Science.gov

Sample records for emphysema show independent

  1. Association of Radiographic Emphysema and Airflow Obstruction with Lung Cancer

    PubMed Central

    Wilson, David O.; Weissfeld, Joel L.; Balkan, Arzu; Schragin, Jeffrey G.; Fuhrman, Carl R.; Fisher, Stephen N.; Wilson, Jonathan; Leader, Joseph K.; Siegfried, Jill M.; Shapiro, Steven D.; Sciurba, Frank C.

    2008-01-01

    Rationale: To study the relationship between emphysema and/or airflow obstruction and lung cancer in a high-risk population. Objective: We studied lung cancer related to radiographic emphysema and spirometric airflow obstruction in tobacco-exposed persons who were screened for lung cancer using chest computed tomography (CT). Methods: Subjects completed questionnaires, spirometry, and low-dose helical chest CT. CT scans were scored for emphysema based on National Emphysema Treatment Trial criteria. Multiple logistic regressions estimated the independent associations between various factors, including radiographic emphysema and airflow obstruction, and subsequent lung cancer diagnosis. Measurements and Main Results: Among 3,638 subjects, 57.5, 18.8, 14.6, and 9.1% had no, trace, mild, and moderate–severe emphysema, and 57.3, 13.6, 22.8, and 6.4% had no, mild (Global Initiative for Chronic Obstructive Lung Disease [GOLD] I), moderate (GOLD II), and severe (GOLD III–IV) airflow obstruction. Of 3,638 subjects, 99 (2.7%) received a lung cancer diagnosis. Adjusting for sex, age, years of cigarette smoking, and number of cigarettes smoked daily, logistic regression showed the expected lung cancer association with the presence of airflow obstruction (GOLD I–IV, odds ratio [OR], 2.09; 95% confidence interval [CI], 1.33–3.27). A second logistic regression showed lung cancer related to emphysema (OR, 3.56; 95% CI, 2.21–5.73). After additional adjustments for GOLD class, emphysema remained a strong and statistically significant factor related to lung cancer (OR, 3.14; 95% CI, 1.91–5.15). Conclusions: Emphysema on CT scan and airflow obstruction on spirometry are related to lung cancer in a high-risk population. Emphysema is independently related to lung cancer. Both radiographic emphysema and airflow obstruction should be considered when assessing lung cancer risk. PMID:18565949

  2. Subcutaneous emphysema

    MedlinePlus

    ... after certain infections, including gas gangrene , and after scuba diving. ... will determine the outcome. Subcutaneous emphysema associated with scuba diving is usually less worrisome or serious.

  3. 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

  4. 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

    2013-04-01

    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

  5. 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.

  6. 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

  7. Bronchoscopic treatments for emphysema.

    PubMed

    Delage, A; Marquette, C-H

    2011-10-01

    In late stage chronic obstructive pulmonary disease, emphysema can worsen respiratory symptoms, not only via the loss of surface for gas exchange, but also via alterations in mechanical properties of the respiratory system (dynamic and static hyperinflation). Emphysematous lung volume reduction aims at improving respiratory mechanics and symptomatology in patients with advanced emphysema. Lung volume reduction surgery (LVRS) has been shown to be effective in selected patient populations, but its morbidity and costs are quite elevated. Alternatives to LVRS do not remove emphysematous lung tissue per se, but rather consist of devices aiming to: 1) reduce the volume that affected lung parenchyma occupies (unidirectional endobronchial valves or plugs, parenchymal injection of bioactive scarring agents); 2) redistribute ventilatory flow (airway bypass systems). Preliminary studies of these devices have shown that they are relatively safe. These also show modest benefits in exercise capacity, although individual subjects can experience spectacular improvement. Current objective is to identify predictors of response to therapy with such devices. PMID:22099415

  8. Image Processing Diagnostics: Emphysema

    NASA Astrophysics Data System (ADS)

    McKenzie, Alex

    2009-10-01

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

  9. National Emphysema Foundation

    MedlinePlus

    ... Yiddish HOME THE LUNG COPD / Emphysema Advice for COPD/Emphysema Patients from Dr. Petty Asthma Interstitial Lung Disease PREVENTION Smoking Pollution and the Environment Occupational Health Hazards Early ...

  10. [Drainage for Subcutaneous Emphysema after Pulmonary Resection].

    PubMed

    Funakoshi, Yasunobu; Ohmori, Kenichi; Takeda, Shinichi

    2016-05-01

    Severe subcutaneous emphysema sometimes develops after pulmonary resection. We report our management of ten patients who were treated with subcutaneous Penrose drainage. Water seal test at chest closure showed no air leakage in 5, and a small amount in 5. Chest X-ray at the progression of massive subcutaneous emphysema showed no obvious pneumothorax in 2, and slight apical pneumothorax in 8. Subcutaneous emphysema developed after removal of chest tubes in 6, and before removal in 4. Subcutaneous drains were inserted at the midclavicular line or the side chest in 8, and both in 2. Subcutaneous emphysema improved immediately after subcutaneous Penrose drainage with active compressive massage. Subcutaneous penrose drainage is easy and useful for relieving massive subcutaneous emphysema. PMID:27220920

  11. Nitric oxide diffusing capacity versus spirometry in the early diagnosis of emphysema in smokers.

    PubMed

    van der Lee, I; Gietema, H A; Zanen, P; van Klaveren, R J; Prokop, M; Lammers, J-W J; van den Bosch, J M M

    2009-12-01

    The diffusion capacity for nitric oxide (DLNO) is independent of pulmonary capillary blood volume and equals the membrane diffusing capacity. Therefore the DLNO could be more sensitive in detecting alveolar destruction than the DLCO. We measured flow-volumes curves, DLNO, DLCO, the transfer coefficients KNO (DLNO/VA) and KCO (DLCO/VA) and performed computed tomography (CT) scans in 263 randomly selected heavy smokers. Subjects with areas > or =1% of the total lung volume showing an attenuation <-950 Hounsfield Units were considered to have emphysema. In 36 subjects emphysema was diagnosed with CT, a low KNO was present in 94 subjects, and in 95 subjects a FEV1/FVC ratio <70% was seen. The area under the ROC curve for detection CT-based emphysema was 0.894 for the KNO, 0.822 for the KCO and 0.795 for FEV1/FVC, meaning that the KNO has a slightly higher sensitivity to detect emphysema than the KCO and FEV1/FVC. The positive predictive value of KNO however was low (34.7%), while the negative predictive value of KNO was very high (98.2%), indicating an emphysema exclusion test. The DLNO/DLCO ratio is significantly higher in the study group compared to normal subjects.

  12. Congenital lobar emphysema

    PubMed Central

    Tural-Kara, Tuğçe; Özdemir, Halil; Çiftçi, Ergin; İnce, Erdal

    2016-01-01

    Congenital lobar emphysema is a rare disease, which is characterized by pulmoner hyperinflation. Depending on the degree of bronchial obstruction, the clinical presentation may be variable. We report a rare case with congenital lobar emphysema in a 38-days-old male infant who presented with severe respiratory distress and hypertension. Air trapping in the left upper lung and significant mediastinal shift to the right were observed on the chest x-ray. Emphysematous changes were detected on the thorax computed tomography and considered as congenital lobar emphysema. The upper left lobectomy was successfully performed by pediatric surgeons. On postoperative follow up, no sign of respiratory distress occurred and the patient was normotensive. In this report, a case with congenital lobar emphysema, which is a rare cause of respiratory distress and hypertension is discussed. PMID:27381542

  13. 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

  14. Expression profiling identifies genes involved in emphysema severity.

    PubMed

    Francis, Santiyagu M Savarimuthu; Larsen, Jill E; Pavey, Sandra J; Bowman, Rayleen V; Hayward, Nicholas K; Fong, Kwun M; Yang, Ian A

    2009-01-01

    Chronic obstructive pulmonary disease (COPD) is a major public health problem. The aim of this study was to identify genes involved in emphysema severity in COPD patients.Gene expression profiling was performed on total RNA extracted from non-tumor lung tissue from 30 smokers with emphysema. Class comparison analysis based on gas transfer measurement was performed to identify differentially expressed genes. Genes were then selected for technical validation by quantitative reverse transcriptase-PCR (qRT-PCR) if also represented on microarray platforms used in previously published emphysema studies. Genes technically validated advanced to tests of biological replication by qRT-PCR using an independent test set of 62 lung samples.Class comparison identified 98 differentially expressed genes (p < 0.01). Fifty-one of those genes had been previously evaluated in differentiation between normal and severe emphysema lung. qRT-PCR confirmed the direction of change in expression in 29 of the 51 genes and 11 of those validated, remaining significant at p < 0.05. Biological replication in an independent cohort confirmed the altered expression of eight genes, with seven genes differentially expressed by greater than 1.3 fold, identifying these as candidate determinants of emphysema severity.Gene expression profiling of lung from emphysema patients identified seven candidate genes associated with emphysema severity including COL6A3, SERPINF1, ZNHIT6, NEDD4, CDKN2A, NRN1 and GSTM3. PMID:19723343

  15. Expression profiling identifies genes involved in emphysema severity

    PubMed Central

    2009-01-01

    Chronic obstructive pulmonary disease (COPD) is a major public health problem. The aim of this study was to identify genes involved in emphysema severity in COPD patients. Gene expression profiling was performed on total RNA extracted from non-tumor lung tissue from 30 smokers with emphysema. Class comparison analysis based on gas transfer measurement was performed to identify differentially expressed genes. Genes were then selected for technical validation by quantitative reverse transcriptase-PCR (qRT-PCR) if also represented on microarray platforms used in previously published emphysema studies. Genes technically validated advanced to tests of biological replication by qRT-PCR using an independent test set of 62 lung samples. Class comparison identified 98 differentially expressed genes (p < 0.01). Fifty-one of those genes had been previously evaluated in differentiation between normal and severe emphysema lung. qRT-PCR confirmed the direction of change in expression in 29 of the 51 genes and 11 of those validated, remaining significant at p < 0.05. Biological replication in an independent cohort confirmed the altered expression of eight genes, with seven genes differentially expressed by greater than 1.3 fold, identifying these as candidate determinants of emphysema severity. Gene expression profiling of lung from emphysema patients identified seven candidate genes associated with emphysema severity including COL6A3, SERPINF1, ZNHIT6, NEDD4, CDKN2A, NRN1 and GSTM3. PMID:19723343

  16. 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.

  17. Patterns of Emphysema Heterogeneity

    PubMed Central

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

    2016-01-01

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

  18. Independently evolved upper jaw protrusion mechanisms show convergent hydrodynamic function in teleost fishes.

    PubMed

    Staab, Katie Lynn; Holzman, Roi; Hernandez, L Patricia; Wainwright, Peter C

    2012-05-01

    A protrusible upper jaw has independently evolved multiple times within teleosts and has been implicated in the success of two groups in particular: Acanthomorpha and Cypriniformes. We use digital particle image velocimetry (DPIV) to compare suction feeding flow dynamics in a representative of each of these clades: goldfish and bluegill. Using DPIV, we contrast the spatial pattern of flow, the temporal relationship between flow and head kinematics, and the contribution of jaw protrusion to the forces exerted on prey. As expected, the spatial patterns of flow were similar in the two species. However, goldfish were slower to reach maximal kinematic excursions, and were more flexible in the relative timing of jaw protrusion, other jaw movements and suction flows. Goldfish were also able to sustain flow speeds for a prolonged period of time as compared with bluegill, in part because goldfish generate lower peak flow speeds. In both species, jaw protrusion increased the force exerted on the prey. However, slower jaw protrusion in goldfish resulted in less augmentation of suction forces. This difference in force exerted on prey corresponds with differences in trophic niches and feeding behavior of the two species. The bluegill uses powerful suction to capture insect larvae whereas the goldfish uses winnowing to sort through detritus and sediment. The kinethmoid of goldfish may permit jaw protrusion that is independent of lower jaw movement, which could explain the ability of goldfish to decouple suction flows (due to buccal expansion) from upper jaw protrusion. Nevertheless, our results show that jaw protrusion allows both species to augment the force exerted on prey, suggesting that this is a fundamental benefit of jaw protrusion to suction feeders. PMID:22496281

  19. 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

  20. 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).

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

    PubMed Central

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

    2016-01-01

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

  2. Agonistic induction of PPARγ reverses cigarette smoke–induced emphysema

    PubMed Central

    Shan, Ming; You, Ran; Yuan, Xiaoyi; Frazier, Michael V.; Porter, Paul; Seryshev, Alexander; Hong, Jeong-Soo; Song, Li-zhen; Zhang, Yiqun; Hilsenbeck, Susan; Whitehead, Lawrence; Zarinkamar, Nazanin; Perusich, Sarah; Corry, David B.; Kheradmand, Farrah

    2014-01-01

    The development of emphysema in humans and mice exposed to cigarette smoke is promoted by activation of an adaptive immune response. Lung myeloid dendritic cells (mDCs) derived from cigarette smokers activate autoreactive Th1 and Th17 cells. mDC-dependent activation of T cell subsets requires expression of the SPP1 gene, which encodes osteopontin (OPN), a pleiotropic cytokine implicated in autoimmune responses. The upstream molecular events that promote SPP1 expression and activate mDCs in response to smoke remain unknown. Here, we show that peroxisome proliferator–activated receptor γ (PPARG/Pparg) expression was downregulated in mDCs of smokers with emphysema and mice exposed to chronic smoke. Conditional knockout of PPARγ in APCs using Cd11c-Cre Ppargflox/flox mice led to spontaneous lung inflammation and emphysema that resembled the phenotype of smoke-exposed mice. The inflammatory phenotype of Cd11c-Cre Ppargflox/flox mice required OPN, suggesting an antiinflammatory mechanism in which PPARγ negatively regulates Spp1 expression in the lung. A 2-month treatment with a PPARγ agonist reversed emphysema in WT mice despite continual smoke exposure. Furthermore, endogenous PPARγ agonists were reduced in the plasma of smokers with emphysema. These findings reveal a proinflammatory pathway, in which reduced PPARγ activity promotes emphysema, and suggest that targeting this pathway in smokers could prevent and reverse emphysema. PMID:24569375

  3. [Bronchoscopic treatment of emphysema].

    PubMed

    Fruchter, Oren; Kramer, Mordechai R

    2012-04-01

    Bronchoscopic techniques for the management of emphysema have evolved from the success of surgical treatment. Lung volume reduction surgery (LVRS) involves the removal of 20% to 30% of each lung and targets the most emphysematous segments. Patients with heterogeneous upper lobe emphysema and a low baseline exercise capacity have been identified as a subgroup within COPD in whom mortality benefits can even be achieved, along with improvements in exercise capacity and quality of life. Increased short-term mortality of approximately 5% and postoperative morbidity are the main limitations of LVRS. The extremely restrictive selection criteria for LVRS coupled with the relatively high mortality/morbidity have been the impetus for developing less invasive endoscopic modalities. Bronchoscopic lung volume reduction (BLVR) researchers have pursued various approaches using a range of modalities, such as blockers, stents, valves, sealants, and implants. BLVR appears to be safer than LVRS in terms of mortality and morbidity. This safety profile presents an attractive alternative for patients with COPD who are fragile physiologically because of the severity of their lung disease and the presence of co-morbid illnesses. The current report aims to describe the various minimally invasive modalities available for the treatment of emphysema. PMID:22616152

  4. 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.

  5. 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…

  6. 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}.

  7. Pitfalls in Radiographic Interpretation of Emphysema Patients.

    PubMed

    Baik, Jun Hyun; Ko, Jeong Min; Park, Hyun Jin

    2016-08-01

    Emphysema commonly accompanies various complications such as pneumonia. Sometimes, these comorbidities look so strange on images, because destroyed airspaces could change the usual disease progression. So, we demonstrated various cases of common comorbidities with unusual radiographic findings in emphysema patients. Awareness of various findings of emphysema with commonly coexistent diseases may aid in the proper diagnosis and management of emphysema patients. PMID:27147485

  8. 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

  9. Combined pulmonary fibrosis and emphysema in hypersensitivity pneumonitis.

    PubMed

    Soumagne, Thibaud; Pana-Katatali, Héloïse; Degano, Bruno; Dalphin, Jean-Charles

    2015-12-21

    Combined pulmonary fibrosis and emphysema is a distinct syndrome reported in patients who smoke. A 72-year-old, never-smoking female dairy farmer was referred for progressive dyspnoea on exertion, basal crackles on auscultation, normal spirometry and normal lung volumes but decreased diffusing capacity of the lung for carbon monoxide, centrilobular emphysema in the upper zones of the lungs and diffuse infiltrative lung disease in the lower zones on high-resolution CT scan. Bronchoalveolar lavage differential cell count showed 35% lymphocytosis, and precipitating antibodies for Wallemia sebi, Trichoderma species and Cladosporium sphaerospermum were identified. The diagnosis of farmer's lung disease with combined pulmonary fibrosis and emphysema was retained. This case highlights for the first time that hypersensitivity pneumonitis should be suspected in the setting of combined pulmonary fibrosis and emphysema in non-smoking patients.

  10. 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.

  11. Massive surgical emphysema after perineal proctosigmoidectomy

    PubMed Central

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

    2014-01-01

    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. PMID:25293686

  12. 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.

  13. 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.

  14. 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

  15. [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.

  16. 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.

  17. 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)

  18. Spontaneous cervical and mediastinal emphysema.

    PubMed

    Parker, G S; Mosborg, D A; Foley, R W; Stiernberg, C M

    1990-09-01

    Subcutaneous cervical emphysema often appears as a result of surgery or trauma. However, when it occurs spontaneously, the patient may present with clinically impressive and dramatic features. The etiology is related to the rupture of terminal alveoli and dissection of air along the pulmonary vasculature. Exercise may contribute to the process by increases in intrathoracic pressure. Six cases of spontaneous cervical emphysema, all related to SCUBA diving training at a Naval facility, were recently seen at our institution. Proper management entails having a high index of suspicion for diagnosis, and then being able to identify potentially life-threatening complications.

  19. 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.

  20. The role of collagenase in emphysema

    PubMed Central

    Foronjy, Robert; D'Armiento, Jeanine

    2001-01-01

    The extracellular matrix is essential for the integrity of the lung and when disrupted can lead to the architectural changes seen in emphysema. The etiology of emphysema is believed to be due to an imbalance in the proteases and antiproteases within the lung. Studies have focused on elastolytic enzymes as the primary agents in disease pathogenesis, however, recent data suggest that collagenases may also be involved in the destruction of lung tissue in emphysema. It is hoped that this expanded understanding of the pathophysiology of emphysema will lead to improved therapy in the treatment of the disease. PMID:11737934

  1. Orbital Emphysema Following Ocular Trauma and Sneezing.

    PubMed

    Gauguet, Jean-Marc; Lindquist, Patricia A; Shaffer, Kitt

    2008-01-01

    Orbital emphysema is typically a benign condition that occurs following forceful injection of air into the orbital soft tissue spaces. In many cases there is a history of trauma and fracture of an orbital bone, which permits air entry. However, other mechanisms of orbital emphysema have been reported including infection, pulmonary barotrauma, injury from compressed-air hoses, and complications from surgery including dental procedures. Here, we describe a report of a teenager who suffered an isolated medial orbital wall fracture while playing basketball, and several hours later developed orbital emphysema acutely after sneezing. We will review the radiological evaluation of orbital fractures and emphysema.

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

    PubMed

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

    2016-08-01

    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. PMID:27210075

  3. 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%.

  4. Do bullae and emphysema increase risk of pneumothorax in silicosis?

    PubMed Central

    Mohebbi, Iraj; Hassani, Ebrahim; Salarilak, Shaker; Bahrami, Abdul Rahman

    2007-01-01

    Background The occurrence of occupational lung diseases is decreasing due to improvements in occupational health in recent years; however, silicosis and its complications remain important occupational health problems. We have studied the role of emphysema and bullae as predictive factors of secondary spontaneous pneumothorax in acute and accelerated silicosis. Methods This study was carried out using questionnaire items on occupational history and conventional computed tomography of lungs. Differences between two groups (silicosis with and without secondary spontaneous pneumothorax) in terms of age, interval of exposure-diagnosis and therefore silica exposure duration were assessed by independent t-test. Fisher's exact test was used to determine the association between secondary spontaneous pneumothorax and both emphysema and bullae. Results We found a significant association between secondary spontaneous pneumothorax and bullae in acute and accelerated silicosis. Conclusion Pneumothorax in silicosis could be attributed to previous bullae. PMID:17868470

  5. The dopamine D4 receptor gene shows a gender-sensitive association with cognitive empathy: evidence from two independent samples.

    PubMed

    Uzefovsky, Florina; Shalev, Idan; Israel, Salomon; Edelman, Shany; Raz, Yael; Perach-Barzilay, Nufar; Mankuta, David; Shamay-Tsoory, Simone G; Knafo, Ariel; Ebstein, Richard P

    2014-08-01

    Increasing evidence points to a role of dopaminergic pathways in modulating social behavior. Specifically, a polymorphic region in the third exon of the Dopamine D4 receptor (DRD4) has been associated with a host of social behaviors, often in an environment-sensitive manner. Empathy is thought to be an important motivator of prosocial behaviors and can be seen as multifaceted, combining cognitive empathy (CE) and emotional empathy (EE). In the current study, we analyzed the association between DRD4 and the 2 aspects of empathy, as well as the effect of gender on this association. In Study 1, a large sample of adult participants (N = 477) was inventoried for general empathy, CE, and EE and genotyped for the DRD4 exon 3 polymorphism. Women scored higher than men on all empathy measures and no main effect of genotype was observed. It is important that a significant interaction between genotype and gender emerged specifically for CE, with women carriers of the 7R-allele scoring higher than noncarriers, whereas in men 7R-carriers scored lower than -7R. Notably, these findings were replicated in an independently recruited sample (N = 121) in Study 2. The current report shows that the DRD4 exon3 polymorphism is associated with CE and the direction of the association is gender-sensitive. PMID:24866520

  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. MicroRNA-22 Inhibits Histone Deacetylase 4 to Promote T Helper-17 Cell-Dependent Emphysema

    PubMed Central

    Lu, Wen; You, Ran; Yuan, Xiaoyi; Yang, Tianshu; Samuel, Errol L. G.; Marcano, Daniela C.; Sikkema, William K. A.; Tour, James M.; Rodriguez, Antony; Kheradmand, Farrah; Corry, David B.

    2015-01-01

    Smoking-related emphysema is a chronic inflammatory disease driven by T helper 17 (TH17) cells through molecular mechanisms that remain obscure. Here we have explored the role of microRNA-22 (miR-22) in emphysema. MiR-22 was upregulated in lung myeloid dendritic cells (mDCs) of smokers with emphysema and antigen-presenting cells (APCs) of mice exposed to smoke or nanoparticulate carbon black (nCB) through a mechanism involving NF-κB. MiR-22-deficient mice, but not wild-type, showed attenuated TH17 responses and failed to develop emphysema after exposure to either smoke or nCB. We further show that miR-22 controls APC activation and TH17 responses through activation of AP-1 transcription factor complexes and histone deacetylase (HDAC) 4. Thus, miR-22 is a critical regulator of both emphysema and TH17 responses. PMID:26437241

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

    PubMed

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

    2015-07-01

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

  9. 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. PMID:27090269

  10. Diaphragm and body weight in emphysema.

    PubMed Central

    Thurlbeck, W M

    1978-01-01

    The weight of the diaphragm has been investigated in 103 male patients and 81 female patients, and the relationship between body weight and emphysema has been assessed in 662 male and 431 female patients. Diaphragm weight is related to body weight in both male (r = + 0.76) and female patients (r = +0.77) and is relatively larger in the former. Dissecting the diaphragm free of fat or freeze drying it does not appreciably improve the relationship between body weight and diaphragm weight. Diaphragm weight is better related to body weight than body length and is diminished in emphysema. Patients with emphysema weigh less. This is apparent with only moderate grades of emphysema, and there is no further loss of body weight as emphysema in the lung becomes more severe. The loss of diaphragm weight not only reflects the loss of body weight that occurs in emphysema, but the diaphragm is also less in weight than predicted from body weight. The diaphragm also appears abnormal on gross inspection in some patients with emphysema. Heart weight and diaphragm weight are related, probably because both are related to body weight. PMID:694801

  11. Role of conventional chest radiography in diagnosis and exclusion of emphysema.

    PubMed

    Pratt, P C

    1987-05-01

    Although recognizing that the subject is controversial, most authors of textbooks about diagnostic radiology conclude that chest radiography is of little value for either confirmation or exclusion of the diagnosis of emphysema. Yet several reports in the literature show a high degree of accuracy in the interpretation of films for presence of this disease. Some of the controversy results from continuing confusion over the current definition of emphysema in terms of lung structure rather than symptoms or physiologic evidence relating to impaired ventilation. Many autopsy studies have shown that emphysema is often present at postmortem examination and can involve as much as 30 percent of the lung tissue, even in subjects with no respiratory symptoms or impairment during life. Since radiographs deal with structure rather than function, interpreters of chest films should have the intention to recognize the presence of structural emphysema. The correct recognition of emphysema is useful even in a patient without symptoms, and the ability to exclude this diagnosis in symptomatic patients is of equal, if not greater value. The degree of success reported in various studies depends upon the criteria used and the strictness applied by the authors in matching their interpretations to the presence or absence of structural emphysema. This review of existing literature deals solely with papers in which radiographic observations have been related to morphologic evidence of emphysema in inflation-fixed autopsy lung specimens. It identifies reasons for discrepancies among reports and emphasizes the very high predictive value of validated radiographic criteria. Applications of radiographic interpretation both for diagnosis and for exclusion of emphysema in clinical situations are described. PMID:3555069

  12. 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.

  13. 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.

  14. Intercellular Adhesion Molecule 1 and Progression of Percent Emphysema: The MESA Lung Study

    PubMed Central

    Aaron, Carrie P.; Schwartz, Joseph E.; Bielinski, Suzette J.; Hoffman, Eric A.; Austin, John H. M.; Oelsner, Elizabeth C.; Donohue, Kathleen M.; Kalhan, Ravi; Berardi, Cecilia; Kaufman, Joel D.; Jacobs, David R.; Tracy, Russell P.; Barr, R.Graham

    2014-01-01

    Endothelial intercellular adhesion molecule (ICAM) 1 binds neutrophils and facilitates their transmigration into the lung; E-selectin facilitates leukocyte rolling. As neutrophils contribute to tissue destruction in emphysema and chronic obstructive pulmonary disease, we hypothesized that soluble ICAM-1 (sICAM-1) and E-selectin (sE-selectin) would be associated with longitudinal progression of emphysema and lung function decline. The Multi-Ethnic Study of Atherosclerosis (MESA) enrolled participants 45-84 years old without clinical cardiovascular disease in 2000-02. The MESA Lung Study assessed percent emphysema (<-950 Hounsfield units) on cardiac (2000-07) and full-lung CT scans (2010-12), and spirometry was assessed twice over five years. sICAM-1 and sE-selectin were measured at baseline. Mixed-effect models adjusted for demographics, anthropometry, smoking, C-reactive protein, sphingomyelin and scanner factors. Among 1,865 MESA Lung participants with measurement of sICAM-1 and percent emphysema the mean log-sICAM-1 was 5.5±0.3 ng/mL and percent emphysema increased 0.73 percentage points (95% CI: 0.34, 1.12; P<0.001) over ten years. A one SD increase in sICAM-1 was associated with an accelerated increase in percent emphysema of 0.23 percentage points over ten years (95% CI: 0.06, 0.39; P=0.007). No significant association was found for sE-selectin, or between any adhesion molecule and lung function. Higher levels of sICAM-1 were independently associated with progression of percent emphysema in a general population sample. PMID:25457724

  15. APOM and high-density lipoprotein cholesterol are associated with lung function and per cent emphysema.

    PubMed

    Burkart, Kristin M; Manichaikul, Ani; Wilk, Jemma B; Ahmed, Firas S; Burke, Gregory L; Enright, Paul; Hansel, Nadia N; Haynes, Demondes; Heckbert, Susan R; Hoffman, Eric A; Kaufman, Joel D; Kurai, Jun; Loehr, Laura; London, Stephanie J; Meng, Yang; O'Connor, George T; Oelsner, Elizabeth; Petrini, Marcy; Pottinger, Tess D; Powell, Charles A; Redline, Susan; Rotter, Jerome I; Smith, Lewis J; Soler Artigas, María; Tobin, Martin D; Tsai, Michael Y; Watson, Karol; White, Wendy; Young, Taylor R; Rich, Stephen S; Barr, R Graham

    2014-04-01

    Chronic obstructive pulmonary disease (COPD) is linked to cardiovascular disease; however, there are few studies on the associations of cardiovascular genes with COPD. We assessed the association of lung function with 2100 genes selected for cardiovascular diseases among 20 077 European-Americans and 6900 African-Americans. We performed replication of significant loci in the other racial group and an independent consortium of Europeans, tested the associations of significant loci with per cent emphysema and examined gene expression in an independent sample. We then tested the association of a related lipid biomarker with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio and per cent emphysema. We identified one new polymorphism for FEV1/FVC (rs805301) in European-Americans (p=1.3×10(-6)) and a second (rs707974) in the combined European-American and African-American analysis (p=1.38×10(-7)). Both single-nucleotide polymorphisms (SNPs) flank the gene for apolipoprotein M (APOM), a component of high-density lipoprotein (HDL) cholesterol. Both were replicated in an independent cohort. SNPs in a second gene related to apolipoprotein M and HDL, PCSK9, were associated with FEV1/FVC ratio among African-Americans. rs707974 was associated with per cent emphysema among European-Americans and African-Americans and APOM expression was related to FEV1/FVC ratio and per cent emphysema. Higher HDL levels were associated with lower FEV1/FVC ratio and greater per cent emphysema. These findings suggest a novel role for the apolipoprotein M/HDL pathway in the pathogenesis of COPD and emphysema.

  16. [Lung hyperinflation after single lung transplantation to treat emphysema].

    PubMed

    Samano, Marcos Naoyuki; Junqueira, Jader Joel Machado; Teixeira, Ricardo Henrique de Oliveira Braga; Caramori, Marlova Luzzi; Pêgo-Fernandes, Paulo Manuel; Jatene, Fabio Biscegli

    2010-01-01

    Despite preventive measures, lung hyperinflation is a relatively common complication following single lung transplantation to treat pulmonary emphysema. The progressive compression of the graft can cause mediastinal shift and respiratory failure. In addition to therapeutic strategies such as independent ventilation, the treatment consists of the reduction of native lung volume by means of lobectomy or lung volume reduction surgery. We report two cases of native lung hyperinflation after single lung transplantation. Both cases were treated by means of lobectomy or lung volume reduction surgery.

  17. Normotensive male offspring of essential hypertensive parents show early changes in left ventricular geometry independent of blood pressure.

    PubMed

    Pelà, Giovanna; Pattoneri, Paolo; Passera, Mariadele; Li Calzi, Mauro; Goldoni, Matteo; Tirabassi, Giovanni; Montanari, Alberto

    2011-09-01

    For the purpose of detecting early left ventricle (LV) abnormalities in normotensive offspring of hypertensive parents (EH+), 23 normotensive sedentary male EH+ (age 25 ± 3 years) and 20 matched offspring of normotensive families (EH-), underwent: clinic bloop pressure (BP) measurement, 24-hour ambulatory BP monitoring (ABPM), frequency-domain parameters of autonomic heart rate control and conventional and Doppler tissue echocardiographic (DTE) study of both ventricles, including relative wall thickness (RWT) as an index of LV remodeling. EH+ subjects had slightly higher office systolic and diastolic (P < 0.05), average 24-hour systolic (P < 0.001), diastolic (P < 0.01), and mean BP (P < 0.05). No between-group differences were detected for heart rate variability, LV mass and systolic and diastolic function in both ventricles. RWT was greater in EH+ (0.38 ± 0.05 vs. 0.34 ± 0.03 SD; P < 0.01), which was significantly related, at the univariate analysis, to the condition of EH+ (P < 0.004) and to the clinic and ambulatory BP parameters as well (P = 0.06-0.01). However, at the stepwise multiple regression analysis, with RWT used as the dependent variable, only the condition of EH+ was independently associated with RWT (P < 0.008), whereas BP did not. RWT, according to receiver operating characteristic curves analysis, predicted the condition of EH+ (cutoff point 0.369, specificity 90%, sensitivity 65%). Our data suggest that an higher RWT, as an index towards LV concentric remodeling, is the earliest change in LV geometry in EH+ subjects, independent of any slight elevation in BP. Thus, RWT measurement may be a quite specific tool to detect early LV alterations due to the condition of EH+.

  18. Orbital emphysema as an ophthalmologic emergency.

    PubMed

    Fleishman, J A; Beck, R W; Hoffman, R O

    1984-11-01

    Orbital emphysema is generally a benign, self-limited condition. However, if a fracture produces a ball-valve effect allowing air to enter but not to leave the orbit, and if the orbital septum remains intact, then extremely high intraorbital pressure and visual loss is possible. Two cases are described of visual loss from orbital emphysema, in a 33-year-old man and a 28-year-old man, which were successfully treated by a lateral canthotomy and cantholysis.

  19. 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.

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

    PubMed Central

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

    2016-01-01

    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. PMID:27673562

  1. 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

    2016-01-01

    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. PMID:27673562

  2. Novel nuclear targeting coiled-coil protein of Helicobacter pylori showing Ca(2+)-independent, Mg(2+)-dependent DNase I activity.

    PubMed

    Kwon, Young Chul; Kim, Sinil; Lee, Yong Seok; Lee, Je Chul; Cho, Myung-Je; Lee, Woo-Kon; Kang, Hyung-Lyun; Song, Jae-Young; Baik, Seung Chul; Ro, Hyeon Su

    2016-05-01

    HP0059, an uncharacterized gene of Helicobacter pylori, encodes a 284-aa-long protein containing a nuclear localization sequence (NLS) and multiple leucine-rich heptad repeats. Effects of HP0059 proteins in human stomach cells were assessed by incubation of recombinant HP0059 proteins with the AGS human gastric carcinoma cell line. Wild-type HP0059 proteins showed cytotoxicity in AGS cells in a concentration-dependent manner, whereas NLS mutant protein showed no effect, suggesting that the cytotoxicity is attributed to host nuclear localization. AGS cells transfected with pEGFP-HP0059 plasmid showed strong GFP signal merged to the chromosomal DNA region. The chromosome was fragmented into multiple distinct dots merged with the GFP signal after 12 h of incubation. The chromosome fragmentation was further explored by incubation of AGS chromosomal DNA with recombinant HP0059 proteins, which leaded to complete degradation of the chromosomal DNA. HP0059 protein also degraded circular plasmid DNA without consensus, being an indication of DNase I activity. The DNase was activated by MgCl2, but not by CaCl2. The activity was completely blocked by EDTA. The optimal pH and temperature for DNase activity were 7.0-8.0 and 55°C, respectively. These results indicate that HP0059 possesses a novel DNase I activity along with a role in the genomic instability of human gastric cells, which may result in the transformation of gastric cells. PMID:27095458

  3. A combined cultivation and cultivation-independent approach shows high bacterial diversity in water-miscible metalworking fluids.

    PubMed

    Lodders, Nicole; Kämpfer, Peter

    2012-06-01

    Ten metalworking fluids (MWF) and seven water preparation basis samples (WPB) were taken from five industrial plants in Germany. Total cells (TCC) and colony forming units (CFU) were counted, strains were isolated and their 16S rRNA gene was sequenced. Additionally, DNA was extracted directly from the samples, and clone libraries of 16S rRNA genes were built and gene sequenced. TCC ranged from 7.6×10(4) TCC/mL MWF to 1.6×10(8) TCC/mL MWF, and from 4.6×10(2) TCC/mL WPB to 7.8×10(7) TCC/mL WPB. The CFU showed similar but often lower results. A total of 70 isolates and 732 clones were 16S rRNA gene sequenced and all isolates, as well as 183 of the nearly full length 16S rRNA of these clones, were gene sequenced. A total of 98 different genera were detected in all 17 samples. The number of genera within each sample varied highly, with 1-22 genera per sample. The dominant genera in MWF were Leucobacter, Desemzia, Sphingomonas and Wautersiella. From these, only Sphingomonas was detected in WPB as well. This study showed that MWF can harbour a high bacterial diversity, which differs significantly from the bacterial flora of the corresponding WPB. PMID:22609341

  4. Resolvin D1 prevents smoking-induced emphysema and promotes lung tissue regeneration

    PubMed Central

    Kim, Kang-Hyun; Park, Tai Sun; Kim, You-Sun; Lee, Jae Seung; Oh, Yeon-Mok; Lee, Sang-Do; Lee, Sei Won

    2016-01-01

    Purpose Emphysema is an irreversible disease that is characterized by destruction of lung tissue as a result of inflammation caused by smoking. Resolvin D1 (RvD1), derived from docosahexaenoic acid, is a novel lipid that resolves inflammation. The present study tested whether RvD1 prevents smoking-induced emphysema and promotes lung tissue regeneration. Materials and methods C57BL/6 mice, 8 weeks of age, were randomly divided into four groups: control, RvD1 only, smoking only, and smoking with RvD1 administration. Four different protocols were used to induce emphysema and administer RvD1: mice were exposed to smoking for 4 weeks with poly(I:C) or to smoking only for 24 weeks, and RvD1 was injected within the smoking exposure period to prevent regeneration or after completion of smoking exposure to assess regeneration. The mean linear intercept and inflammation scores were measured in the lung tissue, and inflammatory cells and cytokines were measured in the bronchoalveolar lavage fluid. Results Measurements of mean linear intercept showed that RvD1 significantly attenuated smoking-induced lung destruction in all emphysema models. RvD1 also reduced smoking-induced inflammatory cell infiltration, which causes the structural derangements observed in emphysema. In the 4-week prevention model, RvD1 reduced the smoking-induced increase in eosinophils and interleukin-6 in the bronchoalveolar lavage fluid. In the 24-week prevention model, RvD1 also reduced the increased neutrophils and total cell counts induced by smoking. Conclusion RvD1 attenuated smoking-induced emphysema in vivo by reducing inflammation and promoting tissue regeneration. This result suggests that RvD1 may be useful in the prevention and treatment of emphysema. PMID:27313451

  5. Circulating desmosine levels do not predict emphysema progression but are associated with cardiovascular risk and mortality in COPD.

    PubMed

    Rabinovich, Roberto A; Miller, Bruce E; Wrobel, Karolina; Ranjit, Kareshma; Williams, Michelle C; Drost, Ellen; Edwards, Lisa D; Lomas, David A; Rennard, Stephen I; Agustí, Alvar; Tal-Singer, Ruth; Vestbo, Jørgen; Wouters, Emiel F M; John, Michelle; van Beek, Edwin J R; Murchison, John T; Bolton, Charlotte E; MacNee, William; Huang, Jeffrey T J

    2016-05-01

    Elastin degradation is a key feature of emphysema and may have a role in the pathogenesis of atherosclerosis associated with chronic obstructive pulmonary disease (COPD). Circulating desmosine is a specific biomarker of elastin degradation. We investigated the association between plasma desmosine (pDES) and emphysema severity/progression, coronary artery calcium score (CACS) and mortality.pDES was measured in 1177 COPD patients and 110 healthy control subjects from two independent cohorts. Emphysema was assessed on chest computed tomography scans. Aortic arterial stiffness was measured as the aortic-femoral pulse wave velocity.pDES was elevated in patients with cardiovascular disease (p<0.005) and correlated with age (rho=0.39, p<0.0005), CACS (rho=0.19, p<0.0005) modified Medical Research Council dyspnoea score (rho=0.15, p<0.0005), 6-min walking distance (rho=-0.17, p<0.0005) and body mass index, airflow obstruction, dyspnoea, exercise capacity index (rho=0.10, p<0.01), but not with emphysema, emphysema progression or forced expiratory volume in 1 s decline. pDES predicted all-cause mortality independently of several confounding factors (p<0.005). In an independent cohort of 186 patients with COPD and 110 control subjects, pDES levels were higher in COPD patients with cardiovascular disease and correlated with arterial stiffness (p<0.05).In COPD, excess elastin degradation relates to cardiovascular comorbidities, atherosclerosis, arterial stiffness, systemic inflammation and mortality, but not to emphysema or emphysema progression. pDES is a good biomarker of cardiovascular risk and mortality in COPD. PMID:27009168

  6. Graphene quantum dots from graphite by liquid exfoliation showing excitation-independent emission, fluorescence upconversion and delayed fluorescence.

    PubMed

    Sarkar, Suprabhat; Gandla, Dayakar; Venkatesh, Yeduru; Bangal, Prakriti Ranjan; Ghosh, Sutapa; Yang, Yang; Misra, Sunil

    2016-08-21

    Facile synthesis of 2-10 nm-sized graphene quantum dots (GQDs) from graphite powder by organic solvent-assisted liquid exfoliation using a sonochemical method is reported in this study. Synthesized GQDs are well dispersed in organic solvents like ethyl acetoacetate (EAA), dimethyl formamide (DMF) and also in water. MALDI-TOF mass spectrometry reveals its selective mass fragmentation. Detailed characterizations by various techniques like X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy and high resolution transmission electron microscopy (HRTEM) confirm the formation of disordered, functional GQDs. Density functional theory (DFT) calculation confirms HOMO-LUMO energy gap variation with changing size and functionalities. Photoluminescence (PL) properties of as-prepared GQDs were studied in detail. The ensemble studies of GQDs showed excellent photoluminescence properties comprising normal and upconverted fluorescence, delayed fluorescence and room-temperature phosphorescence. PL decay dynamics of GQDs has been explored using time-correlated single-photon technique (TCSPC) as well as femtosecond fluorescence upconversion technique. In vitro cytotoxicity study reveals its biocompatibility and high cell viability (>91%) even at high concentration (400 μg mL(-1)) of GQDs in Chinese Hamster Ovary (CHO) cells. PMID:27302411

  7. 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

  8. Facial emphysema after sinus lift.

    PubMed

    Sakakibara, Akiko; Suzuki, Hiroaki; Yamashita, Atsuya; Hasegawa, Takumi; Minamikawa, Tsutomu; Furudoi, Shungo; Komori, Takahide

    2015-01-01

    An 80-year-old man with a history of en bloc resection of squamous cell carcinoma of the hard palate (T4aN0M0) was performed a lateral-window sinus lift of the edentulous area of the left maxillary molar region to facilitate future placement of dental implants.Two hours after the surgery, the patient complained of sudden malar swelling. Marked swelling was present from the left infraorbital region to the buccal region. The swelling was associated with air pockets at the alar base and in the angulus oculi medialis region and subcutaneous malar tissue. Emphysema appeared after the patient blew his nose. Therefore, the mucous membrane of the maxillary sinus might have had a small hole, and air might have entered the subcutaneous tissue via the bone window when the air pressure in the maxillary sinus increased with nose blowing. It is important to advise patients to avoid increasing the intraoral pressure after sinus-lift procedure. PMID:26088054

  9. 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.

  10. The impact of emphysema in pulmonary fibrosis.

    PubMed

    Cottin, Vincent

    2013-06-01

    Several groups have described a syndrome in which idiopathic pulmonary fibrosis (IPF) coexists with pulmonary emphysema. This comes as no surprise since both diseases are associated with a history of exposure to cigarette smoke. The syndrome of combined pulmonary fibrosis and emphysema (CPFE) is characterised by upper lobe emphysema and lower lobe fibrosis. Physiological testing of these patients reveals preserved lung volume indices contrasted by markedly impaired diffusion capacity. The incidence of CPFE remains unknown but several case series suggest that this subgroup may comprise up to 35% of patients with IPF. CPFE is a strong determinant of associated pulmonary hypertension (PH). In addition, CPFE has major effects on measures of physiological function, exercise capacity and prognosis, and may affect the results of pulmonary fibrosis trials. Further studies are needed to ascertain the aetiology, morbidity, mortality and management of the CPFE syndrome, with or without PH, and to evaluate novel therapeutic options in CPFE.

  11. 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.

  12. 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.

  13. Mediastinal bronchogenic cyst mimicking congenital lobar emphysema.

    PubMed

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

    2016-01-01

    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. PMID:27609589

  14. Ethmoid osteoma as a culprit of orbital emphysema: a case report.

    PubMed

    Zhuang, Ai; Li, Yinwei; Lin, Ming; Shi, Wodong; Fan, Xianqun

    2015-05-01

    Orbital emphysema is generally recognized as a complication of orbital fractures involving any paranasal sinuses. The recognition about its etiology has extended beyond sole trauma, but few articles mentioned tumors to be a possible cause.In this case report, we present a patient with orbital emphysema associated with ethmoid osteoma without orbital cellulitis or trauma history. The patient developed sudden proptosis, eyelid swelling, and movement limitation of the left eye, peripheral diplopia, and left periorbital crepitus after a vigorous nose blowing.Complete surgical resection of ethmoid osteoma followed by repair of the orbital medial wall was performed with assistance of combined endoscopy and navigational techniques. Twelve-month follow-up showed no residual lesion or recurrence; the orbital medial wall was accurately repaired with good visual function and facial symmetry.Tumors should be considered for differential diagnosis of orbital emphysema, and combined endoscopy and navigational techniques may improve safety, accuracy, and effectiveness of orbital surgeries.

  15. 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. PMID:26839694

  16. Alpha-1 Antitrypsin Deficiency (Inherited Emphysema)

    MedlinePlus

    ... 1 protein in the blood with normal alpha-1 antitrypsin from healthy plasma donors. It is given in a vein (IV). The dose is adjusted based on body weight. This treatment is often given once a week. There are three ... the management of Alpha-1 related emphysema includes: • Exercise and a healthy lifestyle ...

  17. 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.

  18. Airway mucus obstruction triggers macrophage activation and matrix metalloproteinase 12-dependent emphysema.

    PubMed

    Trojanek, Joanna B; Cobos-Correa, Amanda; Diemer, Stefanie; Kormann, Michael; Schubert, Susanne C; Zhou-Suckow, Zhe; Agrawal, Raman; Duerr, Julia; Wagner, Claudius J; Schatterny, Jolanthe; Hirtz, Stephanie; Sommerburg, Olaf; Hartl, Dominik; Schultz, Carsten; Mall, Marcus A

    2014-11-01

    Whereas cigarette smoking remains the main risk factor for emphysema, recent studies in β-epithelial Na(+) channel-transgenic (βENaC-Tg) mice demonstrated that airway surface dehydration, a key pathophysiological mechanism in cystic fibrosis (CF), caused emphysema in the absence of cigarette smoke exposure. However, the underlying mechanisms remain unknown. The aim of this study was to elucidate mechanisms of emphysema formation triggered by airway surface dehydration. We therefore used expression profiling, genetic and pharmacological inhibition, Foerster resonance energy transfer (FRET)-based activity assays, and genetic association studies to identify and validate emphysema candidate genes in βENaC-Tg mice and patients with CF. We identified matrix metalloproteinase 12 (Mmp12) as a highly up-regulated gene in lungs from βENaC-Tg mice, and demonstrate that elevated Mmp12 expression was associated with progressive emphysema formation, which was reduced by genetic deletion and pharmacological inhibition of MMP12 in vivo. By using FRET reporters, we show that MMP12 activity was elevated on the surface of airway macrophages in bronchoalveolar lavage from βENaC-Tg mice and patients with CF. Furthermore, we demonstrate that a functional polymorphism in MMP12 (rs2276109) was associated with severity of lung disease in CF. Our results suggest that MMP12 released by macrophages activated on dehydrated airway surfaces may play an important role in emphysema formation in the absence of cigarette smoke exposure, and may serve as a therapeutic target in CF and potentially other chronic lung diseases associated with airway mucus dehydration and obstruction. PMID:24828142

  19. Attenuation of Cigarette Smoke-Induced Emphysema in Mice by Apolipoprotein A-1 Overexpression.

    PubMed

    Kim, Chorong; Lee, Ji-Min; Park, Sung-Woo; Kim, Ki-Sun; Lee, Myoung Won; Paik, Sanghyun; Jang, An Soo; Kim, Do Jin; Uh, Sootaek; Kim, Yonghoon; Park, Choon-Sik

    2016-01-01

    Chronic inflammation, oxidative stress, and proteolysis participate primarily in the pathogenesis of chronic obstructive pulmonary disease (COPD)/emphysema. COPD is a highly prevalent smoking-related disease for which no effective therapy exists to improve the disease course. Although apolipoprotein A-1 (ApoA1) has antiinflammatory and antioxidant properties as well as cholesterol efflux potential, its role in cigarette smoke (CS)-induced emphysema has not been determined. Therefore, we investigated whether human ApoA1 transgenic (TG) mice, with conditionally induced alveolar epithelium to overexpress ApoA1, are protected against the CS-induced lung inflammatory response and development of emphysema. In this study, ApoA1 levels were significantly decreased in the lungs of patients with COPD and in the lungs of mice exposed to CS. ApoA1 TG mice did not develop emphysema when chronically exposed to CS. Compared with the control TG mice, ApoA1 overexpression attenuated lung inflammation, oxidative stress, metalloprotease activation, and apoptosis in CS-exposed mouse lungs. To explore a plausible mechanism of antiapoptotic activity of ApoA1, alveolar epithelial cells (A549) were treated with CS extract (CSE). ApoA1 prevented CSE-induced translocation of Fas and downstream death-inducing signaling complex into lipid rafts, thereby inhibiting Fas-mediated apoptosis. Taken together, the data showed that ApoA1 overexpression attenuated CS-induced lung inflammation and emphysema in mice. Augmentation of ApoA1 in the lung may have therapeutic potential in preventing smoking-related COPD/emphysema.

  20. Progression parameters for emphysema: a clinical investigation.

    PubMed

    Stolk, Jan; Putter, Hein; Bakker, Els M; Shaker, Saher B; Parr, David G; Piitulainen, Eeva; Russi, Erich W; Grebski, Elzbieta; Dirksen, Asger; Stockley, Robert A; Reiber, Johan H C; Stoel, Berend C

    2007-09-01

    In patients with airflow limitation caused by cigarette smoking, lung density measured by computed tomography is strongly correlated with quantitative pathology scores of emphysema, but the ability of lung densitometry to detect progression of emphysema is disputed. We assessed the sensitivity of lung densitometry as a parameter of disease progression of emphysema in comparison to FEV(1) and gas transfer. At study baseline and after 30 months we measured computed tomography (CT)-derived lung density, spirometry and carbon monoxide diffusion coefficient in 144 patients with chronic obstructive pulmonary disease (COPD) in five different centers. Annual change in lung density was 1.31 g/L/year (CI 95%: -2.12 to -0.50 HU, p=0.0015, 39.5 mL/year (CI 95%: -100.0-21.0 mL, p=0.2) for FEV(1) (-39.5 mL) and 24.3 micromol/min/kPa/L/year for gas transfer (CI 95%: -61.0-12.5 micromol/min/kPa/L/year, p=0.2). Signal-to-noise ratio (mean change divided by standard error of the change) for the detection of annual change was 3.2 for lung densitometry, but 1.3 for both FEV(1) and gas diffusion. We conclude that detection of progression of emphysema was found to be 2.5-fold more sensitive using lung densitometry than by using currently recommended lung function parameters. Our results support CT scan as an efficacious test for novel drugs for emphysema. PMID:17644366

  1. 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

  2. Paracrine Factors of Multipotent Stromal Cells Ameliorate Lung Injury in an Elastase-induced Emphysema Model

    PubMed Central

    Katsha, Ahmed M; Ohkouchi, Shinya; Xin, Hong; Kanehira, Masahiko; Sun, Ruowen; Nukiwa, Toshihiro; Saijo, Yasuo

    2011-01-01

    Multipotent stromal cells (MSCs) ameliorate several types of lung injury. The differentiation of MSCs into specific cells at the injury site has been considered as the important process in the MSC effect. However, although MSCs reduce destruction in an elastase-induced lung emphysema model, MSC differentiation is relatively rare, suggesting that MSC differentiation into specific cells does not adequately explain the recuperation observed. Humoral factors secreted by MSCs may also play an important role in ameliorating emphysema. To confirm this hypothesis, emphysema was induced in the lungs of C57BL/6 mice by intratracheal elastase injection 14 days before intratracheal MSC or phosphate-buffered saline (PBS) administration. Thereafter, lungs were collected at several time points and evaluated. Our results showed that MSCs reduced the destruction in elastase-induced emphysema. Furthermore, double immunofluorescence staining revealed infrequent MSC engraftment and differentiation into epithelial cells. Real-time PCR showed increased levels of hepatocyte growth factor (HGF) and epidermal growth factor (EGF). Real-time PCR and western blotting showed enhanced production of secretory leukocyte protease inhibitor (SLPI) in the lung. In-vitro coculture studies confirmed the in vivo observations. Our findings suggest that paracrine factors derived from MSCs is the main mechanism for the protection of lung tissues from elastase injury. PMID:20842104

  3. [Surgical therapy of interstitial pulmonary emphysema in a premature infant].

