number of hospitalized patients particularly the critically ill. In spite of the apparent simple insertion technique, nasogastric tube placement has its serious perhaps fatal complications which need to be carefully assessed. Pulmonary misplacement and associated complications are commonplace during nasogastric tube procedure. We present a case of tension pneumothorax and massive surgical emphysema in critically ill ventilated patient due to inadvertent nasogastric tube insertion and also discussed the risk factors, complication list, and arrays of techniques for safer tube placement. PMID:26448883

  10. Tension Pneumothorax and Subcutaneous Emphysema Complicating Insertion of Nasogastric Tube.

    PubMed

    Al Saif, Narjis; Hammodi, Adel; Al-Azem, M Ali; Al-Hubail, Rasheed

    2015-01-01

    Nasogastric tube has a key role in the management of substantial number of hospitalized patients particularly the critically ill. In spite of the apparent simple insertion technique, nasogastric tube placement has its serious perhaps fatal complications which need to be carefully assessed. Pulmonary misplacement and associated complications are commonplace during nasogastric tube procedure. We present a case of tension pneumothorax and massive surgical emphysema in critically ill ventilated patient due to inadvertent nasogastric tube insertion and also discussed the risk factors, complication list, and arrays of techniques for safer tube placement.

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. Effect of emphysema on CT scan measures of airway dimensions in smokers.

    PubMed

    Diaz, Alejandro A; Han, MeiLan K; Come, Carolyn E; San José Estépar, Raúl; Ross, James C; Kim, Victor; Dransfield, Mark T; Curran-Everett, Douglas; Schroeder, Joyce D; Lynch, David A; Tschirren, Juerg; Silverman, Edwin K; Washko, George R

    2013-03-01

    In CT scans of smokers with COPD, the subsegmental airway wall area percent (WA%) is greater and more strongly correlated with FEV1 % predicted than WA% obtained in the segmental airways. Because emphysema is linked to loss of airway tethering and may limit airway expansion, increases in WA% may be related to emphysema and not solely to remodeling. We aimed to first determine whether the stronger association of subsegmental vs segmental WA% with FEV1 % predicted is mitigated by emphysema and, second, to assess the relationships among emphysema, WA%, and total bronchial area (TBA). We analyzed CT scan segmental and subsegmental WA% (WA% = 100 × wall area/TBA) of six bronchial paths and corresponding lobar emphysema, lung function, and clinical data in 983 smokers with COPD. Compared with segmental WA%, the subsegmental WA% had a greater effect on FEV1% predicted (-0.8% to -1.7% vs -1.9% to -2.6% per 1-unit increase in WA%, respectively; P < .05 for most bronchial paths). After adjusting for emphysema, the association between subsegmental WA% and FEV1 % predicted was weakened in two bronchial paths. Increases in WA% between bronchial segments correlated directly with emphysema in all bronchial paths (P < .05). In multivariate regression models, emphysema was directly related to subsegmental WA% in most bronchial paths and inversely related to subsegmental TBA in all bronchial paths. The greater effect of subsegmental WA% on airflow obstruction is mitigated by emphysema. Part of the emphysema effect might be due to loss of airway tethering, leading to a reduction in TBA and an increase in WA%.

  16. Effect of Emphysema on CT Scan Measures of Airway Dimensions in Smokers

    PubMed Central

    Han, MeiLan K.; Come, Carolyn E.; San José Estépar, Raúl; Ross, James C.; Kim, Victor; Dransfield, Mark T.; Curran-Everett, Douglas; Schroeder, Joyce D.; Lynch, David A.; Tschirren, Juerg; Silverman, Edwin K.; Washko, George R.

    2013-01-01

    Background: In CT scans of smokers with COPD, the subsegmental airway wall area percent (WA%) is greater and more strongly correlated with FEV1 % predicted than WA% obtained in the segmental airways. Because emphysema is linked to loss of airway tethering and may limit airway expansion, increases in WA% may be related to emphysema and not solely to remodeling. We aimed to first determine whether the stronger association of subsegmental vs segmental WA% with FEV1 % predicted is mitigated by emphysema and, second, to assess the relationships among emphysema, WA%, and total bronchial area (TBA). Methods: We analyzed CT scan segmental and subsegmental WA% (WA% = 100 × wall area/TBA) of six bronchial paths and corresponding lobar emphysema, lung function, and clinical data in 983 smokers with COPD. Results: Compared with segmental WA%, the subsegmental WA% had a greater effect on FEV1% predicted (−0.8% to −1.7% vs −1.9% to −2.6% per 1-unit increase in WA%, respectively; P < .05 for most bronchial paths). After adjusting for emphysema, the association between subsegmental WA% and FEV1 % predicted was weakened in two bronchial paths. Increases in WA% between bronchial segments correlated directly with emphysema in all bronchial paths (P < .05). In multivariate regression models, emphysema was directly related to subsegmental WA% in most bronchial paths and inversely related to subsegmental TBA in all bronchial paths. Conclusion: The greater effect of subsegmental WA% on airflow obstruction is mitigated by emphysema. Part of the emphysema effect might be due to loss of airway tethering, leading to a reduction in TBA and an increase in WA%. Trial registry: ClinicalTrials.gov; No.: NCT00608764; URL: www.clinicaltrials.gov PMID:23460155

