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Sample records for lung disease patterns

  1. Scintigraphic perfusion patterns in patients with diffuse lung disease

    SciTech Connect

    Newman, G.E.; Sullivan, D.C.; Gottschalk, A.; Putman, C.E.

    1982-04-01

    Perfusion scintigrams of 55 patients with radiographic evidence of diffuse lung disease were reviewed. Thirty-nine had acute and/or chronic changes caused by congestive heart failure, and 16 had diffuse reticulonodular disease. A normal or near-normal perfusion pattern was seen in 40/55 (73%), and this finding was equally common in the two groups. The authors conclude that perfusion scintigraphy is useful in excluding pulmonary embolism in patients with radiographic evidence of diffuse, symmetrical lung disease.

  2. Segmentation of interstitial lung disease patterns in HRCT images

    NASA Astrophysics Data System (ADS)

    Dash, Jatindra K.; Madhavi, Vaddepalli; Mukhopadhyay, Sudipta; Khandelwal, Niranjan; Kumar, Prafulla

    2015-03-01

    Automated segmentation of pathological bearing region is the first step towards the development of lung CAD. Most of the work reported in the literature related to automated analysis of lung tissue aims towards classification of fixed sized block into one of the classes. This block level classification of lung tissues in the image never results in accurate or smooth boundaries between different regions. In this work, effort is taken to investigate the performance of three automated image segmentation algorithms those results in smooth boundaries among lung tissue patterns commonly encountered in HRCT images of the thorax. A public database that consists of HRCT images taken from patients affected with Interstitial Lung Diseases (ILDs) is used for the evaluation. The algorithms considered are Markov Random Field (MRF), Gaussian Mixture Model (GMM) and Mean Shift (MS). 2-fold cross validation approach is followed for the selection of the best parameter value for individual algorithm as well as to evaluate the performance of all the algorithms. Mean shift algorithm is observed as the best performer in terms of Jaccard Index, Modified Hausdorff Distance, accuracy, Dice Similarity Coefficient and execution speed.

  3. Classification of interstitial lung disease patterns with topological texture features

    NASA Astrophysics Data System (ADS)

    Huber, Markus B.; Nagarajan, Mahesh; Leinsinger, Gerda; Ray, Lawrence A.; Wismüller, Axel

    2010-03-01

    Topological texture features were compared in their ability to classify morphological patterns known as 'honeycombing' that are considered indicative for the presence of fibrotic interstitial lung diseases in high-resolution computed tomography (HRCT) images. For 14 patients with known occurrence of honey-combing, a stack of 70 axial, lung kernel reconstructed images were acquired from HRCT chest exams. A set of 241 regions of interest of both healthy and pathological (89) lung tissue were identified by an experienced radiologist. Texture features were extracted using six properties calculated from gray-level co-occurrence matrices (GLCM), Minkowski Dimensions (MDs), and three Minkowski Functionals (MFs, e.g. MF.euler). A k-nearest-neighbor (k-NN) classifier and a Multilayer Radial Basis Functions Network (RBFN) were optimized in a 10-fold cross-validation for each texture vector, and the classification accuracy was calculated on independent test sets as a quantitative measure of automated tissue characterization. A Wilcoxon signed-rank test was used to compare two accuracy distributions and the significance thresholds were adjusted for multiple comparisons by the Bonferroni correction. The best classification results were obtained by the MF features, which performed significantly better than all the standard GLCM and MD features (p < 0.005) for both classifiers. The highest accuracy was found for MF.euler (97.5%, 96.6%; for the k-NN and RBFN classifier, respectively). The best standard texture features were the GLCM features 'homogeneity' (91.8%, 87.2%) and 'absolute value' (90.2%, 88.5%). The results indicate that advanced topological texture features can provide superior classification performance in computer-assisted diagnosis of interstitial lung diseases when compared to standard texture analysis methods.

  4. Tomography patterns of lung disease in systemic sclerosis*

    PubMed Central

    Bastos, Andréa de Lima; Corrêa, Ricardo de Amorim; Ferreira, Gilda Aparecida

    2016-01-01

    Currently, lung impairment is the leading factor responsible for the morbidity and mortality associated with systemic sclerosis. Therefore, the recognition of the various tomography patterns becomes decisive in the clinical management of these patients. In high-resolution computed tomography studies, the most common pattern is that of nonspecific interstitial pneumonia. However, there are other forms of lung involvement that must also be recognized. The aim of this study was to review the literature on the main changes resulting from pulmonary involvement in systemic sclerosis and the corresponding radiological findings, considering the current classification of interstitial diseases. We searched the Medline (PubMed), Lilacs, and SciELO databases in order to select articles related to pulmonary changes in systemic sclerosis and published in English between 2000 and 2015. The pulmonary changes seen on computed tomography in systemic sclerosis are varied and are divided into three main categories: interstitial, alveolar, and vascular. Interstitial changes constitute the most common type of pulmonary involvement in systemic sclerosis. However, alveolar and vascular manifestations must also be recognized and considered in the presence of atypical clinical presentations and inadequate treatment responses. PMID:27818546

  5. Tomography patterns of lung disease in systemic sclerosis.

    PubMed

    Bastos, Andréa de Lima; Corrêa, Ricardo de Amorim; Ferreira, Gilda Aparecida

    2016-01-01

    Currently, lung impairment is the leading factor responsible for the morbidity and mortality associated with systemic sclerosis. Therefore, the recognition of the various tomography patterns becomes decisive in the clinical management of these patients. In high-resolution computed tomography studies, the most common pattern is that of nonspecific interstitial pneumonia. However, there are other forms of lung involvement that must also be recognized. The aim of this study was to review the literature on the main changes resulting from pulmonary involvement in systemic sclerosis and the corresponding radiological findings, considering the current classification of interstitial diseases. We searched the Medline (PubMed), Lilacs, and SciELO databases in order to select articles related to pulmonary changes in systemic sclerosis and published in English between 2000 and 2015. The pulmonary changes seen on computed tomography in systemic sclerosis are varied and are divided into three main categories: interstitial, alveolar, and vascular. Interstitial changes constitute the most common type of pulmonary involvement in systemic sclerosis. However, alveolar and vascular manifestations must also be recognized and considered in the presence of atypical clinical presentations and inadequate treatment responses.

  6. Lung function, breathing pattern, and gas exchange in interstitial lung disease.

    PubMed Central

    Javaheri, S; Sicilian, L

    1992-01-01

    BACKGROUND: The aim of this study was to determine the relation between the severity of abnormalities in ventilatory function tests and tidal breathing pattern and gas exchange indices in interstitial lung disease. METHODS: Pulmonary function, ventilation, carbon dioxide production, oxygen consumption, arterial blood gas tensions, and pH were measured during resting steady state conditions in 60 patients with proved interstitial lung disease. Patients were categorised by forced vital capacity (FVC) (percentage of predicted values) as having a mild, moderate, or severe restrictive defect with means (SD) of 71% (4%), 57% (4%), and 41% (7%) of predicted values, respectively. RESULTS: FVC varied from 29% to 79% of predicted values and from 0.99 l to 4.32 l. The two measurements of FVC correlated strongly with most static lung volumes and with transfer factor for carbon monoxide. Mean respiratory rates (per minute) and tidal volumes (ml) were 17 (4) and 484 (131), 20 (4) and 460 (139), and 23 (5) and 377 (109) in mild, moderate, and severe restrictive defects, respectively. FVC correlated negatively with respiratory rate and positively with tidal volume. Arterial carbon dioxide tension ranged from 30 to 49 mm Hg; only two patients were hypercapnic. Mean arterial oxygen tensions were not significantly different among the three groups, and there were no significant correlations between forced expiratory volume in one second or FVC and arterial carbon dioxide tension or carbon dioxide production. CONCLUSION: Low values of FVC were associated with increased respiratory rate and decreased tidal volume; this pattern of breathing mimics external elastic loading, suggesting that mechanoreceptors may contribute to the rapid and shallow pattern of breathing in interstitial lung disease. Hypercapnia seems to be rare in interstitial lung disease even when functional impairment is severe and tidal volume is small. The increased respiratory rate is important in maintaining adequate

  7. Asbestos lung burden and disease patterns in man

    SciTech Connect

    Churg, A.

    1993-12-31

    This article discusses the relationship between disease and asbestos burden in the human lung. The differences in this relationship for various types of asbestos are also discussed. Finally the outstanding issues in the field of asbestos research and disease are presented including the following: discrepancies between data derived from animal experiments, predictions based on mathematical models, and data derived from actual analysis of autopsied human lungs. 75 refs., 3 figs., 3 tab.

  8. Lung disease

    MedlinePlus

    ... they can't breathe deeply. Pulmonary fibrosis and sarcoidosis are examples of lung tissue disease. Lung circulation ... tuberculosis Pulmonary veno-occlusive disease Rheumatoid lung disease Sarcoidosis Simple pulmonary eosinophilia Patient Instructions Chronic obstructive pulmonary ...

  9. Patterns of Lung Volume Use during an Extemporaneous Speech Task in Persons with Parkinson Disease

    ERIC Educational Resources Information Center

    Bunton, K.

    2005-01-01

    This study examined patterns of lung volume use in speakers with Parkinson disease (PD) during an extemporaneous speaking task. The performance of a control group was also examined. Behaviors described are based on acoustic, kinematic and linguistic measures. Group differences were found in breath group duration, lung volume initiation, and lung…

  10. My approach to interstitial lung disease using clinical, radiological and histopathological patterns

    PubMed Central

    Leslie, K O

    2009-01-01

    The complex world of interstitial lung disease presents nearly insurmountable challenges to the general surgical pathologist faced with a lung biopsy in this setting. The pathology is often inflammatory and always requires clinical and radiological context for a relevant and clinically useful histopathological diagnosis. A pattern-based histopathological approach to interstitial lung disease provides a “map” for the general pathologist to navigate this area successfully, especially so when used with aid of the clinical and radiological patterns of presentation. PMID:19398592

  11. Lung Diseases

    MedlinePlus

    When you breathe, your lungs take in oxygen from the air and deliver it to the bloodstream. The cells in your body need oxygen to ... you breathe nearly 25,000 times. People with lung disease have difficulty breathing. Millions of people in ...

  12. Lung disease - resources

    MedlinePlus

    Resources - lung disease ... The following organizations are good resources for information on lung disease : American Lung Association -- www.lung.org National Heart, Lung, and Blood Institute -- www.nhlbi.nih.gov ...

  13. Rheumatoid lung disease

    MedlinePlus

    Lung disease - rheumatoid arthritis; Rheumatoid nodules; Rheumatoid lung ... Lung problems are common in rheumatoid arthritis. They often cause no symptoms. The cause of lung disease associated with rheumatoid arthritis is unknown. Sometimes, the medicines used to ...

  14. Estimating local scaling properties for the classification of interstitial lung disease patterns

    NASA Astrophysics Data System (ADS)

    Huber, Markus B.; Nagarajan, Mahesh B.; Leinsinger, Gerda; Ray, Lawrence A.; Wismueller, Axel

    2011-03-01

    Local scaling properties of texture regions were compared in their ability to classify morphological patterns known as 'honeycombing' that are considered indicative for the presence of fibrotic interstitial lung diseases in high-resolution computed tomography (HRCT) images. For 14 patients with known occurrence of honeycombing, a stack of 70 axial, lung kernel reconstructed images were acquired from HRCT chest exams. 241 regions of interest of both healthy and pathological (89) lung tissue were identified by an experienced radiologist. Texture features were extracted using six properties calculated from gray-level co-occurrence matrices (GLCM), Minkowski Dimensions (MDs), and the estimation of local scaling properties with Scaling Index Method (SIM). A k-nearest-neighbor (k-NN) classifier and a Multilayer Radial Basis Functions Network (RBFN) were optimized in a 10-fold cross-validation for each texture vector, and the classification accuracy was calculated on independent test sets as a quantitative measure of automated tissue characterization. A Wilcoxon signed-rank test was used to compare two accuracy distributions including the Bonferroni correction. The best classification results were obtained by the set of SIM features, which performed significantly better than all the standard GLCM and MD features (p < 0.005) for both classifiers with the highest accuracy (94.1%, 93.7%; for the k-NN and RBFN classifier, respectively). The best standard texture features were the GLCM features 'homogeneity' (91.8%, 87.2%) and 'absolute value' (90.2%, 88.5%). The results indicate that advanced texture features using local scaling properties can provide superior classification performance in computer-assisted diagnosis of interstitial lung diseases when compared to standard texture analysis methods.

  15. A Systematic Review of the Prevalence and Pattern of Imaging Defined Post-TB Lung Disease

    PubMed Central

    Meghji, Jamilah; Simpson, Hope; Squire, S. Bertel; Mortimer, Kevin

    2016-01-01

    Background Tuberculosis is an important risk factor for chronic respiratory disease in resource poor settings. The persistence of abnormal spirometry and symptoms after treatment are well described, but the structural abnormalities underlying these changes remain poorly defined, limiting our ability to phenotype post-TB lung disease in to meaningful categories for clinical management, prognostication, and ongoing research. The relationship between post-TB lung damage and patient-centred outcomes including functional impairment, respiratory symptoms, and health related quality of life also remains unclear. Methods We performed a systematic literature review to determine the prevalence and pattern of imaging-defined lung pathology in adults after medical treatment for pleural, miliary, or pulmonary TB disease. Data were collected on study characteristics, and the modality, timing, and findings of thoracic imaging. The proportion of studies relating imaging findings to spirometry results and patient morbidity was recorded. Study quality was assessed using a modified Newcastle-Ottowa score. (Prospero Registration number CRD42015027958) Results We identified 37 eligible studies. The principle features seen on CXR were cavitation (8.3–83.7%), bronchiectasis (4.3–11.2%), and fibrosis (25.0–70.4%), but prevalence was highly variable. CT imaging identified a wider range of residual abnormalities than CXR, including nodules (25.0–55.8%), consolidation (3.7–19.2%), and emphysema (15.0–45.0%). The prevalence of cavitation was generally lower (7.4–34.6%) and bronchiectasis higher (35.0–86.0%) on CT vs. CXR imaging. A paucity of prospective data, and data from HIV-infected adults and sub-Saharan Africa (sSA) was noted. Few studies related structural damage to physiological impairment, respiratory symptoms, or patient morbidity. Conclusions Post-TB structural lung pathology is common. Prospective data are required to determine the evolution of this lung damage and

  16. Interstitial Lung Diseases

    MedlinePlus

    Interstitial lung disease is the name for a large group of diseases that inflame or scar the lungs. The inflammation and scarring make it hard to ... air is responsible for some types of interstitial lung diseases. Specific types include Black lung disease among ...

  17. Diffuse lung disease of infancy: a pattern-based, algorithmic approach to histological diagnosis.

    PubMed

    Armes, Jane E; Mifsud, William; Ashworth, Michael

    2015-02-01

    Diffuse lung disease (DLD) of infancy has multiple aetiologies and the spectrum of disease is substantially different from that seen in older children and adults. In many cases, a specific diagnosis renders a dire prognosis for the infant, with profound management implications. Two recently published series of DLD of infancy, collated from the archives of specialist centres, indicate that the majority of their cases were referred, implying that the majority of biopsies taken for DLD of infancy are first received by less experienced pathologists. The current literature describing DLD of infancy takes a predominantly aetiological approach to classification. We present an algorithmic, histological, pattern-based approach to diagnosis of DLD of infancy, which, with the aid of appropriate multidisciplinary input, including clinical and radiological expertise and ancillary diagnostic studies, may lead to an accurate and useful interim report, with timely exclusion of inappropriate diagnoses. Subsequent referral to a specialist centre for confirmatory diagnosis will be dependent on the individual case and the decision of the multidisciplinary team.

  18. Childhood Interstitial Lung Disease

    MedlinePlus

    ... from the NHLBI on Twitter. What Is Childhood Interstitial Lung Disease? Childhood interstitial (in-ter-STISH-al) lung disease, or chILD, ... with similar symptoms—it's not a precise diagnosis. Interstitial lung disease (ILD) also occurs in adults. However, ...

  19. Lung imaging during acute chest syndrome in sickle cell disease: computed tomography patterns and diagnostic accuracy of bedside chest radiograph

    PubMed Central

    Mekontso Dessap, Armand; Deux, Jean-François; Habibi, Anoosha; Abidi, Nour; Godeau, Bertrand; Adnot, Serge; Brun-Buisson, Christian; Rahmouni, Alain; Galacteros, Frederic; Maitre, Bernard

    2014-01-01

    Introduction The lung computed tomography (CT) features of acute chest syndrome (ACS) in sickle cell disease patients is not well described and the diagnostic performance of bedside chest radiograph (CR) has not been tested. Our objectives were to describe CT features of ACS and evaluate the reproducibility and diagnostic performance of bedside CR. Methods We screened 127 consecutive patients during 166 ACS episodes and 145 CT scans (in 118 consecutive patients) were included in the study. Results Among the 145 CT scans, 139 (96%) exhibited a new pulmonary opacity and 84 (58%) exhibited at least one complete lung segment consolidation. Consolidations were predominant as compared to ground-glass opacities and atelectasis. Lung parenchyma was increasingly consolidated from apex to base; the right and left inferior lobes were almost always involved in patients with a new complete lung segment consolidation on CT scan (98% and 95% of cases respectively). Patients with a new complete lung segment consolidation on CT scan had a more severe presentation and course as compared to others. The sensitivity of bedside CR for the diagnosis of ACS using CT as a reference was good (>85%) whereas the specificity was weak (<60%). Conclusion ACS more frequently presented on CT as a consolidation pattern, predominating in lung bases. The reproducibility and diagnostic capacity of bedside CR were far from perfect. These findings may help improve the bedside imaging diagnosis of ACS. PMID:23925645

  20. Particles causing lung disease.

    PubMed Central

    Kilburn, K H

    1984-01-01

    The lung has a limited number of patterns of reaction to inhaled particles. The disease observed depends upon the location: conducting airways, terminal bronchioles and alveoli, and upon the nature of inflammation induced: acute, subacute or chronic. Many different agents cause narrowing of conducting airways (asthma) and some of these cause permanent distortion or obliteration of airways as well. Terminal bronchioles appear to be particularly susceptible to particles which cause goblet cell metaplasia, mucous plugging and ultimately peribronchiolar fibrosis. Cancer is the last outcome at the bronchial level and appears to depend upon continuous exposure to or retention of an agent in the airway and failure of the affected cells to be exfoliated which may be due to squamous metaplasia. Alveoli are populated by endothelial cells, Type I or pavement epithelial cells and metabolically active cuboidal Type II cells that produce the lungs specific surfactant, dipalmytol lecithin. Disturbances of surfactant lead to edema in distal lung while laryngeal edema due to anaphylaxis or fumes may produce asphyxia. Physical retention of indigestible particles or retention by immune memory responses may provoke hyaline membranes, stimulate alveolar lipoproteinosis and finally fibrosis. This later exuberant deposition of connective tissue has been best studied in the occupational pneumoconioses especially silicosis and asbestosis. In contrast emphysema a catabolic response, appears frequently to result from leakage or release of lysosomal proteases into the lung during processing of cigarette smoke particles. The insidious and probably most important human lung disease due to particles is bronchiolar obstruction and obliteration, producing progressive impairment of air flow. The responsible particle is the complex combination of poorly digestive lipids and complex carbohydrates with active chemicals which we call cigarette smoke. More research is needed to perfect, correct and

  1. Occupational and environmental lung disease.

    PubMed

    Seaman, Danielle M; Meyer, Cristopher A; Kanne, Jeffrey P

    2015-06-01

    Occupational and environmental lung disease remains a major cause of respiratory impairment worldwide. Despite regulations, increasing rates of coal worker's pneumoconiosis and progressive massive fibrosis are being reported in the United States. Dust exposures are occurring in new industries, for instance, silica in hydraulic fracking. Nonoccupational environmental lung disease contributes to major respiratory disease, asthma, and COPD. Knowledge of the imaging patterns of occupational and environmental lung disease is critical in diagnosing patients with occult exposures and managing patients with suspected or known exposures.

  2. Particles causing lung disease

    SciTech Connect

    Kilburn, K.H.

    1984-04-01

    The lung has a limited number of patterns of reaction to inhaled particles. The disease observed depends upon the location: conducting airways, terminal bronchioles and alveoli, and upon the nature of inflammation induced: acute, subacute or chronic. Many different agents cause narrowing of conducting airways (asthma) and some of these cause permanent distortion or obliteration of airways as well. Terminal bronchioles appear to be particularly susceptible to particles which cause goblet cell metaplasia, mucous plugging and ultimately peribronchiolar fibrosis. Cancer is the last outcome at the bronchial level and appears to depend upon continuous exposure to or retention of an agent in the airway and failure of the affected cells to be exfoliated which may be due to squamous metaplasia. Alveoli are populated by endothelial cells, Type I or pavement epithelial cells and metabolically active cuboidal Type II cells that produce the lungs specific surfactant, dipalmytol lecithin. Disturbances of surfactant lead to edema in distal lung while laryngeal edema due to anaphylaxis or fumes may produce asphyxia. Physical retention of indigestible particles or retention by immune memory responses may provoke hyaline membranes, stimulate alveolar lipoproteinosis and finally fibrosis. This later exuberant deposition of connective tissue has been best studied in the occupational pneumoconioses especially silicosis and asbestosis. In contrast emphysema a catabolic response appears frequently to result from leakage or release of lysosomal proteases into the lung during processing of cigarette smoke particles. 164 references, 1 figure, 2 tables.

  3. Effects of lung disease on the three-dimensional structure and air flow pattern in the human airway tree

    NASA Astrophysics Data System (ADS)

    van de Moortele, Tristan; Nemes, Andras; Wendt, Christine; Coletti, Filippo

    2016-11-01

    The morphological features of the airway tree directly affect the air flow features during breathing, which determines the gas exchange and inhaled particle transport. Lung disease, Chronic Obstructive Pulmonary Disease (COPD) in this study, affects the structural features of the lungs, which in turn negatively affects the air flow through the airways. Here bronchial tree air volume geometries are segmented from Computed Tomography (CT) scans of healthy and diseased subjects. Geometrical analysis of the airway centerlines and corresponding cross-sectional areas provide insight into the specific effects of COPD on the airway structure. These geometries are also used to 3D print anatomically accurate, patient specific flow models. Three-component, three-dimensional velocity fields within these models are acquired using Magnetic Resonance Imaging (MRI). The three-dimensional flow fields provide insight into the change in flow patterns and features. Additionally, particle trajectories are determined using the velocity fields, to identify the fate of therapeutic and harmful inhaled aerosols. Correlation between disease-specific and patient-specific anatomical features with dysfunctional airflow patterns can be achieved by combining geometrical and flow analysis.

  4. Radiographic Differentiation of Advanced Fibrocystic Lung Diseases.

    PubMed

    Akira, Masanori

    2017-03-01

    The concept of end-stage lung disease suggests a final common pathway for most diffuse parenchymal lung diseases. In accordance with this concept, end-stage disease is characterized radiographically and pathologically by the presence of extensive honeycombing. However, sequential computed tomographic (CT) scans obtained from patients with chronic diffuse lung disease evolve over time to show various advanced lung disease patterns other than honeycombing. In addition, several radiographically distinct honeycomb patterns, including microcystic, macrocystic, mixed, and combined emphysema and honeycombing, differentiate one advanced lung disease from another. For example, usual interstitial pneumonia (IP) usually shows mixed microcystic and macrocystic honeycombing. In contrast, CT images of long-standing fibrotic nonspecific IP typically show only small, scattered foci of honeycombing; instead, most enlarged airspaces observed in the advanced stage of this disease represent dilatation of bronchioles. In desquamative IP and pulmonary Langerhans cell histiocytosis, focal opacities typically evolve into emphysema-like lesions seen on CT imaging. In combined pulmonary fibrosis and emphysema and sarcoidosis, the cysts tend to be larger than those observed in usual IP. Sequential CT scans in other chronic, diffuse lung diseases also show various distinctive changes. This article highlights radiographic patterns of lung destruction that belie a single common pathway to end-stage lung disease. Recognition of distinct radiographic patterns of lung destruction can help differentiate diffuse parenchymal lung diseases, even in advanced stages of disease evolution.

  5. Interstitial lung disease - adults - discharge

    MedlinePlus

    ... lung disease Pulmonary alveolar proteinosis Rheumatoid lung disease Sarcoidosis Patient Instructions Eating extra calories when sick - adults ... team. Related MedlinePlus Health Topics Interstitial Lung Diseases Sarcoidosis Browse the Encyclopedia A.D.A.M., Inc. ...

  6. Lung Diseases and Conditions

    MedlinePlus

    ... Explore How the Lungs Work What Are... The Respiratory System What Happens When You Breathe What Controls Your Breathing Lung Diseases & Conditions Clinical Trials Links Related Topics Asthma Bronchitis COPD How the Heart Works Respiratory Failure Send a link to NHLBI to someone ...

  7. Indium Lung Disease

    PubMed Central

    Nakano, Makiko; Omae, Kazuyuki; Takeuchi, Koichiro; Chonan, Tatsuya; Xiao, Yong-long; Harley, Russell A.; Roggli, Victor L.; Hebisawa, Akira; Tallaksen, Robert J.; Trapnell, Bruce C.; Day, Gregory A.; Saito, Rena; Stanton, Marcia L.; Suarthana, Eva; Kreiss, Kathleen

    2012-01-01

    Background: Reports of pulmonary fibrosis, emphysema, and, more recently, pulmonary alveolar proteinosis (PAP) in indium workers suggested that workplace exposure to indium compounds caused several different lung diseases. Methods: To better understand the pathogenesis and natural history of indium lung disease, a detailed, systematic, multidisciplinary analysis of clinical, histopathologic, radiologic, and epidemiologic data for all reported cases and workplaces was undertaken. Results: Ten men (median age, 35 years) who produced, used, or reclaimed indium compounds were diagnosed with interstitial lung disease 4-13 years after first exposure (n = 7) or PAP 1-2 years after first exposure (n = 3). Common pulmonary histopathologic features in these patients included intraalveolar exudate typical of alveolar proteinosis (n = 9), cholesterol clefts and granulomas (n = 10), and fibrosis (n = 9). Two patients with interstitial lung disease had pneumothoraces. Lung disease progressed following cessation of exposure in most patients and was fatal in two. Radiographic data revealed that two patients with PAP subsequently developed fibrosis and one also developed emphysematous changes. Epidemiologic investigations demonstrated the potential for exposure to respirable particles and an excess of lung abnormalities among coworkers. Conclusions: Occupational exposure to indium compounds was associated with PAP, cholesterol ester crystals and granulomas, pulmonary fibrosis, emphysema, and pneumothoraces. The available evidence suggests exposure to indium compounds causes a novel lung disease that may begin with PAP and progress to include fibrosis and emphysema, and, in some cases, premature death. Prospective studies are needed to better define the natural history and prognosis of this emerging lung disease and identify effective prevention strategies. PMID:22207675

  8. Differentiation of several interstitial lung disease patterns in HRCT images using support vector machine: role of databases on performance

    NASA Astrophysics Data System (ADS)

    Kale, Mandar; Mukhopadhyay, Sudipta; Dash, Jatindra K.; Garg, Mandeep; Khandelwal, Niranjan

    2016-03-01

    Interstitial lung disease (ILD) is complicated group of pulmonary disorders. High Resolution Computed Tomography (HRCT) considered to be best imaging technique for analysis of different pulmonary disorders. HRCT findings can be categorised in several patterns viz. Consolidation, Emphysema, Ground Glass Opacity, Nodular, Normal etc. based on their texture like appearance. Clinician often find it difficult to diagnosis these pattern because of their complex nature. In such scenario computer-aided diagnosis system could help clinician to identify patterns. Several approaches had been proposed for classification of ILD patterns. This includes computation of textural feature and training /testing of classifier such as artificial neural network (ANN), support vector machine (SVM) etc. In this paper, wavelet features are calculated from two different ILD database, publically available MedGIFT ILD database and private ILD database, followed by performance evaluation of ANN and SVM classifiers in terms of average accuracy. It is found that average classification accuracy by SVM is greater than ANN where trained and tested on same database. Investigation continued further to test variation in accuracy of classifier when training and testing is performed with alternate database and training and testing of classifier with database formed by merging samples from same class from two individual databases. The average classification accuracy drops when two independent databases used for training and testing respectively. There is significant improvement in average accuracy when classifiers are trained and tested with merged database. It infers dependency of classification accuracy on training data. It is observed that SVM outperforms ANN when same database is used for training and testing.

  9. [Indium lung disease].

    PubMed

    Nakano, Makiko; Omae, Kazuyuki

    2014-02-01

    "Indium lung" is a new occupational lung disease. The global demand for indium, the major material used in manufacturing flat-screen display panels, has skyrocketed since the 1990s (Japan comprises 85% of the worldwide demand). The first case was reported in Japan in 2003, followed by seven cases (interstitial pneumonia and emphysema) in Japan. Two pulmonary alveolar proteinosis (PAP) cases in the USA followed in 2011. Indium lung has been described as interstitial pneumonia, pneumothorax, emphysema, and PAP. In 2013, The Japan Ministry of Health, Labor and Welfare issued an "Ordinance on the Prevention of Hazards Due to Specified Chemical Substances" requiring employers to provide regular health checks for employees and measurements of work environment concentrations of respirable indium dust.

  10. Asbestos-related lung disease

    SciTech Connect

    Westerfield, B.T. )

    1992-06-01

    Asbestos is a versatile fibrous mineral that can cause lung disease and death. Asbestosis, benign pleural disease, lung cancer, and mesothelioma can all result from inhaling asbestos. The history of disease and exposure risks are discussed. The difficult assessment of risk and the long latency period for development of disease demand evaluation and regular surveillance of asbestos-exposed workers.22 references.

  11. [Smoking-related interstitial lung diseases].

    PubMed

    Marten, Katharina

    2007-03-01

    The most important smoking-related interstitial lung diseases (ILD) are respiratory bronchiolitis, respiratory bronchiolitis-associated interstitial lung disease, desquamative interstitial pneumonia, and Langerhans' cell histiocytosis. Although traditionally considered to be discrete entities, smoking-related ILDs often coexist, thus accounting for the sometimes complex patterns encountered on high-resolution computed tomography (HRCT). Further studies are needed to elucidate the causative role of smoking in the development of pulmonary fibrosis.

  12. Mitochondria in lung disease

    PubMed Central

    Cloonan, Suzanne M.; Choi, Augustine M.K.

    2016-01-01

    Mitochondria are a distinguishing feature of eukaryotic cells. Best known for their critical function in energy production via oxidative phosphorylation (OXPHOS), mitochondria are essential for nutrient and oxygen sensing and for the regulation of critical cellular processes, including cell death and inflammation. Such diverse functional roles for organelles that were once thought to be simple may be attributed to their distinct heteroplasmic genome, exclusive maternal lineage of inheritance, and ability to generate signals to communicate with other cellular organelles. Mitochondria are now thought of as one of the cell’s most sophisticated and dynamic responsive sensing systems. Specific signatures of mitochondrial dysfunction that are associated with disease pathogenesis and/or progression are becoming increasingly important. In particular, the centrality of mitochondria in the pathological processes and clinical phenotypes associated with a range of lung diseases is emerging. Understanding the molecular mechanisms regulating the mitochondrial processes of lung cells will help to better define phenotypes and clinical manifestations associated with respiratory disease and to identify potential diagnostic and therapeutic targets. PMID:26928034

  13. Mitochondria in lung disease.

    PubMed

    Cloonan, Suzanne M; Choi, Augustine M K

    2016-03-01

    Mitochondria are a distinguishing feature of eukaryotic cells. Best known for their critical function in energy production via oxidative phosphorylation (OXPHOS), mitochondria are essential for nutrient and oxygen sensing and for the regulation of critical cellular processes, including cell death and inflammation. Such diverse functional roles for organelles that were once thought to be simple may be attributed to their distinct heteroplasmic genome, exclusive maternal lineage of inheritance, and ability to generate signals to communicate with other cellular organelles. Mitochondria are now thought of as one of the cell's most sophisticated and dynamic responsive sensing systems. Specific signatures of mitochondrial dysfunction that are associated with disease pathogenesis and/or progression are becoming increasingly important. In particular, the centrality of mitochondria in the pathological processes and clinical phenotypes associated with a range of lung diseases is emerging. Understanding the molecular mechanisms regulating the mitochondrial processes of lung cells will help to better define phenotypes and clinical manifestations associated with respiratory disease and to identify potential diagnostic and therapeutic targets.

  14. A support vector machine classifier reduces interscanner variation in the HRCT classification of regional disease pattern in diffuse lung disease: Comparison to a Bayesian classifier

    SciTech Connect

    Chang, Yongjun; Lim, Jonghyuck; Kim, Namkug; Seo, Joon Beom; Lynch, David A.

    2013-05-15

    Purpose: To investigate the effect of using different computed tomography (CT) scanners on the accuracy of high-resolution CT (HRCT) images in classifying regional disease patterns in patients with diffuse lung disease, support vector machine (SVM) and Bayesian classifiers were applied to multicenter data. Methods: Two experienced radiologists marked sets of 600 rectangular 20 Multiplication-Sign 20 pixel regions of interest (ROIs) on HRCT images obtained from two scanners (GE and Siemens), including 100 ROIs for each of local patterns of lungs-normal lung and five of regional pulmonary disease patterns (ground-glass opacity, reticular opacity, honeycombing, emphysema, and consolidation). Each ROI was assessed using 22 quantitative features belonging to one of the following descriptors: histogram, gradient, run-length, gray level co-occurrence matrix, low-attenuation area cluster, and top-hat transform. For automatic classification, a Bayesian classifier and a SVM classifier were compared under three different conditions. First, classification accuracies were estimated using data from each scanner. Next, data from the GE and Siemens scanners were used for training and testing, respectively, and vice versa. Finally, all ROI data were integrated regardless of the scanner type and were then trained and tested together. All experiments were performed based on forward feature selection and fivefold cross-validation with 20 repetitions. Results: For each scanner, better classification accuracies were achieved with the SVM classifier than the Bayesian classifier (92% and 82%, respectively, for the GE scanner; and 92% and 86%, respectively, for the Siemens scanner). The classification accuracies were 82%/72% for training with GE data and testing with Siemens data, and 79%/72% for the reverse. The use of training and test data obtained from the HRCT images of different scanners lowered the classification accuracy compared to the use of HRCT images from the same scanner. For

  15. How Is Childhood Interstitial Lung Disease Treated?

    MedlinePlus

    ... the NHLBI on Twitter. How Is Childhood Interstitial Lung Disease Treated? Childhood interstitial lung disease (chILD) is ... prevent acid reflux, which can lead to aspiration. Lung Transplant A lung transplant may be an option ...

  16. Lung alveolar epithelium and interstitial lung disease.

    PubMed

    Corvol, Harriet; Flamein, Florence; Epaud, Ralph; Clement, Annick; Guillot, Loic

    2009-01-01

    Interstitial lung diseases (ILDs) comprise a group of lung disorders characterized by various levels of inflammation and fibrosis. The current understanding of the mechanisms underlying the development and progression of ILD strongly suggests a central role of the alveolar epithelium. Following injury, alveolar epithelial cells (AECs) may actively participate in the restoration of a normal alveolar architecture through a coordinated process of re-epithelialization, or in the development of fibrosis through a process known as epithelial-mesenchymal transition (EMT). Complex networks orchestrate EMT leading to changes in cell architecture and behaviour, loss of epithelial characteristics and gain of mesenchymal properties. In the lung, AECs themselves may serve as a source of fibroblasts and myofibroblasts by acquiring a mesenchymal phenotype. This review covers recent knowledge on the role of alveolar epithelium in the pathogenesis of ILD. The mechanisms underlying disease progression are discussed, with a main focus on the apoptotic pathway, the endoplasmic reticulum stress response and the developmental pathway.

  17. What Are Asbestos-Related Lung Diseases?

    MedlinePlus

    ... page from the NHLBI on Twitter. What Are Asbestos-Related Lung Diseases? Asbestos-related lung diseases are ... as the peritoneum (PER-ih-to-NE-um). Asbestos-Related Lung Diseases Figure A shows the location ...

  18. Gastroesophageal reflux and lung disease.

    PubMed

    Meyer, Keith C

    2015-08-01

    Gastroesophageal reflux (GER) can cause respiratory symptoms and may trigger, drive and/or worsen airway disorders, interstitial lung diseases and lung allograft dysfunction. Whether lifestyle changes and acid suppression alone can counter and prevent the adverse effects of GER on the respiratory tract remains unclear. Recent data suggest that antireflux surgery may be more effective in preventing lung disease progression in patients with idiopathic pulmonary fibrosis or lung transplant recipients who have evidence of allograft dysfunction associated with the presence of excessive GER. Additional research and clinical trials are needed to determine the role of GER in various lung disorders and identify which interventions are most efficacious in preventing the respiratory consequences of gastroesophageal reflux disease. In addition, measuring biomarkers that indicate that gastric refluxate has been aspirated into the lower respiratory tract (e.g., pepsin and bile acid concentrations in bronchoalveolar lavage fluid) may prove helpful in both diagnosis and therapeutic decision making.

  19. Interstitial Lung Disease (ILD): Treatment

    MedlinePlus

    ... Treatment Living with Chronic Lung Disease Common Feelings Anxiety Depression Sleep Intimacy Importance of Being Together Body Changes with Age Communicating with Your Partner Exercise and Sexual Activity Less Strenuous Positions for Sexual ...