    PubMed

    Storm, W

    1986-07-01

    Pulmonary interstitial emphysema is a frequent complication in the use of respirators in newborn infants suffering from respiratory insufficiency. If it is diffuse and bilateral, treatment often is without success; occasionally, interstitial emphysema may be localized in a lobe, in which case it may persist and lead to therapeutic difficulties. We report a successful surgical approach to a unilateral pulmonary interstitial emphysema in a premature infant.

  4. 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.

  5. Dose response of elastase-induced emphysema in hamsters.

    PubMed

    Raub, J A; Mercer, R R; Miller, F J; Graham, J A; O'Neil, J J

    1982-04-01

    Elastase-induced emphysema in hamsters was studied using pulmonary function tests in an effort to develop techniques for determining the effects of air pollutants on the progression of this disease. Single intratracheal injections of 6, 12, or 24 units of porcine pancreatic elastase produced dose-related changes in pulmonary function after 4 wk when compared with sham-injected control animals. Boyle's law end-expiratory volume and residual volume, measured by gas dilution, increased (p less than 0.05) at 12 and 24 units, respectively, whereas vital capacity, determined plethysmographically, and total lung capacity wee increased (p less than 0.05) at all 3 elastase doses. Respiratory system compliance, calculated by a nonlinear least squares regression fit of the deflation pressure-volume curve, increased (p less than 0.05) at 24 units only. The multiple-breath nitrogen washout slope (N2 slope) and the single-breath diffusing capacity for carbon monoxide (DLCO) decreased (p less than 0.05) at all 3 doses of elastase. Both histologic and physiologic evaluation showed dose-related pulmonary impairment. It appears, therefore, that as little as 6 units of elastase produces mild emphysema in hamsters, which is detectable by pulmonary function testing. Of these tests, the DLCO and N2 slope were the most effective in detecting the degree of impairment. PMID:6918202

  6. Subcutaneous Emphysema following Emergent Surgical Conventional Tracheostomy

    PubMed Central

    Ardekian, Leon; Barak, Michal; Rachmiel, Adi

    2014-01-01

    In maxillofacial surgery, tracheostomy is indicated in congenital, inflammatory, oncologic, or traumatic respiratory obstruction. In traumatic cases, however, it is sometimes hard to implement. We describe subcutaneous emphysema following emergent surgical conventional tracheostomy performed after stab injury to the floor of the mouth. We analyze the course that led to this complication and discuss suggestions on how to avoid it. In addition, we review the literature to improve our knowledge and practice regarding this entity. Massive subcutaneous neck emphysema occurred because ventilation started at the time when the hemorrhage was not completely managed and the tracheal tube was not fully secured. In traumatic cases with profound bleeding, hemorrhage management must be performed carefully. The recommendation not to ventilate until the hemorrhage is completely managed should be observed. PMID:25383149

  7. 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. PMID:22159348

  8. 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.

  9. 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.

  10. 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. PMID:24320897

  11. Congenital lobar emphysema in neonates: Anaesthetic challenges.

    PubMed

    Nath, Mridu Paban; Gupta, Sachin; Kumar, Ashish; Chakrabarty, Anulekha

    2011-05-01

    Congenital lobar emphysema (CLE) is a potentially reversible, though possibly life-threatening, cause of respiratory distress in the neonate. It poses dilemma in diagnosis and management. We are presenting a 6-week-old baby who presented with a sudden onset of respiratory distress related to CLE affecting the left upper lobe. Lobectomy was performed under general anaesthesia with one lung ventilation. The details of anaesthetic challenges and management are described here. PMID:21808403

  12. Nonintubated Thoracoscopic Pneumonectomy for Bullous Emphysema.

    PubMed

    Hung, Wan-Ting; Liao, Hsien-Chi; Cheng, Ya-Jung; Chen, Jin-Shing

    2016-10-01

    Thoracoscopic pneumonectomy without tracheal intubation has not been reported. We describe a woman with severe bullous emphysema of the right upper lobe and hypoplasia of the remaining lung lobes who underwent thoracoscopic pneumonectomy using a nonintubated anesthetic technique of internal intercostal nerve block, vagal block, and targeted sedation. The successful results in this patient suggest that nonintubated thoracoscopic pneumonectomy is technically feasible and can be used in a specific group of patients. PMID:27645981

  13. 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.

  14. Reduction pneumonoplasty for emphysema. Early results.

    PubMed Central

    Little, A G; Swain, J A; Nino, J J; Prabhu, R D; Schlachter, M D; Barcia, T C

    1995-01-01

    OBJECTIVE: The authors determined the role of Nd:YAG laser reduction pneumonoplasty for selected patients with diffuse emphysema. SUMMARY BACKGROUND DATA: The study is based on the concepts introduced 30 years ago by Brantigan regarding the value of lung reduction surgery in patients with emphysema. The authors used minimally invasive techniques with the hopes of providing appropriate clinical results with the least surgical morbidity. METHODS: Fifty-five patients with advanced symptomatic emphysema were treated with unilateral Nd:YAG laser reduction pneumonoplasty to achieve lung volume reduction. RESULTS: Patients experienced significant improvement in exercise capacity and relief of breathlessness. This correlated with improvement in objective measures of pulmonary function and with reduction in lung volume by radiographic and spirometric measures. Significant associated hospital morbidity and a 5.5% mortality were associated. CONCLUSIONS: These encouraging results with treatment of only one lung will be built on with both sequential lung and simultaneous, bilateral lung treatment protocols. Images Figure 1. Figure 2. PMID:7677465

  15. 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.

  16. Emphysema requires the receptor for advanced glycation end-products triggering on structural cells.

    PubMed

    Waseda, Koichi; Miyahara, Nobuaki; Taniguchi, Akihiko; Kurimoto, Etsuko; Ikeda, Genyo; Koga, Hikari; Fujii, Utako; Yamamoto, Yasuhiko; Gelfand, Erwin W; Yamamoto, Hiroshi; Tanimoto, Mitsune; Kanehiro, Arihiko

    2015-04-01

    Pulmonary emphysema is characterized by persistent inflammation and progressive alveolar destruction. The receptor for advanced glycation end-products (RAGE) is a multiligand cell surface receptor reported to be involved in the process of acute alveolar epithelial cell injury. However, studies that address the role of RAGE in pulmonary emphysema are inconclusive. We investigated the role of RAGE in the development of elastase-induced pulmonary inflammation and emphysema in mice. RAGE-sufficient (RAGE(+/+)) mice and RAGE-deficient (RAGE(-/-)) mice were treated with intratracheal elastase on Day 0. Airway inflammation, static lung compliance, lung histology, and the levels of neutrophil-related chemokine and proinflammatory cytokines in bronchoalveolar lavage fluid were determined on Days 4 and 21. Neutrophilia in bronchoalveolar lavage fluid, seen in elastase-treated RAGE(+/+) mice, was reduced in elastase-treated RAGE(-/-) mice on Day 4, and was associated with decreased levels of keratinocyte chemoattractant, macrophage inflammatory protein-2, and IL-1β. Static lung compliance values and emphysematous changes in the lung tissue were decreased in RAGE(-/-) mice compared with RAGE(+/+) mice on Day 21 after elastase treatment. Experiments using irradiated, bone marrow-chimeric mice showed that the mice expressing RAGE on radioresistant structural cells, but not hematopoietic cells, developed elastase-induced neutrophilia and emphysematous change in the lung. In contrast, mice expressing RAGE on hematopoietic cells, but not radioresistant structural cells, showed reduced neutrophilia and emphysematous change in the lung. These data identify the importance of RAGE expressed on lung structural cells in the development of elastase-induced pulmonary inflammation and emphysema. Thus, RAGE represents a novel therapeutic target for preventing pulmonary emphysema.

  17. Impaired Flow-mediated Dilation Is Associated with Low Pulmonary Function and Emphysema in Ex-smokers

    PubMed Central

    Barr, R. Graham; Mesia-Vela, Sonia; Austin, John H. M.; Basner, Robert C.; Keller, Brad M.; Reeves, Anthony P.; Shimbo, Daichi; Stevenson, Lori

    2007-01-01

    Rationale: Basic science research suggests a causal role for endothelial dysfunction in chronic obstructive pulmonary disease (COPD). Clinical studies examining endothelial function are lacking, particularly early in the disease. Flow-mediated dilation (FMD) is a physiologic measure of endothelial reactivity to endogenous nitric oxide. Objectives: We hypothesized that lower FMD among former smokers would be associated with lower post-bronchodilator FEV1, higher percentage of emphysema using computed tomography (CT) and lower diffusing capacity. Methods: We measured FMD, pulmonary function, and CT percentage of emphysema in a random sample of 107 cotinine-confirmed former smokers in the ongoing EMCAP study. FMD was defined as percentage change in the brachial artery diameter with reactive hyperemia. Generalized additive models were used to adjust for potential confounders and assess linearity. Measurements and Main Results: Mean age of participants was 71 ± 5 years, 46% were female, and pack-years averaged 48 ± 26. Mean FMD was 3.8 ± 3.1%; mean post-bronchodilator FEV1, 2.3 ± 0.8 L; and mean CT percentage of emphysema, 26 ± 10%. A 1 SD decrease in FMD was associated with a 132-ml (95% confidence interval, 16–248 ml; P = 0.03) decrement in post-bronchodilator FEV1 and a 2.6% (95% confidence interval, 0.5–4.7%; P = 0.02) increase in CT percentage of emphysema in fully adjusted models. These associations were linear across the spectrum from normality to disease, independent of smoking history, and also significant among participants without COPD. Associations with diffusing capacity were consistent but nonsignificant (P = 0.09). The FMD–FEV1 association was entirely attributable to percentage of emphysema. Conclusions: Impaired endothelial function, as measured by FMD, was associated with lower FEV1 and higher CT percentage of emphysema in former smokers early in COPD. PMID:17761614

  18. A volumetric pulmonary CT segmentation method with applications in emphysema assessment

    NASA Astrophysics Data System (ADS)

    Silva, José Silvestre; Silva, Augusto; Santos, Beatriz S.

    2006-03-01

    A segmentation method is a mandatory pre-processing step in many automated or semi-automated analysis tasks such as region identification and densitometric analysis, or even for 3D visualization purposes. In this work we present a fully automated volumetric pulmonary segmentation algorithm based on intensity discrimination and morphologic procedures. Our method first identifies the trachea as well as primary bronchi and then the pulmonary region is identified by applying a threshold and morphologic operations. When both lungs are in contact, additional procedures are performed to obtain two separated lung volumes. To evaluate the performance of the method, we compared contours extracted from 3D lung surfaces with reference contours, using several figures of merit. Results show that the worst case generally occurs at the middle sections of high resolution CT exams, due the presence of aerial and vascular structures. Nevertheless, the average error is inferior to the average error associated with radiologist inter-observer variability, which suggests that our method produces lung contours similar to those drawn by radiologists. The information created by our segmentation algorithm is used by an identification and representation method in pulmonary emphysema that also classifies emphysema according to its severity degree. Two clinically proved thresholds are applied which identify regions with severe emphysema, and with highly severe emphysema. Based on this thresholding strategy, an application for volumetric emphysema assessment was developed offering new display paradigms concerning the visualization of classification results. This framework is easily extendable to accommodate other classifiers namely those related with texture based segmentation as it is often the case with interstitial diseases.

  19. 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.

  20. 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

  1. 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

  2. A Treatment with a Protease Inhibitor Recombinant from the Cattle Tick (Rhipicephalus Boophilus microplus) Ameliorates Emphysema in Mice

    PubMed Central

    Lourenço, Juliana D.; Neves, Luana P.; Olivo, Clarice R.; Duran, Adriana; Almeida, Francine M.; Arantes, Petra M. M.; Prado, Carla M.; Leick, Edna Aparecida; Tanaka, Aparecida S.; Martins, Mílton A.; Sasaki, Sergio D.; Lopes, Fernanda D. T. Q. S.

    2014-01-01

    Aims To determine whether a serine protease inhibitor treatment can prevent or minimize emphysema in mice. Methods C57BL/6 mice were subjected to porcine pancreatic elastase (PPE) nasal instillation to induce emphysema and were treated with a serine protease inhibitor (rBmTI-A) before (Protocol 1) and after (Protocol 2) emphysema development. In both protocols, we evaluated lung function to evaluate the airway resistance (Raw), tissue damping (Gtis) and tissue elastance (Htis). The inflammatory profile was analyzed in the bronchoalveolar lavage (BALF) and through the use of morphometry; we measured the mean linear intercept (Lm) (to verify alveolar enlargement), the volume proportion of collagen and elastic fibers, and the numbers of macrophages and metalloprotease 12 (MMP-12) positive cells in the parenchyma. We showed that at both time points, even after the emphysema was established, the rBmTI-A treatment was sufficient to reverse the loss of elastic recoil measured by Htis, the alveolar enlargement and the increase in the total number of cells in the BALF, with a primary decrease in the number of macrophages. Although, the treatment did not control the increase in macrophages in the lung parenchyma, it was sufficient to decrease the number of positive cells for MMP-12 and reduce the volume of collagen fibers, which was increased in PPE groups. These findings attest to the importance of MMP-12 in PPE-induced emphysema and suggest that this metalloprotease could be an effective therapeutic target. PMID:24886716

  3. 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.

  4. 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

  5. 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.

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

    PubMed Central

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

    2016-01-01

    Objectives: 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. Methods: A total of 1548 patients who underwent surgery for primary lung cancer between January 2001 and December 2012 were retrospectively reviewed. Results: 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). Conclusions: 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. PMID:27052999

  7. Tracheal necrosis with surgical emphysema following thyroidectomy.

    PubMed

    Chauhan, A; Ganguly, M; Saidha, N; Gulia, P

    2009-01-01

    Tracheal necrosis after thyroidectomy is an extremely rare event with only a few published reports. We present a case of a 65-year-old male who developed rapidly progressive surgical emphysema of face and upper thorax on the seventh day following total thyroidectomy. Prompt surgical exploration of neck revealed a tracheal rent at the level of the second tracheal ring. This hole was then refashioned into a formal tracheostomy. Patient had an eventful recovery. Tracheostomy was closed by the 14th day. The complication was probably related to tracheal injury sustained due to electro-coagulation and subsequent secondary infection. PMID:19884745

  8. Tracheal necrosis with surgical emphysema following thyroidectomy.

    PubMed

    Chauhan, A; Ganguly, M; Saidha, N; Gulia, P

    2009-01-01

    Tracheal necrosis after thyroidectomy is an extremely rare event with only a few published reports. We present a case of a 65-year-old male who developed rapidly progressive surgical emphysema of face and upper thorax on the seventh day following total thyroidectomy. Prompt surgical exploration of neck revealed a tracheal rent at the level of the second tracheal ring. This hole was then refashioned into a formal tracheostomy. Patient had an eventful recovery. Tracheostomy was closed by the 14th day. The complication was probably related to tracheal injury sustained due to electro-coagulation and subsequent secondary infection.

  9. 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. PMID:24101228

  10. 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.

  11. 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.

  12. Diaphragm mechanics in dogs with unilateral emphysema.

    PubMed Central

    Hubmayr, R D; Farkas, G A; Tao, H Y; Sieck, G C; Margulies, S S

    1993-01-01

    We studied dogs with unilateral papain-induced emphysema to answer two questions: (1) Do emphysema lung-apposed hemidiaphragm (DiE) and normal lung-apposed hemidiaphragm (DiN) have equal capacities for lowering lung surface pressure? and (2) Are side-to-side differences in intrathoracic pressure the result of unequal force outputs by DiE and DiN or are they caused by differences in their mechanical efficiency as pressure generators? After the airways of the emphysematous and normal lungs were intubated with a dual lumen endotracheal tube, both phrenic nerves were maximally stimulated at rates between 1 and 50 Hz and the changes in airway occlusion pressure (delta PaoE,N) and diaphragm length (sonomicrometry) were recorded. In all animals, delta PaoN exceeded delta PaoE. Differences in pressure ranged from 1.2 +/- 0.6 cm H2O during a twitch to 6.0 +/- 2.9 cm H2O during a 50-Hz tetanus. Midcostal bundles of DiE shortened less than corresponding bundles of DiN, but both reached the same active length relative to their optimal lengths, which were measured in vitro. There was no significant difference in fiber type distribution, fiber cross-sectional area, or maximal isometric tetanic tensions among midcostal regions of DiE and DiN. We conclude that unilateral hyperinflation impairs the mechanical efficiency of the apposing hemidiaphragm as a pressure generator. PMID:8473503

  13. 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

  14. 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 Central

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

    2016-01-01

    Purpose The outcome of radical surgery for lung cancer was investigated in patients with combined pulmonary fibrosis and emphysema (CPFE). Methods 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. Results 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). Conclusion 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. PMID:27354784

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

    PubMed

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

    2013-05-01

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

  16. Tracheal Perforation and Widespread Subcutaneous Emphysema in a Horse

    PubMed Central

    Caron, J. P.; Townsend, H. G. G.

    1984-01-01

    A twelve year old Quarterhorse mare exhibited subcutaneous emphysema of the head, neck, upper forelimbs and thorax, and walked with a stiff gait, characterized by decreased flexion of the forelimbs. Endoscopy of the trachea revealed a small tracheal wound ninety centimeters from the external nares. The location of the lesion corresponded with a seroma present at the base of the neck. The subcutaneous emphysema and the seroma resolved without specific therapy. Blunt trauma was suggested as the cause of the tracheal lesion and subsequent subcutaneous emphysema. ImagesFigure 1. PMID:17422449

  17. 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. PMID:27549540

  18. [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).

  19. Chronic Obstructive Pulmonary Disease (COPD) Includes: Chronic Bronchitis and Emphysema

    MedlinePlus

    ... 1.5 MB] More Data Age-adjusted death rates for selected causes of death, by sex, race, and Hispanic origin (chronic lower respiratory disease includes chronic bronchitis, emphysema, asthma, and other ...

  20. 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.

  1. Multifocal Endobronchial Fibromas Presenting as Unilobar Emphysema.

    PubMed

    Mumtaz, Seemal; Alkhuziem, Maha; Chow, Jennifer; Yen, Andrew; Lin, Grace; Harrell, James H; Thistlethwaite, Patricia A

    2015-09-01

    Tracheobronchial fibromas are very rare, locally-invasive tumors of the airways. Fewer than 30 cases have been reported within the English-speaking literature. Historically, these neoplasms have been diagnosed as isolated endobronchial masses, with affected patients presenting with wheezing, cough, stridor, hemoptysis, dyspnea, or pneumonia. We report the case of 39-year-old man with multiple, synchronous endobronchial fibromas causing unilobar emphysema. A computed tomographic scan and bronchoscopy with biopsy were performed preoperatively to diagnose these lesions in the orifices of the anterior segment and the lingula within the left upper lobe. The patient underwent successful video-assisted left upper lobectomy, without recurrence at 3 years. This is the first report of a synchronous presentation of multiple pulmonary endobronchial fibromas within the same patient and the first report of endobronchial fibroma presenting as unilobar air trapping. Recognition of the unusual presentation of this uncommon pathology can lead to timely intervention. PMID:26354646

  2. Congenital lobar emphysema: Pitfalls in diagnosis.

    PubMed

    Chinya, Abhishek; Pandey, Prince Raj; Sinha, Shandip Kumar; Sarin, Yogesh Kumar

    2016-01-01

    Congenital lobar emphysema (CLE) is a rare but life-threatening congenital anomaly leading to respiratory distress in early childhood. Diagnosis requires a strong clinical suspicion. We report a case of a 31/2-month-old infant who was initially diagnosed with pneumonia requiring multiple hospital admissions. After computed tomography of the thorax, a diagnosis on CLE was made. The child was planned for surgery in the next available routine operation theatre. However, suddenly in the evening, she developed respiratory distress and needed emergency surgical intervention. The child improved dramatically after surgery, and the postoperative period was uneventful. Early diagnosis and treatment in such cases can lead to dramatic results. PMID:27185998

  3. 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.

  4. 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.

  5. A case of orbital emphysema as an ocular emergency.

    PubMed

    Dobler, A A; Nathenson, A L; Cameron, J D; Carpel, E T; Janda, A M; Pederson, J E

    1993-01-01

    Orbital emphysema is radiologically apparent in 50% of cases of orbital fractures, but it is generally a benign, self-limited condition. However, visual loss may occur if a fracture produces orbital compression via a ball-valve effect, allowing air to enter but not leave the orbit. A case of compressive orbital emphysema complicated by ischemic optic neuropathy is reported. Intraorbital needle aspiration relieved the compression with improvement of visual acuity and normalization of intraocular pressure.

  6. [Intrapulmonary interstitial emphysema in ventilatorsy supported infants (author's transl)].

    PubMed

    Coradello, H; Fodor, M; Simbruner, G

    1980-09-01

    Development of intrapulmonary interstitial emphysema together with other forms of extraalveolar air collections following alveolar rupture was investigated retrospectively in 46 term and preterm newborn infants with respect to gestational age severity of pulmonary disease and mode of ventilatory assistance. Intrapulmonary interstitial emphysema was found in 31 of these 46 infants (67%). Development depended on the severity of pulmonary disease, mode of ventilatory assistance and level of inspiratory pressure. Intrapulmonary interstitial emphysema was found at an average age of 1 day (1-6 days) in 2 out of 23 infants (9%) during unassisted spontaneous breathing, in 8 out of 24 infants (33%) during CPAP and in 21 out of 26 infants (81%) during controlled ventilation. 18 out of these 31 infants (58%) additionally developed other forms of extraalveolar air collections but only in 9 from these interstitial emphysema has been found prior to other forms of extraalveolar air. Mortality rate of infants with intrapulmonary interstitial emphysema alone (10 out of 13; 77%) and infants who additionally developed other forms of extraalveolar air collections (16 out of 18; 89%) did not differ significantly. Development of intrapulmonary interstitial emphysema even in he absence of other forms of extraalveolar air collections has therefore to be judged as a severe complication in infants undergoing different forms of ventilatory assistance.

  7. 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

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

    PubMed

    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

    2015-10-05

    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.

  9. 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.

  10. 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.

  11. 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

  12. Combined pulmonary fibrosis and emphysema: The many aspects of a cohabitation contract.

    PubMed

    Papaioannou, Andriana I; Kostikas, Konstantinos; Manali, Effrosyni D; Papadaki, Georgia; Roussou, Aneza; Kolilekas, Likurgos; Borie, Raphaël; Bouros, Demosthenis; Papiris, Spyridon A

    2016-08-01

    Combined pulmonary fibrosis and emphysema (CPFE) is a clinical entity characterized by the coexistence of upper lobe emphysema and lower lobe fibrosis. Patients with this condition experience severe dyspnea and impaired gas exchange with preserved lung volumes. The diagnosis of the CPFE syndrome is based on HRCT imaging, showing the coexistence of emphysema and pulmonary fibrosis both in varying extent and locations within the lung parenchyma. Individual genetic background seem to predispose to the development of the disease. The risk of the development of pulmonary hypertension in patients with CPFE is high and related to poor prognosis. CPFE patients also present a high risk of lung cancer. Mortality is significant in patients with CPFE and median survival is reported between 2.1 and 8.5 years. Currently, no specific recommendations are available regarding the management of patients with CPFE. In this review we provide information on the existing knowledge on CPFE regarding the pathophysiology, clinical manifestations, imaging, complications, possible therapeutic interventions and prognosis of the disease. PMID:27492509

  13. Combined pulmonary fibrosis and emphysema: The many aspects of a cohabitation contract.

    PubMed

    Papaioannou, Andriana I; Kostikas, Konstantinos; Manali, Effrosyni D; Papadaki, Georgia; Roussou, Aneza; Kolilekas, Likurgos; Borie, Raphaël; Bouros, Demosthenis; Papiris, Spyridon A

    2016-08-01

    Combined pulmonary fibrosis and emphysema (CPFE) is a clinical entity characterized by the coexistence of upper lobe emphysema and lower lobe fibrosis. Patients with this condition experience severe dyspnea and impaired gas exchange with preserved lung volumes. The diagnosis of the CPFE syndrome is based on HRCT imaging, showing the coexistence of emphysema and pulmonary fibrosis both in varying extent and locations within the lung parenchyma. Individual genetic background seem to predispose to the development of the disease. The risk of the development of pulmonary hypertension in patients with CPFE is high and related to poor prognosis. CPFE patients also present a high risk of lung cancer. Mortality is significant in patients with CPFE and median survival is reported between 2.1 and 8.5 years. Currently, no specific recommendations are available regarding the management of patients with CPFE. In this review we provide information on the existing knowledge on CPFE regarding the pathophysiology, clinical manifestations, imaging, complications, possible therapeutic interventions and prognosis of the disease.

  14. 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.

  15. Induction and regulation of murine emphysema by elastin peptides.

    PubMed

    Sellami, Mehdi; Meghraoui-Kheddar, Aïda; Terryn, Christine; Fichel, Caroline; Bouland, Nicole; Diebold, Marie-Daniele; Guenounou, Moncef; Héry-Huynh, Stéphanie; Le Naour, Richard

    2016-01-01

    Emphysema is the major component of chronic obstructive pulmonary disease (COPD). During emphysema, elastin breakdown in the lung tissue originates from the release of large amounts of elastase by inflammatory cells. Elevated levels of elastin-derived peptides (EP) reflect massive pulmonary elastin breakdown in COPD patients. Only the EP containing the GXXPG conformational motif with a type VIII β-turn are elastin receptor ligands inducing biological activities. In addition, the COOH-terminal glycine residue of the GXXPG motif seems a prerequisite to the biological activity. In this study, we endotracheally instilled C57BL/6J mice with GXXPG EP and/or COOH-terminal glycine deleted-EP whose sequences were designed by molecular dynamics and docking simulations. We investigated their effect on all criteria associated with the progression of murine emphysema. Bronchoalveolar lavages were recovered to analyze cell profiles by flow cytometry and lungs were prepared to allow morphological and histological analysis by immunostaining and confocal microscopy. We observed that exposure of mice to EP elicited hallmark features of emphysema with inflammatory cell accumulation associated with increased matrix metalloproteinases and desmosine expression and of remodeling of parenchymal tissue. We also identified an inactive COOH-terminal glycine deleted-EP that retains its binding-activity to EBP and that is able to inhibit the in vitro and in vivo activities of emphysema-inducing EP. This study demonstrates that EP are key actors in the development of emphysema and that they represent pharmacological targets for an alternative treatment of emphysema based on the identification of EP analogous antagonists by molecular modeling studies.

  16. HIV-related cognitive impairment shows bi-directional association with dopamine receptor DRD1 and DRD2 polymorphisms in substance-dependent and substance-independent populations.

    PubMed

    Jacobs, Michelle M; Murray, Jacinta; Byrd, Desiree A; Hurd, Yasmin L; Morgello, Susan

    2013-10-01

    It has been postulated that drugs of abuse act synergistically with HIV, leading to increased neurotoxicity and neurocognitive impairment. The CNS impacts of HIV and drug use converge on the mesocorticolimbic dopamine (DA) system, which contains two main receptor subtypes: dopamine receptors 1 (DRD1) and 2 (DRD2). DRD1 and DRD2 have been linked to substance dependence; whether they predict HIV-associated neurocognitive disorder (HAND) is unclear. Using an advanced-stage HIV+ population, we sought to determine if drug dependence impacts the contribution of DA receptor polymorphisms on neurocognition. We observed that both DRD1 and DRD2 polymorphisms were associated with opiate and cocaine dependence (P < 0.05) in Caucasian subjects, but not African-American individuals. Using linear regression analysis, we examined the polymorphisms for associations with neuropsychological performance in global and cognitive domain T-scores (Motor, Processing Speed, Verbal Fluency, Learning, Memory, Executive Functioning, Working Memory) while controlling for opiate and cocaine dependency. In the Motor domain, we observed an association for two DRD2 polymorphisms (P < 0.05) in Caucasian subjects. The effects differed for substance dependence groups as the direction of the correlations with DRD2 were opposite to what was seen in subjects without these dependencies. In African-American subjects, associations were observed in nearly every domain, and again, the direction of the correlation differed between substance-dependent and substance-independent groups. We conclude that studies to examine genetic risk for HAND must carefully account for substance dependence patterns when assaying dopaminergic systems, as the neurobiological substrates of cognition in HIV populations may vary with tonic alterations secondary to chronic substance exposures.

  17. Contribution of CT quantified emphysema, air trapping and airway wall thickness on pulmonary function in male smokers with and without COPD.

    PubMed

    Mohamed Hoesein, Firdaus A A; de Jong, Pim A; Lammers, Jan-Willem J; Mali, Willem P Th M; Mets, Onno M; Schmidt, Michael; de Koning, Harry J; Aalst, Carlijn van der; Oudkerk, Matthijs; Vliegenthart, Rozemarijn; Ginneken, Bram van; van Rikxoort, Eva M; Zanen, Pieter

    2014-09-01

    Emphysema, airway wall thickening and air trapping are associated with chronic obstructive pulmonary disease (COPD). All three can be quantified by computed tomography (CT) of the chest. The goal of the current study is to determine the relative contribution of CT derived parameters on spirometry, lung volume and lung diffusion testing. Emphysema, airway wall thickening and air trapping were quantified automatically on CT in 1,138 male smokers with and without COPD. Emphysema was quantified by the percentage of voxels below -950 Hounsfield Units (HU), airway wall thickness by the square root of wall area for a theoretical airway with 10 mm lumen perimeter (Pi10) and air trapping by the ratio of mean lung density at expiration and inspiration (E/I-ratio). Spirometry, residual volume to total lung capacity (RV/TLC) and diffusion capacity (Kco) were obtained. Standardized regression coefficients (β) were used to analyze the relative contribution of CT changes to pulmonary function measures. The independent contribution of the three CT measures differed per lung function parameter. For the FEV1 airway wall thickness was the most contributing structural lung change (β = -0.46), while for the FEV1/FVC this was emphysema (β = -0.55). For the residual volume (RV) air trapping was most contributing (β = -0.35). Lung diffusion capacity was most influenced by emphysema (β = -0.42). In a cohort of smokers with and without COPD the effect of different CT changes varies per lung function measure and therefore emphysema, airway wall thickness and air trapping need to be taken in account.

  18. Association of Bone Mineral Density with Airway Obstruction and Emphysema

    PubMed Central

    Sim, Yun Su; Kim, Yookyung; Chang, Jung Hyun

    2012-01-01

    Background Airway obstruction and the extent of emphysema are reported to be responsible for reduced bone mineral density (BMD). Corresponding to different phenotypes of a pulmonary disease, different severity in extra pulmonary features may exist. We compared BMDs of subjects with or without airway obstruction and/or emphysema and investigated the relationships among BMD, the severity of airway obstruction, and the extent of emphysema. Methods Using a university hospital database, we reviewed patients over 40 years old who performed spirometry, computed tomography of chest, and measurement of BMD of the lumbar (L) spine. According to the presence or absence of airway obstruction and/or emphysema, four groups were classified. Results Among a total of 59 subjects, 33 (56%) had osteoporosis. The prevalence of osteoporosis in subjects with no airway obstruction and no emphysema, those with only emphysema, those with only airway obstruction, and those with both airway obstruction and emphysema were 42%, 57%, 64%, and 73%, respectively (p=0.047 by linear-by-linear association). The mean T-scores of BMD of L1 (p=0.032) and L1-4 spines were different among the four groups (p=0.034). Although the T-score of L1 BMD negatively correlated with the extent of emphysema (r=-0.275, p=0.035) and positively with each of body mass index (BMI) (r=0.520, p<0.001), forced expiratory volume in one second (FEV1) (r=0.330, p=0.011), FEV1/forced vital capacity (r=0.409, p=0.001), and forced expiratory flow at 25~75% of FVC (FEF25-75%) (r=0.438, p=0.0001), respectively, multiple linear regression analysis indicated that BMI (p<0.001) and FEF25-75% were predictive of BMD (p=0.012). Conclusion Low BMI and airway obstruction were strongly associated with reduced bone density rather than the extent of emphysema. PMID:23227071

  19. 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.

  20. 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

    2016-08-01

    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. PMID:27444019

  1. 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.

  2. 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

  3. Clinical features and outcomes of patients with lung cancer as well as combined pulmonary fibrosis and emphysema

    PubMed Central

    Otsuka, Hajime; Sugino, Keishi; Hata, Yoshinobu; Makino, Takashi; Koezuka, Satoshi; Isobe, Kazutoshi; Tochigi, Naobumi; Shibuya, Kazutoshi; Homma, Sakae; Iyoda, Akira

    2016-01-01

    The syndrome of combined pulmonary fibrosis and emphysema (CPFE) has been characterized by severely impaired gas exchange and poor survival. However, the clinical features of patients with lung cancer plus CPFE have remained elusive. The present study performed a retrospective analysis to examine the clinical characteristics and outcome of surgically resected patients with lung cancer plus CPFE. Among 831 patients with primary lung cancer who underwent surgical resection, 23 patients (2.8%) were diagnosed with CPFE and 9 patients (1.1%) with solely idiopathic pulmonary fibrosis (IPF). Thirty-five patients were stratified as the solely emphysema group with adjustment of the pathological stage. The clinicopathological characteristics of patients in the CPFE group and their outcomes were evaluated and compared with those with the solely IPF or solely emphysema groups. Within the CPFE group, no significant differences in survival between patients with post-operative acute exacerbation (AE; n=3) and those without AE (n=20) were noted; however, in the solely IPF group, patients with post-operative AE (n=4) had a significantly shorter survival than those without AE (n=5; P=0.022). The 5-year survival rate of patients in the CPFE, solely IPF and solely emphysema groups was 22, 22 and 58%, respectively. Furthermore, the CPFE and solely IPF groups showed a significantly shorter survival than the solely emphysema group (P=0.001 and 0.011, respectively). In conclusion, surgically resected lung cancer patients with CPFE had poor survival, which was, in contrast to that of lung cancer patients with solely IPF, not affected by AE. PMID:27602222

  4. A family showing inheritance of the Anton blood group antigen AnWj and independence of AnWj from Lutheran.

    PubMed

    Poole, J; Levene, C; Bennett, M; Sela, R; van Alphen, L; Spruell, P J

    1991-12-01

    A 43-year-old Arab woman was found to be negative for the high incidence AnWj antigen and her serum contained anti-AnWj. Two of her seven siblings were also AnWj-negative, which provides evidence for the first time that the AnWj-negative phenotype may be an inherited character. Blood groups of the family, in which the parents of the proposita are consanguineous, show that AnWj is not part of the ABO, Rh, MNSs, Kell, Duffy, Kidd, Xg and, notably, Lutheran blood group systems and neither is it X or Y linked.

  5. 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.

  6. Identification of novel Saccharomyces cerevisiae proteins with nuclear export activity: cell cycle-regulated transcription factor ace2p shows cell cycle-independent nucleocytoplasmic shuttling.

    PubMed

    Jensen, T H; Neville, M; Rain, J C; McCarthy, T; Legrain, P; Rosbash, M

    2000-11-01

    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-G(1)-specific genes. We now provide evidence that Ace2p is nuclear not only in late M-early G(1) 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.

  7. 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.

  8. 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. PMID:21998605

  9. 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

  10. 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.

  11. [Rheumatoid arthritis and combined pulmonary fibrosis and emphysema].

    PubMed

    Fernández Casares, Marcelo; Fielli, Mariano; Cristaldo, Laura; Zárate, Lucía; Nieves Capozzi, María

    2015-01-01

    The combination of pulmonary fibrosis and emphysema is a syndrome described in the last years, which has its own characteristics and it is not only the casual association between the two entities. The idiopathic pulmonary fibrosis is the most common type of pulmonary fibrosis. However other interstitial lung diseases could be part of this syndrome. Among them is the connective tissue disease-associated interstitial lung disease. We report a case of this syndrome associated with rheumatoid arthritis. It has the peculiarity that the connective disease became overt several years after the presentation of combined pulmonary fibrosis and emphysema syndrome, which is infrequently reported in the literature.

  12. 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

  13. 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.

  14. 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.

  15. Immunomodulatory strategies prevent the development of autoimmune emphysema

    PubMed Central

    2010-01-01

    Background The presence of anti-endothelial cell antibodies and pathogenic T cells may reflect an autoimmune component in the pathogenesis of emphysema. Whether immune modulatory strategies can protect against the development of emphysema is not known. Methods Sprague Dawley rats were immunized with human umbilical vein endothelial cells (HUVEC) to induce autoimmune emphysema and treated with intrathymic HUVEC-injection and pristane. Measurements of alveolar airspace enlargement, cytokine levels, immuno histochemical, western blot analysis, and T cell repertoire of the lung tissue were performed. Results The immunomodulatory strategies protected lungs against cell death as demonstrated by reduced numbers of TUNEL and active caspase-3 positive cells and reduced levels of active caspase-3, when compared with lungs from HUVEC-immunized rats. Immunomodulatory strategies also suppressed anti-endothelial antibody production and preserved CNTF, IL-1alpha and VEGF levels. The immune deviation effects of the intrathymic HUVEC-injection were associated with an expansion of CD4+CD25+Foxp3+ regulatory T cells. Pristane treatment decreased the proportion of T cells expressing receptor beta-chain, Vβ16.1 in the lung tissue. Conclusions Our data demonstrate that interventions classically employed to induce central T cell tolerance (thymic inoculation of antigen) or to activate innate immune responses (pristane treatment) can prevent the development of autoimmune emphysema. PMID:21162738

  16. Transpleural Ventilation via Spiracles in Severe Emphysema Increases Alveolar Ventilation.

    PubMed

    Chahla, Mayy; Larson, Christopher D; Parekh, Kalpaj R; Reed, Robert M; Terry, Peter; Schmidt, Gregory A; Eberlein, Michael

    2016-06-01

    In emphysema airway resistance can exceed collateral airflow resistance, causing air to flow preferentially through collateral pathways. In severe emphysema ventilation through openings directly through the chest wall into the parenchyma (spiracles) could bypass airway obstruction and increase alveolar ventilation via transpleural expiration. During lung transplant operations, spiracles occasionally can occur inadvertently. We observed transpleural expiration via spiracles in three subjects undergoing lung transplant for emphysema. During transpleural spiracle ventilation, inspiratory tidal volumes (TV) were unchanged; however, expiration was entirely transpleural in two patients whereas the expired TV to the ventilator circuit was reduced to 25% of the inspired TV in one. At baseline, mean PCO2 was 61 ± 5 mm Hg, which decreased to a mean PCO2 of 49 ± 5 mm Hg (P = .05) within minutes after transpleural spiracle ventilation and further decreased at 1 to 2 h (36 ± 4 mm Hg; P = .002 compared with baseline) on unchanged ventilator settings. This observation of increased alveolar ventilation supports further studies of spiracles as a possible therapy for advanced emphysema. PMID:27287591

  17. Pulmonary interstitial emphysema complicating pneumonia in an unventilated term infant.

    PubMed

    Lee, Hyun Seung; Im, Soo Ah

    2010-09-01

    A case of pulmonary interstitial emphysema with pneumothorax and pneumomediastinum complicating pneumonia in a 6-week-old infant is reported. The patient had no history of resuscitation, bag and mask ventilation, nasal continuous positive airway pressure or mechanical ventilation. PMID:20799076

  18. 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.

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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

    2015-01-01

    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. PMID:25757189

  5. Subcutaneous tissue emphysema of the hand secondary to noninfectious etiology: a report of two cases.

    PubMed

    van der Molen, A B; Birndorf, M; Dzwierzynski, W W; Sanger, J R

    1999-05-01

    Subcutaneous emphysema of the hand can be benign and noninfectious in origin. Emphysema from gas-forming organisms is associated with systemic symptoms, whereas benign subcutaneous emphysema is not. High-pressure pneumatic tool injuries are a well-known cause of subcutaneous emphysema. Minor wounds in the web space skin may result in a transport of air across the defect, acting like a ball valve mechanism to trap and then force the air into the subcutaneous tissue, as illustrated by 1 of our patients. In the second patient, use of a high-vibration tool without apparent breach of skin was associated with extensive subcutaneous emphysema. The benign nature of the emphysema was revealed by a lack of local pain and inflammation in the presence of extensive crepitus and a lack of systemic symptoms. A noninfectious cause should always be considered. This may prevent unnecessary surgical intervention, which occurred in 1 of the 2 cases presented here.

  6. Maintaining Independence.

    ERIC Educational Resources Information Center

    Upah-Bant, Marilyn

    1978-01-01

    Describes the over-all business and production operation of the "Daily Illini" at the University of Illinois to show how this college publication has assumed the burdens and responsibilities of true independence. (GW)

  7. Pathological and radiological correlation in an autopsy case of combined pulmonary fibrosis and emphysema.

    PubMed

    Karata, Hiroki; Tanaka, Tomonori; Egashira, Ryoko; Tabata, Kazuhiro; Otani, Kyoko; Hayashi, Ryuji; Hori, Takashi; Fukuoka, Junya

    2015-01-01

    We report an educational autopsy case of combined pulmonary fibrosis and emphysema. Radiological patterns of the upper lung were considered as mostly emphysema, but pathological observation revealed significant interstitial fibrosis of usual interstitial pneumonia as a major pathology. The patient eventually developed acute exacerbation of background interstitial pneumonia. Careful radiological and pathological correlation of the current case indicates that regions with distal acinar emphysema on computed tomography image may possess histologically marked dense fibrosis of lethal interstitial pneumonia.

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

    PubMed

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

    2013-05-22

    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.

  9. 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.

  10. Caveolin-1 expression is required for the development of pulmonary emphysema through activation of the ATM-p53-p21 pathway.

    PubMed

    Volonte, Daniela; Kahkonen, Beth; Shapiro, Steven; Di, Yuanpu; Galbiati, Ferruccio

    2009-02-27

    Free radicals play a role in aging and age-related human diseases, including pulmonary emphysema. Cigarette smoke represents a source of oxidants and is considered an environmental hazard that causes pulmonary emphysema. Here, we show that caveolin-1 activates ataxia telangiectasia-mutated (ATM) after oxidative stress by sequestering the ATM inhibitor, the catalytic subunit of protein phosphatase 2A, into caveolar membranes. We demonstrate that cigarette smoke extracts promote stress-induced premature senescence in wild type but not caveolin-1 null lung fibroblasts and that caveolin-1 expression is required for activation of the ATM-p53-p21(Waf1)(/)(Cip1) pathway following stimulation with cigarette smoke extracts in vitro. In vivo studies show that caveolin-1 expression is necessary for cigarette smoking-induced senescence of lung fibroblasts and pulmonary emphysema. These findings bring new insights into the molecular mechanism underlying free radical activation of the ATM-p53 pathway and indicate that caveolin-1 is a novel therapeutic target for the treatment and/or prevention of pulmonary emphysema.

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

    PubMed

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

    2012-01-01

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

  12. 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.

  13. 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.

  14. Emphysema in an adult with galactosialidosis linked to a defect in primary elastic fiber assembly.

    PubMed

    Lehman, Anna; Mattman, Andre; Sin, Don; Pare, Peter; Zong, Zheyuan; d'Azzo, Alessandra; Campos, Yvan; Sirrs, Sandra; Hinek, Aleksander

    2012-05-01

    Galactosialidosis is a lysosomal storage disorder caused by loss of function of protective protein cathepsin A, which leads to secondary deficiencies of β-galactosidase and neuraminidase-1. Emphysema has not been previously reported as a possible complication of this disorder, but we now describe this condition in a 41-year-old, non-smoking male. Our patient did not display deficiency in α-1-antitrypsin, the most common cause of emphysema in non-smokers, which brings about disseminated elastolysis. We therefore hypothesized that loss of cathepsin A activity was responsible because of previously published evidence showing it is prerequisite for normal elastogenesis. We now present experimental evidence to support this theory by demonstrating impaired primary elastogenesis in cultures of dermal fibroblasts from our patient. The obtained data further endorse our previous finding that functional integrity of the cell surface-targeted molecular complex of cathepsin A, neuraminidase-1 and the elastin-binding protein (spliced variant of β-galactosidase) is prerequisite for the normal assembly of elastic fibers. Importantly, we also found that elastic fiber production was increased after exposure either to losartan, spironolactone, or dexamethasone. Of immediate clinical relevance, our data suggest that surviving patients with galactosialidosis should have periodic assessment of their pulmonary function. We also encourage further experimental exploration of therapeutic potential of the afore-mentioned elastogenesis-stimulating drugs for the alleviation of pathological processes in galactosialidosis that could be mechanistically linked to impaired deposition of elastic fibers.

  15. Pneumomediastinum, subcutaneous emphysema and pneumorrhachis in asthmatic children.

    PubMed

    Colavita, L; Cuppari, C; Pizzino, M R; Sturiale, M; Mondello, B; Monaco, F; Barone, M; Salpietro, C

    2016-01-01

    Pneumomediastinum (PM), subcutaneous emphysema (SE) and pneumorrhachis (also known as epidural air (EDA) or epidural emphysema) are very rare findings in children. PM is defined as the passage of air from intra-alveolar space to interstitium and, later, to the mediastinum. From the mediastinum, the air may catch up subcutaneous tissue (usually of the neck) and/or epidural space via the cervical fascial planes and neural foramina, forming respectively SE and EDA. The PM can be divided in spontaneous (or idiopathic) and secondary PM. Only few studies have evaluated the exact incidence of PM and its complications in children, and to define the correct diagnostic work up, treatment and outpatient follow-up. We report the case of a 9-year-old child with undiagnosed asthma that, during severe asthmatic flare secondary to acute infection of high airway, developed PM, SE and EDA. PMID:27358152

  16. Orbital emphysema: nose blowing leading to a blown orbit.

    PubMed

    Jawaid, M Saad

    2015-01-01

    A 32-year-old woman with a painful swelling around the right eye few hours after blowing her nose, presented to the accident and emergency department. There was no associated history of facial trauma. Examination revealed a grossly swollen right eye and palpable subcutaneous emphysema. The patient's visual acuity and eye movements were normal. A CT scan of the orbit confirmed orbital emphysema secondary to a fracture of the floor of the orbit into the maxillary sinus, as a result of increased intranasal pressure during nose blowing. The patient was admitted and managed conservatively with antibiotics. She made a full recovery with complete resolution of all her symptoms. A nasal bone fracture was also seen on CT scan and even though the patient could not recall any history of facial trauma, it was an incidental finding. PMID:26516251

  17. Do bullae and emphysema increase risk of pneumothorax in silicosis?

    PubMed Central

    Mohebbi, Iraj; Hassani, Ebrahim; Salarilak, Shaker; Bahrami, Abdul Rahman

    2007-01-01

    Background: The occurrence of occupational lung diseases is decreasing due to improvements in occupational health in recent years; however, silicosis and its complications remain important occupational health problems. We have studied the role of emphysema and bullae as predictive factors of secondary spontaneous pneumothorax in acute and accelerated silicosis. Materials and Methods: This study was carried out using questionnaire items on occupational history and conventional computed tomography of lungs. Differences between two groups (silicosis with and without secondary spontaneous pneumothorax) in terms of age, interval of exposure-diagnosis and therefore silica exposure duration were assessed by independentt -test. Fisher’s exact test was used to determine the association between secondary spontaneous pneumothorax and both emphysema and bullae. Results: We found a significant association between secondary spontaneous pneumothorax and bullae in acute and accelerated silicosis. Conclusion: Pneumothorax in silicosis could be attributed to previous bullae. PMID:21957375

  18. Combined pulmonary fibrosis and emphysema in a tyre industry worker.

    PubMed

    Karkhanis, Vinaya S; Joshi, J M

    2012-07-01

    We report a case of combined pulmonary fibrosis and emphysema (CPFE) with severe pulmonary hypertension in a 46-year-old man, nonsmoker, tyre industry worker. CPFE is commonly reported to be associated with tobacco smoking. This case highlights the possible role of environmental dust exposure (talc) in the pathogenesis of the disease and confirms the clinical characteristics of CPFE described in previous studies. PMID:22919169

  19. Combined pulmonary fibrosis and emphysema in a tyre industry worker

    PubMed Central

    Karkhanis, Vinaya S.; Joshi, J. M.

    2012-01-01

    We report a case of combined pulmonary fibrosis and emphysema (CPFE) with severe pulmonary hypertension in a 46-year-old man, nonsmoker, tyre industry worker. CPFE is commonly reported to be associated with tobacco smoking. This case highlights the possible role of environmental dust exposure (talc) in the pathogenesis of the disease and confirms the clinical characteristics of CPFE described in previous studies. PMID:22919169

  20. Lung volume reduction therapies for advanced emphysema: an update.

    PubMed

    Berger, Robert L; Decamp, Malcolm M; Criner, Gerard J; Celli, Bartolome R

    2010-08-01

    Observational and randomized studies provide convincing evidence that lung volume reduction surgery (LVRS) improves symptoms, lung function, exercise tolerance, and life span in well-defined subsets of patients with emphysema. Yet, in the face of an estimated 3 million patients with emphysema in the United States, < 15 LVRS operations are performed monthly under the aegis of Medicare, in part because of misleading reporting in lay and medical publications suggesting that the operation is associated with prohibitive risks and offers minimal benefits. Thus, a treatment with proven potential for palliating and prolonging life may be underutilized. In an attempt to lower risks and cost, several bronchoscopic strategies (bronchoscopic emphysema treatment [BET]) to reduce lung volume have been introduced. The following three methods have been tested in some depth: (1) unidirectional valves that allow exit but bar entry of gas to collapse targeted hyperinflated portions of the lung and reduce overall volume; (2) biologic lung volume reduction (BioLVR) that involves intrabronchial administration of a biocompatible complex to collapse, inflame, scar, and shrink the targeted emphysematous lung; and (3) airway bypass tract (ABT) or creation of stented nonanatomic pathways between hyperinflated pulmonary parenchyma and bronchial tree to decompress and reduce the volume of oversized lung. The results of pilot and randomized pivotal clinical trials suggest that the bronchoscopic strategies are associated with lower mortality and morbidity but are also less efficient than LVRS. Most bronchoscopic approaches improve quality-of-life measures without supportive physiologic or exercise tolerance benefits. Although there is promise of limited therapeutic influence, the available information is not sufficient to recommend use of bronchoscopic strategies for treating emphysema. PMID:20682529

  1. Mesenchymal stem cells transplantation protects against rat pulmonary emphysema.

    PubMed

    Zhen, Guohua; Liu, Hongmei; Gu, Naibing; Zhang, Huilan; Xu, Yongjian; Zhang, Zhenxiang

    2008-05-01

    Pulmonary emphysema is characterized by loss of alveolar structure. Bone marrow mesenchymal stem cells (MSCs) have been shown to differentiate into alveolar epithelial cells. However, the effect of MSCs transplantation on pulmonary emphysema is unknown. To address this question, cultured bone marrow MSCs from male donor rats were infused into female recipients treated with irradiation and instillation of papain. We found that the emphysematous changes in rats received MSCs transplantation were ameliorated when compared with the rats without MSCs transplantation. Y chromosome fluorescent in situ hybridization (FISH) and immunohistochemical staining for SP-C, confirmed that MSCs engrafted in recipient lungs and differentiated into type II alveolar epithelial cells. Additionally, MSCs transplantation reduced the extent of irradiation and papain-induced alveolar cell apoptosis, likely due to the up-regulation of the expression of Bcl-2 and Bax gene. We conclude that MSCs transplantation protects against the irradiation and papain-induced pulmonary emphysema. The mechanisms of protection may involve the engraftment of MSCs in the lungs, differentiation of MSCs into type II alveolar epithelial cells and suppression of alveolar cell apoptosis.

  2. Emphysema: coiling up the lungs, trick or treat?

    PubMed

    Bezzi, M; Mondoni, M; Sorino, C; Solidoro, P

    2015-08-01

    Lung volume reduction coil (LVRC) treatment is a minimally-invasive technique planned to achieve an improvement of exercise capacity and pulmonary function in subjects with advanced emphysema and hyperinflation. It has been proposed together with other bronchoscopic lung volume reduction approaches to reduce lung hyperinflation in emphysema as less invasive alternatives to LVRS and are currently under clinical investigation. Following the successful early experiences in previous pilot trials, recent studies allow further investigation into the feasibility, safety and efficacy of LVR coil treatment in a multi-center setting in a larger group of patients. According to this studies we can state that LVR coil treatment results in significant clinical improvements in patients with severe emphysema, in multicenter analysis, with a good safety profile and sustained results for up to 1 year. The literature on endobronchial coils continues to look promising with an acceptable safety profile, and positive long-term follow-up data are certainly more and more available. However, further well-designed, blinded, placebo (or sham) controlled trials, and even randomized trials against LVRS (lung volume reduction surgery), are needed before routine clinical use can be recommended. This is true not only for endobronchial coils, but also for the whole field of bronchoscopic lung volume reduction. PMID:27427120

  3. Emphysema: coiling up the lungs, trick or treat?

    PubMed

    Bezzi, M; Mondoni, M; Sorino, C; Solidoro, P

    2015-08-01

    Lung volume reduction coil (LVRC) treatment is a minimally-invasive technique planned to achieve an improvement of exercise capacity and pulmonary function in subjects with advanced emphysema and hyperinflation. It has been proposed together with other bronchoscopic lung volume reduction approaches to reduce lung hyperinflation in emphysema as less invasive alternatives to LVRS and are currently under clinical investigation. Following the successful early experiences in previous pilot trials, recent studies allow further investigation into the feasibility, safety and efficacy of LVR coil treatment in a multi-center setting in a larger group of patients. According to this studies we can state that LVR coil treatment results in significant clinical improvements in patients with severe emphysema, in multicenter analysis, with a good safety profile and sustained results for up to 1 year. The literature on endobronchial coils continues to look promising with an acceptable safety profile, and positive long-term follow-up data are certainly more and more available. However, further well-designed, blinded, placebo (or sham) controlled trials, and even randomized trials against LVRS (lung volume reduction surgery), are needed before routine clinical use can be recommended. This is true not only for endobronchial coils, but also for the whole field of bronchoscopic lung volume reduction.