  17. Patients with severe emphysema have a low risk of radiation pneumonitis following stereotactic body radiotherapy

    PubMed Central

    Ishijima, M; Itonaga, T; Tajima, Y; Shiraishi, S; Okubo, M; Mikami, R; Tokuuye, K

    2015-01-01

    Objective: To evaluate the risk of radiation pneumonitis (RP) after stereotactic radiotherapy (SBRT) for patients presenting with severe pulmonary emphysema. Methods: This study included 40 patients with Stage I non-small-cell lung cancer who underwent SBRT, 75 Gy given in 30 fractions, at the Tokyo Medical University, Tokyo, Japan, between February 2010 and February 2013. The median age of the patients was 79 years (range, 49–90 years), and the male:female ratio was 24:16. There were 20 T1 and 20 T2 tumours. 17 patients had emphysema, 6 had slight interstitial changes on CT images and the remaining 17 had no underlying lung disease. The level of emphysema was classified into three groups according to the modified Goddard's criteria (severe: three patients, moderate: eight patients and mild: six patients). Changes in the irradiated lung following SBRT were evaluated by CT. Results: On CT images, RP was detected in 34 (85%) patients, and not in 6 (15%) patients, during a median observation period of 313 days. Of the six patients, three had severe emphysema and three had no underlying lung disease. Patients with severe emphysema had lower risk of RP than those with moderate emphysema (p = 0.01), mild emphysema (p = 0.04) and no underlying lung disease (p = 0.01). Conclusion: Patients with severe emphysema had a low risk of RP following SBRT. Advances in knowledge: Little is known about the association between RP and pulmonary emphysema. Patients with severe emphysema had lower risk of RP than those with no underlying lung disease. PMID:25490255

  18. The role of matrix metalloproteinase-9 in cigarette smoke-induced emphysema.

    PubMed

    Atkinson, Jeffrey J; Lutey, Barbara A; Suzuki, Yoko; Toennies, Holly M; Kelley, Diane G; Kobayashi, Dale K; Ijem, Whitney G; Deslee, Gaetan; Moore, Carla H; Jacobs, M Eileen; Conradi, Susan H; Gierada, David S; Pierce, Richard A; Betsuyaku, Tomoko; Senior, Robert M

    2011-04-01

    Matrix metalloprotease (MMP)-9 is an elastolytic endopeptidase produced by activated macrophages that may be involved in the development of human pulmonary emphysema and could be inhibited with existing compounds. Mouse models have demonstrated that excess MMP-9 production can result in permanent alveolar destruction. To determine if MMP-9 causes cigarette smoke-induced emphysema using MMP-9 knockout mice and human samples. Mouse lungs were analyzed for inflammation and airspace enlargement using a mainstream smoke-exposure model. Human macrophage mRNA was isolated from subjects with emphysema by laser capture microdissection. Human blood monocyte mRNA was isolated from subjects with greater than 30 pack-year smoking history. Human gene expression was determined by quantitative polymerase chain reaction and compared with emphysema severity determined by automated computed tomography analysis. Plasma Clara cell secretory protein and surfactant protein-D were quantified to measure ongoing lung injury. Mice deficient in MMP-9 develop the same degree of cigarette smoke-induced inflammation and airspace enlargement as strain-matched controls. Macrophages are the predominant source of MMP-9 production in human emphysema specimens and similar quantities of macrophage MMP-9 mRNA is present in areas of lung with and without emphysema. Circulating monocytes produce more MMP-9 in individuals with advanced emphysema severity despite no correlation of MMP-9 with markers of ongoing lung damage. These results suggest that MMP-9 in humans who smoke is similar to smoke-exposed mice, where MMP-9 is present in emphysematous lung but not correlated with the emphysema. To the degree that the mechanisms of emphysema in humans who smoke resemble the mouse model, these data suggest specific inhibition of MMP-9 is unlikely to be an effective therapy for cigarette smoke-induced emphysema. Clinical trial registered with www.clinicaltrials.gov (NCT 00757120).