  20. Smoking and interstitial lung diseases.

    PubMed

    Margaritopoulos, George A; Vasarmidi, Eirini; Jacob, Joseph; Wells, Athol U; Antoniou, Katerina M

    2015-09-01

    For many years has been well known that smoking could cause lung damage. Chronic obstructive pulmonary disease and lung cancer have been the two most common smoking-related lung diseases. In the recent years, attention has also focused on the role of smoking in the development of interstitial lung diseases (ILDs). Indeed, there are three diseases, namely respiratory bronchiolitis-associated ILD, desquamative interstitial pneumonia and pulmonary Langerhans cell histiocytosis, that are currently considered aetiologically linked to smoking and a few others which are more likely to develop in smokers. Here, we aim to focus on the most recent findings regarding the role of smoking in the pathogenesis and clinical behaviour of ILDs.

  1. Interstitial lung disease

    MedlinePlus

    ... advanced ILD may have: Abnormal enlargement of the base of the fingernails ( clubbing ) Blue color of the ... scan of the chest Echocardiogram Open lung biopsy Measurement of the blood oxygen level at rest or ...

  2. Complement System in Lung Disease

    PubMed Central

    Pandya, Pankita H.

    2014-01-01

    In addition to its established contribution to innate immunity, recent studies have suggested novel roles for the complement system in the development of various lung diseases. Several studies have demonstrated that complement may serve as a key link between innate and adaptive immunity in a variety of pulmonary conditions. However, the specific contributions of complement to lung diseases based on innate and adaptive immunity are just beginning to emerge. Elucidating the role of complement-mediated immune regulation in these diseases will help to identify new targets for therapeutic interventions. PMID:24901241

  3. Agricultural lung diseases.

    PubMed Central

    Kirkhorn, S R; Garry, V F

    2000-01-01

    Agriculture is considered one of the most hazardous occupations. Organic dusts and toxic gases constitute some of the most common and potentially disabling occupational and environmental hazards. The changing patterns of agriculture have paradoxically contributed to both improved working conditions and increased exposure to respiratory hazards. Animal confinement operations with increasing animal density, particularly swine confinement, have contributed significantly to increased intensity and duration of exposure to indoor air toxins. Ongoing research has implicated bacterial endotoxins, fungal spores, and the inherent toxicity of grain dusts as causes of upper and lower airway inflammation and as immunologic agents in both grain and animal production. Animal confinement gases, particularly ammonia and hydrogen sulfide, have been implicated as additional sources of respiratory irritants. It has become evident that a significant percentage of agricultural workers have clinical symptoms associated with long-term exposure to organic dusts and animal confinement gases. Respiratory diseases and syndromes, including hypersensitivity pneumonitis, organic dust toxic syndrome, chronic bronchitis, mucous membrane inflammation syndrome, and asthmalike syndrome, result from ongoing acute and chronic exposures. In this review we focus upon the emerging respiratory health issues in a changing agricultural economic and technologic environment. Environmental and occupational hazards and exposures will be emphasized rather than clinical diagnosis and treatment. Methods of prevention, from both engineering controls and personal respiratory perspectives, are also addressed. PMID:10931789

  4. Agricultural lung diseases.

    PubMed

    Kirkhorn, S R; Garry, V F

    2000-08-01

    Agriculture is considered one of the most hazardous occupations. Organic dusts and toxic gases constitute some of the most common and potentially disabling occupational and environmental hazards. The changing patterns of agriculture have paradoxically contributed to both improved working conditions and increased exposure to respiratory hazards. Animal confinement operations with increasing animal density, particularly swine confinement, have contributed significantly to increased intensity and duration of exposure to indoor air toxins. Ongoing research has implicated bacterial endotoxins, fungal spores, and the inherent toxicity of grain dusts as causes of upper and lower airway inflammation and as immunologic agents in both grain and animal production. Animal confinement gases, particularly ammonia and hydrogen sulfide, have been implicated as additional sources of respiratory irritants. It has become evident that a significant percentage of agricultural workers have clinical symptoms associated with long-term exposure to organic dusts and animal confinement gases. Respiratory diseases and syndromes, including hypersensitivity pneumonitis, organic dust toxic syndrome, chronic bronchitis, mucous membrane inflammation syndrome, and asthmalike syndrome, result from ongoing acute and chronic exposures. In this review we focus upon the emerging respiratory health issues in a changing agricultural economic and technologic environment. Environmental and occupational hazards and exposures will be emphasized rather than clinical diagnosis and treatment. Methods of prevention, from both engineering controls and personal respiratory perspectives, are also addressed.

  5. Sleep in patients with restrictive lung disease.

    PubMed

    Won, Christine H J; Kryger, Meir

    2014-09-01

    Restrictive lung disease leads to ventilatory defects and diffusion impairments. These changes may contribute to abnormal nocturnal pathophysiology, including sleep architecture disruption and impaired ventilation and oxygenation. Patients with restrictive lung disease may suffer significant daytime fatigue and dysfunction. Hypercarbia and hypoxemia during sleep may impact progression of lung disease and related symptoms. Little is known about the impact of treatment of sleep disruption on sleep quality and overall prognosis in restrictive lung disease. This review discusses the pathophysiology of sleep and comorbid sleep disorders in restrictive lung diseases including interstitial lung disease, neuromuscular disease, and obesity hypoventilation syndrome.

  6. Spectrum of fibrosing diffuse parenchymal lung disease.

    PubMed

    Morgenthau, Adam S; Padilla, Maria L

    2009-02-01

    The interstitial lung diseases are a heterogeneous group of disorders characterized by inflammation and/or fibrosis of the pulmonary interstitium. In 2002, the American Thoracic Society and the European Respiratory Society revised the classification of interstitial lung diseases and introduced the term diffuse parenchymal lung disease. The idiopathic interstitial pneumonias are a subtype of diffuse parenchymal lung disease. The idiopathic interstitial pneumonias are subdivided into usual interstitial pneumonia (with its clinical counterpart idiopathic interstitial pneumonia), nonspecific interstitial pneumonia, cryptogenic organizing pneumonia, acute interstitial pneumonia, desquamative interstitial pneumonia, respiratory bronchiolitis interstitial lung disease, and lymphocytic pneumonia. Sarcoidosis and hypersensitivity pneumonitis are the 2 most common granulomatous diffuse parenchymal lung diseases. Rheumatoid arthritis, systemic sclerosis, and dermatomyositis/polymyositis (causing antisynthetase syndrome) are diffuse parenchymal lung diseases of known association because these conditions are associated with connective tissue disease. Hermansky-Pudlak syndrome is a rare genetic diffuse parenchymal lung disease characterized by the clinical triad of pulmonary disease, oculocutaneous albinism, and bleeding diathesis. This review provides an overview of the chronic fibrosing diffuse parenchymal lung diseases. Its primary objective is to illuminate the clinical challenges encountered by clinicians who manage the diffuse parenchymal lung diseases regularly and to offer potential solutions to those challenges. Treatment for the diffuse parenchymal lung diseases is limited, and for many patients with end-stage disease, lung transplantation remains the best option. Although much has been learned about the diffuse parenchymal lung diseases during the past decade, research in these diseases is urgently needed.

  7. Cilia Dysfunction in Lung Disease

    PubMed Central

    Tilley, Ann E.; Walters, Matthew S.; Shaykhiev, Renat; Crystal, Ronald G.

    2015-01-01

    A characteristic feature of the human airway epithelium is the presence of ciliated cells bearing motile cilia, specialized cell surface projections containing axonemes comprised of microtubules and dynein arms, which provide ATP-driven motility. In the airways, cilia function in concert with airway mucus to mediate the critical function of mucociliary clearance, cleansing the airways of inhaled particles and pathogens. The prototypical disorder of respiratory cilia is primary ciliary dyskinesia, an inherited disorder that leads to impaired mucociliary clearance, repeated chest infections, and progressive destruction of lung architecture. Numerous acquired lung diseases are also marked by abnormalities in both cilia structure and function. In this review we summarize current knowledge regarding airway ciliated cells and cilia, how they function to maintain a healthy epithelium, and how disorders of cilia structure and function contribute to inherited and acquired lung disease. PMID:25386990

  8. Farmer's lung disease in Somerset.

    PubMed Central

    Pether, J V; Greatorex, F B

    1976-01-01

    A survey of laboratory records was made to assess the value of the precipitin test and isolation methods in the diagnosis of farmer's lung disease and also to determine its prevalence in the farming population of Somerset. A link was established between the clinical diagnosis as written on the form that accompanied the specimen and the actual number of positive laboratory diagnoses made. Fifty (43%) of the clinically diagnosed patients were serologically positive for farmer's lung during a four-year period. If the clinically diagnosed but serologically negative cases of farmer's lung disease are added to this number, a prevalence of about 23 per 1000 of the farming population of Somerset is obtained. PMID:999800

  9. Shared gene expression patterns in mesenchymal progenitors derived from lung and epidermis in pulmonary arterial hypertension: identifying key pathways in pulmonary vascular disease

    PubMed Central

    Gaskill, Christa; Marriott, Shennea; Pratap, Sidd; Menon, Swapna; Hedges, Lora K.; Fessel, Joshua P.; Kropski, Jonathan A.; Ames, DeWayne; Wheeler, Lisa; Loyd, James E.; Hemnes, Anna R.; Roop, Dennis R.; Klemm, Dwight J.; Austin, Eric D.

    2016-01-01

    Abstract Rapid access to lung-derived cells from stable subjects is a major challenge in the pulmonary hypertension field, given the relative contraindication of lung biopsy. In these studies, we sought to demonstrate the importance of evaluating a cell type that actively participates in disease processes, as well as the potential to translate these findings to vascular beds in other nonlung tissues, in this instance perivascular skin mesenchymal cells (MCs). We utilized posttransplant or autopsy lung explant–derived cells (ABCG2-expressing mesenchymal progenitor cells [MPCs], fibroblasts) and skin-derived MCs to test the hypothesis that perivascular ABCG2 MPCs derived from pulmonary arterial hypertension (PAH) patient lung and skin would express a gene profile reflective of ongoing vascular dysfunction. By analyzing the genetic signatures and pathways associated with abnormal ABCG2 lung MPC phenotypes during PAH and evaluating them in lung- and skin-derived MCs, we have identified potential predictor genes for detection of PAH as well as a targetable mechanism to restore MPCs and microvascular function. These studies are the first to explore the utility of expanding the study of ABCG2 MPC regulation of the pulmonary microvasculature to the epidermis, in order to identify potential markers for adult lung vascular disease, such as PAH. PMID:28090290

  10. Shared gene expression patterns in mesenchymal progenitors derived from lung and epidermis in pulmonary arterial hypertension: identifying key pathways in pulmonary vascular disease.

    PubMed

    Gaskill, Christa; Marriott, Shennea; Pratap, Sidd; Menon, Swapna; Hedges, Lora K; Fessel, Joshua P; Kropski, Jonathan A; Ames, DeWayne; Wheeler, Lisa; Loyd, James E; Hemnes, Anna R; Roop, Dennis R; Klemm, Dwight J; Austin, Eric D; Majka, Susan M

    2016-12-01

    Rapid access to lung-derived cells from stable subjects is a major challenge in the pulmonary hypertension field, given the relative contraindication of lung biopsy. In these studies, we sought to demonstrate the importance of evaluating a cell type that actively participates in disease processes, as well as the potential to translate these findings to vascular beds in other nonlung tissues, in this instance perivascular skin mesenchymal cells (MCs). We utilized posttransplant or autopsy lung explant-derived cells (ABCG2-expressing mesenchymal progenitor cells [MPCs], fibroblasts) and skin-derived MCs to test the hypothesis that perivascular ABCG2 MPCs derived from pulmonary arterial hypertension (PAH) patient lung and skin would express a gene profile reflective of ongoing vascular dysfunction. By analyzing the genetic signatures and pathways associated with abnormal ABCG2 lung MPC phenotypes during PAH and evaluating them in lung- and skin-derived MCs, we have identified potential predictor genes for detection of PAH as well as a targetable mechanism to restore MPCs and microvascular function. These studies are the first to explore the utility of expanding the study of ABCG2 MPC regulation of the pulmonary microvasculature to the epidermis, in order to identify potential markers for adult lung vascular disease, such as PAH.

  11. Automated Lung Segmentation from HRCT Scans with Diffuse Parenchymal Lung Diseases.

    PubMed

    Pulagam, Ammi Reddy; Kande, Giri Babu; Ede, Venkata Krishna Rao; Inampudi, Ramesh Babu

    2016-08-01

    Performing accurate and fully automated lung segmentation of high-resolution computed tomography (HRCT) images affected by dense abnormalities is a challenging problem. This paper presents a novel algorithm for automated segmentation of lungs based on modified convex hull algorithm and mathematical morphology techniques. Sixty randomly selected lung HRCT scans with different abnormalities are used to test the proposed algorithm, and experimental results show that the proposed approach can accurately segment the lungs even in the presence of disease patterns, with some limitations in the apices and bases of lungs. The algorithm demonstrates a high segmentation accuracy (dice similarity coefficient = 98.62 and shape differentiation metrics dmean = 1.39 mm, and drms = 2.76 mm). Therefore, the developed automated lung segmentation algorithm is a good candidate for the first stage of a computer-aided diagnosis system for diffuse lung diseases.

  12. Cough in interstitial lung disease.

    PubMed

    Garner, Justin; George, Peter M; Renzoni, Elisabetta

    2015-12-01

    Cough in the context of interstitial lung disease (ILD) has not been the focus of many studies. However, chronic cough has a major impact on quality of life in a significant proportion of patients with ILD. For the purpose of this review, we have chosen to highlight some of the more frequently encountered diffuse lung diseases including idiopathic pulmonary fibrosis, sarcoidosis, hypersensitivity pneumonitis and systemic sclerosis associated ILD. Many of the underlying mechanisms remain speculative and further research is now required to elucidate the complex pathways involved in the pathogenesis of chronic cough in ILD. This will hopefully pave the way for the identification of new therapeutic agents to alleviate this distressing and often intractable symptom.

  13. What makes a blood cell based miRNA expression pattern disease specific? - A miRNome analysis of blood cell subsets in lung cancer patients and healthy controls

    PubMed Central

    Dahmke, Indra N.; Galata, Valentina; Huwer, Hanno; Stehle, Ingo; Bals, Robert; Keller, Andreas; Meese, Eckart

    2014-01-01

    There is evidence of blood-borne miRNA signatures for various human diseases. To dissect the origin of disease-specific miRNA expression in human blood, we separately analyzed the miRNome of different immune cell subtypes, each in lung cancer patients and healthy individuals. Each immune cell type revealed a specific miRNA expression pattern also dependinging on the cell origin, line of defense, and function. The overall expression pattern of each leukocyte subtype showed great similarities between patients and controls. However, for each cell subtype we identified miRNAs that were deregulated in lung cancer patients including hsa-miR-21, a well-known oncomiR associated with poor lung cancer prognosis that was up-regulated in all leukocyte subtype comparisons of cancer versus controls. While the miRNome of cells of the adaptive immune system allowed only a weak separation between patients and controls, cells of the innate immune system allowed perfect or nearly perfect classification. Leukocytes of lung cancer patients show a cancer-specific miRNA expression profile. Our data also show that cancer specific miRNA expression pattern of whole blood samples are not determined by a single cell type. The data indicate that additional blood components, like erythrocytes, platelets, or exosomes might contribute to the disease specificity of a miRNA signature. PMID:25344866

  14. Farmer's Lung Disease. A Review.

    PubMed

    Cano-Jiménez, Esteban; Acuña, Adelaida; Botana, María Isabel; Hermida, Teresa; González, María Guadalupe; Leiro, Virginia; Martín, Irene; Paredes, Sonia; Sanjuán, Pilar

    2016-06-01

    Farmer's lung disease (FLD) is a form of hypersensitivity pneumonitis (HP) caused by inhaling microorganisms from hay or grain stored in conditions of high humidity in the agricultural workplace. It is probably underdiagnosed, especially in northern Spain, where climatic conditions favor the development of this disease. According to previous studies, the most common antigens are usually thermophilic actinomycetes and fungi. The epidemiology of the disease is not well known, and is based on studies conducted by Central European and Asian groups. The clinical presentation may vary, differentiating the chronic (exposure to lower concentrations of the antigen over a longer period time) and the acute forms (after exposure to high concentrations of the antigen). In patients with respiratory symptoms and agricultural occupational exposure, radiological, lung function and/or anatomical pathology findings must be compatible with FLD, bronchoalveolar lavage must show lymphocytosis, and tests must find sensitivity to the antigen. The main treatment is avoidance of the antigen, so it is essential to educate patients on preventive measures. To date, no controlled studies have assessed the role of immunosuppressive therapy in this disease. Corticosteroid treatment has only been shown to accelerate resolution of the acute forms, but there is no evidence that it is effective in preventing disease progression in the long-term or reducing mortality.

  15. Hard metal lung disease: a case series

    PubMed Central

    Mizutani, Rafael Futoshi; Terra-Filho, Mário; Lima, Evelise; Freitas, Carolina Salim Gonçalves; Chate, Rodrigo Caruso; Kairalla, Ronaldo Adib; Carvalho-Oliveira, Regiani; Santos, Ubiratan Paula

    2016-01-01

    ABSTRACT Objective: To describe diagnostic and treatment aspects of hard metal lung disease (HMLD) and to review the current literature on the topic. Methods: This was a retrospective study based on the medical records of patients treated at the Occupational Respiratory Diseases Clinic of the Instituto do Coração, in the city of São Paulo, Brazil, between 2010 and 2013. Results: Of 320 patients treated during the study period, 5 (1.56%) were diagnosed with HMLD. All of those 5 patients were male (mean age, 42.0 ± 13.6 years; mean duration of exposure to hard metals, 11.4 ± 8.0 years). Occupational histories were taken, after which the patients underwent clinical evaluation, chest HRCT, pulmonary function tests, bronchoscopy, BAL, and lung biopsy. Restrictive lung disease was found in all subjects. The most common chest HRCT finding was ground glass opacities (in 80%). In 4 patients, BALF revealed multinucleated giant cells. In 3 patients, lung biopsy revealed giant cell interstitial pneumonia. One patient was diagnosed with desquamative interstitial pneumonia associated with cellular bronchiolitis, and another was diagnosed with a hypersensitivity pneumonitis pattern. All patients were withdrawn from exposure and treated with corticosteroid. Clinical improvement occurred in 2 patients, whereas the disease progressed in 3. Conclusions: Although HMLD is a rare entity, it should always be included in the differential diagnosis of respiratory dysfunction in workers with a high occupational risk of exposure to hard metal particles. A relevant history (clinical and occupational) accompanied by chest HRCT and BAL findings suggestive of the disease might be sufficient for the diagnosis. PMID:28117477

  16. Interstitial Lung Disease in Scleroderma

    PubMed Central

    Schoenfeld, Sara R.; Castelino, Flavia V.

    2015-01-01

    Synopsis Systemic sclerosis (SSc) is a heterogeneous disease of unknown etiology and with limited effective therapies. It is characterized by autoimmunity, vasculopathy and fibrosis and is clinically manifested by multi-organ involvement. Interstitial lung disease (ILD) is a common complication of the disease and is associated with significant morbidity and mortality. The diagnosis of ILD hinges upon careful clinical evaluation as well as pulmonary function tests (PFTs) and high resolution computed tomography (HRCT). A number of pro-inflammatory and pro-fibrotic mediators are involved in the pathogenesis of SSc-ILD, with transforming growth factor-beta (TGF-β) playing a key role in the development of fibrosis. Despite recent advances in the understanding of the mechanisms of disease initiation and progression, effective therapeutic options are still limited. A number of experimental therapies are currently in early phase clinical trials and show promise. PMID:25836640

  17. Rheumatoid Arthritis-Associated Interstitial Lung Disease and Idiopathic Pulmonary Fibrosis: Shared Mechanistic and Phenotypic Traits Suggest Overlapping Disease Mechanisms.

    PubMed

    Paulin, Francisco; Doyle, Tracy J; Fletcher, Elaine A; Ascherman, Dana P; Rosas, Ivan O

    2015-01-01

    The prevalence of clinically evident interstitial lung disease in patients with rheumatoid arthritis is approximately 10%. An additional 33% of undiagnosed patients have interstitial lung abnormalities that can be detected with high-resolution computed tomography. Rheumatoid arthritis-interstitial lung disease patients have three times the risk of death compared to those with rheumatoid arthritis occurring in the absence of interstitial lung disease, and the mortality related to interstitial lung disease is rising. Rheumatoid arthritis-interstitial lung disease is most commonly classified as the usual interstitial pneumonia pattern, overlapping mechanistically and phenotypically with idiopathic pulmonary fibrosis, but can occur in a non-usual interstitial pneumonia pattern, mainly nonspecific interstitial pneumonia. Based on this, we propose two possible pathways to explain the coexistence of rheumatoid arthritis and interstitial lung disease: (i) Rheumatoid arthritis-interstitial lung disease with a non-usual interstitial pneumonia pattern may come about when an immune response against citrullinated peptides taking place in another site (e.g. the joints) subsequently affects the lungs; (ii) Rheumatoid arthritis-interstitial lung disease with a usual interstitial pneumonia pattern may represent a disease process in which idiopathic pulmonary fibrosis-like pathology triggers an immune response against citrullinated proteins that promotes articular disease indicative of rheumatoid arthritis. More studies focused on elucidating the basic mechanisms leading to different sub-phenotypes of rheumatoid arthritis-interstitial lung disease and the overlap with idiopathic pulmonary fibrosis are necessary to improve our understanding of the disease process and to define new therapeutic targets.

  18. Gallium scintigraphic pattern in lung CMV infections

    SciTech Connect

    Ganz, W.I.; Cohen, D.; Mallin, W.

    1994-05-01

    Due to extensive use of prophylactic therapy for Pneumonitis Carinii Pneumonia (PCP), Cytomegalic Viral (CMV) infection may now be the most common lung infection in AIDS patients. This study was performed to determine Gallium-67 patterns in AIDS patients with CMV. Pathology reports were reviewed in AIDS patients who had a dose of 5 to 10 mCi of Gallium-67 citrate. Analysis of images were obtained 48-72 hours later of the entire body was performed. Gallium-67 scans in 14 AIDS patients with biopsy proven CMV, were evaluated for eye, colon, adrenal, lung and renal uptake. These were compared to 40 AIDS patients without CMV. These controls had infections including PCP, Mycobacterial infections, and lymphocytic interstitial pneumonitis. 100% of CMV patients had bowel uptake greater than or equal to liver. Similar bowel activity was seen in 50% of AIDS patients without CMV. 71% had intense eye uptake which was seen in only 10% of patients without CMV. 50% of CMV patients had renal uptake compared to 5% of non-CMV cases. Adrenal uptake was suggested in 50%, however, SPECT imaging is needed for confirmation. 85% had low grade lung uptake. The low grade lung had perihilar prominence. The remaining 15% had high grade lung uptake (greater than sternum) due to superimposed PCP infection. Colon uptake is very sensitive indicator for CMV infection. However, observing eye, renal, and or adrenal uptake improved the diagnostic specificity. SPECT imaging is needed to confirm renal or adrenal abnormalities due to intense bowel activity present in 100% of cases. When high grade lung uptake is seen superimposed PCP is suggested.

  19. Cystic Lung Diseases: Algorithmic Approach.

    PubMed

    Raoof, Suhail; Bondalapati, Praveen; Vydyula, Ravikanth; Ryu, Jay H; Gupta, Nishant; Raoof, Sabiha; Galvin, Jeff; Rosen, Mark J; Lynch, David; Travis, William; Mehta, Sanjeev; Lazzaro, Richard; Naidich, David

    2016-10-01

    Cysts are commonly seen on CT scans of the lungs, and diagnosis can be challenging. Clinical and radiographic features combined with a multidisciplinary approach may help differentiate among various disease entities, allowing correct diagnosis. It is important to distinguish cysts from cavities because they each have distinct etiologies and associated clinical disorders. Conditions such as emphysema, and cystic bronchiectasis may also mimic cystic disease. A simplified classification of cysts is proposed. Cysts can occur in greater profusion in the subpleural areas, when they typically represent paraseptal emphysema, bullae, or honeycombing. Cysts that are present in the lung parenchyma but away from subpleural areas may be present without any other abnormalities on high-resolution CT scans. These are further categorized into solitary or multifocal/diffuse cysts. Solitary cysts may be incidentally discovered and may be an age related phenomenon or may be a remnant of prior trauma or infection. Multifocal/diffuse cysts can occur with lymphoid interstitial pneumonia, Birt-Hogg-Dubé syndrome, tracheobronchial papillomatosis, or primary and metastatic cancers. Multifocal/diffuse cysts may be associated with nodules (lymphoid interstitial pneumonia, light-chain deposition disease, amyloidosis, and Langerhans cell histiocytosis) or with ground-glass opacities (Pneumocystis jirovecii pneumonia and desquamative interstitial pneumonia). Using the results of the high-resolution CT scans as a starting point, and incorporating the patient's clinical history, physical examination, and laboratory findings, is likely to narrow the differential diagnosis of cystic lesions considerably.

  20. Interstitial lung diseases in children

    PubMed Central

    2010-01-01

    Interstitial lung disease (ILD) in infants and children comprises a large spectrum of rare respiratory disorders that are mostly chronic and associated with high morbidity and mortality. These disorders are characterized by inflammatory and fibrotic changes that affect alveolar walls. Typical features of ILD include dyspnea, diffuse infiltrates on chest radiographs, and abnormal pulmonary function tests with restrictive ventilatory defect and/or impaired gas exchange. Many pathological situations can impair gas exchange and, therefore, may contribute to progressive lung damage and ILD. Consequently, diagnosis approach needs to be structured with a clinical evaluation requiring a careful history paying attention to exposures and systemic diseases. Several classifications for ILD have been proposed but none is entirely satisfactory especially in children. The present article reviews current concepts of pathophysiological mechanisms, etiology and diagnostic approaches, as well as therapeutic strategies. The following diagnostic grouping is used to discuss the various causes of pediatric ILD: 1) exposure-related ILD; 2) systemic disease-associated ILD; 3) alveolar structure disorder-associated ILD; and 4) ILD specific to infancy. Therapeutic options include mainly anti-inflammatory, immunosuppressive, and/or anti-fibrotic drugs. The outcome is highly variable with a mortality rate around 15%. An overall favorable response to corticosteroid therapy is observed in around 50% of cases, often associated with sequelae such as limited exercise tolerance or the need for long-term oxygen therapy. PMID:20727133

  1. Fluid Therapy in Lung Disease.

    PubMed

    Rozanski, Elizabeth; Lynch, Alex

    2017-03-01

    Fluid therapy is the cornerstone of supportive care in veterinary medicine. In dogs and cats with preexisting confirmed or suspected pulmonary disease, concerns may exist that the fluid therapy may impair gas exchange, either through increases in hydrostatic pressures or extravasation. Colloidal therapy is more likely to magnify lung injury compared with isotonic crystalloids. Radiographic evidence of fluid overload is a late-stage finding, whereas point-of-care ultrasound may provide earlier information that can also be assessed periodically at the patient side. Cases should be evaluated individually, but generally a conservative fluid therapy plan is preferred with close monitoring of its tolerance.

  2. Pulmonary nuclear medicine: Techniques in diagnosis of lung disease

    SciTech Connect

    Atkins, H.L.

    1984-01-01

    This book presents papers on the application of nuclear medicine to the diagnosis of lung diseases. Topics considered include lung physiology and anatomy, radiopharmaceuticals in pulmonary medicine, pulmonary embolism, obstructive pulmonary disease, diffuse infiltrative lung disease, pneumoconioses, tumor localization scans in primary lung tumors, the interactions of heart diseases and lung diseases on radionuclide tests of lung anatomy and function, radionuclide imaging in pediatric lung diseases, and future possibilities in pulmonary nuclear medicine.

  3. Sex Steroid Signaling: Implications for Lung Diseases

    PubMed Central

    Sathish, Venkatachalem; Martin, Yvette N.; Prakash, Y.S.

    2015-01-01

    There is increasing recognition that the sex hormones (estrogen, progesterone, and testosterone) have biological and pathophysiological actions in peripheral, non-reproductive organs, including the lung. Clinically, sex differences in the incidence, morbidity and mortality of lung diseases such as asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, lung cancer and pulmonary hypertension have been noted, although intrinsic sex differences vs. the roles of sex steroids are still not well-understood. Accordingly, it becomes important to ask the following questions: 1) Which sex steroids are involved? 2) How do they affect different components of the lung under normal circumstances? 3) How does sex steroid signaling change in or contribute to lung disease, and in this regard, are sex steroids detrimental or beneficial? As our understanding of sex steroid signaling in the lung improves, it is important to consider whether such information can be used to develop new therapeutic strategies to target lung diseases, perhaps in both sexes or in a sex-specific manner. In this review, we focus on the basics of sex steroid signaling, and the current state of knowledge regarding how they influence structure and function of specific lung components across the life span and in the context of some important lung diseases. We then summarize the potential for sex steroids as useful biomarkers and therapeutic targets in these lung diseases as a basis for future translational research in the area of gender and individualized medicine. PMID:25595323

  4. Neurotrophins in lung health and disease

    PubMed Central

    Prakash, YS; Thompson, Michael A; Meuchel, Lucas; Pabelick, Christina M; Mantilla, Carlos B; Zaidi, Syed; Martin, Richard J

    2010-01-01

    Neurotrophins (NTs) are a family of growth factors that are well-known in the nervous system. There is increasing recognition that NTs (nerve growth factor, brain-derived neurotrophic factor and NT3) and their receptors (high-affinity TrkA, TrkB and TrkC, and low-affinity p75NTR) are expressed in lung components including the nasal and bronchial epithelium, smooth muscle, nerves and immune cells. NT signaling may be important in normal lung development, developmental lung disease, allergy and inflammation (e.g., rhinitis, asthma), lung fibrosis and even lung cancer. In this review, we describe the current status of our understanding of NT signaling in the lung, with hopes of using aspects of the NT signaling pathway in the diagnosis and therapy of lung diseases. PMID:20524922

  5. Types of Childhood Interstitial Lung Disease

    MedlinePlus

    ... in certain age groups. Diseases more common in infancy include: Surfactant (sur-FAK-tant) dysfunction mutations Developmental ... dysplasia Lung growth abnormalities Neuroendocrine cell hyperplasia of infancy (NEHI) Pulmonary interstitial glycogenosis (PIG) Diseases more common ...

  6. Lung Disease Including Asthma and Adult Vaccination

    MedlinePlus

    ... Healthcare Professionals Lung Disease including Asthma and Adult Vaccination Language: English Español (Spanish) Recommend on Facebook Tweet ... more about health insurance options. Learn about adult vaccination and other health conditions Asplenia Diabetes Heart Disease, ...

  7. [Basic lung ultrasound. Part 2. Parenchymal diseases].

    PubMed

    de la Quintana Gordon, F B; Nacarino Alcorta, B; Fajardo Pérez, M

    2015-01-01

    In this second part, an analysis is made of the pathology of lung parenchyma. This text is structured into different sections, including the study of atelectasias, pneumonia and abscess, interstitial/alveolar or Blines patterns, and finally an analysis is made of pulmonary embolism. With this second part, the basic knowledge to develop lung ultrasound in the anesthesia department has been presented.

  8. Connective Tissue Disease-associated Interstitial Lung Disease: A review

    PubMed Central

    Gutsche, Markus; Rosen, Glenn D.; Swigris, Jeffrey J.

    2012-01-01

    Interstitial lung disease (ILD) is commonly encountered in patients with connective tissue diseases (CTD). Besides the lung parenchyma, the airways, pulmonary vasculature and structures of the chest wall may all be involved, depending on the type of CTD. As a result of this so-called multi-compartment involvement, airflow limitation, pulmonary hypertension, vasculitis and extrapulmonary restriction can occur alongside fibro-inflammatory parenchymal abnormalities in CTD. Rheumatoid arthritis (RA), systemic sclerosis (SSc), poly-/dermatomyositis (PM/DM), Sjögren’s syndrome (SjS), systemic lupus erythematosus (SLE), and undifferentiated (UCTD) as well as mixed connective tissue disease (MCTD) can all be associated with the development of ILD. Non-specific interstitial pneumonia (NSIP) is the most commonly observed histopathological pattern in CTD-ILD, but other patterns including usual interstitial pneumonia (UIP), organizing pneumonia (OP), diffuse alveolar damage (DAD) and lymphocytic interstitial pneumonia (LIP) may occur. Although the majority of patients with CTD-ILD experience stable or slowly advancing ILD, a small yet significant group exhibits a more severe and progressive course. Randomized placebo-controlled trials evaluating the efficacy of immunomodulatory treatments have been conducted only in SSc-associated ILD. However, clinical experience suggests that a handful of immunosuppressive medications are potentially effective in a sizeable portion of patients with ILD caused by other CTDs. In this manuscript, we review the clinical characteristics and management of the most common CTD-ILDs. PMID:23125954

  9. Animal Models of Fibrotic Lung Disease

    PubMed Central

    Lawson, William E.; Oury, Tim D.; Sisson, Thomas H.; Raghavendran, Krishnan; Hogaboam, Cory M.

    2013-01-01

    Interstitial lung fibrosis can develop as a consequence of occupational or medical exposure, as a result of genetic defects, and after trauma or acute lung injury leading to fibroproliferative acute respiratory distress syndrome, or it can develop in an idiopathic manner. The pathogenesis of each form of lung fibrosis remains poorly understood. They each result in a progressive loss of lung function with increasing dyspnea, and most forms ultimately result in mortality. To better understand the pathogenesis of lung fibrotic disorders, multiple animal models have been developed. This review summarizes the common and emerging models of lung fibrosis to highlight their usefulness in understanding the cell–cell and soluble mediator interactions that drive fibrotic responses. Recent advances have allowed for the development of models to study targeted injuries of Type II alveolar epithelial cells, fibroblastic autonomous effects, and targeted genetic defects. Repetitive dosing in some models has more closely mimicked the pathology of human fibrotic lung disease. We also have a much better understanding of the fact that the aged lung has increased susceptibility to fibrosis. Each of the models reviewed in this report offers a powerful tool for studying some aspect of fibrotic lung disease. PMID:23526222

  10. Cystic fibrosis lung disease in adult patients.

    PubMed

    Vender, Robert L

    2008-04-01

    As the longevity of all patients with cystic fibrosis (CF) continues to increase (median 2005 survival=36.8 years), more adult patients will be receiving their medical care from nonpediatric adult-care providers. Cystic fibrosis remains a fatal disease, with more than 80% of patients dying after the age of 18 years, and most deaths resulting from pulmonary disease. The changing epidemiology requires adult-care providers to become knowledgeable and competent in the clinical management of adults with CF. Physicians must understand the influence of specific genotype on phenotypic disease presentation and severity, the pathogenic factors determining lung disease onset and progression, the impact of comorbid disease factors such as CF-related diabetes and malnutrition upon lung disease severity, and the currently approved or standard accepted therapies used for chronic management of CF lung disease. This knowledge is critical to help alleviate morbidity and improve mortality for the rapidly expanding population of adults with CF.

  11. Lung disease in mice with cystic fibrosis.

    PubMed Central

    Kent, G; Iles, R; Bear, C E; Huan, L J; Griesenbach, U; McKerlie, C; Frndova, H; Ackerley, C; Gosselin, D; Radzioch, D; O'Brodovich, H; Tsui, L C; Buchwald, M; Tanswell, A K

    1997-01-01

    The leading cause of mortality and morbidity in humans with cystic fibrosis is lung disease. Advances in our understanding of the pathogenesis of the lung disease of cystic fibrosis, as well as development of innovative therapeutic interventions, have been compromised by the lack of a natural animal model. The utility of the CFTR-knockout mouse in studying the pathogenesis of cystic fibrosis has been limited because of their failure, despite the presence of severe intestinal disease, to develop lung disease. Herein, we describe the phenotype of an inbred congenic strain of CFTR-knockout mouse that develops spontaneous and progressive lung disease of early onset. The major features of the lung disease include failure of effective mucociliary transport, postbronchiolar over inflation of alveoli and parenchymal interstitial thickening, with evidence of fibrosis and inflammatory cell recruitment. We speculate that the basis for development of lung disease in the congenic CFTR-knockout mice is their observed lack of a non-CFTR chloride channel normally found in CFTR-knockout mice of mixed genetic background. PMID:9399953

  12. VARIATION OF LUNG DEPOSITION OF MICRON SIZE PARTICLES WITH LUNG VOLUME AND BREATHING PATTERN

    EPA Science Inventory

    Lung volume and breathing pattern are the source of inter-and intra-subject variability of lung deposition of inhaled particles. Controlling these factors may help optimize delivery of aerosol medicine to the target site within the lung. In the present study we measured total lu...