  4. 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.

  5. 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. PMID:27442681

  6. 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.

  7. 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

  8. 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.

  9. 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.

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

    PubMed Central

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

    2014-01-01

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

  11. 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.

  12. Nitrogen dioxide exposure and development of pulmonary emphysema

    SciTech Connect

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

    1986-01-01

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

  13. Lung Volume Reduction in Emphysema Improves Chest Wall Asynchrony

    PubMed Central

    LoMauro, Antonella; Aliverti, Andrea; Nelson, Christopher; Ward, Simon; Jordan, Simon; Polkey, Michael I.; Shah, Pallav L.; Hopkinson, Nicholas S.

    2015-01-01

    BACKGROUND: Lung volume reduction (LVR) techniques improve lung function in selected patients with emphysema, but the impact of LVR procedures on the asynchronous movement of different chest wall compartments, which is a feature of emphysema, is not known. METHODS: We used optoelectronic plethysmography to assess the effect of surgical and bronchoscopic LVR on chest wall asynchrony. Twenty-six patients were assessed before and 3 months after LVR (surgical [n = 9] or bronchoscopic [n = 7]) or a sham/unsuccessful bronchoscopic treatment (control subjects, n = 10). Chest wall volumes were divided into six compartments (left and right of each of pulmonary ribcage [Vrc,p], abdominal ribcage [Vrc,a], and abdomen [Vab]) and phase shift angles (θ) calculated for the asynchrony between Vrc,p and Vrc,a (θRC), and between Vrc,a and Vab (θDIA). RESULTS: Participants had an FEV1 of 34.6 ± 18% predicted and a residual volume of 217.8 ± 46.0% predicted with significant chest wall asynchrony during quiet breathing at baseline (θRC, 31.3° ± 38.4°; and θDIA, −38.7° ± 36.3°). Between-group difference in the change in θRC and θDIA during quiet breathing following treatment was 44.3° (95% CI, −78 to −10.6; P = .003) and 34.5° (95% CI, 1.4 to 67.5; P = .007) toward 0° (representing perfect synchrony), respectively, favoring the LVR group. Changes in θRC and θDIA were statistically significant on the treated but not the untreated sides. CONCLUSIONS: Successful LVR significantly reduces chest wall asynchrony in patients with emphysema. PMID:25654309

  14. 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.

  15. Fitness to fly in an infant with congenital lobar emphysema.

    PubMed

    MacLean, Joanna E; Manson, David; Gray, Gary; O'Brodovich, Hugh

    2005-10-01

    Determining fitness to fly is a difficult task for physicians, especially for those caring for children with respiratory disorders, as the available information for guidance is scarce. This case describes the use of a flight simulation in a decompression chamber in order to assess fitness to fly in an 18-mo-old infant with congenital lobar emphysema (CLE). The case discussion focuses on the need for an understanding of flight physiology in order for physicians to determine the most appropriate method to assess fitness to fly in children with medical concerns.

  16. Recurrent spontaneous subcutaneous emphysema in a patient with rheumatoid arthritis.

    PubMed

    Adelowo, Olufemi; Akintayo, Richard Oluyinka; Olaosebikan, Hakeem; Oba, Rasheedat

    2015-10-15

    Pulmonary air leak syndromes are extremely rare complications of systemic autoimmune connective tissue diseases and the occurrence of spontaneous subcutaneous emphysema (SSE) from pulmonary leak in the absence of pneumothorax or pneumomediastinum is even rarer. We report a case of recurrent SSE in a patient with rheumatoid arthritis and interstitial lung disease. The SSE was managed conservatively each time and it resorbed over several days. There has been no previous documented report of SSE in the absence of pneumomediastinum, pneumothorax or pulmonary nodules in a patient with RA.

  17. [Results of surgical treatment of generalized emphysema of the lungs].

    PubMed

    Iaitskiĭ, N A; Varlamov, V V; Gorbunkov, S D; Akopov, A L; Chernyĭ, S M; Lukina, O V; Chermenskiĭ, A G; Gembitskaia, T E

    2014-01-01

    An analysis of examination and treatment results was made in 123 patients with generalized emphysema of the lungs and respiratory failure of II-III degree. The patients were divided into two groups according to the age: younger than 40 years old (group A - 9 patients),40 years old and older (group B - 114). A surgical reduction of lung volume was performed to correct the respiratory failure in 69 patients. The rate of postoperative complications consisted of 14.7% in group A and it was 42.2% in group B. PMID:25055526

  18. 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

  19. Spontaneous subcutaneous emphysema and pneumomediastinum during second stage of labour.

    PubMed

    McGregor, Andrew; Ogwu, Christopher; Uppal, Talat; Wong, Muh Geot

    2011-01-01

    A 27-year-old healthy primigravida presented with spontaneous labour at 40 weeks gestation and proceeded to an unassisted vaginal delivery of a 3.2 kg infant. She immediately developed swelling in the neck and facial area associated with pleuritic chest pain. There was palpable crepitus throughout her anterior chest wall and neck. CT confirmed pneumomediastinum. She was managed with oxygen and analgesia in the intensive care unit and subsequently discharged with resolution of her symptoms. Postpartum pneumomediastinum with subcutaneous emphysema is treated conservatively after cardiac and embolic causes have been excluded; however, there is no consensus on the management of subsequent pregnancies.

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

    PubMed

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

    2013-02-01

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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. Alpha-1 Antitrypsin Investigations Using Animal Models of Emphysema.

    PubMed

    Ni, Kevin; Serban, Karina A; Batra, Chanan; Petrache, Irina

    2016-08-01

    Animal models of disease help accelerate the translation of basic science discoveries to the bedside, because they permit experimental interrogation of mechanisms at relatively high throughput, while accounting for the complexity of an intact organism. From the groundbreaking observation of emphysema-like alveolar destruction after direct instillation of elastase in the lungs to the more clinically relevant model of airspace enlargement induced by chronic exposure to cigarette smoke, animal models have advanced our understanding of alpha-1 antitrypsin (AAT) function. Experimental in vivo models that, at least in part, replicate clinical human phenotypes facilitate the translation of mechanistic findings into individuals with chronic obstructive pulmonary disease and with AAT deficiency. In addition, unexpected findings of alveolar enlargement in various transgenic mice have led to novel hypotheses of emphysema development. Previous challenges in manipulating the AAT genes in mice can now be overcome with new transgenic approaches that will likely advance our understanding of functions of this essential, lung-protective serine protease inhibitor (serpin). PMID:27564666

  6. Lung volume reduction for advanced emphysema: surgical and bronchoscopic approaches.

    PubMed

    Tidwell, Sherry L; Westfall, Elizabeth; Dransfield, Mark T

    2012-01-01

    Chronic obstructive pulmonary disease is the third leading cause of death in the United States, affecting more than 24 million people. Inhaled bronchodilators are the mainstay of therapy; they improve symptoms and quality of life and reduce exacerbations. These and smoking cessation and long-term oxygen therapy for hypoxemic patients are the only medical treatments definitively demonstrated to reduce mortality. Surgical approaches include lung transplantation and lung volume reduction and the latter has been shown to improve exercise tolerance, quality of life, and survival in highly selected patients with advanced emphysema. Lung volume reduction surgery results in clinical benefits. The procedure is associated with a short-term risk of mortality and a more significant risk of cardiac and pulmonary perioperative complications. Interest has been growing in the use of noninvasive, bronchoscopic methods to address the pathological hyperinflation that drives the dyspnea and exercise intolerance that is characteristic of emphysema. In this review, the mechanism by which lung volume reduction improves pulmonary function is outlined, along with the risks and benefits of the traditional surgical approach. In addition, the emerging bronchoscopic techniques for lung volume reduction are introduced and recent clinical trials examining their efficacy are summarized. PMID:22189668

  7. 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.

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

    PubMed Central

    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. PMID:27555760

  9. 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.

  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. PMID:27555760

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

    PubMed Central

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

    2011-01-01

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

  12. 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.

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

    PubMed

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

    2011-01-01

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

  14. "The Show"

    ERIC Educational Resources Information Center

    Gehring, John

    2004-01-01

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

  15. 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.

  16. Bullous emphysema as first presentation of Ehlers-Danlos syndrome in monozygotic twins.

    PubMed

    Ruggeri, Paolo; Calcaterra, Salvatore; Girbino, Giuseppe

    2015-01-01

    Ehlers-Danlos syndrome, characterized by hyperextensible skin, hypermobile joints, and fragile vessels, is the most common heritable disorder of connective tissue and has an estimated prevalence of 1 in 5000. Pulmonary involvement with signs of lung destruction (bullous emphysema) as first presentation is unusual. We report a case of monozygotic twins 37 years old men with occasional evidence of bullous emphysema with previously undiagnosed Ehlers-Danlos syndrome type IV. We emphasize the importance of considering uncommon genetic causes of emphysema in young adults, discuss underlining pathophysiological mechanisms and propose a conservative management and follow-up. PMID:26029576

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

    PubMed Central

    2010-01-01

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

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

    SciTech Connect

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

    1984-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2010-03-01

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

  20. Contemporary surgical management of advanced end stage emphysema: an evidence based review.

    PubMed

    Sachithanandan, Anand; Badmanaban, Balaji

    2012-06-01

    Emphysema is a progressive unrelenting component of chronic obstructive pulmonary disease and a major source of mortality and morbidity globally. The prevalence of moderate to severe emphysema is approximately 5% in Malaysia and likely to increase in the future. Hence advanced emphysema will emerge as a leading cause of hospital admission and a major consumer of healthcare resources in this country in the future. Patients with advanced disease have a poor quality of life and reduced survival. Medical therapy has been largely ineffective for many patients however certain subgroups have disease amenable to surgical palliation. Effective surgical therapies include lung volume reduction surgery, lung transplantation and bullectomy. This article is a comprehensive evidence based review of the literature evaluating the rationale, efficacy, safety and limitations of surgery for advanced emphysema highlighting the importance of meticulous patient selection and local factors relevant to Malaysia.

  1. Novel Endoscopic Approaches to Treating Chronic Obstructive Pulmonary Disease and Emphysema.

    PubMed

    Gompelmann, D; Eberhardt, R; Herth, F J F

    2015-08-01

    Chronic obstructive pulmonary disease (COPD) is a widespread disease associated with high morbidity and mortality. The principal aim of therapy is preventing disease progression. Besides rehabilitation and pharmacological treatment, different endoscopic approaches were developed in the past decade extending the therapeutic spectrum. Various endoscopic lung volume reduction (ELVR) techniques are available that differ in the implementation, mechanism of action, complication spectrum, and reversibility. So far, the data on efficacy and safety are variable and still very limited. The most comprehensive data are available for endoscopic valve therapy. This reversible technique leads to lobar atelectasis and thus significant lobar volume reduction in patients with severe emphysema and low collateral ventilation. Implantation of coils leading to parenchymal compression and bronchoscopic thermal vapor ablation inducing an inflammatory reaction are nonblocking ELVR techniques and thus independent of collateral ventilation. Besides ELVR techniques, targeted lung denervation has evolved as the latest development in the field of endoscopic therapy in COPD. The aim of this endoscopic method is sustainable bronchodilation by minimizing the influence of parasympathetic pulmonary nerves on smooth muscles of the airways. This review summarizes the different endoscopic procedures, their mechanism of action, and the results of the clinical trials including efficacy and safety. PMID:26238645

  2. Quantitative computed tomography measurements of emphysema for diagnosing asthma-chronic obstructive pulmonary disease overlap syndrome

    PubMed Central

    Xie, Mengshuang; Wang, Wei; Dou, Shuang; Cui, Liwei; Xiao, Wei

    2016-01-01

    Background The diagnostic criteria of asthma–COPD overlap syndrome (ACOS) are controversial. Emphysema is characteristic of COPD and usually does not exist in typical asthma patients. Emphysema in patients with asthma suggests the coexistence of COPD. Quantitative computed tomography (CT) allows repeated evaluation of emphysema noninvasively. We investigated the value of quantitative CT measurements of emphysema in the diagnosis of ACOS. Methods This study included 404 participants; 151 asthma patients, 125 COPD patients, and 128 normal control subjects. All the participants underwent pulmonary function tests and a high-resolution CT scan. Emphysema measurements were taken with an Airway Inspector software. The asthma patients were divided into high and low emphysema index (EI) groups based on the percentage of low attenuation areas less than −950 Hounsfield units. The characteristics of asthma patients with high EI were compared with those having low EI or COPD. Results The normal value of percentage of low attenuation areas less than −950 Hounsfield units in Chinese aged >40 years was 2.79%±2.37%. COPD patients indicated more severe emphysema and more upper-zone-predominant distribution of emphysema than asthma patients or controls. Thirty-two (21.2%) of the 151 asthma patients had high EI. Compared with asthma patients with low EI, those with high EI were significantly older, more likely to be male, had more pack-years of smoking, had more upper-zone-predominant distribution of emphysema, and had greater airflow limitation. There were no significant differences in sex ratios, pack-years of smoking, airflow limitation, or emphysema distribution between asthma patients with high EI and COPD patients. A greater number of acute exacerbations were seen in asthma patients with high EI compared with those with low EI or COPD. Conclusion Asthma patients with high EI fulfill the features of ACOS, as described in the Global Initiative for Asthma and Global

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-06-01

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

  5. Comparison of Serum Adiponectin in Smoke-induced Pulmonary Emphysema Rats Fed Different Diets

    PubMed Central

    Wang, Rui-Ying; Liu, Hu; Ma, Li-Juan; Xu, Jian-Ying

    2016-01-01

    Background: Smoking and body mass index (BMI) are the key risk factors for chronic obstructive pulmonary disease (COPD). Adiponectin with both anti-inflammatory and pro-inflammatory properties is a vital modulator of inflammatory processes, which is expressed in epithelial cells in the airway in COPD-emphysema. The aim of this study was to examine the effects of adiponectin on tobacco smoke-induced emphysema in rats, which were fed different diets. Methods: Seventy-six adult (6–8 weeks old) male Sprague-Dawley rats (average weight 220 ± 20 g) were exposed to smoke or smoke-free room atmosphere and fed different diets (regular, high-fat, or low-fat diets) for 6 months. The rats were randomly divided into six groups. They are nonsmoke-exposed regular diet (n = 10), nonsmoke-exposed high-fat diet (n = 14), nonsmoke-exposed low-fat diet (n = 14), smoke-exposed regular diet (n = 10), smoke-exposed high-fat diet (n = 14), and smoke-exposed low-fat diet groups (n = 14). A full 23 factorial design was used to evaluate the effect of independent variables on smoke exposure and different rearing methods. Serum adiponectin and inflammatory cytokines were measured by the enzyme-linked immunosorbent assay (ELISA). Results: Serum adiponectin levels in rats fed low-fat and regular diets exposed to smoke exposure were remarkably higher than that of rats exposed to room air while serum adiponectin levels of fat-rich diet rats exposed to tobacco smoke were lower than that of rats exposed to room air. Compared with regular diet or low-fat diet group, serum adiponectin levels in high-fat diet rats exposed to tobacco smoke were lower (t = 6.932, 11.026; all P < 0.001). BMI was inversely correlated with serum adiponectin levels (r = −0.751, P = 0.012). Serum interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and 4-hydroxy 2-nonenal (HNE) levels in rats exposed to low-fat or fat-rich diets were remarkably higher than that of rats exposed to normal diets (IL-6, t = 4.196, 3

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

    NASA Astrophysics Data System (ADS)

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

    2011-03-01

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

  7. 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. PMID:24450478

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

    PubMed Central

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

    2003-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

  10. Understanding independence

    NASA Astrophysics Data System (ADS)

    Annan, James; Hargreaves, Julia

    2016-04-01

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

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

    PubMed

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

    2014-07-01

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

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

    PubMed

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

    2010-02-01

    The aim of this study was to determine the impact of HRCT-confirmed emphysema on biomarkers evaluating airway and systemic inflammation in COPD patients. Forty-nine consecutive male COPD outpatients with stable COPD were divided in two groups according to the presence or absence of emphysema on HRCT. Patients underwent pulmonary function tests, plus assessment of exercise capacity, body composition and quality of life. Biomarkers were measured in serum (CRP, interleukin-6, TNF-alpha, leptin, adiponectin, osteocalcin, insulin growth factor-1, and systemic oxidative stress), in plasma (fibrinogen and VEGF) and in whole blood (B-type natriuretic peptide). TNF-alpha, 8-isoprostane and pH were additionally measured in exhaled breath condensate. Patients with emphysema had more severe lung function impairment, lower body-mass index and fat-free mass index, and poorer quality of life. Additionally, they presented increased systemic oxidative stress and plasma fibrinogen and lower BNP compared to patients without emphysema. After proper adjustment for disease severity, all differences remained with the exceptions of body-mass index, fat-free mass index and BNP. COPD patients with HRCT-confirmed emphysema present increased systemic oxidative stress and fibrinogen, suggesting that they may be more prone to the systemic consequences of COPD compared to patients without emphysema. PMID:19854037

  13. [Anesthetic management of a patient with severe subcutaneous and mediastinal emphysema due to pertussis infection].

    PubMed

    Ideno, Satoshi; Miyazawa, Noriko; Ishikawa, Saki; Wakamiya, Rie; Shinto, Atsushi; Mikasa, Hiromi; Yamamoto, Shinichi

    2014-06-01

    A 20-month-old girl, with respiratory failure due to severe subcutaneous and mediastinal emphysema, was scheduled to undergo percutaneous drainage of emphysema and induction of extracorporeal membrane oxygenation. Paroxysm, a symptom of the infection of Bordetella pertussis, was the cause of emphysema. In patients with severe neck subcutaneous emphysema, management of difficult airway is the most important safety issue in the practice of anesthesia. Following the American Society of Anesthesiologist (ASA) guidelines for management of difficult airway, we prepared various types of equipment to facilitate intubation and surgeons were beside the patient during induction of anesthesia for emergency invasive airway access. To prevent the progression of emphysema, preservation of spontaneous breathing during the perioperative period was also important. Combined with propofol and midazolam, pethidine was an effective agent for safe anesthetic induction because it produces less respiratory depression compared to other opiate analgesics. In conclusion, this case demonstrates the importance of prediction of and preparation for difficult airway. Furthermore, anesthesiologists should consider the optimization of anesthesia to avoid progression of emphysema.

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2009-02-01

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

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

    PubMed

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

    2015-01-01

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

  17. Mesenchymal stem cells alleviate airway inflammation and emphysema in COPD through down-regulation of cyclooxygenase-2 via p38 and ERK MAPK pathways

    PubMed Central

    Gu, Wen; Song, Lin; Li, Xiao-Ming; Wang, Di; Guo, Xue-Jun; Xu, Wei-Guo

    2015-01-01

    Bone marrow-derived mesenchymal stem cells (MSCs) have been identified as one possible strategy for the treatment of chronic obstructive pulmonary disease (COPD). Our previous studies have demonstrated that MSC administration has therapeutic potential in airway inflammation and emphysema via a paracrine mechanism. We proposed that MSCs reverse the inflammatory process and restore impaired lung function through their interaction with macrophages. In our study, the rats were exposed to cigarette smoke (CS), followed by the administration of MSCs into the lungs for 5 weeks. Here we show that MSC administration alleviated airway inflammation and emphysema through the down-regulation of cyclooxygenase-2 (COX-2) and COX-2-mediated prostaglandin E2 (PGE2) production, possibly through the effect on alveolar macrophages. In vitro co-culture experiments provided evidence that MSCs down-regulated COX-2/PGE2 in macrophages through inhibition of the activation-associated phosphorylation of p38 MAPK and ERK. Our data suggest that MSCs may relieve airway inflammation and emphysema in CS-exposed rat models, through the inhibition of COX-2/PGE2 in alveolar macrophages, mediated in part by the p38 MAPK and ERK pathways. This study provides a compelling mechanism for MSC treatment in COPD, in addition to its paracrine mechanism. PMID:25736434

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

    PubMed Central

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

    2006-01-01

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

  19. Perforin, granzyme B, and FasL expression by peripheral blood T lymphocytes in emphysema

    PubMed Central

    Morissette, Mathieu C; Parent, Julie; Milot, Julie

    2007-01-01

    Background It is generally accepted that emphysematous lungs are characterized by an increase in the numbers of neutrophils, macrophages, and CD8+ T lymphocytes, the lasts having increased cytotoxic activity. Because systemic inflammation is also a component of emphysema, we hypothesize that peripheral CD8+ T lymphocytes of emphysematous smokers who show evidence of systemic inflammation will have higher expression of cytotoxic molecules. Methods We assessed parameters of systemic inflammation in normal individuals (smokers or non-smokers) and in emphysematous subjects with an active smoking history by measuring serum interleukine-6, C-reactive protein, and tumor necrosis factor. Expression of perforin, granzyme B, and FasL protein by CD8+ T lymphocytes, CD4+ T lymphocytes, and natural killer cells were assessed by flow cytometry while perforin, granzyme B, and FasL mRNA expression were measured on purified systemic CD8+ T lymphocytes by real-time PCR. Results Emphysematous smokers had higher levels of serum interleukine-6 than normal subjects. Even with the presence of systemic inflammation in emphysematous smokers, the percentage of peripheral CD8+ T lymphocytes, CD4+ T lymphocytes, and NK cells expressing perforin and granzyme B protein was not different between the three groups. Conclusion Despite evidence of systemic inflammation, peripheral T lymphocytes of emphysematous smokers did not show higher levels of cytotoxic markers, suggesting that increase of activated T lymphocytes in the emphysematous lung may be due to either activation in the lung or specific peripheral recruitment. PMID:17822550

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

    NASA Astrophysics Data System (ADS)

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

    2013-03-01

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

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

    SciTech Connect

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

    1990-05-01

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

  2. Ceramide upregulation causes pulmonary cell apoptosis and emphysema-like disease in mice.

    PubMed

    Petrache, Irina; Natarajan, Viswanathan; Zhen, Lijie; Medler, Terry R; Richter, Amy T; Cho, Chung; Hubbard, Walter C; Berdyshev, Evgeny V; Tuder, Rubin M

    2005-05-01

    Alveolar cell apoptosis is involved in the pathogenesis of emphysema, a prevalent disease primarily caused by cigarette smoking. We report that ceramide, a second messenger lipid, is a crucial mediator of alveolar destruction in emphysema. Inhibition of enzymes controlling de novo ceramide synthesis prevented alveolar cell apoptosis, oxidative stress and emphysema caused by blockade of the vascular endothelial growth factor (VEGF) receptors in both rats and mice. Emphysema was reproduced with intratracheal instillation of ceramide in naive mice. Excessive ceramide triggers a feed-forward mechanism mediated by activation of secretory acid sphingomyelinase, as suggested by experiments with neutralizing ceramide antibody in mice and with acid sphingomyelinase-deficient fibroblasts. Concomitant augmentation of signaling initiated by a prosurvival metabolite, sphingosine-1-phosphate, prevented lung apoptosis, implying that a balance between ceramide and sphingosine-1-phosphate is required for maintenance of alveolar septal integrity. Finally, increased lung ceramides in individuals with smoking-induced emphysema suggests that ceramide upregulation may be a crucial pathogenic element and a promising target in this disease that currently lacks effective therapies. PMID:15852018

  3. Active relearning for robust supervised classification of pulmonary emphysema

    NASA Astrophysics Data System (ADS)

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

    2012-03-01

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

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

    PubMed Central

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

    2016-01-01

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

  5. Congenital Lobar Emphysema: An Approach of Anesthetic Management.

    PubMed

    Mourya, Meenakshi; Meena, Dharam Singh

    2016-08-01

    Congenital Lobar Emphysema (CLE) is a medical condition which is quiet rarely seen especially in neonates. The disease is characterized by over inflation of lungs which is produced due to inhibition of escape of inspired air from lungs. This condition usually occurs in infants due to partial obstruction of the bronchus and can be reversed with timely and planned anaesthetic management. Here in, we are presenting a case of an infant who was merely four months of age. CLE was affecting his left upper lobe since birth which was being treated as lobar pneumonia outside at some peripheral health center. The case presented to hospital with the symptoms acute respiratory distress and was taken up for urgent surgical management. Left upper lobectomy was performed which relived his symptoms. Case was discharged from hospital after 10 days of uneventful hospital stay. The case was challenging, as it involved careful and planned anaesthetic management of lung separation as well as prevention of hyperventilation of the un-involved lung. PMID:27656534

  6. Congenital Lobar Emphysema: An Approach of Anesthetic Management

    PubMed Central

    Meena, Dharam Singh

    2016-01-01

    Congenital Lobar Emphysema (CLE) is a medical condition which is quiet rarely seen especially in neonates. The disease is characterized by over inflation of lungs which is produced due to inhibition of escape of inspired air from lungs. This condition usually occurs in infants due to partial obstruction of the bronchus and can be reversed with timely and planned anaesthetic management. Here in, we are presenting a case of an infant who was merely four months of age. CLE was affecting his left upper lobe since birth which was being treated as lobar pneumonia outside at some peripheral health center. The case presented to hospital with the symptoms acute respiratory distress and was taken up for urgent surgical management. Left upper lobectomy was performed which relived his symptoms. Case was discharged from hospital after 10 days of uneventful hospital stay. The case was challenging, as it involved careful and planned anaesthetic management of lung separation as well as prevention of hyperventilation of the un-involved lung. PMID:27656534

  7. Subcutaneous Emphysema, Pneumomediastinum, and Pneumorrhachis after Cocaine Inhalation

    PubMed Central

    Atmaca Temrel, Tuğba; Şener, Alp; İçme, Ferhat; Pamukçu Günaydın, Gül; Gökhan, Şervan; Otal, Yavuz; Kurtoğlu Çelik, Gülhan; Özhasenekler, Ayhan

    2015-01-01

    Introduction. The most prominent complications of cocaine use are adverse effects in the cardiovascular and central nervous systems. Free air in the mediastinum and subcutaneous tissue may be observed less frequently, whereas free air in the spinal canal (pneumorrhachis) is a very rare complication of cocaine abuse. In this report we present a case of pneumorrhachis that developed after cocaine use. Case. A 28-year-old male patient was admitted to the emergency department with shortness of breath, chest pain, and swelling in the neck and face which started four hours after he had sniffed cocaine. On physical examination, subcutaneous crepitations were felt with palpation of the jaw, neck, and upper chest area. Diffuse subcutaneous emphysema, pneumomediastinum, and pneumorrhachis were detected in the computed tomography imaging. The patient was treated conservatively and discharged uneventfully. Discussion. Complications such as pneumothorax, pneumomediastinum, and pneumoperitoneum that are associated with cocaine use may be seen due to increased intrathoracic pressure. The air then may flow into the spinal canal resulting in pneumorrhachis. Emergency physicians should know the possible complications of cocaine use and be prepared for rare complications such as pneumorrhachis. PMID:26236511

  8. Independence Is.

    ERIC Educational Resources Information Center

    Stickney, Sharon

    This workbook is designed to help participants of the Independence Training Program (ITP) to achieve a definition of "independence." The program was developed for teenage girls. The process for developing the concept of independence consists of four steps. Step one instructs the participant to create an imaginary situation where she is completely…

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

    SciTech Connect

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

    2009-08-15

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

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

    PubMed

    Velickovic, Mirko; Hockertz, Thomas

    2016-01-01

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

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

    PubMed Central

    Hockertz, Thomas

    2016-01-01

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

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

    PubMed

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

    2014-08-15

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

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

    PubMed Central

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

    2016-01-01

    Uncontrolled pilot studies demonstrated promising results of endoscopic lung volume reduction using emphysematous lung sealant (ELS) in patients with advanced, upper lobe predominant emphysema. We aimed to evaluate the safety and efficacy of ELS in a randomised controlled setting. Patients were randomised to ELS plus medical treatment or medical treatment alone. Despite early termination for business reasons and inability to assess the primary 12-month end-point, 95 out of 300 patients were successfully randomised, providing sufficient data for 3- and 6-month analysis. 57 patients (34 treatment and 23 control) had efficacy results at 3 months; 34 (21 treatment and 13 control) at 6 months. In the treatment group, 3-month lung function, dyspnoea, and quality of life improved significantly from baseline when compared to control. Improvements persisted at 6 months with >50% of treated patients experiencing clinically important improvements, including some whose lung function improved by >100%. 44% of treated patients experienced adverse events requiring hospitalization (2.5-fold more than control, p=0.01), with two deaths in the treated cohort. Treatment responders tended to be those experiencing respiratory adverse events. Despite early termination, results show that minimally invasive ELS may be efficacious, yet significant risks (probably inflammatory) limit its current utility. PMID:25837041

  14. Are Independent Probes Truly Independent?

    ERIC Educational Resources Information Center

    Camp, Gino; Pecher, Diane; Schmidt, Henk G.; Zeelenberg, Rene

    2009-01-01

    The independent cue technique has been developed to test traditional interference theories against inhibition theories of forgetting. In the present study, the authors tested the critical criterion for the independence of independent cues: Studied cues not presented during test (and unrelated to test cues) should not contribute to the retrieval…

  15. Gastric Emphysema a Spectrum of Pneumatosis Intestinalis: A Case Report and Literature Review

    PubMed Central

    López-Medina, Guillermo; Castillo Díaz de León, Roxana; Heredia-Salazar, Alberto Carlos; Hernández-Salcedo, Daniel Ramón

    2014-01-01

    The finding of gas within the gastric wall is not a disease by itself, rather than a sign of an underlying condition which could be systemic or gastric. We present the case of a woman identified with gastric emphysema secondary to the administration of high doses of steroids, with the purpose of differentiating emphysematous gastritis versus gastric emphysema due to the divergent prognostic implications. Gastric emphysema entails a more benign course, opposed to emphysematous gastritis which often presents as an acute abdomen and carries a worse prognosis. Owing to the lack of established diagnostic criteria, computed tomography is the assessment method of choice. Currently no guidelines are available for the management of this entity, since the evidence is limited to a few case series and a considerable number of single case reports. PMID:25093129

  16. Respiratory function responses of animals and man to oxidant gases and to pulmonary emphysema

    SciTech Connect

    Mauderly, J.L.

    1984-01-01

    Data on the respiratory functional responses of animals and humans to inhaled oxidant gases and to pulmonary emphysema were reviewed and compared. Comparisons included responses to short-term inhalation of ozone, nitrogen dioxide, and oxygen and the functional manifestations of chronic emphysema. The comparisons illustrated that animals and humans have qualitatively similar functional responses to the irritant, bronchoconstrictive, and sensitizing effects of acutely inhaled ozone and nitrogen dioxide. Animals and humans responded similarly to the inflammatory and edematous effects of inhaled oxygen. Similar changes in maximal expiratory flow-volume curves, pressure-volume curves, lung volumes, and alveolar-capillary gas exchange occurred in animals and humans with emphysema. These results suggest that similar respiratory functional changes occur in both animals and humans when similar morphological changes result from lung injury. This observation lends confidence to the use of laboratory animals in studies to predict the effects of long-term exposure of humans to inhaled oxidant gases. 42 references.

  17. Hyperpolarized 83Kr magnetic resonance imaging of alveolar degradation in a rat model of emphysema.

    PubMed

    Lilburn, David M L; Lesbats, Clémentine; Six, Joseph S; Dubuis, Eric; Yew-Booth, Liang; Shaw, Dominick E; Belvisi, Maria G; Birrell, Mark A; Pavlovskaya, Galina E; Meersmann, Thomas

    2015-06-01

    Hyperpolarized (83)Kr surface quadrupolar relaxation (SQUARE) generates MRI contrast that was previously shown to correlate with surface-to-volume ratios in porous model surface systems. The underlying physics of SQUARE contrast is conceptually different from any other current MRI methodology as the method uses the nuclear electric properties of the spin I = 9/2 isotope (83)Kr. To explore the usage of this non-radioactive isotope for pulmonary pathophysiology, MRI SQUARE contrast was acquired in excised rat lungs obtained from an elastase-induced model of emphysema. A significant (83)Kr T1 relaxation time increase in the SQUARE contrast was found in the elastase-treated lungs compared with the baseline data from control lungs. The SQUARE contrast suggests a reduction in pulmonary surface-to-volume ratio in the emphysema model that was validated by histology. The finding supports usage of (83)Kr SQUARE as a new biomarker for surface-to-volume ratio changes in emphysema.

  18. Subcutaneous cervical emphysema and pneumomediastinum due to a diastatic rupture of the cecum

    PubMed Central

    VECCHIO, R.; INTAGLIATA, E.; BASILE, F.; SPATARO, C.; GIULIA, G.; LEANZA, V.; MARCHESE, S.

    2015-01-01

    Pneumomediastinum usually occurs after esophageal or chest trauma. Subcutaneous cervical emphysema as a presentation of non-traumatic colonic perforation following colorectal cancer or diverticulitis, is very rare. We report a case of a patient with rectal cancer who developed a diastatic cecum retroperitoneal perforation with a secondary pneumo-mediastinum and cervical emphysema. The patient was in treatment with a neoadjuvant chemo-radiotherapy for a low rectal cancer. Treatment consisted in an emergency right hemi-colectomy with ileostomy and performance of distal colonic fistula. The Authors discuss the occurrence of pneumomediastinum and cervical emphysema complicating rectal cancer, pointing out ethio-pathogenesis, clinical presentation, diagnosis and treatment. The importance of performing a diverting colostomy when neoadjuvant chemotherapy is scheduled in patients with stenotic rectal cancer, although not clinically occluded PMID:26888704

  19. Cotinine Concentration in Serum Correlates with Tobacco Smoke-Induced Emphysema in Mice

    NASA Astrophysics Data System (ADS)

    Xu, Xin; Su, Yunchao; Fan, Z. Hugh

    2014-01-01

    Secondhand smoke (SHS) has been associated with a variety of adverse health outcomes in nonsmokers, including emphysema (a chronic obstructive pulmonary disease). One way to detect SHS exposure is to measure the concentration of cotinine, the primary metabolite of nicotine, in bodily fluids. We have developed a method for cotinine analysis by combining micellar electrokinetic chromatography with enrichment techniques. We employed the method to measure cotinine concentrations in serum samples of mice exposed to tobacco smoke for 12 or 24 weeks and found that it was 3.1-fold or 4.8-fold higher than those exposed to room air for the same period. Further, we investigated the morphological changes in lungs of mice and observed tobacco smoke induced emphysema. Our results indicate that the method can be used to measure cotinine and there is an association between the serum cotinine concentration and tobacco smoke-induced emphysema in mice.

  20. Incidental lung volume reduction following fulminant pulmonary hemorrhage in a patient with severe emphysema.

    PubMed

    Hetzel, Juergen; Spengler, Werner; Horger, Marius; Boeckeler, Michael

    2015-06-01

    Endoscopic lung volume reduction is an emerging technique meant to improve lung function parameters, quality of life, and exercise tolerance in patients with severe lung emphysema. This is the first report of lung volume reduction by autologous blood in a patient with non-bullous lung emphysema. A 74-year-old woman with heterogeneous lung emphysema developed accidentally diffuse lobar bleeding immediately after valve placement. Due to persistent hemorrhage, the valves had to be removed shortly thereafter. Despite extraction of the valves, respiratory function of the patient improved rapidly indicated also by a drop in the COPD assessment test questionnaire, 3 months later. This was consistent with both improvement of lung function tests and six-minute walking test.

  1. Pulmonary imaging abnormalities in an adult case of congenital lobar emphysema.

    PubMed

    Pike, Damien; Mohan, Sindu; Ma, Weijing; Lewis, James F; Parraga, Grace

    2015-02-01

    Congenital lobar emphysema is mainly diagnosed in infants, although rare cases are reported in adults. A 20-yr-old female with acute dyspnea, chest pain and left upper lobe (LUL) chest x-ray hyperlucency underwent 3He magnetic resonance imaging (MRI) for ventilation and apparent diffusion coefficient (ADC) measurements, as well as CT for emphysema and airway wall measurements. Forced expiratory volume in 1s, residual volume, and airways-resistance were abnormal, but there was normal carbon-monoxide-diffusing-capacity. The LUL relative area of the density histogram <-950 HU and airway morphology were highly abnormal compared with the other lobes and coincident with highly abnormal MRI-derived acinar duct dimensions. CT also identified bronchial atresia and congenital lobar emphysema as the source of symptoms in this case where there was also functional imaging evidence of collateral ventilation from the fissure (and not the abnormally terminated airway) into the emphysematous LUL.

  2. Vitamin C prevents cigarette smoke-induced pulmonary emphysema in mice and provides pulmonary restoration.

    PubMed

    Koike, Kengo; Ishigami, Akihito; Sato, Yasunori; Hirai, Toyohiro; Yuan, Yiming; Kobayashi, Etsuko; Tobino, Kazunori; Sato, Tadashi; Sekiya, Mitsuaki; Takahashi, Kazuhisa; Fukuchi, Yoshinosuke; Maruyama, Naoki; Seyama, Kuniaki

    2014-02-01

    Vitamin C (VC) is a potent antioxidant and is essential for collagen synthesis. We investigated whether VC treatment prevents and cures smoke-induced emphysema in senescence marker protein-30 knockout (SMP30-KO) mice, which cannot synthesize VC. Two smoke-exposure experiments using SMP30-KO mice were conducted. In the first one (a preventive study), 4-month-old mice received minimal VC (0.0375 g/l) [VC(L)] or physiologically sufficient VC (1.5 g/l) [VC(S)] and exposed to cigarette smoke or smoke-free air for 2 months. Pulmonary evaluations followed when the mice were 6 months of age. The second study began after the establishment of smoke-induced emphysema (a treatment study). These mice no longer underwent smoke exposure but received VC(S) or VC(L) treatment for 2 months. Morphometric analysis was performed, and measurements of oxidative stress, collagen synthesis, and vascular endothelial growth factor in the lungs were evaluated. Chronic smoke exposure caused emphysema (29.6% increases of mean linear intercepts [MLI] and 106.5% increases of destructive index compared with the air-only group) in 6-month-old SMP30-KO mice, and this emphysema closely resembled human chronic obstructive pulmonary disease. Smoke-induced emphysema persisted in the VC(L) group after smoking cessation, whereas VC treatment provided pulmonary restoration (18.5% decrease of MLI and 41.3% decrease of destructive index compared with VC(L) group). VC treatment diminished oxidative stress, increased collagen synthesis, and improved vascular endothelial growth factor levels in the lungs. Our results suggest that VC not only prevents smoke-induced emphysema in SMP30-KO mice but also restores emphysematous lungs. Therefore, VC may provide a new therapeutic strategy for treating chronic obstructive pulmonary disease in humans.

  3. Serum Levels of Surfactant Proteins in Patients with Combined Pulmonary Fibrosis and Emphysema (CPFE)

    PubMed Central

    Papaioannou, Andriana I.; Kostikas, Konstantinos; Manali, Effrosyni D.; Papadaki, Georgia; Roussou, Aneza; Spathis, Aris; Mazioti, Argyro; Tomos, Ioannis; Papanikolaou, Ilias; Loukides, Stelios; Chainis, Kyriakos; Karakitsos, Petros; Griese, Matthias; Papiris, Spyros

    2016-01-01

    Introduction Emphysema and idiopathic pulmonary fibrosis (IPF) present either per se or coexist in combined pulmonary fibrosis and emphysema (CPFE). Serum surfactant proteins (SPs) A, B, C and D levels may reflect lung damage. We evaluated serum SP levels in healthy controls, emphysema, IPF, and CPFE patients and their associations to disease severity and survival. Methods 122 consecutive patients (31 emphysema, 62 IPF, and 29 CPFE) and 25 healthy controls underwent PFTs, ABG-measurements, 6MWT and chest HRCT. Serum levels of SPs were measured. Patients were followed-up for 1-year. Results SP-A and SP-D levels differed between groups (p = 0.006 and p<0.001 respectively). In post-hoc analysis, SP-A levels differed only between controls and CPFE (p<0.05) and CPFE and emphysema (p<0.05). SP-D differed between controls and IPF or CPFE (p<0.001 for both comparisons). In IPF SP-B correlated to pulmonary function while SP-A, correlated to the Composite Physiological Index (CPI). Controls current smokers had higher SP-A and SP-D levels compared to non-smokers (p = 0.026 and p = 0.023 respectively). SP-D levels were higher in CPFE patients with extended emphysema (p = 0.042). In patients with IPF, SP-B levels at the upper quartile of its range (≥26 ng/mL) presented a weak association with reduced survival (p = 0.05). Conclusion In conclusion, serum SP-A and SP-D levels were higher where fibrosis exists or coexists and related to disease severity, suggesting that serum SPs relate to alveolar damage in fibrotic lungs and may reflect either local overproduction or overleakage. The weak association between high levels of SP-B and survival needs further validation in clinical trials. PMID:27337142

  4. Distinct Quantitative Computed Tomography Emphysema Patterns Are Associated with Physiology and Function in Smokers

    PubMed Central

    San José Estépar, Raúl; Mendoza, Carlos S.; Hersh, Craig P.; Laird, Nan; Crapo, James D.; Lynch, David A.; Silverman, Edwin K.; Washko, George R.

    2013-01-01

    Rationale: Emphysema occurs in distinct pathologic patterns, but little is known about the epidemiologic associations of these patterns. Standard quantitative measures of emphysema from computed tomography (CT) do not distinguish between distinct patterns of parenchymal destruction. Objectives: To study the epidemiologic associations of distinct emphysema patterns with measures of lung-related physiology, function, and health care use in smokers. Methods: Using a local histogram-based assessment of lung density, we quantified distinct patterns of low attenuation in 9,313 smokers in the COPDGene Study. To determine if such patterns provide novel insights into chronic obstructive pulmonary disease epidemiology, we tested for their association with measures of physiology, function, and health care use. Measurements and Main Results: Compared with percentage of low-attenuation area less than −950 Hounsfield units (%LAA-950), local histogram-based measures of distinct CT low-attenuation patterns are more predictive of measures of lung function, dyspnea, quality of life, and health care use. These patterns are strongly associated with a wide array of measures of respiratory physiology and function, and most of these associations remain highly significant (P < 0.005) after adjusting for %LAA-950. In smokers without evidence of chronic obstructive pulmonary disease, the mild centrilobular disease pattern is associated with lower FEV1 and worse functional status (P < 0.005). Conclusions: Measures of distinct CT emphysema patterns provide novel information about the relationship between emphysema and key measures of physiology, physical function, and health care use. Measures of mild emphysema in smokers with preserved lung function can be extracted from CT scans and are significantly associated with functional measures. PMID:23980521

  5. Metabolomics screening identifies reduced L-carnitine to be associated with progressive emphysema.

    PubMed

    Conlon, Thomas M; Bartel, Jörg; Ballweg, Korbinian; Günter, Stefanie; Prehn, Cornelia; Krumsiek, Jan; Meiners, Silke; Theis, Fabian J; Adamski, Jerzy; Eickelberg, Oliver; Yildirim, Ali Önder

    2016-02-01

    Chronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitis, small airway remodelling and emphysema. Emphysema is the destruction of alveolar structures, leading to enlarged airspaces and reduced surface area impairing the ability for gaseous exchange. To further understand the pathological mechanisms underlying progressive emphysema, we used MS-based approaches to quantify the lung, bronchoalveolar lavage fluid (BALF) and serum metabolome during emphysema progression in the established murine porcine pancreatic elastase (PPE) model on days 28, 56 and 161, compared with PBS controls. Partial least squares (PLS) analysis revealed greater changes in the metabolome of lung followed by BALF rather than serum during emphysema progression. Furthermore, we demonstrate for the first time that emphysema progression is associated with a reduction in lung-specific L-carnitine, a metabolite critical for transporting long-chain fatty acids into the mitochondria for their subsequent β-oxidation. In vitro, stimulation of the alveolar epithelial type II (ATII)-like LA4 cell line with L-carnitine diminished apoptosis induced by both PPE and H2O2. Moreover, PPE-treated mice demonstrated impaired lung function compared with PBS-treated controls (lung compliance; 0.067±0.008 ml/cmH20 compared with 0.035±0.005 ml/cmH20, P<0.0001), which improved following supplementation with L-carnitine (0.051±0.006, P<0.01) and was associated with a reduction in apoptosis. In summary, our results provide a new insight into the role of L-carnitine and, importantly, suggest therapeutic avenues for COPD.

  6. Lack of Transcription Factor p53 Exacerbates Elastase-Induced Emphysema in Mice.

    PubMed

    Chrusciel, Sandra; Zysman, Maéva; Caramelle, Philippe; Tiendrebeogo, Arnaud; Baskara, Indoumady; Le Gouvello, Sabine; Chabot, François; Giraudier, Stéphane; Boczkowski, Jorge; Boyer, Laurent

    2016-02-01

    The transcription factor p53 is overexpressed in the lung of patients with emphysema, but it remains unclear if it has a deleterious or protective effect in disease progression. We investigated the role of p53 in the elastase-induced emphysema model and the molecular underlining mechanisms. Wild-type (WT) and p53(-/-) mice were instilled with pancreatic porcine elastase. We quantified emphysema (morphometric analysis), chemokine (C-C motif) ligand 2 (CCL2), and TNF-α in bronchoalveolar lavage (BAL) (ELISA), oxidative stress markers [heme oxygenase 1 (HO1), NAD(P)H dehydrogenase quinone 1 (NQO1), and quantitative RT-PCR], matrix metalloproteinase 12 (MMP12) expression, and macrophage apoptosis (cleaved caspase-3, immunofluorescence). p53 gene expression was up-regulated in the lung of elastase-instilled mice. p53 deletion aggravated elastase-induced emphysema severity, pulmonary inflammation (macrophage and neutrophil numbers and CCL2 and TNF-α levels in BAL), and lung oxidative stress. These findings, except for the increase in CCL2, were reproduced in WT mice transplanted with p53(-/-) bone marrow cells. The increased number of macrophages in p53(-/-) mice was not a consequence of reduced apoptosis or an excess of chemotaxis toward CCL2. Macrophage expression of MMP12 was higher in p53(-/-) mice compared with WT mice after elastase instillation. These findings provide evidence that p53(-/-) mice and WT mice grafted with p53(-/-) bone marrow cells are more prone to developing elastase-induced emphysema, supporting a protective role of p53, and more precisely p53 expressed in macrophages, against emphysema development. The pivotal role played by macrophages in this phenomenon may involve the MMP12-TNF-α pathway.

  7. Subcutaneous emphysema, pneumomediastinum and pneumoperitoneum after unsuccessful ERCP: a case report

    PubMed Central

    2009-01-01

    Background The presence of subcutaneous emphysema, pneumomediastinum and pneumoperitoneum simultaneously is a rare complication of upper gastrointestinal endoscopy that usually indicates free perforation to the peritoneal cavity or the retroperitoneal space. Case presentation We report an unusual case of a self-limited subcutaneous emphysema, pneumomediastinum and pneumoperitoneum following an unsuccessful ERCP for removal of a common bile duct stone. Conclusion There was no radiological evidence of peritoneal or retroperitoneal perforation. This complication is distinct from pneumomediastinum and pneumoperitoneum due to perforation, and must be recognized, because it is benign and needs no surgical or radiological intervention. PMID:19192290

  8. Cavitary lung cancer presenting as subcutaneous emphysema on the contralateral side.

    PubMed

    Yalçinkaya, Serhat; Vural, Ahmet Hakan; Göncü, Mehmet Tugrul; Özyazicioglu, Ahmet Fatih

    2012-03-01

    Bronchocutaneous fistula is an extremely rare complication of lung cancer and is frequently seen following biopsy or radiotherapy. A 67-year old male patient was administered to our hospital due to sudden onset of shortness of breath and subcutaneous emphysema on the right side. Chest computed tomography revealed a cavitary lesion in the left upper lobe in connection with the subcutaneous emphysema on the right side through sternum and anterior chest wall. The pathological examination of the biopsy performed during tube insertion revealed a well-differentiated squamous cell carcinoma of the lung. The patient was referred for adjuvant therapy to local oncology hospital. He passed away 9 months following diagnosis. PMID:22159307

  9. Assessment of multislice CT to quantify pulmonary emphysema function and physiology in a rat model

    NASA Astrophysics Data System (ADS)

    Cao, Minsong; Stantz, Keith M.; Liang, Yun; Krishnamurthi, Ganapathy; Presson, Robert G., Jr.

    2005-04-01

    Purpose: The purpose of this study is to evaluate multi-slice computed tomography technology to quantify functional and physiologic changes in rats with pulmonary emphysema. Method: Seven rats were scanned using a 16-slice CT (Philips MX8000 IDT) before and after artificial inducement of emphysema. Functional parameters i.e. lung volumes were measured by non-contrast spiral scan during forced breath-hold at inspiration and expiration followed by image segmentation based on attenuation threshold. Dynamic CT imaging was performed immediately following the contrast injection to estimate physiology changes. Pulmonary perfusion, fractional blood volume, and mean transit times (MTTs) were estimated by fitting the time-density curves of contrast material using a compartmental model. Results: The preliminary results indicated that the lung volumes of emphysema rats increased by 3.52+/-1.70mL (p<0.002) at expiration and 4.77+/-3.34mL (p<0.03) at inspiration. The mean lung densities of emphysema rats decreased by 91.76+/-68.11HU (p<0.01) at expiration and low attenuation areas increased by 5.21+/-3.88% (p<0.04) at inspiration compared with normal rats. The perfusion for normal and emphysema rats were 0.25+/-0.04ml/s/ml and 0.32+/-0.09ml/s/ml respectively. The fractional blood volumes for normal and emphysema rats were 0.21+/-0.04 and 0.15+/-0.02. There was a trend toward faster MTTs for emphysema rats (0.42+/-0.08s) than normal rats (0.89+/-0.19s) with p<0.006, suggesting that blood flow crossing the capillaries increases as the capillary volume decreases and which may cause the red blood cells to leave the capillaries incompletely saturated with oxygen if the MTTs become too short. Conclusion: Quantitative measurement using CT of structural and functional changes in pulmonary emphysema appears promising for small animals.

  10. A Case of Pulmonary Interstitial Emphysema Treated by Percutaneous Catheter Insertion in Extremely Low Birth Weight Infant.

    PubMed

    Kim, Changsin; Shin, Jeong Eun; Lee, Soon Min; Eun, Ho Seon; Park, Min Soo; Park, Kook In; Namgung, Ran; Lee, Sungsoo; Yoon, Choon Sik

    2016-11-01

    The pulmonary interstitial emphysema (PIE) is a life-threatening illness in premature infants with mechanical ventilation. While most are managed conservatively, decompression would be necessary. Here, we report the first case of PIE treated by percutaneous catheter insertion in an extremely low birth weight (ELBW) infant in Korea. The patient, born with 660 g in 23+2 weeks of gestation, showed PIE in left lower lung on postnatal day 12. Percutaneous catheter insertion was performed on postnatal day 25. The size of PIE decreased, but didn't disappear completely. On postnatal day 42, we exchanged catheter and inserted additional catheter in pleural space. However, sudden desaturation and pneumothorax occurred on postnatal day 44. We changed catheter in pleural space, and pneumothorax and PIE improved. Finally, we successfully removed catheters, and weaned patient out. As in our case, percutaneous catheter insertion would be a useful option for ELBW infants with PIE. PMID:27593885

  11. Effect of mixing scanner types and reconstruction kernels on the characterization of lung parenchymal pathologies: emphysema, interstitial pulmonary fibrosis and normal non-smokers

    NASA Astrophysics Data System (ADS)

    Xu, Ye; van Beek, Edwin J.; McLennan, Geoffrey; Guo, Junfeng; Sonka, Milan; Hoffman, Eric

    2006-03-01

    In this study we utilize our texture characterization software (3-D AMFM) to characterize interstitial lung diseases (including emphysema) based on MDCT generated volumetric data using 3-dimensional texture features. We have sought to test whether the scanner and reconstruction filter (kernel) type affect the classification of lung diseases using the 3-D AMFM. We collected MDCT images in three subject groups: emphysema (n=9), interstitial pulmonary fibrosis (IPF) (n=10), and normal non-smokers (n=9). In each group, images were scanned either on a Siemens Sensation 16 or 64-slice scanner, (B50f or B30 recon. kernel) or a Philips 4-slice scanner (B recon. kernel). A total of 1516 volumes of interest (VOIs; 21x21 pixels in plane) were marked by two chest imaging experts using the Iowa Pulmonary Analysis Software Suite (PASS). We calculated 24 volumetric features. Bayesian methods were used for classification. Images from different scanners/kernels were combined in all possible combinations to test how robust the tissue classification was relative to the differences in image characteristics. We used 10-fold cross validation for testing the result. Sensitivity, specificity and accuracy were calculated. One-way Analysis of Variances (ANOVA) was used to compare the classification result between the various combinations of scanner and reconstruction kernel types. This study yielded a sensitivity of 94%, 91%, 97%, and 93% for emphysema, ground-glass, honeycombing, and normal non-smoker patterns respectively using a mixture of all three subject groups. The specificity for these characterizations was 97%, 99%, 99%, and 98%, respectively. The F test result of ANOVA shows there is no significant difference (p <0.05) between different combinations of data with respect to scanner and convolution kernel type. Since different MDCT and reconstruction kernel types did not show significant differences in regards to the classification result, this study suggests that the 3-D AMFM can

  12. Annexin V decreases PS-mediated macrophage efferocytosis and deteriorates elastase-induced pulmonary emphysema in mice.