  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. 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.

  1. 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.

  2. 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

  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. 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.

  5. 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.

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

    PubMed

    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.

  8. 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.

  9. Predictors of mortality in patients with emphysema and severe airflow obstruction.

    PubMed

    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

    2006-06-15

    Limited data exist describing risk factors for mortality in patients having predominantly emphysema. 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). 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). 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.

  10. 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.

  11. 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.

  12. 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.

  13. Proteomic differences with and without ozone-exposure in a smoking-induced emphysema lung model

    PubMed Central

    Uh, Soo-Taek; Koo, So-My; Jang, An Soo; Park, Sung Woo; Choi, Jae Sung; Kim, Yong-Hoon

    2015-01-01

    Background/Aims Acute exacerbations in chronic obstructive pulmonary disease may be related to air pollution, of which ozone is an important constituent. In this study, we investigated the protein profiles associated with ozone-induced exacerbations in a smoking-induced emphysema model. Methods Mice were divided into the following groups: group I, no smoking and no ozone (NS + NO); group II, no smoking and ozone (NS + O); group III, smoking and no ozone (S + NO); and group IV, smoking and ozone (S + O). Bronchoalveolar lavage, the mean linear intercept (MLI) on hematoxylin and eosin staining, nano-liquid chromatography-tandem mass spectrometry (LC-MS/MS), and Western blotting analyses were performed. Results The MLIs of groups III (S + NO) and IV (S + O) (45 ± 2 and 44 ± 3 µm, respectively) were significantly higher than those of groups I (NS + NO) and II (NS + O) (26 ± 2 and 23 ± 2 µm, respectively; p < 0.05). Fourteen spots that showed significantly different intensities on image analyses of two-dimensional (2D) protein electrophoresis in group I (NS + NO) were identified by LC-MS/MS. The levels of six proteins were higher in group IV (S + O). The levels of vimentin, lactate dehydrogenase A, and triose phosphate isomerase were decreased by both smoking and ozone treatment in Western blotting and proteomic analyses. In contrast, TBC1 domain family 5 (TBC1D5) and lamin A were increased by both smoking and ozone treatment. Conclusions TBC1D5 could be a biomarker of ozone-induced lung injury in emphysema. PMID:25589837

  14. Statin reverses smoke-induced pulmonary hypertension and prevents emphysema but not airway remodeling.

    PubMed

    Wright, Joanne L; Zhou, Steven; Preobrazhenska, Olena; Marshall, Caroline; Sin, Don D; Laher, Ismail; Golbidi, Saeid; Churg, Andrew M

    2011-01-01

    the potential role of statins in treating chronic obstructive pulmonary disease (COPD) is controversial, and it is unclear what anatomic COPD lesions statins affect. to determine whether an intervention of simvastatin could alter cigarette smoke-induced pulmonary hypertension. we exposed guinea pigs to cigarette smoke for 6 months. In half the animals, simvastatin therapy was initiated after 3 months of smoke exposure. Pulmonary arterial systolic pressures were monitored weekly with a radiotelemetric catheter; additional physiologic and morphologic measurements were made at sacrifice after 6 months. Precision-cut lung explants were assessed for evidence of endothelial dysfunction, and in situ vascular nitric oxide generation was measured with 4,5-diaminofluorescein diacetate. cigarette smoke increased the pulmonary arterial systolic pressure after approximately 4 weeks. Simvastatin returned the pressure to control levels within 4 weeks of starting treatment, and ameliorated smoke-induced small arterial remodeling as well as emphysema measured both physiologically and morphometrically at 6 months, but did not prevent smoke-induced small airway remodeling either physiologically or morphologically. In precision-cut lung slices simvastatin reversed small arterial endothelial dysfunction, and partially reversed smoke-induced loss of vascular nitric oxide generation. simvastatin, as an intervention therapy, reverses the pulmonary vascular effects of cigarette smoke, including pulmonary hypertension, and prevents smoke-induced emphysema, but does not prevent small airway remodeling. This is the first demonstration that an intervention can reverse a COPD-associated cigarette smoke-induced anatomic abnormality. The study also shows the importance of examining all three anatomic lung compartments when assessing the effects of a potential drug intervention in patients with COPD.

  15. 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.

  16. 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).