  13. Aeroparticles, Composition, and Lung Diseases

    PubMed Central

    Falcon-Rodriguez, Carlos I.; Osornio-Vargas, Alvaro R.; Sada-Ovalle, Isabel; Segura-Medina, Patricia

    2016-01-01

    Urban air pollution is a serious worldwide problem due to its impact on human health. In the past 60 years, growing evidence established a correlation between exposure to air pollutants and the developing of severe respiratory diseases. Recently particulate matter (PM) is drawing more public attention to various aspects including historical backgrounds, physicochemical characteristics, and its pathological role. Therefore, this review is focused on these aspects. The most famous air pollution disaster happened in London on December 1952; it has been calculated that more than 4,000 deaths occurred during this event. Air pollution is a complex mix of gases and particles. Gaseous pollutants disseminate deeply into the alveoli, allowing its diffusion through the blood–air barrier to several organs. Meanwhile, PM is a mix of solid or liquid particles suspended in the air. PM is deposited at different levels of the respiratory tract, depending on its size: coarse particles (PM10) in upper airways and fine particles (PM2.5) can be accumulated in the lung parenchyma, inducing several respiratory diseases. Additionally to size, the composition of PM has been associated with different toxicological outcomes on clinical and epidemiological, as well as in vivo and in vitro animal and human studies. PM can be constituted by organic, inorganic, and biological compounds. All these compounds are capable of modifying several biological activities, including alterations in cytokine production, coagulation factors balance, pulmonary function, respiratory symptoms, and cardiac function. It can also generate different modifications during its passage through the airways, like inflammatory cells recruitment, with the release of cytokines and reactive oxygen species (ROS). These inflammatory mediators can activate different pathways, such as MAP kinases, NF-κB, and Stat-1, or induce DNA adducts. All these alterations can mediate obstructive or restrictive respiratory diseases like

  14. Preclinical lung disease in early rheumatoid arthritis.

    PubMed

    Robles-Perez, Alejandro; Luburich, Patricio; Rodriguez-Sanchon, Benigno; Dorca, Jordi; Nolla, Joan Miquel; Molina-Molina, Maria; Narvaez-Garcia, Javier

    2016-02-01

    Early detection and treatment of lung disease in patients with rheumatoid arthritis (RA) may ameliorate disease progression. The objectives of this study were to investigate the frequency of asymptomatic lung abnormalities in early RA patients and the potential association of positive RA blood reactive biomolecules with lung involvement. A prospective observational study was performed in a cohort of patients with early RA (joint symptoms < 2 years) without respiratory symptoms, who were included in a screening program for lung disease with a baseline chest radiograph (CR) and complete pulmonary function tests (PFTs). In those patients with lung abnormalities on the CR or PFTs, a high-resolution chest computed tomography scan (HRCT) was performed. We included 40 patients (30 women). Altered PFTs were detected in 18 (45%) of these patients. These cases had a diffusion lung transfer capacity of carbon monoxide (DLCO) of <80% of predicted, without a significant reduction in the forced vital capacity. The HRCT detected abnormalities in 11 of the 18 patients. Diffuse bronchiectasis was the main finding. An inverse correlation between the anti-citrullinated peptide antibody (ACPA) levels and DLCO was found. Asymptomatic lung disease is present in up to 45% of early RA patients and can be determined by PFTs and ACPA levels.

  15. Classifying interstitial lung diseases in a fractal lung: a morphologist's view "anno Domini 2000".

    PubMed

    Verbeken, E K

    2001-09-01

    Interstitial lung diseases (ILDs) remain a challenging problem for the pathologist. New insights in aetiology and pathogenesis, new diagnostic tools and successful research have led to a renewed interest in ILDs during the last few years, and highlighted the need for a novel classification, particularly of the chronic and/or idiopathic categories of interstitial pneumonias. The present paper compares the terminology of the latter categories in current and previous classifications and briefly discusses the pathological basis for the classifications of ILDs in general, and for the idiopathic interstitial pneumonias (IIPs) in particular. The difference between high versus low morphological specificity determines the pathological classifications. The classification of lIPs relies upon a pattern recognition taking temporal and spatial distribution into consideration. The last section of this paper discusses recent research opposing the conventional pathological approach, analogous to the mechanical two-compartment model of the lung, in which a discontinuity is considered between these two compartments, and thus, a distinction is made between interstitial lung diseases with and without bronchiolitis. In the recent "fractal" concept, the continuity of the lung architecture is emphasized: the lung is a so-called fractal tree with noninteger dimensions. In this fractal model, an interstitial lung disease effects a peripheral part of the pulmonary fractal tree and this may or may not include bronchioles.

  16. Immune mechanisms in beryllium lung disease

    SciTech Connect

    Deodhar, S.D.; Barna, B.P. )

    1991-03-01

    The role of the immune system in the pathogenesis of beryllium lung disease has been suspected for years. The observation of cutaneous hypersensitivity to beryllium led to the development of the lymphocyte blast transformation test; the test clearly distinguishes between healthy subjects, who show little or no blast transformation response, and patients with beryllium lung disease, who demonstrate significant responses. The degree of blast transformation also correlates with the severity of the clinical disease. Animal studies have demonstrated the importance of histocompatibility antigens in development of the disease, and support the participation of cellular immune mechanisms.22 references.

  17. Common lung conditions: environmental pollutants and lung disease.

    PubMed

    Delzell, John E

    2013-06-01

    Exposure to environmental pollutants can have short- and long-term effects on lung health. Sources of air pollution include gases (eg, carbon monoxide, ozone) and particulate matter (eg, soot, dust). In the United States, the Environmental Protection Agency regulates air pollution. Elevated ozone concentrations are associated with increases in lung-related hospitalizations and mortality. Elevated particulate matter pollution increases the risk of cardiopulmonary and lung cancer mortality. Occupations with high exposures to pollutants (eg, heavy construction work, truck driving, auto mechanics) pose higher risk of chronic obstructive lung disease. Some industrial settings (eg, agriculture, sawmills, meat packing plants) also are associated with higher risks from pollutants. The Environmental Protection Agency issues an air quality index for cities and regions in the United States. The upper levels on the index are associated with increases in asthma-related emergency department visits and hospitalizations. Damp and moldy housing might make asthma symptoms worse; individuals from lower socioeconomic groups who live in lower quality housing are particularly at risk. Other household exposures that can have negative effects on lung health include radon, nanoparticles, and biomass fuels.

  18. The bacterial microbiota in inflammatory lung diseases.

    PubMed

    Huffnagle, Gary B; Dickson, Robert P

    2015-08-01

    Numerous lines of evidence, ranging from recent studies back to those in the 1920s, have demonstrated that the lungs are NOT bacteria-free during health. We have recently proposed that the entire respiratory tract should be considered a single ecosystem extending from the nasal and oral cavities to the alveoli, which includes gradients and niches that modulate microbiome dispersion, retention, survival and proliferation. Bacterial exposure and colonization of the lungs during health is most likely constant and transient, respectively. Host microanatomy, cell biology and innate defenses are altered during chronic lung disease, which in turn, alters the dynamics of bacterial turnover in the lungs and can lead to longer term bacterial colonization, as well as blooms of well-recognized respiratory bacterial pathogens. A few new respiratory colonizers have been identified by culture-independent methods, such as Pseudomonas fluorescens; however, the role of these bacteria in respiratory disease remains to be determined.

  19. NADPH Oxidases in Lung Health and Disease

    PubMed Central

    Bernard, Karen; Hecker, Louise; Luckhardt, Tracy R.; Cheng, Guangjie

    2014-01-01

    Abstract Significance: The evolution of the lungs and circulatory systems in vertebrates ensured the availability of molecular oxygen (O2; dioxygen) for aerobic cellular metabolism of internal organs in large animals. O2 serves as the physiologic terminal acceptor of mitochondrial electron transfer and of the NADPH oxidase (Nox) family of oxidoreductases to generate primarily water and reactive oxygen species (ROS), respectively. Recent advances: The purposeful generation of ROS by Nox family enzymes suggests important roles in normal physiology and adaptation, most notably in host defense against invading pathogens and in cellular signaling. Critical issues: However, there is emerging evidence that, in the context of chronic stress and/or aging, Nox enzymes contribute to the pathogenesis of a number of lung diseases. Future Directions: Here, we review evolving functions of Nox enzymes in normal lung physiology and emerging pathophysiologic roles in lung disease. Antioxid. Redox Signal. 20, 2838–2853. PMID:24093231

  20. Lung volumes and airway resistance in patients with a possible restrictive pattern on spirometry

    PubMed Central

    Schultz, Kenia; D'Aquino, Luiz Carlos; Soares, Maria Raquel; Gimenez, Andrea; Pereira, Carlos Alberto de Castro

    2016-01-01

    ABSTRACT Objective: Many patients with proportional reductions in FVC and FEV1 on spirometry show no reduction in TLC. The aim of this study was to evaluate the role that measuring lung volumes and airway resistance plays in the correct classification of patients with a possible restrictive pattern on spirometry. Methods: This was a prospective study involving adults with reduced FVC and FEV1, as well as an FEV1/FV(C) ratio within the predicted range. Restrictive lung disease (RLD) was characterized by TLC below the 5th percentile, as determined by plethysmography. Obstructive lung disease (OLD) was characterized by high specific airway resistance, significant changes in post-bronchodilator FEV1, or an FEF25-75% < 50% of predicted, together with a high RV/TLC ratio. Nonspecific lung disease (NLD) was characterized by TLC within the predicted range and no obstruction. Combined lung disease (CLD) was characterized by reduced TLC and findings indicative of airflow obstruction. Clinical diagnoses were based on clinical suspicion, a respiratory questionnaire, and the review of tests of interest. Results: We included 300 patients in the study, of whom 108 (36%) were diagnosed with RLD. In addition, 120 (40%) and 72 (24%) were diagnosed with OLD/CLD and NLD, respectively. Among the latter, 24 (33%) were clinically diagnosed with OLD. In this sample, 151 patients (50.3%) were obese, and obesity was associated with all patterns of lung disease. Conclusions: Measuring lung volumes and airway resistance is often necessary in order to provide an appropriate characterization of the pattern of lung disease in patients presenting with a spirometry pattern suggestive of restriction. Airflow obstruction is common in such cases. PMID:27812633

  1. Timolol-induced interstitial lung disease

    PubMed Central

    Patel, Hetain; Wilches, Lina Vanessa; Guerrero, Jorge

    2015-01-01

    Timolol maleate is a non-selective beta-adrenergic receptor blocking agent with demonstrated efficacy in the treatment of open-angle glaucoma. A 76 year old female who presented with productive cough, progressive dyspnea and hypoxia after starting timolol maleate opthalamic drops following glaucoma surgery. The patient was diagnosed with interstitial lung disease secondary to timolol treatment and after cessation of the offending agent along with corticosteroid treatment, symptoms improved drastically. Elimination of other possible causes of disease along with evolution of radiological and functional signs left us with a diagnosis of timolol-induced interstitial lung disease. To our knowledge, this is the second reported case of timolol-induced interstitial lung disease. PMID:26236595

  2. Pulmonary Hypertension in Diffuse Parenchymal Lung Diseases.

    PubMed

    Shlobin, Oksana A; Brown, A Whitney; Nathan, Steven D

    2017-01-01

    Pulmonary hypertension (PH) can be triggered by any number of disease processes that result in increased pulmonary vascular resistance. Although historically associated with idiopathic pulmonary arterial hypertension (PAH), most patients with PH do not have the idiopathic subtype, but rather PH associated with another underlying diagnosis, such as left heart or lung disease. The World Health Organization (WHO) classification of PH helps conceptualize the different categories based on presumed etiology. WHO group 3 is PH associated with lung disease. This review focuses on PH in diffuse parenchymal lung diseases (DPLDs), such as the idiopathic interstitial pneumonias and other more rare forms of DPLD. Although there are clear associations of PH with DPLD, the exact pathophysiologic mechanisms and full clinical significance remain uncertain. Treatment of PH related to DPLD remains investigational, but an area of great interest given the negative prognostic implications and the growing number of available pulmonary vasoactive agents.

  3. Inflammatory lung disease in Rett syndrome.

    PubMed

    De Felice, Claudio; Rossi, Marcello; Leoncini, Silvia; Chisci, Glauco; Signorini, Cinzia; Lonetti, Giuseppina; Vannuccini, Laura; Spina, Donatella; Ginori, Alessandro; Iacona, Ingrid; Cortelazzo, Alessio; Pecorelli, Alessandra; Valacchi, Giuseppe; Ciccoli, Lucia; Pizzorusso, Tommaso; Hayek, Joussef

    2014-01-01

    Rett syndrome (RTT) is a pervasive neurodevelopmental disorder mainly linked to mutations in the gene encoding the methyl-CpG-binding protein 2 (MeCP2). Respiratory dysfunction, historically credited to brainstem immaturity, represents a major challenge in RTT. Our aim was to characterize the relationships between pulmonary gas exchange abnormality (GEA), upper airway obstruction, and redox status in patients with typical RTT (n = 228) and to examine lung histology in a Mecp2-null mouse model of the disease. GEA was detectable in ~80% (184/228) of patients versus ~18% of healthy controls, with "high" (39.8%) and "low" (34.8%) patterns dominating over "mixed" (19.6%) and "simple mismatch" (5.9%) types. Increased plasma levels of non-protein-bound iron (NPBI), F2-isoprostanes (F2-IsoPs), intraerythrocyte NPBI (IE-NPBI), and reduced and oxidized glutathione (i.e., GSH and GSSG) were evidenced in RTT with consequently decreased GSH/GSSG ratios. Apnea frequency/severity was positively correlated with IE-NPBI, F2-IsoPs, and GSSG and negatively with GSH/GSSG ratio. A diffuse inflammatory infiltrate of the terminal bronchioles and alveoli was evidenced in half of the examined Mecp2-mutant mice, well fitting with the radiological findings previously observed in RTT patients. Our findings indicate that GEA is a key feature of RTT and that terminal bronchioles are a likely major target of the disease.

  4. Inflammatory Lung Disease in Rett Syndrome

    PubMed Central

    De Felice, Claudio; Rossi, Marcello; Chisci, Glauco; Lonetti, Giuseppina; Vannuccini, Laura; Spina, Donatella; Iacona, Ingrid; Cortelazzo, Alessio; Ciccoli, Lucia; Pizzorusso, Tommaso; Hayek, Joussef

    2014-01-01

    Rett syndrome (RTT) is a pervasive neurodevelopmental disorder mainly linked to mutations in the gene encoding the methyl-CpG-binding protein 2 (MeCP2). Respiratory dysfunction, historically credited to brainstem immaturity, represents a major challenge in RTT. Our aim was to characterize the relationships between pulmonary gas exchange abnormality (GEA), upper airway obstruction, and redox status in patients with typical RTT (n = 228) and to examine lung histology in a Mecp2-null mouse model of the disease. GEA was detectable in ~80% (184/228) of patients versus ~18% of healthy controls, with “high” (39.8%) and “low” (34.8%) patterns dominating over “mixed” (19.6%) and “simple mismatch” (5.9%) types. Increased plasma levels of non-protein-bound iron (NPBI), F2-isoprostanes (F2-IsoPs), intraerythrocyte NPBI (IE-NPBI), and reduced and oxidized glutathione (i.e., GSH and GSSG) were evidenced in RTT with consequently decreased GSH/GSSG ratios. Apnea frequency/severity was positively correlated with IE-NPBI, F2-IsoPs, and GSSG and negatively with GSH/GSSG ratio. A diffuse inflammatory infiltrate of the terminal bronchioles and alveoli was evidenced in half of the examined Mecp2-mutant mice, well fitting with the radiological findings previously observed in RTT patients. Our findings indicate that GEA is a key feature of RTT and that terminal bronchioles are a likely major target of the disease. PMID:24757286

  5. Treatment of Lung Carcinoid by Type and Extent of Disease

    MedlinePlus

    ... Carcinoid Tumor Treating Lung Carcinoid Tumors Treatment of Lung Carcinoid, by Type and Extent of Disease The ... those that can’t be removed completely Resectable lung carcinoid tumors Resectable carcinoid tumors haven’t spread ...

  6. How Are Asbestos-Related Lung Diseases Treated?

    MedlinePlus

    ... the NHLBI on Twitter. How Are Asbestos-Related Lung Diseases Treated? No treatments can reverse the effects ... then draw out the excess fluid. Treatments for Lung Cancer and Mesothelioma If you have lung cancer ...

  7. Bronchoalveolar lavage cell pattern from healthy human lung

    PubMed Central

    Heron, M; Grutters, J C; ten Dam-Molenkamp, K M; Hijdra, D; van Heugten-Roeling, A; Claessen, A M E; Ruven, H J T; van den Bosch, J M M; van Velzen-Blad, H

    2012-01-01

    Bronchoalveolar lavage (BAL) is widely accepted as a key diagnostic procedure in interstitial lung diseases (ILD). We performed a study to obtain reference intervals of differential cell patterns in BAL fluid with special attention to the origin of lavage fluid, e.g. bronchial/alveolar, to atopy and smoking status and to age of the healthy people. We performed bronchoalveolar lavage in 55 healthy subjects with known atopy status (age: 18–64 years, non-smokers/smokers: 34/21) and determined differential cell counts and lymphocyte subsets in BAL fluid and blood. Moreover, in a subgroup of non-smoking healthy individuals we measured the expression of the regulatory T cell marker forkhead box protein 3 (FoxP3) on blood and BAL fluid lymphocytes in addition to a comprehensive set of activation markers. Differential cell counts from the alveolar lavage fraction differed significantly from calculated pooled fractions (n = 11). In contrast, marginal differences were found between atopic and non-atopic subjects. Interestingly, the BAL fluid CD4+/CD8+ ratio correlated strongly with age (r2 = 0·50, P < 0·0001). We consider the bronchial and alveolar fraction to be lavage fluid from fundamentally different compartments and recommend analysis of the alveolar fraction in diagnostic work-up of ILD. In addition, our data suggest that age corrected BAL fluid CD4+/CD8+ ratios should be used in the clinical evaluation of patients with interstitial lung diseases. PMID:22288596

  8. The Therapeutic Potential of Differentiated Lung Cells from Embryonic Stem Cells in Lung Diseases.

    PubMed

    Mokhber Dezfouli, Mohammad Reza; Chaleshtori, Sirous Sadeghian; Dehghan, Mohammad Mehdi; Tavanaeimanesh, Hamid; Baharvand, Hossein; Tahamtani, Yaser

    2017-01-01

    Lung diseases cause great morbidity and mortality. The choice of effective medical treatment is limited and the number of lung diseases are difficult to treat with current treatments. The embryonic stem cells (ESCs) have the potential to differentiate into cell types of all three germinal layers, including lung epithelial cells. So they can be a potential source for new cell therapies for hereditary or acquired diseases of the airways and lungs. One method for treatment of lung diseases is cell therapy and the use of ESCs that can replace the damaged epithelial and endothelial cells. Progress using ESCs has developed slowly for lung regeneration because differentiation of lung cells from ESCs is more difficult as compared to differentiation of other cells. The review studies the therapeutic effects of differentiated lung cells from embryonic stem cells in lung diseases. There are few studies of differentiation of ESCs into a lineage of respiratory and then investigation of this cell in experimental model of lung diseases.

  9. Host-microorganism interactions in lung diseases.

    PubMed

    Marsland, Benjamin J; Gollwitzer, Eva S

    2014-12-01

    Until recently, the airways were thought to be sterile unless infected; however, a shift towards molecular methods for the quantification and sequencing of bacterial DNA has revealed that the airways harbour a unique steady-state microbiota. This paradigm shift is changing the way that respiratory research is approached, with a clear need now to consider the effects of host-microorganism interactions in both healthy and diseased lungs. We propose that akin to recent discoveries in intestinal research, dysbiosis of the airway microbiota could underlie susceptibility to, and progression and chronicity of lung disease. In this Opinion article, we summarize current knowledge of the airway microbiota and outline how host-microorganism interactions in the lungs and other tissues might influence respiratory health and disease.

  10. Genetic therapies for cystic fibrosis lung disease.

    PubMed

    Sinn, Patrick L; Anthony, Reshma M; McCray, Paul B

    2011-04-15

    The aim of gene therapy for cystic fibrosis (CF) lung disease is to efficiently and safely express the CF transmembrane conductance regulator (CFTR) in the appropriate pulmonary cell types. Although CF patients experience multi-organ disease, the chronic bacterial lung infections and associated inflammation are the primary cause of shortened life expectancy. Gene transfer-based therapeutic approaches are feasible, in part, because the airway epithelium is directly accessible by aerosol delivery or instillation. Improvements in standard delivery vectors and the development of novel vectors, as well as emerging technologies and new animal models, are propelling exciting new research forward. Here, we review recent developments that are advancing this field of investigation.

  11. Classification of diffuse lung diseases: why and how.

    PubMed

    Hansell, David M

    2013-09-01

    The understanding of complex lung diseases, notably the idiopathic interstitial pneumonias and small airways diseases, owes as much to repeated attempts over the years to classify them as to any single conceptual breakthrough. One of the many benefits of a successful classification scheme is that it allows workers, within and between disciplines, to be clear that they are discussing the same disease. This may be of particular importance in the recruitment of individuals for a clinical trial that requires a standardized and homogeneous study population. Different specialties require fundamentally different things from a classification: for epidemiologic studies, a classification that requires categorization of individuals according to histopathologic pattern is not usually practicable. Conversely, a scheme that simply divides diffuse parenchymal disease into inflammatory and noninflammatory categories is unlikely to further the understanding about the pathogenesis of disease. Thus, for some disease groupings, for example, pulmonary vasculopathies, there may be several appropriate classifications, each with its merits and demerits. There has been an interesting shift in the past few years, from the accepted primacy of histopathology as the sole basis on which the classification of parenchymal lung disease has rested, to new ways of considering how these entities relate to each other. Some inventive thinking has resulted in new classifications that undoubtedly benefit patients and clinicians in their endeavor to improve management and outcome. The challenge of understanding the logic behind current classifications and their shortcomings are explored in various examples of lung diseases.

  12. Biomarkers in Paediatric Cystic Fibrosis Lung Disease.

    PubMed

    Ramsey, Kathryn A; Schultz, André; Stick, Stephen M

    2015-09-01

    Biomarkers in cystic fibrosis are used i. for the measurement of cystic fibrosis transmembrane regulator function in order to diagnose cystic fibrosis, and ii. to assess aspects of lung disease severity (e.g. inflammation, infection). Effective biomarkers can aid disease monitoring and contribute to the development of new therapies. The tests of cystic fibrosis transmembrane regulator function each have unique strengths and weaknesses, and biomarkers of inflammation, infection and tissue destruction have the potential to enhance the management of cystic fibrosis through the early detection of disease processes. The development of biomarkers of cystic fibrosis lung disease, in particular airway inflammation and infection, is influenced by the challenges of obtaining relevant samples from infants and children for whom early detection and treatment of disease might have the greatest long term benefits.

  13. Autophagy in lung disease pathogenesis and therapeutics.

    PubMed

    Ryter, Stefan W; Choi, Augustine M K

    2015-01-01

    Autophagy, a cellular pathway for the degradation of damaged organelles and proteins, has gained increasing importance in human pulmonary diseases, both as a modulator of pathogenesis and as a potential therapeutic target. In this pathway, cytosolic cargos are sequestered into autophagosomes, which are delivered to the lysosomes where they are enzymatically degraded and then recycled as metabolic precursors. Autophagy exerts an important effector function in the regulation of inflammation, and immune system functions. Selective pathways for autophagic degradation of cargoes may have variable significance in disease pathogenesis. Among these, the autophagic clearance of bacteria (xenophagy) may represent a crucial host defense mechanism in the pathogenesis of sepsis and inflammatory diseases. Our recent studies indicate that the autophagic clearance of mitochondria, a potentially protective program, may aggravate the pathogenesis of chronic obstructive pulmonary disease by activating cell death programs. We report similar findings with respect to the autophagic clearance of cilia components, which can contribute to airways dysfunction in chronic lung disease. In certain diseases such as pulmonary hypertension, autophagy may confer protection by modulating proliferation and cell death. In other disorders, such as idiopathic pulmonary fibrosis and cystic fibrosis, impaired autophagy may contribute to pathogenesis. In lung cancer, autophagy has multiple consequences by limiting carcinogenesis, modulating therapeutic effectiveness, and promoting tumor cell survival. In this review we highlight the multiple functions of autophagy and its selective autophagy subtypes that may be of significance to the pathogenesis of human disease, with an emphasis on lung disease and therapeutics.

  14. Interstitial Lung Disease Induced by Pazopanib Treatment

    PubMed Central

    Ide, Shotaro; Sakamoto, Noriho; Hara, Shintaro; Hara, Atsuko; Kakugawa, Tomoyuki; Nakamura, Yoichi; Futsuki, Yoji; Izumikawa, Koichi; Ishimatsu, Yuji; Yanagihara, Katsunori; Mukae, Hiroshi

    2017-01-01

    Although pneumothorax has been reported to be a major pulmonary adverse event in patients treated with pazopanib, a multikinase inhibitor, drug-induced interstitial lung disease (DILD) has not been reported. A 74-year-old Japanese man who received pazopanib for the treatment of femoral leiomyosarcoma and lung metastasis presented with dyspnea and fatigue. He had mild interstitial pneumonia when pazopanib treatment was initiated. Chest computed tomography revealed progressive bilateral ground-glass opacity (GGO) and traction bronchiectasis. We diagnosed DILD due to pazopanib. The patient's pazopanib treatment was interrupted and a steroid was administered. The symptoms and GGO were improved with treatment. Physicians should be aware of DILD due to pazopanib in patients with pre-existing interstitial lung disease. PMID:28050004

  15. Mast cells in airway diseases and interstitial lung disease.

    PubMed

    Cruse, Glenn; Bradding, Peter

    2016-05-05

    Mast cells are major effector cells of inflammation and there is strong evidence that mast cells play a significant role in asthma pathophysiology. There is also a growing body of evidence that mast cells contribute to other inflammatory and fibrotic lung diseases such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. This review discusses the role that mast cells play in airway diseases and highlights how mast cell microlocalisation within specific lung compartments and their cellular interactions are likely to be critical for their effector function in disease.

  16. Detecting Lung Diseases from Exhaled Aerosols: Non-Invasive Lung Diagnosis Using Fractal Analysis and SVM Classification

    PubMed Central

    Xi, Jinxiang; Zhao, Weizhong; Yuan, Jiayao Eddie; Kim, JongWon; Si, Xiuhua; Xu, Xiaowei

    2015-01-01

    Background Each lung structure exhales a unique pattern of aerosols, which can be used to detect and monitor lung diseases non-invasively. The challenges are accurately interpreting the exhaled aerosol fingerprints and quantitatively correlating them to the lung diseases. Objective and Methods In this study, we presented a paradigm of an exhaled aerosol test that addresses the above two challenges and is promising to detect the site and severity of lung diseases. This paradigm consists of two steps: image feature extraction using sub-regional fractal analysis and data classification using a support vector machine (SVM). Numerical experiments were conducted to evaluate the feasibility of the breath test in four asthmatic lung models. A high-fidelity image-CFD approach was employed to compute the exhaled aerosol patterns under different disease conditions. Findings By employing the 10-fold cross-validation method, we achieved 100% classification accuracy among four asthmatic models using an ideal 108-sample dataset and 99.1% accuracy using a more realistic 324-sample dataset. The fractal-SVM classifier has been shown to be robust, highly sensitive to structural variations, and inherently suitable for investigating aerosol-disease correlations. Conclusion For the first time, this study quantitatively linked the exhaled aerosol patterns with their underlying diseases and set the stage for the development of a computer-aided diagnostic system for non-invasive detection of obstructive respiratory diseases. PMID:26422016

  17. Interstitial lung disease probably caused by imipramine.

    PubMed

    Deshpande, Prasanna R; Ravi, Ranjani; Gouda, Sinddalingana; Stanley, Weena; Hande, Manjunath H

    2014-01-01

    Drugs are rarely associated with causing interstitial lung disease (ILD). We report a case of a 75-year-old woman who developed ILD after exposure to imipramine. To our knowledge, this is one of the rare cases of ILD probably caused due to imipramine. There is need to report such rare adverse effects related to ILD and drugs for better management of ILD.

  18. Lymphomatoid granulomatosis mimicking interstitial lung disease.

    PubMed

    Braham, Emna; Ayadi-Kaddour, Aïda; Smati, Belhassen; Ben Mrad, Sonia; Besbes, Mohammed; El Mezni, Faouzi

    2008-11-01

    Lymphoid granulomatosis is a rare form of pulmonary angiitis. This case report presents a patient with lymphoid granulomatosis in whom the clinical presentation, radiological features and the partial response to corticosteroid therapy mimicked interstitial lung disease. Lymphoid granulomatosis was only diagnosed at post-mortem examination. The range of reported clinical presentations, diagnostic approaches and outcomes are described.

  19. Eosinophilic lung diseases: a clinical, radiologic, and pathologic overview.

    PubMed

    Jeong, Yeon Joo; Kim, Kun-Il; Seo, Im Jeong; Lee, Chang Hun; Lee, Ki Nam; Kim, Ki Nam; Kim, Jeung Sook; Kwon, Woon Jung

    2007-01-01

    Eosinophilic lung diseases are a diverse group of pulmonary disorders associated with peripheral or tissue eosinophilia. They are classified as eosinophilic lung diseases of unknown cause (simple pulmonary eosinophilia [SPE], acute eosinophilic pneumonia [AEP], chronic eosinophilic pneumonia [CEP], idiopathic hypereosinophilic syndrome [IHS]), eosinophilic lung diseases of known cause (allergic bronchopulmonary aspergillosis [ABPA], bronchocentric granulomatosis [BG], parasitic infections, drug reactions), and eosinophilic vasculitis (allergic angiitis, granulomatosis [Churg-Strauss syndrome]). The percentages of eosinophils in peripheral blood and bronchoalveolar lavage fluid are essential parts of the evaluation. Chest computed tomography (CT) demonstrates a more characteristic pattern and distribution of parenchymal opacities than does conventional chest radiography. At CT, SPE and IHS are characterized by single or multiple nodules with a surrounding ground-glass-opacity halo, AEP mimics radiologically hydrostatic pulmonary edema, and CEP is characterized by nonsegmental airspace consolidations with peripheral predominance. ABPA manifests with bilateral central bronchiectasis with or without mucoid impaction. The CT manifestations of BG are nonspecific and consist of a focal mass or lobar consolidation with atelectasis. The most common CT findings in Churg-Strauss syndrome include sub-pleural consolidation with lobular distribution, centrilobular nodules, bronchial wall thickening, and interlobular septal thickening. The integration of clinical, radiologic, and pathologic findings facilitates the initial and differential diagnoses of various eosinophilic lung diseases.

  20. Epigenetic targets for novel therapies of lung diseases.

    PubMed

    Comer, Brian S; Ba, Mariam; Singer, Cherie A; Gerthoffer, William T

    2015-03-01

    In spite of substantial advances in defining the immunobiology and function of structural cells in lung diseases there is still insufficient knowledge to develop fundamentally new classes of drugs to treat many lung diseases. For example, there is a compelling need for new therapeutic approaches to address severe persistent asthma that is insensitive to inhaled corticosteroids. Although the prevalence of steroid-resistant asthma is 5-10%, severe asthmatics require a disproportionate level of health care spending and constitute a majority of fatal asthma episodes. None of the established drug therapies including long-acting beta agonists or inhaled corticosteroids reverse established airway remodeling. Obstructive airways remodeling in patients with chronic obstructive pulmonary disease (COPD), restrictive remodeling in idiopathic pulmonary fibrosis (IPF) and occlusive vascular remodeling in pulmonary hypertension are similarly unresponsive to current drug therapy. Therefore, drugs are needed to achieve long-acting suppression and reversal of pathological airway and vascular remodeling. Novel drug classes are emerging from advances in epigenetics. Novel mechanisms are emerging by which cells adapt to environmental cues, which include changes in DNA methylation, histone modifications and regulation of transcription and translation by noncoding RNAs. In this review we will summarize current epigenetic approaches being applied to preclinical drug development addressing important therapeutic challenges in lung diseases. These challenges are being addressed by advances in lung delivery of oligonucleotides and small molecules that modify the histone code, DNA methylation patterns and miRNA function.

  1. Interstitial lung disease in connective tissue disease--mechanisms and management.

    PubMed

    Wells, Athol U; Denton, Christopher P

    2014-12-01

    Pulmonary complications are an important extra-articular feature of autoimmune rheumatic diseases and a major cause of mortality. The underlying pathogenesis probably involves multiple cellular compartments, including the epithelium, lung fibroblasts, and the innate and adaptive immune system. Heterogeneity in the extent and progression of lung fibrosis probably reflects differences in underlying pathogenic mechanisms. Growing understanding of the key pathogenic drivers of lung fibrosis might lead to the development of more effective targeted therapies to replicate the treatment advances in other aspects of these diseases. Interstitial lung disease (ILD) in connective tissue disease (CTD) is characterized using the classification of the idiopathic interstitial pneumonias. Systemic sclerosis is most frequently associated with ILD and, in most of these patients, ILD manifests as a histological pattern of nonspecific interstitial pneumonia. Conversely, in rheumatoid arthritis, the pattern of ILD is most often usual interstitial pneumonia. The key goals of clinical assessment of patients with both ILD and CTD are the detection of ILD and prognostic evaluation to determine which patients should be treated. Data from treatment trials in systemic sclerosis support the use of immunosuppressive therapy, with the treatment benefit largely relating to the prevention of progression of lung disease.

  2. Antioxidant vitamins and prevention of lung disease

    SciTech Connect

    Menzel, D.B. )

    1992-09-30

    Although the evidence for oxidative stress for air pollution in the human lung is fragmentary, the hypothesis that oxidative stress is an important, if not the sole, mechanism of toxicity of oxidizing air pollutants and tobacco smoke is compelling and growing. First, biochemical mechanisms have been worked out for oxidation of lung lipids by the gas phase of cigarette smoke, NO[sub 2] and O[sub 3]. The oxidation of lung lipids can be prevented by both vitamins C and E. Vitamin C is more effective in preventing oxidation by NO[sub 2], and vitamin E is more effective against O[sub 3]. Second, multiple species of experimental animals develop lung disease similar to human bronchitis and emphysema from exposure to NO[sub 2] and O[sub 3], respectively. The development of these diseases occurs over a near lifetime exposure when the levels of NO[sub 2] or O[sub 3] are at near ambient air pollution values. Third, isolated human cells are protected against oxidative damage from NO[sub 2] and O[sub 3] by both vitamins C and E. Fourth, the vitamin C level in the lung either declines on exposure to NO[sub 2] for short-term exposures or increases on chronic cigarette smoke exposure. The effects of cigarette smoking on serum vitamin C is apparently complex and may be related to the daily intake of vitamin C as well as smoking. Serum vitamin C levels may be poor indicators of lung demands when daily vitamin C intakes are above 100 mg/day. Fifth, vitamin C supplementation protects against the effects of ambient levels of air pollution in adults as measured by histamine challenge. An augmented response to histamine challenge may represent increased lung permeability brought about by air pollution. In experimental animal and human experiments, the amount of vitamin C or E that afforded protection was in excess of the current recommended dietary allowance.

  3. Extracellular matrix mechanics in lung parenchymal diseases.

    PubMed

    Suki, Béla; Bates, Jason H T

    2008-11-30

    In this review, we examine how the extracellular matrix (ECM) of the lung contributes to the overall mechanical properties of the parenchyma, and how these properties change in disease. The connective tissues of the lung are composed of cells and ECM, which includes a variety of biological macromolecules and water. The macromolecules that are most important in determining the mechanical properties of the ECM are collagen, elastin, and proteoglycans. We first discuss the various components of the ECM and how their architectural organization gives rise to the mechanical properties of the parenchyma. Next, we examine how mechanical forces can affect the physiological functioning of the lung parenchyma. Collagen plays an especially important role in determining the homeostasis and cellular responses to injury because it is the most important load-bearing component of the parenchyma. We then demonstrate how the concept of percolation can be used to link microscopic pathologic alterations in the parenchyma to clinically measurable lung function during the progression of emphysema and fibrosis. Finally, we speculate about the possibility of using targeted tissue engineering to optimize treatment of these two major lung diseases.

  4. Pathophysiology of Pulmonary Hypertension in Chronic Parenchymal Lung Disease.

    PubMed

    Singh, Inderjit; Ma, Kevin Cong; Berlin, David Adam

    2016-04-01

    Pulmonary hypertension commonly complicates chronic obstructive pulmonary disease and interstitial lung disease. The association of chronic lung disease and pulmonary hypertension portends a worse prognosis. The pathophysiology of pulmonary hypertension differs in the presence or absence of lung disease. We describe the physiological determinants of the normal pulmonary circulation to better understand the pathophysiological factors implicated in chronic parenchymal lung disease-associated pulmonary hypertension. This review will focus on the pathophysiology of 3 forms of chronic lung disease-associated pulmonary hypertension: idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, and sarcoidosis.

  5. Building a reference multimedia database for interstitial lung diseases.

    PubMed

    Depeursinge, Adrien; Vargas, Alejandro; Platon, Alexandra; Geissbuhler, Antoine; Poletti, Pierre-Alexandre; Müller, Henning

    2012-04-01

    This paper describes the methodology used to create a multimedia collection of cases with interstitial lung diseases (ILDs) at the University Hospitals of Geneva. The dataset contains high-resolution computed tomography (HRCT) image series with three-dimensional annotated regions of pathological lung tissue along with clinical parameters from patients with pathologically proven diagnoses of ILDs. The motivations for this work is to palliate the lack of publicly available collections of ILD cases to serve as a basis for the development and evaluation of image-based computerized diagnostic aid. After 38 months of data collection, the library contains 128 patients affected with one of the 13 histological diagnoses of ILDs, 108 image series with more than 41l of annotated lung tissue patterns as well as a comprehensive set of 99 clinical parameters related to ILDs. The database is available for research on request and after signature of a license agreement.

  6. Flavorings-Related Lung Disease

    MedlinePlus

    ... Symptoms Medical Tests Medical Management Disease Reporting This topic page provides a resource for findings and recommendations by ... NIOSH Homepage NIOSH A-Z Workplace Safety & Health Topics Publications and ... file RIS file Page last reviewed: August 11, 2011 Page last updated: ...