    PubMed

    Yoshida, S; Minematsu, N; Chubachi, S; Nakamura, H; Miyazaki, M; Tsuduki, K; Takahashi, S; Miyasho, T; Iwabuchi, T; Takamiya, R; Tateno, H; Mouded, M; Shapiro, S D; Asano, K; Betsuyaku, T

    2012-11-15

    Efferocytosis is believed to be a key regulator for lung inflammation in chronic obstructive pulmonary disease. In this study we pharmacologically inhibited efferocytosis with annexin V and attempted to determine its impact on the progression of pulmonary emphysema in mouse. We first demonstrated in vitro and in vivo efferocytosis experiments using annexin V, an inhibitor for phosphatidylserine-mediated efferocytosis. We then inhibited efferocytosis in porcine pancreatic elastase (PPE)-treated mice. PPE-treated mice were instilled annexin V intranasally starting from day 8 until day 20. Mean linear intercept (Lm) was measured, and cell apoptosis was assessed in lung specimen obtained on day 21. Cell profile, apoptosis, and mRNA expression of matrix metalloproteinases (MMPs) and growth factors were evaluated in bronchoalveolar lavage (BAL) cells on day 15. Annexin V attenuated macrophage efferocytosis both in vitro and in vivo. PPE-treated mice had a significant higher Lm, and annexin V further increased that by 32%. More number of macrophages was found in BAL fluid in this group. Interestingly, cell apoptosis was not increased by annexin V treatment both in lung specimens and BAL fluid, but macrophages from mice treated with both PPE and annexin V expressed higher MMP-2 mRNA levels and had a trend for higher MMP-12 mRNA expression. mRNA expression of keratinocyte growth factor tended to be downregulated. We showed that inhibited efferocytosis with annexin V worsened elastase-induced pulmonary emphysema in mice, which was, at least partly, attributed to a lack of phenotypic change in macrophages toward anti-inflammatory one.

  13. Quantitative computed tomography of lung parenchyma in patients with emphysema: analysis of higher-density lung regions

    NASA Astrophysics Data System (ADS)

    Lederman, Dror; Leader, Joseph K.; Zheng, Bin; Sciurba, Frank C.; Tan, Jun; Gur, David

    2011-03-01

    Quantitative computed tomography (CT) has been widely used to detect and evaluate the presence (or absence) of emphysema applying the density masks at specific thresholds, e.g., -910 or -950 Hounsfield Unit (HU). However, it has also been observed that subjects with similar density-mask based emphysema scores could have varying lung function, possibly indicating differences of disease severity. To assess this possible discrepancy, we investigated whether density distribution of "viable" lung parenchyma regions with pixel values > -910 HU correlates with lung function. A dataset of 38 subjects, who underwent both pulmonary function testing and CT examinations in a COPD SCCOR study, was assembled. After the lung regions depicted on CT images were automatically segmented by a computerized scheme, we systematically divided the lung parenchyma into different density groups (bins) and computed a number of statistical features (i.e., mean, standard deviation (STD), skewness of the pixel value distributions) in these density bins. We then analyzed the correlations between each feature and lung function. The correlation between diffusion lung capacity (DLCO) and STD of pixel values in the bin of -910HU <= PV < -750HU was -0.43, as compared with a correlation of -0.49 obtained between the post-bronchodilator ratio (FEV1/FVC) measured by the forced expiratory volume in 1 second (FEV1) dividing the forced vital capacity (FVC) and the STD of pixel values in the bin of -1024HU <= PV < -910HU. The results showed an association between the distribution of pixel values in "viable" lung parenchyma and lung function, which indicates that similar to the conventional density mask method, the pixel value distribution features in "viable" lung parenchyma areas may also provide clinically useful information to improve assessments of lung disease severity as measured by lung functional tests.

  14. Ascorbate attenuates pulmonary emphysema by inhibiting tobacco smoke and Rtp801-triggered lung protein modification and proteolysis.

    PubMed

    Gupta, Indranil; Ganguly, Souradipta; Rozanas, Christine R; Stuehr, Dennis J; Panda, Koustubh

    2016-07-19

    Cigarette smoking causes emphysema, a fatal disease involving extensive structural and functional damage of the lung. Using a guinea pig model and human lung cells, we show that oxidant(s) present in tobacco smoke not only cause direct oxidative damage of lung proteins, contributing to the major share of lung injury, but also activate Rtp801, a key proinflammatory cellular factor involved in tobacco smoke-induced lung damage. Rtp801 triggers nuclear factor κB and consequent inducible NOS (iNOS)-mediated overproduction of NO, which in combination with excess superoxide produced during Rtp801 activation, contribute to increased oxido-nitrosative stress and lung protein nitration. However, lung-specific inhibition of iNOS with a iNOS-specific inhibitor, N6-(1-iminoethyl)-L-lysine, dihydrochloride (L-NIL) solely restricts lung protein nitration but fails to prevent or reverse the major tobacco smoke-induced oxidative lung injury. In comparison, the dietary antioxidant, ascorbate or vitamin C, can substantially prevent such damage by inhibiting both tobacco smoke-induced lung protein oxidation as well as activation of pulmonary Rtp801 and consequent iNOS/NO-induced nitration of lung proteins, that otherwise lead to increased proteolysis of such oxidized or nitrated proteins by endogenous lung proteases, resulting in emphysematous lung damage. Vitamin C also restricts the up-regulation of matrix-metalloproteinase-9, the major lung protease involved in the proteolysis of such modified lung proteins during tobacco smoke-induced emphysema. Overall, our findings implicate tobacco-smoke oxidant(s) as the primary etiopathogenic factor behind both the noncellular and cellular damage mechanisms governing emphysematous lung injury and demonstrate the potential of vitamin C to accomplish holistic prevention of such damage. PMID:27382160

  15. Ascorbate attenuates pulmonary emphysema by inhibiting tobacco smoke and Rtp801-triggered lung protein modification and proteolysis.

    PubMed

    Gupta, Indranil; Ganguly, Souradipta; Rozanas, Christine R; Stuehr, Dennis J; Panda, Koustubh

    2016-07-19

    Cigarette smoking causes emphysema, a fatal disease involving extensive structural and functional damage of the lung. Using a guinea pig model and human lung cells, we show that oxidant(s) present in tobacco smoke not only cause direct oxidative damage of lung proteins, contributing to the major share of lung injury, but also activate Rtp801, a key proinflammatory cellular factor involved in tobacco smoke-induced lung damage. Rtp801 triggers nuclear factor κB and consequent inducible NOS (iNOS)-mediated overproduction of NO, which in combination with excess superoxide produced during Rtp801 activation, contribute to increased oxido-nitrosative stress and lung protein nitration. However, lung-specific inhibition of iNOS with a iNOS-specific inhibitor, N6-(1-iminoethyl)-L-lysine, dihydrochloride (L-NIL) solely restricts lung protein nitration but fails to prevent or reverse the major tobacco smoke-induced oxidative lung injury. In comparison, the dietary antioxidant, ascorbate or vitamin C, can substantially prevent such damage by inhibiting both tobacco smoke-induced lung protein oxidation as well as activation of pulmonary Rtp801 and consequent iNOS/NO-induced nitration of lung proteins, that otherwise lead to increased proteolysis of such oxidized or nitrated proteins by endogenous lung proteases, resulting in emphysematous lung damage. Vitamin C also restricts the up-regulation of matrix-metalloproteinase-9, the major lung protease involved in the proteolysis of such modified lung proteins during tobacco smoke-induced emphysema. Overall, our findings implicate tobacco-smoke oxidant(s) as the primary etiopathogenic factor behind both the noncellular and cellular damage mechanisms governing emphysematous lung injury and demonstrate the potential of vitamin C to accomplish holistic prevention of such damage.

  16. Left Upper Lobectomy for Congenital Lobar Emphysema in a Low Weight Infant

    PubMed Central

    Petsios, Konstantinos; Bobos, Dimitrios; Sarafidis, Kosmas; Nikopoulos, Stefanos; Kyriakoulis, Konstantinos; Lioulias, Achilleas; Giannopoulos, Nicholas

    2016-01-01

    Congenital lobar emphysema (CLE) is a rare lung congenital malformation. Differential diagnosis of the disease remains challenging in an infant with acute respiratory distress. We report a case of a 3-week-old female infant with a weight of 2.1 kg who presented respiratory distress related to CLE. Left upper lobectomy was performed and she had an uneventful recovery.

  17. Three-dimensional analysis of alveolar wall destruction in the early stage of pulmonary emphysema.

    PubMed

    Kobayashi, Yukihiro; Uehara, Takeshi; Kawasaki, Kenji; Sugano, Mitsutoshi; Matsumoto, Takehisa; Matsumoto, Gou; Honda, Takayuki

    2015-03-01

    The morphological mechanism of alveolar wall destruction during pulmonary emphysema has not been clarified. The aim of this study was to elucidate this process three-dimensionally. Lung specimens from five patients with pulmonary emphysema were used, and five controls with normal alveolar structure were also examined. Sections 150 μm thick were stained with hematoxylin and eosin, elastica, and silver impregnation, and immunostained with selected antibodies. We examined these sections three-dimensionally using a laser confocal microscope and a light microscope. There were only a few Kohn's pores and no fenestrae in the normal alveoli from the controls. In the lungs of the emphysema patients a small rupture appeared in the extremely thin alveolar wall among the alveolar capillaries. This rupture enlarged to form a circle surrounded by the capillaries, which was called an alveolar fenestra. Two neighboring fenestrae fused by breakdown of the collapsed or cord-like capillary between them to form a large fenestra. The large fenestrae fused repeatedly to become larger, and these were bordered by thick elastic fibers constructing an alveolar framework. Alveolar wall destruction during emphysema could start from small ruptures of the alveolar wall that become fenestrae surrounded by capillaries, which fuse repeatedly to become larger fenestrae rimmed with elastic fibers. The alveolar capillary network could initially prevent enlargement of the fenestrae, and the thick elastic fibers constituting the alveolar framework could secondarily prevent destruction of the alveolar wall structure.

  18. Development and analysis of a finite element model to simulate pulmonary emphysema in CT imaging.

    PubMed

    Diciotti, Stefano; Nobis, Alessandro; Ciulli, Stefano; Landini, Nicholas; Mascalchi, Mario; Sverzellati, Nicola; Innocenti, Bernardo

    2015-01-01

    In CT imaging, pulmonary emphysema appears as lung regions with Low-Attenuation Areas (LAA). In this study we propose a finite element (FE) model of lung parenchyma, based on a 2-D grid of beam elements, which simulates pulmonary emphysema related to smoking in CT imaging. Simulated LAA images were generated through space sampling of the model output. We employed two measurements of emphysema extent: Relative Area (RA) and the exponent D of the cumulative distribution function of LAA clusters size. The model has been used to compare RA and D computed on the simulated LAA images with those computed on the models output. Different mesh element sizes and various model parameters, simulating different physiological/pathological conditions, have been considered and analyzed. A proper mesh element size has been determined as the best trade-off between reliable results and reasonable computational cost. Both RA and D computed on simulated LAA images were underestimated with respect to those calculated on the models output. Such underestimations were larger for RA (≈ -44 ÷ -26%) as compared to those for D (≈ -16 ÷ -2%). Our FE model could be useful to generate standard test images and to design realistic physical phantoms of LAA images for the assessment of the accuracy of descriptors for quantifying emphysema in CT imaging.

  19. Recurrent spontaneous pneumothoraces and bullous emphysema. A novel mutation causing Birt-Hogg-Dube syndrome.

    PubMed

    Burkett, Andrew; Coffey, Niamh; Tomiak, Eva; Voduc, Nha

    2016-01-01

    Birt-Hogg-Dube syndrome (BHDS) is a rare form of classically cystic lung disease that may present with spontaneous pneumothorax. The associated skin manifestations (fibrofolliculomas) are not always present. This article describes a case of spontaneous pneumothorax secondary to bullous emphysema in an otherwise healthy gentleman caused by a novel mutation in the folliculin (FLCN) gene. PMID:27642565

  20. Left Upper Lobectomy for Congenital Lobar Emphysema in a Low Weight Infant.

    PubMed

    Kanakis, Meletios; Petsios, Konstantinos; Bobos, Dimitrios; Sarafidis, Kosmas; Nikopoulos, Stefanos; Kyriakoulis, Konstantinos; Lioulias, Achilleas; Giannopoulos, Nicholas

    2016-01-01

    Congenital lobar emphysema (CLE) is a rare lung congenital malformation. Differential diagnosis of the disease remains challenging in an infant with acute respiratory distress. We report a case of a 3-week-old female infant with a weight of 2.1 kg who presented respiratory distress related to CLE. Left upper lobectomy was performed and she had an uneventful recovery.

  1. A human surfactant peptide-elastase inhibitor construct as a treatment for emphysema

    PubMed Central

    Guarnieri, Frank; Spencer, Jean L.; Lucey, Edgar C.; Nugent, Matthew A.; Stone, Phillip J.

    2010-01-01

    Two million Americans suffer from pulmonary emphysema, costing $2.5 billion/year and contributing to 100,000 deaths/year. Emphysema is thought to result from an imbalance between elastase and endogenous inhibitors of elastase, leading to tissue destruction and a loss of alveoli. Decades of research have still not resulted in an effective treatment other than stopping cigarette smoking, a highly addictive behavior. On the basis of our previous work, we hypothesize that small molecule inhibitors of human neutrophil elastase are ineffective because of rapid clearance from the lungs. To develop a long-acting elastase inhibitor with a lung pharmacodynamic profile that has minimal immunogenicity, we covalently linked an elastase inhibitor, similar to a trifluoro inhibitor that was used in clinical trials, to a 25-amino-acid fragment of human surfactant peptide B. We used this construct to prevent human neutrophil elastase-induced emphysema in a rodent model. The elastase inhibitor alone, although in a 70-fold molar excess to elastase in a mixture with <0.6% residual elastase activity, provided no protection from elastase-induced emphysema. Covalently combining an endogenous peptide from the target organ with a synthetic small molecule inhibitor is a unique way of endowing an active compound with the pharmacodynamic profile needed to create in vivo efficacy. PMID:20534582

  2. Salam's independence

    NASA Astrophysics Data System (ADS)

    Fraser, Gordon

    2009-01-01

    In his kind review of my biography of the Nobel laureate Abdus Salam (December 2008 pp45-46), John W Moffat wrongly claims that Salam had "independently thought of the idea of parity violation in weak interactions".

  3. Role of LTB₄ in the pathogenesis of elastase-induced murine pulmonary emphysema.

    PubMed

    Shim, Y Michael; Paige, Mikell; Hanna, Halim; Kim, Su H; Burdick, Marie D; Strieter, Robert M

    2010-12-01

    Exaggerated levels of the leukotriene B₄ (LTB₄) frequently coexist at sites of inflammation and tissue remodeling. Therefore, we hypothesize that the LTB₄ pathway plays an important role in the pathogenesis of neutrophilic inflammation that contributes to pulmonary emphysema. In this study, significant levels of LTB₄ were detected in human lung tissues with emphysema compared with lungs without emphysema (9,497 ± 2,839 vs. 4,142 ± 1,173 pg/ml, n = 9 vs. 10, P = 0.04). To further determine the biological role of LTB₄ in the pathogenesis of emphysema, we compared the lungs of wild-type (WT) and LTA₄ hydrolase-/- mice (LTB₄ deficient, LTA₄H-/-) exposed to intranasal elastase or vehicle control. We found that intranasal elastase induced accumulation of LTB₄ in the lungs and caused progressively worsening emphysema between 14 and 28 days after elastase exposure in WT mice but not in LTA₄H-/- mice. Premortem physiology documented increased lung compliance in elastase-exposed WT mice compared with elastase-exposed LTA₄H-/- mice as measured by Flexivent (0.058 ± 0.005 vs. 0.041 ± 0.002 ml/cmH₂O pressure). Postmortem morphometry documented increased total lung volume and alveolar sizes in elastase-exposed WT mice compared with elastase-exposed LTA₄H-/- mice as measured by volume displacement and alveolar chord length assessment. Furthermore, elastase-exposed LTA₄H-/- mice were found to have significantly delayed influx of the CD45(high)CD11b(high)Ly6G(high) leukocytes compatible with neutrophils compared with elastase-exposed WT mice. Mechanistic insights to these phenotypes were provided by demonstrating protection from elastase-induced murine emphysema with neutrophil depletion in the elastase-exposed WT mice and by demonstrating time-dependent modulation of cysteinyl leukotriene biosynthesis in the elastase-exposed LTA₄H-/- mice compared with elastase-exposed WT mice. Together, these findings demonstrated that LTB₄ played an important

  4. Comparison of biophysical factors influencing on emphysema quantification with low-dose CT

    NASA Astrophysics Data System (ADS)

    Heo, Chang Yong; Kim, Jong Hyo

    2014-03-01

    Emphysema Index(EI) measurements in MDCT is known to be influenced by various biophysical factors such as total lung volume, and body size. We investigated the association of the four biophysical factors with emphysema index in low-dose MDCT. In particular, we attempted to identify a potentially stronger biophysical factor than total lung volume. A total of 400 low-dose MDCT volumes taken at 120kVp, 40mAs, 1mm thickness, and B30f reconstruction kernel were used. The lungs, airways, and pulmonary vessels were automatically segmented, and two Emphysema Indices, relative area below -950HU(RA950) and 15th percentile(Perc15), were extracted from the segmented lungs. The biophysical factors such as total lung volume(TLV), mode of lung attenuation(ModLA), effective body diameter(EBD), and the water equivalent body diameter(WBD) were estimated from the segmented lung and body area. The association of biophysical factors with emphysema indices were evaluated by correlation coefficients. The mean emphysema indices were 8.3±5.5(%) in RA950, and -930±18(HU) in Perc15. The estimates of biophysical factors were 4.7±1.0(L) in TLV, -901±21(HU) in ModLA, 26.9±2.2(cm) in EBD, and 25.9±2.6(cm) in WBD. The correlation coefficients of biophysical factors with RA950 were 0.73 in TLV, 0.94 in ModLA, 0.31 in EBD, and 0.18 WBD, the ones with Perc15 were 0.74 in TLV, 0.98 in ModLA, 0.29 in EBD, and 0.15 WBD. Study results revealed that two biophysical factors, TLV and ModLA, mostly affects the emphysema indices. In particular, the ModLA exhibited strongest correlation of 0.98 with Perc15, which indicating the ModLA is the most significant confounding biophysical factor in emphysema indices measurement.

  5. Role of Cigarette Smoke-Induced Aggresome Formation in Chronic Obstructive Pulmonary Disease-Emphysema Pathogenesis.

    PubMed

    Tran, Ian; Ji, Changhoon; Ni, Inzer; Min, Taehong; Tang, Danni; Vij, Neeraj

    2015-08-01

    Cigarette smoke (CS) exposure is known to induce proteostasis imbalance that can initiate accumulation of ubiquitinated proteins. Therefore, the primary goal of this study was to determine if first- and secondhand CS induces localization of ubiquitinated proteins in perinuclear spaces as aggresome bodies. Furthermore, we sought to determine the mechanism by which smoke-induced aggresome formation contributes to chronic obstructive pulmonary disease (COPD)-emphysema pathogenesis. Hence, Beas2b cells were treated with CS extract (CSE) for in vitro experimental analysis of CS-induced aggresome formation by immunoblotting, microscopy, and reporter assays, whereas chronic CS-exposed murine model and human COPD-emphysema lung tissues were used for validation. In preliminary analysis, we observed a significant (P < 0.01) increase in ubiquitinated protein aggregation in the insoluble protein fraction of CSE-treated Beas2b cells. We verified that CS-induced ubiquitin aggregrates are localized in the perinuclear spaces as aggresome bodies. These CS-induced aggresomes (P < 0.001) colocalize with autophagy protein microtubule-associated protein 1 light chain-3B(+) autophagy bodies, whereas U.S. Food and Drug Administration-approved autophagy-inducing drug (carbamazepine) significantly (P < 0.01) decreases their colocalization and expression, suggesting CS-impaired autophagy. Moreover, CSE treatment significantly increases valosin-containing protein-p62 protein-protein interaction (P < 0.0005) and p62 expression (aberrant autophagy marker; P < 0.0001), verifying CS-impaired autophagy as an aggresome formation mechanism. We also found that inhibiting protein synthesis by cycloheximide does not deplete CS-induced ubiquitinated protein aggregates, suggesting the role of CS-induced protein synthesis in aggresome formation. Next, we used an emphysema murine model to verify that chronic CS significantly (P < 0.0005) induces aggresome formation. Moreover, we

  6. [Lung volume reduction surgery for emphysema. Long term results].

    PubMed

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

    2002-01-01

    We prospectively analyzed 19 patients submitted to lung volume reduction surgery (LVRS). Mean age 54 years. Fourteen patients, with predominant emphysema of upper lobes, were approached through a median sternotomy. Five patients with predominant lower lobes lesions, were approached through a bilateral anterolateral thoracotomy. Surgery consisted in resection of 20 to 30% of lung volume corresponding to areas of severe parenchymal destruction by stapling suture additioned with bovine pericardium. Changes in lung function and physical performance were evaluated by FEV1, FVC and RV, 6 minutes walk test and dyspnea index according to Medical Research Council at 3, 12, 24, 36 and 48 months. Variance analysis with correction of Bonferroni was performed. One patient died of acute myocardial infarction. There was a significant average improvement in all parameters measured at 3, 12, 24 and 36 months with regard to preoperative values. Comparing the preoperative and 3 months values, there was an increment in FEV1 from 0.94 +/- 0.37 (31% of predicted) to 1.35 +/- 0.40 L (45%) (p < 0.05), in FVC from 2.24 +/- 0.69 (54%) to 3.05 +/- 0.80 L (75%) (p < 0.05) and in 6 minutes walk test from 395 +/- 66 to 517 +/- 50 mts (p < 0.001). There was also a decrease in the RV of 4.78 +/- 1.14 L (284%) to 3 +/- 0.68 L (180%) (p < 0.001) and in dyspnea index of 3.34 +/- 0.82 to 0.53 +/- 0.53 (p < 0.001). The percentage of average increment in FEV1 was 53% at 3 months (n = 18), 72% at 12 months (n = 13), 58% at 24 months (n = 10), 53% at 36 months (n = 6) and 60% at 48 months (n = 3). LVRS can be performed with acceptable morbidity and mortality in highly selected emphysematous patients. Decrease of dyspnea and improvement in physical performance reach a maximum between 3 and 12 months and may remain so after four years.

  7. Bilateral periorbital and cervicofacial emphysema following retinal surgery and fluid gas exchange in a case of inadvertent globe perforation

    PubMed Central

    Asnani, Haresh T; Mehta, Vinod C; Nair, Akshay Gopinathan; Jain, Vandana

    2015-01-01

    Surgical emphysema is defined as gas or air trapped in the subcutaneous tissue plane. Here, we report a rare case of bilateral periorbital and cervicofacial subcutaneous emphysema following a vitreoretinal surgery for inadvertent globe perforation during the administration of peribulbar anesthesia. This condition, although self-resolving when restricted to the subcutaneous plane has the potential to spread into deeper tissue planes such as the retropharyngeal space. The presence of crepitus helps to distinguish it from angioneurotic edema. Ophthalmologists must be sensitive to the fact that surgical emphysema can be a very rare, but possible complication of an intraocular surgery following globe perforation. PMID:26265649

  8. Computed Tomography-Based Centrilobular Emphysema Subtypes Relate with Pulmonary Function

    PubMed Central

    Takahashi, Mamoru; Yamada, Gen; Koba, Hiroyuki; Takahashi, Hiroki

    2013-01-01

    Introduction: Centrilobular emphysema (CLE) is recognized as low attenuation areas (LAA) with centrilobular pattern on high-resolution computed tomography (CT). However, several shapes of LAA are observed. Our preliminary study showed three types of LAA in CLE by CT-pathologic correlations. This study was performed to investigate whether the morphological features of LAA affect pulmonary functions. Materials and Methods: A total of 73 Japanese patients with stable CLE (63 males, 10 females) were evaluated visually by CT and classified into three subtypes based on the morphology of LAA including shape and sharpness of border; patients with CLE who shows round or oval LAA with well-defined border (Subtype A), polygonal or irregular-shaped LAA with ill-defined border (Subtype B), and irregular-shaped LAA with ill-defined border coalesced with each other (Subtype C). CT score, pulmonary function test and smoking index were compared among three subtypes. Results: Twenty (27%), 45 (62%) and 8 cases (11%) of the patients were grouped into Subtype A, Subtype B and Subtype C, respectively. In CT score and smoking index, both Subtype B and Subtype C were significantly higher than Subtype A. In FEV1%, Subtype C was significantly lower than both Subtype A and Subtype B. In diffusing capacity of lung for carbon monoxide, Subtype B was significantly lower than Subtype A. Conclusion: The morphological differences of LAA may relate with an airflow limitation and alveolar diffusing capacity. To assess morphological features of LAA may be helpful for the expectation of respiratory function. PMID:23935765

  9. Efficacy of alpha1-antitrypsin augmentation therapy in conditions other than pulmonary emphysema.

    PubMed

    Blanco, Ignacio; Lara, Beatriz; de Serres, Frederick

    2011-04-12

    Up to now alpha 1-antitrypsin (AAT) augmentation therapy has been approved only for commercial use in selected adults with severe AAT deficiency-related pulmonary emphysema (i.e. PI*ZZ genotypes as well as combinations of Z, rare and null alleles expressing AAT serum concentrations <11 μmol/L). However, the compassionate use of augmentation therapy in recent years has proven outstanding efficacy in small cohorts of patients suffering from uncommon AAT deficiency-related diseases other than pulmonary emphysema, such as fibromyalgia, systemic vasculitis, relapsing panniculitis and bronchial asthma. Moreover, a series of preclinical studies provide evidence of the efficacy of AAT augmentation therapy in several infectious diseases, diabetes mellitus and organ transplant rejection. These facts have generated an expanding number of medical applications and patents with claims for other indications of AAT besides pulmonary emphysema. The aim of the present study is to compile and analyze both clinical and histological features of the aforementioned published case studies and reports where AAT augmentation therapy was used for conditions other than pulmonary emphysema. Particularly, our research refers to ten case reports and two clinical trials on AAT augmentation therapy in patients with both AAT deficiency and, at least, one of the following diseases: fibromyalgia, vasculitis, panniculitis and bronchial asthma. In all the cases, AAT was successfully applied whereas previous maximal conventional therapies had failed. In conclusion, laboratory studies in animals and humans as well as larger clinical trials should be, thus, performed in order to determine both the strong clinical efficacy and security of AAT in the treatment of conditions other than pulmonary emphysema.

  10. Characterization of a Mouse Model of Emphysema Induced by Multiple Instillations of Low-Dose Elastase

    PubMed Central

    Oliveira, Milena V.; Abreu, Soraia C.; Padilha, Gisele A.; Rocha, Nazareth N.; Maia, Lígia A.; Takiya, Christina M.; Xisto, Debora G.; Suki, Bela; Silva, Pedro L.; Rocco, Patricia R. M.

    2016-01-01

    Many experimental models have been proposed to study the pathophysiological features of emphysema, as well as to search for new therapeutic approaches for acute or chronically injured lung parenchyma. We aimed to characterize an emphysema model induced by multiple instillations of elastase by tracking changes in inflammation, remodeling, and cardiac function after each instillation. Forty-eight C57BL/6 mice were randomly assigned across two groups. Emphysema (ELA) animals received 1, 2, 3, or 4 intratracheal instillations of pancreatic porcine elastase (PPE, 0.2 IU) with a 1-week interval between them. Controls (C) received saline following the same protocol. Before and after implementation of the protocol, animals underwent echocardiographic analysis. After the first instillation of PPE, the percentage of mononuclear cells in the lung parenchyma increased compared to C (p = 0.0001). The second instillation resulted in hyperinflated alveoli, increased mean linear intercept, and reduced elastic fiber content in lung parenchyma compared to C (p = 0.0197). Following the third instillation, neutrophils and collagen fiber content in alveolar septa and airways increased, whereas static lung elastance was reduced compared to C (p = 0.0094). After the fourth instillation, the percentage of M1 macrophages in lungs; levels of interleukin-1β (IL-1β), keratinocyte-derived chemokine, hepatocyte growth factor (HGF), and vascular endothelial growth factor (VEGF); and collagen fiber content in the pulmonary vessel wall were increased compared to C (p = 0.0096). At this time point, pulmonary arterial hypertension was apparent, with increased diastolic right ventricular wall thickness. In conclusion, the initial phase of emphysema was characterized by lung inflammation with predominance of mononuclear cells, whereas at the late stage, impairment of pulmonary and cardiovascular functions was observed. This model enables analysis of therapies at different time points during

  11. Lung perfusion and emphysema distribution affect the outcome of endobronchial valve therapy

    PubMed Central

    Thomsen, Christian; Theilig, Dorothea; Herzog, Dominik; Poellinger, Alexander; Doellinger, Felix; Schreiter, Nils; Schreiter, Vera; Schürmann, Dirk; Temmesfeld-Wollbrueck, Bettina; Hippenstiel, Stefan; Suttorp, Norbert; Hubner, Ralf-Harto

    2016-01-01

    The exclusion of collateral ventilation (CV) and other factors affect the clinical success of endoscopic lung volume reduction (ELVR). However, despite its benefits, the outcome of ELVR remains difficult to predict. We investigated whether clinical success could be predicted by emphysema distribution assessed by computed tomography scan and baseline perfusion assessed by perfusion scintigraphy. Data from 57 patients with no CV in the target lobe (TL) were retrospectively analyzed after ELVR with valves. Pulmonary function tests (PFT), St George’s Respiratory Questionnaire (SGRQ), and 6-minute walk tests (6MWT) were performed on patients at baseline. The sample was grouped into high and low levels at the median of TL perfusion, ipsilateral nontarget lobe (INL) perfusion, and heterogeneity index (HI). These groups were analyzed for association with changes in outcome parameters from baseline to 3 months follow-up. Compared to baseline, patients showed significant improvements in PFT, SGRQ, and 6MWT (all P≤0.001). TL perfusion was not associated with changes in the outcome. High INL perfusion was significantly associated with increases in 6MWT (P=0.014), and high HI was associated with increases in forced expiratory volume in 1 second (FEV1), (P=0.012). Likewise, there were significant correlations for INL perfusion and improvement of 6MWT (r=0.35, P=0.03) and for HI and improvement in FEV1 (r=0.45, P=0.001). This study reveals new attributes that associate with positive outcomes for patient selection prior to ELVR. Patients with high perfusions in INL demonstrated greater improvements in 6MWT, while patients with high HI were more likely to respond in FEV1. PMID:27354783

  12. Severe pulmonary emphysema in a girl with interstitial deletion of 2q24.2q24.3 including ITGB6.

    PubMed

    Takatsuki, Shinichi; Nakamura, Rina; Haga, Youichi; Mitsui, Kazumasa; Hashimoto, Takuji; Shimojima, Keiko; Saji, Tsutomu; Yamamoto, Toshiyuki

    2010-04-01

    Owing to the large size of chromosome 2, partial monosomy of the long arm of this chromosome gives rise to many specific phenotypes. We report on a 2-month-old girl with an interstitial deletion of 2q24.2q24.3, which was confirmed by microarray-based comparative genomic hybridization analysis. The patient showed delayed growth and mental retardation, early myoclonic seizures, and characteristic dysmorphic features including thick arched eyebrows, upslanting palpebral fissures, long eyelashes, depressed nasal bridge, short nose, long philtrum, small mouth, micrognathia, and low set ears. Her early myoclonic seizures were likely due to haploinsufficiency of SCN1A and SCN2A, which are included in the deletion region. When she experienced acute bronchopneumonia, she showed severe pulmonary emphysema. The deletion region of 2q24.2 includes the integrin beta6 gene (ITGB6), which may prevent acute lung injury and pulmonary emphysema. Many previously reported patients with deletions of 2q24.2 showed poor outcomes because of respiratory failure. These observations suggest the possibility of a strong relationship between haploinsufficiency of ITGB6 and pulmonary dysfunction. PMID:20358620

  13. Distinct subcutaneous emphysema following surgical wisdom tooth extraction in a patient suffering from 'Gilles de la Tourette syndrome'.

    PubMed

    Tomasetti, Patrick; Kuttenberger, Johannes; Bassetti, Renzo

    2015-01-01

    Subcutaneous emphysema is a rare complication in oral surgery. In most cases, it resolves spontaneously. However, air might disperse into deeper facial spaces causing life-threatening complications such as compression of the tracheobronchial tree or the development of pneumomediastinum. Moreover, microorganisms might spread from the oral cavity into deeper spaces. Hence, rapid diagnosis of subcutaneous emphysema is important. Characteristic signs are both a shiftable swelling and crepitation. In this case report, a 30-year-old man, suffering from the Gilles de la Tourette Syndrome, with a distinct subcutaneous emphysema after bilateral surgical wisdom tooth extraction is presented. Induced by a specific motor tic, air accumulated from the periorbital through to the parapharyngeal region. Applying a 10-cm-long Redon drainage tube as air valve, 10 days after wisdom teeth extraction, the patient was asymptomatic with complete resolution of the emphysema.

  14. Independent Living.

    ERIC Educational Resources Information Center

    Nathanson, Jeanne H., Ed.

    1994-01-01

    This issue of "OSERS" addresses the subject of independent living of individuals with disabilities. The issue includes a message from Judith E. Heumann, the Assistant Secretary of the Office of Special Education and Rehabilitative Services (OSERS), and 10 papers. Papers have the following titles and authors: "Changes in the Rehabilitation Act of…

  15. [Subcutaneous emphysema of the oral floor during cleaning of a bridge fixed on an IMZ implant. Case report].

    PubMed

    Van de Velde, E; Thielens, P; Schautteet, H; Vanclooster, R

    1991-01-01

    A case of subcutaneous emphysema following intraoral elimination of plaque and tooth shading, on a bridge fixed on implants, is presented. An instrument that produces a cleaning spray with a water-air-powder mixture was used. A few minutes after this cleaning procedure there was facial swelling. The patient experienced difficulties in breathing and in swallowing; symptoms of unilateral hearing loss were also noticed. The emphysema lasted for three days. Etiology, diagnosis, differential diagnosis, complications and management are discussed.

  16. Causation of cigarette smoke-induced emphysema by p-benzoquinone and its prevention by vitamin C.

    PubMed

    Ghosh, Arunava; Ganguly, Shinjini; Dey, Neekkan; Banerjee, Santanu; Das, Archita; Chattopadhyay, Dhruba J; Chatterjee, Indu B

    2015-03-01

    Cigarette smoke (CS) is the strongest risk factor for emphysema. However, the mechanism of the disease is not clear. One reason is that each puff of CS is a complex mixture of approximately 4,000 chemicals, and it is yet to be known which of these chemical(s) are directly involved in the pathogenesis of lung injury in emphysema. The purpose of this study was to demonstrate that p-benzoquinone (p-BQ) produced in the lungs of CS-exposed guinea pigs is a causative factor for destruction of alveolar cells resulting in emphysema that is prevented by vitamin C. Vitamin C-restricted guinea pigs were subjected to whole-body CS exposure from five Kentucky research cigarettes (3R4F) per day or intramuscular injection of p-BQ in amounts approximately produced in the lung from CS exposure with and without oral supplementation of vitamin C. Progressive exposure of CS or p-BQ treatment caused progressive accumulation of p-BQ in the lung that was accompanied by destruction of alveolar cells and emphysema. The pathogenesis involved was arylation, oxidative stress, inflammation, and apoptosis. Vitamin C (30 mg/kg body weight/d), a potential antagonist of p-BQ, prevented accumulation of p-BQ in the lung and the pathogenesis of emphysema. Our study provides the first proof that inactivation of p-BQ, a causative factor of emphysema in CS-exposed lung, could constitute a novel and effective approach in the prevention of emphysema. We consider that a moderately high dose of vitamin C may be a simple preventive therapy for emphysema in chronic smokers. PMID:25057895

  17. Influence of emphysema distribution on pulmonary function parameters in COPD patients

    PubMed Central

    Bastos, Helder Novais e; Neves, Inês; Redondo, Margarida; Cunha, Rui; Pereira, José Miguel; Magalhães, Adriana; Fernandes, Gabriela

    2015-01-01

    ABSTRACT OBJECTIVE: To evaluate the impact that the distribution of emphysema has on clinical and functional severity in patients with COPD. METHODS: The distribution of the emphysema was analyzed in COPD patients, who were classified according to a 5-point visual classification system of lung CT findings. We assessed the influence of emphysema distribution type on the clinical and functional presentation of COPD. We also evaluated hypoxemia after the six-minute walk test (6MWT) and determined the six-minute walk distance (6MWD). RESULTS: Eighty-six patients were included. The mean age was 65.2 ± 12.2 years, 91.9% were male, and all but one were smokers (mean smoking history, 62.7 ± 38.4 pack-years). The emphysema distribution was categorized as obviously upper lung-predominant (type 1), in 36.0% of the patients; slightly upper lung-predominant (type 2), in 25.6%; homogeneous between the upper and lower lung (type 3), in 16.3%; and slightly lower lung-predominant (type 4), in 22.1%. Type 2 emphysema distribution was associated with lower FEV1, FVC, FEV1/FVC ratio, and DLCO. In comparison with the type 1 patients, the type 4 patients were more likely to have an FEV1 < 65% of the predicted value (OR = 6.91, 95% CI: 1.43-33.45; p = 0.016), a 6MWD < 350 m (OR = 6.36, 95% CI: 1.26-32.18; p = 0.025), and post-6MWT hypoxemia (OR = 32.66, 95% CI: 3.26-326.84; p = 0.003). The type 3 patients had a higher RV/TLC ratio, although the difference was not significant. CONCLUSIONS: The severity of COPD appears to be greater in type 4 patients, and type 3 patients tend to have greater hyperinflation. The distribution of emphysema could have a major impact on functional parameters and should be considered in the evaluation of COPD patients. PMID:26785956

  18. Medial Wall Fracture and Orbital Emphysema Mimicking Inferior Rectus Entrapment in a Child.

    PubMed

    Collin, John; Afshar, Farid; Thomas, Steven

    2015-12-01

    Orbital emphysema is commonly associated with fractures of the orbital floor or medial wall. The air often dissipates spontaneously, but rarely can cause increased intraocular pressure and even loss of vision. Entrapment of the extraocular muscles can also occur with orbital fractures and may require prompt treatment in the pediatric patient due to the risk muscle ischemia. Both conditions can cause diplopia due to restriction of eye movement and differentiation of the two etiologies is important to prevent unnecessary surgical exploration. Identification and prompt management of raised intraocular pressure is essential in patients with orbital trauma. We present a case of orbital emphysema mimicking inferior rectus entrapment following trauma in an 11-year-old boy.

  19. Pulmonary Artery Aneurysm Thrombosis with Combined Pulmonary Fibrosis and Emphysema: A Case Report.

    PubMed

    Agrawal, Mitali Bharat; Awad, Nilkant Tukaram

    2016-05-01

    We report a rare case of Pulmonary Artery Aneurysm (PAA) thrombosis with Combined Pulmonary Fibrosis and Emphysema (CPFE) with pulmonary hypertension. A 75-year-old male presented with haemoptysis, dyspnoea, clubbing and bilateral fine end inspiratory rales on examination. He was diagnosed to have PAA thrombosis with CPFE on the basis of computed tomographical angiography and high resolution computed tomography. He was then managed conservatively with pirfenidone for the interstitial lung disease. PMID:27437277

  20. Quantitative assessment of emphysema from whole lung CT scans: comparison with visual grading

    NASA Astrophysics Data System (ADS)

    Keller, Brad M.; Reeves, Anthony P.; Apanosovich, Tatiyana V.; Wang, Jianwei; Yankelevitz, David F.; Henschke, Claudia I.

    2009-02-01

    Emphysema is a disease of the lungs that destroys the alveolar air sacs and induces long-term respiratory dysfunction. CT scans allow for imaging of the anatomical basis of emphysema and for visual assessment by radiologists of the extent present in the lungs. Several measures have been introduced for the quantification of the extent of disease directly from CT data in order to add to the qualitative assessments made by radiologists. In this paper we compare emphysema index, mean lung density, histogram percentiles, and the fractal dimension to visual grade in order to evaluate the predictability of radiologist visual scoring of emphysema from low-dose CT scans through quantitative scores, in order to determine which measures can be useful as surrogates for visual assessment. All measures were computed over nine divisions of the lung field (whole lung, individual lungs, and upper/middle/lower thirds of each lung) for each of 148 low-dose, whole lung scans. In addition, a visual grade of each section was also given by an expert radiologist. One-way ANOVA and multinomial logistic regression were used to determine the ability of the measures to predict visual grade from quantitative score. We found that all measures were able to distinguish between normal and severe grades (p<0.01), and between mild/moderate and all other grades (p<0.05). However, no measure was able to distinguish between mild and moderate cases. Approximately 65% prediction accuracy was achieved from using quantitative score to predict visual grade, with 73% if mild and moderate cases are considered as a single class.

  1. Curcumin attenuates elastase- and cigarette smoke-induced pulmonary emphysema in mice.

    PubMed

    Suzuki, Masaru; Betsuyaku, Tomoko; Ito, Yoko; Nagai, Katsura; Odajima, Nao; Moriyama, Chinatsu; Nasuhara, Yasuyuki; Nishimura, Masaharu

    2009-04-01

    Curcumin, a yellow pigment obtained from turmeric (Curcumina longa), is a dietary polyphenol that has been reported to possess anti-inflammatory and antioxidant properties. The effect of curcumin against the development of pulmonary emphysema in animal models is unknown. The aim of this study was to determine whether curcumin is able to attenuate the development of pulmonary emphysema in mice. Nine-week-old male C57BL/6J mice were treated with intratracheal porcine pancreatic elastase (PPE) or exposed to mainstream cigarette smoke (CS) (60 min/day for 10 consecutive days or 5 days/wk for 12 wk) to induce pulmonary inflammation and emphysema. Curcumin (100 mg/kg) or vehicle was administrated daily by oral gavage 1 h and 24 h before intratracheal PPE treatment and daily thereafter throughout a 21-day period in PPE-exposed mice and 1 h before each CS exposure in CS-exposed mice. As a result, curcumin treatment significantly inhibited PPE-induced increase of neutrophils in bronchoalveolar lavage fluid at 6 h and on day 1 after PPE administration, with an increase in antioxidant gene expression at 6 h and significantly attenuated PPE-induced air space enlargement on day 21. It was also found that curcumin treatment significantly inhibited CS-induced increase of neutrophils and macrophages in bronchoalveolar lavage fluid after 10 consecutive days of CS exposure and significantly attenuated CS-induced air space enlargement after 12 wk of CS exposure. In conclusion, oral curcumin administration attenuated PPE- and CS-induced pulmonary inflammation and emphysema in mice.

  2. Influence of experimental pulmonary emphysema on the toxicological effects from inhaled nitrogen dioxide and diesel exhaust

    SciTech Connect

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

    1989-10-01

    This project examined the influence of preexisting, experimentally induced pulmonary emphysema on the adverse health effects in rats of chronic inhalation exposure to either nitrogen dioxide or automotive diesel-engine exhaust. Previous reports indicated that humans with chronic lung disease were among those most severely affected by episodic exposures to high concentrations of airborne toxicants. There were no previous reports comparing the effects of chronic inhalation exposure to components of automotive emissions in emphysematous and normal animals. The hypothesis tested in this project was that rats with preexisting pulmonary emphysema were more susceptible than rats with normal lungs to the adverse effects of the toxicant exposures. Young adult rats were housed continuously in inhalation exposure chambers and exposed seven hours per day, five days per week, for 24 months to nitrogen dioxide at 9.5 parts per million (ppm)2, or to diesel exhaust at 3.5 mg soot/m3, or to clean air as control animals. These concentrations were selected to produce mild, but distinct, effects in rats with normal lungs. Pulmonary emphysema was induced in one-half of the rats by intratracheal instillation of the proteolytic enzyme elastase six weeks before the toxicant exposures began. Health effects were evaluated after 12, 18, and 24 months of exposure. The measurements included respiratory function, clearance of inhaled radiolabeled particles, pulmonary immune responses to instilled antigen, biochemistry and cytology of airway fluid, total lung collagen, histopathology, lung morphometry, and lung burdens of diesel soot. The significance of influences of emphysema and toxicant exposure, and interactions between influences of the two treatments, were evaluated by analysis of variance.

  3. Curcumin attenuates elastase- and cigarette smoke-induced pulmonary emphysema in mice.

    PubMed

    Suzuki, Masaru; Betsuyaku, Tomoko; Ito, Yoko; Nagai, Katsura; Odajima, Nao; Moriyama, Chinatsu; Nasuhara, Yasuyuki; Nishimura, Masaharu

    2009-04-01

    Curcumin, a yellow pigment obtained from turmeric (Curcumina longa), is a dietary polyphenol that has been reported to possess anti-inflammatory and antioxidant properties. The effect of curcumin against the development of pulmonary emphysema in animal models is unknown. The aim of this study was to determine whether curcumin is able to attenuate the development of pulmonary emphysema in mice. Nine-week-old male C57BL/6J mice were treated with intratracheal porcine pancreatic elastase (PPE) or exposed to mainstream cigarette smoke (CS) (60 min/day for 10 consecutive days or 5 days/wk for 12 wk) to induce pulmonary inflammation and emphysema. Curcumin (100 mg/kg) or vehicle was administrated daily by oral gavage 1 h and 24 h before intratracheal PPE treatment and daily thereafter throughout a 21-day period in PPE-exposed mice and 1 h before each CS exposure in CS-exposed mice. As a result, curcumin treatment significantly inhibited PPE-induced increase of neutrophils in bronchoalveolar lavage fluid at 6 h and on day 1 after PPE administration, with an increase in antioxidant gene expression at 6 h and significantly attenuated PPE-induced air space enlargement on day 21. It was also found that curcumin treatment significantly inhibited CS-induced increase of neutrophils and macrophages in bronchoalveolar lavage fluid after 10 consecutive days of CS exposure and significantly attenuated CS-induced air space enlargement after 12 wk of CS exposure. In conclusion, oral curcumin administration attenuated PPE- and CS-induced pulmonary inflammation and emphysema in mice. PMID:19168576

  4. Left Upper Lobectomy for Congenital Lobar Emphysema in a Low Weight Infant

    PubMed Central

    Petsios, Konstantinos; Bobos, Dimitrios; Sarafidis, Kosmas; Nikopoulos, Stefanos; Kyriakoulis, Konstantinos; Lioulias, Achilleas; Giannopoulos, Nicholas

    2016-01-01

    Congenital lobar emphysema (CLE) is a rare lung congenital malformation. Differential diagnosis of the disease remains challenging in an infant with acute respiratory distress. We report a case of a 3-week-old female infant with a weight of 2.1 kg who presented respiratory distress related to CLE. Left upper lobectomy was performed and she had an uneventful recovery. PMID:27597924

  5. Smokers with emphysema and small airway disease on computed tomography have lower bone density

    PubMed Central

    Pompe, Esther; de Jong, Pim A; van Rikxoort, Eva M; Gallardo Estrella, Leticia; de Jong, Werner U; Vliegenthart, Rozemarijn; Oudkerk, Matthijs; van der Aalst, Carlijn M; van Ginneken, Bram; Lammers, Jan-Willem J; Mohamed Hoesein, Firdaus AA

    2016-01-01

    Osteoporosis is more common in patients with COPD and in smokers. The aim of this study was to assess whether measures of emphysema and airway disease on computed tomography (CT) were associated with lower bone density or vertebral fractures in smokers with and without COPD. For this purpose, we included participants from the NELSON lung cancer screening trial. Bone density was measured as Hounsfield Units in the first lumbar vertebra, and vertebral fractures were assessed semiquantitatively. The 15th percentile method (Perc15) was used to assess emphysema, and the airway lumen perimeter (Pi10) was used for airway wall thickness. Expiratory/inspiratory-ratiomean lung density (E/I-ratioMLD) was used as a measure for air trapping and tracheal index to assess tracheal deformity. Linear regression models and logistic regression models were used to assess associations between CT biomarkers, bone density, and presence of fractures. Exactly 1,093 male participants were eligible for analysis. Lower Perc15 and higher E/I-ratioMLD were significantly associated with lower bone density (b=−1.27, P=0.02 and b=−0.37, P=0.02, respectively). Pi10 and tracheal index were not associated with bone density changes. CT-derived biomarkers were not associated with fracture prevalence. Bone density is lower with increasing extent of emphysema and small airway disease but is not associated with large airway disease and tracheal deformity. This may indicate the necessity to measure bone density early in smokers with emphysema and air trapping to prevent vertebral fractures. PMID:27354779

  6. Smokers with emphysema and small airway disease on computed tomography have lower bone density.

    PubMed

    Pompe, Esther; de Jong, Pim A; van Rikxoort, Eva M; Gallardo Estrella, Leticia; de Jong, Werner U; Vliegenthart, Rozemarijn; Oudkerk, Matthijs; van der Aalst, Carlijn M; van Ginneken, Bram; Lammers, Jan-Willem J; Mohamed Hoesein, Firdaus Aa

    2016-01-01

    Osteoporosis is more common in patients with COPD and in smokers. The aim of this study was to assess whether measures of emphysema and airway disease on computed tomography (CT) were associated with lower bone density or vertebral fractures in smokers with and without COPD. For this purpose, we included participants from the NELSON lung cancer screening trial. Bone density was measured as Hounsfield Units in the first lumbar vertebra, and vertebral fractures were assessed semiquantitatively. The 15th percentile method (Perc15) was used to assess emphysema, and the airway lumen perimeter (Pi10) was used for airway wall thickness. Expiratory/inspiratory-ratiomean lung density (E/I-ratioMLD) was used as a measure for air trapping and tracheal index to assess tracheal deformity. Linear regression models and logistic regression models were used to assess associations between CT biomarkers, bone density, and presence of fractures. Exactly 1,093 male participants were eligible for analysis. Lower Perc15 and higher E/I-ratioMLD were significantly associated with lower bone density (b=-1.27, P=0.02 and b=-0.37, P=0.02, respectively). Pi10 and tracheal index were not associated with bone density changes. CT-derived biomarkers were not associated with fracture prevalence. Bone density is lower with increasing extent of emphysema and small airway disease but is not associated with large airway disease and tracheal deformity. This may indicate the necessity to measure bone density early in smokers with emphysema and air trapping to prevent vertebral fractures.