  17. 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

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

    PubMed Central

    An, Chang Hyeok; Wang, Xiao Mei; Lam, Hilaire C.; Ifedigbo, Emeka; Washko, George R.; Ryter, Stefan W.

    2012-01-01

    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. PMID:22983353

  19. Proteomic differences with and without ozone-exposure in a smoking-induced emphysema lung model.

    PubMed

    Uh, Soo-Taek; Koo, So-My; Jang, An Soo; Park, Sung Woo; Choi, Jae Sung; Kim, Yong-Hoon; Park, Choon Sik

    2015-01-01

    Acute exacerbations in chronic obstructive pulmonary disease may be related to air pollution, of which ozone is an important constituent. In this study, we investigated the protein profiles associated with ozone-induced exacerbations in a smoking-induced emphysema model. Mice were divided into the following groups: group I, no smoking and no ozone (NS + NO); group II, no smoking and ozone (NS + O); group III, smoking and no ozone (S + NO); and group IV, smoking and ozone (S + O). Bronchoalveolar lavage, the mean linear intercept (MLI) on hematoxylin and eosin staining, nano-liquid chromatography-tandem mass spectrometry (LC-MS/MS), and Western blotting analyses were performed. The MLIs of groups III (S + NO) and IV (S + O) (45 ± 2 and 44 ± 3 µm, respectively) were significantly higher than those of groups I (NS + NO) and II (NS + O) (26 ± 2 and 23 ± 2 µm, respectively; p < 0.05). Fourteen spots that showed significantly different intensities on image analyses of two-dimensional (2D) protein electrophoresis in group I (NS + NO) were identified by LC-MS/MS. The levels of six proteins were higher in group IV (S + O). The levels of vimentin, lactate dehydrogenase A, and triose phosphate isomerase were decreased by both smoking and ozone treatment in Western blotting and proteomic analyses. In contrast, TBC1 domain family 5 (TBC1D5) and lamin A were increased by both smoking and ozone treatment. TBC1D5 could be a biomarker of ozone-induced lung injury in emphysema.

  20. 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.

  1. 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.

  2. Increased Matrix Metalloproteinase (MMPs) Levels Do Not Predict Disease Severity or Progression in Emphysema

    PubMed Central

    D’Armiento, Jeanine M.; Goldklang, Monica P.; Hardigan, Andrew A.; Geraghty, Patrick; Roth, Michael D.; Connett, John E.; Wise, Robert A.; Sciurba, Frank C.; Scharf, Steven M.; Thankachen, Jincy; Islam, Monirul; Ghio, Andrew J.; Foronjy, Robert F.

    2013-01-01

    Rationale Though matrix metalloproteinases (MMPs) are critical in the pathogenesis of COPD, their utility as a disease biomarker remains uncertain. This study aimed to determine whether bronchoalveolar lavage (BALF) or plasma MMP measurements correlated with disease severity or functional decline in emphysema. Methods Enzyme-linked immunosorbent assay and luminex assays measured MMP-1, -9, -12 and tissue inhibitor of matrix metalloproteinase-1 in the BALF and plasma of non-smokers, smokers with normal lung function and moderate-to-severe emphysema subjects. In the cohort of 101 emphysema subjects correlative analyses were done to determine if MMP or TIMP-1 levels were associated with key disease parameters or change in lung function over an 18-month time period. Main Results Compared to non-smoking controls, MMP and TIMP-1 BALF levels were significantly elevated in the emphysema cohort. Though MMP-1 was elevated in both the normal smoker and emphysema groups, collagenase activity was only increased in the emphysema subjects. In contrast to BALF, plasma MMP-9 and TIMP-1 levels were actually decreased in the emphysema cohort compared to the control groups. Both in the BALF and plasma, MMP and TIMP-1 measurements in the emphysema subjects did not correlate with important disease parameters and were not predictive of subsequent functional decline. Conclusions MMPs are altered in the BALF and plasma of emphysema; however, the changes in MMPs correlate poorly with parameters of disease intensity or progression. Though MMPs are pivotal in the pathogenesis of COPD, these findings suggest that measuring MMPs will have limited utility as a prognostic marker in this disease. PMID:23441181

  3. Increased matrix metalloproteinase (MMPs) levels do not predict disease severity or progression in emphysema.

    PubMed

    D'Armiento, Jeanine M; Goldklang, Monica P; Hardigan, Andrew A; Geraghty, Patrick; Roth, Michael D; Connett, John E; Wise, Robert A; Sciurba, Frank C; Scharf, Steven M; Thankachen, Jincy; Islam, Monirul; Ghio, Andrew J; Foronjy, Robert F