  7. Risk of lung cancer in Parkinson's disease

    PubMed Central

    Xie, Xin; Luo, Xiaoguang; Xie, Mingliang; Liu, Yang; Wu, Ting

    2016-01-01

    Recently, growing evidence has revealed the significant association between Parkinson's disease (PD) and cancer. However, controversy still exists concerning the association between PD and lung cancer. A comprehensive article search for relevant studies published was performed using the following online databases: PubMed, Web of Science and Embase up to August 31, 2016. The pooled risk ratio (RR) and their 95 % confidence intervals (CI) were calculated using the method of inverse variance with the random-effects model. Fifteen studies comprising 348,780 PD patients were included in this study. The pooled result indicated that patients with PD were significantly associated with a decreased risk of lung cancer (RR: 0.53, 95% CI: 0.41−0.70, P < 0.001). In addition, subgroup analyses performed in Western population also confirmed the significant inverse relationship between PD and risk of lung cancer (RR: 0.48, 95% CI: 0.39−0.60, P < 0.001). In the subgroup analysis, a reduced risk of lung cancer in PD patients from Western population was consistent regardless of study design, gender, or study quality. In conclusion, PD patients were significantly associated with a reduced risk of lung cancer in Western population. The relationship between them in Asian population needs to be confirmed by future studies. PMID:27801674

  8. Clinical significance of respiratory bronchiolitis on open lung biopsy and its relationship to smoking related interstitial lung disease

    PubMed Central

    Moon, J.; du Bois, R. M; Colby, T.; Hansell, D.; Nicholson, A.

    1999-01-01

    BACKGROUND—Respiratory bronchiolitis-associated interstitial lung disease (RBILD) is a rare form of interstitial lung disease which may present in similar fashion to other types of chronic interstitial pneumonia. The purpose of this study was to undertake a clinicopathological review of 10 patients with RBILD and to examine the clinical and imaging data related to its histopathological pattern, in particular the relationship of RBILD to smoking.
METHODS—Thirteen out of 168 retrospectively reviewed patients, from whom biopsy specimens were taken for suspected diffuse lung disease, were identified with a histopathological pattern of RBILD. Three cases were rejected as follow up data were unavailable. The 10remaining cases constituted the study group and both clinical and imaging data were collected from patients' notes and referring physicians.
RESULTS—Histopathologically, four cases of RBILD overlapped with the pattern of desquamative interstitial pneumonitis (DIP) and nine also had microscopic evidence of centrilobular emphysema. Nine patients were smokers, ranging from 3 to 80 pack years. The one non-smoker had an occupational exposure to the fumes of solder flux. The sex distribution was equal with an age range of 32-65 years. Two patients were clubbed. Lung function tests showed both restrictive and obstructive patterns together with severe reductions in carbon monoxide transfer factor in seven patients. Chest radiographs showed reticular or reticulonodular infiltrates in five patients and a ground glass pattern in two. CT scans were consistent with either DIP or RBILD in six of eight patients. Although seven patients remained stable or improved, either with or without treatment, three patients deteriorated.
CONCLUSIONS—This study adds weight to the hypothesis that smoking can cause clinically significant interstitial lung disease, with deterioration in pulmonary function despite treatment. Given the overlapping histopathological patterns of RBILD

  9. Pericardial Fat Is Associated With Impaired Lung Function and a Restrictive Lung Pattern in Adults

    PubMed Central

    Liu, Jiankang; Bidulescu, Aurelian; Burchfiel, Cecil M.; Taylor, Herman A.; Petrini, Marcy F.

    2011-01-01

    Background: Impaired lung function has been linked to obesity and systemic inflammation. Pericardial fat has been shown to be associated with anomalies in cardiac structure, function, and atherosclerosis. We hypothesized that pericardial fat may have a similar role in the impairment of lung function. Methods: Cross-sectional associations of pericardial fat volumes, quantified by multidetector CT scan, with FEV1 and FVC assessed by spirometry, were investigated in 1,293 participants (54.5 ± 10.8 years; 66.4% women) in the Jackson Heart Study. We also examined whether these associations were independent of visceral adipose tissue (VAT). Results: Pericardial fat was associated with impaired lung function after multivariable adjustment, but these associations generally did not remain after adjustment for VAT. An exception was the FEV1/FVC ratio. Higher pericardial fat volumes were associated with higher odds of a restrictive lung pattern and lower odds of airway obstruction. Participants in the highest quartile had the highest odds of a restrictive lung pattern (OR, 1.85; 95% CI, 1.22-2.79, compared with quartile 1), even after adjustment for VAT. The odds of obstruction decreased across increasing quartiles of pericardial fat. These relationships were generally graded, suggesting dose-response trends. Conclusions: Pericardial fat is generally associated with lower lung function and independently associated with a restrictive lung pattern in middle-aged and elderly adults. Further research is needed to fully understand the mechanisms through which pericardial fat contributes to pulmonary anomalies. PMID:21737489

  10. Gastroesophageal Reflux Disease in Children with Interstitial Lung Disease.

    PubMed

    Dziekiewicz, M A; Karolewska-Bochenek, K; Dembiński, Ł; Gawronska, A; Krenke, K; Lange, J; Banasiuk, M; Kuchar, E; Kulus, M; Albrecht, P; Banaszkiewicz, A

    2016-01-01

    Gastroesophageal reflux disease is common in adult patients with interstitial lung disease. However, no data currently exist regarding the prevalence and characteristics of the disease in pediatric patients with interstitial lung disease. The aim of the present study was to prospectively assess the incidence of gastroesophageal reflux disease and characterize its features in children with interstitial lung disease. Gastroesophageal reflux disease was established based on 24 h pH-impedance monitoring (MII-pH). Gastroesophageal reflux episodes (GERs) were classified according to widely recognized criteria as acid, weakly acid, weakly alkaline, or proximal. Eighteen consecutive patients (15 boys, aged 0.2-11.6 years) were enrolled in the study. Gastroesophageal reflux disease was diagnosed in a half (9/18) of children. A thousand GERs were detected by MII-pH (median 53.5; IQR 39.0-75.5). Of these, 585 (58.5 %) episodes were acidic, 407 (40.7 %) were weakly acidic, and eight (0.8 %) were weakly alkaline. There were 637 (63.7 %) proximal GERs. The patients in whom gastroesophageal reflux disease was diagnosed had a significantly higher number of proximal and total GERs. We conclude that the prevalence of gastroesophageal reflux disease in children with interstitial lung disease is high; thus, the disease should be considered regardless of presenting clinical symptoms. A high frequency of non-acid and proximal GERs makes the MII-pH method a preferable choice for the detection of reflux episodes in this patient population.

  11. Using lung cancer mortality to indirectly approximate smoking patterns in space.

    PubMed

    Jürgens, Verena; Ess, Silvia; Schwenkglenks, Matthias; Cerny, Thomas; Vounatsou, Penelope

    2015-01-01

    Smoking is the leading cause of lung cancer. Non-smoking factors have been associated with the disease. Existing Swiss survey data only capture the country partially and temporal coverage does not allow for a time lag between exposure to tobacco and lung cancer outbreak. Knowledge about the distribution of tobacco-use is essential to estimate its contribution to disease burden. Bayesian regression models were applied to estimate spatial smoking patterns. Data were provided from the Swiss Health Survey (14521 participants). Regression models with spatial random effects (SREs) were employed to obtain smoking proxies based on mortality rates and SREs adjusted for environmental exposures. Population attributable fractions were estimated to assess the burden of tobacco-use on lung cancer mortality. Correlation between observed smoking prevalence with smoking proxies was moderate and stronger in females. In the absence of sufficient survey data, smooth unadjusted mortality rates can be used to assess smoking patterns in Switzerland.

  12. Genetic therapies for cystic fibrosis lung disease

    PubMed Central

    Sinn, Patrick L.; Anthony, Reshma M.; McCray, Paul B.

    2011-01-01

    The aim of gene therapy for cystic fibrosis (CF) lung disease is to efficiently and safely express the CF transmembrane conductance regulator (CFTR) in the appropriate pulmonary cell types. Although CF patients experience multi-organ disease, the chronic bacterial lung infections and associated inflammation are the primary cause of shortened life expectancy. Gene transfer-based therapeutic approaches are feasible, in part, because the airway epithelium is directly accessible by aerosol delivery or instillation. Improvements in standard delivery vectors and the development of novel vectors, as well as emerging technologies and new animal models, are propelling exciting new research forward. Here, we review recent developments that are advancing this field of investigation. PMID:21422098

  13. Lung and Heart Disease Secondary to Liver Disease

    PubMed Central

    Goldberg, David S.; Fallon, Michael B.

    2015-01-01

    Patients with chronic liver disease are at risk of extra-hepatic complications related to cirrhosis and portal hypertension, as well organ-specific complications of certain liver diseases. These complications can compromise quality-of-life, while also increasing morbidity and mortality pre- and post-liver transplantation. Patients with chronic liver disease are at risk for pulmonary complications of hepaotpulmonary syndrome and portopulmonary syndrome; the major cardiac complication falls under the general concept of the cirrhotic cardiomyopathy, which can affect systolic and diastolic function, as well as cardiac conduction. In addition, patients with certain diseases are at risk of lung and/or cardiac complications that are specific to the primary disease (i.e., emphysema in alpha-1-antitrypsin deficiency) or occur with increased incidence in certain conditions (i.e., ischemic heart disease associated with non-alcoholic steatohepatitis. This section will focus on the epidemiology, clinical presentation, pathogenesis, treatment options, and role of transplantation for lung and heart diseases secondary to liver disease, while also highlighting select liver diseases that directly affect the lungs and hearts. PMID:25934564

  14. Asbestos-induced lung diseases: an update

    PubMed Central

    KAMP, DAVID W.

    2009-01-01

    Asbestos causes asbestosis (pulmonary fibrosis caused by asbestos inhalation) and malignancies (bronchogenic carcinoma and mesothelioma) by mechanisms that are not fully elucidated. Despite a dramatic reduction in asbestos use worldwide, asbestos-induced lung diseases remain a substantial health concern primarily because of the vast amounts of fibers that have been mined, processed, and used during the 20th century combined with the long latency period of up to 40 years between exposure and disease presentation. This review summarizes the important new epidemiologic and pathogenic information that has emerged over the past several years. Whereas the development of asbestosis is directly associated with the magnitude and duration of asbestos exposure, the development of a malignant clone of cells can occur in the setting of low-level asbestos exposure. Emphasis is placed on the recent epidemiologic investigations that explore the malignancy risk that occurs from nonoccupational, environmental asbestos exposure. Accumulating studies are shedding light on novel mechanistic pathways by which asbestos damages the lung. Attention is focused on the importance of alveolar epithelial cell (AEC) injury and repair, the role of iron-derived reactive oxygen species (ROS), and apoptosis by the p53- and mitochondria-regulated death pathways. Furthermore, recent evidence underscores crucial roles for specific cellular signaling pathways that regulate the production of cytokines and growth factors. An evolving role for epithelial-mesenchymal transition (EMT) is also reviewed. The translational significance of these studies is evident in providing the molecular basis for developing novel therapeutic strategies for asbestos-related lung diseases and, importantly, other pulmonary diseases, such as interstitial pulmonary fibrosis and lung cancer. PMID:19304273

  15. Pulmonary hypertension in chronic lung diseases.

    PubMed

    Seeger, Werner; Adir, Yochai; Barberà, Joan Albert; Champion, Hunter; Coghlan, John Gerard; Cottin, Vincent; De Marco, Teresa; Galiè, Nazzareno; Ghio, Stefano; Gibbs, Simon; Martinez, Fernando J; Semigran, Marc J; Simonneau, Gerald; Wells, Athol U; Vachiéry, Jean-Luc

    2013-12-24

    Chronic obstructive lung disease (COPD) and diffuse parenchymal lung diseases (DPLD), including idiopathic pulmonary fibrosis (IPF) and sarcoidosis, are associated with a high incidence of pulmonary hypertension (PH), which is linked with exercise limitation and a worse prognosis. Patients with combined pulmonary fibrosis and emphysema (CPFE) are particularly prone to the development of PH. Echocardiography and right heart catheterization are the principal modalities for the diagnosis of COPD and DPLD. For discrimination between group 1 PH patients with concomitant respiratory abnormalities and group 3 PH patients (PH caused by lung disease), patients should be transferred to a center with expertise in both PH and lung diseases for comprehensive evaluation. The task force encompassing the authors of this article provided criteria for this discrimination and suggested using the following definitions for group 3 patients, as exemplified for COPD, IPF, and CPFE: COPD/IPF/CPFE without PH (mean pulmonary artery pressure [mPAP] <25 mm Hg); COPD/IPF/CPFE with PH (mPAP ≥25 mm Hg); PH-COPD, PH-IPF, and PH-CPFE); COPD/IPF/CPFE with severe PH (mPAP ≥35 mm Hg or mPAP ≥25 mm Hg with low cardiac index [CI <2.0 l/min/m(2)]; severe PH-COPD, severe PH-IPF, and severe PH-CPFE). The "severe PH group" includes only a minority of chronic lung disease patients who are suspected of having strong general vascular abnormalities (remodeling) accompanying the parenchymal disease and with evidence of an exhausted circulatory reserve rather than an exhausted ventilatory reserve underlying the limitation of exercise capacity. Exertional dyspnea disproportionate to pulmonary function tests, low carbon monoxide diffusion capacity, and rapid decline of arterial oxygenation upon exercise are typical clinical features of this subgroup with poor prognosis. Studies evaluating the effect of pulmonary arterial hypertension drugs currently not approved for group 3 PH patients should focus on

  16. [Pulmonary hypertension in chronic lung diseases].

    PubMed

    Seeger, Werner; Adir, Yochai; Barberà, Joan Albert; Champion, Hunter; Coghlan, John Gerard; Cottin, Vincent; De Marco, Teresa; Galiè, Nazzareno; Ghio, Stefano; Gibbs, Simon; Martinez, Fernando J; Semigran, Marc J; Simonneau, Gerald; Wells, Athol U; Vachiéy, Jean-Luc

    2014-10-01

    Chronic obstructive lung disease (COPD) and diffuse parenchymal lung diseases (DPLD), including idiopathic pulmonary fibrosis (IPF) and sarcoidosis, are associated with a high incidence of pulmonary hypertension (PH), which is linked with exercise limitation and a worse prognosis. Patients with combined pulmonary fibrosis and emphysema (CPFE) are particularly prone to the development of PH. Echocardiography and right heart catheterization are the principal modalities for the diagnosis of COPD and DPLD. For discrimination between group 1 PH patients with concomitant respiratory abnormalities and group 3 PH patients (PH caused by lung disease), patients should be transferred to a center with expertise in both PH and lung diseases for comprehensive evaluation. The task force encompassing the .authors of this article provided criteria for this discrimination and suggested using the following definitions for group 3 patients, as exemplified for COPD, IPF, and CPFE: COPD/IPF/CPFE without PH (mean pulmonary artery pressure [mPAP]<25mmHg); COPD/IPF/CPFE with PH (mPAP25mmHg); PH-COPD, PH-IPF, and PH-CPFE); COPD/IPF/CPFE with severe PH (mPAP 35 mmHg or mPAP 25 mmHg with low cardiac index [CI <2.0.l/min/m2]; severe PH-COPD, severe PH-IPF, and severe PH-CPFE). The "severe PH group" includes only a minority of chronic lung disease patients who are suspected of having strong general vascular abnormalities (remodeling) accompanying the parenchymal disease and with evidence of an exhausted circulatory reserve rather than an exhausted ventilatory reserve underlying the limitation of exercise capacity. Exertional dyspnea disproportionate to pulmonary function tests, low carbon monoxide diffusion capacity, and rapid decline of arterial oxygenation upon exercise are typical clinical features of this subgroup with poor prognosis. Studies evaluating the effect of pulmonary arterial hypertension drugs currently not approved for group 3 PH patients should focus on this severe PH group

  17. Obstructive lung disease models: what is valid?

    PubMed

    Ferdinands, Jill M; Mannino, David M

    2008-12-01

    Use of disease simulation models has led to scrutiny of model methods and demand for evidence that models credibly simulate health outcomes. We sought to describe recent obstructive lung disease simulation models and their validation. Medline and EMBASE were used to identify obstructive lung disease simulation models published from January 2000 to June 2006. Publications were reviewed to assess model attributes and four types of validation: first-order (verification/debugging), second-order (comparison with studies used in model development), third-order (comparison with studies not used in model development), and predictive validity. Six asthma and seven chronic obstructive pulmonary disease models were identified. Seven (54%) models included second-order validation, typically by comparing observed outcomes to simulations of source study cohorts. Seven (54%) models included third-order validation, in which modeled outcomes were usually compared qualitatively for agreement with studies independent of the model. Validation endpoints included disease prevalence, exacerbation, and all-cause mortality. Validation was typically described as acceptable, despite near-universal absence of criteria for judging adequacy of validation. Although over half of recent obstructive lung disease simulation models report validation, inconsistencies in validation methods and lack of detailed reporting make assessing adequacy of validation difficult. For simulation modeling to be accepted as a tool for evaluating clinical and public health programs, models must be validated to credibly simulate health outcomes of interest. Defining the required level of validation and providing guidance for quantitative assessment and reporting of validation are important future steps in promoting simulation models as practical decision tools.

  18. Divers' lung function: small airways disease?

    PubMed Central

    Thorsen, E; Segadal, K; Kambestad, B; Gulsvik, A

    1990-01-01

    Pulmonary function was measured in 152 professional saturation divers and in a matched control group of 106 subjects. Static lung volumes, dynamic lung volumes and flows, transfer factor for carbon monoxide (T1CO), transfer volume per unit alveolar volume (KCO), delta-N2, and closing volume (CV) were measured and compared with reference values from recent Scandinavian studies, British submariners, and the European Community for Coal and Steel (ECCS) recommended reference values. Diving exposure was assessed as years of diving experience, total number of days in saturation and depth, and as the product of days in saturation and mean depth. Divers had significantly lower values for forced expired volume in one second (FEV1), FEV1/forced vital capacity (FVC) ratio, FEF25-75%, FEF75-85%, FEF50%, FEF75%, T1CO, and KCO compared with the controls and a significantly higher CV. There was a positive correlation between diving exposure and CV, whereas the other variables had negative correlations with diving exposure. Values for the control group were not different from the predictive values of Scandinavian reference studies or British submariners, although the ECCS standard predicted significantly lower values for the lung function variables both in divers and the control group. The pattern of the differences in lung function variables between the divers and controls is consistent with small airways dysfunction and with the transient changes in lung function found immediately after a single saturation dive. The association between reduced pulmonary function and previous diving exposure further indicates the presence of cumulative long term effects of diving on pulmonary function. PMID:2393630

  19. Bag-of-features approach for improvement of lung tissue classification in diffuse lung disease

    NASA Astrophysics Data System (ADS)

    Kato, Noriji; Fukui, Motofumi; Isozaki, Takashi

    2009-02-01

    Many automated techniques have been proposed to classify diffuse lung disease patterns. Most of the techniques utilize texture analysis approaches with second and higher order statistics, and show successful classification result among various lung tissue patterns. However, the approaches do not work well for the patterns with inhomogeneous texture distribution within a region of interest (ROI), such as reticular and honeycombing patterns, because the statistics can only capture averaged feature over the ROI. In this work, we have introduced the bag-of-features approach to overcome this difficulty. In the approach, texture images are represented as histograms or distributions of a few basic primitives, which are obtained by clustering local image features. The intensity descriptor and the Scale Invariant Feature Transformation (SIFT) descriptor are utilized to extract the local features, which have significant discriminatory power due to their specificity to a particular image class. In contrast, the drawback of the local features is lack of invariance under translation and rotation. We improved the invariance by sampling many local regions so that the distribution of the local features is unchanged. We evaluated the performance of our system in the classification task with 5 image classes (ground glass, reticular, honeycombing, emphysema, and normal) using 1109 ROIs from 211 patients. Our system achieved high classification accuracy of 92.8%, which is superior to that of the conventional system with the gray level co-occurrence matrix (GLCM) feature especially for inhomogeneous texture patterns.

  20. Pulmonary hypertension in chronic interstitial lung diseases.

    PubMed

    Caminati, Antonella; Cassandro, Roberto; Harari, Sergio

    2013-09-01

    Pulmonary hypertension (PH) is a common complication of interstitial lung diseases (ILDs), particularly in idiopathic pulmonary fibrosis and ILD associated with connective tissue disease. However, other lung diseases, such as combined pulmonary fibrosis and emphysema syndrome, pulmonary Langerhans cell histiocytosis, and lymphangioleiomyomatosis, may also include PH in their clinical manifestations. In all of these diseases, PH is associated with reduced exercise capacity and poor prognosis. The degree of PH in ILDs is typically mild-to-moderate. However, some of these patients may develop a disproportionate increase in PH that cannot be justified solely by hypoxia and parenchymal injury: this condition has been termed "out-of-proportion" PH. The pathogenesis of PH in these diseases is various, incompletely understood and may be multifactorial. The clinical suspicion (i.e. increased dyspnoea, low diffusion capacity) and echocardiographic assessment are the first steps towards proper diagnosis of PH; however, right heart catheterisation remains the current gold standard for diagnosis of PH. At present, no specific therapies have been approved for the treatment of PH in patients with ILDs.

  1. Nontuberculous mycobacterial pulmonary disease mimicking lung cancer

    PubMed Central

    Hong, Su Jin; Kim, Tae Jung; Lee, Jae-Ho; Park, Jeong-Soo

    2016-01-01

    Abstract To describe the features and clinical implications of computed tomography (CT), positron emission tomography (PET), and percutaneous needle aspiration biopsy (PCNB) in pulmonary nontuberculous mycobacterial (NTM) disease manifesting as a solitary nodule, mass, or mass-like consolidation mimicking malignancy. Among a cohort of 388 patients with NTM pulmonary disease, 14 patients with clinically and radiologically suspected lung cancer were included in our study. Two chest radiologists evaluated CT features, including lesion type (nodule, mass, or mass-like consolidation), morphologic features (margin, degree of enhancement, calcification), and presence of accompanying findings suggestive of NTM pulmonary disease (bronchiectasis with clustered centrilobular nodules or upper-lobe cavitary lesions) by consensus. Diagnostic procedures for microbiologic diagnosis of NTM disease and clinical outcome were reviewed. Incidence of NTM pulmonary disease presenting as solitary nodule/mass (n = 8) or mass-like consolidation (n = 6) was 3.6% (14 of 388). Most lesions were detected incidentally during routine health check-up or evaluation of other disease (11 of 14, 79%). Lesions typically showed poor contrast-enhancement (9 of 12) and internal calcification (6 of 14). No lesions had CT features suggestive of NTM pulmonary disease. All 4 lesions for which PET/CT imaging was performed showed strong fluorodeoxyglucose uptake simulating malignant lesions (mean, 4.9; range, 3.6–7.8). PCNB revealed mycobacterial histology in 6 of 11 specimens and positive culture results were obtained for 7 of 7 specimens. NTM pulmonary disease may present as a solitary nodule, mass, or mass-like consolidation mimicking malignancy. CT features and PCNB are important to diagnose NTM disease mimicking lung cancer to avoid unnecessary surgery. PMID:27367996

  2. Diagnosis and Treatment of Nontuberculous Mycobacterial Lung Disease.

    PubMed

    Kwon, Yong-Soo; Koh, Won-Jung

    2016-05-01

    Nontuberculous mycobacteria (NTM) are ubiquitous organisms; their isolation from clinical specimens does not always indicate clinical disease. The incidence of NTM lung diseases has been increasing worldwide. Although the geographic diversity of NTM species is well known, Mycobacterium avium complex (MAC), M. abscessus complex (MABC), and M. kansasii are the most commonly encountered and important etiologic organisms. Two distinct types of NTM lung diseases have been reported, namely fibrocavitary and nodular bronchiectatic forms. For laboratory diagnosis of NTM lung diseases, both liquid and solid media cultures and species-level identification are strongly recommended to enhance growth detection and determine the clinical relevance of isolates. Treatment for NTM lung diseases consists of a multidrug regimen and a long course of therapy, lasting more than 12 months after negative sputum conversion. For MAC lung disease, several new macrolide-based regimens are now recommended. For nodular bronchiectatic forms of MAC lung diseases, an intermittent three-time-weekly regimen produces outcomes similar to those of daily therapy. Treatment of MABC lung disease is very difficult, requiring long-term use of parenteral agents in combination with new macrolides. Treatment outcomes are much better for M. massiliense lung disease than for M. abscessus lung disease. Thus, precise identification of species in MABC infection is needed for the prediction of antibiotic response. Likewise, increased efforts to improve treatment outcomes and develop new agents for NTM lung disease are needed.

  3. Diagnosis and Treatment of Nontuberculous Mycobacterial Lung Disease

    PubMed Central

    2016-01-01

    Nontuberculous mycobacteria (NTM) are ubiquitous organisms; their isolation from clinical specimens does not always indicate clinical disease. The incidence of NTM lung diseases has been increasing worldwide. Although the geographic diversity of NTM species is well known, Mycobacterium avium complex (MAC), M. abscessus complex (MABC), and M. kansasii are the most commonly encountered and important etiologic organisms. Two distinct types of NTM lung diseases have been reported, namely fibrocavitary and nodular bronchiectatic forms. For laboratory diagnosis of NTM lung diseases, both liquid and solid media cultures and species-level identification are strongly recommended to enhance growth detection and determine the clinical relevance of isolates. Treatment for NTM lung diseases consists of a multidrug regimen and a long course of therapy, lasting more than 12 months after negative sputum conversion. For MAC lung disease, several new macrolide-based regimens are now recommended. For nodular bronchiectatic forms of MAC lung diseases, an intermittent three-time-weekly regimen produces outcomes similar to those of daily therapy. Treatment of MABC lung disease is very difficult, requiring long-term use of parenteral agents in combination with new macrolides. Treatment outcomes are much better for M. massiliense lung disease than for M. abscessus lung disease. Thus, precise identification of species in MABC infection is needed for the prediction of antibiotic response. Likewise, increased efforts to improve treatment outcomes and develop new agents for NTM lung disease are needed. PMID:27134484

  4. Changing patterns of wildlife diseases

    USGS Publications Warehouse

    McLean, R.G.

    2001-01-01

    The purpose of this paper was not to analyze the effects of global warming on wildlife disease patterns, but to serve as a springboard for future efforts to identify those wildlife diseases, including zoonotic diseases, that could be influenced the most by warming climates and to encourage the development of models to examine the potential effects. Hales et al. (1999) examined the relationship of the incidence of a vector-borne human disease, Dengue fever, and El Nino southern oscillations for South Pacific Island nations. The development of similar models on specific wildlife diseases which have environmental factors strongly associated with transmission would provide information and options for the future management of our wildlife resources.

  5. Diagnosis and treatment of cystic lung disease

    PubMed Central

    Park, Sanghoon; Lee, Eun Joo

    2017-01-01

    Cystic lung disease (CLD) is a group of lung disorders characterized by the presence of multiple cysts, defined as air-filled lucencies or low-attenuating areas, bordered by a thin wall (usually < 2 mm). The recognition of CLDs has increased with the widespread use of computed tomography. This article addresses the mechanisms of cyst formation and the diagnostic approaches to CLDs. A number of assessment methods that can be used to confirm CLDs are discussed, including high-resolution computed tomography, pathologic approaches, and genetic/ serologic markers, together with treatment modalities, including new therapeutic drugs currently being evaluated. The CLDs covered by this review are lymphangioleiomyomatosis, pulmonary Langerhans cell histiocytosis, Birt-Hogg-Dube syndrome, lymphocytic interstitial pneumonia/follicular bronchiolitis, and amyloidosis. PMID:28264540

  6. Rare lung diseases II: Pulmonary alveolar proteinosis

    PubMed Central

    Juvet, Stephen C; Hwang, David; Waddell, Thomas K; Downey, Gregory P

    2008-01-01

    The present article is the second in a series on rare lung diseases. It focuses on pulmonary alveolar proteinosis (PAP), a disorder in which lipoproteinaceous material accumulates in the alveolar space. PAP was first described in 1958, and for many years the nature of the material accumulating in the lungs was unknown. Major insights into PAP have been made in the past decade, and these have led to the notion that PAP is an autoimmume disorder in which autoantibodies interfere with signalling through the granulocyte-macrophage colony-stimulating factor receptor, leading to macrophage and neutrophil dysfunction. This has spurred new therapeutic approaches to this disorder. The discussion of PAP will begin with a case report, then will highlight the classification of PAP and review recent insights into the pathogenesis of PAP. The approach to therapy and the prognosis of PAP will also be discussed. PMID:18551202

  7. Unclassifiable interstitial lung disease: A review.

    PubMed

    Skolnik, Kate; Ryerson, Christopher J

    2016-01-01

    Accurate classification of interstitial lung disease (ILD) requires a multidisciplinary approach that incorporates input from an experienced respirologist, chest radiologist and lung pathologist. Despite a thorough multidisciplinary evaluation, up to 15% of ILD patients have unclassifiable ILD and cannot be given a specific diagnosis. The objectives of this review are to discuss the definition and features of unclassifiable ILD, identify the barriers to ILD classification and outline an approach to management of unclassifiable ILD. Several recent studies have described the characteristics of these patients; however, there are inconsistencies in the definition and terminology of unclassifiable ILD due to limited research in this population. Additional studies are required to determine the appropriate evaluation and management of patients with unclassifiable ILD.

  8. Directional Multi-scale Modeling of High-Resolution Computed Tomography (HRCT) Lung Images for Diffuse Lung Disease Classification

    NASA Astrophysics Data System (ADS)

    Vo, Kiet T.; Sowmya, Arcot

    A directional multi-scale modeling scheme based on wavelet and contourlet transforms is employed to describe HRCT lung image textures for classifying four diffuse lung disease patterns: normal, emphysema, ground glass opacity (GGO) and honey-combing. Generalized Gaussian density parameters are used to represent the detail sub-band features obtained by wavelet and contourlet transforms. In addition, support vector machines (SVMs) with excellent performance in a variety of pattern classification problems are used as classifier. The method is tested on a collection of 89 slices from 38 patients, each slice of size 512x512, 16 bits/pixel in DICOM format. The dataset contains 70,000 ROIs of those slices marked by experienced radiologists. We employ this technique at different wavelet and contourlet transform scales for diffuse lung disease classification. The technique presented here has best overall sensitivity 93.40% and specificity 98.40%.

  9. Interstitial Lung Disease with ANCA-associated Vasculitis

    PubMed Central

    Katsumata, Yasuhiro; Kawaguchi, Yasushi; Yamanaka, Hisashi

    2015-01-01

    The association between interstitial lung disease (ILD) and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), particularly microscopic polyangiitis (MPA), has been described in a number of case reports and case series reports in the last 2 decades. In addition, patients with pulmonary fibrosis and ANCA positivity but without other manifestations of systemic vasculitis have also been reported. Pulmonary fibrosis was clinically manifested at the time of diagnosis in the majority of AAV patients that developed this condition. Moreover, ANCA-positive conversion occurs in patients initially diagnosed with idiopathic pulmonary fibrosis, and as a result, other manifestations of systemic vasculitis develop in some of these patients. There is significant predominance of myeloperoxidase (MPO)-ANCA and MPA in patients with AAV and ILD. Radiological and pathological findings generally demonstrate usual interstitial pneumonia (pattern) in the lungs of these patients. In most studies, AAV patients with ILD have a worse prognosis than those without it. PMID:26448696

  10. Pemphigus vulgaris-associated interstitial lung disease.

    PubMed

    Bai, Yi-Xiu; Chu, Jin-Gang; Xiao, Ting; Chen, Hong-Duo

    2016-07-01

    Autoimmune bullous diseases (AIBDs)-associated interstitial lung disease (ILD) is extremely rare. Pemphigus vulgaris (PV) is an intraepidermal autoimmune blistering disease caused by circulating autoantibodies against desmoglein. To date, PV-associated ILD has rarely been reported in English literature. We report a rare association of PV and ILD. A 53-year-old Chinese female with PV for 8 months developed ILD after a relapse of PV for 2 months due to discontinuation of oral prednisone by herself. She was successfully treated by systemic methylprednisolone. Taken previously reported bullous pemphigoid-associated ILD and linear IgA/IgG bullous dermatosis-associated ILD together, in general, AIBDs-associated ILD occurs when AIBDs relapse or are not controlled, responds well to systemic corticosteroids, and has a relatively better prognosis when compared with rheumatoid arthritis- or dermatomyositis-associated ILD.

  11. Ferritin, finger clubbing, and lung disease.

    PubMed Central

    Shneerson, J M; Jones, B M

    1981-01-01

    The serum ferritin concentration has been determined by an immunoradiometric assay in 90 subjects with a variety of pulmonary diseases. No association between ferritin concentrations and finger clubbing has been found in any of the diseases studied. Ferritin levels were significantly raised in the subjects with bronchial carcinoma, but were not useful in monitoring recurrence of the tumour. Pulmonary artery and pulmonary vein ferritin concentrations were similar to systemic venous concentrations. It is therefore unlikely that the tumour releases ferritin into the pulmonary circulation. Ferritin levels were raised in patients with acute pneumonias but did not correlate with the total white cell count or erythrocyte sedimentation rate. Serum ferritin concentrations were also increased in a variety of chronic lung diseases but were normal in subjects with asbestosis. PMID:7314044

  12. Genetic susceptibility and dietary patterns in lung cancer.

    PubMed

    Tsai, Ya-Yu; McGlynn, Katherine A; Hu, Ying; Cassidy, Anna B; Arnold, John; Engstrom, Paul F; Buetow, Kenneth H

    2003-09-01

    Cigarette smoking is the dominant risk factor for lung cancer, but only a minority of smokers ever develops tumors. Though genetic susceptibility is likely to explain some of the variability in risk, results from previous studies of genetic polymorphisms have been inconclusive. As diet may also affect the risk of lung cancer, it is possible that the degree of risk produced by smoking and genetic susceptibility varies, depending on diet. To assess this hypothesis, we conducted a case-control study to examine the effect of cigarette smoking, dietary patterns and variation in genes involved in phase II metabolism. A total of 254 individuals with lung cancer and 184 healthy controls were recruited for the study. To identify persons with similar dietary patterns, cluster analysis was performed using nutrient densities of four major dietary constituents: protein, carbohydrate, animal fat, and dietary fiber. Two groups of individuals were identified with distinct dietary patterns: (1) a group (n=241) with a high intake of animal fat and protein and a low intake of carbohydrates and dietary fiber (the 'unhealthy' pattern) and (2) a group (n=197) with a high intake of fiber and carbohydrate and a low intake of protein and animal fat (the 'healthy' pattern) [corrected]. On stratified analysis, several genotype/dietary pattern combinations were found to affect risk of lung cancer. Smokers who were not homozygous for the most common GSTP1 allele and had a healthy dietary pattern were at significantly lower risk than smokers who were homozygous for the GSTP1 common allele and who had an unhealthy dietary pattern (OR=0.16, 95%CI: 0.04-0.57). Among smokers who were GSTM1 null, persons with a healthy dietary pattern were at lower risk than persons with an unhealthy dietary pattern (OR: 0.46, 95%CI: 0.21-1.01). Among smokers with an unhealthy dietary patterns, persons with a His/His genotype in the exon 3 polymorphism of EPHX1 were at significantly lower risk that persons who were

  13. Matrix metalloproteinases in destructive lung disease.

    PubMed

    Houghton, A McGarry

    2015-01-01

    Matrix metalloproteinases (MMPs) play essential physiologic roles in numerous processes ranging from development to wound repair. Unfortunately, given the broad substrate specificity of the MMP family as a whole, aberrant degradation of extracellular matrix proteins can result in destructive disease. Emphysema, the result of destroyed lung elastin and collagen matrix, is the prototypical example of such a destructive process. More recent data has highlighted that MMPs play much more elaborate physiologic and pathophysiologic roles than simple matrix protein cleavage. Key pathophysiological roles for MMPs in emphysema will be discussed herein.

  14. Tracheal lipoma mimicking obstructive lung disease.

    PubMed

    Mota, Vinícius Turano; Maia, José Geraldo Soares; Barbosa, Ana Teresa Fernandes; Fernandes, Diego Franco Silveira; Rocha, Emanuelly Botelho

    2010-01-01

    Tracheal tumors are rare and can be difficult to diagnose due to their capacity to mimic other obstructive lung diseases, such as asthma and COPD. We report the case of a female patient with a tracheal tumor. She had previously been treated for asthma and COPD, with little response to the treatment. The onset of infectious complications prompted further investigation. Chest CT images suggested the presence of a tumor, which was confirmed by fiberoptic bronchoscopy. The tumor was endoscopically resected. However, the patient evolved to death due to pneumonia and septic shock.

  15. [Swimming pool lung -- extrinsic allergic alveolitis or mycobacterial disease?].

    PubMed

    Koschel, D; Pietrzyk, C; Sennekamp, J; Müller-Wening, D

    2006-05-01

    There have been several recent reports of pulmonary disease resulting from exposure to Mycobacterium avium complex in indoor hot tubs. The disease is thought to be due either to infection or extrinsic allergic alveolitis (EAA). In this report we describe the case of a patient who developed episodes of fever, dyspnea and cough 4-6 hours after cleaning his indoor swimming pool. A diagnosis of EAA was made on finding a restrictive lung function pattern with gas exchange abnormalities, a predominant lymphocytosis in the bronchoalveolar lavage, diffuse ground-glass opacities in the lower lobes on high-resolution computer tomography, and specific IgG antibody activity to the swimming pool water. There was no precipitin reaction or specific IgG antibody activity to microbes extracted from the water. Interestingly, the water contained Mycobacterium avium complex (MAC) in huge amounts and in this case the histopathological features of the lung biopsy specimens differed from those seen in typical EAA, but were similar to those described in "hot tub lung" caused by mycobacteria. Solely by avoidance of cleaning the swimming pool, without any pharmacological treatment, the patient recovered completely within three months. To the best of our knowledge, this is the first report of EAA possibly associated with MAC exposure in a swimming pool environment.