  7. Left Upper Lobectomy for Congenital Lobar Emphysema in a Low Weight Infant.

    PubMed

    Kanakis, Meletios; Petsios, Konstantinos; Bobos, Dimitrios; Sarafidis, Kosmas; Nikopoulos, Stefanos; Kyriakoulis, Konstantinos; Lioulias, Achilleas; Giannopoulos, Nicholas

    2016-01-01

    Congenital lobar emphysema (CLE) is a rare lung congenital malformation. Differential diagnosis of the disease remains challenging in an infant with acute respiratory distress. We report a case of a 3-week-old female infant with a weight of 2.1 kg who presented respiratory distress related to CLE. Left upper lobectomy was performed and she had an uneventful recovery. PMID:27597924

  8. Smokers with emphysema and small airway disease on computed tomography have lower bone density.

    PubMed

    Pompe, Esther; de Jong, Pim A; van Rikxoort, Eva M; Gallardo Estrella, Leticia; de Jong, Werner U; Vliegenthart, Rozemarijn; Oudkerk, Matthijs; van der Aalst, Carlijn M; van Ginneken, Bram; Lammers, Jan-Willem J; Mohamed Hoesein, Firdaus Aa

    2016-01-01

    Osteoporosis is more common in patients with COPD and in smokers. The aim of this study was to assess whether measures of emphysema and airway disease on computed tomography (CT) were associated with lower bone density or vertebral fractures in smokers with and without COPD. For this purpose, we included participants from the NELSON lung cancer screening trial. Bone density was measured as Hounsfield Units in the first lumbar vertebra, and vertebral fractures were assessed semiquantitatively. The 15th percentile method (Perc15) was used to assess emphysema, and the airway lumen perimeter (Pi10) was used for airway wall thickness. Expiratory/inspiratory-ratiomean lung density (E/I-ratioMLD) was used as a measure for air trapping and tracheal index to assess tracheal deformity. Linear regression models and logistic regression models were used to assess associations between CT biomarkers, bone density, and presence of fractures. Exactly 1,093 male participants were eligible for analysis. Lower Perc15 and higher E/I-ratioMLD were significantly associated with lower bone density (b=-1.27, P=0.02 and b=-0.37, P=0.02, respectively). Pi10 and tracheal index were not associated with bone density changes. CT-derived biomarkers were not associated with fracture prevalence. Bone density is lower with increasing extent of emphysema and small airway disease but is not associated with large airway disease and tracheal deformity. This may indicate the necessity to measure bone density early in smokers with emphysema and air trapping to prevent vertebral fractures. PMID:27354779

  9. Small-animal dark-field radiography for pulmonary emphysema evaluation

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

    Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality worldwide and emphysema is one of its main components. The disorder is characterized by irreversible destruction of the alveolar walls and enlargement of distal airspaces. Despite the severe changes in the lung tissue morphology, conventional chest radiographs have only a limited sensitivity for the detection of mild to moderate emphysema. X-ray dark-field is an imaging modality that can significantly increase the visibility of lung tissue on radiographic images. The dark-field signal is generated by coherent, small-angle scattering of x-rays on the air-tissue interfaces in the lung. Therefore, morphological changes in the lung can be clearly visualized on dark-field images. This is demonstrated by a preclinical study with a small-animal emphysema model. To generate a murine model of pulmonary emphysema, a female C57BL/6N mouse was treated with a single orotracheal application of porcine pancreatic elastase (80 U/kg body weight) dissolved in phosphate-buffered saline (PBS). Control mouse received PBS. The mice were imaged using a small-animal dark-field scanner. While conventional x-ray transmission radiography images revealed only subtle indirect signs of the pulmonary disorder, the difference between healthy and emphysematous lungs could be clearly directly visualized on the dark-field images. The dose applied to the animals is compatible with longitudinal studies. The imaging results correlate well with histology. The results of this study reveal the high potential of dark-field radiography for clinical lung imaging.

  10. Exercise testing in severe emphysema: association with quality of life and lung function.

    PubMed

    Brown, Cynthia D; Benditt, Joshua O; Sciurba, Frank C; Lee, Shing M; Criner, Gerard J; Mosenifar, Zab; Shade, David M; Slivka, William A; Wise, Robert A

    2008-04-01

    Six-minute walk testing (6MWT) and cardiopulmonary exercise testing (CPX) are used to evaluate impairment in emphysema. However, the extent of impairment in these tests as well as the correlation of these tests with each other and lung function in advanced emphysema is not well characterized. During screening for the National Emphysema Treatment Trial, maximum ergometer CPX and 6MWT were performed in 1,218 individuals with severe COPD with an average FEV(1) of 26.9 +/- 7.1 % predicted. Predicted values for 6MWT and CPX were calculated from reference equations. Correlation coefficients and multivariable regression models were used to determine the association between lung function, quality of life (QOL) scores, and exercise measures. The two forms of exercise testing were correlated with each other (r = 0.57, p < 0.0001). However, the impairment of performance on CPX was greater than on the 6MWT (27.6 +/- 16.8 vs. 67.9 +/- 18.9 % predicted). Both exercise tests had similar correlation with measures of QOL, but maximum exercise capacity was better correlated with lung function measures than 6-minute walk distance. After adjustment, 6MWD had a slightly greater association with total SGRQ score than maximal exercise (effect size 0.37 +/- 0.04 vs. 0.25 +/- 0.03 %predicted/unit). Despite advanced emphysema, patients are able to maintain 6MWD to a greater degree than maximum exercise capacity. Moreover, the 6MWT may be a better test of functional capacity given its greater association with QOL measures whereas CPX is a better test of physiologic impairment.

  11. Pulmonary Artery Aneurysm Thrombosis with Combined Pulmonary Fibrosis and Emphysema: A Case Report

    PubMed Central

    Awad, Nilkant Tukaram

    2016-01-01

    We report a rare case of Pulmonary Artery Aneurysm (PAA) thrombosis with Combined Pulmonary Fibrosis and Emphysema (CPFE) with pulmonary hypertension. A 75-year-old male presented with haemoptysis, dyspnoea, clubbing and bilateral fine end inspiratory rales on examination. He was diagnosed to have PAA thrombosis with CPFE on the basis of computed tomographical angiography and high resolution computed tomography. He was then managed conservatively with pirfenidone for the interstitial lung disease. PMID:27437277

  12. Three-dimensional accurate detection of lung emphysema in rats using ultra-short and zero echo time MRI.

    PubMed

    Bianchi, Andrea; Tibiletti, Marta; Kjørstad, Åsmund; Birk, Gerald; Schad, Lothar R; Stierstorfer, Birgit; Rasche, Volker; Stiller, Detlef

    2015-11-01

    Emphysema is a life-threatening pathology that causes irreversible destruction of alveolar walls. In vivo imaging techniques play a fundamental role in the early non-invasive pre-clinical and clinical detection and longitudinal follow-up of this pathology. In the present study, we aimed to evaluate the feasibility of using high resolution radial three-dimensional (3D) zero echo time (ZTE) and 3D ultra-short echo time (UTE) MRI to accurately detect lung pathomorphological changes in a rodent model of emphysema.Porcine pancreas elastase (PPE) was intratracheally administered to the rats to produce the emphysematous changes. 3D ZTE MRI, low and high definition 3D UTE MRI and micro-computed tomography images were acquired 4 weeks after the PPE challenge. Signal-to-noise ratios (SNRs) were measured in PPE-treated and control rats. T2* values were computed from low definition 3D UTE MRI. Histomorphometric measurements were made after euthanizing the animals. Both ZTE and UTE MR images showed a significant decrease in the SNR measured in PPE-treated lungs compared with controls, due to the pathomorphological changes taking place in the challenged lungs. A significant decrease in T2* values in PPE-challenged animals compared with controls was measured using UTE MRI. Histomorphometric measurements showed a significant increase in the mean linear intercept in PPE-treated lungs. UTE yielded significantly higher SNR compared with ZTE (14% and 30% higher in PPE-treated and non-PPE-treated lungs, respectively).This study showed that optimized 3D radial UTE and ZTE MRI can provide lung images of excellent quality, with high isotropic spatial resolution (400 µm) and SNR in parenchymal tissue (>25) and negligible motion artifacts in freely breathing animals. These techniques were shown to be useful non-invasive instruments to accurately and reliably detect the pathomorphological alterations taking place in emphysematous lungs, without incurring the risks of cumulative radiation

  13. Modern concepts in the management of emphysema in the aged and infirm.

    PubMed

    Riccitelli, M L

    1966-05-01

    The haphazard method of treating patients seriously ill with emphysema is gradually being replaced by modern, well organized cardiopulmonary therapeutic and rehabilitation programs. This evolution is the result of a further expansion in our knowledge of cardiopulmonary physiology and biochemistry; an additional factor is the recent public awareness of the seriousness of the problem, brought about by public educational programs. Emphysema is chiefly a disease of old age. It develops as a result of a degenerative process in which the alveolar walls become thinner and the lungs less elastic. Senile emphysema per se may not be disabling, but it is often associated with a severe chronic pulmonary disorder and thus can become the most distressing disease of old age, with shortness of breath even on such slight exertion as dressing or talking. Disturbances in cardiopulmonary physiology due to obstruction in the free flow of air and to superimposed infections require the use of all available procedures designed to obtain maximal pulmonary ventilation. The magnitude, the difficulty and the many controversial aspects of this problem are evident. The eventual solution will come gradually with continued interest and research.

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

    SciTech Connect

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

    2009-09-28

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

  15. An application to pulmonary emphysema classification based on model of texton learning by sparse representation

    NASA Astrophysics Data System (ADS)

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

    2012-03-01

    We aim at using a new texton based texture classification method in the classification of pulmonary emphysema in computed tomography (CT) images of the lungs. Different from conventional computer-aided diagnosis (CAD) pulmonary emphysema classification methods, in this paper, firstly, the dictionary of texton is learned via applying sparse representation(SR) to image patches in the training dataset. Then the SR coefficients of the test images over the dictionary are used to construct the histograms for texture presentations. Finally, classification is performed by using a nearest neighbor classifier with a histogram dissimilarity measure as distance. The proposed approach is tested on 3840 annotated regions of interest consisting of normal tissue and mild, moderate and severe pulmonary emphysema of three subtypes. The performance of the proposed system, with an accuracy of about 88%, is comparably higher than state of the art method based on the basic rotation invariant local binary pattern histograms and the texture classification method based on texton learning by k-means, which performs almost the best among other approaches in the literature.

  16. Inhibition of elastase-pulmonary emphysema in dominant-negative MafB transgenic mice.

    PubMed

    Aida, Yasuko; Shibata, Yoko; Abe, Shuichi; Inoue, Sumito; Kimura, Tomomi; Igarashi, Akira; Yamauchi, Keiko; Nunomiya, Keiko; Kishi, Hiroyuki; Nemoto, Takako; Sato, Masamichi; Sato-Nishiwaki, Michiko; Nakano, Hiroshi; Sato, Kento; Kubota, Isao

    2014-01-01

    Alveolar macrophages (AMs) play important roles in the pathogenesis of chronic obstructive pulmonary disease (COPD). We previously demonstrated upregulation of the transcription factor MafB in AMs of mice exposed to cigarette smoke. The aim of this study was to elucidate the roles of MafB in the development of pulmonary emphysema. Porcine pancreatic elastase was administered to wild-type (WT) and dominant-negative (DN)-MafB transgenic (Tg) mice in which MafB activity was suppressed only in macrophages. We measured the mean linear intercept and conducted cell differential analysis of bronchoalveolar lavage (BAL) cells, surface marker analysis using flow cytometry, and immunohistochemical staining using antibodies to matrix metalloproteinase (MMP)-9 and MMP-12. Airspace enlargement of the lungs was suppressed significantly in elastase-treated DN-MafB Tg mice compared with treated WT mice. AMs with projected pseudopods were decreased in DN-MafB Tg mice. The number of cells intermediately positive for F4/80 and weakly or intermediately positive for CD11b, which are considered cell subsets of matured AMs, decreased in the BAL of DN-MafB Tg mice. Furthermore, MMP-9 and -12 were significantly downregulated in BAL cells of DN-MafB Tg mice. Because MMPs exacerbate emphysema, MafB may be involved in pulmonary emphysema development through altered maturation of macrophages and MMP expression.

  17. Quantifying lung morphology with respiratory-gated micro-CT in a murine model of emphysema

    NASA Astrophysics Data System (ADS)

    Ford, N. L.; Martin, E. L.; Lewis, J. F.; Veldhuizen, R. A. W.; Holdsworth, D. W.; Drangova, M.

    2009-04-01

    Non-invasive micro-CT imaging techniques have been developed to investigate lung structure in free-breathing rodents. In this study, we investigate the utility of retrospectively respiratory-gated micro-CT imaging in an emphysema model to determine if anatomical changes could be observed in the image-derived quantitative analysis at two respiratory phases. The emphysema model chosen was a well-characterized, genetically altered model (TIMP-3 knockout mice) that exhibits a homogeneous phenotype. Micro-CT scans of the free-breathing, anaesthetized mice were obtained in 50 s and retrospectively respiratory sorted and reconstructed, providing 3D images representing peak inspiration and end expiration with 0.15 mm isotropic voxel spacing. Anatomical measurements included the volume and CT density of the lungs and the volume of the major airways, along with the diameters of the trachea, left bronchus and right bronchus. From these measurements, functional parameters such as functional residual capacity and tidal volume were calculated. Significant differences between the wild-type and TIMP-3 knockout groups were observed for measurements of CT density over the entire lung, indicating increased air content in the lungs of TIMP-3 knockout mice. These results demonstrate retrospective respiratory-gated micro-CT, providing images at multiple respiratory phases that can be analyzed quantitatively to investigate anatomical changes in murine models of emphysema.

  18. Promotion of adipogenesis by an EP2 receptor agonist via stimulation of angiogenesis in pulmonary emphysema.

    PubMed

    Tsuji, Takao; Yamaguchi, Kazuhiro; Kikuchi, Ryota; Itoh, Masayuki; Nakamura, Hiroyuki; Nagai, Atsushi; Aoshiba, Kazutetsu

    2014-08-01

    Body weight loss is a common manifestation in patients with chronic obstructive pulmonary disease (COPD), particularly those with severe emphysema. Adipose angiogenesis is a key mediator of adipogenesis and use of pro-angiogenic agents may serve as a therapeutic option for lean COPD patients. Since angiogenesis is stimulated by PGE2, we examined whether ONO-AE1-259, a selective E-prostanoid (EP) 2 receptor agonist, might promote adipose angiogenesis and adipogenesis in a murine model of elastase-induced pulmonary emphysema (EIE mice). Mice were intratracheally instilled with elastase or saline, followed after 4 weeks by intraperitoneal administration of ONO-AE1-259 for 4 weeks. The subcutaneous adipose tissue (SAT) weight decreased in the EIE mice, whereas in the EIE mice treated with ONO-AE1-259, the SAT weight was largely restored, which was associated with significant increases in SAT adipogenesis, angiogenesis, and VEGF protein production. In contrast, ONO-AE1-259 administration induced no alteration in the weight of the visceral adipose tissue. These results suggest that in EIE mice, ONO-AE1-259 stimulated adipose angiogenesis possibly via VEGF production, and thence, adipogenesis. Our data pave the way for the development of therapeutic interventions for weight loss in emphysema patients, e.g., use of pro-angiogenic agents targeting the adipose tissue vascular component.

  19. Promotion of adipogenesis by an EP2 receptor agonist via stimulation of angiogenesis in pulmonary emphysema.

    PubMed

    Tsuji, Takao; Yamaguchi, Kazuhiro; Kikuchi, Ryota; Itoh, Masayuki; Nakamura, Hiroyuki; Nagai, Atsushi; Aoshiba, Kazutetsu

    2014-08-01

    Body weight loss is a common manifestation in patients with chronic obstructive pulmonary disease (COPD), particularly those with severe emphysema. Adipose angiogenesis is a key mediator of adipogenesis and use of pro-angiogenic agents may serve as a therapeutic option for lean COPD patients. Since angiogenesis is stimulated by PGE2, we examined whether ONO-AE1-259, a selective E-prostanoid (EP) 2 receptor agonist, might promote adipose angiogenesis and adipogenesis in a murine model of elastase-induced pulmonary emphysema (EIE mice). Mice were intratracheally instilled with elastase or saline, followed after 4 weeks by intraperitoneal administration of ONO-AE1-259 for 4 weeks. The subcutaneous adipose tissue (SAT) weight decreased in the EIE mice, whereas in the EIE mice treated with ONO-AE1-259, the SAT weight was largely restored, which was associated with significant increases in SAT adipogenesis, angiogenesis, and VEGF protein production. In contrast, ONO-AE1-259 administration induced no alteration in the weight of the visceral adipose tissue. These results suggest that in EIE mice, ONO-AE1-259 stimulated adipose angiogenesis possibly via VEGF production, and thence, adipogenesis. Our data pave the way for the development of therapeutic interventions for weight loss in emphysema patients, e.g., use of pro-angiogenic agents targeting the adipose tissue vascular component. PMID:24911647

  20. A new experimental model of cigarette smoke-induced emphysema in Wistar rats*, **

    PubMed Central

    Kozma, Rodrigo de las Heras; Alves, Edson Marcelino; Barbosa-de-Oliveira, Valter Abraão; Lopes, Fernanda Degobbi Tenorio Quirino dos Santos; Guardia, Renan Cenize; Buzo, Henrique Vivi; de Faria, Carolina Arruda; Yamashita, Camila; Cavazzana, Manzelio; Frei, Fernando; Ribeiro-Paes, Maria José de Oliveira; Ribeiro-Paes, João Tadeu

    2014-01-01

    OBJECTIVE: To describe a new murine model of cigarette smoke-induced emphysema. METHODS: Twenty-four male Wistar rats were divided into two groups: the cigarette smoke group, comprising 12 rats exposed to smoke from 12 commercial filter cigarettes three times a day (a total of 36 cigarettes per day) every day for 30 weeks; and the control group, comprising 12 rats exposed to room air three times a day every day for 30 weeks. Lung function was assessed by mechanical ventilation, and emphysema was morphometrically assessed by measurement of the mean linear intercept (Lm). RESULTS: The mean weight gain was significantly (approximately ten times) lower in the cigarette smoke group than in the control group. The Lm was 25.0% higher in the cigarette smoke group. There was a trend toward worsening of lung function parameters in the cigarette smoke group. CONCLUSIONS: The new murine model of cigarette smoke-induced emphysema and the methodology employed in the present study are effective and reproducible, representing a promising and economically viable option for use in studies investigating the pathophysiology of and therapeutic approaches to COPD. PMID:24626269

  1. Hyperpolarized 83Kr magnetic resonance imaging of alveolar degradation in a rat model of emphysema

    PubMed Central

    Lilburn, David M. L.; Lesbats, Clémentine; Six, Joseph S.; Dubuis, Eric; Yew-Booth, Liang; Shaw, Dominick E.; Belvisi, Maria G.; Birrell, Mark A.; Pavlovskaya, Galina E.; Meersmann, Thomas

    2015-01-01

    Hyperpolarized 83Kr surface quadrupolar relaxation (SQUARE) generates MRI contrast that was previously shown to correlate with surface-to-volume ratios in porous model surface systems. The underlying physics of SQUARE contrast is conceptually different from any other current MRI methodology as the method uses the nuclear electric properties of the spin I = 9/2 isotope 83Kr. To explore the usage of this non-radioactive isotope for pulmonary pathophysiology, MRI SQUARE contrast was acquired in excised rat lungs obtained from an elastase-induced model of emphysema. A significant 83Kr T1 relaxation time increase in the SQUARE contrast was found in the elastase-treated lungs compared with the baseline data from control lungs. The SQUARE contrast suggests a reduction in pulmonary surface-to-volume ratio in the emphysema model that was validated by histology. The finding supports usage of 83Kr SQUARE as a new biomarker for surface-to-volume ratio changes in emphysema. PMID:25994296

  2. Identification of Clinical Phenotypes in Idiopathic Interstitial Pneumonia with Pulmonary Emphysema.

    PubMed

    Sato, Suguru; Tanino, Yoshinori; Misa, Kenichi; Fukuhara, Naoko; Nikaido, Takefumi; Uematsu, Manabu; Fukuhara, Atsuro; Wang, Xintao; Ishida, Takashi; Munakata, Mitsuru

    2016-01-01

    Objective Since the term "combined pulmonary fibrosis and emphysema" (CPFE) was first proposed, the co-existence of pulmonary fibrosis and pulmonary emphysema (PE) has drawn considerable attention. However, conflicting results on the clinical characteristics of patients with both pulmonary fibrosis and PE have been published because of the lack of an exact definition of CPFE. The goal of this study was thus to clarify the clinical characteristics and phenotypes of idiopathic interstitial pneumonia (IIP) with PE. Methods We retrospectively analyzed IIP patients who had been admitted to our hospital. Their chest high-resolution computed tomography images were classified into two groups according to the presence of PE. We then performed a cluster analysis to identify the phenotypes of IIP patients with PE. Results Forty-four (53.7%) out of 82 patients had at least mild emphysema in their bilateral lungs. The cluster analysis separated the IIP patients with PE into three clusters. The overall survival rate of one cluster that consisted of mainly idiopathic pulmonary fibrosis (IPF) patients was significantly worse than those of the other clusters. Conclusion Three different phenotypes can be identified in IIP patients with PE, and IPF with PE is a distinct clinical phenotype with a poor prognosis.

  3. Conductivity in Exhaled Breath Condensate from Subjects with Emphysema and Type ZZ alpha-1-Antitrypsin Deficiency.

    PubMed

    Stolk, Jan; Fumagalli, Marco; Viglio, Simona; Iadarola, Paolo

    2015-05-01

    The assessment of biomarkers in biological samples from the lung has long been employed. Upon cooling water vapor present in exhaled breath, variable amounts of droplets of condensate (EBC) containing volatile and non-volatile compounds may be easily and non-invasively obtained from patients of any age.Objective of the present study was to compare the level of EBC conductivity determined for cohorts of individuals with different inflammatory lung disorders with that of healthy never-smoking individuals.The conductivity in EBC of PiZZ-Alpha-1-antitrypsin deficiency patients with a diagnosis of emphysema (PiZZ-AATD) was 3 fold lower than in spouse controls (54.5 ± 11.6 vs 165.3 ± 10.7 μS/cm). Non-PiZZ emphysema patients had conductivity in EBC of 59.6 ± 5.8 μS/cm and patients with sarcoidosis without airflow obstruction had EBC conductivity of 178,8 ± 6,2 μS/cm, 
not significantly different (p = 0.5) from healthy controls. Conductivity in serial EBC samples from patients with PiZZ-AATD emphysema and healthy controls was stable in 6 different samples collected over a period of 14 months. We conclude that conductivity values in EBC can be used as a correction factor for dilution of non-volatile components in EBC.

  4. Identification of Clinical Phenotypes in Idiopathic Interstitial Pneumonia with Pulmonary Emphysema.

    PubMed

    Sato, Suguru; Tanino, Yoshinori; Misa, Kenichi; Fukuhara, Naoko; Nikaido, Takefumi; Uematsu, Manabu; Fukuhara, Atsuro; Wang, Xintao; Ishida, Takashi; Munakata, Mitsuru

    2016-01-01

    Objective Since the term "combined pulmonary fibrosis and emphysema" (CPFE) was first proposed, the co-existence of pulmonary fibrosis and pulmonary emphysema (PE) has drawn considerable attention. However, conflicting results on the clinical characteristics of patients with both pulmonary fibrosis and PE have been published because of the lack of an exact definition of CPFE. The goal of this study was thus to clarify the clinical characteristics and phenotypes of idiopathic interstitial pneumonia (IIP) with PE. Methods We retrospectively analyzed IIP patients who had been admitted to our hospital. Their chest high-resolution computed tomography images were classified into two groups according to the presence of PE. We then performed a cluster analysis to identify the phenotypes of IIP patients with PE. Results Forty-four (53.7%) out of 82 patients had at least mild emphysema in their bilateral lungs. The cluster analysis separated the IIP patients with PE into three clusters. The overall survival rate of one cluster that consisted of mainly idiopathic pulmonary fibrosis (IPF) patients was significantly worse than those of the other clusters. Conclusion Three different phenotypes can be identified in IIP patients with PE, and IPF with PE is a distinct clinical phenotype with a poor prognosis. PMID:27301501

  5. Hyperpolarized 83Kr magnetic resonance imaging of alveolar degradation in a rat model of emphysema.

    PubMed

    Lilburn, David M L; Lesbats, Clémentine; Six, Joseph S; Dubuis, Eric; Yew-Booth, Liang; Shaw, Dominick E; Belvisi, Maria G; Birrell, Mark A; Pavlovskaya, Galina E; Meersmann, Thomas

    2015-06-01

    Hyperpolarized (83)Kr surface quadrupolar relaxation (SQUARE) generates MRI contrast that was previously shown to correlate with surface-to-volume ratios in porous model surface systems. The underlying physics of SQUARE contrast is conceptually different from any other current MRI methodology as the method uses the nuclear electric properties of the spin I = 9/2 isotope (83)Kr. To explore the usage of this non-radioactive isotope for pulmonary pathophysiology, MRI SQUARE contrast was acquired in excised rat lungs obtained from an elastase-induced model of emphysema. A significant (83)Kr T1 relaxation time increase in the SQUARE contrast was found in the elastase-treated lungs compared with the baseline data from control lungs. The SQUARE contrast suggests a reduction in pulmonary surface-to-volume ratio in the emphysema model that was validated by histology. The finding supports usage of (83)Kr SQUARE as a new biomarker for surface-to-volume ratio changes in emphysema. PMID:25994296

  6. The Impact of Homogeneous Versus Heterogeneous Emphysema on Dynamic Hyperinflation in Patients With Severe COPD Assessed for Lung Volume Reduction.

    PubMed

    Boutou, Afroditi K; Zoumot, Zaid; Nair, Arjun; Davey, Claire; Hansell, David M; Jamurtas, Athanasios; Polkey, Michael I; Hopkinson, Nicholas S

    2015-01-01

    Dynamic hyperinflation (DH) is a pathophysiologic hallmark of Chronic Obstructive Pulmonary Disease (COPD). The aim of this study was to investigate the impact of emphysema distribution on DH during a maximal cardiopulmonary exercise test (CPET) in patients with severe COPD. This was a retrospective analysis of prospectively collected data among severe COPD patients who underwent thoracic high-resolution computed tomography, full lung function measurements and maximal CPET with inspiratory manouvers as assessment for a lung volume reduction procedure. ΔIC was calculated by subtracting the end-exercise inspiratory capacity (eIC) from resting IC (rIC) and expressed as a percentage of rIC (ΔIC%). Emphysema quantification was conducted at 3 predefined levels using the syngo PULMO-CT (Siemens AG); a difference >25% between best and worse slice was defined as heterogeneous emphysema. Fifty patients with heterogeneous (62.7% male; 60.9 ± 7.5 years old; FEV1% = 32.4 ± 11.4) and 14 with homogeneous emphysema (61.5% male; 62.5 ± 5.9 years old; FEV1% = 28.1 ± 10.3) fulfilled the enrolment criteria. The groups were matched for all baseline variables. ΔIC% was significantly higher in homogeneous emphysema (39.8% ± 9.8% vs.31.2% ± 13%, p = 0.031), while no other CPET parameter differed between the groups. Upper lobe predominance of emphysema correlated positively with peak oxygen pulse, peak oxygen uptake and peak respiratory rate, and negatively with ΔIC%. Homogeneous emphysema is associated with more DH during maximum exercise in COPD patients.

  7. Heme oxygenase-1-mediated autophagy protects against pulmonary endothelial cell death and development of emphysema in cadmium-treated mice.

    PubMed

    Surolia, Ranu; Karki, Suman; Kim, Hyunki; Yu, Zhihong; Kulkarni, Tejaswini; Mirov, Sergey B; Carter, A Brent; Rowe, Steven M; Matalon, Sadis; Thannickal, Victor J; Agarwal, Anupam; Antony, Veena B

    2015-08-01

    Pulmonary exposure to cadmium, a major component of cigarette smoke, has a dramatic impact on lung function and the development of emphysema. Cigarette smoke exposure induces heme oxygenase-1 (HO-1), a cytoprotective enzyme. In this study, we employed a truncated mouse model of emphysema by intratracheal instillation of cadmium (CdCl2) solution (0.025% per 1 mg/kg body wt) in HO-1(+/+), HO-1(-/-), and overexpressing humanized HO-1 bacterial artificial chromosome (hHO-1BAC) mice. We evaluated the role of HO-1 in cadmium-induced emphysema in mice by analyzing histopathology, micro-computed tomography scans, and lung function tests. CdCl2-exposed HO-1(-/-) mice exhibited more severe emphysema compared with HO-1(+/+) or hHO-1BAC mice. Loss of pulmonary endothelial cells (PECs) from the alveolar capillary membrane is recognized to be a target in emphysema. PECs from HO-1(+/+), HO-1(-/-), and hHO-1BAC were employed to define the underlying molecular mechanism for the protection from emphysema by HO-1. Electron microscopy, expression of autophagic markers (microtubule-associated protein 1B-light chain 3 II, autophagy protein 5, and Beclin1) and apoptotic marker (cleaved caspase 3) suggested induction of autophagy and apoptosis in PECs after CdCl2 treatment. CdCl2-treated HO-1(-/-) PECs exhibited downregulation of autophagic markers and significantly increased cleaved caspase 3 expression and activity (∼4-fold higher). Moreover, hHO-1BAC PECs demonstrated upregulated autophagy and absence of cleaved caspase 3 expression or activity. Pretreatment of HO-1(+/+) PECs with rapamycin induced autophagy and resulted in reduced cell death upon cadmium treatment. Induction of autophagy following CdCl2 treatment was found to be protective from apoptotic cell death. HO-1 induced protective autophagy in PECs and mitigated cadmium-induced emphysema.

  8. Heme oxygenase-1-mediated autophagy protects against pulmonary endothelial cell death and development of emphysema in cadmium-treated mice

    PubMed Central

    Surolia, Ranu; Karki, Suman; Kim, Hyunki; Yu, Zhihong; Kulkarni, Tejaswini; Mirov, Sergey B.; Carter, A. Brent; Rowe, Steven M.; Matalon, Sadis; Thannickal, Victor J.; Agarwal, Anupam

    2015-01-01

    Pulmonary exposure to cadmium, a major component of cigarette smoke, has a dramatic impact on lung function and the development of emphysema. Cigarette smoke exposure induces heme oxygenase-1 (HO-1), a cytoprotective enzyme. In this study, we employed a truncated mouse model of emphysema by intratracheal instillation of cadmium (CdCl2) solution (0.025% per 1 mg/kg body wt) in HO-1+/+, HO-1−/−, and overexpressing humanized HO-1 bacterial artificial chromosome (hHO-1BAC) mice. We evaluated the role of HO-1 in cadmium-induced emphysema in mice by analyzing histopathology, micro-computed tomography scans, and lung function tests. CdCl2-exposed HO-1−/− mice exhibited more severe emphysema compared with HO-1+/+ or hHO-1BAC mice. Loss of pulmonary endothelial cells (PECs) from the alveolar capillary membrane is recognized to be a target in emphysema. PECs from HO-1+/+, HO-1−/−, and hHO-1BAC were employed to define the underlying molecular mechanism for the protection from emphysema by HO-1. Electron microscopy, expression of autophagic markers (microtubule-associated protein 1B-light chain 3 II, autophagy protein 5, and Beclin1) and apoptotic marker (cleaved caspase 3) suggested induction of autophagy and apoptosis in PECs after CdCl2 treatment. CdCl2-treated HO-1−/− PECs exhibited downregulation of autophagic markers and significantly increased cleaved caspase 3 expression and activity (∼4-fold higher). Moreover, hHO-1BAC PECs demonstrated upregulated autophagy and absence of cleaved caspase 3 expression or activity. Pretreatment of HO-1+/+ PECs with rapamycin induced autophagy and resulted in reduced cell death upon cadmium treatment. Induction of autophagy following CdCl2 treatment was found to be protective from apoptotic cell death. HO-1 induced protective autophagy in PECs and mitigated cadmium-induced emphysema. PMID:26071551

  9. Loss-of-function mutations in the RNA biogenesis factor NAF1 predispose to pulmonary fibrosis-emphysema.

    PubMed

    Stanley, Susan E; Gable, Dustin L; Wagner, Christa L; Carlile, Thomas M; Hanumanthu, Vidya Sagar; Podlevsky, Joshua D; Khalil, Sara E; DeZern, Amy E; Rojas-Duran, Maria F; Applegate, Carolyn D; Alder, Jonathan K; Parry, Erin M; Gilbert, Wendy V; Armanios, Mary

    2016-08-10

    Chronic obstructive pulmonary disease and pulmonary fibrosis have been hypothesized to represent premature aging phenotypes. At times, they cluster in families, but the genetic basis is not understood. We identified rare, frameshift mutations in the gene for nuclear assembly factor 1, NAF1, a box H/ACA RNA biogenesis factor, in pulmonary fibrosis-emphysema patients. The mutations segregated with short telomere length, low telomerase RNA levels, and extrapulmonary manifestations including myelodysplastic syndrome and liver disease. A truncated NAF1 was detected in cells derived from patients, and, in cells in which the frameshift mutation was introduced by genome editing, telomerase RNA levels were reduced. The mutant NAF1 lacked a conserved carboxyl-terminal motif, which we show is required for nuclear localization. To understand the disease mechanism, we used CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein-9 nuclease) to generate Naf1(+/-) mice and found that they had half the levels of telomerase RNA. Other box H/ACA RNA levels were also decreased, but rRNA pseudouridylation, which is guided by snoRNAs, was intact. Moreover, first-generation Naf1(+/-) mice showed no evidence of ribosomal pathology. Our data indicate that disease in NAF1 mutation carriers is telomere-mediated; they show that NAF1 haploinsufficiency selectively disturbs telomere length homeostasis by decreasing the levels of telomerase RNA while sparing rRNA pseudouridylation. PMID:27510903

  10. Comparison between Variable and Conventional Volume-Controlled Ventilation on Cardiorespiratory Parameters in Experimental Emphysema.

    PubMed

    Henriques, Isabela; Padilha, Gisele A; Huhle, Robert; Wierzchon, Caio; Miranda, Paulo J B; Ramos, Isalira P; Rocha, Nazareth; Cruz, Fernanda F; Santos, Raquel S; de Oliveira, Milena V; Souza, Sergio A; Goldenberg, Regina C; Luiz, Ronir R; Pelosi, Paolo; de Abreu, Marcelo G; Silva, Pedro L; Rocco, Patricia R M

    2016-01-01

    Emphysema is characterized by loss of lung tissue elasticity and destruction of structures supporting alveoli and capillaries. The impact of mechanical ventilation strategies on ventilator-induced lung injury (VILI) in emphysema is poorly defined. New ventilator strategies should be developed to minimize VILI in emphysema. The present study was divided into two protocols: (1) characterization of an elastase-induced emphysema model in rats and identification of the time point of greatest cardiorespiratory impairment, defined as a high specific lung elastance associated with large right ventricular end-diastolic area; and (2) comparison between variable (VV) and conventional volume-controlled ventilation (VCV) on lung mechanics and morphometry, biological markers, and cardiac function at that time point. In the first protocol, Wistar rats (n = 62) received saline (SAL) or porcine pancreatic elastase (ELA) intratracheally once weekly for 4 weeks, respectively. Evaluations were performed 1, 3, 5, or 8 weeks after the last intratracheal instillation of saline or elastase. After identifying the time point of greatest cardiorespiratory impairment, an additional 32 Wistar rats were randomized into the SAL and ELA groups and then ventilated with VV or VCV (n = 8/group) [tidal volume (VT) = 6 mL/kg, positive end-expiratory pressure (PEEP) = 3 cmH2O, fraction of inspired oxygen (FiO2) = 0.4] for 2 h. VV was applied on a breath-to-breath basis as a sequence of randomly generated VT values (mean VT = 6 mL/kg), with a 30% coefficient of variation. Non-ventilated (NV) SAL and ELA animals were used for molecular biology analysis. The time point of greatest cardiorespiratory impairment, was observed 5 weeks after the last elastase instillation. At this time point, interleukin (IL)-6, cytokine-induced neutrophil chemoattractant (CINC)-1, amphiregulin, angiopoietin (Ang)-2, and vascular endothelial growth factor (VEGF) mRNA levels were higher in ELA compared to SAL. In ELA animals

  11. Comparison between Variable and Conventional Volume-Controlled Ventilation on Cardiorespiratory Parameters in Experimental Emphysema.

    PubMed

    Henriques, Isabela; Padilha, Gisele A; Huhle, Robert; Wierzchon, Caio; Miranda, Paulo J B; Ramos, Isalira P; Rocha, Nazareth; Cruz, Fernanda F; Santos, Raquel S; de Oliveira, Milena V; Souza, Sergio A; Goldenberg, Regina C; Luiz, Ronir R; Pelosi, Paolo; de Abreu, Marcelo G; Silva, Pedro L; Rocco, Patricia R M

    2016-01-01

    Emphysema is characterized by loss of lung tissue elasticity and destruction of structures supporting alveoli and capillaries. The impact of mechanical ventilation strategies on ventilator-induced lung injury (VILI) in emphysema is poorly defined. New ventilator strategies should be developed to minimize VILI in emphysema. The present study was divided into two protocols: (1) characterization of an elastase-induced emphysema model in rats and identification of the time point of greatest cardiorespiratory impairment, defined as a high specific lung elastance associated with large right ventricular end-diastolic area; and (2) comparison between variable (VV) and conventional volume-controlled ventilation (VCV) on lung mechanics and morphometry, biological markers, and cardiac function at that time point. In the first protocol, Wistar rats (n = 62) received saline (SAL) or porcine pancreatic elastase (ELA) intratracheally once weekly for 4 weeks, respectively. Evaluations were performed 1, 3, 5, or 8 weeks after the last intratracheal instillation of saline or elastase. After identifying the time point of greatest cardiorespiratory impairment, an additional 32 Wistar rats were randomized into the SAL and ELA groups and then ventilated with VV or VCV (n = 8/group) [tidal volume (VT) = 6 mL/kg, positive end-expiratory pressure (PEEP) = 3 cmH2O, fraction of inspired oxygen (FiO2) = 0.4] for 2 h. VV was applied on a breath-to-breath basis as a sequence of randomly generated VT values (mean VT = 6 mL/kg), with a 30% coefficient of variation. Non-ventilated (NV) SAL and ELA animals were used for molecular biology analysis. The time point of greatest cardiorespiratory impairment, was observed 5 weeks after the last elastase instillation. At this time point, interleukin (IL)-6, cytokine-induced neutrophil chemoattractant (CINC)-1, amphiregulin, angiopoietin (Ang)-2, and vascular endothelial growth factor (VEGF) mRNA levels were higher in ELA compared to SAL. In ELA animals

  12. Comparison between Variable and Conventional Volume-Controlled Ventilation on Cardiorespiratory Parameters in Experimental Emphysema

    PubMed Central

    Henriques, Isabela; Padilha, Gisele A.; Huhle, Robert; Wierzchon, Caio; Miranda, Paulo J. B.; Ramos, Isalira P.; Rocha, Nazareth; Cruz, Fernanda F.; Santos, Raquel S.; de Oliveira, Milena V.; Souza, Sergio A.; Goldenberg, Regina C.; Luiz, Ronir R.; Pelosi, Paolo; de Abreu, Marcelo G.; Silva, Pedro L.; Rocco, Patricia R. M.

    2016-01-01

    Emphysema is characterized by loss of lung tissue elasticity and destruction of structures supporting alveoli and capillaries. The impact of mechanical ventilation strategies on ventilator-induced lung injury (VILI) in emphysema is poorly defined. New ventilator strategies should be developed to minimize VILI in emphysema. The present study was divided into two protocols: (1) characterization of an elastase-induced emphysema model in rats and identification of the time point of greatest cardiorespiratory impairment, defined as a high specific lung elastance associated with large right ventricular end-diastolic area; and (2) comparison between variable (VV) and conventional volume-controlled ventilation (VCV) on lung mechanics and morphometry, biological markers, and cardiac function at that time point. In the first protocol, Wistar rats (n = 62) received saline (SAL) or porcine pancreatic elastase (ELA) intratracheally once weekly for 4 weeks, respectively. Evaluations were performed 1, 3, 5, or 8 weeks after the last intratracheal instillation of saline or elastase. After identifying the time point of greatest cardiorespiratory impairment, an additional 32 Wistar rats were randomized into the SAL and ELA groups and then ventilated with VV or VCV (n = 8/group) [tidal volume (VT) = 6 mL/kg, positive end-expiratory pressure (PEEP) = 3 cmH2O, fraction of inspired oxygen (FiO2) = 0.4] for 2 h. VV was applied on a breath-to-breath basis as a sequence of randomly generated VT values (mean VT = 6 mL/kg), with a 30% coefficient of variation. Non-ventilated (NV) SAL and ELA animals were used for molecular biology analysis. The time point of greatest cardiorespiratory impairment, was observed 5 weeks after the last elastase instillation. At this time point, interleukin (IL)-6, cytokine-induced neutrophil chemoattractant (CINC)-1, amphiregulin, angiopoietin (Ang)-2, and vascular endothelial growth factor (VEGF) mRNA levels were higher in ELA compared to SAL. In ELA animals

  13. Differentiating Smoking-Related Interstitial Fibrosis (SRIF) from Usual Interstitial Pneumonia (UIP) with Emphysema Using CT Features Based on Pathologically Proven Cases

    PubMed Central

    Chae, Kum Ju; Jin, Gong Yong; Jung, Hyun Nyeong; Kwon, Keun Sang; Choi, Hyemi; Lee, Yong Chul; Chung, Myoung Ja; Park, Ho Sung

    2016-01-01

    Objective To differentiate smoking-related interstitial fibrosis (SRIF) from usual interstitial pneumonia (UIP) with emphysema on CT in combined pulmonary fibrosis and emphysema (CPFE) patients. Materials and Methods This study was approved by the institutional review board and informed consent was waived. We included 65 patients who underwent lung biopsy under the suspicion of UIP pattern on HRCT, and after radiologic-pathologic correlation, they were divided into three groups: UIP without emphysema (n = 30), UIP with emphysema (n = 26), and SRIF (n = 9). The quantitative extent of emphysema in the entire lung was visually assessed and fibrotic patterns were qualitatively analyzed based on six characteristics (asymmetry, juxta-subpleural sparing, emphysema beside the honeycombing area, absence of ground grass attenuation/reticulation in honeycombing area, inhomogeneous honeycombing, and absence of honeycombing in the upper lobes). Kaplan-Meier analysis was used for survival analysis, and logistic regression with a receiver operating characteristic curve was used to predict the possibility of SRIF. Results In qualitative analysis of fibrotic patterns, SRIF tended to exhibit more than three of six fibrotic features, whereas UIP with emphysema demonstrated about two of these characteristics (p = 0.035). In addition, SRIF had a higher extent of emphysema than UIP with emphysema when they have same amount of fibrosis (p = 0.014). In patients with SRIF, 5-year survival rate was 85.7%, while it was 40.7% in UIP with emphysema patients (p = 0.035). Conclusion Fibrotic CT patterns and survival rate differed between SRIF and UIP with emphysema among CPFE patients, which explains the variable prognosis of CPFE. PMID:27611866

  14. Developing independence.

    PubMed

    Turnbull, A P; Turnbull, H R

    1985-03-01

    The transition from living a life as others want (dependence) to living it as the adolescent wants to live it (independence) is extraordinarily difficult for most teen-agers and their families. The difficulty is compounded in the case of adolescents with disabilities. They are often denied access to the same opportunities of life that are accessible to the nondisabled. They face special problems in augmenting their inherent capacities so that they can take fuller advantage of the accommodations that society makes in an effort to grant them access. In particular, they need training designed to increase their capacities to make, communicate, implement, and evaluate their own life-choices. The recommendations made in this paper are grounded in the long-standing tradition of parens patriae and enlightened paternalism; they seek to be deliberately and cautiously careful about the lives of adolescents with disabilities and their families. We based them on the recent tradition of anti-institutionalism and they are also consistent with some of the major policy directions of the past 15-20 years. These include: normalization, integration, and least-restrictive alternatives; the unity and integrity of the family; the importance of opportunities for self-advocacy; the role of consumer consent and choice in consumer-professional relationships; the need for individualized services; the importance of the developmental model as a basis for service delivery; the value of economic productivity of people with disabilities; and the rights of habilitation, amelioration, and prevention. PMID:3156827

  15. Developing independence.

    PubMed

    Turnbull, A P; Turnbull, H R

    1985-03-01

    The transition from living a life as others want (dependence) to living it as the adolescent wants to live it (independence) is extraordinarily difficult for most teen-agers and their families. The difficulty is compounded in the case of adolescents with disabilities. They are often denied access to the same opportunities of life that are accessible to the nondisabled. They face special problems in augmenting their inherent capacities so that they can take fuller advantage of the accommodations that society makes in an effort to grant them access. In particular, they need training designed to increase their capacities to make, communicate, implement, and evaluate their own life-choices. The recommendations made in this paper are grounded in the long-standing tradition of parens patriae and enlightened paternalism; they seek to be deliberately and cautiously careful about the lives of adolescents with disabilities and their families. We based them on the recent tradition of anti-institutionalism and they are also consistent with some of the major policy directions of the past 15-20 years. These include: normalization, integration, and least-restrictive alternatives; the unity and integrity of the family; the importance of opportunities for self-advocacy; the role of consumer consent and choice in consumer-professional relationships; the need for individualized services; the importance of the developmental model as a basis for service delivery; the value of economic productivity of people with disabilities; and the rights of habilitation, amelioration, and prevention.

  16. Automated measurement of pulmonary emphysema and small airway remodeling in cigarette smoke-exposed mice.

    PubMed

    Laucho-Contreras, Maria E; Taylor, Katherine L; Mahadeva, Ravi; Boukedes, Steve S; Owen, Caroline A

    2015-01-16

    COPD is projected to be the third most common cause of mortality world-wide by 2020((1)). Animal models of COPD are used to identify molecules that contribute to the disease process and to test the efficacy of novel therapies for COPD. Researchers use a number of models of COPD employing different species including rodents, guinea-pigs, rabbits, and dogs((2)). However, the most widely-used model is that in which mice are exposed to cigarette smoke. Mice are an especially useful species in which to model COPD because their genome can readily be manipulated to generate animals that are either deficient in, or over-express individual proteins. Studies of gene-targeted mice that have been exposed to cigarette smoke have provided valuable information about the contributions of individual molecules to different lung pathologies in COPD((3-5)). Most studies have focused on pathways involved in emphysema development which contributes to the airflow obstruction that is characteristic of COPD. However, small airway fibrosis also contributes significantly to airflow obstruction in human COPD patients((6)), but much less is known about the pathogenesis of this lesion in smoke-exposed animals. To address this knowledge gap, this protocol quantifies both emphysema development and small airway fibrosis in smoke-exposed mice. This protocol exposes mice to CS using a whole-body exposure technique, then measures respiratory mechanics in the mice, inflates the lungs of mice to a standard pressure, and fixes the lungs in formalin. The researcher then stains the lung sections with either Gill's stain to measure the mean alveolar chord length (as a readout of emphysema severity) or Masson's trichrome stain to measure deposition of extracellular matrix (ECM) proteins around small airways (as a readout of small airway fibrosis). Studies of the effects of molecular pathways on both of these lung pathologies will lead to a better understanding of the pathogenesis of COPD.

  17. Effects of the association of diabetes and pulmonary emphysema on cardiac structure and function in rats.

    PubMed

    Di Petta, Antonio; Simas, Rafael; Ferreira, Clebson L; Capelozzi, Vera L; Salemi, Vera M C; Moreira, Luiz F P; Sannomiya, Paulina

    2015-10-01

    Chronic obstructive pulmonary disease is often associated with chronic comorbid conditions of cardiovascular disease, diabetes mellitus and hypertension. This study aimed to investigate the effects of the association of diabetes and pulmonary emphysema on cardiac structure and function in rats. Wistar rats were divided into control non-diabetic instilled with saline (CS) or elastase (CE), diabetic instilled with saline (DS) or elastase (DE), DE treated with insulin (DEI) groups and echocardiographic measurements, morphometric analyses of the heart and lungs, and survival analysis conducted 50 days after instillation. Diabetes mellitus was induced [alloxan, 42 mg/kg, intravenously (iv)] 10 days before the induction of emphysema (elastase, 0.25 IU/100 g). Rats were treated with NPH insulin (4 IU before elastase plus 2 IU/day, 50 days). Both CE and DE exhibited similar increases in mean alveolar diameter, which are positively correlated with increases in right ventricular (RV) wall thickness (P = 0.0022), cavity area (P = 0.0001) and cardiomyocyte thickness (P = 0.0001). Diabetic saline group demonstrated a reduction in left ventricular (LV) wall, interventricular (IV) septum, cardiomyocyte thickness and an increase in cavity area, associated with a reduction in LV fractional shortening (P < 0.05), and an increase in LViv relaxation time (P < 0.05). Survival rate decreased from 80% in DS group to 40% in DE group. In conclusion, alloxan diabetes did not affect RV hypertrophy secondary to chronic emphysema, even in the presence of insulin. Diabetes per se induced left ventricular dysfunction, which was less evident in the presence of RV hypertrophy. Survival rate was substantially reduced as a consequence, at least in part, of the coexistence of RV hypertrophy and diabetic cardiomyopathy.

  18. Repeated cadmium nebulizations induce pulmonary MMP-2 and MMP-9 production and emphysema in rats.

    PubMed

    Kirschvink, Nathalie; Vincke, Grégoire; Fiévez, Laurence; Onclinx, Cécile; Wirth, Delphine; Belleflamme, Michèle; Louis, Renaud; Cataldo, Didier; Peck, Michael J; Gustin, Pascal

    2005-07-01

    This study describes induction of pulmonary inflammation, production of matrix metalloprotease of type 2 (MMP-2) and type 9 (MMP-9), and emphysema in cadmium (Cd)-exposed rats. Sprague-Dawley rats were randomly distributed into two groups: one placebo-exposed group undergoing saline (NaCl 0.9%) inhalation (n=30) and one Cd-exposed group undergoing cadmium (CdCl(2) 0.1%) inhalation (n=30). The animals of the placebo- and Cd-exposed groups were divided in five subgroups (n=6). Subgroups underwent either a single exposure of 1h or repeated exposures three times weekly for 1h during 3 weeks (3W), 5 weeks (5W), 5 weeks followed by 2 weeks without exposure (5W+2) or 5 weeks followed by 4 weeks without exposure (5W+4). Each animal underwent determination of enhanced pause (Penh) as index of airflow limitation prior to the first exposure as well as before sacrifice. The animals were sacrificed the day after their last exposure. The left lung was fixed for histomorphometric analysis (determination of median interwall distance (MIWD)), whilst bronchoalveolar lavage fluid (BALF) was collected from the right lung. BALF was analyzed cytologically, and MMP-2 and MMP-9 levels were determined by gelatine zymography. Twelve rats previously instilled with pancreatic elastase were used as positive emphysema controls and underwent the same investigations. Cd-exposure induced a significant increase of BALF macrophages, neutrophils and MMP-9 up to 5W+4, whereas MMP-2 gelatinolytic activity returned to baseline levels within 5W. MIWD was significantly increased in all repeatedly Cd-exposed groups and elastase-treated rats. Penh was increased in Cd-exposed rats after a single exposure and after 3W. MMP gelatinolytic activity was significantly correlated with macrophages, neutrophils and Penh. In repeatedly exposed rats, MIWD was positively and significantly correlated with MMP gelatinolytic activity, suggesting that increased MMP-2 and MMP-9 production favours the development of emphysema.

  19. Association between radiological findings and total and regional function in emphysema

    PubMed Central

    Nairn, Jean R.; Prime, F. J.; Simon, G.