    2013-01-01

    Though matrix metalloproteinases (MMPs) are critical in the pathogenesis of COPD, their utility as a disease biomarker remains uncertain. This study aimed to determine whether bronchoalveolar lavage (BALF) or plasma MMP measurements correlated with disease severity or functional decline in emphysema. Enzyme-linked immunosorbent assay and luminex assays measured MMP-1, -9, -12 and tissue inhibitor of matrix metalloproteinase-1 in the BALF and plasma of non-smokers, smokers with normal lung function and moderate-to-severe emphysema subjects. In the cohort of 101 emphysema subjects correlative analyses were done to determine if MMP or TIMP-1 levels were associated with key disease parameters or change in lung function over an 18-month time period. Compared to non-smoking controls, MMP and TIMP-1 BALF levels were significantly elevated in the emphysema cohort. Though MMP-1 was elevated in both the normal smoker and emphysema groups, collagenase activity was only increased in the emphysema subjects. In contrast to BALF, plasma MMP-9 and TIMP-1 levels were actually decreased in the emphysema cohort compared to the control groups. Both in the BALF and plasma, MMP and TIMP-1 measurements in the emphysema subjects did not correlate with important disease parameters and were not predictive of subsequent functional decline. MMPs are altered in the BALF and plasma of emphysema; however, the changes in MMPs correlate poorly with parameters of disease intensity or progression. Though MMPs are pivotal in the pathogenesis of COPD, these findings suggest that measuring MMPs will have limited utility as a prognostic marker in this disease.

  4. 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.

  5. Spontaneous subcutaneous emphysema of the scalp following hair coloring/treatment.

    PubMed

    Tewari, Sanjit O; Faroqui, Raihan M; Fuca, Nicholas; Khan, Mansoor; Mantello, Michael T

    2017-03-01

    Subcutaneous emphysema of the scalp is a process often attributed to secondary factors such as trauma, infection, or a myriad of iatrogenic etiologies. Here, we are presenting a case report of an adult patient with spontaneous subcutaneous emphysema of the scalp following a hair coloring/treatment. We performed an extensive review of literature on this topic, however, could not find a single case with similar presentation of subcutaneous emphysema. This case demonstrates an unreported etiology for this diagnosis and is thus being reported for its uniqueness and to raise clinical awareness.

  6. 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.

  7. 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.

  8. 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

  9. Bronchoscopic lung-volume reduction with Exhale airway stents for emphysema (EASE trial): randomised, sham-controlled, multicentre trial.

    PubMed

    Shah, P L; Slebos, D-J; Cardoso, P F G; Cetti, E; Voelker, K; Levine, B; Russell, M E; Goldin, J; Brown, M; Cooper, J D; Sybrecht, G W

    2011-09-10

    Airway bypass is a bronchoscopic lung-volume reduction procedure for emphysema whereby transbronchial passages into the lung are created to release trapped air, supported with paclitaxel-coated stents to ease the mechanics of breathing. The aim of the EASE (Exhale airway stents for emphysema) trial was to evaluate safety and efficacy of airway bypass in people with severe homogeneous emphysema. We undertook a randomised, double-blind, sham-controlled study in 38 specialist respiratory centres worldwide. We recruited 315 patients who had severe hyperinflation (ratio of residual volume [RV] to total lung capacity of ≥0·65). By computer using a random number generator, we randomly allocated participants (in a 2:1 ratio) to either airway bypass (n=208) or sham control (107). We divided investigators into team A (masked), who completed pre-procedure and post-procedure assessments, and team B (unmasked), who only did bronchoscopies without further interaction with patients. Participants were followed up for 12 months. The 6-month co-primary efficacy endpoint required 12% or greater improvement in forced vital capacity (FVC) and 1 point or greater decrease in the modified Medical Research Council dyspnoea score from baseline. The composite primary safety endpoint incorporated five severe adverse events. We did Bayesian analysis to show the posterior probability that airway bypass was superior to sham control (success threshold, 0·965). Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00391612. All recruited patients were included in the analysis. At 6 months, no difference between treatment arms was noted with respect to the co-primary efficacy endpoint (30 of 208 for airway bypass vs 12 of 107 for sham control; posterior probability 0·749, below the Bayesian success threshold of 0·965). The 6-month composite primary safety endpoint was 14·4% (30 of 208) for airway bypass versus 11·2% (12 of 107) for sham control

  10. 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