  16. Stem Cells and Regenerative Medicine in Lung Biology and Diseases

    PubMed Central

    Lau, Allison N; Goodwin, Meagan; Kim, Carla F; Weiss, Daniel J

    2012-01-01

    A number of novel approaches for repair and regeneration of injured lung have developed over the past several years. These include a better understanding of endogenous stem and progenitor cells in the lung that can function in reparative capacity as well as extensive exploration of the potential efficacy of administering exogenous stem or progenitor cells to function in lung repair. Recent advances in ex vivo lung engineering have also been increasingly applied to the lung. The current status of these approaches as well as initial clinical trials of cell therapies for lung diseases are reviewed below. PMID:22395528

  17. Interpretation of autoantibody positivity in interstitial lung disease and lung-dominant connective tissue disease*

    PubMed Central

    Pereira, Daniel Antunes Silva; Kawassaki, Alexandre de Melo; Baldi, Bruno Guedes

    2013-01-01

    The initial evaluation of patients with interstitial lung disease (ILD) primarily involves a comprehensive, active search for the cause. Autoantibody assays, which can suggest the presence of a rheumatic disease, are routinely performed at various referral centers. When interstitial lung involvement is the condition that allows the definitive diagnosis of connective tissue disease and the classical criteria are met, there is little debate. However, there is still debate regarding the significance, relevance, specificity, and pathophysiological role of autoimmunity in patients with predominant pulmonary involvement and only mild symptoms or formes frustes of connective tissue disease. The purpose of this article was to review the current knowledge of autoantibody positivity and to discuss its possible interpretations in patients with ILD and without clear etiologic associations, as well as to enhance the understanding of the natural history of an allegedly new disease and to describe the possible prognostic implications. We also discuss the proposition of a new term to be used in the classification of ILDs: lung-dominant connective tissue disease. PMID:24473767

  18. Interpretation of autoantibody positivity in interstitial lung disease and lung-dominant connective tissue disease.

    PubMed

    Pereira, Daniel Antunes Silva; Kawassaki, Alexandre de Melo; Baldi, Bruno Guedes

    2013-01-01

    The initial evaluation of patients with interstitial lung disease (ILD) primarily involves a comprehensive, active search for the cause. Autoantibody assays, which can suggest the presence of a rheumatic disease, are routinely performed at various referral centers. When interstitial lung involvement is the condition that allows the definitive diagnosis of connective tissue disease and the classical criteria are met, there is little debate. However, there is still debate regarding the significance, relevance, specificity, and pathophysiological role of autoimmunity in patients with predominant pulmonary involvement and only mild symptoms or formes frustes of connective tissue disease. The purpose of this article was to review the current knowledge of autoantibody positivity and to discuss its possible interpretations in patients with ILD and without clear etiologic associations, as well as to enhance the understanding of the natural history of an allegedly new disease and to describe the possible prognostic implications. We also discuss the proposition of a new term to be used in the classification of ILDs: lung-dominant connective tissue disease.

  19. [Chronic obstructive lung disease. Systemic manifestations].

    PubMed

    Grassi, Vittorio; Carminati, Luisa; Cossi, Stefania; Marengoni, Alessandra; Tantucci, Claudio

    2003-05-01

    Chronic obstructive lung diseases (COPD) are a complex disease state which not rarely can be associated with significant systemic manifestations. These alterations, though recognized since long time, are currently under extensive research, due to the increasing appreciation of their relevant negative role in the prognosis and health-related quality of life (Hr-QoL) of the COPD patients. The most clinically important are the decrease in body weight with loss of skeletal muscle mass (cachexia), osteoporosis, hypercapnia-induced peripheral edema, neuro-psychiatric disorders, such as oxygen-related cognitive impairment and depression, excessive polycytaemia and sleep disorders. Chronic systemic inflammation, oxidative stress and chronic hypoxia are believed as the main factors involved in the pathogenesis of systemic effects seen in COPD. Their adequate control with nutritional support, change of life-style and targeted pharmacological treatment is able to improve the prognosis and Hr-QoL among these COPD patients.

  20. Pathologic Review of Cystic and Cavitary Lung Diseases

    PubMed Central

    Kim, Na Rae

    2012-01-01

    Pulmonary cystic and cavitary lesions caused by diverse etiologies are commonly encountered in chest imaging. The terms "cyst" and "cavity" are used to describe air-filled regions in the center of a nodule or consolidation of the lung. To date, only radiologic aspects of these lesions have been addressed. The morphologies of pulmonary cystic and cavitary lesions exhibit a broad spectrum, ranging from benign to malignant pulmonary diseases of acquired or congenital origin, including variable infectious diseases. In this review, we summarized the differential diagnosis of pathological entities to provide pathologists and radiologists with an overview of the diseases most commonly associated with pulmonary cystic and cavitary lesions in adults and children. The results showed slightly different patterns in the distribution of the diseases in the two groups. The most common causes of cavitary lesions include malignancy and infection in adults, and congenital malformation in children. Therefore, identification of pathologic entities correlating with the radiologic findings, clinical course, and location of the lesion is important in the evaluation of cystic and cavitary lung lesions in order to avoid unnecessary surgical procedures or delayed treatment. PMID:23136566

  1. Common lung conditions: chronic obstructive pulmonary disease.

    PubMed

    Delzell, John E

    2013-06-01

    The etiology of chronic obstructive pulmonary disease (COPD) is chronic lung inflammation. In the United States, this inflammation most commonly is caused by smoking. COPD is diagnosed when an at-risk patient presents with respiratory symptoms and has irreversible airway obstruction indicated by a forced expiratory volume in 1 second/forced vital capacity ratio of less than 0.7. Management goals for COPD include smoking cessation, symptom reduction, exacerbation reduction, hospitalization avoidance, and improvement of quality of life. Stable patients with COPD who remain symptomatic despite using short-acting bronchodilators should start inhaled maintenance drugs to reduce symptoms and exacerbations, avoid hospitalizations, and improve quality of life. A long-acting anticholinergic or a long-acting beta2-agonist (LABA) can be used for initial therapy; these drugs have fewer adverse effects than inhaled corticosteroids (ICS). If patients remain symptomatic despite monotherapy, dual therapy with a long-acting anticholinergic and a LABA, or a LABA and an ICS, may be beneficial. Triple therapy (ie, a long-acting anticholinergic, a LABA, and an ICS) also is used, but it is unclear if triple therapy is superior to dual therapy. Roflumilast, an oral selective inhibitor of phosphodiesterase 4, is used to manage moderate to severe COPD. Continuous oxygen therapy is indicated for patients with COPD who have severe hypoxemia (ie, PaO2 less than 55 mm Hg or an oxygen saturation less than 88% on room air). Nonpharmacologic strategies also are useful to improve patient outcomes. Pulmonary rehabilitation improves dyspnea and quality of life. Pulmonary rehabilitation after an acute exacerbation reduces hospitalizations and mortality, and improves quality of life and exercise capacity. Smoking cessation is the most effective management strategy for reducing morbidity and mortality in patients with COPD. Lung volume reduction surgery, bullectomy, and lung transplantation are

  2. Malignant ameloblastoma (metastatic ameloblastoma) in the lung: 3 cases of misdiagnosis as primary lung tumor with a unique growth pattern.

    PubMed

    Bi, Rui; Shen, Lei; Zhu, Xiongzeng; Xu, Xiaoli

    2015-07-25

    Malignant ameloblastoma (metastatic ameloblastoma, MA) is currently defined as a distinct pathologic entity, MA, despite its histologically benign appearance. According to the new criteria, the histological and clinical features of MA are more homogenous. Here, we report three cases of histologically confirmed pulmonary MA. Two of the three patients complained of chest pain as the primary symptom, and the other case was detected upon the evaluation of pulmonary nodules found during a health examination after a local recurrence of mandible ameloblastoma. All three patients were female with an average age of 48 years. The intervals between the primary ameloblastoma and metastasis to the lung were 14 years, 19 years and 10 years, averaging 14.3 years. Prior to metastasis to the lung, only one patient experienced local recurrences, at 5 and 19 years after the primary tumor resection, while the other two patients both remained disease-free. Computed tomography (CT) or X-ray evaluation demonstrated multiple bilateral lung nodules ranging in size from several millimeters up to 2 cm. Histologically, the pulmonary metastatic tumors showed a unique growth pattern: the tumor cells grew among the interstitial alveoli but did not appear to destructively infiltrate the surrounding tissue. Immunohistochemically, the MA cells expressed squamous differentiation markers, such as CK10/13 and p63, while the alveolar epithelial cells stained for TTF1 and PE10. In this paper, we discuss the clinical behavior, differential diagnosis and unique growth pattern of pulmonary MA.

  3. Pleural mesothelial cells in pleural and lung diseases

    PubMed Central

    Antony, Veena B.

    2015-01-01

    During development, the mesoderm maintains a complex relationship with the developing endoderm giving rise to the mature lung. Pleural mesothelial cells (PMCs) derived from the mesoderm play a key role during the development of the lung. The pleural mesothelium differentiates to give rise to the endothelium and smooth muscle cells via epithelial-to-mesenchymal transition (EMT). An aberrant recapitulation of such developmental pathways can play an important role in the pathogenesis of disease processes such as idiopathic pulmonary fibrosis (IPF). The PMC is the central component of the immune responses of the pleura. When exposed to noxious stimuli, it demonstrates innate immune responses such as Toll-like receptor (TLR) recognition of pathogen associated molecular patterns as well as causes the release of several cytokines to activate adaptive immune responses. Development of pleural effusions occurs due to an imbalance in the dynamic interaction between junctional proteins, n-cadherin and β-catenin, and phosphorylation of adherens junctions between PMCs, which is caused in part by vascular endothelial growth factor (VEGF) released by PMCs. PMCs play an important role in defense mechanisms against bacterial and mycobacterial pleural infections, and in pathogenesis of malignant pleural effusion, asbestos related pleural disease and malignant pleural mesothelioma. PMCs also play a key role in the resolution of inflammation, which can occur with or without fibrosis. Fibrosis occurs as a result of disordered fibrin turnover and due to the effects of cytokines such as transforming growth factor-β, platelet-derived growth factor (PDGF), and basic fibroblast growth factor; which are released by PMCs. Recent studies have demonstrated a role for PMCs in the pathogenesis of IPF suggesting their potential as a cellular biomarker of disease activity and as a possible therapeutic target. Pleural-based therapies targeting PMCs for treatment of IPF and other lung diseases need

  4. MicroRNAs in Human Diseases: From Lung, Liver and Kidney Diseases to Infectious Disease, Sickle Cell Disease and Endometrium Disease.

    PubMed

    Ha, Tai-You

    2011-12-01

    MicroRNAs (miRNAs) are a class of naturally occurring small non-coding RNAs of about 22 nucleotides that have recently emerged as important regulators of gene expression at the posttranscriptional level. Recent studies provided clear evidence that microRNAs are abundant in the lung, liver and kidney and modulate a diverse spectrum of their functions. Moreover, a large number of studies have reported links between alterations of miRNA homeostasis and pathological conditions such as infectious diseases, sickle cell disease and endometrium diseases as well as lung, liver and kidney diseases. As a consequence of extensive participation of miRNAs in normal functions, alteration and/or abnormalities in miRNAs should have importance in human diseases. Beside their important roles in patterning and development, miRNAs also orchestrated responses to pathogen infections. Particularly, emerging evidence indicates that viruses use their own miRNAs to manipulate both cellular and viral gene expression. Furthermore, viral infection can exert a profound impact on the host cellular miRNA expression profile, and several RNA viruses have been reported to interact directly with cellular miRNAs and/or to use these miRNAs to augment their replication potential. Here I briefly summarize the newly discovered roles of miRNAs in various human diseases including infectious diseases, sickle cell disease and enodmetrium diseases as well as lung, liver and kidney diseases.

  5. MicroRNAs in Human Diseases: From Lung, Liver and Kidney Diseases to Infectious Disease, Sickle Cell Disease and Endometrium Disease

    PubMed Central

    2011-01-01

    MicroRNAs (miRNAs) are a class of naturally occurring small non-coding RNAs of about 22 nucleotides that have recently emerged as important regulators of gene expression at the posttranscriptional level. Recent studies provided clear evidence that microRNAs are abundant in the lung, liver and kidney and modulate a diverse spectrum of their functions. Moreover, a large number of studies have reported links between alterations of miRNA homeostasis and pathological conditions such as infectious diseases, sickle cell disease and endometrium diseases as well as lung, liver and kidney diseases. As a consequence of extensive participation of miRNAs in normal functions, alteration and/or abnormalities in miRNAs should have importance in human diseases. Beside their important roles in patterning and development, miRNAs also orchestrated responses to pathogen infections. Particularly, emerging evidence indicates that viruses use their own miRNAs to manipulate both cellular and viral gene expression. Furthermore, viral infection can exert a profound impact on the host cellular miRNA expression profile, and several RNA viruses have been reported to interact directly with cellular miRNAs and/or to use these miRNAs to augment their replication potential. Here I briefly summarize the newly discovered roles of miRNAs in various human diseases including infectious diseases, sickle cell disease and enodmetrium diseases as well as lung, liver and kidney diseases. PMID:22346770

  6. Connective Tissue Disease-Associated Interstitial Lung Diseases: Unresolved Issues.

    PubMed

    Aparicio, Irene Jarana; Lee, Joyce S

    2016-06-01

    Interstitial lung disease (ILD) complicating connective tissue disorders, such as scleroderma and rheumatoid arthritis, is associated with significant morbidity and mortality. Progress has been made in our understanding of these collective diseases; however, there are still many unanswered questions. In this review, we describe the current views on epidemiology, clinical presentation, treatment, and prognosis in patients with connective tissue disease (CTD)-associated ILD. We also highlight several areas that remain unresolved and in need of further investigation, including interstitial pneumonia with autoimmune features, histopathologic phenotype, and pharmacologic management. A multidisciplinary and multidimensional approach to diagnosis, management, and investigation of CTD-associated ILD patients is essential to advance our understanding of the epidemiology and pathobiology of this challenging group of diseases.

  7. Exhaled Aerosol Pattern Discloses Lung Structural Abnormality: A Sensitivity Study Using Computational Modeling and Fractal Analysis

    PubMed Central

    Xi, Jinxiang; Si, Xiuhua A.; Kim, JongWon; Mckee, Edward; Lin, En-Bing

    2014-01-01

    Background Exhaled aerosol patterns, also called aerosol fingerprints, provide clues to the health of the lung and can be used to detect disease-modified airway structures. The key is how to decode the exhaled aerosol fingerprints and retrieve the lung structural information for a non-invasive identification of respiratory diseases. Objective and Methods In this study, a CFD-fractal analysis method was developed to quantify exhaled aerosol fingerprints and applied it to one benign and three malign conditions: a tracheal carina tumor, a bronchial tumor, and asthma. Respirations of tracer aerosols of 1 µm at a flow rate of 30 L/min were simulated, with exhaled distributions recorded at the mouth. Large eddy simulations and a Lagrangian tracking approach were used to simulate respiratory airflows and aerosol dynamics. Aerosol morphometric measures such as concentration disparity, spatial distributions, and fractal analysis were applied to distinguish various exhaled aerosol patterns. Findings Utilizing physiology-based modeling, we demonstrated substantial differences in exhaled aerosol distributions among normal and pathological airways, which were suggestive of the disease location and extent. With fractal analysis, we also demonstrated that exhaled aerosol patterns exhibited fractal behavior in both the entire image and selected regions of interest. Each exhaled aerosol fingerprint exhibited distinct pattern parameters such as spatial probability, fractal dimension, lacunarity, and multifractal spectrum. Furthermore, a correlation of the diseased location and exhaled aerosol spatial distribution was established for asthma. Conclusion Aerosol-fingerprint-based breath tests disclose clues about the site and severity of lung diseases and appear to be sensitive enough to be a practical tool for diagnosis and prognosis of respiratory diseases with structural abnormalities. PMID:25105680

  8. Blue journal conference. Aging and susceptibility to lung disease.

    PubMed

    Thannickal, Victor J; Murthy, Mahadev; Balch, William E; Chandel, Navdeep S; Meiners, Silke; Eickelberg, Oliver; Selman, Moisés; Pardo, Annie; White, Eric S; Levy, Bruce D; Busse, Paula J; Tuder, Rubin M; Antony, Veena B; Sznajder, Jacob I; Budinger, G R Scott

    2015-02-01

    The aging of the population in the United States and throughout the developed world has increased morbidity and mortality attributable to lung disease, while the morbidity and mortality from other prevalent diseases has declined or remained stable. Recognizing the importance of aging in the development of lung disease, the American Thoracic Society (ATS) highlighted this topic as a core theme for the 2014 annual meeting. The relationship between aging and lung disease was discussed in several oral symposiums and poster sessions at the annual ATS meeting. In this article, we used the input gathered at the conference to develop a broad framework and perspective to stimulate basic, clinical, and translational research to understand how the aging process contributes to the onset and/or progression of lung diseases. A consistent theme that emerged from the conference was the need to apply novel, systems-based approaches to integrate a growing body of genomic, epigenomic, transcriptomic, and proteomic data and elucidate the relationship between biologic hallmarks of aging, altered lung function, and increased susceptibility to lung diseases in the older population. The challenge remains to causally link the molecular and cellular changes of aging with age-related changes in lung physiology and disease susceptibility. The purpose of this review is to stimulate further research to identify new strategies to prevent or treat age-related lung disease.

  9. Progressive lung disease in a malt-worker.

    PubMed Central

    Ellis, M E; Friend, J A

    1981-01-01

    We described a malt-worker whose initial symptoms suggested extrinsic allergic alveolitis. The ensuing cavitating lung disease, Aspergillus fumigatus infection with mycetomata, vigorous immune response, and granulomatous liver disease are unusual features. Images PMID:7031969

  10. Chronic suppurative lung disease in adults

    PubMed Central

    Mangardich, Antranik

    2016-01-01

    Chronic suppurative lung disease (CSLD), characterized by a bronchiectasis-like syndrome in the absence of bronchial dilatation, is well described in the pediatric literature. In some patients, it may be a precursor of bronchiectasis. In adults, this syndrome has not been well described. We present four adult patients without obvious causative exposures who presented with prolonged cough and purulent sputum. Sputum cultures revealed a variety of Gram negative bacteria, fungi and mycobacteria. High resolution CT scanning did not reveal bronchiectasis. Evaluation revealed underlying causes including immunodeficiency in two, and Mycobacterium avium infection. One patient subsequently developed bronchiectasis. All patients improved with therapy. CSLD occurs in adults and has characteristics that distinguish it from typical chronic bronchitis. These include the lack of causative environmental exposures and infection with unusual pathogens. Evaluation and treatment of these patients similar to bronchiectasis patients may lead to clinical improvement. PMID:27747039

  11. Smart Technology in Lung Disease Clinical Trials.

    PubMed

    Geller, Nancy L; Kim, Dong-Yun; Tian, Xin

    2016-01-01

    This article describes the use of smart technology by investigators and patients to facilitate lung disease clinical trials and make them less costly and more efficient. By "smart technology" we include various electronic media, such as computer databases, the Internet, and mobile devices. We first describe the use of electronic health records for identifying potential subjects and then discuss electronic informed consent. We give several examples of using the Internet and mobile technology in clinical trials. Interventions have been delivered via the World Wide Web or via mobile devices, and both have been used to collect outcome data. We discuss examples of new electronic devices that recently have been introduced to collect health data. While use of smart technology in clinical trials is an exciting development, comparison with similar interventions applied in a conventional manner is still in its infancy. We discuss advantages and disadvantages of using this omnipresent, powerful tool in clinical trials, as well as directions for future research.

  12. Quantification of nonuniform distribution of hemi-lung perfusion in chronic obstructive pulmonary disease.

    PubMed

    Mitomo, Osamu

    2016-01-01

    Nonuniform distribution (NUD) of perfusion on single photon emission computed tomography (SPECT) is caused by impaired perfusion-related fluctuations of the functional volume (FFV). It was determined if digital analysis of NUD in each hemi-lung damaged by chronic obstructive pulmonary disease (COPD) could improve the whole lung impairment assessment. We examined 665 subjects and 8 controls by SPECT. The basic whole lung SPECT volume was defined at 10% of maximum whole lung count cutoff threshold (T h). For the whole lung and each hemi-lung, the 10% T h width volume, FFV rate, and misfit from the control were calculated at every T h width number (n) from 1 to 9 for every additional 10% T h from 10 to 100%. The misfit value integrated from 1 to 9 of n was defined by 3 NUD indices: D, whole lung NUD index; D rl , the index for the sum of each hemi-lung NUD; and D (I) , the NUD index with every interpolating pattern in which FFV rates of hemi-lungs comprised negative and positive value at the same n. D rl index was the sum of D and D (I) indices in all patients. D rl and D indices significantly increased in pulmonary disease subjects relative to those of the normal group and non-pulmonary disease subjects. D rl and D indices increased in COPD subjects. Progressive COPD subjects had larger D rl index values and "diffuse and even" hemi-lung impairment. The three indices quantizing FFV itself leading to NUD helped to digitally evaluate the degree of lung impairment of perfusion. Clinically, it is expected that the NUD indices and images obtained by SPECT, which visually and digitally show the pathological fluctuations in perfusion caused by lung impairment, will be able to provide specific and useful information for improving treatment and/or care of subjects with COPD.

  13. Stem cells and cell therapies in lung biology and lung diseases.

    PubMed

    Weiss, Daniel J; Bertoncello, Ivan; Borok, Zea; Kim, Carla; Panoskaltsis-Mortari, Angela; Reynolds, Susan; Rojas, Mauricio; Stripp, Barry; Warburton, David; Prockop, Darwin J

    2011-06-01

    The University of Vermont College of Medicine and the Vermont Lung Center, with support of the National Heart, Lung, and Blood Institute (NHLBI), the Alpha-1 Foundation, the American Thoracic Society, the Emory Center for Respiratory Health,the Lymphangioleiomyomatosis (LAM) Treatment Alliance,and the Pulmonary Fibrosis Foundation, convened a workshop,‘‘Stem Cells and Cell Therapies in Lung Biology and Lung Diseases,’’ held July 26-29, 2009 at the University of Vermont,to review the current understanding of the role of stem and progenitor cells in lung repair after injury and to review the current status of cell therapy approaches for lung diseases. These are rapidly expanding areas of study that provide further insight into and challenge traditional views of the mechanisms of lung repair after injury and pathogenesis of several lung diseases. The goals of the conference were to summarize the current state of the field, discuss and debate current controversies, and identify future research directions and opportunities for both basic and translational research in cell-based therapies for lung diseases.

  14. Phospholipids of the lung in normal, toxic, and diseased states

    SciTech Connect

    Akino, T.; Ohno, K.

    1981-01-01

    The highly pulmonary concentration of 1,2-dipalmitoyl-sn-glycerol-3-phosphorylcholine (dipalmitoyllecithin) and its implication as an important component of lung surfactant have promoted investigation of phospholipid metabolism in the lung. This review will set the contents including recent informations for better understanding of phospholipid metabolism of the lung in normal state (physiological significances of lung phospholipids, characteristics of phospholipids in lung tissue and alveolar washing, biosynthetic pathways of dipalmitoyllecithin, etc.) as well as in toxic states (pulmonary oxygen toxicity, etc.) and in diseased states (idiopathic respiratory distress syndrome, pulmonary alveolar proteinosis, etc.) Since our main concern has been to clarify the most important route for supplying dipalmitoyllecithin, this review will be focused upon the various biosynthetic pathways leading to the formation of different molecular species of lecithin and their potential significance in the normal, toxic, and diseased lungs.

  15. Rheumatoid arthritis associated interstitial lung disease: a review.

    PubMed

    Assayag, Deborah; Lee, Joyce S; King, Talmadge E

    2014-01-01

    Rheumatoid arthritis is a common inflammatory disease affecting about 1% of the population. Interstitial lung disease is a serious and frequent complication of rheumatoid arthritis. Rheumatoid arthritis associated interstitial lung disease (RA-ILD) is characterized by several histopathologic subtypes. This article reviews the proposed pathogenesis and risk factors for RA-ILD. We also outline the important steps involved in the work-up of RA-ILD and review the evidence for treatment and prognosis.

  16. Heart lung transplantation in a patient with end stage lung disease due to common variable immunodeficiency

    PubMed Central

    Hill, A; Thompson, R; Wallwork, J; Stableforth, D

    1998-01-01

    The case history is presented of a patient with common variable immunodeficiency in whom heart lung transplantation has been carried out with success. Transplantation was the only long term therapeutic option in this patient due to the progressive respiratory failure resulting from bronchiectasis, emphysema, and granulomatous lung disease.

 PMID:9797766

  17. The multifaceted aspects of interstitial lung disease in rheumatoid arthritis.

    PubMed

    Cavagna, Lorenzo; Monti, Sara; Grosso, Vittorio; Boffini, Nicola; Scorletti, Eva; Crepaldi, Gloria; Caporali, Roberto

    2013-01-01

    Interstitial lung disease (ILD) is a relevant extra-articular manifestation of rheumatoid arthritis (RA) that may occur either in early stages or as a complication of long-standing disease. RA related ILD (RA-ILD) significantly influences the quoad vitam prognosis of these patients. Several histopathological patterns of RA-ILD have been described: usual interstitial pneumonia (UIP) is the most frequent one, followed by nonspecific interstitial pneumonia (NSIP); other patterns are less commonly observed. Several factors have been associated with an increased risk of developing RA-ILD. The genetic background plays a fundamental but not sufficient role; smoking is an independent predictor of ILD, and a correlation with the presence of rheumatoid factor and anti-cyclic citrullinated peptide antibodies has also been reported. Moreover, both exnovo occurrence and progression of ILD have been related to drug therapies that are commonly prescribed in RA, such as methotrexate, leflunomide, anti-TNF alpha agents, and rituximab. A greater understanding of the disease process is necessary in order to improve the therapeutic approach to ILD and RA itself and to reduce the burden of this severe extra-articular manifestation.

  18. Sex Differences and Sex Steroids in Lung Health and Disease

    PubMed Central

    Townsend, Elizabeth A.; Miller, Virginia M.

    2012-01-01

    Sex differences in the biology of different organ systems and the influence of sex hormones in modulating health and disease are increasingly relevant in clinical and research areas. Although work has focused on sex differences and sex hormones in cardiovascular, musculoskeletal, and neuronal systems, there is now increasing clinical evidence for sex differences in incidence, morbidity, and mortality of lung diseases including allergic diseases (such as asthma), chronic obstructive pulmonary disease, pulmonary fibrosis, lung cancer, as well as pulmonary hypertension. Whether such differences are inherent and/or whether sex steroids play a role in modulating these differences is currently under investigation. The purpose of this review is to define sex differences in lung structure/function under normal and specific disease states, with exploration of whether and how sex hormone signaling mechanisms may explain these clinical observations. Focusing on adult age groups, the review addresses the following: 1) inherent sex differences in lung anatomy and physiology; 2) the importance of certain time points in life such as puberty, pregnancy, menopause, and aging; 3) expression and signaling of sex steroid receptors under normal vs. disease states; 4) potential interplay between different sex steroids; 5) the question of whether sex steroids are beneficial or detrimental to the lung; and 6) the potential use of sex steroid signaling as biomarkers and therapeutic avenues in lung diseases. The importance of focusing on sex differences and sex steroids in the lung lies in the increasing incidence of lung diseases in women and the need to address lung diseases across the life span. PMID:22240244

  19. Computerized scheme for detection of diffuse lung diseases on CR chest images

    NASA Astrophysics Data System (ADS)

    Pereira, Roberto R., Jr.; Shiraishi, Junji; Li, Feng; Li, Qiang; Doi, Kunio

    2008-03-01

    We have developed a new computer-aided diagnostic (CAD) scheme for detection of diffuse lung disease in computed radiographic (CR) chest images. One hundred ninety-four chest images (56 normals and 138 abnormals with diffuse lung diseases) were used. The 138 abnormal cases were classified into three levels of severity (34 mild, 60 moderate, and 44 severe) by an experienced chest radiologist with use of five different patterns, i.e., reticular, reticulonodular, nodular, air-space opacity, and emphysema. In our computerized scheme, the first moment of the power spectrum, the root-mean-square variation, and the average pixel value were determined for each region of interest (ROI), which was selected automatically in the lung fields. The average pixel value and its dependence on the location of the ROI were employed for identifying abnormal patterns due to air-space opacity or emphysema. A rule-based method was used for determining three levels of abnormality for each ROI (0: normal, 1: mild, 2: moderate, and 3: severe). The distinction between normal lungs and abnormal lungs with diffuse lung disease was determined based on the fractional number of abnormal ROIs by taking into account the severity of abnormalities. Preliminary results indicated that the area under the ROC curve was 0.889 for the 44 severe cases, 0.825 for the 104 severe and moderate cases, and 0.794 for all cases. We have identified a number of problems and reasons causing false positives on normal cases, and also false negatives on abnormal cases. In addition, we have discussed potential approaches for improvement of our CAD scheme. In conclusion, the CAD scheme for detection of diffuse lung diseases based on texture features extracted from CR chest images has the potential to assist radiologists in their interpretation of diffuse lung diseases.

  20. Interstitial lung disease in infancy: A general approach.

    PubMed

    Hines, Erica J; Walsh, Mark; Armes, Jane E; Douglas, Tonia; Chawla, Jasneek

    2016-04-01

    Childhood Interstitial lung disease (chILD) is an umbrella term used to define a broad range of rare, diffuse pulmonary disorders with altered interstitial structure that leads to abnormal gas exchange. Presentation of chILD in infancy can be difficult to differentiate from other common causes of diffuse lung disease. This article aimed at paediatricians provides an overview of interstitial lung disease presenting in infancy and includes key clinical features, a suggested approach to investigation and a summary of management. An overview of three clinical cases has been included to demonstrate the diagnostic approach, characteristic investigation findings and varied clinical outcomes.

  1. Update in diagnosis and management of interstitial lung disease.

    PubMed

    Mikolasch, Theresia A; Garthwaite, Helen S; Porter, Joanna C

    2016-12-01

    The field of interstitial lung disease (ILD) has undergone significant evolution in recent years, with an increasing incidence and more complex, ever expanding disease classification. In their most severe forms, these diseases lead to progressive loss of lung function, respiratory failure and eventually death. Despite notable advances, progress has been challenged by a poor understanding of pathological mechanisms and patient heterogeneity, including variable progression. The diagnostic pathway is thus being continually refined, with the introduction of tools such as transbronchial cryo lung biopsy and a move towards genetically aided, precision medicine. In this review, we focus on how to approach a patient with ILD and the diagnostic process.

  2. Pulmonary hypertension associated with lung diseases and hypoxemia.

    PubMed

    Cuttica, Michael J

    2016-05-01

    Pulmonary hypertension that develops in the setting of underlying lung diseases such as COPD or idiopathic pulmonary fibrosis (IPF) is associated with decreased functional status, worsening hypoxemia and quality of life, and increased mortality. This complication of lung disease is complex in its origin and carries a unique set of diagnostic and therapeutic issues. This review attempts to provide an overview of mechanisms associated with the onset of pulmonary hypertension in COPD and IPF, touches on appropriate evaluation, and reviews the state of knowledge on treating pulmonary hypertension related to underlying lung disease.

  3. Genetically manipulated mouse models of lung disease: potential and pitfalls

    PubMed Central

    Choi, Alexander J. S.; Owen, Caroline A.; Choi, Augustine M. K.

    2012-01-01

    Gene targeting in mice (transgenic and knockout) has provided investigators with an unparalleled armamentarium in recent decades to dissect the cellular and molecular basis of critical pathophysiological states. Fruitful information has been derived from studies using these genetically engineered mice with significant impact on our understanding, not only of specific biological processes spanning cell proliferation to cell death, but also of critical molecular events involved in the pathogenesis of human disease. This review will focus on the use of gene-targeted mice to study various models of lung disease including airways diseases such as asthma and chronic obstructive pulmonary disease, and parenchymal lung diseases including idiopathic pulmonary fibrosis, pulmonary hypertension, pneumonia, and acute lung injury. We will attempt to review the current technological approaches of generating gene-targeted mice and the enormous dataset derived from these studies, providing a template for lung investigators. PMID:22198907

  4. Angiotensin-converting enzyme 2 in lung diseases.

    PubMed

    Kuba, Keiji; Imai, Yumiko; Penninger, Josef M

    2006-06-01

    The renin-angiotensin system (RAS) plays a key role in maintaining blood pressure homeostasis, as well as fluid and salt balance. Angiotensin II, a key effector peptide of the system, causes vasoconstriction and exerts multiple biological functions. Angiotensin-converting enzyme (ACE) plays a central role in generating angiotensin II from angiotensin I, and capillary blood vessels in the lung are one of the major sites of ACE expression and angiotensin II production in the human body. The RAS has been implicated in the pathogenesis of pulmonary hypertension and pulmonary fibrosis, both commonly seen in chronic lung diseases such as chronic obstructive lung disease. Recent studies indicate that the RAS also plays a critical role in acute lung diseases, especially acute respiratory distress syndrome (ARDS). ACE2, a close homologue of ACE, functions as a negative regulator of the angiotensin system and was identified as a key receptor for SARS (severe acute respiratory syndrome) coronavirus infections. In the lung, ACE2 protects against acute lung injury in several animal models of ARDS. Thus, the RAS appears to play a critical role in the pathogenesis of acute lung injury. Indeed, increasing ACE2 activity might be a novel approach for the treatment of acute lung failure in several diseases.

  5. Surgical management of Aspergillus colonization associated with lung hydatid disease.

    PubMed

    Vasquez, Julio C; Montesinos, Efrain; Rojas, Luis; Peralta, Julio; Delarosa, Jacob; Leon, Juan J

    2008-04-01

    Colonization with Aspergillus sp. usually occurs in previously formed lung cavities. Cystectomy is a widely used surgical technique for hydatid lung disease that can also leave residual cavities and potentially result in aspergilloma. We present two cases of this rare entity and a case with Aspergillus sp. colonization of an existing ruptured hydatid cyst.

  6. Sonic hedgehog signaling in the lung. From development to disease.

    PubMed

    Kugler, Matthias C; Joyner, Alexandra L; Loomis, Cynthia A; Munger, John S

    2015-01-01

    Over the past two decades, the secreted protein sonic hedgehog (SHH) has emerged as a critical morphogen during embryonic lung development, regulating the interaction between epithelial and mesenchymal cell populations in the airway and alveolar compartments. There is increasing evidence that the SHH pathway is active in adult lung diseases such as pulmonary fibrosis, asthma, chronic obstructive pulmonary disease, and lung cancer, which raises two questions: (1) What role does SHH signaling play in these diseases? and (2) Is it a primary driver of the disease or a response (perhaps beneficial) to the primary disturbance? In this review we aim to fill the gap between the well-studied period of embryonic lung development and the adult diseased lung by reviewing the hedgehog (HH) pathway during the postnatal period and in adult uninjured and injured lungs. We elucidate the similarities and differences in the epithelial-mesenchymal interplay during the fibrosis response to injury in lung compared with other organs and present a critical appraisal of tools and agents available to evaluate HH signaling.

  7. Evaluation and Diagnosis of HIV-Associated Lung Disease.

    PubMed

    Maximous, Stephanie; Huang, Laurence; Morris, Alison

    2016-04-01

    There are myriad pulmonary conditions associated with HIV, ranging from acute infections to chronic noncommunicable diseases. The epidemiology of these diseases has changed significantly in the era of widespread antiretroviral therapy. Evaluation of the HIV-infected patient involves assessment of the severity of illness and a thorough yet efficient pursuit of definitive diagnosis, which may involve multiple etiologies simultaneously. Important clues to a diagnosis include medical and social history, demographic details such as travel and geography of residence, substance use, sexual practices, and domiciliary and incarceration status. CD4 cell count is a tremendously useful measure of immune function and risk for HIV-related diseases, and helps narrow down the differential. Careful history of current symptoms and physical examination with particular attention to extrapulmonary signs are crucial early steps. Many adjunctive laboratory studies can suggest or rule out particular diagnoses. Pulmonary function testing (PFT) may aid in characterization of several chronic noninfectious illnesses accelerated by HIV. Chest radiograph and computed tomography (CT) scan allow for classification of diseases by pathognomonic imaging patterns, although many infectious conditions present atypically, particularly with lower CD4 counts. Ultimately, definitive diagnosis with sputum, bronchoscopy with bronchoalveolar lavage, or lung tissue is often needed. It is of utmost importance to maintain a high degree of suspicion for HIV in otherwise undiagnosed patients, as the first presentation of HIV may be via an acute pulmonary illness.

  8. CT in the diagnosis of interstitial lung disease

    SciTech Connect

    Bergin, C.J.; Mueller, N.L.

    1985-09-01

    The computed tomographic (CT) appearance of interstitial lung disease was assessed in 23 patients with known interstitial disease. These included seven patients with fibrosing alveolitis, six with silicosis, two with hypersensitivity pneumonitis, three with lymphangitic spread of tumor, two with sarcoidosis, one with rheumatoid lung disease, and two with neurofibromatosis. The CT appearance of the interstitial changes in the different disease entities was assessed. Nodules were a prominent CT feature in silicosis, sarcoidosis, and lymphangitic spread of malignancy. Distribution of nodules and associated interlobular septal thickening provided further distinguishing features in these diseases. Reticular densities were the predominant CT change in fibrosing alveolitis, rheumatoid lung disease, and extrinsic allergic alveolitis. CT can be useful in the investigation of selected instances of interstitial pulmonary disease.