    1969-01-01

    Tests of overall and regional lung function using xenon-133 with fixed counters were carried out on 49 patients who were judged on specified radiological grounds to have emphysema: 31 of them also had clinical evidence of chronic bronchitis. The radiological extent of the disease was classified as generalized, extensive localized or localized. The results of the tests were compared with the radiographic extent of the disease and with the local radiographic appearances. Derangements of total lung function agreed well with the radiological extent of the disease; in particular, the average level of Paco2 was lower than that predicted from the F.E.V.1 when generalized and extensive localized emphysema were present. Co-existing chronic bronchitis was associated with higher levels of Paco2. The resting Pao2 was higher if one or both lower regions were normally ventilated despite unevenness of ventilation elsewhere, emphasizing the importance of the lower lung regions in determining the overall V/Q of the lungs. Regional derangements of ventilation coincided fairly well with the radiographic distribution of vascular narrowing or loss but the blood flow was found to be diminished in less than 5% of upper and middle regions with radiological changes. Ventilation was impaired in parts of the lungs where the vascular shadows were apparently normal. This finding was attributed to the effects of chronic bronchitis, because it was also found in seven patients with this disease who did not have radiographic evidence of emphysema; in these, impairment of ventilation in the middle and lower regions was a salient feature. PMID:5821623

  20. Predictors of pneumothorax following endoscopic valve therapy in patients with severe emphysema

    PubMed Central

    Gompelmann, Daniela; Lim, Hyun-ju; Eberhardt, Ralf; Gerovasili, Vasiliki; Herth, Felix JF; Heussel, Claus Peter; Eichinger, Monika

    2016-01-01

    Background Endoscopic valve implantation is an effective treatment for patients with advanced emphysema. Despite the minimally invasive procedure, valve placement is associated with risks, the most common of which is pneumothorax. This study was designed to identify predictors of pneumothorax following endoscopic valve implantation. Methods Preinterventional clinical measures (vital capacity, forced expiratory volume in 1 second, residual volume, total lung capacity, 6-minute walk test), qualitative computed tomography (CT) parameters (fissure integrity, blebs/bulla, subpleural nodules, pleural adhesions, partial atelectasis, fibrotic bands, emphysema type) and quantitative CT parameters (volume and low attenuation volume of the target lobe and the ipsilateral untreated lobe, target air trapping, ipsilateral lobe volume/hemithorax volume, collapsibility of the target lobe and the ipsilateral untreated lobe) were retrospectively evaluated in patients who underwent endoscopic valve placement (n=129). Regression analysis was performed to compare those who developed pneumothorax following valve therapy (n=46) with those who developed target lobe volume reduction without pneumothorax (n=83). Finding Low attenuation volume% of ipsilateral untreated lobe (odds ratio [OR] =1.08, P=0.001), ipsilateral untreated lobe volume/hemithorax volume (OR =0.93, P=0.017), emphysema type (OR =0.26, P=0.018), pleural adhesions (OR =0.33, P=0.012) and residual volume (OR =1.58, P=0.012) were found to be significant predictors of pneumothorax. Fissure integrity (OR =1.16, P=0.075) and 6-minute walk test (OR =1.05, P=0.077) were also indicative of pneumothorax. The model including the aforementioned parameters predicted whether a patient would experience a pneumothorax 84% of the time (area under the curve =0.84). Interpretation Clinical and CT parameters provide a promising tool to effectively identify patients at high risk of pneumothorax following endoscopic valve therapy. PMID:27536088

  1. Long-term dynamics of death rates of emphysema, asthma, and pneumonia and improving air quality

    PubMed Central

    Kravchenko, Julia; Akushevich, Igor; Abernethy, Amy P; Holman, Sheila; Ross, William G; Lyerly, H Kim

    2014-01-01

    Background The respiratory tract is a major target of exposure to air pollutants, and respiratory diseases are associated with both short- and long-term exposures. We hypothesized that improved air quality in North Carolina was associated with reduced rates of death from respiratory diseases in local populations. Materials and methods We analyzed the trends of emphysema, asthma, and pneumonia mortality and changes of the levels of ozone, sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and particulate matters (PM2.5 and PM10) using monthly data measurements from air-monitoring stations in North Carolina in 1993–2010. The log-linear model was used to evaluate associations between air-pollutant levels and age-adjusted death rates (per 100,000 of population) calculated for 5-year age-groups and for standard 2000 North Carolina population. The studied associations were adjusted by age group-specific smoking prevalence and seasonal fluctuations of disease-specific respiratory deaths. Results Decline in emphysema deaths was associated with decreasing levels of SO2 and CO in the air, decline in asthma deaths–with lower SO2, CO, and PM10 levels, and decline in pneumonia deaths–with lower levels of SO2. Sensitivity analyses were performed to study potential effects of the change from International Classification of Diseases (ICD)-9 to ICD-10 codes, the effects of air pollutants on mortality during summer and winter, the impact of approach when only the underlying causes of deaths were used, and when mortality and air-quality data were analyzed on the county level. In each case, the results of sensitivity analyses demonstrated stability. The importance of analysis of pneumonia as an underlying cause of death was also highlighted. Conclusion Significant associations were observed between decreasing death rates of emphysema, asthma, and pneumonia and decreases in levels of ambient air pollutants in North Carolina. PMID:25018627

  2. Automated Measurement of Pulmonary Emphysema and Small Airway Remodeling in Cigarette Smoke-exposed Mice

    PubMed Central

    Laucho-Contreras, Maria E.; Taylor, Katherine L.; Mahadeva, Ravi; Boukedes, Steve S.; Owen, Caroline A.

    2015-01-01

    COPD is projected to be the third most common cause of mortality world-wide by 2020(1). Animal models of COPD are used to identify molecules that contribute to the disease process and to test the efficacy of novel therapies for COPD. Researchers use a number of models of COPD employing different species including rodents, guinea-pigs, rabbits, and dogs(2). However, the most widely-used model is that in which mice are exposed to cigarette smoke. Mice are an especially useful species in which to model COPD because their genome can readily be manipulated to generate animals that are either deficient in, or over-express individual proteins. Studies of gene-targeted mice that have been exposed to cigarette smoke have provided valuable information about the contributions of individual molecules to different lung pathologies in COPD(3-5). Most studies have focused on pathways involved in emphysema development which contributes to the airflow obstruction that is characteristic of COPD. However, small airway fibrosis also contributes significantly to airflow obstruction in human COPD patients(6), but much less is known about the pathogenesis of this lesion in smoke-exposed animals. To address this knowledge gap, this protocol quantifies both emphysema development and small airway fibrosis in smoke-exposed mice. This protocol exposes mice to CS using a whole-body exposure technique, then measures respiratory mechanics in the mice, inflates the lungs of mice to a standard pressure, and fixes the lungs in formalin. The researcher then stains the lung sections with either Gill’s stain to measure the mean alveolar chord length (as a readout of emphysema severity) or Masson’s trichrome stain to measure deposition of extracellular matrix (ECM) proteins around small airways (as a readout of small airway fibrosis). Studies of the effects of molecular pathways on both of these lung pathologies will lead to a better understanding of the pathogenesis of COPD. PMID:25651034

  3. Heme oxygenase-1 attenuates inflammation and oxidative damage in a rat model of smoke-induced emphysema.

    PubMed

    Wei, Jingjing; Fan, Guoquan; Zhao, Hui; Li, Jianqiang

    2015-11-01

    Emphysema is a serious disease of the respiratory system and is associated with inflammation and oxidative stress. Heme oxygenase-1 (HO-1), a rate-limiting enzyme involved in heme biosynthesis, exerts potent anti-inflammatory, antioxidant, anti-apoptotic and anti‑proliferative effects in various diseases. In the present study, we examined the effects of HO-1 on smoke‑induced emphysema, as well as the underlying mechanisms in a rat model of smoke-induced emphysema. Rats were either exposed to cigarette smoke or sham‑exposed for 20 weeks to establish the model of smoke-induced emphysema. The rats were subcutaneously injected with protoporphyrin IX [tin-protoporphyrin IX (SnPP) or ferriprotoporphyrin IX chloride (hemin)] during this period to examine the protective effects of HO-1. Subsequently, the development of emphysema, inflammatory cells, the levels of inflammatory mediators, particularly interleukin (IL)-17, tumor necrosis factor (TNF)‑α, monocyte chemotactic protein‑1 [MCP‑1, also known as chemokine (C-C motif) ligand 2 (CCL2)], IL-8 [also known as chemokine (C-X-C motif) ligand 8 (CXCL8)], macrophage inflammatory protein‑2α [MIP-2α, also known as chemokine (C-X-C motif) ligand 2 (CXCL2)] and IL-10, as well as the malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) content were determined. Exposure to smoke increased the total cell, neutrophil and macrophage counts in the bronchoalveolar lavage fluid (BALF). It also increased the levels of the inflammatory mediators, IL-17, TNF-α, MCP-1, IL-8 and MIP-2α, as well as the MDA content and induced emphysema. Treatment with hemin upregulated HO-1 expression and attenuated the development of smoke-induced emphysema by reducing inflammatory cell infiltration, decreasing the levels of inflammatory mediators and attenuating oxidative damage, to a certain extent. In conclusion, our findings demonstrate that HO-1 exerts anti-inflammatory and antioxidant effects, thus attenuating the

  4. Single-lung transplantation in emphysema: Retrospective study analyzing survival and waiting list mortality

    PubMed Central

    Borro, José M; Delgado, María; Coll, Elisabeth; Pita, Salvador

    2016-01-01

    AIM: To performed remains a subject of debate and is the principal aim of the study. METHODS: This retrospective analysis included 73 patients with emphysema (2000-2012). The outcomes of patients undergoing single-lung transplantation (SL) (n = 40) or double-lung transplant (DL) (n = 33) were compared in a Cox multivariate analysis to study the impact of the technique, postoperative complications and acute and chronic rejection on survival rates. Patients were selected for inclusion in the waiting list according to the International Society of Heart Lung Transplantation criteria. Pre and postoperative rehabilitation and prophylaxis, surgical technique and immunosuppressive treatment were similar in every patients. Lung transplantation waiting list information on a national level and retrospective data on emphysema patient survival transplanted in Spain during the study period, was obtained from the lung transplantation registry managed by the National Transplant Organization (ONT). RESULTS: Both groups were comparable in terms of gender and clinical characteristics. We found significant differences in the mean age between the groups, the DL patients being younger as expected from the inclusion criteria. Perioperative complications occurred in 27.6% SL vs 54% DL (P = 0.032). Excluding perioperative mortality, median survival was 65.3 mo for SL and 59.4 mo for DL (P = 0.96). Bronchiolitis obliterans and overall 5-year survival were similar in both groups. Bacterial respiratory infection, cytomegalovirus and fungal infection rates were higher but not significant in SL. No differences were found between type of transplant and survival (P = 0.48). To support our results, national data on all patients with emphysema in waiting list were obtained (n = 1001). Mortality on the waiting list was 2.4% for SL vs 6.2% for DL. There was no difference in 5 year survival between 235 SL and 430 DL patients transplanted (P = 0.875). CONCLUSION: Our results suggest that SL

  5. Lung Volume Reduction After Stereotactic Ablative Radiation Therapy of Lung Tumors: Potential Application to Emphysema

    SciTech Connect

    Binkley, Michael S.; Shrager, Joseph B.; Leung, Ann N.; Popat, Rita; Trakul, Nicholas; Atwood, Todd F.; Chaudhuri, Aadel; Maxim, Peter G.; Diehn, Maximilian; Loo, Billy W.

    2014-09-01

    Purpose: Lung volume reduction surgery (LVRS) improves dyspnea and other outcomes in selected patients with severe emphysema, but many have excessive surgical risk for LVRS. We analyzed the dose-volume relationship for lobar volume reduction after stereotactic ablative radiation therapy (SABR) of lung tumors, hypothesizing that SABR could achieve therapeutic volume reduction if applied in emphysema. Methods and Materials: We retrospectively identified patients treated from 2007 to 2011 who had SABR for 1 lung tumor, pre-SABR pulmonary function testing, and ≥6 months computed tomographic (CT) imaging follow-up. We contoured the treated lobe and untreated adjacent lobe(s) on CT before and after SABR and calculated their volume changes relative to the contoured total (bilateral) lung volume (TLV). We correlated lobar volume reduction with the volume receiving high biologically effective doses (BED, α/β = 3). Results: 27 patients met the inclusion criteria, with a median CT follow-up time of 14 months. There was no grade ≥3 toxicity. The median volume reduction of the treated lobe was 4.4% of TLV (range, −0.4%-10.8%); the median expansion of the untreated adjacent lobe was 2.6% of TLV (range, −3.9%-11.6%). The volume reduction of the treated lobe was positively correlated with the volume receiving BED ≥60 Gy (r{sup 2}=0.45, P=.0001). This persisted in subgroups determined by high versus low pre-SABR forced expiratory volume in 1 second, treated lobe CT emphysema score, number of fractions, follow-up CT time, central versus peripheral location, and upper versus lower lobe location, with no significant differences in effect size between subgroups. Volume expansion of the untreated adjacent lobe(s) was positively correlated with volume reduction of the treated lobe (r{sup 2}=0.47, P<.0001). Conclusions: We identified a dose-volume response for treated lobe volume reduction and adjacent lobe compensatory expansion after lung tumor SABR, consistent across

  6. Postcard from Independence, Mo.

    ERIC Educational Resources Information Center

    Archer, Jeff

    2004-01-01

    This article reports results showing that the Independence, Missori school district failed to meet almost every one of its improvement goals under the No Child Left Behind Act. The state accreditation system stresses improvement over past scores, while the federal law demands specified amounts of annual progress toward the ultimate goal of 100…

  7. Detection and classification of interstitial lung diseases and emphysema using a joint morphological-fuzzy approach

    NASA Astrophysics Data System (ADS)

    Chang Chien, Kuang-Che; Fetita, Catalin; Brillet, Pierre-Yves; Prêteux, Françoise; Chang, Ruey-Feng

    2009-02-01

    Multi-detector computed tomography (MDCT) has high accuracy and specificity on volumetrically capturing serial images of the lung. It increases the capability of computerized classification for lung tissue in medical research. This paper proposes a three-dimensional (3D) automated approach based on mathematical morphology and fuzzy logic for quantifying and classifying interstitial lung diseases (ILDs) and emphysema. The proposed methodology is composed of several stages: (1) an image multi-resolution decomposition scheme based on a 3D morphological filter is used to detect and analyze the different density patterns of the lung texture. Then, (2) for each pattern in the multi-resolution decomposition, six features are computed, for which fuzzy membership functions define a probability of association with a pathology class. Finally, (3) for each pathology class, the probabilities are combined up according to the weight assigned to each membership function and two threshold values are used to decide the final class of the pattern. The proposed approach was tested on 10 MDCT cases and the classification accuracy was: emphysema: 95%, fibrosis/honeycombing: 84% and ground glass: 97%.

  8. Idiopathic interstitial pneumonias and emphysema: detection and classification using a texture-discriminative approach

    NASA Astrophysics Data System (ADS)

    Fetita, C.; Chang-Chien, K. C.; Brillet, P. Y.; Pr"teux, F.; Chang, R. F.

    2012-03-01

    Our study aims at developing a computer-aided diagnosis (CAD) system for fully automatic detection and classification of pathological lung parenchyma patterns in idiopathic interstitial pneumonias (IIP) and emphysema using multi-detector computed tomography (MDCT). The proposed CAD system is based on three-dimensional (3-D) mathematical morphology, texture and fuzzy logic analysis, and can be divided into four stages: (1) a multi-resolution decomposition scheme based on a 3-D morphological filter was exploited to discriminate the lung region patterns at different analysis scales. (2) An additional spatial lung partitioning based on the lung tissue texture was introduced to reinforce the spatial separation between patterns extracted at the same resolution level in the decomposition pyramid. Then, (3) a hierarchic tree structure was exploited to describe the relationship between patterns at different resolution levels, and for each pattern, six fuzzy membership functions were established for assigning a probability of association with a normal tissue or a pathological target. Finally, (4) a decision step exploiting the fuzzy-logic assignments selects the target class of each lung pattern among the following categories: normal (N), emphysema (EM), fibrosis/honeycombing (FHC), and ground glass (GDG). According to a preliminary evaluation on an extended database, the proposed method can overcome the drawbacks of a previously developed approach and achieve higher sensitivity and specificity.

  9. Costs of pulmonary rehabilitation and predictors of adherence in the National Emphysema Treatment Trial.

    PubMed

    Fan, Vincent S; Giardino, Nicholas D; Blough, David K; Kaplan, Robert M; Ramsey, Scott D

    2008-04-01

    This study reports the costs associated with rehabilitation among participants in the National Emphysema Treatment Trial (NETT), and evaluates factors associated with adherence to rehabilitation. Pulmonary rehabilitation is recommended for moderate-to-severe COPD and required by the Centers for Medicare and Medicaid Services (CMS) prior to lung volume reduction surgery (LVRS). Between January 1998 and July 2002, 1,218 subjects with emphysema and severe airflow limitation (FEV(1) < or = 45% predicted) were randomized. Primary outcome measures were designated as mortality and maximal exercise capacity 2 years after randomization. Pre-randomization, estimated mean total cost per patient of rehabilitation was $2,218 (SD $314; 2006 dollars) for the medical group and $2,187 (SD $304) for the surgical group. Post-randomization, mean cost per patient in the medical and surgical groups was $766 and $962 respectively. Among patients who attended > or = 1 post-randomization rehabilitation session, LVRS patients, patients with an FEV(1) > or = 20% predicted, and higher education were significantly more likely to complete rehabilitation. Patients with depressive and anxiety symptoms, and those who live > 36 miles compared to < 6 miles away were less likely to be adherent. Patients who underwent LVRS completed more exercise sessions than those in the medical group and were more likely to be adherent with post-randomization rehabilitation. A better understanding of patient factors such as socioeconomic status, depression, anxiety and transportation issues may improve adherence to pulmonary rehabilitation.

  10. The fissure: interlobar collateral ventilation and implications for endoscopic therapy in emphysema

    PubMed Central

    Koster, Theodoor David; Slebos, Dirk-Jan

    2016-01-01

    In patients with severe emphysema, bronchoscopic lung volume reduction using one-way valves is a promising therapeutic option to improve lung function and quality of life. The goal of this treatment is to achieve a complete lobar atelectasis. In a significant proportion of patients, this atelectasis cannot be achieved due to interlobar collateral ventilation. This collateral ventilation is generated through incomplete lobar fissures. Therefore, only patients with complete fissures and no collateral ventilation can be selected for endobronchial therapy with one-way valves. Incomplete fissures are very common and exhibit a great variation in anatomy. The reported prevalence is 17%–85% for the right major fissure, 19%–74% for the left major fissure, and 20%–90% for the minor fissure. There are several methods of measuring or predicting the presence of collateral ventilation, with computed tomography (CT)-fissure analysis and the Chartis measurement being the most important. CT-fissure analysis is an indirect method to measure the completeness of fissures as a surrogate for collateral ventilation. The Chartis system is an endobronchial method to directly measure the presence of collateral ventilation. Both methods have unique value, and the combination of both can accurately predict the treatment response to the bronchoscopic placement of endobronchial valves. This review provides an in-depth view of lung fissure and collateral ventilation to help understand its importance in selecting the appropriate patients for new emphysema treatments and thus avoid useless treatment in unsuitable patients. PMID:27110109

  11. [Surgical treatment of respiratory failure in young patients with diffuse lung emphysema].

    PubMed

    Gorbunkov, S D; Chernyĭ, S M; Akopov, A L; Varlamov, V V; Lukina, O V; Kiriukhina, L D; Agishev, A S; Gembitskaia, T E

    2012-01-01

    An analysis of results of examination and treatment of 8 young patients (from 25 to 17 years of age) with generalized emphysema of the lungs, pulmonary failure of the II and III degrees was made. The functional examination of the patients before operation has revealed changed respiration by obstructive type. Symptoms of dysplasia of the connective tissue were found in 4 patients. Surgical reduction of the lung volume was performed in 5 patients for correction of respiratory failure. There were neither serious complications nor lethality. Dyspnea by MMRC scale decreased in all the patients at minimum by 1 point during the first months after operation. Three years later 4 out of the operated patients (80%) had retained positive effect of operation. In patients who had no operative treatment the frequency of infectious complications, level of dyspnea during three years of follow-up remained at the same level, while functional indices continued worsening. The surgical method of treatment of severe respiratory failure allowed tolerance of physical exercise to be increased and quality of life of patients with diffuse lung emphysema to be improved. PMID:23488258

  12. Response of Inflammatory Mediators, Extracellular Matrix Proteins and Stem and Progenitor Cells to Emphysema.

    PubMed

    Skurikhin, E G; Pakhomova, A V; Krupin, V A; Pershina, O V; Pan, E S; Ermolaeva, L A; Vaizova, O E; Rybalkina, O Yu; Dygai, A M

    2016-08-01

    Inflammation, extracellular matrix proteins (hydroxyproline, connective tissue growth factor, collagen, and fibronectin), stem and progenitor cells (multipotent mesenchymal stromal cells, Clara cells, angiogenesis, precursors, endothelial and epithelial cells) were studied in female C57Bl/6 mice with experimental elastase-induced emphysema. Diffuse emphysema reduced the number of endothelial (CD45(-)CD31(+)CD34(+)) and epithelial (CD45(-)CD117(+)CD49f(+)) cells, induced microcirculation disturbances, and decreased the area occupied by the connective tissue. Emphysematous changes in the lungs were accompanied by infiltration of the alveolar septa with macrophages and lymphocytes, increase in the serum and lung concentrations of transforming growth factor-β, IL-1β, IL-2, IL-5, IL-10, and IL-13, and lung concentration of IL-17. In the lungs, inflammation was associated with marked increase in the number of multipotent mesenchymal stromal cells CD90(+)CD73(+)CD106(+)CD44(+)) and Clara cells (CD45(-)CD34(-)CD31(-)Sca1(+)) and overexpression of extracellular matrix proteins (hydroxyproline, connective tissue growth factor, collagen, fibronectin) and Clara cells protein. On the other hand, elastase reduced the number of angiogenic precursor cells (CD45(-)CD117(+)Flk1(+)). PMID:27591877

  13. Correlation of emphysema score with perceived malignancy of pulmonary nodules: a multi-observer study using the LIDC-IDRI CT lung database

    NASA Astrophysics Data System (ADS)

    Wiemker, Rafael; Bülow, Thomas; Blaffert, Thomas; Dharaiya, Ekta

    2009-02-01

    Presence of emphysema is recognized to be one of the single most significant risk factors in risk models for the prediction of lung cancer. Therefore, an automatically computed emphysema score would be a prime candidate as an additional numerical feature for computer aided diagnosis (CADx) for indeterminate pulmonary nodules. We have applied several histogram-based emphysema scores to 460 thoracic CT scans from the IDRI CT lung image database, and analyzed the emphysema scores in conjunction with 3000 nodule malignancy ratings of 1232 pulmonary nodules made by expert observers. Despite the emphysema being a known risk factor, we have not found any impact on the readers' malignancy rating of nodules found in a patient with higher emphysema score. We have also not found any correlation between the number of expert-detected nodules in a patient and his emphysema score, or the relative craniocaudal location of the nodules and their malignancy rating. The inter-observer agreement of the expert ratings was excellent on nodule diameter (as derived from manual delineations), good for calcification, and only modest for malignancy and shape descriptions such as spiculation, lobulation, margin, etc.

  14. Subcutaneous emphysema of the neck, chest, and abdomen as a symptom of colonic diverticular perforation into the retroperitoneum

    PubMed Central

    Janczak, Dariusz; Ziomek, Agnieszka; Dorobisz, Tadeusz; Dorobisz, Karolina; Janczak, Dawid; Pawłowski, Wiktor

    2016-01-01

    We describe a rare case of a patient with colonic diverticular perforation manifested only by subcutaneous emphysema of the neck, chest, and abdomen, as visualized by a computed tomography (CT) scan. The 76-year-old female patient with a history of internal diseases was urgently admitted to the Clinic of Internal Diseases due to a urinary tract infection. During the hospitalization, further diagnostic procedures were performed due to palpable subcutaneous emphysema of the neck, chest, and abdomen. Computed tomography examination revealed massive intra-abdominal, intramuscular, and subcutaneous emphysema. A decision was made to perform exploratory laparotomy; the procedure exposed an inveterate diverticular perforation of the sigmoid-rectal flexure as well as air-inflated retroperitoneal tissue. The perforated colon was resected, and a stoma was formed. On the 15th postoperative day, the patient died due to cardiorespiratory failure. Although subcutaneous emphysema is a common symptom in everyday medical practice, its etiology remains complex. One should consider this clinical presentation of colonic diverticular perforation, especially in elderly patients in whom the perforation signs may be clinically less marked. PMID:27212982

  15. High incidence of subcutaneous emphysema in children in a Somali refugee cAMP during measles outbreak.

    PubMed

    Moons, Peter; Thallinger, Monica

    2014-01-01

    During an outbreak of measles in a refugee camp in Ethiopia, 9 patients (age range 4 months to 18 years) were diagnosed with subcutaneous emphysema. Incidence of this rare complication of measles in this refugee camp was higher than previously reported. We hypothesize that the high incidence is most likely related to poor physical state of the refugee population with high rates of malnutrition.

  16. Emphysema Quantification in Inflation-Fixed Lungs Using Low-Dose Computed Tomography and 3He Magnetic Resonance Imaging

    SciTech Connect

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

    2010-09-02

    Abstract: Objective: To evaluate the use of inflation-fixed lung tissue for emphysema quantification with CT and 3He MR diffusion imaging. Methods: Fourteen subjects representing a range of chronic obstructive pulmonary disease severity who underwent complete or lobar lung resection were studied. CT measurements of lung attenuation and MR measurements of the hyperpolarized 3He apparent diffusion coefficient (ADC) in resected specimens fixed in inflation with heated formalin vapor were compared with measurements obtained before fixation. Results: The mean CT emphysema index was 56% ± 17% before and 58% ± 19% after fixation (P=0.77;R=0.76). Index differences correlated with differences in lung volume (R2=0.47). The mean 3He ADC was 0.40 ± 0.15 cm2/sec before and 0.39 ± 0.14 cm2/sec after fixation (P=0.03, R=0.98). The CT emphysema index and the 3He ADC were correlated before (R=0.89) and after fixation (R=0.79). Conclusion: Concordance of CT and 3He MR imaging measurements in unfixed and inflation-fixed lungs supports the use of inflation-fixed lungs for quantitative imaging studies in emphysema.

  17. Premedication with Clarithromycin Is Effective against Secondary Bacterial Pneumonia during Influenza Virus Infection in a Pulmonary Emphysema Mouse Model.

    PubMed

    Harada, Tatsuhiko; Ishimatsu, Yuji; Hara, Atsuko; Morita, Towako; Nakashima, Shota; Kakugawa, Tomoyuki; Sakamoto, Noriho; Kosai, Kosuke; Izumikawa, Koichi; Yanagihara, Katsunori; Mukae, Hiroshi; Kohno, Shigeru

    2016-09-01

    Secondary bacterial pneumonia (SBP) during influenza increases the severity of chronic obstructive pulmonary disease (COPD) and its associated mortality. Macrolide antibiotics, including clarithromycin (CAM), are potential treatments for a variety of chronic respiratory diseases owing to their pharmacological activities, in addition to antimicrobial action. We examined the efficacy of CAM for the treatment of SBP after influenza infection in COPD. Specifically, we evaluated the effect of CAM in elastase-induced emphysema mice that were inoculated with influenza virus (strain A/PR8/34) and subsequently infected with macrolide-resistant Streptococcus pneumoniae CAM was administered to the emphysema mice 4 days prior to influenza virus inoculation. Premedication with CAM improved pathologic responses and bacterial load 2 days after S. pneumoniae inoculation. Survival rates were higher in emphysema mice than control mice. While CAM premedication did not affect viral titers or exert antibacterial activity against S. pneumoniae in the lungs, it enhanced host defense and reduced inflammation, as evidenced by the significant reductions in total cell and neutrophil counts and interferon (IFN)-γ levels in bronchoalveolar lavage fluid and lung homogenates. These results suggest that CAM protects against SBP during influenza in elastase-induced emphysema mice by reducing IFN-γ production, thus enhancing immunity to SBP, and by decreasing neutrophil infiltration into the lung to prevent injury. Accordingly, CAM may be an effective strategy to prevent secondary bacterial pneumonia in COPD patients in areas in which vaccines are inaccessible or limited.

  18. Premedication with Clarithromycin Is Effective against Secondary Bacterial Pneumonia during Influenza Virus Infection in a Pulmonary Emphysema Mouse Model.

    PubMed

    Harada, Tatsuhiko; Ishimatsu, Yuji; Hara, Atsuko; Morita, Towako; Nakashima, Shota; Kakugawa, Tomoyuki; Sakamoto, Noriho; Kosai, Kosuke; Izumikawa, Koichi; Yanagihara, Katsunori; Mukae, Hiroshi; Kohno, Shigeru

    2016-09-01

    Secondary bacterial pneumonia (SBP) during influenza increases the severity of chronic obstructive pulmonary disease (COPD) and its associated mortality. Macrolide antibiotics, including clarithromycin (CAM), are potential treatments for a variety of chronic respiratory diseases owing to their pharmacological activities, in addition to antimicrobial action. We examined the efficacy of CAM for the treatment of SBP after influenza infection in COPD. Specifically, we evaluated the effect of CAM in elastase-induced emphysema mice that were inoculated with influenza virus (strain A/PR8/34) and subsequently infected with macrolide-resistant Streptococcus pneumoniae CAM was administered to the emphysema mice 4 days prior to influenza virus inoculation. Premedication with CAM improved pathologic responses and bacterial load 2 days after S. pneumoniae inoculation. Survival rates were higher in emphysema mice than control mice. While CAM premedication did not affect viral titers or exert antibacterial activity against S. pneumoniae in the lungs, it enhanced host defense and reduced inflammation, as evidenced by the significant reductions in total cell and neutrophil counts and interferon (IFN)-γ levels in bronchoalveolar lavage fluid and lung homogenates. These results suggest that CAM protects against SBP during influenza in elastase-induced emphysema mice by reducing IFN-γ production, thus enhancing immunity to SBP, and by decreasing neutrophil infiltration into the lung to prevent injury. Accordingly, CAM may be an effective strategy to prevent secondary bacterial pneumonia in COPD patients in areas in which vaccines are inaccessible or limited. PMID:27489022

  19. Air Pollution and Percent Emphysema Identified by Computed Tomography in the Multi-Ethnic Study of Atherosclerosis

    PubMed Central

    Kaufman, Joel D.; Diez-Roux, Ana V.; Hoffman, Eric A.; D’Souza, Jennifer; Stukovsky, Karen H.; Rich, Stephen S.; Rotter, Jerome I.; Guo, Xiuqing; Raffel, Leslie J.; Sampson, Paul D.; Oron, Assaf P.; Raghunathan, Trivellore; Barr, R. Graham

    2014-01-01

    Background: Air pollution is linked to low lung function and to respiratory events, yet little is known of associations with lung structure. Objectives: We examined associations of particulate matter (PM2.5, PM10) and nitrogen oxides (NOx) with percent emphysema-like lung on computed tomography (CT). Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) recruited participants (45–84 years of age) in six U.S. states. Percent emphysema was defined as lung regions < –910 Hounsfield Units on cardiac CT scans acquired following a highly standardized protocol. Spirometry was also conducted on a subset. Individual-level 1- and 20-year average air pollution exposures were estimated using spatiotemporal models that included cohort-specific measurements. Multivariable regression was conducted to adjust for traditional risk factors and study location. Results: Among 6,515 participants, we found evidence of an association between percent emphysema and long-term pollution concentrations in an analysis leveraging between-city exposure contrasts. Higher concentrations of PM2.5 (5 μg/m3) and NOx (25 ppb) over the previous year were associated with 0.6 (95% CI: 0.1, 1.2%) and 0.5 (95% CI: 0.1, 0.9%) higher average percent emphysema, respectively. However, after adjustment for study site the associations were –0.6% (95% CI: –1.5, 0.3%) for PM2.5 and –0.5% (95% CI: –1.1, 0.02%) for NOx. Lower lung function measures (FEV1 and FVC) were associated with higher PM2.5 and NOx levels in 3,791 participants before and after adjustment for study site, though most associations were not statistically significant. Conclusions: Associations between ambient air pollution and percentage of emphysema-like lung were inconclusive in this cross-sectional study, thus longitudinal analyses may better clarify these associations with percent emphysema. Citation: Adar SD, Kaufman JD, Diez-Roux AV, Hoffman EA, D’Souza J, Stukovsky KH, Rich SS, Rotter JI, Guo X, Raffel LJ, Sampson PD, Oron

  20. A gene expression signature of emphysema-related lung destruction and its reversal by the tripeptide GHK

    PubMed Central

    2012-01-01

    Background Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease consisting of emphysema, small airway obstruction, and/or chronic bronchitis that results in significant loss of lung function over time. Methods In order to gain insights into the molecular pathways underlying progression of emphysema and explore computational strategies for identifying COPD therapeutics, we profiled gene expression in lung tissue samples obtained from regions within the same lung with varying amounts of emphysematous destruction from smokers with COPD (8 regions × 8 lungs = 64 samples). Regional emphysema severity was quantified in each tissue sample using the mean linear intercept (Lm) between alveolar walls from micro-CT scans. Results We identified 127 genes whose expression levels were significantly associated with regional emphysema severity while controlling for gene expression differences between individuals. Genes increasing in expression with increasing emphysematous destruction included those involved in inflammation, such as the B-cell receptor signaling pathway, while genes decreasing in expression were enriched in tissue repair processes, including the transforming growth factor beta (TGFβ) pathway, actin organization, and integrin signaling. We found concordant differential expression of these emphysema severity-associated genes in four cross-sectional studies of COPD. Using the Connectivity Map, we identified GHK as a compound that can reverse the gene-expression signature associated with emphysematous destruction and induce expression patterns consistent with TGFβ pathway activation. Treatment of human fibroblasts with GHK recapitulated TGFβ-induced gene-expression patterns, led to the organization of the actin cytoskeleton, and elevated the expression of integrin β1. Furthermore, addition of GHK or TGFβ restored collagen I contraction and remodeling by fibroblasts derived from COPD lungs compared to fibroblasts from former smokers without

  1. Emphysema and fibrosis: risk factors in responsiveness to air pollution

    SciTech Connect

    Costa, D.L.; Lehmann, J.R.

    1984-01-01

    Episodic and epidemiologic data appear to support the belief that chronic non-specific lung disease imposes an additional risk to affected individuals when challenged by air pollution. While this concept has been implicitly enacted into law, little knowledge or understanding of the tenets of disease-based hyper-susceptibility exists. The clinical and animal experimental data show trends, but in general, have provided little substance to defend or challenge the legitimacy of the margins of safety incorporated into the standards of the EPA regulated pollutants. As more data on so-called normal individuals are being collected, many of these safety margins appear to be eroding, thus offering little encouragement that susceptible subgroups of the population are actually being protected. 39 references, 8 tables.

  2. Oxidative status and chymotrypsin-like activity in right and left ventricle hypertrophy in an experimental model of emphysema.

    PubMed

    Tonon, Jair; Guarnier, Flávia Alessandra; Brunnquell, Cláudia Roberta; Bernardes, Sara Santos; Cecchini, Alessandra Lourenço; Cecchini, Rubens

    2013-09-01

    Although cardiac muscle hypertrophy has been studied in association with several diseases, its mechanism in patients with emphysema, in particular in relation to oxidative stress and proteolysis, remains unknown. The role of oxidative stress and proteolysis in right and left ventricle hypertrophy was investigated in hamsters with emphysema induced by 2 different doses of papain (20mg/mL, E20 and 40mg/mL, E40). The thickness of the ventricles, total and cardiac weight, lipid peroxidation, carbonyl proteins, total antioxidant capacity (TAC), and proteasomal proteolytic activity were evaluated in the right ventricle (RV) and the left ventricle (LV) of control and emphysema hamsters. RV thickness was increased by 12% in the E20 group and by 29% in the E40 group. Lipid peroxidation measured by chemiluminescence was increased in the E40 group (from 3350.68±392.44URL/g tissue to 4696.63±1076.70URL/g tissue, p<0.05). TAC also increased only in the E40 group. In the LV, chemiluminescence values increased from 4044.77±503.39 to 5517.10±388.27 in the E20 group and to 8169.14±1748.77URL/g tissue in the E40 group (p<0.05, both). TAC significantly increased in the E20 and E40 groups. No differences were detected in substances reactive to thiobarbituric acid or carbonyl proteins when comparing ventricles or doses. Chymotrypsin-like proteolytic activity significantly decreased in both groups and ventricles. Emphysema can induce right and left ventricle lipid peroxidation and result in antioxidant mobilization. These data together support the idea that cardiac hypertrophy in response to emphysema is mediated in part by proteolytic pathways with involvement of reactive species. PMID:24149056

  3. The nutritional status in advanced emphysema associated with chronic bronchitis. A study of amino acid and catecholamine levels.

    PubMed

    Hofford, J M; Milakofsky, L; Vogel, W H; Sacher, R S; Savage, G J; Pell, S

    1990-04-01

    Advanced emphysema with bronchitis is associated with significant weight loss and malnutrition, the true cause of which has not been clearly identified. The purpose of this exploratory study was to compare plasma amino acids and related compounds and catecholamines in a group of patients with advanced end-stage emphysema with a control group of similar age and sex in an effort to further understand this malnourished state. Fasting blood samples were obtained by venipuncture after a rest period. Plasma amino acid levels were determined by ion exchange high pressure liquid chromatography with fluorometric detection. Plasma catecholamines were determined by radioenzymatic analysis. Anthropometric measurements, the usually accepted biochemical markers of nutrition, dietary analysis, pulmonary function tests, and a historical analysis of the state of health including drug use and smoking history in each subject were analyzed. Ages and heights were comparable, whereas weights were significantly decreased in the patients with emphysema. Total serum protein and serum albumin values were significantly lower in the patient group. Significant respiratory muscle weakness was indicated by reduced negative inspiratory force in these end-stage patients, contrasting with well-preserved muscle strength usually found in obstructive lung disease. The dietary caloric intake of the patients was comparable to that of the control subjects. We conclude that the fine balance of the amino acid pool in patients with bronchitis and emphysema is well preserved, except for significant elevations of aspartic acid, glutamine, and cystine, and a decreased level of leucine. In addition, norepinephrine levels were significantly increased. Weight loss in patients with emphysema and bronchitis is likely due to increased energy demands related to hypermetabolism. PMID:2327654

  4. Television Quiz Show Simulation

    ERIC Educational Resources Information Center

    Hill, Jonnie Lynn

    2007-01-01

    This article explores the simulation of four television quiz shows for students in China studying English as a foreign language (EFL). It discusses the adaptation and implementation of television quiz shows and how the students reacted to them.

  5. Application of electrical impedance tomography in diagnosis of emphysema--a clinical study.

    PubMed

    Eyüboğlu, B M; Oner, A F; Baysal, U; Biber, C; Keyf, A I; Yilmaz, U; Erdoğan, Y

    1995-08-01

    In this paper, electrical impedance tomography (EIT) ventilation images from a group of 12 patients (11 patients with emphysema and one patient with only chronic obstructive pulmonary disease (COPD) (chronic bronchitis) and a group of 15 normal subjects were acquired using a Sheffield mark 1 EIT system, at the levels of second, fourth and sixth intercostal spaces. Patients were diagnosed based on CT scans of the thorax, pulmonary function tests and posteroanterior x-ray graphs. One of the patients with emphysema has also a malignant lung tumour. Ventilation-related conductivity changes at total lung capacity (TLC) relative to residual volume were measured quantitatively in EIT images. These quantitative values demonstrate marked differences compared to those values obtained from the EIT images of 15 normal subjects. The EIT images of the patients were also compared with the CT images. In addition to the visual examination of the EIT images a statistical confidence test is applied to compare the images of the patients with the images of the normal subjects. Prior to statistical analysis all images are normalized with TLC to minimize the effect of mismatch between the TLC of different subjects. A normal mean image is created by averaging the normalized images from the normal subjects, at each intercostal space level. Than a 95% confidence interval is defined for each normal mean image. For each image of the patients, a confidence test image, which represents the deviations from the 95% confidence interval of the normal mean image, is created. The regions with emphysematous bulla and parencyhma are detectable in the confidence test images as regions of positive and negative deviations from the confidence interval of the normal mean, respectively. In the test images, it is possible to differentiate emphysematous parenchyma from emphysematous bulla, tumour structure, and COPD. However, the emphysematous bulla, the tumour structure, and COPD result in the same type of

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

    NASA Astrophysics Data System (ADS)

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

    2008-03-01

    Emphysema patients have the tendency to increase due to aging and smoking. Emphysematous disease destroys alveolus and to repair is impossible, thus early detection is essential. CT value of lung tissue decreases due to the destruction of lung structure. This CT value becomes lower than the normal lung- low density absorption region or referred to as Low Attenuation Area (LAA). So far, the conventional way of extracting LAA by simple thresholding has been proposed. However, the CT value of CT image fluctuates due to the measurement conditions, with various bias components such as inspiration, expiration and congestion. It is therefore necessary to consider these bias components in the extraction of LAA. We removed these bias components and we proposed LAA extraction algorithm. This algorithm has been applied to the phantom image. Then, by using the low dose CT(normal: 30 cases, obstructive lung disease: 26 cases), we extracted early stage LAA and quantitatively analyzed lung lobes using lung structure.

  7. Stratified Pulmonary Blood Flow: Some Consequences in Emphysema and Pulmonary Embolism

    PubMed Central

    Read, John

    1969-01-01

    Both ventilation and blood flow in the secondary lobule of the lung are stratified; each unit of lung tissue in the proximal portion of the lobule receives up to four times the blood flow of units in the peripheral portion. Questions of the limiting role of gas diffusion within the small airways become virtually irrelevant in the face of this stratification of function. The central portion of the lobule, with its high ventilation, blood flow, and gas exchange, is very vulnerable; small lesions at this site will produce disproportionately large disturbances of gas exchange and of pulmonary vascular resistance. This may well account for some of the phenomena of conditions such as centrilobular emphysema and pulmonary microembolism. PMID:5776220

  8. Pneumomediastinum, pneumorachis, subcutaneous emphysema: An unusual complication of leukemia in a child

    PubMed Central

    Showkat, Hakim Irfan; Jan, Aleem; Sarmast, Arif Hussain; Bhat, Gull Mohammad; Jan, Basharat Mujtaba; Bashir, Yasir

    2013-01-01

    Pneumorrhachis (PR), or epidural emphysema, denotes the presence of air in the spinal epidural space. It can be associated with a variety of etiologies, including trauma; recent iatrogenic manipulations during surgical, anesthesiological and diagnostic interventions; malignancy and its associated therapy. It usually represents an asymptomatic epiphenomenon but also can be symptomatic by itself, as well as by its underlying pathology, and rarely can be fatal. The pathogenesis and etiology of PR are varied and can sometimes be a diagnostic challenge. As such, there are no standard guidelines for the management of symptomatic PR and its treatment is often individualized. Here, we present a case of a 14-year-old boy treated for leukemia who developed this complication and whether chemotherapy related or not, it proved to be fatal for him. To our knowledge, this is the first case in the literature of this complication with acute lymphoblastic leukemia. PMID:24340272

  9. [A case of respiratory distress syndrome complicated by the development of interstitial emphysema and pneumomediastinum].

    PubMed

    Zhidkov, K P; Bogatyr', M N; Chezhin, A N; Leĭman, V A; Smirnova, O R

    2000-01-01

    A 15-year-old patient has been admitted to the intensive care unit for severe respiratory distress syndrome that developed as a result of pneumonia. Interstitial lung edema was confirmed by computer-aided tomography. It was successfully treated by positive pressure ventilation (PPV). Although PEEP did not exceed 7 cm H2O, PPV was complicated by interstitial emphysema, pneumomediastinum, and bilateral pneumothorax as a result of barotrauma. Pulmonary artery pressure (PAP) and pulmonary capillary wedge pressure (PCWP) were monitored. High PCWP values were inconsistent with the diagnosis of acute respiratory distress syndrome. The authors suggest that high PCWP was caused by high intraalveolar pressure, pneumomediastinum, and venule constriction in the hypoxic sites of the lung.

  10. Automated diagnosis of interstitial lung diseases and emphysema in MDCT imaging

    NASA Astrophysics Data System (ADS)

    Fetita, Catalin; Chang Chien, Kuang-Che; Brillet, Pierre-Yves; Prêteux, Françoise

    2007-09-01

    Diffuse lung diseases (DLD) include a heterogeneous group of non-neoplasic disease resulting from damage to the lung parenchyma by varying patterns of inflammation. Characterization and quantification of DLD severity using MDCT, mainly in interstitial lung diseases and emphysema, is an important issue in clinical research for the evaluation of new therapies. This paper develops a 3D automated approach for detection and diagnosis of diffuse lung diseases such as fibrosis/honeycombing, ground glass and emphysema. The proposed methodology combines multi-resolution 3D morphological filtering (exploiting the sup-constrained connection cost operator) and graph-based classification for a full characterization of the parenchymal tissue. The morphological filtering performs a multi-level segmentation of the low- and medium-attenuated lung regions as well as their classification with respect to a granularity criterion (multi-resolution analysis). The original intensity range of the CT data volume is thus reduced in the segmented data to a number of levels equal to the resolution depth used (generally ten levels). The specificity of such morphological filtering is to extract tissue patterns locally contrasting with their neighborhood and of size inferior to the resolution depth, while preserving their original shape. A multi-valued hierarchical graph describing the segmentation result is built-up according to the resolution level and the adjacency of the different segmented components. The graph nodes are then enriched with the textural information carried out by their associated components. A graph analysis-reorganization based on the nodes attributes delivers the final classification of the lung parenchyma in normal and ILD/emphysematous regions. It also makes possible to discriminate between different types, or development stages, among the same class of diseases.

  11. Elastase induces lung epithelial cell autophagy through placental growth factor: a new insight of emphysema pathogenesis.

    PubMed

    Hou, Hsin-Han; Cheng, Shih-Lung; Chung, Kuei-Pin; Kuo, Mark Yen-Ping; Yeh, Cheng-Chang; Chang, Bei-En; Lu, Hsuan-Hsuan; Wang, Hao-Chien; Yu, Chong-Jen

    2014-09-01

    Chronic obstructive pulmonary disease (COPD) is a devastating disease, which is associated with increasing mortality and morbidity. Therefore, there is a need to clearly define the COPD pathogenic mechanism and to explore effective therapies. Previous studies indicated that cigarette smoke (CS) induces autophagy and apoptosis in lung epithelial (LE) cells. Excessive ELANE/HNE (elastase, neutrophil elastase), a factor involved in protease-antiprotease imbalance and the pathogenesis of COPD, causes LE cell apoptosis and upregulates the expression of several stimulus-responsive genes. However, whether or not elastase induces autophagy in LE cell remains unknown. The level of PGF (placental growth factor) is higher in COPD patients than non-COPD controls. We hypothesize that elastase induces PGF expression and causes autophagy in LE cells. In this study, we demonstrated that porcine pancreatic elastase (PPE) induced PGF expression and secretion in LE cells in vitro and in vivo. The activation of MAPK8/JNK1 (mitogen-activated protein kinase 8) and MAPK14/p38alpha MAPK signaling pathways was involved in the PGF mediated regulation of the TSC (tuberous sclerosis complex) pathway and autophagy in LE cells. Notably, PGF-induced MAPK8 and MAPK14 signaling pathways mediated the inactivation of MTOR (mechanistic target of rapamycin), the upregulation of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3 β) and the increase of autophagosome formation in mice. Furthermore, the PPE-induced autophagy promotes further apoptosis in vitro and in vivo. In summary, elastase-induced autophagy promotes LE cell apoptosis and pulmonary emphysema through the upregulation of PGF. PGF and its downstream MAPK8 and MAPK14 signaling pathways are potential therapeutic targets for the treatment of emphysema and COPD.

  12. [Arterial CO2- and O2 partial pressure at rest and during exertion in pulmonary emphysema].

    PubMed

    Scherrer, M; Zeller, C; Bachofen, H

    1977-07-30

    In 83 patients with severe, largely irreversible bronchial obstruction (FEV1/VC less than 40% and FEV1 after orciprenaline inhalation less than 120% of the control value) and radiologie evidence of AD-emphysema, arterial PCO2 and PO2 were measured at rest in supine position and on the bicycle ergometer during a steady-state exercice of 5 min. Alveolar hypoventilation (PCO2 greater than 45 mm Hg) was most often observed in the cases with FEV1 less than 1.01 (in 22 patients [27%] at rest and in 26 patients [31%] during exercise). However, there was no significant correlation of the PCO2 increase with the degree of bronchial obstruction. In all patients there was a marked inhomogeneity of the alveolar ventilation or the alveolar-capillary O2 transfer in relation to alveolar blood perfusion. Indeed, the alveolar-arterial PO2 difference was increased (40 mm Hg at rest and 45 mm Hg during exercise). The additional increase of this gradient during exercise was due to an unequal distribution of alveolar O2 diffusing capacities in connection with the alveolar blood flow (preceding measurements of the N2 gradient between alveolar air and arterial blood revealed a mean fall from 18 at rest to 8 mm Hg during exercise). The observed deterioration of hypoxemia during exercise (without additional hypercapnia) is to a great extent related to the degree of bronchial obstruction measured by simple spirometry. Thus, measurements of PCO2 and PO2 at rest and during exercise appear to be a helpful adjuvant to routine spirometry in the diagnosis of subclinical emphysema.

  13. Lung Cancer in Combined Pulmonary Fibrosis and Emphysema: A Systematic Review and Meta-Analysis

    PubMed Central

    Koo, Hyun Jung; Do, Kyung-Hyun; Lee, Jung Bok; Alblushi, Sania; Lee, Sang Min

    2016-01-01

    Purpose Patients with combined pulmonary fibrosis and emphysema (CPFE) have been suggested to have an increased risk of lung cancer. We conducted a systematic review of all published data and performed a meta-analysis to define the characteristics of lung cancer that develops in CPFE. Method We searched Pubmed, Embase, and Cochrane to find original articles about lung cancer and CPFE published prior to September 2015. All titles/abstracts were reviewed by two radiologists to identify articles that used predefined selection criteria. Summary estimates were generated using a random-effect model and odds ratios (ORs) to develop squamous cell carcinoma (SqCC) were calculated. Kaplan–Meier survival curves were obtained for the survival of patients with CPFE and non-CPFE. Results Nine original articles that assessed 620 patients were included in this review. In the pooled data, patients were older age (70.4 years), almost all were heavy smokers (53.5 pack years), and males were predominant (92.6%). SqCC was the most common type (42.3%), followed by adenocarcinoma (34.4%). Compared with lung cancer population with an otherwise normal lung, the OR to develop SqCC in CPFE was 9.06 (95% CI, 6.08–13.5). The ORs in CPFE compared with lung cancers that developed in lungs with fibrosis or emphysema were also higher. The median survival for CPFE patients with lung cancer (19.5 months) was significantly shorter than in non-CPFE (53.1 months). Conclusions Lung cancer in CPFE, most commonly SqCC, presents in elderly heavy smokers with a male predominance. The median survival for CPFE patients with lung cancer is 19.5 months. PMID:27618692

  14. A Holographic Road Show.

    ERIC Educational Resources Information Center

    Kirkpatrick, Larry D.; Rugheimer, Mac

    1979-01-01

    Describes the viewing sessions and the holograms of a holographic road show. The traveling exhibits, believed to stimulate interest in physics, include a wide variety of holograms and demonstrate several physical principles. (GA)

  15. The Ozone Show.

    ERIC Educational Resources Information Center

    Mathieu, Aaron

    2000-01-01

    Uses a talk show activity for a final assessment tool for students to debate about the ozone hole. Students are assessed on five areas: (1) cooperative learning; (2) the written component; (3) content; (4) self-evaluation; and (5) peer evaluation. (SAH)

  16. Show What You Know

    ERIC Educational Resources Information Center

    Eccleston, Jeff

    2007-01-01

    Big things come in small packages. This saying came to the mind of the author after he created a simple math review activity for his fourth grade students. Though simple, it has proven to be extremely advantageous in reinforcing math concepts. He uses this activity, which he calls "Show What You Know," often. This activity provides the perfect…

  17. Showing What They Know

    ERIC Educational Resources Information Center

    Cech, Scott J.

    2008-01-01

    Having students show their skills in three dimensions, known as performance-based assessment, dates back at least to Socrates. Individual schools such as Barrington High School--located just outside of Providence--have been requiring students to actively demonstrate their knowledge for years. The Rhode Island's high school graduating class became…

  18. Stage a Water Show

    ERIC Educational Resources Information Center

    Frasier, Debra

    2008-01-01

    In the author's book titled "The Incredible Water Show," the characters from "Miss Alaineus: A Vocabulary Disaster" used an ocean of information to stage an inventive performance about the water cycle. In this article, the author relates how she turned the story into hands-on science teaching for real-life fifth-grade students. The author also…

  19. What Do Maps Show?

    ERIC Educational Resources Information Center

    Geological Survey (Dept. of Interior), Reston, VA.

    This curriculum packet, appropriate for grades 4-8, features a teaching poster which shows different types of maps (different views of Salt Lake City, Utah), as well as three reproducible maps and reproducible activity sheets which complement the maps. The poster provides teacher background, including step-by-step lesson plans for four geography…

  20. Obesity in show cats.

    PubMed

    Corbee, R J

    2014-12-01

    Obesity is an important disease with a high prevalence in cats. Because obesity is related to several other diseases, it is important to identify the population at risk. Several risk factors for obesity have been described in the literature. A higher incidence of obesity in certain cat breeds has been suggested. The aim of this study was to determine whether obesity occurs more often in certain breeds. The second aim was to relate the increased prevalence of obesity in certain breeds to the official standards of that breed. To this end, 268 cats of 22 different breeds investigated by determining their body condition score (BCS) on a nine-point scale by inspection and palpation, at two different cat shows. Overall, 45.5% of the show cats had a BCS > 5, and 4.5% of the show cats had a BCS > 7. There were significant differences between breeds, which could be related to the breed standards. Most overweight and obese cats were in the neutered group. It warrants firm discussions with breeders and cat show judges to come to different interpretations of the standards in order to prevent overweight conditions in certain breeds from being the standard of beauty. Neutering predisposes for obesity and requires early nutritional intervention to prevent obese conditions. PMID:24612018

  1. Show Me the Way

    ERIC Educational Resources Information Center

    Dicks, Matthew J.

    2005-01-01

    Because today's students have grown up steeped in video games and the Internet, most of them expect feedback, and usually gratification, very soon after they expend effort on a task. Teachers can get quick feedback to students by showing them videotapes of their learning performances. The author, a 3rd grade teacher describes how the seemingly…

  2. The Art Show

    ERIC Educational Resources Information Center

    Scolarici, Alicia

    2004-01-01

    This article describes what once was thought to be impossible--a formal art show extravaganza at an elementary school with 1,000 students, a Department of Defense Dependent School (DODDS) located overseas, on RAF Lakenheath, England. The dream of this this event involved the transformation of the school cafeteria into an elegant art show…

  3. Honored Teacher Shows Commitment.

    ERIC Educational Resources Information Center

    Ratte, Kathy

    1987-01-01

    Part of the acceptance speech of the 1985 National Council for the Social Studies Teacher of the Year, this article describes the censorship experience of this honored social studies teacher. The incident involved the showing of a videotape version of the feature film entitled "The Seduction of Joe Tynan." (JDH)

  4. Independent Peer Reviews

    SciTech Connect

    2012-03-16

    Independent Assessments: DOE's Systems Integrator convenes independent technical reviews to gauge progress toward meeting specific technical targets and to provide technical information necessary for key decisions.

  5. "Punk" rock can be bad for you: a case of surgical emphysema from a "punk" rocker's leather jacket

    PubMed Central

    Lane, N; Graudins, A

    2006-01-01

    Stab wounds to the thorax are seen in the emergency department (ED) and can be caused by a variety of mechanisms. This case highlights an unusual cause of injury: a leather jacket with spikes on the back of it. This type of jacket is often worn by "punks" as a fashion statement. We report that falling onto such a jacket may result in accidental thoracic injury leading to subcutaneous emphysema. A thorough clinical assessment is mandatory to exclude underlying lung injury or pneumothorax. In patients with subcutaneous emphysema and an otherwise normal chest radiograph, an in hospital observation period of 24 hours to check for any delayed complications is adequate if the patient remains clinically stable. PMID:16714489

  6. "Punk" rock can be bad for you: a case of surgical emphysema from a "punk" rocker's leather jacket.

    PubMed

    Lane, N; Graudins, A

    2006-06-01

    Stab wounds to the thorax are seen in the emergency department (ED) and can be caused by a variety of mechanisms. This case highlights an unusual cause of injury: a leather jacket with spikes on the back of it. This type of jacket is often worn by "punks" as a fashion statement. We report that falling onto such a jacket may result in accidental thoracic injury leading to subcutaneous emphysema. A thorough clinical assessment is mandatory to exclude underlying lung injury or pneumothorax. In patients with subcutaneous emphysema and an otherwise normal chest radiograph, an in hospital observation period of 24 hours to check for any delayed complications is adequate if the patient remains clinically stable.

  7. Spontaneous pneumopericardium, pneumomediastinum and subcutaneous emphysema: unusual complications of asthma in a 2-year-old boy.

    PubMed

    Ameh, V; Jenner, R; Jilani, N; Bradbury, A

    2006-06-01

    A 2-year-old boy presented to the emergency department with a history of sudden onset of cough, dyspnoea and a slight expiratory wheeze on the right lung base. He also had subcutaneous emphysema on the left side of the chest anteriorly. Chest x ray confirmed subcutaneous emphysema and also revealed pneumomediastinum and pneumopericardium. He had had no previous episode and was not known to have asthma. He was apyrexial but had a raised white cell count. The eosinophil count was within normal limits. He was successfully treated with nebulised salbutamol, steroids, antibiotics and high flow oxygen. He made a good recovery and was discharged after 7 days. This case highlights the need for a high index of suspicion of asthma in very young children presenting for the first time with such complications.

  8. Taking in a Show.

    PubMed

    Boden, Timothy W

    2016-01-01

    Many medical practices have cut back on education and staff development expenses, especially those costs associated with conventions and conferences. But there are hard-to-value returns on your investment in these live events--beyond the obvious benefits of acquired knowledge and skills. Major vendors still exhibit their services and wares at many events, and the exhibit hall is a treasure-house of information and resources for the savvy physician or administrator. Make and stick to a purposeful plan to exploit the trade show. You can compare products, gain new insights and ideas, and even negotiate better deals with representatives anxious to realize returns on their exhibition investments. PMID:27249887

  9. Taking in a Show.

    PubMed

    Boden, Timothy W

    2016-01-01

    Many medical practices have cut back on education and staff development expenses, especially those costs associated with conventions and conferences. But there are hard-to-value returns on your investment in these live events--beyond the obvious benefits of acquired knowledge and skills. Major vendors still exhibit their services and wares at many events, and the exhibit hall is a treasure-house of information and resources for the savvy physician or administrator. Make and stick to a purposeful plan to exploit the trade show. You can compare products, gain new insights and ideas, and even negotiate better deals with representatives anxious to realize returns on their exhibition investments.

  10. Obesity in show dogs.

    PubMed

    Corbee, R J

    2013-10-01

    Obesity is an important disease with a growing incidence. Because obesity is related to several other diseases, and decreases life span, it is important to identify the population at risk. Several risk factors for obesity have been described in the literature. A higher incidence of obesity in certain breeds is often suggested. The aim of this study was to determine whether obesity occurs more often in certain breeds. The second aim was to relate the increased prevalence of obesity in certain breeds to the official standards of that breed. To this end, we investigated 1379 dogs of 128 different breeds by determining their body condition score (BCS). Overall, 18.6% of the show dogs had a BCS >5, and 1.1% of the show dogs had a BCS>7. There were significant differences between breeds, which could be correlated to the breed standards. It warrants firm discussions with breeders and judges in order to come to different interpretations of the standards to prevent overweight conditions from being the standard of beauty. PMID:22882163

  11. Inactivation of alpha 1-antitrypsin by aqueous coal solutions: Possible relation to the emphysema of coal workers

    SciTech Connect

    Huang, X.; Laurent, P.A.; Zalma, R.; Pezerat, H. )

    1993-07-01

    Increasing evidence demonstrates that emphysema in coal workers may be related to their exposure to coal dusts. The hypothesis that emphysema could be related to the production of reactive oxygen species (ROS) generated by inhaled coal dusts was examined in the present study. Using ESR, we investigated whether the interaction of different coals with dissolved oxygen in aqueous medium could generate ROS. Indeed, we found that one of the five examined French coal samples, Vouters coal, was effective in oxidizing formate anions or ethanol by a radical pathway. Inactivation of alpha 1-antitrypsin (alpha 1-AT) in vitro was then examined for all five coal filtrates. The Vouters coal filtrate, which exhibits oxidative activity, can also inactivate alpha 1-AT. When this coal filtrate was crystallized and redissolved, its oxidative activity was found to be conserved. By use of various analytical techniques, the active component of this coal filtrate was identified to be primarily ferrous sulfate. We confirmed that pure ferrous sulfate can effectively reduce oxygen to produce ROS in aqueous medium in vitro and can also inactivate alpha 1-AT. In this report, the nature of the coal-generated oxidative species, the origin of ferrous sulfate, and the stability of ferrous sulfate in the different coal samples are discussed. These results offer evidence that some inhaled coal dusts are capable of producing ROS, which may play an important role in the development of coal workers' emphysema.

  12. Decitabine enhances stem cell antigen-1 expression in cigarette smoke extract-induced emphysema in animal model

    PubMed Central

    He, Zhi-Hui; Chen, Ping; He, Sheng-Dong; Ye, Ji-Ru; Liu, Da

    2015-01-01

    Stem cell antigen-1 (Sca-1) is a mouse glycosyl phosphatidylinositol-anchored protein and a cell surface marker found on hematopoietic stem cells (HSCs). Despite decades of study, its biological functions remain little known. Sca-1 is a typical marker of bone marrow-derived HSCs, it is also expressed by a mixture of tissue-resident stem, progenitor cells in nonhematopoietic organs. Endothelial progenitor cell (EPC) is a subtype of HSC and contributes to endothelial repair by homing in on locations of injury. Abnormal genetic methylation has been detected in smoking-related diseases. The present study aimed to investigate the lung function and histomorphology, the expression of Sca-1 gene in lung tissues, and bone marrow-derived EPCs in cigarette smoke extract (CSE)-induced emphysema mice, and to further determine whether Decitabine (Dec), the most widely used inhibitor of DNA methylation, could protect against the damages caused by CSE. The results of the present study demonstrated that Dec could partly protect against CSE-induced emphysema in mice, enhance Sca-1 expression in lung tissue, and bone marrow-derived EPCs. The results suggested that the depletion of the progenitor cell pool and DNA methylation of Sca-1 gene may be involved in the progression of emphysema in mice. PMID:26264445

  13. Decitabine enhances stem cell antigen-1 expression in cigarette smoke extract-induced emphysema in animal model.

    PubMed

    He, Zhi-Hui; Chen, Yan; Chen, Ping; He, Sheng-Dong; Ye, Ji-Ru; Liu, Da

    2016-01-01

    Stem cell antigen-1 (Sca-1) is a mouse glycosyl phosphatidylinositol-anchored protein and a cell surface marker found on hematopoietic stem cells (HSCs). Despite decades of study, its biological functions remain little known. Sca-1 is a typical marker of bone marrow-derived HSCs, it is also expressed by a mixture of tissue-resident stem, progenitor cells in nonhematopoietic organs. Endothelial progenitor cell (EPC) is a subtype of HSC and contributes to endothelial repair by homing in on locations of injury. Abnormal genetic methylation has been detected in smoking-related diseases. The present study aimed to investigate the lung function and histomorphology, the expression of Sca-1 gene in lung tissues, and bone marrow-derived EPCs in cigarette smoke extract (CSE)-induced emphysema mice, and to further determine whether Decitabine (Dec), the most widely used inhibitor of DNA methylation, could protect against the damages caused by CSE. The results of the present study demonstrated that Dec could partly protect against CSE-induced emphysema in mice, enhance Sca-1 expression in lung tissue, and bone marrow-derived EPCs. The results suggested that the depletion of the progenitor cell pool and DNA methylation of Sca-1 gene may be involved in the progression of emphysema in mice.

  14. Not a "reality" show.

    PubMed

    Wrong, Terence; Baumgart, Erica

    2013-01-01

    The authors of the preceding articles raise legitimate questions about patient and staff rights and the unintended consequences of allowing ABC News to film inside teaching hospitals. We explain why we regard their fears as baseless and not supported by what we heard from individuals portrayed in the filming, our decade-long experience making medical documentaries, and the full un-aired context of the scenes shown in the broadcast. The authors don't and can't know what conversations we had, what documents we reviewed, and what protections we put in place in each televised scene. Finally, we hope to correct several misleading examples cited by the authors as well as their offhand mischaracterization of our program as a "reality" show. PMID:23631336

  15. Not a "reality" show.

    PubMed

    Wrong, Terence; Baumgart, Erica

    2013-01-01

    The authors of the preceding articles raise legitimate questions about patient and staff rights and the unintended consequences of allowing ABC News to film inside teaching hospitals. We explain why we regard their fears as baseless and not supported by what we heard from individuals portrayed in the filming, our decade-long experience making medical documentaries, and the full un-aired context of the scenes shown in the broadcast. The authors don't and can't know what conversations we had, what documents we reviewed, and what protections we put in place in each televised scene. Finally, we hope to correct several misleading examples cited by the authors as well as their offhand mischaracterization of our program as a "reality" show.

  16. Public medical shows.

    PubMed

    Walusinski, Olivier

    2014-01-01

    In the second half of the 19th century, Jean-Martin Charcot (1825-1893) became famous for the quality of his teaching and his innovative neurological discoveries, bringing many French and foreign students to Paris. A hunger for recognition, together with progressive and anticlerical ideals, led Charcot to invite writers, journalists, and politicians to his lessons, during which he presented the results of his work on hysteria. These events became public performances, for which physicians and patients were transformed into actors. Major newspapers ran accounts of these consultations, more like theatrical shows in some respects. The resultant enthusiasm prompted other physicians in Paris and throughout France to try and imitate them. We will compare the form and substance of Charcot's lessons with those given by Jules-Bernard Luys (1828-1897), Victor Dumontpallier (1826-1899), Ambroise-Auguste Liébault (1823-1904), Hippolyte Bernheim (1840-1919), Joseph Grasset (1849-1918), and Albert Pitres (1848-1928). We will also note their impact on contemporary cinema and theatre. PMID:25273491

  17. The Great Cometary Show

    NASA Astrophysics Data System (ADS)

    2007-01-01

    its high spatial and spectral resolution, it was possible to zoom into the very heart of this very massive star. In this innermost region, the observations are dominated by the extremely dense stellar wind that totally obscures the underlying central star. The AMBER observations show that this dense stellar wind is not spherically symmetric, but exhibits a clearly elongated structure. Overall, the AMBER observations confirm that the extremely high mass loss of Eta Carinae's massive central star is non-spherical and much stronger along the poles than in the equatorial plane. This is in agreement with theoretical models that predict such an enhanced polar mass-loss in the case of rapidly rotating stars. ESO PR Photo 06c/07 ESO PR Photo 06c/07 RS Ophiuchi in Outburst Several papers from this special feature focus on the later stages in a star's life. One looks at the binary system Gamma 2 Velorum, which contains the closest example of a star known as a Wolf-Rayet. A single AMBER observation allowed the astronomers to separate the spectra of the two components, offering new insights in the modeling of Wolf-Rayet stars, but made it also possible to measure the separation between the two stars. This led to a new determination of the distance of the system, showing that previous estimates were incorrect. The observations also revealed information on the region where the winds from the two stars collide. The famous binary system RS Ophiuchi, an example of a recurrent nova, was observed just 5 days after it was discovered to be in outburst on 12 February 2006, an event that has been expected for 21 years. AMBER was able to detect the extension of the expanding nova emission. These observations show a complex geometry and kinematics, far from the simple interpretation of a spherical fireball in extension. AMBER has detected a high velocity jet probably perpendicular to the orbital plane of the binary system, and allowed a precise and careful study of the wind and the shockwave

  18. Mortality and functional performance in severe emphysema after lung volume reduction or transplant.

    PubMed

    Weinstein, Michael S; Martin, Ubaldo J; Crookshank, Aaron D; Chatila, Wissam; Vance, Gwendolyn B; Gaughan, John P; Furukawa, Satoshi; Criner, Gerard J

    2007-03-01

    The purpose of this endeavor is to compare the morbidity, mortality and costs of LVRS versus transplantation in severe emphysema. This was a retrospective review of severe emphysema patients who received LVRS (n = 70) from 1994-1999, or transplant (n = 87) from 1994-2004. Change in functional status was calculated by the change in modified BODE (mBODE) score. Financial data included physician, hospital and medication costs. Preoperatively, there was no significant difference between the transplant and LVRS groups (mean +/- SD) in age (57.7 +/- 5.7 vs. 59.1 +/- 8.3 years), BMI, Borg dyspnea score, 6-minute walk distance or mBODE (10.4 +/- 2.6 vs. 9.6 +/- 2.7, p = 0.4). Preoperatively, FEV1% (23.6 +/- 8.5 vs. 31.9 +/- 17.7, p = 0.008) was significantly lower in the transplant group. One year post-operatively, transplantation patients had a significantly greater improvement in mBODE (-5.7 vs. -2.0, p = 0.0004), FEV1% (43.4 vs. 2.2%, p = 0.0004) and Borg score (-3.0 vs. -1.4, p = 0.04). Transplantation patients had lower long-term survival compared to LVRS patients (p = 0.01). The only variable that affected survival was type of surgery favoring LVRS (hazard ratio 1.7, 95% confidence limits 1.05-2.77). During a mean follow-up of 2.4 +/- 2.5 years after transplant and 5.0 +/- 3.1 years after LVRS, transplantation mean total costs were greater ($381,732 vs. $140,637, p < 0.0001). Transplantation patients spent more time in the hospital (74.3 +/- 81.3 vs. 39.5 +/- 66.7 days, p = 0.009) and had more outpatient visits (29.9 +/- 28.8 vs. 12.3 +/- 12.6 visits, p < 0.0001). In patients who survive over 1 year, transplantation provides a higher level of functional status and a greater improvement in airflow obstruction, dyspnea, exercise tolerance, and mBODE score, but costs more and carries greater mortality.

  19. Involvement of B-cell CLL/lymphoma 2 promoter methylation in cigarette smoke extract-induced emphysema

    PubMed Central

    Zeng, Huihui; Shi, Zhihui; Kong, Xianglong; Chen, Yan; Zhang, Hongliang; Peng, Hong; Luo, Hong

    2016-01-01

    Abnormal apoptotic events play an important role in the pathogenesis of emphysema. The B-cell CLL/lymphoma 2 (Bcl-2) family proteins are essential and critical regulators of apoptosis. We determined whether the anti-apoptotic Bcl-2 play a role in the cigarette smoke extract (CSE)-induced emphysema. Furthermore, given the involvement of epigenetics in chronic obstructive pulmonary disease, we hypothesized that the deregulation of Bcl-2 might be caused by gene methylation. The emphysema in BALB/C mice was established by intraperitoneally injection of CSE. 5-aza-2′-deoxycytidine (AZA; a demethylation reagent) and phosphate-buffered saline were also administered intraperitoneally as CSE. TUNEL assay was used to assess apoptotic index of pulmonary cells. The methylation status of CpG dinucleotides within the Bcl-2 promoter was observed in all groups by bisulfite sequencing PCR. Pulmonary expression of Bcl-2, Bax, and cytochrome C were measured after four weeks of treatment. The apoptotic index of pulmonary cells in CSE injection group was much higher than control ((25.88 ± 7.55)% vs. (6.28 ± 2.96)%). Compared to control mice, decreased expression of Bcl-2 and high methylation of Bcl-2 promoter was observed in CSE injected mice (0.88 ± 0.08 vs. 0.49 ± 0.11, (3.82 ± 1.34)% vs. (35.68 ± 5.99)%, P < 0.01).CSE treatment induced lung cell apoptosis and decreased lung function. AZA treatment increased Bcl-2 expression with Bcl-2 promoter demethylation. AZA also alleviated the lung cell apoptosis and function failure caused by CSE treatment. The decreased expression of anti-apoptotic Bcl-2 might account for the increased apoptosis in CSE induced-emphysema. Apparently, epigenetic alternation played a role in this deregulation of Bcl-2 expression, and it might support the involvement of epigenetic events in the pathogenesis of emphysema. PMID:26924842

  20. Stretched View Showing 'Victoria'

    NASA Technical Reports Server (NTRS)

    2006-01-01

    [figure removed for brevity, see original site] Stretched View Showing 'Victoria'

    This pair of images from the panoramic camera on NASA's Mars Exploration Rover Opportunity served as initial confirmation that the two-year-old rover is within sight of 'Victoria Crater,' which it has been approaching for more than a year. Engineers on the rover team were unsure whether Opportunity would make it as far as Victoria, but scientists hoped for the chance to study such a large crater with their roving geologist. Victoria Crater is 800 meters (nearly half a mile) in diameter, about six times wider than 'Endurance Crater,' where Opportunity spent several months in 2004 examining rock layers affected by ancient water.

    When scientists using orbital data calculated that they should be able to detect Victoria's rim in rover images, they scrutinized frames taken in the direction of the crater by the panoramic camera. To positively characterize the subtle horizon profile of the crater and some of the features leading up to it, researchers created a vertically-stretched image (top) from a mosaic of regular frames from the panoramic camera (bottom), taken on Opportunity's 804th Martian day (April 29, 2006).

    The stretched image makes mild nearby dunes look like more threatening peaks, but that is only a result of the exaggerated vertical dimension. This vertical stretch technique was first applied to Viking Lander 2 panoramas by Philip Stooke, of the University of Western Ontario, Canada, to help locate the lander with respect to orbiter images. Vertically stretching the image allows features to be more readily identified by the Mars Exploration Rover science team.

    The bright white dot near the horizon to the right of center (barely visible without labeling or zoom-in) is thought to be a light-toned outcrop on the far wall of the crater, suggesting that the rover can see over the low rim of Victoria. In figure 1, the northeast and southeast rims are labeled

  1. Biographical factors of occupational independence.

    PubMed

    Müller, G F

    2001-10-01

    The present study examined biographical factors of occupational independence including any kind of nonemployed profession. Participants were 59 occupationally independent and 58 employed persons of different age (M = 36.3 yr.), sex, and profession. They were interviewed on variables like family influence, educational background, occupational role models, and critical events for choosing a particular type of occupational career. The obtained results show that occupationally independent people reported stronger family ties, experienced fewer restrictions of formal education, and remembered fewer negative role models than the employed people. Implications of these results are discussed. PMID:11783553

  2. Recovery of pulmonary structure and exercise capacity by treatment with granulocyte-colony stimulating factor (G-CSF) in a mouse model of emphysema.

    PubMed

    Fortunato, Gustavo; Vidal, Daniel T A; Klein, Wilfried; Neto, Alberto; Angrizani, André; Vasconcelos, Juliana F; Kaneto, Carla; Souza, Bruno Solano de Freitas; Ribeiro-dos-Santos, Ricardo; Soares, Milena B P; Macambira, Simone G

    2014-04-01

    Emphysema is a chronic obstructive pulmonary disease characterized abnormal dilatation of alveolar spaces, which impairs alveolar gas exchange, compromising the physical capacity of a patient due to airflow limitations. Here we tested the effects of G-CSF administration in pulmonary tissue and exercise capacity in emphysematous mice. C57Bl/6 female mice were treated with elastase intratracheally to induce emphysema. Their exercise capacities were evaluated in a treadmill. Lung histological sections were prepared to evaluate mean linear intercept measurement. Emphysematous mice were treated with G-CSF (3 cycles of 200 μg/kg/day for 5 consecutive days, with 7-day intervals) or saline and submitted to a third evaluation 8 weeks after treatment. Values of run distance and linear intercept measurement were expressed as mean ± SD and compared applying a paired t-test. Effects of treatment on these parameters were analyzed applying a Repeated Measures ANOVA, followed by Tukey's post hoc analysis. p < 0.05 was considered statistically significant. Twenty eight days later, animals ran significantly less in a treadmill compared to normal mice (549.7 ± 181.2 m and 821.7 ± 131.3 m, respectively; p < 0.01). Treatment with G-CSF significantly increased the exercise capacity of emphysematous mice (719.6 ± 200.5 m), whereas saline treatment had no effect on distance run (595.8 ± 178.5 m). The PCR cytokines genes analysis did not detect difference between experimental groups. Morphometric analyses in the lung showed that saline-treated mice had a mean linear intercept significantly higher (p < 0.01) when compared to mice treated with G-CSF, which did not significantly differ from that of normal mice. Treatment with G-CSF promoted the recovery of exercise capacity and regeneration of alveolar structural alterations in emphysematous mice.

  3. Elastase-induced emphysema: retention of instilled proteinase in the rat

    SciTech Connect

    Sandhaus, R.A.; Janoff, A.

    1982-11-01

    Airway instillation of proteinases with the ability to degrade elastin has been used to produce disease in the rat analogous to human pulmonary emphysema. This study examined the retention, localization, and fate of endotracheally instilled elastase using /sup 125/I labeled enzyme and immunoperoxidase histochemistry. Porcine pancreatic elastase labeled with /sup 125/I was detected in rat lungs through 96 h after instillation; over half of the label was still present after 7 h. Similar results were obtained when elastase was reacted with a specific, catalytic site inactivator prior to instillation. Trypsin and denatured elastase, however, were cleared much more rapidly from the lung (less than half of the label present after 30 min). When lungs were homogenized after instillation of active elastase, the soluble fraction contained elastase bound to rat alpha1-antitrypsin. In addition, a small amount of label (less than 10%) appeared bound to insoluble components for extended periods of time. Using immunoperoxidase histochemistry, it was found that exogenous elastase was rapidly contained with pulmonary alveolar macrophages, as well as associated with alveolar septums and other parenchymal structures. Similar results were obtained with elastase from both porcine pancreas and human neutrophils. These results suggest that exogenous elastase in the rat, and perhaps endogenous elastolytic enzymes in humans, may have several fates in the lungs: complex formation with endogenous inhibitors, containment within the macrophage, and/or association with connective tissue targets.

  4. [Role of stem cells in the pathogenesis of chronic obstructive pulmonary disease and of pulmonary emphysema].

    PubMed

    Caramori, Gaetano; Casolari, Paolo; Garofano, Elvira; Mazzoni, Federico; Marchi, Irene; Contoli, Marco; Papi, Alberto

    2012-01-01

    There are only few human translational studies performed in the area of stem cell research in patients with chronic obstructive pulmonary disease (COPD) and/or pulmonary emphysema. Before progress to clinical trials with stem cells we believe that more human translational studies are necessaries, otherwise the clinical rationale would be solely based on limited in vitro and animal studies. In the future, stem cell therapy could be a treatment for this disease. Currently, stem cell therapy is still to be considered as an area of active research, lacking a strong rationale for performing clinical trials in COPD. Although stem cells would be likely to represent a heterogeneous population of cells, the different cell subsets and their importance in the pathogenesis of the different clinical phenotypes need to be fully characterised before progressing to clinical trials. Moreover, the potential side effects of the stem cell therapy are often underestimated. We should not ignore that some of the most deadly neoplasms are arising from stem cells.

  5. The Role of Interleukin-23 in the Early Development of Emphysema in HIV1+ Smokers

    PubMed Central

    Barjaktarevic, Igor Z.; Crystal, Ronald G.

    2016-01-01

    Rationale. Matrix metalloproteinase-9 (MMP-9) expression is upregulated in alveolar macrophages (AM) of HIV1+ smokers who develop emphysema. Knowing that lung epithelial lining fluid (ELF) of HIV1+ smokers contains increased levels of inflammatory cytokines compared to HIV1− smokers, we hypothesized that upregulation of lung cytokines in HIV1+ smokers may be functionally related to increased MMP-9 expression. Methods. Cytokine arrays evaluated cytokine protein levels in ELF obtained from 5 groups of individuals: HIV1− healthy nonsmokers, HIV1− healthy smokers, HIV1− smokers with low diffusing capacity (DLCO), HIV1+ nonsmokers, and HIV1+ smokers with low DLCO. Results. Increased levels of the Th17 related cytokine IL-23 were found in HIV1− smokers with low DLCO and HIV1+ smokers and nonsmokers. Relative IL-23 gene expression was increased in AM of HIV1+ individuals, with greater expression in AM of HIV1+ smokers with low DLCO. Infection with HIV1 in vitro induced IL-23 expression in normal AM. IL-23 stimulation of AM/lymphocyte cocultures in vitro induced upregulation of MMP-9. Lung T lymphocytes express receptor IL-23R and interact with AM in order to upregulate MMP-9. Conclusion. This mechanism may contribute to the increased tissue destruction in the lungs of HIV1+ smokers and suggests that Th17 related inflammation may play a role. PMID:27446965

  6. Delayed functional improvement after near-fatal bleeding complication following endobronchial valve therapy for emphysema.

    PubMed

    Baldi, Sergio; Coni, Francesco; Limerutti, Giorgio; Baccega, Massimo; Ruffini, Enrico; Solidoro, Paolo

    2016-01-01

    Endoscopic treatment of emphysema is supported by different methods, including valves, coils and sealants. The mechanism is mainly related to volume reduction of targeted area. Endobronchial valves (EBV) appear the most studied method. In a multicentre randomised study, placement of unidirectional endobronchial valves resulted in a statistically significant functional improvement in the treated cohort compared to the control. Adverse events, occurring post procedure, included COPD exacerbations, haemoptysis, pneumothorax and pneumonia. In our centre we treated 30 patients, between January 2009 and February 2012, with variable improvement of lung function and only mild postoperative complications. The case we report here appears very interesting for the unusual near-fatal complication (massive alveolar haemorrage) followed by delayed strong functional improvement (FEV1 +23%; RV -18%; 6MWD:+33%) six months after the valve placement. This improvement could be attributable to the EBV procedure, but an alternative explanation is that the lung volume reduction may have been enhanced by the complication itself, as an effect of alveolar collapse. PMID:27374220

  7. Acute pulmonary emphysema in death by hanging: a morphometric digital study.

    PubMed

    Castiglioni, Claudia; Baumann, Pia; Fracasso, Tony

    2016-09-01

    Acute pulmonary emphysema (APE) has been described in cases of mechanical asphyxia such as ligature or manual strangulation but not in cases of hanging. In this study, we wanted to verify by morphometric digital analysis of lung tissue whether APE occurs in death by hanging.We investigated 16 cases of hanging (eight complete, eight incomplete), 10 cases of freshwater drowning (positive control group), and 10 cases of acute external bleeding (negative control group). Tissue sections were obtained from each pulmonary lobe. For each slide, five fields were randomly selected. The area of every alveolar space was measured by image analysis software. The mean alveolar area (MAA) was calculated for each group.In incomplete hanging, MAA was significantly higher than that observed in complete hanging and similar to the one observed in freshwater drowning.APE in cases of incomplete hanging can be considered as a sign of vitality. The high number of conditions that can cause alveolar distension (that were excluded in this study) limits the applicability of this vital sign in the routine forensic practice.

  8. The Role of Interleukin-23 in the Early Development of Emphysema in HIV1(+) Smokers.

    PubMed

    Barjaktarevic, Igor Z; Crystal, Ronald G; Kaner, Robert J

    2016-01-01

    Rationale. Matrix metalloproteinase-9 (MMP-9) expression is upregulated in alveolar macrophages (AM) of HIV1(+) smokers who develop emphysema. Knowing that lung epithelial lining fluid (ELF) of HIV1(+) smokers contains increased levels of inflammatory cytokines compared to HIV1(-) smokers, we hypothesized that upregulation of lung cytokines in HIV1(+) smokers may be functionally related to increased MMP-9 expression. Methods. Cytokine arrays evaluated cytokine protein levels in ELF obtained from 5 groups of individuals: HIV1(-) healthy nonsmokers, HIV1(-) healthy smokers, HIV1(-) smokers with low diffusing capacity (DLCO), HIV1(+) nonsmokers, and HIV1(+) smokers with low DLCO. Results. Increased levels of the Th17 related cytokine IL-23 were found in HIV1(-) smokers with low DLCO and HIV1(+) smokers and nonsmokers. Relative IL-23 gene expression was increased in AM of HIV1(+) individuals, with greater expression in AM of HIV1(+) smokers with low DLCO. Infection with HIV1 in vitro induced IL-23 expression in normal AM. IL-23 stimulation of AM/lymphocyte cocultures in vitro induced upregulation of MMP-9. Lung T lymphocytes express receptor IL-23R and interact with AM in order to upregulate MMP-9. Conclusion. This mechanism may contribute to the increased tissue destruction in the lungs of HIV1(+) smokers and suggests that Th17 related inflammation may play a role. PMID:27446965

  9. Acute pulmonary emphysema in death by hanging: a morphometric digital study.

    PubMed

    Castiglioni, Claudia; Baumann, Pia; Fracasso, Tony

    2016-09-01

    Acute pulmonary emphysema (APE) has been described in cases of mechanical asphyxia such as ligature or manual strangulation but not in cases of hanging. In this study, we wanted to verify by morphometric digital analysis of lung tissue whether APE occurs in death by hanging.We investigated 16 cases of hanging (eight complete, eight incomplete), 10 cases of freshwater drowning (positive control group), and 10 cases of acute external bleeding (negative control group). Tissue sections were obtained from each pulmonary lobe. For each slide, five fields were randomly selected. The area of every alveolar space was measured by image analysis software. The mean alveolar area (MAA) was calculated for each group.In incomplete hanging, MAA was significantly higher than that observed in complete hanging and similar to the one observed in freshwater drowning.APE in cases of incomplete hanging can be considered as a sign of vitality. The high number of conditions that can cause alveolar distension (that were excluded in this study) limits the applicability of this vital sign in the routine forensic practice. PMID:27448112

  10. Multicentre European study for the treatment of advanced emphysema with bronchial valves.

    PubMed

    Ninane, Vincent; Geltner, Christian; Bezzi, Michela; Foccoli, Pierfranco; Gottlieb, Jens; Welte, Tobias; Seijo, Luis; Zulueta, Javier J; Munavvar, Mohammed; Rosell, Antoni; Lopez, Marta; Jones, Paul W; Coxson, Harvey O; Springmeyer, Steven C; Gonzalez, Xavier

    2012-06-01

    This multicentre, blinded, sham-controlled study was performed to assess the safety and effectiveness of bronchial valve therapy using a bilateral upper lobe treatment approach without the goal of lobar atelectasis. Patients with upper lobe predominant severe emphysema were randomised to bronchoscopy with (n = 37) or without (n = 36) IBV Valves for a 3-month blinded phase. A positive responder was defined as having both a ≥ 4-point improvement in St George's Respiratory Questionnaire (SGRQ) and a lobar volume shift as measured by quantitative computed tomography. At 3 months, there were eight (24%) positive responders in the treated group versus none (0%) in the control group (p = 0.002). Also, there was a significant shift in volume in the treated group from the upper lobes (mean ± SD -7.3 ± 9.0%) to the non-treated lobes (6.7 ± 14.5%), with minimal change in the control group (p<0.05). Mean SGRQ total score improved in both groups (treatment: -4.3 ± 16.2; control: -3.6 ± 10.7). The procedure and devices were well tolerated and there were no differences in adverse events reported in the treatment and control groups. Treatment with bronchial valves without complete lobar occlusion in both upper lobes was safe, but not effective in the majority of patients.

  11. Lung regeneration by fetal lung tissue implantation in a mouse pulmonary emphysema model.

    PubMed

    Uyama, Koh; Sakiyama, Shoji; Yoshida, Mitsuteru; Kenzaki, Koichiro; Toba, Hiroaki; Kawakami, Yukikiyo; Okumura, Kazumasa; Takizawa, Hiromitsu; Kondo, Kazuya; Tangoku, Akira

    2016-01-01

    The mortality and morbidity of chronic obstructive pulmonary disease are high. However, no radical therapy has been developed to date. The purpose of this study was to evaluate whether fetal mouse lung tissue can grow and differentiate in the emphysematous lung. Fetal lung tissue from green fluorescent protein C57BL/6 mice at 16 days' gestation was used as donor material. Twelve-month-old pallid mice were used as recipients. Donor lungs were cut into small pieces and implanted into the recipient left lung by performing thoracotomy under anesthesia. The recipient mice were sacrificed at day 7, 14, and 28 after implantation and used for histological examination. Well-developed spontaneous pulmonary emphysema was seen in 12-month-old pallid mice. Smooth and continuous connection between implanted fetal lung tissue and recipient lung was recognized. Air space expansion and donor tissue differentiation were observed over time. We could clearly distinguish the border zones between injected tissue and native tissue by the green fluorescence of grafts. Fetal mouse lung fragments survived and differentiated in the emphysematous lung of pallid mice. Implantation of fetal lung tissue in pallid mice might lead to further lung regeneration research from the perspective of respiratory and exercise function. J. Med. Invest. 63: 182-186, August, 2016. PMID:27644555

  12. 107. TOWER STAIRHALL, SECOND FLOOR LANDING, SOUTH WALL, ENTABLATURE SHOWING ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    107. TOWER STAIRHALL, SECOND FLOOR LANDING, SOUTH WALL, ENTABLATURE SHOWING SECTION WITH ALL PAINT REMOVED RANGING FROM TWENTY-FIVE TO FIFTY COATS OF PAINT ON SECTIONS - Independence Hall Complex, Independence Hall, 500 Chestnut Street, Philadelphia, Philadelphia County, PA

  13. Childhood smoking is an independent risk factor for obstructive airways disease in women

    PubMed Central

    Patel, B; Luben, R; Welch, A; Bingham, S; Khaw, K; Day, N; Lomas, D; Wareham, N

    2004-01-01

    Objective: To assess whether starting to smoke in childhood increases the risk of obstructive airways disease (OAD) in adult life. Methods: A retrospective cohort analysis was undertaken of 12 504 current and ex-smokers in the EPIC-Norfolk cohort. The main exposure was starting to smoke during childhood (age <16 years). Three definitions of OAD were used: doctor diagnosed asthma, doctor diagnosed bronchitis/emphysema, and "any OAD" (doctor diagnosed asthma or bronchitis/emphysema, or taking medication used in the treatment of OAD). Results: Childhood smokers had significantly more pack years of exposure and poorer lung function than subjects who started to smoke in adulthood (⩾16 years). Compared with starting in adulthood, starting to smoke in childhood was associated with a greater risk of bronchitis/emphysema in female smokers (OR 1.79, 95% CI 1.25 to 2.56) and ex-smokers of both sexes (OR 1.29, 95% CI 1.07 to 1.55 in men and OR 1.40, 95% CI 1.05 to 1.85 in women), and of "any OAD" in female smokers (OR 1.72, 95% CI 1.24 to 2.38) and male and female ex-smokers (OR 1.20, 95% CI 1.03 to 1.40 in men and 1.34, 95% CI 1.07 to 1.57 in women). After adjustment for pack years, childhood smoking was associated with poorer lung function (FEV1 92.3% predicted in adult smokers and 89.5% in childhood smokers, p = 0.03) and a greater risk of bronchitis/emphysema (adjusted OR 1.55, 95% CI 1.08 to 2.24) and for "any OAD" (OR 1.54, 95% CI 1.10 to 2.13) in female smokers but not in male and female ex-smokers. Conclusion: Starting to smoke in childhood is associated with an increased risk of airways disease because of the extra pack years smoked. In women, childhood smoking is itself an independent risk factor for the development of airways disease. PMID:15282389

  14. Massive pneumatic expansion of lymphatic vessel resulting in cystic lesions in the pulmonary parenchyma: a rare case of persistent interstitial pulmonary emphysema in a non-ventilated infant.

    PubMed

    Fujishiro, Jun; Komuro, Hiroaki; Ono, Kentaro; Urita, Yasuhisa; Shinkai, Toko; Minami, Yuko; Kawabata, Yoshinori; Kishimoto, Hiroshi; Masumoto, Kouji

    2012-12-01

    We report the case of 2-week-old female infant with cystic lung disease who presented with mild tachypnea and had no history of mechanical ventilation. Chest CT demonstrated multiple air-filled cystic lesions in right upper lobe, and the patient subsequently underwent a right upper lobectomy. Histology revealed cystic lesions located in the pulmonary parenchyma and showed that the lesions were lined by lymphatic endothelium and were communicating with dilated lymphatic vessels in the interstitium. Additionally, multinucleated foreign body giant cells were attached to the lumen of the cyst. On the basis of these findings, we considered this a case of persistent interstitial pulmonary emphysema (PIPE) with massive pneumatic expansion of the lymphatic vessels, resulting in cystic lesions with lymphatic endothelium in the pulmonary parenchyma. While PIPE is extremely rare in term non-ventilated infants, our case demonstrated that this disease should be added to the differential diagnosis of cystic lung diseases with lymphatic endothelium even in infants without mechanical ventilation. When cystic lesions and symptoms persist despite conservative treatment, open or thoracoscopic resection is an appropriate option for diagnosis and treatment.

  15. A New Variant of Combined Pulmonary Fibrosis and Emphysema From Second-Hand Smoke: A Case Report and Review of Literature

    PubMed Central

    Khan, Rafay; Tulpule, Sunil; Iroka, Nneka; Sen, Shuvendu; Mathew, Teena; Islam, Mohammad; Yousif, Abdalla; Longo, Stacey

    2015-01-01

    The findings of combined pulmonary fibrosis along with emphysema have been increasingly recognized in the medical literature. Patients presenting with such findings are usually found to be heavy smokers or former smokers. Their presentations begin with severe respiratory distress that gets progressively worse. They are found to have low diffusion capacity (DLCO) although spirometry will show preserved lung volumes. No prior research has presented a documented case of such a fatal condition in a young person with no prior history of smoking. In this case report, we discuss the presentation, diagnosis, and management of a young 29-year-old non-smoker with increasing shortness of breath with a complicated hospital course discovered to have an abnormal variant or presentation of “combined pulmonary fibrosis and emphysema” (CPFE). As most published studies have attributed these findings as a secondary response to a history of smoking, other etiologies and risk factors have yet to be properly analyzed resulting in prolonged hospital course and often missed diagnoses. PMID:26346712

  16. Learning Dilemmas in Undergraduate Student Independent Essays

    ERIC Educational Resources Information Center

    Wendt, Maria; Åse, Cecilia

    2015-01-01

    Essay-writing is generally viewed as the primary learning activity to foster independence and analytical thinking. In this article, we show that independent research projects do not necessarily lead to critical thinking. University-level education on conducting independent projects can, in several respects, counteract enhanced analytical skills.…

  17. Diagnostic Values For Club Cell Secretory Protein (CC16) in Serum of Patients of Combined Pulmonary Fibrosis and Emphysema.

    PubMed

    Kokuho, Nariaki; Ishii, Takeo; Kamio, Koichiro; Hayashi, Hiroki; Kurahara, Misuzu; Hattori, Kumiko; Motegi, Takashi; Azuma, Arata; Gemma, Akihiko; Kida, Kozui

    2015-08-01

    Combined pulmonary fibrosis and emphysema (CPFE) is an under-recognized syndrome for which the diagnostic use of serum biomarkers is an attractive possibility. We hypothesized that CC16 and/or TGF-β1 or combinations with other biomarkers are useful for diagnosing CPFE. Patients with respiratory symptoms and a smoking history, with or without chronic obstructive pulmonary disease, were divided into the following three groups according to findings of high-resolution computed tomography of the chest: controls without either emphysema or fibrosis, patients with emphysema alone, and patients compatible with the diagnosis of CPFE. Serum concentrations of CC16, TGF-β1, SP-D, and KL-6 were measured in patients whose condition was stable for at least 3 months. To investigate changes in biomarkers of lung fibrosis in patients with a life-long smoking history, additional measurements were performed on the patients with idiopathic pulmonary fibrosis (IPF) of smoking history. The mean age of the first three groups was 68.0 years, whereas that of the IPF group was 71.8 years, and the groups contained 36, 115, 27, and 10 individuals, respectively. The serum concentration of CC16 in the four groups was 5.67 ± 0.42, 5.66 ± 0.35, 9.38 ± 1.04 and 22.15 ± 4.64 ng/ml, respectively, indicating that those patients with lung fibrosis had a significantly higher concentration. The combined use of CC16, SP-D, and KL-6 provided supportive diagnosis in conjunction with radiological imaging in diagnosis of CPFE. We conclude that a combination of biomarkers including CC16 could provide useful information to screen and predict the possible diagnosis of CPFE.

  18. Veno-venous extracorporeal membrane oxygenation support during lung volume reduction surgery for a severe respiratory failure patient with emphysema

    PubMed Central

    Li, Xuyan; He, Hangyong

    2016-01-01

    The use of extracorporeal membrane oxygenation (ECMO) in adults has increased in popularity and importance for the support of patients with cardiac or pulmonary failure, but rarely been described as a means of support during anaesthesia and surgery. We report the case of a patient who required lung volume reduction because of emphysema where veno-venous ECMO was required both during surgery and for the first four days postoperatively. We describe the anaesthetic management of this patient who had severe respiratory failure, review other alternatives and discuss why ECMO was particularly suited to this case. PMID:27076979

  19. Inhalation administration of all-trans-retinoic acid for treatment of elastase-induced pulmonary emphysema in Fischer 344 rats.

    PubMed

    March, Thomas H; Cossey, Patricia Y; Esparza, Dolores C; Dix, Kelly J; McDonald, Jacob D; Bowen, Larry E

    2004-01-01

    A past study demonstrated that all-trans-retinoic acid (ATRA) treatment by intraperitoneal injection in a rat model of elastase-induced emphysema caused tissue regeneration as evidenced by a decrease in alveolar size and lung volume and an increase in alveolar number. We postulated that treatment with this retinoid by nose-only inhalation exposure would be a more efficient means of targeting damaged lung tissue. Emphysema was induced in male Fischer 344 rats by intratracheal instillation of pancreatic elastase (0.5 IU/g body weight). Four weeks after elastase instillation, animals were treated once daily, 4 days/week, for 3 weeks by exposing them nose-only to aerosolized ATRA (target concentration-time of 3000 or 15,000 mg-min/m3) or by injecting them intraperitoneally with ATRA in cottonseed oil (0.5 or 2.5 mg/kg). Based on estimates of particle deposition in the respiratory tract, inhalation doses were chosen to be consistent with injected doses. Lungs were fixed by inflation with formalin (constant pressure for 6 hours followed by >48 hours of immersion) and were embedded in paraffin. Sections were evaluated by histopathology and stereology. Inhalation exposure to ATRA at both aerosol concentrations caused significant elevations of ATRA in the lung, whereas only the high-dose injection treatment was associated with an elevation of lung ATRA. The mean ATRA concentration from lungs of rats in the high-dose inhalation exposure groups as measured by liquid chromatography--mass spectrometry was approximately 12-fold greater than that of high-dose injection-treated rats. Elastase instillation caused increased lung volumes, irregular alveolar air space enlargement, and fragmentation and attenuation of alveolar septa. Neither inhaled nor injected ATRA reduced the enlarged lung volumes associated with this emphysema model. Stereology demonstrated that alveolar air space enlargement in ATRA-treated rats was similar to that in sham-treated emphysematous animals. Thus

  20. Influence of pulmonary emphysema on COPD assessment test-oriented categorization in GOLD document

    PubMed Central

    Suzuki, Toshio; Tada, Yuji; Kawata, Naoko; Ikari, Jun; Kasahara, Yasunori; Sakurai, Yoriko; Iesato, Ken; Nishimura, Rintaro; West, James; Tatsumi, Koichiro

    2015-01-01

    Background The COPD assessment test (CAT) score is a key component of the multifactorial assessment of COPD in the Global initiative for chronic Obstructive Lung Disease (GOLD) guidelines of 2014. Nevertheless, little is known regarding the differences among COPD categories in terms of clinical parameters such as pulmonary function or radiological findings. Thus, our aims in this study were to evaluate the associations between CAT scores and pulmonary clinical parameters, and to investigate factors that could discriminate between a “less symptomatic group” (categories A and C) and a “more symptomatic group” (categories B and D) among stable COPD patients. Methods We enrolled 200 outpatients at Chiba University Hospital. Study subjects were assessed by CAT, pulmonary function testing, and multidetector computed tomography (MDCT). We assessed possible correlations between these indices. Results CAT scores were negatively correlated with percentage of the forced expiratory volume in 1 second predicted value (FEV1 %predicted) and percentage of the diffusing capacity for carbon monoxide per liter of lung volume predicted value (DLCO/VA [%predicted]) results and positively correlated with low attenuation volume percentage (LAV%) and residual volume to total lung capacity ratios (RV/TLC). In the “more symptomatic group” (category B or D), the mean DLCO/VA (%predicted) was significantly lower and the mean LAV% and RV/TLC was significantly higher than those in the “less symptomatic group” (category A or C), respectively. Interestingly, those in category B had higher mean LAV% compared to those in category C. Conclusion CAT scores were significantly correlated with pulmonary function parameters and emphysematous changes on MDCT. The new GOLD classification system would be a step toward a phenotypic approach, especially taking into account the degree of emphysema and hyperinflation. PMID:26150711

  1. Congenital lobar emphysema: 30-year case series in two university hospitals*

    PubMed Central

    Cataneo, Daniele Cristina; Rodrigues, Olavo Ribeiro; Hasimoto, Erica Nishida; Schmidt, Aurelino Fernandes; Cataneo, Antonio José Maria

    2013-01-01

    OBJECTIVE: To review the cases of patients with congenital lobar emphysema (CLE) submitted to surgical treatment at two university hospitals over a 30-year period. METHODS: We reviewed the medical records of children with CLE undergoing surgical treatment between 1979 and 2009 at the Botucatu School of Medicine Hospital das Clínicas or the Mogi das Cruzes University Hospital. We analyzed data regarding symptoms, physical examination, radiographic findings, diagnosis, surgical treatment, and postoperative follow-up. RESULTS: During the period studied, 20 children with CLE underwent surgery. The mean age at the time of surgery was 6.9 months (range, 9 days to 4 years). All of the cases presented with symptoms at birth or during the first months of life. In all cases, chest X-rays were useful in defining the diagnosis. In cases of moderate respiratory distress, chest CT facilitated the diagnosis. One patient with severe respiratory distress was misdiagnosed with hypertensive pneumothorax and underwent chest tube drainage. Only patients with moderate respiratory distress were submitted to bronchoscopy, which revealed no tracheobronchial abnormalities. The surgical approach was lateral muscle-sparing thoracotomy. The left upper and middle lobes were the most often affected, followed by the right upper lobe. Lobectomy was performed in 18 cases, whereas bilobectomy was performed in 2 (together with bronchogenic cyst resection in 1 of those). No postoperative complications were observed. Postoperative follow-up time was at least 24 months (mean, 60 months), and no late complications were observed. CONCLUSIONS: Although CLE is an uncommon, still neglected disease of uncertain etiology, the radiological diagnosis is easily made and surgical treatment is effective. PMID:24068262

  2. Haptic Tracking Permits Bimanual Independence

    ERIC Educational Resources Information Center

    Rosenbaum, David A.; Dawson, Amanda A.; Challis, John H.

    2006-01-01

    This study shows that in a novel task--bimanual haptic tracking--neurologically normal human adults can move their 2 hands independently for extended periods of time with little or no training. Participants lightly touched buttons whose positions were moved either quasi-randomly in the horizontal plane by 1 or 2 human drivers (Experiment 1), in…

  3. Fostering Musical Independence

    ERIC Educational Resources Information Center

    Shieh, Eric; Allsup, Randall Everett

    2016-01-01

    Musical independence has always been an essential aim of musical instruction. But this objective can refer to everything from high levels of musical expertise to more student choice in the classroom. While most conceptualizations of musical independence emphasize the demonstration of knowledge and skills within particular music traditions, this…

  4. Independent vs. Laboratory Papers.

    ERIC Educational Resources Information Center

    Wilson, Clint C., II

    1981-01-01

    Comparisons of independent and laboratory newspapers at selected California colleges indicated that (1) the independent newspapers were superior in editorial opinion and leadership characteristics; (2) the laboratory newspapers made better use of photography, art, and graphics; and (3) professional journalists highly rated their laboratory…

  5. Independence of Internal Auditors.

    ERIC Educational Resources Information Center

    Montondon, Lucille; Meixner, Wilda F.

    1993-01-01

    A survey of 288 college and university auditors investigated patterns in their appointment, reporting, and supervisory practices as indicators of independence and objectivity. Results indicate a weakness in the positioning of internal auditing within institutions, possibly compromising auditor independence. Because the auditing function is…

  6. American Independence. Fifth Grade.

    ERIC Educational Resources Information Center

    Crosby, Annette

    This fifth grade teaching unit covers early conflicts between the American colonies and Britain, battles of the American Revolutionary War, and the Declaration of Independence. Knowledge goals address the pre-revolutionary acts enforced by the British, the concepts of conflict and independence, and the major events and significant people from the…

  7. [Bronchoscopic lung volume reduction (BLVR) in advanced pulmonary emphysema: dreams of the future or much ado about nothing?].

    PubMed

    Stanzel, F

    2012-01-01

    Bronchoscopic lung volume reduction (BLVR) is a rapidly developing area and at present it is being intensively evaluated and discussed. There is a great interest in developing new treatment modalities that can reduce lung volume and air trapping without the risk of a surgical intervention. The different techniques of BLVR are characterised by lower morbidity and mortality, but by a more limited effect too. The placement of valves leads to blockade of the airway and sometimes to absorption atelectasis. The valves have been most intensively evaluated and are frequently applied. Beside the blocking devices there are partially blocking or deforming devices available as coils that are introduced in heterogeneous emphysema. Irreversible procedures such as polymeric lung volume reduction or thermal vapour ablation are used too. The creation of airway bypasses to allow trapped air to escape is mainly employed in homogenous emphysema. Following such by-pass creation there is an increase of lung function tests and a reduction of dyspnea, but only for a limited time. The bypass procedure has disappeared from bronchoscopy units completely. We give a review of the recent developments regarding BLVR and the state of the art.

  8. 1. DELAWARE AVE. (right, looking north) AND WASHINGTON AVE. SHOWING ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. DELAWARE AVE. (right, looking north) AND WASHINGTON AVE. SHOWING GLORIA DEI CHURCH (note steeple) - Independence National Historical Park, Walnut, Sixth, Chestnut & Second Streets, Philadelphia, Philadelphia County, PA

  9. Evaluating Reanalysis - Independent Observations and Observation Independence

    NASA Astrophysics Data System (ADS)

    Wahl, S.; Bollmeyer, C.; Danek, C.; Friederichs, P.; Keller, J. D.; Ohlwein, C.

    2014-12-01

    Reanalyses on global to regional scales are widely used for validation of meteorological or hydrological models and for many climate applications. However, the evaluation of the reanalyses itself is still a crucial task. A major challenge is the lack of independent observations, since most of the available observational data is already included, e. g. by the data assimilation scheme. Here, we focus on the evaluation of dynamical reanalyses which are obtained by using numerical weather prediction models with a fixed data assimilation scheme. Precipitation is generally not assimilated in dynamical reanalyses (except for e.g. latent heat nudging) and thereby provides valuable data for the evaluation of reanalysis. Since precipitation results from the complex dynamical and microphysical atmospheric processes, an accurate representation of precipitation is often used as an indicator for a good model performance. Here, we use independent observations of daily precipitation accumulations from European rain gauges (E-OBS) of the years 2008 and 2009 for the intercomparison of various regional reanalyses products for the European CORDEX domain (Hirlam reanalysis at 0.2°, Metoffice UM reanalysis at 0.11°, COSMO reanalysis at 0.055°). This allows for assessing the benefits of increased horizontal resolution compared to global reanalyses. Furthermore, the effect of latent heat nudging (assimilation of radar-derived rain rates) is investigated using an experimental setup of the COSMO reanalysis with 6km and 2km resolution for summer 2011. Further, we present an observation independent evaluation based on kinetic energy spectra. Such spectra should follow a k-3 dependence of the wave number k for the larger scale, and a k-5/3 dependence on the mesoscale. We compare the spectra of the aforementioned regional reanalyses in order to investigate the general capability of the reanalyses to resolve events on the mesoscale (e.g. effective resolution). The intercomparison and

  10. In vivo lung morphometry with hyperpolarized 3He diffusion MRI in canines with induced emphysema: disease progression and comparison with computed tomography.