  9. CXCR4+ granulocytes reflect fungal cystic fibrosis lung disease.

    PubMed

    Carevic, Melanie; Singh, Anurag; Rieber, Nikolaus; Eickmeier, Olaf; Griese, Matthias; Hector, Andreas; Hartl, Dominik

    2015-08-01

    Cystic fibrosis airways are frequently colonised with fungi. However, the interaction of these fungi with immune cells and the clinical relevance in cystic fibrosis lung disease are incompletely understood.We characterised granulocytes in airway fluids and peripheral blood from cystic fibrosis patients with and without fungal colonisation, non-cystic fibrosis disease controls and healthy control subjects cross-sectionally and longitudinally and correlated these findings with lung function parameters.Cystic fibrosis patients with chronic fungal colonisation by Aspergillus fumigatus were characterised by an accumulation of a distinct granulocyte subset, expressing the HIV coreceptor CXCR4. Percentages of airway CXCR4(+) granulocytes correlated with lung disease severity in patients with cystic fibrosis.These studies demonstrate that chronic fungal colonisation with A. fumigatus in cystic fibrosis patients is associated with CXCR4(+) airway granulocytes, which may serve as a potential biomarker and therapeutic target in fungal cystic fibrosis lung disease.

  10. Radiation-induced heart disease in lung cancer radiotherapy

    PubMed Central

    Ming, Xin; Feng, Yuanming; Yang, Chengwen; Wang, Wei; Wang, Ping; Deng, Jun

    2016-01-01

    Abstract Background: Radiation-induced heart disease (RIHD), which affects the patients’ prognosis with both acute and late side effects, has been published extensively in the radiotherapy of breast cancer, lymphoma and other benign diseases. Studies on RIHD in lung cancer radiotherapy, however, are less extensive and clear even though the patients with lung cancer are delivered with higher doses to the heart during radiation treatment. Methods: In this article, after extensive literature search and analysis, we reviewed the current evidence on RIHD in lung cancer patients after their radiation treatments and investigated the potential risk factors for RIHD as compared to other types of cancers. Result: Cardiac toxicity has been found highly relevant in lung cancer radiotherapy. So far, the crude incidence of cardiac complications in the lung cancer patients after radiotherapy has been up to 33%. Conclusion: The dose to the heart, the lobar location of tumor, the treatment modality, the history of heart and pulmonary disease and smoking were considered as potential risk factors for RIHD in lung cancer radiotherapy. As treatment techniques improve over the time with better prognosis for lung cancer survivors, an improved prediction model can be established to further reduce the cardiac toxicity in lung cancer radiotherapy. PMID:27741117

  11. Early interstitial lung disease in microscopic polyangiitis: Case report and literature review.

    PubMed

    García-Nava, Marcos; Mateos-Toledo, Heidegger; Guevara-Canseco, Ana Patricia Georgina; Infante-González, Cesar Eduardo; Reyes-Nava, Diego Alberto; Estrada-Castro, Emilio

    2016-12-02

    Microscopic polyangiitis (MPA) is a systemic disease included in the Chapel Hill 2012 Classification as necrotizing vasculitis affecting capillaries, venules and arterioles. It usually expresses antineutrophil cytoplasmic antibodies (ANCA) and has a perinuclear immunofluorescence pattern and correlation with anti-myeloperoxidase (MPO) antibodies. Capillaritis with alveolar hemorrhage is the most common manifestation of lung disease. Interstitial lung disease (ILD) is uncommon, with usual interstitial pneumonia being the predominant pattern. However, other patterns such as organizing pneumonia have been described. No guidelines exist for treating patients with ILD and, currently, ANCA-associated vasculitis (AAV) is managed along the lines of small vessel vasculitis. The prognosis with this association is uncertain, with possibilities of relapse and a fatal outcome. We present a case in which ILD was the first manifestation of MPA, without alveolar hemorrhage, with subsequent renal involvement and, in which, the established treatment produced a significant clinical improvement.

  12. Diagnosis and Treatment of Nontuberculous Mycobacterial Lung Disease: Clinicians' Perspectives

    PubMed Central

    Ryu, Yon Ju; Koh, Won-Jung

    2016-01-01

    Nontuberculous mycobacteria (NTM) are emerging pathogens that affect both immunocompromised and immunocompetent patients. The incidence and prevalence of NTM lung disease are increasing worldwide and rapidly becoming a major public health problem. For the diagnosis of NTM lung disease, patients suspected to have NTM lung disease are required to meet all clinical and microbiologic criteria. The development of molecular methods allows the characterization of new species and NTM identification at a subspecies level. Even after the identification of NTM species from respiratory specimens, clinicians should consider the clinical significance of such findings. Besides the limited options, treatment is lengthy and varies by species, and therefore a challenge. Treatment may be complicated by potential toxicity with discouraging outcomes. The decision to start treatment for NTM lung disease is not easy and requires careful individualized analysis of risks and benefits. Clinicians should be alert to those unique aspects of NTM lung disease concerning diagnosis with advanced molecular methods and treatment with limited options. Current recommendations and recent advances for diagnosis and treatment of NTM lung disease are summarized in this article. PMID:27066084

  13. Pulmonary hypertension in chronic obstructive and interstitial lung diseases.

    PubMed

    Andersen, Charlotte U; Mellemkjær, Søren; Nielsen-Kudsk, Jens Erik; Bendstrup, Elisabeth; Hilberg, Ole; Simonsen, Ulf

    2013-10-03

    The purpose of the present review is to summarize the current knowledge on PH in relation to COPD and ILD from a clinical perspective with emphasis on diagnosis, biomarkers, prevalence, impact, treatment, and practical implications. PH in COPD and ILD is associated with a poor prognosis, and is considered one of the most frequent types of PH. However, the prevalence of PH among patients with COPD and ILD is not clear. The diagnosis of PH in chronic lung disease is often established by echocardiographic screening, but definitive diagnosis requires right heart catheterization, which is not systematically performed in clinical practice. Given the large number of patients with chronic lung disease, biomarkers to preclude or increase suspicion of PH are needed. NT-proBNP may be used as a rule-out test, but biomarkers with a high specificity for PH are still required. It is not known whether specific treatment with existent drugs effective in pulmonary arterial hypertension (PAH) is beneficial in lung disease related PH. Studies investigating existing PAH drugs in animal models of lung disease related PH have indicated a positive effect, and so have case reports and open label studies. However, treatment with systemically administered pulmonary vasodilators implies the risk of worsening the ventilation-perfusion mismatch in patients with lung disease. Inhaled vasodilators may be better suited for PH in lung disease, but new treatment modalities are also required.

  14. Chronic obstructive lung diseases and risk of non-small cell lung cancer in women

    PubMed Central

    Schwartz, Ann G.; Cote, Michele L.; Wenzlaff, Angela S.; Van Dyke, Alison; Chen, Wei; Ruckdeschel, John C.; Gadgeel, Shirish; Soubani, Ayman O.

    2009-01-01

    Introduction The link between lung cancer and chronic obstructive lung diseases (COPD) has not been well studied in women even though lung cancer and COPD account for significant and growing morbidity and mortality among women. Methods We evaluated the relationship between COPD and non-small cell lung cancer (NSCLC) in a population-based case-control study of women and constructed a time course of chronic lung diseases in relation to onset of lung cancer. Five hundred sixty-two women aged 18–74, diagnosed with NSCLC and 564 population-based controls matched on race and age participated. Multivariable unconditional logistic regression models were used to estimate risk associated with a history of COPD, chronic bronchitis or emphysema. Results Lung cancer risk increased significantly for white women with a history of COPD (OR=1.85; 95% CI 1.21–2.81), but this was not seen in African American women. Risk associated with a history of chronic bronchitis was strongest when diagnosed at age 25 or earlier (OR=2.35, 95% CI 1.17–4.72); emphysema diagnosed within nine years of lung cancer was also associated with substantial risk (OR=6.36, 95% CI 2.36–17.13). Race, pack-years of smoking, exposure to environmental tobacco smoke as an adult, childhood asthma and exposure to asbestos were associated with a history of COPD among lung cancer cases. Conclusions In women, COPD is associated with risk of lung cancer differentially by race. Untangling whether COPD is in the causal pathway or simply shares risk factors will require future studies to focus on specific COPD features while exploring underlying genetic susceptibility to these diseases. PMID:19190518

  15. Coal mine dust lung disease. New lessons from old exposure.

    PubMed

    Petsonk, Edward L; Rose, Cecile; Cohen, Robert

    2013-06-01

    Coal mining remains a sizable industry, with millions of working and retired coal miners worldwide. This article provides an update on recent advances in the understanding of respiratory health issues in coal miners and focuses on the spectrum of disease caused by inhalation of coal mine dust, termed coal mine dust lung disease. In addition to the historical interstitial lung diseases (coal worker's pneumoconiosis, silicosis, and mixed dust pneumoconiosis), coal miners are at risk for dust-related diffuse fibrosis and chronic airway diseases, including emphysema and chronic bronchitis. Recent recognition of rapidly progressive pneumoconiosis in younger miners, mainly in the eastern United States, has increased the sense of urgency and the need for vigilance in medical research, clinical diagnosis, and exposure prevention. Given the risk for disease progression even after exposure removal, along with few medical treatment options, there is an important role for chest physicians in the recognition and management of lung disease associated with work in coal mining.

  16. Understanding Exercise, Diet and Lung Disease

    MedlinePlus

    ... of the system for breathing. This is the respiratory system. The respiratory system serves to provide oxygen to the blood, which ... quality of life through education, exercise and diet. respiratory system Referring to the mouth and nose, trachea, lungs ...

  17. Bronchoalveolar lavage in talc induced lung disease.

    PubMed Central

    Redondo, A A; Ettensohn, D B; Khan, M; Kessimian, N

    1988-01-01

    A 65 year old woman with a history of occupational talc inhalation presented with hypoxaemia, cough, and dyspnoea with a normal chest radiograph. Bronchoalveolar lavage showed considerable lymphocytosis, with a predominance of T8+ T lymphocytes, and open lung biopsy showed peribronchiolar granulomas containing talc crystals. Corticosteroid treatment resulted in dramatic improvement. Bronchoalveolar lavage may aid in the diagnosis of talc related lung injury. Images PMID:3238633

  18. Mycobacterium abscessus Lung Disease in a Patient with Kartagener Syndrome.

    PubMed

    Kim, Jung Hoon; Song, Won Jun; Jun, Ji Eun; Ryu, Duck Hyun; Lee, Ji Eun; Jeong, Ho Jung; Jeong, Suk Hyeon; Kang, Hyung Koo; Kim, Jung Soo; Lee, Hyun; Chon, Hae Ri; Jeon, Kyeongman; Kim, Dohun; Kim, Jhingook; Koh, Won-Jung

    2014-09-01

    Primary ciliary dyskinesia (PCD) is characterized by the congenital impairment of mucociliary clearance. When accompanied by situs inversus, chronic sinusitis and bronchiectasis, PCD is known as Kartagener syndrome. The main consequence of impaired ciliary function is a reduced mucus clearance from the lungs, and susceptibility to chronic respiratory infections due to opportunistic pathogens, including nontuberculous mycobacteria (NTM). There has been no report of NTM lung disease combined with Kartagener syndrome in Korea. Here, we report an adult patient with Kartagener syndrome complicated with Mycobacterium abscessus lung disease. A 37-year-old female presented to our hospital with chronic cough and sputum. She was ultimately diagnosed with M. abscessus lung disease and Kartagener syndrome. M. abscessus was repeatedly isolated from sputum specimens collected from the patient, despite prolonged antibiotic treatment. The patient's condition improved and negative sputum culture conversion was achieved after sequential bilateral pulmonary resection.

  19. Animal models of beryllium-induced lung disease

    SciTech Connect

    Finch, G.L.; Hoover, M.D.; Hahn, F.F.

    1996-10-01

    The Inhalation Toxicology Research Institute (ITRI) is conducting research to improve the understanding of chronic beryllium disease (CBD) and beryllium-induced lung cancer. Initial animal studies examined beagle dogs that inhaled BeO calcined at either 500 or 1000{degrees}C. At similar lung burdens, the 500{degrees}C BeO induced more severe and extensive granulomatous pneumonia, lymphocytic infiltration into the lung, and positive Be-specific lymphocyte proliferative responses in vitro than the 1000{degrees}C BeO. However, the progressive nature of human CBD was not duplicated. More recently, Strains A/J and C3H/HeJ mice were exposed to Be metal by inhalation. This produced a marked granulomatous pneumonia, diffuse infiltrates, and multifocal aggregates of interstitial lymphocytes with a pronounced T helper component and pulmonary in situ lymphocyte proliferation. With respect to lung cancer, at a mean lung burden as low as 17 pg Be/g lung, inhaled Be metal induced benign and/or malignant lung tumors in over 50% of male and female F344 rats surviving {ge}1 year on study. Substantial tumor multiplicity was found, but K-ras and p53 gene mutations were virtually absent. In mice, however, a lung burden of approximately 60 {mu}g ({approximately}300 {mu}g Be/g lung) caused only a slight increase in crude lung tumor incidence and multiplicity over controls in strain A/J mice and no elevated incidence in strain C3H mice. Taken together, this research program constitutes a coordinated effort to understand beryllium-induced lung disease in experimental animal models. 47 refs., 1 fig., 3 tabs.

  20. Heritability of Lung Disease Severity in Cystic Fibrosis

    PubMed Central

    Vanscoy, Lori L.; Blackman, Scott M.; Collaco, Joseph M.; Bowers, Amanda; Lai, Teresa; Naughton, Kathleen; Algire, Marilyn; McWilliams, Rita; Beck, Suzanne; Hoover-Fong, Julie; Hamosh, Ada; Cutler, Dave; Cutting, Garry R.

    2007-01-01

    Rationale: Obstructive lung disease, the major cause of mortality in cystic fibrosis (CF), is poorly correlated with mutations in the disease-causing gene, indicating that other factors determine severity of lung disease. Objectives: To quantify the contribution of modifier genes to variation in CF lung disease severity. Methods: Pulmonary function data from patients with CF living with their affected twin or sibling were converted into reference values based on both healthy and CF populations. The best measure of FEV1 within the last year was used for cross-sectional analysis. FEV1 measures collected over at least 4 years were used for longitudinal analysis. Genetic contribution to disease variation (i.e., heritability) was estimated in two ways: by comparing similarity of lung function in monozygous (MZ) twins (∼ 100% gene sharing) with that of dizygous (DZ) twins/siblings (∼ 50% gene sharing), and by comparing similarity of lung function measures for related siblings to similarity for all study subjects. Measurements and Main Results: Forty-seven MZ twin pairs, 10 DZ twin pairs, and 231 sibling pairs (of a total of 526 patients) with CF were studied. Correlations for all measures of lung function for MZ twins (0.82–0.91, p < 0.0001) were higher than for DZ twins and siblings (0.50–0.64, p < 0.001). Heritability estimates from both methods were consistent for each measure of lung function and ranged from 0.54 to 1.0. Heritability estimates generally increased after adjustment for differences in nutritional status (measured as body mass index z-score). Conclusions: Our heritability estimates indicate substantial genetic control of variation in CF lung disease severity, independent of CFTR genotype. PMID:17332481

  1. Tumor Necrosis Factor–α Overexpression in Lung Disease

    PubMed Central

    Lundblad, Lennart K. A.; Thompson-Figueroa, John; Leclair, Timothy; Sullivan, Michael J.; Poynter, Matthew E.; Irvin, Charles G.; Bates, Jason H. T.

    2005-01-01

    Rationale: Tumor necrosis factor α (TNF-α) has been implicated as a key cytokine in many inflammatory lung diseases. These effects are currently unclear, because a transgenic mouse overexpressing TNF-α in the lung has been shown in separate studies to produce elements of both emphysema and pulmonary fibrosis. Objectives: We sought to elucidate the phenotypic effects of TNF-α overexpression in a mouse model. Measurements: We established the phenotype by measuring lung impedance and thoracic gas volume, and using micro–computed tomography and histology. Main Results: We found that airways resistance in this mouse was not different to control mice, but that lung tissue dampening, elastance, and hysteresivity were significantly elevated. Major heterogeneous abnormalities of the parenchyma were also apparent in histologic sections and in micro–computed tomography images of the lung. These changes included airspace enlargement, loss of small airspaces, increased collagen, and thickened pleural septa. We also found significant increases in lung and chest cavity volumes in the TNF-α–overexpressing mice. Conclusions: We conclude that TNF-α overexpression causes pathologic changes consistent with both emphysema and pulmonary fibrosis combined with a general lung inflammation, and consequently does not model any single human disease. Our study thus confirms the pleiotropic effects of TNF-α, which has been implicated in multiple inflammatory disorders, and underscores the necessity of using a wide range of investigative techniques to link gene expression and phenotype in animal models of disease. PMID:15805183

  2. [Therapeutic training and sports in chronic diseases of the lung].

    PubMed

    Podolsky, A; Haber, P

    1993-01-01

    Training is defined as systematic physical activity in order to improve the physical working capacity, which causes measurable morphological and functional changes in organs. Effects and the rules of applying aerobic endurance training in patients with chronic diseases of the lungs are dealt with. Training does not replace the normal medication, but is an additional therapeutic mean in order to regain physical working capacity, lost by chronic immobilization in the natural course of disease. Contraindications are acute diseases and exacerbations, but not a certain degree of the disease. Training does not improve the lung function, but the function of the other organs, the physical working capacity ist based on (circulation, musculature). This helps to use optimally the remaining reserves of lung function. Methods of aerobic endurance training are described, the definition of aims, performance diagnostic and the finding of the exact doses of training according to intensity, duration, frequency and the weekly netto training time. The training in different diseases of the lungs is discussed: In asthma bronchiale the prophylaxis of the exercise induced asthma and permitted and forbidden drugs for asthmatics according to the rules of international olympic committee. In chronic bronchitis with arterial hypoxemia, in restrictive lung diseases and in pulmonary hypertension. At last the way to prescribing training for patients with chronic pulmonary diseases is described as well as the advising of patients wishing to do sport by their own motivation or planning projects, for instance touristic ones, which require physical stress.

  3. [Severe interstitial lung disease from pathologic gastroesophageal reflux in children].

    PubMed

    Ahrens, P; Weimer, B; Hofmann, D

    1999-07-01

    Interstitial lung diseases comprise a heterogeneous group of pulmonary conditions that cause restrictive lung disease of poor prognosis, especially if growth failure, pulmonary hypertension and fibrosis appears. We report on the case of a girl of 11 years of age who suffered from severe nonallergic asthma in early childhood and who developed severe interstitial pulmonary disease caused by gastro-oesophageal reflux at the age of 8 years. This diagnosis was established by lung biopsy, bronchoalveolar lavage and a high amount of lipid-laden alveolar macrophages, 2-level pH measurement and oesophageal biopsy. Because therapy with oral and inhaled steroids failed and Omeprazol showed benificial effects, hemifundoplication according to THAL was performed. At present the lung function is clearly normal and there is no need of any medicaments. Following the history, we can assume the pathological gastro-oesophageal reflux to be the cause of the disease. It is important to state that there were no typical symptoms at any time pointing to gastro-oesophageal reflux disease. The development of pulmonary disease by pathological reflux is very often caused by "silent aspiration". Very typically there are no symptoms such as vomiting, heartburn and pain but only signs of chronic lung disease.

  4. Parenchymal lung involvement in adult-onset Still disease

    PubMed Central

    Gerfaud-Valentin, Mathieu; Cottin, Vincent; Jamilloux, Yvan; Hot, Arnaud; Gaillard-Coadon, Agathe; Durieu, Isabelle; Broussolle, Christiane; Iwaz, Jean; Sève, Pascal

    2016-01-01

    Abstract Parenchymal lung involvement (PLI) in adult-onset Still's disease (AOSD) has seldom, if ever, been studied. We examine here retrospective cohort AOSD cases and present a review of the literature (1971–2014) on AOSD-related PLI cases. Patients with PLI were identified in 57 AOSD cases. For inclusion, the patients had to fulfill Yamaguchi or Fautrel classification criteria, show respiratory symptoms, and have imaging evidence of pulmonary involvement, and data allowing exclusion of infectious, cardiogenic, toxic, or iatrogenic cause of PLI should be available. This AOSD + PLI group was compared with a control group (non–PLI-complicated AOSD cases from the same cohort). AOSD + PLI was found in 3 out of the 57 patients with AOSD (5.3%) and the literature mentioned 27 patients. Among these 30 AOSD + PLI cases, 12 presented an acute respiratory distress syndrome (ARDS) and the remaining 18 another PLI. In the latter, a nonspecific interstitial pneumonia computed tomography pattern prevailed in the lower lobes, pulmonary function tests showed a restrictive lung function, the alveolar differential cell count was neutrophilic in half of the cases, and the histological findings were consistent with bronchiolitis and nonspecific interstitial pneumonia. Corticosteroids were fully efficient in all but 3 patients. Ten out of 12 ARDS cases occurred during the first year of the disease course. All ARDS-complicated AOSD cases received corticosteroids with favorable outcomes in 10 (2 deceased). Most PLIs occurred during the systemic onset of AOSD. PLI may occur in 5% of AOSDs, of which ARDS is the most severe. Very often, corticosteroids are efficient in controlling this complication. PMID:27472698

  5. Airbag lung: an unusual case of sarcoid-like granulomatous lung disease after a rollover motor vehicle accident.

    PubMed

    Waring, Thomas P; Hegde, Poornima; Foley, Raymond J

    2014-05-01

    Sarcoid-like granulomatous lung disease (SLGLD) is a condition associated with the formation of noncaseating, nonnecrotizing granulomas. The final by-product of airbag deployment is alkaline silicates or glass. Silicates trapped and sequestered in the lung parenchyma are a potential mediator for immune system activation and development of sarcoid-like granulomatous lung disease.

  6. Behavior patterns and coronary heart disease

    NASA Technical Reports Server (NTRS)

    Townsend, J. C.; Cronin, J. P.

    1975-01-01

    The relationships between two behavioral patterns, cardiac risk factors, and coronary heart disease are investigated. Risk factors used in the analysis were family history of coronary disease, smoking, cholesterol, obesity, systotic blood pressure, diastolic blood pressure, blood sugar, uric acid, erythrocyte sedimentation rate, and white blood unit. It was found that conventional, non-behavioral pattern risk factors alone were not significantly related to coronary heart disease.

  7. Legionella (Legionnaires' Disease and Pontiac Fever): History and Disease Patterns

    MedlinePlus

    ... Search The CDC Cancel Submit Search The CDC Legionella (Legionnaires' Disease and Pontiac Fever) Note: Javascript is disabled or ... Materials Publications Related Links ELITE Program Application CDC Legionella Healthy Swimming CDC Vessel Sanitation ... and Disease Patterns ...

  8. Systems biology approaches to identify developmental bases for lung diseases.

    PubMed

    Bhattacharya, Soumyaroop; Mariani, Thomas J

    2013-04-01

    A greater understanding of the regulatory processes contributing to lung development could be helpful to identify strategies to ameliorate morbidity and mortality in premature infants and to identify individuals at risk for congenital and/or chronic lung diseases. Over the past decade, genomics technologies have enabled the production of rich gene expression databases providing information for all genes across developmental time or in diseased tissue. These data sets facilitate systems biology approaches for identifying underlying biological modules and programs contributing to the complex processes of normal development and those that may be associated with disease states. The next decade will undoubtedly see rapid and significant advances in redefining both lung development and disease at the systems level.

  9. The Role of the Bacterial Microbiome in Lung Disease

    PubMed Central

    Dickson, Robert P.; Erb-Downward, John R.; Huffnagle, Gary B.

    2014-01-01

    Novel culture-independent techniques have recently demonstrated that the lower respiratory tract, historically considered sterile in health, contains diverse communities of microbes: the lung microbiome. A growing literature has demonstrated that a distinct microbiota of the lower respiratory tract is present both in health and in various respiratory diseases, though the biological and clinical significance of these findings remains undetermined. In this article, we review and synthesize published reports of the lung microbiota of healthy and diseased subjects, discuss trends of microbial diversity and constitution across disease states, and look to the extra-pulmonary microbiome for hypotheses and future directions for study. PMID:23734647

  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. Clinical Trials for Rare Lung Diseases: Lessons from Lymphangioleiomyomatosis

    PubMed Central

    McCormack, Francis X.

    2010-01-01

    Abstract Lymphangioleiomyomatosis (LAM) is a rare, slowly progressive neoplasm that causes gradual but often life-threatening cystic destruction of the lung. Advances in our understanding of the molecular and cellular pathogenesis have LAM have identified a number of promising targets for testing in therapeutic trials. However, the design, prioritization, organization, and implementation of clinical trials in rare lung diseases poses unique challenges, including geographically disperse populations, sluggish enrollment, off- label drug use, burdensome regulations, and paucity of validated surrogate endpoints. PMID:20235889

  12. Lung adenocarcinoma with giant cyst formation showing a variety of histologic patterns: a case report

    PubMed Central

    2010-01-01

    Introduction Lung cancer with large cyst formation is relatively rare. This is a case report of a patient with lung cystic adenocarcinoma with multiple histologic patterns. This type of lung adenocarcinoma is believed to be the first reported case in English language medical literature. Case presentation A 60-year-old Japanese woman was admitted to hospital complaining of dyspnea and died of respiratory failure. She had been suffering from lung cancer with pleural effusion for five years. Autopsy analysis revealed lung adenocarcinoma with large cyst formation showing a variety of histologic patterns. Conclusions Autopsy analysis of this atypical case of lung cancer may provide insight and lead to a better understanding of the heterogeneity and clonal expansion of lung adenocarcinoma. PMID:21108775

  13. Patterns of Care for Lung Cancer in Radiation Oncology Departments of Turkey

    SciTech Connect

    Demiral, Ayse Nur Alicikus, Zuemre Arican; Isil Ugur, Vahide; Karadogan, Ilker; Yoeney, Adnan; Andrieu, Meltem Nalca; Yalman, Deniz; Pak, Yuecel; Aksu, Gamze; Ozyigit, Goekhan; Ozkan, Luetfi; Kilciksiz, Sevil; Koca, Sedat; Caloglu, Murat; Yavuz, Ali Aydin; Basak Caglar, Hale; Beyzadeoglu, Murat; Igdem, Sefik

    2008-12-01

    Purpose: To determine the patterns of care for lung cancer in Turkish radiation oncology centers. Methods and Materials: Questionnaire forms from 21 of 24 (87.5%) centers that responded were evaluated. Results: The most frequent histology was non-small cell lung cancer (NSCLC) (81%). The most common postoperative radiotherapy (RT) indications were close/(+) surgical margins (95%) and presence of pN2 disease (91%). The most common indications for postoperative chemotherapy (CHT) were '{>=} IB' disease (19%) and the presence of pN2 disease (19%). In Stage IIIA potentially resectable NSCLC, the most frequent treatment approach was neoadjuvant concomitant chemoradiotherapy (CHRT) (57%). In Stage IIIA unresectable and Stage IIIB disease, the most frequent approach was definitive concomitant CHRT (91%). In limited SCLC, the most common treatment approach was concomitant CHRT with cisplatin+etoposide for cycles 1-3, completion of CHT to cycles 4-6, and finally prophylactic cranial irradiation in patients with complete response (71%). Six cycles of cisplatin + etoposide CHT and palliative thoracic RT, when required, was the most commonly used treatment (81%) in extensive SCLC. Sixty-two percent of centers did not have endobronchial brachytherapy (EBB) facilities. Conclusion: There is great variation in diagnostic testing, treatment strategies, indications for postoperative RT and CHT, RT features, and EBB availability for LC cases. To establish standards, national guidelines should be prepared using a multidisciplinary approach.

  14. [Occupational lung diseases other than asbestos- and indium-related disease].

    PubMed

    Kimura, Kiyonobu; Nakano, Ikuo; Ohtsuka, Yosinori; Igarashi, Takeshi; Okamoto, Kenzo

    2014-02-01

    In our country, pneumoconiosis used to hold an overwhelmingly majority in respiratory occupational lung diseases. Although the number of pneumoconiosis cases has been decreasing certainly, new cases have been arising even today. In addition, in place of pneumoconiosis or asbestos-related diseases, occupational asthma has become the most common forms of occupational lung disease in many industrialized countries. Occupational asthma has been implicated in 9 to 15% of adult asthma in the United States. Although the environmental causes of occupational lung disease are clear, the mechanisms of the diseases are not fully understood and need to be further elucidated.

  15. Lung tissues in systemic sclerosis have gene expression patterns unique to pulmonary fibrosis and pulmonary hypertension

    PubMed Central

    Hsu, Eileen; Shi, Haiwen; Jordan, Rick M.; Lyons-Weiler, James; Pilewski, Joseph M.; Feghali-Bostwick, Carol A.

    2010-01-01

    Objective Pulmonary complications in systemic sclerosis (SSc), including pulmonary fibrosis (PF) and pulmonary arterial hypertension (PAH), are the leading cause of mortality. We compared the molecular fingerprint of SSc lung tissues and matching primary lung fibroblasts to those of normal donors, and patients with idiopathic pulmonary fibrosis (IPF) and idiopathic pulmonary arterial hypertension (IPAH). Methods Lung tissues were obtained from 33 patients with SSc who underwent lung transplantation. Tissues and cells from a subgroup of SSc patients with predominantly PF or PAH were compared to those from normal donors, patients with IPF, or IPAH. Microarray data was analyzed using Efficiency Analysis for determination of optimal data processing methods. Real time PCR and immunohistochemistry were used to confirm differential levels of mRNA and protein, respectively. Results We identified a consensus of 242 and 335 genes that were differentially expressed in lungs and primary fibroblasts, respectively. Enriched function groups in SSc-PF and IPF lungs included fibrosis, insulin-like growth factor signaling and caveolin-mediated endocytosis. Functional groups shared by SSc-PAH and IPAH lungs included antigen presentation, chemokine activity, and IL-17 signaling. Conclusion Using microarray analysis on carefully phenotyped SSc and comparator lung tissues, we demonstrated distinct molecular profiles in tissues and fibroblasts of patients with SSc-associated lung disease compared to idiopathic forms of lung disease. Unique molecular signatures were generated that are disease- (SSc) and phenotype- (PF vs PAH) specific. These signatures provide new insights into pathogenesis and potential therapeutic targets for SSc lung disease. PMID:21360508

  16. NET balancing: a problem in inflammatory lung diseases

    PubMed Central

    Cheng, Olivia Z.; Palaniyar, Nades

    2013-01-01

    Neutrophil extracellular traps (NETs) are beneficial antimicrobial defense structures that can help fight against invading pathogens in the host. However, recent studies reveal that NETs exert adverse effects in a number of diseases including those of the lung. Many inflammatory lung diseases are characterized with a massive influx of neutrophils into the airways. Neutrophils contribute to the pathology of these diseases. To date, NETs have been identified in the lungs of cystic fibrosis (CF), acute lung injury (ALI), allergic asthma, and lungs infected with bacteria, virus, or fungi. These microbes and several host factors can stimulate NET formation, or NETosis. Different forms of NETosis have been identified and are dependent on varying types of stimuli. All of these pathways however appear to result in the formation of NETs that contain DNA, modified extracellular histones, proteases, and cytotoxic enzymes. Some of the NET components are immunogenic and damaging to host tissue. Innate immune collectins, such as pulmonary surfactant protein D (SP-D), bind NETs, and enhance the clearance of dying cells and DNA by alveolar macrophages. In many inflammatory lung diseases, bronchoalveolar SP-D levels are altered and its deficiency results in the accumulation of DNA in the lungs. Some of the other therapeutic molecules under consideration for treating NET-related diseases include DNases, antiproteases, myeloperoxidase (MPO) inhibitors, peptidylarginine deiminase-4 inhibitors, and anti-histone antibodies. NETs could provide important biological advantage for the host to fight against certain microbial infections. However, too much of a good thing can be a bad thing. Maintaining the right balance of NET formation and reducing the amount of NETs that accumulate in tissues are essential for harnessing the power of NETs with minimal damage to the hosts. PMID:23355837

  17. Previous Lung Diseases and Lung Cancer Risk: A Systematic Review and Meta-Analysis

    PubMed Central

    Brenner, Darren R.; McLaughlin, John R.; Hung, Rayjean J.

    2011-01-01

    Background In order to review the epidemiologic evidence concerning previous lung diseases as risk factors for lung cancer, a meta-analysis and systematic review was conducted. Methods Relevant studies were identified through MEDLINE searches. Using random effects models, summary effects of specific previous conditions were evaluated separately and combined. Stratified analyses were conducted based on smoking status, gender, control sources and continent. Results A previous history of COPD, chronic bronchitis or emphysema conferred relative risks (RR) of 2.22 (95% confidence interval (CI): 1.66, 2.97) (from 16 studies), 1.52 (95% CI: 1.25, 1.84) (from 23 studies) and 2.04 (95% CI: 1.72, 2.41) (from 20 studies), respectively, and for all these diseases combined 1.80 (95% CI: 1.60, 2.11) (from 39 studies). The RR of lung cancer for subjects with a previous history of pneumonia was 1.43 (95% CI: 1.22–1.68) (from 22 studies) and for subjects with a previous history of tuberculosis was 1.76 (95% CI = 1.49, 2.08), (from 30 studies). Effects were attenuated when restricting analysis to never smokers only for COPD/emphysema/chronic bronchitis (RR = 1.22, 0.97–1.53), however remained significant for pneumonia 1.36 (95% CI: 1.10, 1.69) (from 8 studies) and tuberculosis 1.90 (95% CI: 1.45, 2.50) (from 11 studies). Conclusions Previous lung diseases are associated with an increased risk of lung cancer with the evidence among never smokers supporting a direct relationship between previous lung diseases and lung cancer. PMID:21483846

  18. Asbestos content of lung tissue in asbestos associated diseases: a study of 110 cases.

    PubMed Central

    Roggli, V L; Pratt, P C; Brody, A R

    1986-01-01

    Diseases associated with asbestos exposure include asbestosis, malignant mesothelioma, carcinoma of the lung, and parietal pleural plaques. In this study the asbestos content of lung tissue was examined in groups of cases representing each of these diseases and in several cases with non-occupational idiopathic pulmonary fibrosis. Asbestos bodies (AB), which are the hallmark of asbestos exposure, were present in the lungs of virtually everyone in the general population and present at increased levels in individuals with asbestos associated diseases. The highest numbers of AB occurred in individuals with asbestosis, all of whom had levels greater than or equal to 2000 ABs/g wet lung tissue. Every case with a content of 100,000 ABs/g or higher had asbestosis. Intermediate levels occurred in individuals with malignant mesothelioma and the lowest levels in patients with parietal pleural plaques. There was no overlap between the asbestos content of lung tissue from patients with asbestosis and those with idiopathic pulmonary fibrosis. Lung cancer was present in half the patients with asbestosis, and the distribution of histological patterns did not differ from that in patients with lung cancer without asbestosis. The asbestos body content in patients with lung cancer was highly variable. Control cases had values within our previously established normal range (0-20 ABs/g). There was a significant correlation (p less than 0.001) between AB counted by light microscope and AB and uncoated fibres counted by scanning electron microscopy. The previous observation that the vast majority of asbestos bodies isolated from human tissues have an amphibole core was confirmed. Images PMID:3947558

  19. A Case of Sarcoidosis with Interstitial Lung Disease Mimicking Clinically Amyopathic Dermatomyositis and Rapidly Progressive Interstitial Lung Disease

    PubMed Central

    Nogi, Shinichi; Sasaki, Noriko; Chinen, Naofumi; Honda, Kiri; Saito, Eiko; Wakabayashi, Takayuki; Yamada, Chiho; Suzuki, Yasuo

    2014-01-01

    Here, we report a patient with sarcoidosis who developed edematous erythema and interstitial lung disease. At the initial visit, clinically amyopathic dermatomyositis (CADM) with rapidly progressive interstitial lung disease (RP-ILD) was suspected because he had progressive dyspnea but no muscle weakness. The presence of anti-CADM-140/MDA5 autoantibodies was immediately assessed to facilitate a precise diagnosis, with negative results. Thereafter, skin and transbronchial lung biopsies revealed noncaseating granuloma with Langhans giant cells in both specimens, leading to a diagnosis of sarcoidosis. In this case, clinical features of skin and lung were unable to distinguish DM (including CADM) from sarcoidosis, but the lack of anti-CADM-140/MDA5 antibody was useful for differentiating CADM with RP-ILD mimicking sarcoidosis from bona fide sarcoidosis. PMID:25431723

  20. CT of chronic infiltrative lung disease: Prevalence of mediastinal lymphadenopathy

    SciTech Connect

    Niimi, Hiroshi; Kang, Eun-Young; Kwong, S.

    1996-03-01

    Our goal was to determine the prevalence of mediastinal lymph node enlargement at CT in patients with diffuse infiltrative lung disease. The study was retrospective and included 175 consecutive patients with diffuse infiltrative lung diseases. Diagnoses included idiopathic pulmonary fibrosis (IPF) (n = 61), usual interstitial pneumonia associated with collagen vascular disease (CVD) (n = 20), idiopathic bronchiolitis obliterans organizing pneumonia (BOOP) (n = 22), extrinsic allergic alveolitis (EAA) (n = 17), and sarcoidosis (n = 55). Fifty-eight age-matched patients with CT of the chest performed for unrelated conditions served as controls. The presence, number, and sites of enlarged nodes (short axis {ge}10 mm in diameter) were recorded. Enlarged mediastinal nodes were present in 118 of 175 patients (67%) with infiltrative lung disease and 3 of 58 controls (5%) (p < 0.001). The prevalence of enlarged nodes was 84% (46 of 55) in sarcoidosis, 67% (41 of 61) in IPF, 70% (14 of 20) in CVD, 53% (9 of 17) in EAA, and 36% (8 of 22) in BOOP. The mean number of enlarged nodes was higher in sarcoidosis (mean 3.2) than in the other infiltrative diseases (mean 1.2) (p < 0.001). Enlarged nodes were most commonly present in station 10R, followed by 7, 4R, and 5. Patients with infiltrative lung disease frequently have enlarged mediastinal lymph nodes. However, in diseases other than sarcoid, usually only one or two nodes are enlarged and their maximal short axis diameter is <15 mm. 11 refs., 2 figs., 1 tab.