    PubMed

    Tanoli, Tariq S K; Woods, Jason C; Conradi, Mark S; Bae, Kyongtae Ty; Gierada, David S; Hogg, James C; Cooper, Joel D; Yablonskiy, Dmitriy A

    2007-01-01

    Despite a long history of development, diagnostic tools for in vivo regional assessment of lungs in patients with pulmonary emphysema are not yet readily available. Recently, a new imaging technique, in vivo lung morphometry, was introduced by our group. This technique is based on MRI measurements of diffusion of hyperpolarized (3)He gas in lung air spaces and provides quantitative in vivo tomographic information on lung microstructure at the level of the acinar airways. Compared with standard diffusivity measurements that strongly depend on pulse sequence parameters (mainly diffusion time), our approach evaluates a "hard number," the average acinar airway radius. For healthy dogs, we find here a mean acinar airway radius of approximately 0.3 mm compared with 0.36 mm in healthy humans. The purpose of the present study is the application of this technique for quantification of emphysema progression in dogs with experimentally induced disease. The diffusivity measurements and resulting acinar airway geometrical characteristics were correlated with the local lung density and local lung-specific air volume calculated from quantitative computed tomography data obtained on the same dogs. The results establish an important association between the two modalities. The observed sensitivity of our method to emphysema progression suggests that this technique has potential for the diagnosis of emphysema and tracking of disease progression or improvement via a pharmaceutical intervention.

  11. Breakdown of lung framework and an increase in pores of Kohn as initial events of emphysema and a cause of reduction in diffusing capacity

    PubMed Central

    Yoshikawa, Akira; Sato, Shuntaro; Tanaka, Tomonori; Hashisako, Mikiko; Kashima, Yukio; Tsuchiya, Tomoshi; Yamasaki, Naoya; Nagayasu, Takeshi; Yamamoto, Hiroshi; Fukuoka, Junya

    2016-01-01

    Purpose Pulmonary emphysema is the pathological prototype of chronic obstructive pulmonary disease and is also associated with other lung diseases. We considered that observation with different approaches may provide new insights for the pathogenesis of emphysema. Patients and methods We reviewed tissue blocks of the lungs of 25 cases with/without emphysema and applied a three-dimensional observation method to the blocks. Based on the three-dimensional characteristics of the alveolar structure, we considered one face of the alveolar polyhedron as a structural unit of alveoli and called it a framework unit (FU). We categorized FUs based on their morphological characteristics and counted their number to evaluate the destructive changes in alveoli. We also evaluated the number and the area of pores of Kohn in FUs. We performed linear regression analysis to estimate the effect of these data on pulmonary function tests. Results In multivariable regression analysis, a decrease in the number of FUs without an alveolar wall led to a significant decrease in the diffusing capacity of the lung for carbon monoxide (DLCO) and DLCO per unit alveolar volume, and an increase in the area of pores of Kohn had a significant effect on an increase in residual capacity. Conclusion A breakdown in the lung framework and an increase in pores of Kohn are associated with a decrease in DLCO and DLCO per unit alveolar volume with/without emphysema. PMID:27695315

  12. Beta-cryptoxanthin restores nicotine-reduced lung SIRT1 to normal levels and inhibits nicotine-promoted lung tumorigenesis and emphysema in A/J mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nicotine, a large constituent of cigarette smoke, is associated with an increased risk of lung cancer, but the data supporting this relationship are inconsistent. Here, we found that nicotine treatment not only induced emphysema but also increased both lung tumor multiplicity and volume in 4-nitrosa...

  13. Keratinocyte Growth Factor Gene Electroporation into Skeletal Muscle as a Novel Gene Therapeutic Approach for Elastase-Induced Pulmonary Emphysema in Mice

    PubMed Central

    Tobinaga, Shuichi; Matsumoto, Keitaro; Nagayasu, Takeshi; Furukawa, Katsuro; Abo, Takafumi; Yamasaki, Naoya; Tsuchiya, Tomoshi; Miyazaki, Takuro; Koji, Takehiko

    2015-01-01

    Pulmonary emphysema is a progressive disease with airspace destruction and an effective therapy is needed. Keratinocyte growth factor (KGF) promotes pulmonary epithelial proliferation and has the potential to induce lung regeneration. The aim of this study was to determine the possibility of using KGF gene therapy for treatment of a mouse emphysema model induced by porcine pancreatic elastase (PPE). Eight-week-old BALB/c male mice treated with intra-tracheal PPE administration were transfected with 80 μg of a recombinant human KGF (rhKGF)-expressing FLAG-CMV14 plasmid (pKGF-FLAG gene), or with the pFLAG gene expressing plasmid as a control, into the quadriceps muscle by electroporation. In the lung, the expression of proliferating cell nuclear antigen (PCNA) was augmented, and surfactant protein A (SP-A) and KGF receptor (KGFR) were co-expressed in PCNA-positive cells. Moreover, endogenous KGF and KGFR gene expression increased significantly by pKGF-FLAG gene transfection. Arterial blood gas analysis revealed that the PaO2 level was not significantly reduced on day 14 after PPE instillation with pKGF-FLAG gene transfection compared to that of normal mice. These results indicated that KGF gene therapy with electroporation stimulated lung epithelial proliferation and protected depression of pulmonary function in a mouse emphysema model, suggesting a possible method of treating pulmonary emphysema. PMID:26160987

  14. Keratinocyte Growth Factor Gene Electroporation into Skeletal Muscle as a Novel Gene Therapeutic Approach for Elastase-Induced Pulmonary Emphysema in Mice.

    PubMed

    Tobinaga, Shuichi; Matsumoto, Keitaro; Nagayasu, Takeshi; Furukawa, Katsuro; Abo, Takafumi; Yamasaki, Naoya; Tsuchiya, Tomoshi; Miyazaki, Takuro; Koji, Takehiko

    2015-06-29

    Pulmonary emphysema is a progressive disease with airspace destruction and an effective therapy is needed. Keratinocyte growth factor (KGF) promotes pulmonary epithelial proliferation and has the potential to induce lung regeneration. The aim of this study was to determine the possibility of using KGF gene therapy for treatment of a mouse emphysema model induced by porcine pancreatic elastase (PPE). Eight-week-old BALB/c male mice treated with intra-tracheal PPE administration were transfected with 80 μg of a recombinant human KGF (rhKGF)-expressing FLAG-CMV14 plasmid (pKGF-FLAG gene), or with the pFLAG gene expressing plasmid as a control, into the quadriceps muscle by electroporation. In the lung, the expression of proliferating cell nuclear antigen (PCNA) was augmented, and surfactant protein A (SP-A) and KGF receptor (KGFR) were co-expressed in PCNA-positive cells. Moreover, endogenous KGF and KGFR gene expression increased significantly by pKGF-FLAG gene transfection. Arterial blood gas analysis revealed that the PaO2 level was not significantly reduced on day 14 after PPE instillation with pKGF-FLAG gene transfection compared to that of normal mice. These results indicated that KGF gene therapy with electroporation stimulated lung epithelial proliferation and protected depression of pulmonary function in a mouse emphysema model, suggesting a possible method of treating pulmonary emphysema.

  15. Breakdown of lung framework and an increase in pores of Kohn as initial events of emphysema and a cause of reduction in diffusing capacity

    PubMed Central

    Yoshikawa, Akira; Sato, Shuntaro; Tanaka, Tomonori; Hashisako, Mikiko; Kashima, Yukio; Tsuchiya, Tomoshi; Yamasaki, Naoya; Nagayasu, Takeshi; Yamamoto, Hiroshi; Fukuoka, Junya

    2016-01-01

    Purpose Pulmonary emphysema is the pathological prototype of chronic obstructive pulmonary disease and is also associated with other lung diseases. We considered that observation with different approaches may provide new insights for the pathogenesis of emphysema. Patients and methods We reviewed tissue blocks of the lungs of 25 cases with/without emphysema and applied a three-dimensional observation method to the blocks. Based on the three-dimensional characteristics of the alveolar structure, we considered one face of the alveolar polyhedron as a structural unit of alveoli and called it a framework unit (FU). We categorized FUs based on their morphological characteristics and counted their number to evaluate the destructive changes in alveoli. We also evaluated the number and the area of pores of Kohn in FUs. We performed linear regression analysis to estimate the effect of these data on pulmonary function tests. Results In multivariable regression analysis, a decrease in the number of FUs without an alveolar wall led to a significant decrease in the diffusing capacity of the lung for carbon monoxide (DLCO) and DLCO per unit alveolar volume, and an increase in the area of pores of Kohn had a significant effect on an increase in residual capacity. Conclusion A breakdown in the lung framework and an increase in pores of Kohn are associated with a decrease in DLCO and DLCO per unit alveolar volume with/without emphysema.

  16. Data Machine Independence

    1994-12-30

    Data-machine independence achieved by using four technologies (ASN.1, XDR, SDS, and ZEBRA) has been evaluated by encoding two different applications in each of the above; and their results compared against the standard programming method using C.

  17. Media independent interface

    NASA Technical Reports Server (NTRS)

    1987-01-01

    The work done on the Media Independent Interface (MII) Interface Control Document (ICD) program is described and recommendations based on it were made. Explanations and rationale for the content of the ICD itself are presented.

  18. Plan Showing Cross Bracing Under Upper Stringers, Typical Section Showing ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Plan Showing Cross Bracing Under Upper Stringers, Typical Section Showing End Framing, Plan Showing Cross Bracing Under Lower Stringers, End Elevation - Covered Bridge, Spanning Contoocook River, Hopkinton, Merrimack County, NH

  19. Independent NOAA considered

    NASA Astrophysics Data System (ADS)

    Richman, Barbara T.

    A proposal to pull the National Oceanic and Atmospheric Administration (NOAA) out of the Department of Commerce and make it an independent agency was the subject of a recent congressional hearing. Supporters within the science community and in Congress said that an independent NOAA will benefit by being more visible and by not being tied to a cabinet-level department whose main concerns lie elsewhere. The proposal's critics, however, cautioned that making NOAA independent could make it even more vulnerable to the budget axe and would sever the agency's direct access to the President.The separation of NOAA from Commerce was contained in a June 1 proposal by President Ronald Reagan that also called for all federal trade functions under the Department of Commerce to be reorganized into a new Department of International Trade and Industry (DITI).

  20. Independent technical review, handbook

    SciTech Connect

    Not Available

    1994-02-01

    Purpose Provide an independent engineering review of the major projects being funded by the Department of Energy, Office of Environmental Restoration and Waste Management. The independent engineering review will address questions of whether the engineering practice is sufficiently developed to a point where a major project can be executed without significant technical problems. The independent review will focus on questions related to: (1) Adequacy of development of the technical base of understanding; (2) Status of development and availability of technology among the various alternatives; (3) Status and availability of the industrial infrastructure to support project design, equipment fabrication, facility construction, and process and program/project operation; (4) Adequacy of the design effort to provide a sound foundation to support execution of project; (5) Ability of the organization to fully integrate the system, and direct, manage, and control the execution of a complex major project.

  1. Pneumomediastinum, subcutaneous emphysema, and pneumothorax after a pulmonary function testing in a patient with bleomycin-induced interstitial pneumonitis*

    PubMed Central

    Araujo, Mariana Sponholz; Fernandes, Frederico Leon Arrabal; Kay, Fernando Uliana; Carvalho, Carlos Roberto Ribeiro

    2013-01-01

    Spontaneous pneumomediastinum is an uncommon event, the clinical picture of which includes retrosternal chest pain, subcutaneous emphysema, dyspnea, and dysphonia. The pathophysiological mechanism involved is the emergence of a pressure gradient between the alveoli and surrounding structures, causing alveolar rupture with subsequent dissection of the peribronchovascular sheath and infiltration of the mediastinum and subcutaneous tissue with air. Known triggers include acute exacerbations of asthma and situations that require the Valsalva maneuver. We described and documented with HRCT scans the occurrence of pneumomediastinum after a patient with bleomycin-induced interstitial lung disease underwent pulmonary function testing. Although uncommon, the association between pulmonary function testing and air leak syndromes has been increasingly reported in the literature, and lung diseases, such as interstitial lung diseases, include structural changes that facilitate the occurrence of this complication. PMID:24310635

  2. Independence and Survival.

    ERIC Educational Resources Information Center

    James, H. Thomas

    Independent schools that are of viable size, well managed, and strategically located to meet competition will survive and prosper past the current financial crisis. We live in a complex technological society with insatiable demands for knowledgeable people to keep it running. The future will be marked by the orderly selection of qualified people,…

  3. Independence, Disengagement, and Discipline

    ERIC Educational Resources Information Center

    Rubin, Ron

    2012-01-01

    School disengagement is linked to a lack of opportunities for students to fulfill their needs for independence and self-determination. Young people have little say about what, when, where, and how they will learn, the criteria used to assess their success, and the content of school and classroom rules. Traditional behavior management discourages…

  4. Caring about Independent Lives

    ERIC Educational Resources Information Center

    Christensen, Karen

    2010-01-01

    With the rhetoric of independence, new cash for care systems were introduced in many developed welfare states at the end of the 20th century. These systems allow local authorities to pay people who are eligible for community care services directly, to enable them to employ their own careworkers. Despite the obvious importance of the careworker's…

  5. Independent School Governance.

    ERIC Educational Resources Information Center

    Beavis, Allan K.

    Findings of a study that examined the role of the governing body in the independent school's self-renewing processes are presented in this paper. From the holistic paradigm, the school is viewed as a self-renewing system that is able to maintain its identity despite environmental changes through existing structures that define and create…

  6. 8. Detail showing concrete abutment, showing substructure of bridge, specifically ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    8. Detail showing concrete abutment, showing substructure of bridge, specifically west side of arch and substructure. - Presumpscot Falls Bridge, Spanning Presumptscot River at Allen Avenue extension, 0.75 mile west of U.S. Interstate 95, Falmouth, Cumberland County, ME

  7. 28. MAP SHOWING LOCATION OF ARVFS FACILITY AS BUILT. SHOWS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    28. MAP SHOWING LOCATION OF ARVFS FACILITY AS BUILT. SHOWS LINCOLN BOULEVARD, BIG LOST RIVER, AND NAVAL REACTORS FACILITY. F.C. TORKELSON DRAWING NUMBER 842-ARVFS-101-2. DATED OCTOBER 12, 1965. INEL INDEX CODE NUMBER: 075 0101 851 151969. - Idaho National Engineering Laboratory, Advanced Reentry Vehicle Fusing System, Scoville, Butte County, ID

  8. Agent independent task planning

    NASA Technical Reports Server (NTRS)

    Davis, William S.

    1990-01-01

    Agent-Independent Planning is a technique that allows the construction of activity plans without regard to the agent that will perform them. Once generated, a plan is then validated and translated into instructions for a particular agent, whether a robot, crewmember, or software-based control system. Because Space Station Freedom (SSF) is planned for orbital operations for approximately thirty years, it will almost certainly experience numerous enhancements and upgrades, including upgrades in robotic manipulators. Agent-Independent Planning provides the capability to construct plans for SSF operations, independent of specific robotic systems, by combining techniques of object oriented modeling, nonlinear planning and temporal logic. Since a plan is validated using the physical and functional models of a particular agent, new robotic systems can be developed and integrated with existing operations in a robust manner. This technique also provides the capability to generate plans for crewmembers with varying skill levels, and later apply these same plans to more sophisticated robotic manipulators made available by evolutions in technology.

  9. International exploration by independents

    SciTech Connect

    Bertagne, R.G. )

    1991-03-01

    Recent industry trends indicate that the smaller US independents are looking at foreign exploration opportunities as one of the alternatives for growth in the new age of exploration. It is usually accepted that foreign finding costs per barrel are substantially lower than domestic because of the large reserve potential of international plays. To get involved overseas requires, however, an adaptation to different cultural, financial, legal, operational, and political conditions. Generally foreign exploration proceeds at a slower pace than domestic because concessions are granted by the government, or are explored in partnership with the national oil company. First, a mid- to long-term strategy, tailored to the goals and the financial capabilities of the company, must be prepared; it must be followed by an ongoing evaluation of quality prospects in various sedimentary basins, and a careful planning and conduct of the operations. To successfully explore overseas also requires the presence on the team of a minimum number of explorationists and engineers thoroughly familiar with the various exploratory and operational aspects of foreign work, having had a considerable amount of onsite experience in various geographical and climatic environments. Independents that are best suited for foreign expansion are those that have been financially successful domestically, and have a good discovery track record. When properly approached foreign exploration is well within the reach of smaller US independents and presents essentially no greater risk than domestic exploration; the reward, however, can be much larger and can catapult the company into the big leagues.

  10. International exploration by independent

    SciTech Connect

    Bertragne, R.G.

    1992-04-01

    Recent industry trends indicate that the smaller U.S. independents are looking at foreign exploration opportunities as one of the alternatives for growth in the new age of exploration. Foreign finding costs per barrel usually are accepted to be substantially lower than domestic costs because of the large reserve potential of international plays. To get involved in overseas exploration, however, requires the explorationist to adapt to different cultural, financial, legal, operational, and political conditions. Generally, foreign exploration proceeds at a slower pace than domestic exploration because concessions are granted by a country's government, or are explored in partnership with a national oil company. First, the explorationist must prepare a mid- to long-term strategy, tailored to the goals and the financial capabilities of the company; next, is an ongoing evaluation of quality prospects in various sedimentary basins, and careful planning and conduct of the operations. To successfully explore overseas also requires the presence of a minimum number of explorationists and engineers thoroughly familiar with the various exploratory and operational aspects of foreign work. Ideally, these team members will have had a considerable amount of on-site experience in various countries and climates. Independents best suited for foreign expansion are those who have been financially successful in domestic exploration. When properly approached, foreign exploration is well within the reach of smaller U.S. independents, and presents essentially no greater risk than domestic exploration; however, the reward can be much larger and can catapult the company into the 'big leagues.'

  11. 5. GENERAL VIEW OF ENTRANCE ROAD SHOWING WALKWAY TO ADMINISTRATIVE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. GENERAL VIEW OF ENTRANCE ROAD SHOWING WALKWAY TO ADMINISTRATIVE SITE, INTERNAL POLICE POST AND MILITARY POLICE POST, LOOKING NORTHNORHTEAST. - Manzanar War Relocation Center, Owens Valley off U.S. Highway 395, 6 miles South of Independence, Independence, Inyo County, CA

  12. Experimental study of pulmonary emphysema in rats exposed to coal dust and papain: effects on the infrastructure and the cell dynamics

    SciTech Connect

    Martin, J.C.; Daniel, H.; LeBouffant, L.

    1980-01-01

    Experimental lesions of emphysema were produced in SPF rats after laryngotracheal injection of papain and coal dust. The infrastructural changes were investigated at different intervals. The lesions observed are progressive, characterized by atrophy and ruptures of the interalveolar septa, and the disappearance of pneumocytes II. Passage through the septa of mineral particles is enhanced and total dust clearance seems to be increased. The results are discussed in the light of alveolar clearance studies using Fe-59 and surface tension measurements on pulmonary washings.

  13. Cigarette smoke-induced emphysema in A/J mice is associated with pulmonary oxidative stress, apoptosis of lung cells, and global alterations in gene expression

    PubMed Central

    Rangasamy, Tirumalai; Misra, Vikas; Zhen, Lijie; Tankersley, Clarke G.; Tuder, Rubin M.; Biswal, Shyam

    2009-01-01

    Cigarette smoking is the major risk factor for developing chronic obstructive pulmonary disease, the fourth leading cause of deaths in the United States. Despite recent advances, the molecular mechanisms involved in the initiation and progression of this disease remain elusive. We used Affymetrix Gene Chip arrays to determine the temporal alterations in global gene expression during the progression of pulmonary emphysema in A/J mice. Chronic cigarette smoke (CS) exposure caused pulmonary emphysema in A/J mice, which was associated with pronounced bronchoalveolar inflammation, enhanced oxidative stress, and increased apoptosis of alveolar septal cells. Microarray analysis revealed the upregulation of 1,190, 715, 260, and 246 genes and the downregulation of 1,840, 730, 442, and 236 genes in the lungs of mice exposed to CS for 5 h, 8 days, and 1.5 and 6 mo, respectively. Most of the genes belong to the functional categories of phase I genes, Nrf2-regulated antioxidant and phase II genes, phase III detoxification genes, and others including immune/inflammatory response genes. Induction of the genes encoding multiple phase I enzymes was markedly higher in the emphysematous lungs, whereas reduced expression of various cytoprotective genes constituting ubiquitin-proteasome complex, cell survival pathways, solute carriers and transporters, transcription factors, and Nrf2-regulated antioxidant and phase II-responsive genes was noted. Our data indicate that the progression of CS-induced emphysema is associated with a steady decline in the expression of various genes involved in multiple pathways in the lungs of A/J mice. Many of the genes discovered in this study could rationally play an important role in the susceptibility to CS-induced emphysema. PMID:19286929

  14. What Do Blood Tests Show?

    MedlinePlus

    ... shows the ranges for blood glucose levels after 8 to 12 hours of fasting (not eating). It shows the normal range and the abnormal ranges that are a sign of prediabetes or diabetes. Plasma Glucose Results (mg/dL)* Diagnosis 70 to 99 ...

  15. Influence of experimental pulmonary emphysema on toxicological effects from inhaled nitrogen dioxide and diesel exhaust. Research report, January 1984-September 1987

    SciTech Connect

    Mauderly, J.L.; Bice, D.E.; Cheng, Y.S.; Gillett, N.A.; Henderson, R.F.

    1990-02-01

    The hypothesis tested in the project was that rats with preexisting experimentally-induced pulmonary emphysema were more susceptible than rats with normal lungs to the adverse effects of exposure to NO(sub 2) or diesel exhaust. Rats were exposed by inhalation seven hr/day, five day/wk, for 24 months to NO(sub 2) at 9.5 ppm, or to diesel exhaust at 3.5 mg soot/cu m, or to clean air. Pulmonary emphysema was induced in one-half of the rats by intratracheal instillation of elastase, six weeks before exposures. Nonneoplastic endpoints were evaluated after 12, 18, and 24 months of exposure. Nitrogen dioxide exposure of normal rats caused mild epithelial hyperplasia and inflammation in proximal alveoli. Significant interactions between the influences of emphysema and nitrogen dioxide were demonstrated to be additive for four parameters (out of 61 parameters). Diesel-exhaust exposure of normal rats caused progressive, focal inflammation, and epithelial proliferation. The final soot lung burden was only one-third of that in nonemphysematous lungs.

  16. Circulating soluble receptor for advanced glycation end products (sRAGE) as a biomarker of emphysema and the RAGE axis in the lung.

    PubMed

    Yonchuk, John G; Silverman, Edwin K; Bowler, Russell P; Agustí, Alvar; Lomas, David A; Miller, Bruce E; Tal-Singer, Ruth; Mayer, Ruth J

    2015-10-01

    Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disease that has been traditionally characterized by incompletely reversible airflow limitation. Yet, the latter is poorly correlated with many other clinically relevant characteristics of the disease. Thus, the identification of biomarkers to more accurately assess this heterogeneity and disease severity may facilitate the discovery and development of new treatments and better management of patients with COPD. One molecule that has attracted attention as a potentially useful biomarker specifically for the emphysema subpopulation is the soluble receptor for advanced glycation end products (sRAGE). As the soluble isoform of a key proinflammatory signaling receptor, sRAGE acts as a "decoy" for RAGE ligands and prevents their interaction with the receptor. Multiple reports have now linked sRAGE to COPD, and more specifically to emphysema, and evidence is accumulating that this link is likely mechanistic in nature. Here we review the current state of knowledge about sRAGE biology, the mechanistic links to COPD, and the evidence for using it as a biomarker for emphysema. We also discuss sRAGE as a potential target for therapeutic intervention in COPD.

  17. Independent Component Analysis of Textures

    NASA Technical Reports Server (NTRS)

    Manduchi, Roberto; Portilla, Javier

    2000-01-01

    A common method for texture representation is to use the marginal probability densities over the outputs of a set of multi-orientation, multi-scale filters as a description of the texture. We propose a technique, based on Independent Components Analysis, for choosing the set of filters that yield the most informative marginals, meaning that the product over the marginals most closely approximates the joint probability density function of the filter outputs. The algorithm is implemented using a steerable filter space. Experiments involving both texture classification and synthesis show that compared to Principal Components Analysis, ICA provides superior performance for modeling of natural and synthetic textures.

  18. Cary Potter on Independent Education

    ERIC Educational Resources Information Center

    Potter, Cary

    1978-01-01

    Cary Potter was President of the National Association of Independent Schools from 1964-1978. As he leaves NAIS he gives his views on education, on independence, on the independent school, on public responsibility, on choice in a free society, on educational change, and on the need for collective action by independent schools. (Author/RK)

  19. Myth or Truth: Independence Day.

    ERIC Educational Resources Information Center

    Gardner, Traci

    Most Americans think of the Fourth of July as Independence Day, but is it really the day the U.S. declared and celebrated independence? By exploring myths and truths surrounding Independence Day, this lesson asks students to think critically about commonly believed stories regarding the beginning of the Revolutionary War and the Independence Day…

  20. Satellite Movie Shows Erika Dissipate

    NASA Video Gallery

    This animation of visible and infrared imagery from NOAA's GOES-West satellite from Aug. 27 to 29 shows Tropical Storm Erika move through the Eastern Caribbean Sea and dissipate near eastern Cuba. ...

  1. Products of Independent Elliptic Random Matrices

    NASA Astrophysics Data System (ADS)

    O'Rourke, Sean; Renfrew, David; Soshnikov, Alexander; Vu, Van

    2015-07-01

    For fixed , we study the product of independent elliptic random matrices as tends to infinity. Our main result shows that the empirical spectral distribution of the product converges, with probability , to the -th power of the circular law, regardless of the joint distribution of the mirror entries in each matrix. This leads to a new kind of universality phenomenon: the limit law for the product of independent random matrices is independent of the limit laws for the individual matrices themselves. Our result also generalizes earlier results of Götze-Tikhomirov (On the asymptotic spectrum of products of independent random matrices, available at http://arxiv.org/abs/1012.2710) and O'Rourke-Soshnikov (J Probab 16(81):2219-2245, 2011) concerning the product of independent iid random matrices.

  2. 16. DETAIL, WEST PARAPET, FROM EAST, SHOWING SIMPLY ORNAMENTED SOLID ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    16. DETAIL, WEST PARAPET, FROM EAST, SHOWING SIMPLY ORNAMENTED SOLID PARAPET PANEL AT STIFF TOWER, SUPPORTING ORIGINAL METAL LIGHT STANDARD - Fifth Street Viaduct, Spanning Bacon's Quarter Branch Valley on Fifth Street, Richmond, Independent City, VA

  3. View from water showing south facade and adjacent boat slips ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View from water showing south facade and adjacent boat slips (Facility Nos. S375 & S376) - U.S. Naval Base, Pearl Harbor, Boat House, Hornet Avenue at Independence Street, Pearl City, Honolulu County, HI

  4. 8. View Southeast, showing front elevation of Brewery (Buildings 6 ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    8. View Southeast, showing front elevation of Brewery (Buildings 6 and 7 are not visible - behind Brewery) - Weissner Brewery, Building Nos. 6 & 7, 1700 North Gay Street, Baltimore, Independent City, MD

  5. 7. PARTIAL ELEVATION, FROM SOUTHEAST, SHOWING STRUCTURAL CONFIGURATION, INCLUDING DOUBLESPAN ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. PARTIAL ELEVATION, FROM SOUTHEAST, SHOWING STRUCTURAL CONFIGURATION, INCLUDING DOUBLE-SPAN REINFORCED CONCRETE RIGID FRAME AS BASIC STRUCTURAL UNIT OF BRIDGE - Fifth Street Viaduct, Spanning Bacon's Quarter Branch Valley on Fifth Street, Richmond, Independent City, VA

  6. 11. INTERIOR DETAIL, BASEMENT, SHOWING CONDUITS LEADING UNDERGROUND TO SWITCHES ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    11. INTERIOR DETAIL, BASEMENT, SHOWING CONDUITS LEADING UNDERGROUND TO SWITCHES AND SIGNALS - Baltimore & Potomac Interlocking Tower, Adjacent to AMTRAK railroad tracks in block bounded by Howard Street, Jones Falls Expressway, Maryland Avenue & Falls Road, Baltimore, Independent City, MD

  7. 6. HISTORIC AMERICAN BUILDINGS SURVEY, INTERIOR SHOWING ORIGINAL GRANITE COLUMNS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    6. HISTORIC AMERICAN BUILDINGS SURVEY, INTERIOR SHOWING ORIGINAL GRANITE COLUMNS AND COLUMN BRICKFACED AFTER THE GREAT FIRE 1904 - Old U.S. Appraisers Stores, Gay & Lombard Streets, Baltimore, Independent City, MD

  8. 2. ENVIRONMENT, FROM EAST, SHOWING BOSTON STREET BRIDGE CARRYING BOSTON ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    2. ENVIRONMENT, FROM EAST, SHOWING BOSTON STREET BRIDGE CARRYING BOSTON STREET OVER HARRIS CREEK SEWER - Boston Street Bridge, Spanning Harris Creek Sewer at Boston Street, Baltimore, Independent City, MD

  9. 1. ENVIRONMENT, FROM SOUTH, SHOWING BOSTON STREET BRIDGE CARRYING BOSTON ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. ENVIRONMENT, FROM SOUTH, SHOWING BOSTON STREET BRIDGE CARRYING BOSTON STREET OVER HARRIS CREEK SEWER OUTLET AT NORTHWEST BRANCH OF PATAPSCO RIVER (BALTIMORE HARBOR) - Boston Street Bridge, Spanning Harris Creek Sewer at Boston Street, Baltimore, Independent City, MD

  10. 3. ENVIRONMENT, FROM WEST, SHOWING BOSTON STREET BRIDGE CARRYING BOSTON ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. ENVIRONMENT, FROM WEST, SHOWING BOSTON STREET BRIDGE CARRYING BOSTON STREET OVER HARRIS CREEK SEWER, WITH PORTION OF AMERICAN CAN COMPANY COMPLEX - Boston Street Bridge, Spanning Harris Creek Sewer at Boston Street, Baltimore, Independent City, MD

  11. 16. VIEW LOOKING DOWN WALKWAY INSIDE CENTRAL POWER PLANT SHOWING ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    16. VIEW LOOKING DOWN WALKWAY INSIDE CENTRAL POWER PLANT SHOWING BOTTOM OF COAL HOPPERS. - Baltimore & Ohio Railroad, Mount Clare Shops, South side of Pratt Street between Carey & Poppleton Streets, Baltimore, Independent City, MD

  12. 17. CABLE CAR #22, VIEW SHOWING CAR ROUNDING CORNER IN ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    17. CABLE CAR #22, VIEW SHOWING CAR ROUNDING CORNER IN LOADING AREA NEXT TO CAR DUMP AND CAR DUMP BUILDING - Pennsylvania Railroad, Canton Coal Pier, Clinton Street at Keith Avenue (Canton area), Baltimore, Independent City, MD

  13. CLOSE VIEW ALONG WATERFRONT TO SHOW BULKHEAD Southwest Washington, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    CLOSE VIEW ALONG WATERFRONT TO SHOW BULKHEAD - Southwest Washington, Urban Renewal Area, Bounded by Independence Avenue, Washington Avenue, South Capitol Street, Canal Street, P Street, Maine Avenue & Washington Channel, Fourteenth Street, D Street, & Twelfth Street, Washington, District of Columbia, DC

  14. 63. VIEW SHOWING THE RELATIONSHIP BETWEEN THE SWITCH CABIN AND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    63. VIEW SHOWING THE RELATIONSHIP BETWEEN THE SWITCH CABIN AND THE LAMP/GENERATOR BUILDING FOUNDATION ADJACENT TO IT, LOOKING NORTHEAST - Independent Coal & Coke Company, Kenilworth, Carbon County, UT

  15. 3. VIEW NORTH, DETAIL SHOWING TRIPARTITE, PROJECTING BAY AT SECOND, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. VIEW NORTH, DETAIL SHOWING TRI-PARTITE, PROJECTING BAY AT SECOND, THIRD AND FOURTH FLOORS, FEATURING TERRA COTTA PANELS - West Lexington Street, Number 308 (Commercial Building), 308 West Lexington Street, Baltimore, Independent City, MD

  16. 4. VIEW NORTH, DETAIL SHOWING TERRA COTTA ROUND ARCH AND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. VIEW NORTH, DETAIL SHOWING TERRA COTTA ROUND ARCH AND STRING COURSE AT FOURTH FLOOR LEVEL AND FRIEZE AT FIFTH FLOOR LEVEL - West Lexington Street, Number 308 (Commercial Building), 308 West Lexington Street, Baltimore, Independent City, MD

  17. 2. EXTERIOR, SOUTH FRONT, UPPER LEVELS SHOWING ROOF CORNICE AND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    2. EXTERIOR, SOUTH FRONT, UPPER LEVELS SHOWING ROOF CORNICE AND BAY WINDOW UNIT WITH PRESSED TIN SPANDREL - West Lexington Street, Number 314 (Commercial Building), 314 West Lexington Street, Baltimore, Independent City, MD

  18. 4. GENERAL VIEW FROM THE WEST, SHOWING REFLECTING POOL IN ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. GENERAL VIEW FROM THE WEST, SHOWING REFLECTING POOL IN FOREGROUND (CLOSER VIEW) - Washington Monument, High ground West of Fifteenth Street, Northwest, between Independence & Constitution Avenues, Washington, District of Columbia, DC

  19. 3. GENERAL VIEW FROM THE WEST, SHOWING REFLECTING POOL IN ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. GENERAL VIEW FROM THE WEST, SHOWING REFLECTING POOL IN FOREGROUND - Washington Monument, High ground West of Fifteenth Street, Northwest, between Independence & Constitution Avenues, Washington, District of Columbia, DC

  20. 11. Detail, southeast corner, showing decorative elements of main structure, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    11. Detail, southeast corner, showing decorative elements of main structure, and window at the second story of the hose tower. - Independent Hose Company No. 3, Nineteenth & Belmont Streets, Bellaire, Belmont County, OH

  1. 223. FREQUENTLY REPRODUCED VIEW OF GWMP SHOWING VARIABLE WIDTH MEDIANS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    223. FREQUENTLY REPRODUCED VIEW OF GWMP SHOWING VARIABLE WIDTH MEDIANS WITH INDEPENDENT ALIGNMENTS FROM KEY BRIDGE LOOKING NORTHWEST, 1953. - George Washington Memorial Parkway, Along Potomac River from McLean to Mount Vernon, VA, Mount Vernon, Fairfax County, VA

  2. 158. View looking SE showing 'Centennial Anniversary of the Declaration ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    158. View looking SE showing 'Centennial Anniversary of the Declaration of Independence' fountain on Aquarium Drive with north facade of Art Museum in right background. - Fairmount Waterworks, East bank of Schuylkill River, Aquarium Drive, Philadelphia, Philadelphia County, PA

  3. 4. VIEW FROM SOUTHWEST SHOWING WEST SIDE OF PIER AND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. VIEW FROM SOUTHWEST SHOWING WEST SIDE OF PIER AND PEDESTRIAN BRIDGE CONNECTING MARINE MAMMAL PAVILION WITH BALTIMORE AQUARIUM - Baltimore Inner Harbor, Pier 4, South side of Pratt Street between Frederick Street & Market Place, Baltimore, Independent City, MD

  4. 4. GENERAL VIEW OF THE ARCH FROM THE NORTHWEST SHOWING ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. GENERAL VIEW OF THE ARCH FROM THE NORTHWEST SHOWING THE PARK GROUND IN THE FOREGROUND - Jefferson National Expansion Memorial Arch, Mississippi River between Washington & Poplar Streets, Saint Louis, Independent City, MO

  5. Independent component analysis for brain fMRI does not select for independence

    PubMed Central

    Daubechies, I.; Roussos, E.; Takerkart, S.; Benharrosh, M.; Golden, C.; D'Ardenne, K.; Richter, W.; Cohen, J. D.; Haxby, J.

    2009-01-01

    InfoMax and FastICA are the independent component analysis algorithms most used and apparently most effective for brain fMRI. We show that this is linked to their ability to handle effectively sparse components rather than independent components as such. The mathematical design of better analysis tools for brain fMRI should thus emphasize other mathematical characteristics than independence. PMID:19556548

  6. Independent component analysis for brain FMRI does indeed select for maximal independence.

    PubMed

    Calhoun, Vince D; Potluru, Vamsi K; Phlypo, Ronald; Silva, Rogers F; Pearlmutter, Barak A; Caprihan, Arvind; Plis, Sergey M; Adalı, Tülay

    2013-01-01

    A recent paper by Daubechies et al. claims that two independent component analysis (ICA) algorithms, Infomax and FastICA, which are widely used for functional magnetic resonance imaging (fMRI) analysis, select for sparsity rather than independence. The argument was supported by a series of experiments on synthetic data. We show that these experiments fall short of proving this claim and that the ICA algorithms are indeed doing what they are designed to do: identify maximally independent sources.

  7. Executive Function, Survival, and Hospitalization in Chronic Obstructive Pulmonary Disease. A Longitudinal Analysis of the National Emphysema Treatment Trial (NETT)

    PubMed Central

    Dodd, James W.; Novotny, Paul; Sciurba, Frank C.

    2015-01-01

    Rationale: Cognitive dysfunction has been demonstrated in chronic obstructive pulmonary disease (COPD), but studies are limited to cross-sectional analyses or incompletely characterized populations. Objectives: We examined longitudinal changes in sensitive measures of executive function in a well-characterized population of patients with severe COPD. Methods: This study was performed on patients enrolled in the National Emphysema Treatment Trial. To assess executive function, we analyzed trail making (TM) A and B times at enrollment in the trial (2,128 patients), and at 12 (731 patients) and 24 months (593 patients) after enrollment, adjusted for surgery, marriage status, age, education, income, depression, PaO2, PaCO2, and smoking. Associations with survival and hospitalizations were examined using Cox regression and linear regression models. Measurements and Main Results: The average age of the patients was 66.4 years, and the average FEV1 was 23.9% predicted. At the time of enrolment, 38% had executive dysfunction. Compared with those who did not, these patients were older, less educated, had higher oxygen use, higher PaCO2, worse quality of life as measured by the St. George’s Respiratory Quotient, reduced well-being, and lower social function. There was no significant change over 2 years in TM A or B times after adjustment for covariables. Changes in TM B times were modestly associated with survival, but changes in TM B − A times were not. Changes in TM scores were not associated with frequency of hospitalization. Lung function, PaO2, smoking, survival, and hospitalizations were not significantly different in those with executive dysfunction. Conclusions: In this large population of patients with severe emphysema and heavy cigarette smoking exposure, there was no significant decline over 2 years in cognitive executive function as measured by TM tests. There was no association between executive function impairment and frequency of hospitalization, and

  8. National Orange Show Photovoltaic Demonstration

    SciTech Connect

    Dan Jimenez Sheri Raborn, CPA; Tom Baker

    2008-03-31

    National Orange Show Photovoltaic Demonstration created a 400KW Photovoltaic self-generation plant at the National Orange Show Events Center (NOS). The NOS owns a 120-acre state fairground where it operates an events center and produces an annual citrus fair known as the Orange Show. The NOS governing board wanted to employ cost-saving programs for annual energy expenses. It is hoped the Photovoltaic program will result in overall savings for the NOS, help reduce the State's energy demands as relating to electrical power consumption, improve quality of life within the affected grid area as well as increase the energy efficiency of buildings at our venue. In addition, the potential to reduce operational expenses would have a tremendous effect on the ability of the NOS to service its community.

  9. Arches showing UV flaring activity

    NASA Technical Reports Server (NTRS)

    Fontenla, J. M.

    1988-01-01

    The UVSP data obtained in the previous maximum activity cycle show the frequent appearance of flaring events in the UV. In many cases these flaring events are characterized by at least two footpoints which show compact impulsive non-simultaneous brightenings and a fainter but clearly observed arch developes between the footpoints. These arches and footpoints are observed in line corresponding to different temperatures, as Lyman alpha, N V, and C IV, and when observed above the limb display large Doppler shifts at some stages. The size of the arches can be larger than 20 arcsec.

  10. Create a Polarized Light Show.

    ERIC Educational Resources Information Center

    Conrad, William H.

    1992-01-01

    Presents a lesson that introduces students to polarized light using a problem-solving approach. After illustrating the concept using a slinky and poster board with a vertical slot, students solve the problem of creating a polarized light show using Polya's problem-solving methods. (MDH)

  11. Pembrolizumab Shows Promise for NSCLC.

    PubMed

    2015-06-01

    Data from the KEYNOTE-001 trial show that pembrolizumab improves clinical outcomes for patients with advanced non-small cell lung cancer, and is well tolerated. PD-L1 expression in at least 50% of tumor cells correlated with improved efficacy.

  12. Frame independent cosmological perturbations

    SciTech Connect

    Prokopec, Tomislav; Weenink, Jan E-mail: j.g.weenink@uu.nl

    2013-09-01

    We compute the third order gauge invariant action for scalar-graviton interactions in the Jordan frame. We demonstrate that the gauge invariant action for scalar and tensor perturbations on one physical hypersurface only differs from that on another physical hypersurface via terms proportional to the equation of motion and boundary terms, such that the evolution of non-Gaussianity may be called unique. Moreover, we demonstrate that the gauge invariant curvature perturbation and graviton on uniform field hypersurfaces in the Jordan frame are equal to their counterparts in the Einstein frame. These frame independent perturbations are therefore particularly useful in relating results in different frames at the perturbative level. On the other hand, the field perturbation and graviton on uniform curvature hypersurfaces in the Jordan and Einstein frame are non-linearly related, as are their corresponding actions and n-point functions.

  13. Magic Carpet Shows Its Colors

    NASA Technical Reports Server (NTRS)

    2004-01-01

    The upper left image in this display is from the panoramic camera on the Mars Exploration Rover Spirit, showing the 'Magic Carpet' region near the rover at Gusev Crater, Mars, on Sol 7, the seventh martian day of its journey (Jan. 10, 2004). The lower image, also from the panoramic camera, is a monochrome (single filter) image of a rock in the 'Magic Carpet' area. Note that colored portions of the rock correlate with extracted spectra shown in the plot to the side. Four different types of materials are shown: the rock itself, the soil in front of the rock, some brighter soil on top of the rock, and some dust that has collected in small recesses on the rock face ('spots'). Each color on the spectra matches a line on the graph, showing how the panoramic camera's different colored filters are used to broadly assess the varying mineral compositions of martian rocks and soils.

  14. Relationship between lung function and quantitative computed tomographic parameters of airway remodeling, air trapping, and emphysema in patients with asthma and chronic obstructive pulmonary disease: A single-center study

    PubMed Central

    Hartley, Ruth A.; Barker, Bethan L.; Newby, Chris; Pakkal, Mini; Baldi, Simonetta; Kajekar, Radhika; Kay, Richard; Laurencin, Marie; Marshall, Richard P.; Sousa, Ana R.; Parmar, Harsukh; Siddiqui, Salman; Gupta, Sumit; Brightling, Chris E.

    2016-01-01

    Background There is a paucity of studies comparing asthma and chronic obstructive pulmonary disease (COPD) based on thoracic quantitative computed tomographic (QCT) parameters. Objectives We sought to compare QCT parameters of airway remodeling, air trapping, and emphysema between asthmatic patients and patients with COPD and explore their relationship with airflow limitation. Methods Asthmatic patients (n = 171), patients with COPD (n = 81), and healthy subjects (n = 49) recruited from a single center underwent QCT and clinical characterization. Results Proximal airway percentage wall area (%WA) was significantly increased in asthmatic patients (62.5% [SD, 2.2]) and patients with COPD (62.7% [SD, 2.3]) compared with that in healthy control subjects (60.3% [SD, 2.2], P < .001). Air trapping measured based on mean lung density expiratory/inspiratory ratio was significantly increased in patients with COPD (mean, 0.922 [SD, 0.037]) and asthmatic patients (mean, 0.852 [SD, 0.061]) compared with that in healthy subjects (mean, 0.816 [SD, 0.066], P < .001). Emphysema assessed based on lung density measured by using Hounsfield units below which 15% of the voxels lie (Perc15) was a feature of COPD only (patients with COPD: mean, −964 [SD, 19.62] vs asthmatic patients: mean, −937 [SD, 22.7] and healthy subjects: mean, −937 [SD, 17.1], P < .001). Multiple regression analyses showed that the strongest predictor of lung function impairment in asthmatic patients was %WA, whereas in the COPD and asthma subgrouped with postbronchodilator FEV1 percent predicted value of less than 80%, it was air trapping. Factor analysis of QCT parameters in asthmatic patients and patients with COPD combined determined 3 components, with %WA, air trapping, and Perc15 values being the highest loading factors. Cluster analysis identified 3 clusters with mild, moderate, or severe lung function impairment with corresponding decreased lung density (Perc15 values) and increased air

  15. Assessing the Relationship between Lung Density and Function with Oxygen-Enhanced Magnetic Resonance Imaging in a Mouse Model of Emphysema

    PubMed Central

    Zurek, Magdalena; Sladen, Louise; Johansson, Edvin; Olsson, Marita; Jackson, Sonya; Zhang, Hui; Mayer, Gaell; Hockings, Paul D.

    2016-01-01

    Purpose A magnetic resonance imaging method is presented that allows for the simultaneous assessment of oxygen delivery, oxygen uptake, and parenchymal density. The technique is applied to a mouse model of porcine pancreatic elastase (PPE) induced lung emphysema in order to investigate how structural changes affect lung function. Method Nine-week-old female C57BL6 mice were instilled with saline or PPE at days 0 and 7. At day 19, oxygen delivery, oxygen uptake, and lung density were quantified from T1 and proton-density measurements obtained via oxygen-enhanced magnetic resonance imaging (OE-MRI) using an ultrashort echo-time imaging sequence. Subsequently, the lungs were sectioned for histological observation. Blood-gas analyses and pulmonary functional tests via FlexiVent were performed in separate cohorts. Principal Findings PPE-challenged mice had reduced density when assessed via MRI, consistent with the parenchyma loss observed in the histology sections, and an increased lung compliance was detected via FlexiVent. The oxygenation levels, as assessed via the blood-gas analysis, showed no difference between PPE-challenged animals and control. This finding was mirrored in the global MRI assessments of oxygen delivery and uptake, where the changes in relaxation time indices were matched between the groups. The heterogeneity of the same parameters however, were increased in PPE-challenged animals. When the oxygenation status was investigated in regions of varying density, a reduced oxygen-uptake was found in low-density regions of PPE-challenged mice. In high-density regions the uptake was higher than that of regions of corresponding density in control animals. The oxygen delivery was proportional to the oxygen uptake in both groups. Conclusions The proposed method allowed for the regional assessment of the relationship between lung density and two aspects of lung function, the oxygen delivery and uptake. When compared to global indices of lung function, an

  16. Independence Day for IgA.

    PubMed

    Macpherson, Andrew J; McCoy, Kathy D

    2015-09-15

    IgA is induced through T-cell-dependent and -independent pathways. In this issue, Bunker et al. (2015) now show that the T-cell-independent pathway is sufficient to coat most small intestinal microbes specifically, and Fransen et al. (2015) find that IgA coating promotes uptake of microbes into Peyer's patches and drives further induction in a positive-feedback loop. PMID:26377894

  17. Premature lung aging and cellular senescence in the pathogenesis of idiopathic pulmonary fibrosis and COPD/emphysema.

    PubMed

    Chilosi, Marco; Carloni, Angelo; Rossi, Andrea; Poletti, Venerino

    2013-09-01

    Different anatomic and physiological changes occur in the lung of aging people that can affect pulmonary functions, and different pulmonary diseases, including deadly diseases such as chronic obstructive pulmonary disease (COPD)/emphysema and idiopathic pulmonary fibrosis (IPF), can be related to an acceleration of the aging process. The individual genetic background, as well as exposure to a variety of toxic substances (cigarette smoke in primis) can contribute significantly to accelerating pulmonary senescence. Premature aging can impair lung function by different ways: by interfering specifically with tissue repair mechanisms after damage, thus perturbing the correct crosstalk between mesenchymal and epithelial components; by inducing systemic and/or local alteration of the immune system, thus impairing the complex mechanisms of lung defense against infections; and by stimulating a local and/or systemic inflammatory condition (inflammaging). According to recently proposed pathogenic models in COPD and IPF, premature cellular senescence likely affects distinct progenitors cells (mesenchymal stem cells in COPD, alveolar epithelial precursors in IPF), leading to stem cell exhaustion. In this review, the large amount of data supporting this pathogenic view are discussed, with emphasis on the possible molecular and cellular mechanisms leading to the severe parenchymal remodeling that characterizes, in different ways, these deadly diseases.

  18. Carbon dioxide insufflation in esophageal endoscopic submucosal dissection reduces mediastinal emphysema: A randomized, double-blind, controlled trial

    PubMed Central

    Maeda, Yuki; Hirasawa, Dai; Fujita, Naotaka; Ohira, Tetsuya; Harada, Yoshihiro; Yamagata, Taku; Koike, Yoshiki; Suzuki, Kenjirou

    2016-01-01

    AIM To assess the efficacy of CO2 insufflation for reduction of mediastinal emphysema (ME) immediately after endoscopic submucosal dissection (ESD). METHODS A total of 46 patients who were to undergo esophageal ESD were randomly assigned to receive either CO2 insufflation (CO2 group, n = 24) or air insufflation (Air group, n = 22). Computed tomography (CT) was carried out immediately after ESD and the next morning. Pain and abdominal distention were chronologically recorded using a 100-mm visual analogue scale (VAS). The volume of residual gas in the digestive tract was measured using CT imaging. RESULTS The incidence of ME immediately after ESD in the CO2 group was significantly lower than that in the Air group (17% vs 55%, P = 0.012). The incidence of ME the next morning was 8.3% vs 32% respectively (P = 0.066). There were no differences in pain scores or distention scores at any post-procedure time points. The volume of residual gas in the digestive tract immediately after ESD was significantly smaller in the CO2 group than that in the Air group (808 mL vs 1173 mL, P = 0.013). CONCLUSION CO2 insufflation during esophageal ESD significantly reduced postprocedural ME. CO2 insufflation also reduced the volume of residual gas in the digestive tract immediately after ESD, but not the VAS scores of pain and distention.

  19. Carbon dioxide insufflation in esophageal endoscopic submucosal dissection reduces mediastinal emphysema: A randomized, double-blind, controlled trial

    PubMed Central

    Maeda, Yuki; Hirasawa, Dai; Fujita, Naotaka; Ohira, Tetsuya; Harada, Yoshihiro; Yamagata, Taku; Koike, Yoshiki; Suzuki, Kenjirou

    2016-01-01

    AIM To assess the efficacy of CO2 insufflation for reduction of mediastinal emphysema (ME) immediately after endoscopic submucosal dissection (ESD). METHODS A total of 46 patients who were to undergo esophageal ESD were randomly assigned to receive either CO2 insufflation (CO2 group, n = 24) or air insufflation (Air group, n = 22). Computed tomography (CT) was carried out immediately after ESD and the next morning. Pain and abdominal distention were chronologically recorded using a 100-mm visual analogue scale (VAS). The volume of residual gas in the digestive tract was measured using CT imaging. RESULTS The incidence of ME immediately after ESD in the CO2 group was significantly lower than that in the Air group (17% vs 55%, P = 0.012). The incidence of ME the next morning was 8.3% vs 32% respectively (P = 0.066). There were no differences in pain scores or distention scores at any post-procedure time points. The volume of residual gas in the digestive tract immediately after ESD was significantly smaller in the CO2 group than that in the Air group (808 mL vs 1173 mL, P = 0.013). CONCLUSION CO2 insufflation during esophageal ESD significantly reduced postprocedural ME. CO2 insufflation also reduced the volume of residual gas in the digestive tract immediately after ESD, but not the VAS scores of pain and distention. PMID:27621583

  20. ShowMe3D

    SciTech Connect

    Sinclair, Michael B

    2012-01-05

    ShowMe3D is a data visualization graphical user interface specifically designed for use with hyperspectral image obtained from the Hyperspectral Confocal Microscope. The program allows the user to select and display any single image from a three dimensional hyperspectral image stack. By moving a slider control, the user can easily move between images of the stack. The user can zoom into any region of the image. The user can select any pixel or region from the displayed image and display the fluorescence spectrum associated with that pixel or region. The user can define up to 3 spectral filters to apply to the hyperspectral image and view the image as it would appear from a filter-based confocal microscope. The user can also obtain statistics such as intensity average and variance from selected regions.