  1. Staging of Bilateral Lung Transplantation for High-Risk Patients With Interstitial Lung Disease: One Lung at a Time.

    PubMed

    Hartwig, M G; Ganapathi, A M; Osho, A A; Hirji, S A; Englum, B R; Speicher, P J; Palmer, S M; Davis, R D; Snyder, L D

    2016-11-01

    The choice of a single or bilateral lung transplant for interstitial lung disease (ILD) is controversial, as surgical risk, long-term survival and organ allocation are competing factors. In an effort to balance risk and benefit, our center adopted a staged bilateral lung transplant approach for higher surgical risk ILD patients where the patient has a single lung transplant followed by a second single transplant at a later date. We sought to understand the surgical risk, organ allocation and early outcomes of these staged bilateral recipients as a group and in comparison to matched single and bilateral recipients. Our analysis demonstrates that staged bilateral lung transplant recipients (n = 12) have a higher lung allocation score (LAS), lower pulmonary function tests and a lower glomerular filtration rate prior to the first transplant compared to the second (p < 0.01). There was a shorter length of hospital stay for the second transplant (p = 0.02). The staged bilateral compared to the single and bilateral case-matched controls had comparable short-term survival (p = 0.20) and pulmonary function tests at 1 year. There was a higher incidence of renal injury in the conventional bilateral group compared to the single and staged bilateral groups. The staged bilateral procedure is a viable option in select ILD patients.

  2. Oxidative Stress and Therapeutic Development in Lung Diseases

    PubMed Central

    Villegas, Leah; Stidham, Timothy; Nozik-Grayck, Eva

    2016-01-01

    Oxidative stress has many implications in the pathogenesis of lung diseases. In this review, we provide an overview of Reactive Oxygen Species (ROS) and nitrogen (RNS) species and antioxidants, how they relate to normal physiological function and the pathophysiology of different lung diseases, and therapeutic strategies. The production of ROS/RNS from endogenous and exogenous sources is first discussed, followed by antioxidant systems that restore oxidative balance and cellular homeostasis. The contribution of oxidant/antioxidant imbalance in lung disease pathogenesis is also discussed. An overview of therapeutic strategies is provided, such as augmenting NO bioactivity, blocking the production of ROS/RNS and replacement of deficient antioxidants. The limitations of current strategies and failures of clinical trials are then addressed, followed by discussion of novel experimental approaches for the development of improved antioxidant therapies. PMID:27019769

  3. Oxidative Stress and Therapeutic Development in Lung Diseases.

    PubMed

    Villegas, Leah; Stidham, Timothy; Nozik-Grayck, Eva

    2014-08-01

    Oxidative stress has many implications in the pathogenesis of lung diseases. In this review, we provide an overview of Reactive Oxygen Species (ROS) and nitrogen (RNS) species and antioxidants, how they relate to normal physiological function and the pathophysiology of different lung diseases, and therapeutic strategies. The production of ROS/RNS from endogenous and exogenous sources is first discussed, followed by antioxidant systems that restore oxidative balance and cellular homeostasis. The contribution of oxidant/antioxidant imbalance in lung disease pathogenesis is also discussed. An overview of therapeutic strategies is provided, such as augmenting NO bioactivity, blocking the production of ROS/RNS and replacement of deficient antioxidants. The limitations of current strategies and failures of clinical trials are then addressed, followed by discussion of novel experimental approaches for the development of improved antioxidant therapies.

  4. Computerized detection of diffuse lung disease in MDCT: the usefulness of statistical texture features

    NASA Astrophysics Data System (ADS)

    Wang, Jiahui; Li, Feng; Doi, Kunio; Li, Qiang

    2009-11-01

    Accurate detection of diffuse lung disease is an important step for computerized diagnosis and quantification of this disease. It is also a difficult clinical task for radiologists. We developed a computerized scheme to assist radiologists in the detection of diffuse lung disease in multi-detector computed tomography (CT). Two radiologists selected 31 normal and 37 abnormal CT scans with ground glass opacity, reticular, honeycombing and nodular disease patterns based on clinical reports. The abnormal cases in our database must contain at least an abnormal area with a severity of moderate or severe level that was subjectively rated by the radiologists. Because statistical texture features may lack the power to distinguish a nodular pattern from a normal pattern, the abnormal cases that contain only a nodular pattern were excluded. The areas that included specific abnormal patterns in the selected CT images were then delineated as reference standards by an expert chest radiologist. The lungs were first segmented in each slice by use of a thresholding technique, and then divided into contiguous volumes of interest (VOIs) with a 64 × 64 × 64 matrix size. For each VOI, we determined and employed statistical texture features, such as run-length and co-occurrence matrix features, to distinguish abnormal from normal lung parenchyma. In particular, we developed new run-length texture features with clear physical meanings to considerably improve the accuracy of our detection scheme. A quadratic classifier was employed for distinguishing between normal and abnormal VOIs by the use of a leave-one-case-out validation scheme. A rule-based criterion was employed to further determine whether a case was normal or abnormal. We investigated the impact of new and conventional texture features, VOI size and the dimensionality for regions of interest on detecting diffuse lung disease. When we employed new texture features for 3D VOIs of 64 × 64 × 64 voxels, our system achieved the

  5. Usual interstitial pneumonia-pattern fibrosis in surgical lung biopsies. Clinical, radiological and histopathological clues to aetiology

    PubMed Central

    Smith, Maxwell; Dalurzo, Mercedes; Panse, Prasad; Parish, James; Leslie, Kevin

    2013-01-01

    Pulmonary fibrosis in surgical lung biopsies is said to have a ‘usual interstitial pneumonia-pattern’ (UIP-pattern) of disease when scarring of the parenchyma is present in a patchy, ‘temporally heterogeneous’ distribution. These biopsies are one of the more common non-neoplastic specimens surgical pathologists encounter and often pose a number of challenges. UIP is the expected histopathological pattern in patients with clinical idiopathic pulmonary fibrosis (IPF), but the UIP-pattern can be seen in other conditions on occasion. Most important among these are the rheumatic interstitial lung diseases (RILD) and chronic hypersensitivity pneumonitis (CHrHP). Because theses entities have different mechanisms of injury, approach to therapy, and expected clinical progression, it is imperative for the surgical pathologist to correctly classify them. Taken in isolation, the UIP-pattern seen in patients with IPF may appear to overlap with that of RILD and CHrHP, at least when using the broadest definition of this term (patchy fibrosis). However, important distinguishing features are nearly always present in our experience, and the addition of a multidisciplinary approach will often resolve the critical differences between these diseases. In this manuscript, we review the distinguishing clinical, radiologic and histopathological features of UIP of IPF, RILD and CHrHP, based, in part, on the existing literature, but also lessons learned from a busy lung biopsy consultation practice. PMID:23703852

  6. Lung Regeneration Therapy for Chronic Obstructive Pulmonary Disease.

    PubMed

    Oh, Dong Kyu; Kim, You-Sun; Oh, Yeon-Mok

    2017-01-01

    Chronic obstructive pulmonary disease (COPD) is a critical condition with high morbidity and mortality. Although several medications are available, there are no definite treatments. However, recent advances in the understanding of stem and progenitor cells in the lung, and molecular changes during re-alveolization after pneumonectomy, have made it possible to envisage the regeneration of damaged lungs. With this background, numerous studies of stem cells and various stimulatory molecules have been undertaken, to try and regenerate destroyed lungs in animal models of COPD. Both the cell and drug therapies show promising results. However, in contrast to the successes in laboratories, no clinical trials have exhibited satisfactory efficacy, although they were generally safe and tolerable. In this article, we review the previous experimental and clinical trials, and summarize the recent advances in lung regeneration therapy for COPD. Furthermore, we discuss the current limitations and future perspectives of this emerging field.

  7. Lung Regeneration Therapy for Chronic Obstructive Pulmonary Disease

    PubMed Central

    Oh, Dong Kyu; Kim, You-Sun

    2017-01-01

    Chronic obstructive pulmonary disease (COPD) is a critical condition with high morbidity and mortality. Although several medications are available, there are no definite treatments. However, recent advances in the understanding of stem and progenitor cells in the lung, and molecular changes during re-alveolization after pneumonectomy, have made it possible to envisage the regeneration of damaged lungs. With this background, numerous studies of stem cells and various stimulatory molecules have been undertaken, to try and regenerate destroyed lungs in animal models of COPD. Both the cell and drug therapies show promising results. However, in contrast to the successes in laboratories, no clinical trials have exhibited satisfactory efficacy, although they were generally safe and tolerable. In this article, we review the previous experimental and clinical trials, and summarize the recent advances in lung regeneration therapy for COPD. Furthermore, we discuss the current limitations and future perspectives of this emerging field. PMID:28119741

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

    PubMed

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

    2011-01-01

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

  9. Proteomics of lung cell biology and pulmonary disease.

    PubMed

    Levine, Stewart J

    2007-10-01

    Proteomics has the goal of defining the complete protein complement of biological systems, which can then be analyzed in a comparative fashion to generate informative data regarding protein expression and function. Proteomic analyses can also facilitate the discovery of biomarkers that can be used to diagnose and monitor disease severity, activity and therapeutic response, as well as to identify new targets for drug development. A major challenge for proteomics, however, has been detecting low-abundance proteins in complex biological fluids. This review summarizes how proteomic analyses have advanced lung cell biology and facilitated the identification of new mechanisms of disease pathogenesis in respiratory disorders, such as asthma, cystic fibrosis, lung cancer, acute lung injury and sarcoidosis. The impact of nanotechnology and microfluidics, as well as studies of post-translational modifications and protein-protein interactions (the interactome), are considered. Furthermore, the application of systems-biology approaches to organize and analyze data regarding the lung proteome, interactome, genome, transcriptome, metabolome, glycome and small RNAome (regulatory RNAs), should facilitate future conceptual advances regarding lung cell biology, disease pathogenesis, biomarker discovery and drug development.

  10. Childhood Wheezing, Asthma, Allergy, Atopy, and Lung Function: Different Socioeconomic Patterns for Different Phenotypes

    PubMed Central

    Galobardes, Bruna; Granell, Raquel; Sterne, Jonathan; Hughes, Rachael; Mejia-Lancheros, Cilia; Davey Smith, George; Henderson, John

    2015-01-01

    Identifying preventable exposures that lead to asthma and associated allergies has proved challenging, partly because of the difficulty in differentiating phenotypes that define homogeneous disease groups. Understanding the socioeconomic patterns of disease phenotypes can help distinguish which exposures are preventable. In the present study, we identified disease phenotypes that are susceptible to socioeconomic variation, and we determined which life-course exposures were associated with these inequalities in a contemporary birth cohort. Participants included children from the Avon Longitudinal Study of Parents and Children, a population-based birth cohort in England, who were born in 1991 and 1992 and attended the clinic at 7–8 years of age (n = 6,378). Disease phenotypes included asthma, atopy, wheezing, altered lung function, and bronchial reactivity phenotypes. Combining atopy with a diagnosis of asthma from a doctor captured the greatest socioeconomic variation, including opposing patterns between phenotype groups: Children with a low socioeconomic position (SEP) had more asthma alone (adjusted multinomial odds ratio = 1.50, 95% confidence interval: 1.21, 1.87) but less atopy alone (adjusted multinomial odds ratio = 0.80, 95% confidence interval: 0.66, 0.98) than did children with high SEP. Adjustment for maternal exposure to tobacco smoke during pregnancy and childhood exposure to tobacco smoke reduced the odds of asthma alone in children with a low SEP. Current inequalities among children who have asthma but not atopy can be prevented by eliminating exposure to tobacco smoke. Other disease phenotypes were not socially patterned or had SEP patterns that were not related to smoke exposure. PMID:26443417

  11. Open lung biopsy: a safe, reliable and accurate method for diagnosis in diffuse lung disease.

    PubMed

    Shah, S S; Tsang, V; Goldstraw, P

    1992-01-01

    The ideal method for obtaining lung tissue for diagnosis should provide high diagnostic yield with low morbidity and mortality. We reviewed all 432 patients (mean age 55 years) who underwent an open lung biopsy at this hospital over a 10-year period. Twenty-four patients (5.5%) were immunocompromised. One hundred and twenty-five patients were on steroid therapy at the time of operation. Open lung biopsy provided a firm diagnosis in 410 cases overall (94.9%) and in 20 out of 24 patients in the immunocompromised group (83.3%). The commonest diagnosis was cryptogenic fibrosing alveolitis (173 patients). Twenty-two patients (5.1%) suffered complications following the procedure: wound infection 11 patients, pneumothorax 9 patients and haemothorax 1 patient. Thirteen patients (3.0%) died following open lung biopsy, but in only 1 patient was the death attributable to the procedure itself. We conclude that open lung biopsy is an accurate and safe method for establishing a diagnosis in diffuse lung disease with a high yield and minimal risk.

  12. Predictors of mortality in rheumatoid arthritis-associated interstitial lung disease.

    PubMed

    Solomon, Joshua J; Chung, Jonathan H; Cosgrove, Gregory P; Demoruelle, M Kristen; Fernandez-Perez, Evans R; Fischer, Aryeh; Frankel, Stephen K; Hobbs, Stephen B; Huie, Tristan J; Ketzer, Jill; Mannina, Amar; Olson, Amy L; Russell, Gloria; Tsuchiya, Yutaka; Yunt, Zulma X; Zelarney, Pearlanne T; Brown, Kevin K; Swigris, Jeffrey J

    2016-02-01

    Interstitial lung disease (ILD) is a common pulmonary manifestation of rheumatoid arthritis. There is lack of clarity around predictors of mortality and disease behaviour over time in these patients.We identified rheumatoid arthritis-related interstitial lung disease (RA-ILD) patients evaluated at National Jewish Health (Denver, CO, USA) from 1995 to 2013 whose baseline high-resolution computed tomography (HRCT) scans showed either a nonspecific interstitial pneumonia (NSIP) or a "definite" or "possible" usual interstitial pneumonia (UIP) pattern. We used univariate, multivariate and longitudinal analytical methods to identify clinical predictors of mortality and to model disease behaviour over time.The cohort included 137 subjects; 108 had UIP on HRCT (RA-UIP) and 29 had NSIP on HRCT (RA-NSIP). Those with RA-UIP had a shorter survival time than those with RA-NSIP (log rank p=0.02). In a model controlling for age, sex, smoking and HRCT pattern, a lower baseline % predicted forced vital capacity (FVC % pred) (HR 1.46; p<0.0001) and a 10% decline in FVC % pred from baseline to any time during follow up (HR 2.57; p<0.0001) were independently associated with an increased risk of death.Data from this study suggest that in RA-ILD, disease progression and survival differ between subgroups defined by HRCT pattern; however, when controlling for potentially influential variables, pulmonary physiology, but not HRCT pattern, independently predicts mortality.

  13. Cholesterol, lipoproteins and subclinical interstitial lung disease: the MESA study.

    PubMed

    Podolanczuk, Anna J; Raghu, Ganesh; Tsai, Michael Y; Kawut, Steven M; Peterson, Eric; Sonti, Rajiv; Rabinowitz, Daniel; Johnson, Craig; Barr, R Graham; Hinckley Stukovsky, Karen; Hoffman, Eric A; Carr, J Jeffrey; Ahmed, Firas S; Jacobs, David R; Watson, Karol; Shea, Steven J; Lederer, David J

    2017-01-27

    We investigated associations of plasma lipoproteins with subclinical interstitial lung disease (ILD) by measuring high attenuation areas (HAA: lung voxels between -600 and -250 Hounsfield units) in 6700 adults and serum MMP-7 and SP-A in 1216 adults age 45-84 without clinical cardiovascular disease in Multi-Ethnic Study of Atherosclerosis. In cross-sectional analyses, each SD decrement in high density lipoprotein cholesterol (HDL-C) was associated with a 2.12% HAA increment (95% CI 1.44% to 2.79%), a 3.53% MMP-7 increment (95% CI 0.93% to 6.07%) and a 6.37% SP-A increment (95% CI 1.35% to 11.13%), independent of demographics, smoking and inflammatory biomarkers. These findings support a novel hypothesis that HDL-C might influence subclinical lung injury and extracellular matrix remodelling.

  14. Rheumatoid interstitial lung disease presenting as cor pulmonale.

    PubMed

    Acharya, Sourya; Mahajan, S N; Shukla, Samarth; Diwan, S K; Banode, Pankaj; Kothari, Nirmesh

    2010-10-01

    Rheumatiod arthritis (RA) is a multisystem connective tissue disorder. The predominant presentation is polyarticular, symmetric peripheral arthritis with relative sparing of axial skeleton. Inflammatory synovitis is the pathologic hallmark. Extra-articular manifestations of RA can involve several other organ systems and amongst them pulmonary manifestations occur commonly. We report a case of rheumatoid interstitial lung disease presenting as cor pulmonale.

  15. Occupational lung diseases and the mining industry in Mongolia

    SciTech Connect

    Lkhasuren, O.; Takahashi, K.; Dash-Onolt, L.

    2007-04-15

    Mining production has accounted for around 50% of the gross industrial product in Mongolia since 1998. Dust-induced chronic bronchitis and pneumoconiosis currently account for the largest relative share (67.8%) of occupational diseases in Mongolia, and cases are increasing annually. In 1967-2004, medically diagnosed cases of occupational diseases in Mongolia numbered 7,600. Of these, 5,154 were confirmed cases of dust-induced chronic bronchitis and pneumoconiosis. Lung diseases and other mining-sector health risks pose major challenges for Mongolia. Gold and coal mines, both formal and informal, contribute significantly to economic growth, but the prevalence of occupational lung diseases is high and access to health care is limited. Rapid implementation of an effective national program of silicosis elimination and pneumoconiosis reduction is critical to ensure the health and safety of workers in this important sector of the Mongolian economy.

  16. Occupational lung diseases and the mining industry in Mongolia.

    PubMed

    Lkhasuren, Oyuntogos; Takahashi, Ken; Dash-Onolt, Lkhamsuren

    2007-01-01

    Mining production has accounted for around 50% of the gross industrial product in Mongolia since 1998. Dust-induced chronic bronchitis and pneumoconiosis currently account for the largest relative share (67.8%) of occupational diseases in Mongolia, and cases are increasing annually. In 1967-2004, medically diagnosed cases of occupational diseases in Mongolia numbered 7,600. Of these, 5,154 were confirmed cases of dust-induced chronic bronchitis and pneumoconiosis. Lung diseases and other mining-sector health risks pose major challenges for Mongolia. Gold and coal mines, both formal and informal, contribute significantly to economic growth, but the prevalence of occupational lung diseases is high and access to health care is limited. Rapid implementation of an effective national program of silicosis elimination and pneumoconiosis reduction is critical to ensure the health and safety of workers in this important sector of the Mongolian economy.

  17. Observations on a model of proliferative lung disease

    PubMed Central

    Strauss, B.; Caldwell, P. R. B.; Fritts, H. W.

    1970-01-01

    Intravenous injections of complete Freund's adjuvant, used by others to stimulate the reticuloendothelial system of small laboratory animals, produced granulomas resembling sarcoid in the lung of the dog. At the height of the disease, when granulomas occupied more than half of the alveolar tissues, transpulmonary arteriovenous (A-[unk]V) differences of lactate, pyruvate, and glucose were measured. When the diseased dogs breathed room air, the A-[unk]V differences of lactate and pyruvate were greater than normal; and when the dogs breathed an hypoxic mixture, the differences increased further. Hence the model affords the opportunity for studying the in vivo metabolism of diseased lungs. It may also prove useful for studying other aspects of granulomatous disease which cannot be easily approached in man. PMID:5432367

  18. Temporal complexity in clinical manifestations of lung disease.

    PubMed

    Frey, Urs; Maksym, Geoffrey; Suki, Béla

    2011-06-01

    In this review, we summarize results of recent research on the temporal variability of lung function, symptoms, and inflammatory biomarkers. Specifically, we demonstrate how fluctuation analysis borrowed from statistical physics can be used to gain insight into neurorespiratory control and complex chronic dynamic diseases such as asthma viewed as a system of interacting components (e.g., inflammatory, immunological, and mechanical). Fluctuation analysis tools are based on quantifying the distribution and the short- and long-term temporal history of tidal breathing and lung function parameters to assess neurorespiratory control and monitor chronic disease. The latter includes the assessment of severity and disease control, the impact of treatment and environmental triggers, the temporal characterization of disease phenotypes, and the individual risk of exacerbation. While in many cases specific mechanistic insight into the fluctuations still awaits further research, appropriate analyses of the fluctuations already impact on clinical science and practice.

  19. Pattern of extrapyramidal signs in Alzheimer's disease.

    PubMed

    Tosto, Giuseppe; Monsell, Sarah E; Hawes, Stephen E; Mayeux, Richard

    2015-11-01

    Patients with Alzheimer's disease (AD) often develop extrapyramidal signs (EPS), which increase in frequency as the disease progresses. We aimed to investigate the patterns of presentation of EPS in AD and their correlation with clinical and neuropathological features. 4284 subjects diagnosed with AD from the National Alzheimer's Coordinating Center (NACC) database with at least one abnormal Unified Parkinson's Disease Rating Scale (UPDRS) assessment were included. Individuals were assigned to a discovery sample and a sensitivity analysis sample (moderate and mild dementia, respectively) and a subset of subjects provided neuropathological data (n = 284). Individuals from the Washington Heights and Inwood Columbia Aging Project (WHICAP) served as validation sample. Patterns of presentation of EPS were identified employing categorical principal component analysis (CATPCA). Six principal components were identified in both mild and moderate AD samples: (I) hand movements, alternating movements, finger tapping, leg agility ("limbs bradykinesia"); (II) posture, postural instability, arising from chair, gait and body bradykinesia/hypokinesia ("axial"); (III) limb rigidity ("rigidity"); (IV) postural tremor; (V) resting tremor; (VI) speech and facial expression. Similar results were obtained in the WHICAP cohort. Individuals with hallucinations, apathy, aberrant night behaviors and more severe dementia showed higher axial and limb bradykinesia scores. "Limb bradykinesia" component was associated with a neuropathological diagnosis of Lewy body disease and "axial" component with reduced AD-type pathology. Patterns of EPS in AD show distinct clinical and neuropathological correlates; they share a pattern of presentation similar to that seen in Parkinson's disease, suggesting common pathogenic mechanisms across neurodegenerative diseases.

  20. What Are the Signs and Symptoms of Asbestos-Related Lung Diseases?

    MedlinePlus

    ... and Symptoms of Asbestos-Related Lung Diseases? Explore Asbestos-Related Lung Diseases What Are... Other Names Causes Who Is at Risk Signs & Symptoms Diagnosis Treatments Prevention Living With Clinical Trials Links Related Topics ...

  1. Computational modeling of the obstructive lung diseases asthma and COPD.

    PubMed

    Burrowes, Kelly Suzanne; Doel, Tom; Brightling, Chris

    2014-11-28

    Asthma and chronic obstructive pulmonary disease (COPD) are characterized by airway obstruction and airflow imitation and pose a huge burden to society. These obstructive lung diseases impact the lung physiology across multiple biological scales. Environmental stimuli are introduced via inhalation at the organ scale, and consequently impact upon the tissue, cellular and sub-cellular scale by triggering signaling pathways. These changes are propagated upwards to the organ level again and vice versa. In order to understand the pathophysiology behind these diseases we need to integrate and understand changes occurring across these scales and this is the driving force for multiscale computational modeling. There is an urgent need for improved diagnosis and assessment of obstructive lung diseases. Standard clinical measures are based on global function tests which ignore the highly heterogeneous regional changes that are characteristic of obstructive lung disease pathophysiology. Advances in scanning technology such as hyperpolarized gas MRI has led to new regional measurements of ventilation, perfusion and gas diffusion in the lungs, while new image processing techniques allow these measures to be combined with information from structural imaging such as Computed Tomography (CT). However, it is not yet known how to derive clinical measures for obstructive diseases from this wealth of new data. Computational modeling offers a powerful approach for investigating this relationship between imaging measurements and disease severity, and understanding the effects of different disease subtypes, which is key to developing improved diagnostic methods. Gaining an understanding of a system as complex as the respiratory system is difficult if not impossible via experimental methods alone. Computational models offer a complementary method to unravel the structure-function relationships occurring within a multiscale, multiphysics system such as this. Here we review the currentstate

  2. [Interstitial lung disease: auto-antibodies in routine practice].

    PubMed

    Papo, Thomas

    2005-06-01

    The clinical, computed tomography, cytological, and histological aspects of interstitial lung disease complicating an autoimmune disease lack specificity. Search for autoantibodies in the serum is thus warranted once the essentially clinical diagnosis has been established. An exhaustive history taking should aim at identifying extrathoracic elements of a possible systemic autoimmune disease. The battery of the biological tests which can be useful are discussed here in light of the diagnostic, prognostic, therapeutic, and even conceptual aspects of the disease. For the clinician, a simplified analysis of the main methods and the interpretation of immunological tests is discussed together with new tools currently under development.

  3. Sleep complaints and sleep breathing disorders in upper and lower obstructive lung diseases

    PubMed Central

    Ferrando, Matteo; Bagnasco, Diego; Roustan, Valeria; Canonica, Giorgio Walter; Braido, Fulvio

    2016-01-01

    Upper and lower obstructive lung diseases can induce sleep complaints and can be part of the pathogenesis of sleep breathing disorders. In fact, the physiological changes of the pattern of respiration during sleep, added to the airways disease can lead to symptomatic worsening of rhinitis, asthma and chronic obstructive pulmonary diseases (COPD); moreover, their functional and anatomical features can lead to sleep breathing disorders such as obstructive sleep apnea syndrome (OSAS). This review highlights the above-mentioned relationships and the effect of disease management on its comorbidities and the patient’s quality of life. Rhinitis, asthma and COPD represent causes of sleep complaints that may be reduced with optimal management of these obstructive airways diseases. Continuous positive airway pressure (CPAP) treatment of sleep apnea needs to be tailored after optimization of the therapy of concomitant diseases, but it can often ameliorate comorbid disease. PMID:27621908

  4. 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%.

  5. Impact of Preexisting Interstitial Lung Disease on Acute, Extensive Radiation Pneumonitis: Retrospective Analysis of Patients with Lung Cancer

    PubMed Central

    Ozawa, Yuichi; Abe, Takefumi; Omae, Minako; Matsui, Takashi; Kato, Masato; Hasegawa, Hirotsugu; Enomoto, Yasunori; Ishihara, Takeaki; Inui, Naoki; Yamada, Kazunari; Yokomura, Koshi; Suda, Takafumi

    2015-01-01

    Introduction This study investigated the clinical characteristics and predictive factors for developing acute extended radiation pneumonitis with a focus on the presence and radiological characteristics of preexisting interstitial lung disease. Methods Of 1429 irradiations for lung cancer from May 2006 to August 2013, we reviewed 651 irradiations involving the lung field. The presence, compatibility with usual interstitial pneumonia, and occupying area of preexisting interstitial lung disease were retrospectively evaluated by pretreatment computed tomography. Cases of non-infectious, non-cardiogenic, acute respiratory failure with an extended bilateral shadow developing within 30 days after the last irradiation were defined as acute extended radiation pneumonitis. Results Nine (1.4%) patients developed acute extended radiation pneumonitis a mean of 6.7 days after the last irradiation. Although preexisting interstitial lung disease was found in 13% of patients (84 patients), 78% of patients (7 patients) with acute extended radiation pneumonitis cases had preexisting interstitial lung disease, which resulted in incidences of acute extended radiation pneumonitis of 0.35 and 8.3% in patients without and with preexisting interstitial lung disease, respectively. Multivariate logistic analysis indicated that the presence of preexisting interstitial lung disease (odds ratio = 22.6; 95% confidence interval = 5.29–155; p < 0.001) and performance status (≥2; odds ratio = 4.22; 95% confidence interval = 1.06–20.8; p = 0.049) were significant predictive factors. Further analysis of the 84 patients with preexisting interstitial lung disease revealed that involvement of more than 10% of the lung field was the only independent predictive factor associated with the risk of acute extended radiation pneumonitis (odds ratio = 6.14; 95% confidence interval = 1.0–37.4); p = 0.038). Conclusions Pretreatment computed tomography evaluations of the presence of and area size occupied

  6. Lung function in infants and young children with chronic lung disease of infancy: the next steps?

    PubMed

    Stocks, Janet; Coates, Allan; Bush, Andrew

    2007-01-01

    Over the past year, a series of papers have reviewed the literature concerning assessment and interpretation of lung function in infants and young children with chronic lung disease of infancy. This manuscript, which represents the final paper in that series, summarizes the findings to date and highlights key areas for future research. Despite the huge literature in this field, interpretation of results and their use in guiding clinical management are still limited by difficulties in 'normalizing data' according to body size and maturation and selection of appropriate control groups. Furthermore, sensitive tests that more closely reflect the underlying pathophysiology of 'new' bronchopulmonary dysplasia, together with simple and reliable methods of assessing lung maturity at birth and true oxygen requirements at specified time points are urgently required. Research in this field is also challenged by the need to separate the independent effects of genetic predisposition, gene-environment interactions, preterm delivery, neonatal respiratory disorders and various treatment strategies on the growing lung. The extent to which disruption of lung growth following premature exposure to the extra-uterine environment leads to an earlier or more aggravated decline in respiratory function in later adult life remains to be elucidated. Whatever its origin, given the increasing survival of smaller and more immature infants, the long term sequelae of neonatal lung disease, are likely to continue to change, requiring ongoing, carefully designed longitudinal studies. Future research strategies need to encompass a multicenter, multi-disciplinary, collaborative approach with closer links between clinicians and basic scientists, to ensure that the most relevant research questions are addressed using appropriate methodology and that findings are implemented into clinical practice in a more timely fashion.

  7. Dietary patterns: biomarkers and chronic disease risk.

    PubMed

    Kant, Ashima K

    2010-04-01

    With increasing appreciation of the complexity of diets consumed by free-living individuals, there is interest in the assessment of the overall diet or dietary patterns in which multiple related dietary characteristics are considered as a single exposure. The 2 most frequently used methods to derive dietary patterns use (i) scores or indexes based on prevailing hypotheses about the role of dietary factors in disease prevention; and (ii) factors and clusters from exploration of available dietary data. A third method, a hybrid of the hypothesis-driven and data-driven methods, attempts to predict food combinations related to nutrients or biomarkers with hypothesized associations with particular health outcomes. Dietary patterns derived from the first 2 approaches have been examined in relation to nutritional and disease biomarkers and various health outcomes, and generally show the desirable dietary pattern to be consistent with prevalent beliefs about what constitutes a healthful diet. Results from observational studies suggest that the healthful dietary patterns were associated with significant but modest risk reduction (15%-30%) for all-cause mortality and coronary heart disease. Findings for various cancers have been inconsistent. The available randomized controlled intervention trials with a long-term follow-up to examine dietary patterns in relation to health outcome have generally produced null findings. Novel findings with the potential to change existing beliefs about diet and health relationships are yet to emerge from the dietary patterns research. The field requires innovation in methods to derive dietary patterns, validation of prevalent methods, and assessment of the effect of dietary measurement error on dietary patterns.

  8. Small airways involvement in coal mine dust lung disease.

    PubMed

    Long, Joshua; Stansbury, Robert C; Petsonk, Edward L

    2015-06-01

    Inhalation of coal mine dust results in a spectrum of symptoms, dysfunction, and pathological changes in the respiratory tract that collectively have been labeled coal mine dust lung disease. Recent reports from periodic health surveillance among underground and surface coal miners in the United States have demonstrated an increasing prevalence and severity of dust diseases, and have also documented that some miners experience rapid disease progression. The coal macule is an inflammatory lesion associated with deposited dust, and occurs in the region of the most distal conducting airways and proximal respiratory bronchioles. Inflammatory changes in the small airways have long been recognized as the signature lung pathology among coal miners. Human and laboratory studies have suggested oxidant injury, and increased recruitment and activity of macrophages play important roles in dust-induced lung injury. However, the functional importance of the small airway changes was debated for many years. We reviewed published literature that documents a pervasive occurrence of both physiologic and structural abnormalities in small airways among coal miners and other workers exposed to airborne particulates. There is increasing evidence supporting an important association of abnormalities in the small peripheral airways with the development of respiratory symptoms, deficits in spirometry values, and accelerated declines in ventilatory lung function. Pathologic changes associated with mineral dust deposition in the small airways may be of particular importance in contemporary miners with rapidly progressive respiratory impairment.

  9. Processing of CT images for analysis of diffuse lung disease in the lung tissue research consortium

    NASA Astrophysics Data System (ADS)

    Karwoski, Ronald A.; Bartholmai, Brian; Zavaletta, Vanessa A.; Holmes, David; Robb, Richard A.

    2008-03-01

    The goal of Lung Tissue Resource Consortium (LTRC) is to improve the management of diffuse lung diseases through a better understanding of the biology of Chronic Obstructive Pulmonary Disease (COPD) and fibrotic interstitial lung disease (ILD) including Idiopathic Pulmonary Fibrosis (IPF). Participants are subjected to a battery of tests including tissue biopsies, physiologic testing, clinical history reporting, and CT scanning of the chest. The LTRC is a repository from which investigators can request tissue specimens and test results as well as semi-quantitative radiology reports, pathology reports, and automated quantitative image analysis results from the CT scan data performed by the LTRC core laboratories. The LTRC Radiology Core Laboratory (RCL), in conjunction with the Biomedical Imaging Resource (BIR), has developed novel processing methods for comprehensive characterization of pulmonary processes on volumetric high-resolution CT scans to quantify how these diseases manifest in radiographic images. Specifically, the RCL has implemented a semi-automated method for segmenting the anatomical regions of the lungs and airways. In these anatomic regions, automated quantification of pathologic features of disease including emphysema volumes and tissue classification are performed using both threshold techniques and advanced texture measures to determine the extent and location of emphysema, ground glass opacities, "honeycombing" (HC) and "irregular linear" or "reticular" pulmonary infiltrates and normal lung. Wall thickness measurements of the trachea, and its branches to the 3 rd and limited 4 th order are also computed. The methods for processing, segmentation and quantification are described. The results are reviewed and verified by an expert radiologist following processing and stored in the public LTRC database for use by pulmonary researchers. To date, over 1200 CT scans have been processed by the RCL and the LTRC project is on target for recruitment of the

  10. Global Patterns of Zoonotic Disease in Mammals.

    PubMed

    Han, Barbara A; Kramer, Andrew M; Drake, John M

    2016-07-01

    As the frequency and prevalence of zoonotic diseases increase worldwide, investigating how mammal host distributions determine patterns of human disease and predicting which regions are at greatest risk for future zoonotic disease emergence are two goals which both require better understanding of the current distributions of zoonotic hosts and pathogens. We review here the existing data about mammalian host species, comparing and contrasting these patterns against global maps of zoonotic hosts from all 27 orders of terrestrial mammals. We discuss the zoonotic potential of host species from the top six most species-rich mammal groups, and review the literature to identify analytical and conceptual gaps that must be addressed to improve our ability to generate testable predictions about zoonotic diseases originating from wild mammals.

  11. Probiotics in the management of lung diseases.

    PubMed

    Mortaz, Esmaeil; Adcock, Ian M; Folkerts, Gert; Barnes, Peter J; Paul Vos, Arjan; Garssen, Johan

    2013-01-01

    The physiology and pathology of the respiratory and gastrointestinal tracts are closely related. This similarity between the two organs may underlie why dysfunction in one organ may induce illness in the other. For example, smoking is a major risk factor for COPD and IBD and increases the risk of developing Crohn's disease. Probiotics have been defined as "live microorganisms which, when administered in adequate amounts, confer health benefits on the host." In model systems probiotics regulate innate and inflammatory immune responses. Commonly used probiotics include lactic acid bacteria, particularly Lactobacillus, Bifidobacterium, and Saccharomyces, and these are often used as dietary supplements to provide a health benefit in gastrointestinal diseases including infections, inflammatory bowel disease, and colon cancer. In this respect, probiotics probably act as immunomodulatory agents and activators of host defence pathways which suggest that they could influence disease severity and incidence at sites distal to the gut. There is increasing evidence that orally delivered probiotics are able to regulate immune responses in the respiratory system. This review provides an overview of the possible role of probiotics and their mechanisms of action in the prevention and treatment of respiratory diseases.

  12. Nose and lungs: one way, one disease

    PubMed Central

    2012-01-01

    It’s well established that asthma, allergic rhinitis and rhinosinusitis are three closely related disease. In pediatrics, these conditions represent a common issue in daily practice. The scientific community has recently started to simply evaluate them as different manifestations of a common pathogenic phenomenon. This consideration relates to important implications in the clinical management of these diseases, which may affect the daily activity of a pediatrician. The unity of the respiratory tract is confirmed both from a morphological and from a functional point of view. When treating rhinitis, it is often necessary to assess the presence of asthma. Patients with sinusitis should be evaluated for a possible concomitant asthma. Conversely, patients with asthma should always be evaluated for possible nasal disease, especially those suffering from difficult-to-treat asthma, in which an occult sinusitis may be detected. The medications that treat nasal diseases appear to be useful in improving asthma control and in reducing bronchial hyperresponsiveness. It seems therefore important to analyze the link between asthma and sinusitis, both in terms of clinical and pathogenic features, as well the therapeutic approach of those patients presenting with these diseases. PMID:23098057

  13. Relationship between occupations and asbestosfibre content of the lungs in patients with pleural mesothelioma, lung cancer, and other diseases

    PubMed Central

    Whitwell, F.; Scott, Jean; Grimshaw, Myra

    1977-01-01

    Whitwell, F., Scott, Jean, and Grimshaw, Myra (1977).Thorax, 32, 377-386. Relationship between occupations and asbestos-fibre content of the lungs in patients with pleural mesothelioma, lung cancer, and other diseases. The light-visible asbestos-fibre content of 300 lung specimens has been measured using a potash-digestion and phase-contrast microscopy technique, and the results have been correlated with the occupations of the patients. Among 100 pleural mesothelioma specimens were 88 where the patients had been exposed to asbestos, and in 73 of these (83%) the lung tissue contained over 100 000 asbestos fibres per gram of dried lung, and only one specimen showed less than 20 000 fibres per gram. When asbestosis was present, the lungs nearly always showed over 3 million fibres per gram. In 100 control lungs (those without industrial disease or lung cancer) there were less than 20 000 fibres per gram of dried lung in 71% of specimens. Lungs from 100 patients with lung cancer but no industrial disease contained less than 20 000 fibres per gram of dried lung in 80% of cases. Patients with parietal pleural plaques nearly all had over 20 000 fibres per gram in their lungs. The number of asbestos fibres found in the lungs was closely related to the occupations of the patients but not to their home environment. Patients who had lived near likely sources of atmospheric asbestos pollution did not have higher asbestos fibre counts than the rest of the patients. It is concluded that there is a definite dose relationship between asbestos exposure and mesothelioma formation but that' `sub-asbestosis' levels of asbestos exposure do not contribute to the formation of lung cancer in those not subjected to industrial asbestos exposure. Images PMID:929482

  14. The Lung Microbiome and Airway Disease.

    PubMed

    Lynch, Susan V

    2016-12-01

    A growing body of literature has demonstrated relationships between the composition of the airway microbiota (mixed-species communities of microbes that exist in the respiratory tract) and critical features of immune response and pulmonary function. These studies provide evidence that airway inflammatory status and capacity for repair are coassociated with specific taxonomic features of the airway microbiome. Although directionality has yet to be established, the fact that microbes are known drivers of inflammation and tissue damage suggests that in the context of chronic inflammatory airway disease, the composition and, more importantly, the function, of the pulmonary microbiome represent critical factors in defining airway disease outcomes.

  15. Travel to high altitude with pre-existing lung disease.

    PubMed

    Luks, A M; Swenson, E R

    2007-04-01

    The pathophysiology of high-altitude illnesses has been well studied in normal individuals, but little is known about the risks of high-altitude travel in patients with pre-existing lung disease. Although it would seem self-evident that any patient with lung disease might not do well at high altitude, the type and severity of disease will determine the likelihood of difficulty in a high-altitude environment. The present review examines whether these individuals are at risk of developing one of the main forms of acute or chronic high-altitude illness and whether the underlying lung disease itself will get worse at high elevations. Several groups of pulmonary disorders are considered, including obstructive, restrictive, vascular, control of ventilation, pleural and neuromuscular diseases. Attempts will be made to classify the risks faced by each of these groups at high altitude and to provide recommendations regarding evaluation prior to high-altitude travel, advice for or against taking such excursions, and effective prophylactic measures.

  16. Monitoring of Nonsteroidal Immunosuppressive Drugs in Patients With Lung Disease and Lung Transplant Recipients

    PubMed Central

    Meyer, Keith C; Nathanson, Ian; Angel, Luis; Bhorade, Sangeeta M; Chan, Kevin M; Culver, Daniel; Harrod, Christopher G; Hayney, Mary S; Highland, Kristen B; Limper, Andrew H; Patrick, Herbert; Strange, Charlie; Whelan, Timothy

    2012-01-01

    Objectives: Immunosuppressive pharmacologic agents prescribed to patients with diffuse interstitial and inflammatory lung disease and lung transplant recipients are associated with potential risks for adverse reactions. Strategies for minimizing such risks include administering these drugs according to established, safe protocols; monitoring to detect manifestations of toxicity; and patient education. Hence, an evidence-based guideline for physicians can improve safety and optimize the likelihood of a successful outcome. To maximize the likelihood that these agents will be used safely, the American College of Chest Physicians established a committee to examine the clinical evidence for the administration and monitoring of immunosuppressive drugs (with the exception of corticosteroids) to identify associated toxicities associated with each drug and appropriate protocols for monitoring these agents. Methods: Committee members developed and refined a series of questions about toxicities of immunosuppressives and current approaches to administration and monitoring. A systematic review was carried out by the American College of Chest Physicians. Committee members were supplied with this information and created this evidence-based guideline. Conclusions: It is hoped that these guidelines will improve patient safety when immunosuppressive drugs are given to lung transplant recipients and to patients with diffuse interstitial lung disease. PMID:23131960

  17. Antimicrobial Peptides and Innate Lung Defenses: Role in Infectious and Noninfectious Lung Diseases and Therapeutic Applications.

    PubMed

    Hiemstra, Pieter S; Amatngalim, Gimano D; van der Does, Anne M; Taube, Christian

    2016-02-01

    Respiratory infections are a major clinical problem, and treatment is increasingly complicated by the emergence of microbial antibiotic resistance. Development of new antibiotics is notoriously costly and slow; therefore, alternative strategies are needed. Antimicrobial peptides, central effector molecules of the immune system, are being considered as alternatives to conventional antibiotics. These peptides display a range of activities, including not only direct antimicrobial activity, but also immunomodulation and wound repair. In the lung, airway epithelial cells and neutrophils in particular contribute to their synthesis. The relevance of antimicrobial peptides for host defense against infection has been demonstrated in animal models and is supported by observations in patient studies, showing altered expression and/or unfavorable circumstances for their action in a variety of lung diseases. Importantly, antimicrobial peptides are active against microorganisms that are resistant against conventional antibiotics, including multidrug-resistant bacteria. Several strategies have been proposed to use these peptides in the treatment of infections, including direct administration of antimicrobial peptides, enhancement of their local production, and creation of more favorable circumstances for their action. In this review, recent developments in antimicrobial peptides research in the lung and clinical applications for novel therapies of lung diseases are discussed.

  18. Effects of fiber characteristics on lung deposition, retention, and disease.

    PubMed Central

    Lippmann, M

    1990-01-01

    There is abundant epidemiologic evidence that asbestos fibers can cause lung fibrosis (asbestosis), bronchial cancer, and mesothelioma in humans, as well as limited evidence for such effects in workers exposed to slag and rockwool fibers. Epidemiological evidence for human disease from inhalation exposures to conventional fibrous glass is negative. While health concerns based on the morphological and toxicological similarities between man-made fibers and asbestos are warranted, it is important to note that most of the toxicological evidence for glass fiber toxicity in laboratory animals is based on nonphysiological exposures such as intratracheal instillation or intraperitoneal injection of fiber suspensions. Man-made fibers have produced lung fibrosis and mesotheliomas in such tests, albeit at much lower yields than asbestos. For all durable mineral fibers, critical length limits must be exceeded to warrant concern about chronic toxicity; i.e., 2 microns for asbestosis, 5 microns for mesothelioma, and 10 microns for lung cancer. Fiber width must be less than 0.1 microns for mesothelioma, and larger than this limit for asbestosis and lung cancer. The human health risks for most fibrous glass products are either low or negligible for a variety of reasons. First, most commercial fibrous glass products have mean fiber diameters of approximately 7.5 microns, which results in mean aero-dynamic diameters approximately 22 microns. Thus, most glass fibers, even if dispersed into the air, do not penetrate into the lung to any great extent. Second, the small fraction of smaller diameter fibers that do penetrate into the lungs are not persistent within the lungs for most fibrous glass products due to mechanical breakage into shorter lengths and overall dissolution.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2272328

  19. Mesenchymal stem cell therapy in lung disorders: pathogenesis of lung diseases and mechanism of action of mesenchymal stem cell.

    PubMed

    Inamdar, Ajinkya C; Inamdar, Arati A

    2013-10-01

    Lung disorders such as asthma, acute respiratory distress syndrome (ARDS), chronic obstructive lung disease (COPD), and interstitial lung disease (ILD) show a few common threads of pathogenic mechanisms: inflammation, aberrant immune activity, infection, and fibrosis. Currently no modes of effective treatment are available for ILD or emphysema. Being anti-inflammatory, immunomodulatory, and regenerative in nature, the administration of mesenchymal stem cells (MSCs) has shown the capacity to control immune dysfunction and inflammation in the lung. The intravenous infusion of MSCs, the common mode of delivery, is followed by their entrapment in lung vasculature before MSCs reach to other organ systems thus indicating the feasible and promising approach of MSCs therapy for lung diseases. In this review, we discuss the mechanistic basis for MSCs therapy for asthma, ARDS, COPD, and ILD.

  20. Hypertransaminasemia and fatal lung disease: a case report

    PubMed Central

    2013-01-01

    Glycogenosis type II (Pompe disease) is a rare autosomal recessive genetic disorder caused by mutations in the gene encoding the lysosomal enzyme acid α-glucosidase. The classic form is characterized by severe cardiac involvement, generalized hypotonia and exitus early in life. Presenting symptoms and signs of the disease may be neglected or underestimated, thus delaying the diagnosis. Respiratory manifestations mainly occur because of respiratory muscle weakness. However, additional mechanisms can favor the development of pulmonary complications that result in fatal respiratory failure. We herein describe a case of an infant with glycogenosis type II presenting with hepatomegaly and hypertransaminasemia, who rapidly developed fatal lung disease. PMID:23391190

  1. Terminology in chronic obstructive lung diseases.

    PubMed Central

    Fletcher, C H

    1978-01-01

    Until the 1960's there was great confusion, both within and between countries, on the meaning of diagnostic terms such as emphysema, asthma, and chronic brochitis. Proposals made by a group of British doctors in 1959 gradually received widespread acceptance but in recent years some new problems have developed. These include difficulties in the definition of airflow obstruction, recognition that what used to be regarded as a single disease, chronic bronchitis, comprises at least two distinct pathological processes, and uncertainty about the degree of variability which distinguishes asthmatic from more persistent forms of airflow obstruction. These are all problems which could be solved by continuance of appropriate research and of riqorous attention to the principles which determine accurate and acceptable definitions of disease. PMID:744819

  2. Rationale for hypertonic saline therapy for cystic fibrosis lung disease.

    PubMed

    Tarran, Robert; Donaldson, Scott; Boucher, Richard C

    2007-06-01

    Cystic fibrosis (CF) is caused by alterations in the CF transmembrane conductance regulator ( CFTCR) gene. More than 1400 mutations in the CFTCR gene have been described, but the most common mutation (noted in 70% of CF chromosomes) is DeltaF508. Alterations in the CFTCR gene result in deranged sodium and chloride ion transport channels. This leads to failure of airway epithelia to hydrate their surfaces normally, particularly in response to infectious or toxic insults. Additional effects include mucus adhesion to airway surface, chronic inflammation, and infections. The concept that airway surface dehydration can cause CF-like lung disease is supported by in vitro data and in vivo animal models. Rehydrating airway surfaces may reduce or prevent lung injury and damage. Short- and longer term studies have shown that inhalation of hypertonic saline is well tolerated and improves lung function, reduces exacerbations, and improves quality of life in CF patients. This review discusses the importance of airway epithelial sodium and chloride channels in the pathogenesis of CF, and strategies (particularly the use of inhaled hypertonic saline) to reverse or minimize lung inflammation and injury in this disease.

  3. Airway Epithelial Cell Cilia and Obstructive Lung Disease

    PubMed Central

    Yaghi, Asma; Dolovich, Myrna B.

    2016-01-01

    Airway epithelium is the first line of defense against exposure of the airway and lung to various inflammatory stimuli. Ciliary beating of airway epithelial cells constitutes an important part of the mucociliary transport apparatus. To be effective in transporting secretions out of the lung, the mucociliary transport apparatus must exhibit a cohesive beating of all ciliated epithelial cells that line the upper and lower respiratory tract. Cilia function can be modulated by exposures to endogenous and exogenous factors and by the viscosity of the mucus lining the epithelium. Cilia function is impaired in lung diseases such as COPD and asthma, and pharmacologic agents can modulate cilia function and mucus viscosity. Cilia beating is reduced in COPD, however, more research is needed to determine the structural-functional regulation of ciliary beating via all signaling pathways and how this might relate to the initiation or progression of obstructive lung diseases. Additionally, genotypes and how these can influence phenotypes and epithelial cell cilia function and structure should be taken into consideration in future investigations. PMID:27845721

  4. Microstructural alterations of sputum in cystic fibrosis lung disease

    PubMed Central

    Duncan, Gregg A.; Jung, James; Joseph, Andrea; Thaxton, Abigail L.; West, Natalie E.; Boyle, Michael P.; Hanes, Justin

    2016-01-01

    The stasis of mucus secretions in the lungs of cystic fibrosis (CF) patients leads to recurrent infections and pulmonary exacerbations, resulting in decreased survival. Prior studies have assessed the biochemical and biophysical features of airway mucus in individuals with CF. However, these measurements are unable to probe mucus structure on microscopic length scales relevant to key players in the progression of CF-related lung disease, namely, viruses, bacteria, and neutrophils. In this study, we quantitatively determined sputum microstructure based on the diffusion of muco-inert nanoparticle probes in CF sputum and found that a reduction in sputum mesh pore size is characteristic of CF patients with reduced lung function, as indicated by measured FEV1. We also discovered that the effect of ex vivo treatment of CF sputum with rhDNase I (Pulmozyme) on microstructure is dependent upon the time interval between the most recent inhaled rhDNase I treatment and the sample collection. Microstructure of mucus may serve as a marker for the extent of CF lung disease and as a parameter for assessing the effectiveness of mucus-altering agents. PMID:27812540

  5. Lung Infections in Systemic Rheumatic Disease: Focus on Opportunistic Infections

    PubMed Central

    Di Franco, Manuela; Lucchino, Bruno; Spaziante, Martina; Iannuccelli, Cristina; Valesini, Guido; Iaiani, Giancarlo

    2017-01-01

    Systemic rheumatic diseases have significant morbidity and mortality, due in large part to concurrent infections. The lung has been reported among the most frequent sites of infection in patients with rheumatic disease, who are susceptible to developing pneumonia sustained both by common pathogens and by opportunistic microorganisms. Patients with rheumatic disease show a peculiar vulnerability to infectious complications. This is due in part to intrinsic disease-related immune dysregulation and in part to the immunosuppressive treatments. Several therapeutic agents have been associated to a wide spectrum of infections, complicating the management of rheumatic diseases. This review discusses the most frequent pulmonary infections encountered in rheumatic diseases, focusing on opportunistic agents, consequent diagnostic challenges and appropriate therapeutic strategies. PMID:28146077

  6. [Foamy alveolar macrophages in various lung diseases, and their origin in rabbit lungs].

    PubMed

    Yuasa, K; Kanazawa, T

    1995-07-01

    The present studies were done to clarify the significance of foamy alveolar macrophages (FAM) in lung diseases, and the mechanism of the production of macrophages in rabbit lungs. Human subjects consisted of 18 normal volunteers (NV) and 47 patients with lung disorders: chronic bronchitis (CB), 7 cases; pulmonary fibrosis (PF), 8 cases; old pulmonary tuberculosis (OPT), 7 cases; lung cancer (LC), 20 cases; and bronchiectasis (BE), 5 cases. In each case, over 30 macrophages in the BALF were observed by transmission electron microscopy. There were no significant differences in the percentage of FAm in the BALF among NV, CB, and PF. Furthermore, OPT and LC were not significantly different. Many more FAM were seen in OPT and LC than in NV, CB, and PF (p < 0.005). The percentage of FAM obtained from BE was much higher than that from OPT and LC (p < 0.005). These results suggest that the grade of foamy change in macrophages differs among lung diseases. Three groups of rabbits were studied. Group I rabbits (n = 6) were control, Group II rabbits (n = 6) underwent bronchial clamping, and Group III rabbits (n = 6) underwent complete replacement of blood with saline. The number of macrophages and type II cells was much greater in Group II rabbits than in Group I rabbits. In Group III rabbits, the number of macrophages was lower than in Group I rabbits. In Group III rabbits, vacuole-like structures were seen in the cytoplasma of type II cells, but not from in macrophages. These findings suggest that anoxia and blood flow are important for the appearance of macrophages in alveolar space. Group III rabbits had few alveolar macrophages. Therefore, alveolar macrophages may be derived from monocytes in blood.

  7. Focal lung infiltrate complicating PD-1 inhibitor use: A new pattern of drug-associated lung toxicity?

    PubMed

    Sehgal, Sameep; Velcheti, Vamsidhar; Mukhopadhyay, Sanjay; Stoller, James K

    2016-01-01

    A 58-year-old woman with stage 4 adenocarcinoma of the lung being treated with pembrolizumab developed dyspnea, non-productive cough, and a right middle lobe infiltrate. Complete resolution of the infiltrate with cessation of pembrolizumab, initiation of prednisone and no antibiotic therapy suggested drug-associated lung toxicity as the cause. While the programmed death-1 (PD-1) inhibitors -pembrolizumab and nivolumab - have been implicated as a cause of diffuse or multifocal pulmonary infiltrates, the current case represents, to our knowledge, the first instance of a unilobar, focal infiltrate associated with their use. We speculate that the blockade of immune tolerance that is the hallmark of PD-1 inhibitors might cause atypical inflammatory reactions such as the focal lobar infiltrate seen in the current patient. Awareness of this novel radiographic pattern of drug-associated lung toxicity may enhance clinicians' management of patients receiving.

  8. Nanomedicine and therapy of lung diseases

    PubMed Central

    Garcia, Fabrício de Melo

    2014-01-01

    The use of nanotechnology has significantly increased in different fields of science, including the development of drug delivery systems. Currently, the most modern pharmaceutical nanocarriers, such as liposomes, micelles, nanoemulsions and polymeric nanoparticles, demonstrate extremely useful properties from the point of view of drug therapy. In this context, the development of nanocarriers for pulmonary application has been much debated by the scientific community in recent decades. Although research on the use of nanoparticles for pulmonary application are still in the initial phase, the studies conducted to date suggest that the development of drug delivery systems for systemic or local treatment of diseases that affect the respiratory system may be promising. PMID:25628213

  9. Update in Diffuse Parenchymal Lung Disease 2013

    PubMed Central

    Kaminski, Naftali

    2015-01-01

    The period covered by this update can be considered as the most exciting period in idiopathic pulmonary fibrosis (IPF) research. It started with the identification of genetic variants that are associated with IPF in the majority of patients and continued with discovery of molecular and genetic biomarkers that predict distinct clinical presentations of patients with IPF and potential new biological mechanisms. More importantly, the period ends with the publication of two groundbreaking studies that confirmed that two drugs, pirfenidone and nintedanib, slowed disease progression, leading to a historic approval by the FDA. In this update, we describe these key advances, their scientific and significant clinical implications, and future directions. PMID:25635490

  10. Lung Microbiome for Clinicians. New Discoveries about Bugs in Healthy and Diseased Lungs

    PubMed Central

    Rom, William N.; Weiden, Michael D.

    2014-01-01

    Microbes are readily cultured from epithelial surfaces of the skin, mouth, and colon. In the last 10 years, culture-independent DNA-based techniques demonstrated that much more complex microbial communities reside on most epithelial surfaces; this includes the lower airways, where bacterial culture had failed to reliably demonstrate resident bacteria. Exposure to a diverse bacterial environment is important for adequate immunological development. The most common microbes found in the lower airways are also found in the upper airways. Increasing abundance of oral characteristic taxa is associated with increased inflammatory cells and exhaled nitric oxide, suggesting that the airway microbiome induces an immunological response in the lung. Furthermore, rhinovirus infection leads to outgrowth of Haemophilus in patients with chronic obstructive pulmonary disease, and human immunodeficiency virus–infected subjects have more Tropheryma whipplei in the lower airway, suggesting a bidirectional interaction in which the host immune defenses also influence the microbial niche. Quantitative and/or qualitative changes in the lung microbiome may be relevant for disease progression and exacerbations in a number of pulmonary diseases. Future investigations with longitudinal follow-up to understand the dynamics of the lung microbiome may lead to the development of new therapeutic targets. PMID:24460444

  11. Nanomedicine as an innovative therapeutic strategy for pediatric lung diseases.

    PubMed

    Tian, Ye; Chen, Jian; Zahtabi, Fatemeh; Keijzer, Richard; Xing, Malcolm

    2013-11-01

    Nanomedicine is a rapidly emerging technology and represents an innovative field for therapy. Nanomaterials have intrinsically defined features for biomedical applications due to the high specific surface area, the amazing diversity, versatility in structure and function and the possibility of surface charge. In particular, the functionalization of targeting or stimuli-responsive unit on the surface of these materials gives them specific targeted therapeutic properties. There are many pediatric lung diseases that could potentially benefit from nanomedicine. Herein, we aim to review various drug carrier systems and release systems specifically targeting pediatric lung diseases. The injection of nanomedicine into in vivo models and their elimination will also be discussed. Finally, the potential toxicity of nanomaterials will be addressed.

  12. Genetic Susceptibility to Interstitial Lung Disease Associated with Systemic Sclerosis

    PubMed Central

    Tochimoto, Akiko; Kawaguchi, Yasushi; Yamanaka, Hisashi

    2015-01-01

    Systemic sclerosis (SSc) is a connective tissue disease that is characterized by tissue fibrosis, microvasculopathy, and autoimmunity. Interstitial lung disease (ILD) is a common complication of SSc and is one of the frequent causes of mortality in SSc. Although the exact etiology of SSc remains unknown, clinical and experimental investigations have suggested that genetic and environmental factors are relevant to the pathogenesis of SSc and SSc-ILD. More than 30 genes have been identified as susceptibility loci for SSc, most of which are involved in immune regulation and inflammation. It is thought that the key pathogenesis of SSc-ILD is caused by the release of profibrotic mediators such as transforming growth factor β1 and connective tissue growth factor from lung cells induced by a persistent damage. This review presents the genetic susceptibility to SSc-ILD, including human leukocyte antigen and non-human leukocyte antigen genes, especially focusing on connective tissue growth factor. PMID:26997879

  13. Pulmonary veins in the normal lung and pulmonary hypertension due to left heart disease.

    PubMed

    Hunt, James M; Bethea, Brian; Liu, Xiang; Gandjeva, Aneta; Mammen, Pradeep P A; Stacher, Elvira; Gandjeva, Marina R; Parish, Elisabeth; Perez, Mario; Smith, Lynelle; Graham, Brian B; Kuebler, Wolfgang M; Tuder, Rubin M

    2013-11-15

    Despite the importance of pulmonary veins in normal lung physiology and the pathobiology of pulmonary hypertension with left heart disease (PH-LHD), pulmonary veins remain largely understudied. Difficult to identify histologically, lung venous endothelium or smooth muscle cells display no unique characteristic functional and structural markers that distinguish them from pulmonary arteries. To address these challenges, we undertook a search for unique molecular markers in pulmonary veins. In addition, we addressed the expression pattern of a candidate molecular marker and analyzed the structural pattern of vascular remodeling of pulmonary veins in a rodent model of PH-LHD and in lung tissue of patients with PH-LHD obtained at time of placement on a left ventricular assist device. We detected urokinase plasminogen activator receptor (uPAR) expression preferentially in normal pulmonary veins of mice, rats, and human lungs. Expression of uPAR remained elevated in pulmonary veins of rats with PH-LHD; however, we also detected induction of uPAR expression in remodeled pulmonary arteries. These findings were validated in lungs of patients with PH-LHD. In selected patients with sequential lung biopsy at the time of removal of the left ventricular assist device, we present early data suggesting improvement in pulmonary hemodynamics and venous remodeling, indicating potential regression of venous remodeling in response to assist device treatment. Our data indicate that remodeling of pulmonary veins is an integral part of PH-LHD and that pulmonary veins share some key features present in remodeled yet not normotensive pulmonary arteries.

  14. [Intersticial lung disease as the sole manifestation of antisynthetase syndrome].

    PubMed

    Monteiro, Paulo; Coutinho, Margarida; Machado, Pedro; Garcia, Jorge; Salvador, Maria João; Inês, Luís; Silva, Jorge; Malcata, Armando

    2009-01-01

    The authors report a clinical case of a woman who had a 3 years diagnosis of hipersensitivity pneumonitis based on intersticial lung disease without other manifestations. The diagnosis of antisynthetase syndrome was made three years after the initial symptoms upon the onset of systemic manifestations with articular involvement, myositis and determination of anti-PL 7 antibodies. In this syndrome, the isolated pulmonary involvement is rare.

  15. Pleuroparenchymal lung disease secondary to nonoccupational exposure to vermiculite.

    PubMed

    Al-Ghimlas, Fahad; Hoffstein, Victor

    2007-04-01

    An unusual case of pleuroparenchymal lung disease caused by the inhalation of vermiculite dust, presumably containing asbestos fibers is described. The uniqueness of the case lies in the very indirect nature of exposure -- the wife of a factory owner, rather than a worker exposed to asbestos, whose factory manufactured vermiculite. The present case illustrates the importance of taking careful occupational histories of all household members when presented with a patient whose chest radiograph exhibits features consistent with asbestos exposure.

  16. Quantification of Regional Interstitial Lung Disease from CT-derived Fractional Tissue Volume: A Lung Tissue Research Consortium Study

    PubMed Central

    Yilmaz, Cuneyt; Watharkar, Snehal S.; de Leon, Alberto Diaz; Garcia, Christine K.; Patel, Nova C.; Jordan, Kirk G.; Hsia, Connie C.W.

    2011-01-01

    Rationale and Objectives Evaluation of chest CT is usually qualitative or semi-quantitative, resulting in subjective descriptions often by different observers over time and imprecise determinations of disease severity within distorted lobes. There is a need for standardized imaging biomarkers to quantify regional disease, maximize diagnostic yield, and facilitate multi-center comparisons. We applied lobe-based voxelwise image analysis to derive regional air (Vair) and tissue (Vtissue) volumes and fractional tissue volume (FTV=tissue/[tissue+air] volume) as internally standardized parameter for assessing interstitial lung disease (ILD). Materials and Methods High-resolution CT was obtained at supine and prone end-inspiration and supine end-expiration in 29 patients with ILD and 20 normal subjects. Lobar Vair, Vtissue, and FTV were expressed along standard coordinate axes. Results In normal subjects from end-inspiration to end-expiration, total Vair declined 43%, FTV increased ~80% while Vtissue remained unchanged. With increasing ILD, Vair declined and Vtissue rose in all lobes; FTV increased with a peripheral-to-central progression inversely correlated to spirometry and lung diffusing capacity (R2=0.57–0.75, prone end-inspiration). Inter- and intra-lobar coefficients of variation (CVs) of FTV increased 84–148% in mild-to-moderate ILD, indicating greater spatial heterogeneity, then normalized in severe ILD. Analysis of discontinuous images incurs <3% error compared to consecutive images. Conclusions These regional attenuation-based biomarkers could quantify heterogeneous parenchymal disease in distorted lobes, detect mild ILD involvement in all lobes and describe the pattern of disease progression. The next step would be to study a larger series, examine reproducibility and follow longitudinal changes in correlation with clinical and functional indices. PMID:21596593

  17. Optimal Determination of Respiratory Airflow Patterns Using a Nonlinear Multicompartment Model for a Lung Mechanics System

    PubMed Central

    Li, Hancao; Haddad, Wassim M.

    2012-01-01

    We develop optimal respiratory airflow patterns using a nonlinear multicompartment model for a lung mechanics system. Specifically, we use classical calculus of variations minimization techniques to derive an optimal airflow pattern for inspiratory and expiratory breathing cycles. The physiological interpretation of the optimality criteria used involves the minimization of work of breathing and lung volume acceleration for the inspiratory phase, and the minimization of the elastic potential energy and rapid airflow rate changes for the expiratory phase. Finally, we numerically integrate the resulting nonlinear two-point boundary value problems to determine the optimal airflow patterns over the inspiratory and expiratory breathing cycles. PMID:22719793

  18. Optimal determination of respiratory airflow patterns using a nonlinear multicompartment model for a lung mechanics system.

    PubMed

    Li, Hancao; Haddad, Wassim M

    2012-01-01

    We develop optimal respiratory airflow patterns using a nonlinear multicompartment model for a lung mechanics system. Specifically, we use classical calculus of variations minimization techniques to derive an optimal airflow pattern for inspiratory and expiratory breathing cycles. The physiological interpretation of the optimality criteria used involves the minimization of work of breathing and lung volume acceleration for the inspiratory phase, and the minimization of the elastic potential energy and rapid airflow rate changes for the expiratory phase. Finally, we numerically integrate the resulting nonlinear two-point boundary value problems to determine the optimal airflow patterns over the inspiratory and expiratory breathing cycles.

  19. Mechanisms of Physical Activity Limitation in Chronic Lung Diseases

    PubMed Central

    Vogiatzis, Ioannis; Zakynthinos, George; Andrianopoulos, Vasileios

    2012-01-01

    In chronic lung diseases physical activity limitation is multifactorial involving respiratory, hemodynamic, and peripheral muscle abnormalities. The mechanisms of limitation discussed in this paper relate to (i) the imbalance between ventilatory capacity and demand, (ii) the imbalance between energy demand and supply to working respiratory and peripheral muscles, and (iii) the factors that induce peripheral muscle dysfunction. In practice, intolerable exertional symptoms (i.e., dyspnea) and/or leg discomfort are the main symptoms that limit physical performance in patients with chronic lung diseases. Furthermore, the reduced capacity for physical work and the adoption of a sedentary lifestyle, in an attempt to avoid breathlessness upon physical exertion, cause profound muscle deconditioning which in turn leads to disability and loss of functional independence. Accordingly, physical inactivity is an important component of worsening the patients' quality of life and contributes importantly to poor prognosis. Identifying the factors which prevent a patient with lung disease to easily carry out activities of daily living provides a unique as well as important perspective for the choice of the appropriate therapeutic strategy. PMID:23365738

  20. Risk factors for lung diseases after renal transplantation

    PubMed Central

    Pencheva, Ventsislava P.; Petrova, Daniela S.; Genov, Diyan K.; Georgiev, Ognian B.

    2015-01-01

    Background: Lung diseases are one of the major causes of morbidity and mortality after renal transplantation. The aim of the study is to define the risk factors for infectious and noninfectious pulmonary complications in kidney transplant patients. Materials and Methods: We prospectively studied 267 patients after renal transplantation. The kidney recipients were followed-up for the development of pulmonary complications for a period of 7 years. Different noninvasive and invasive diagnostic tests were used in cases suspected of lung disease. Results: The risk factors associated with the development of pulmonary complications were diabetes mellitus (odds ratio [OR] = 4.60; P = 0.001), arterial hypertension (OR = 1.95; P = 0.015), living related donor (OR = 2.69; P = 0.004), therapy for acute graft rejection (OR = 2.06; P = 0.038), immunosuppressive regimens that includes mycophenolate (OR = 2.40; P = 0.011), azathioprine (OR = 2.25; P = 0.023), and tacrolimus (OR = 1.83; P = 0.041). The only factor associated with the lower risk of complications was a positive serology test for Cytomegalovirus of the recipient before transplantation (OR = 0.1412; P = 0.001). Conclusion: The risk factors can be used to identify patients at increased risk for posttransplant lung diseases. Monitoring of higher-risk patients allow timely diagnosis and early adequate treatment and can reduce the morbidity and mortality after renal transplantation. PMID:26958045

  1. Pulmonary hypertension and right heart dysfunction in chronic lung disease.

    PubMed

    Zangiabadi, Amirmasoud; De Pasquale, Carmine G; Sajkov, Dimitar

    2014-01-01

    Group 3 pulmonary hypertension (PH) is a common complication of chronic lung disease (CLD), including chronic obstructive pulmonary disease (COPD), interstitial lung disease, and sleep-disordered breathing. Development of PH is associated with poor prognosis and may progress to right heart failure, however, in the majority of the patients with CLD, PH is mild to moderate and only a small number of patients develop severe PH. The pathophysiology of PH in CLD is multifactorial and includes hypoxic pulmonary vasoconstriction, pulmonary vascular remodeling, small vessel destruction, and fibrosis. The effects of PH on the right ventricle (RV) range between early RV remodeling, hypertrophy, dilatation, and eventual failure with associated increased mortality. The golden standard for diagnosis of PH is right heart catheterization, however, evidence of PH can be appreciated on clinical examination, serology, radiological imaging, and Doppler echocardiography. Treatment of PH in CLD focuses on management of the underlying lung disorder and hypoxia. There is, however, limited evidence to suggest that PH-specific vasodilators such as phosphodiesterase-type 5 inhibitors, endothelin receptor antagonists, and prostanoids may have a role in the treatment of patients with CLD and moderate-to-severe PH.

  2. Timing Matters: Circadian Rhythm in Sepsis, Obstructive Lung Disease, Obstructive Sleep Apnea, and Cancer.

    PubMed

    Truong, Kimberly K; Lam, Michael T; Grandner, Michael A; Sassoon, Catherine S; Malhotra, Atul

    2016-07-01

    Physiological and cellular functions operate in a 24-hour cyclical pattern orchestrated by an endogenous process known as the circadian rhythm. Circadian rhythms represent intrinsic oscillations of biological functions that allow for adaptation to cyclic environmental changes. Key clock genes that affect the persistence and periodicity of circadian rhythms include BMAL1/CLOCK, Period 1, Period 2, and Cryptochrome. Remarkable progress has been made in our understanding of circadian rhythms and their role in common medical conditions. A critical review of the literature supports the association between circadian misalignment and adverse health consequences in sepsis, obstructive lung disease, obstructive sleep apnea, and malignancy. Circadian misalignment plays an important role in these disease processes and can affect disease severity, treatment response, and survivorship. Normal inflammatory response to acute infections, airway resistance, upper airway collapsibility, and mitosis regulation follows a robust circadian pattern. Disruption of normal circadian rhythm at the molecular level affects severity of inflammation in sepsis, contributes to inflammatory responses in obstructive lung diseases, affects apnea length in obstructive sleep apnea, and increases risk for cancer. Chronotherapy is an underused practice of delivering therapy at optimal times to maximize efficacy and minimize toxicity. This approach has been shown to be advantageous in asthma and cancer management. In asthma, appropriate timing of medication administration improves treatment effectiveness. Properly timed chemotherapy may reduce treatment toxicities and maximize efficacy. Future research should focus on circadian rhythm disorders, role of circadian rhythm in other diseases, and modalities to restore and prevent circadian disruption.

  3. Cartography of Pathway Signal Perturbations Identifies Distinct Molecular Pathomechanisms in Malignant and Chronic Lung Diseases.

    PubMed

    Arakelyan, Arsen; Nersisyan, Lilit; Petrek, Martin; Löffler-Wirth, Henry; Binder, Hans

    2016-01-01

    Lung diseases are described by a wide variety of developmental mechanisms and clinical manifestations. Accurate classification and diagnosis of lung diseases are the bases for development of effective treatments. While extensive studies are conducted toward characterization of various lung diseases at molecular level, no systematic approach has been developed so far. Here we have applied a methodology for pathway-centered mining of high throughput gene expression data to describe a wide range of lung diseases in the light of shared and specific pathway activity profiles. We have applied an algorithm combining a Pathway Signal Flow (PSF) algorithm for estimation of pathway activity deregulation states in lung diseases and malignancies, and a Self Organizing Maps algorithm for classification and clustering of the pathway activity profiles. The analysis results allowed clearly distinguish between cancer and non-cancer lung diseases. Lung cancers were characterized by pathways implicated in cell proliferation, metabolism, while non-malignant lung diseases were characterized by deregulations in pathways involved in immune/inflammatory response and fibrotic tissue remodeling. In contrast to lung malignancies, chronic lung diseases had relatively heterogeneous pathway deregulation profiles. We identified three groups of interstitial lung diseases and showed that the development of characteristic pathological processes, such as fibrosis, can be initiated by deregulations in different signaling pathways. In conclusion, this paper describes the pathobiology of lung diseases from systems viewpoint using pathway centered high-dimensional data mining approach. Our results contribute largely to current understanding of pathological events in lung cancers and non-malignant lung diseases. Moreover, this paper provides new insight into molecular mechanisms of a number of interstitial lung diseases that have been studied to a lesser extent.

  4. Cartography of Pathway Signal Perturbations Identifies Distinct Molecular Pathomechanisms in Malignant and Chronic Lung Diseases

    PubMed Central

    Arakelyan, Arsen; Nersisyan, Lilit; Petrek, Martin; Löffler-Wirth, Henry; Binder, Hans

    2016-01-01

    Lung diseases are described by a wide variety of developmental mechanisms and clinical manifestations. Accurate classification and diagnosis of lung diseases are the bases for development of effective treatments. While extensive studies are conducted toward characterization of various lung diseases at molecular level, no systematic approach has been developed so far. Here we have applied a methodology for pathway-centered mining of high throughput gene expression data to describe a wide range of lung diseases in the light of shared and specific pathway activity profiles. We have applied an algorithm combining a Pathway Signal Flow (PSF) algorithm for estimation of pathway activity deregulation states in lung diseases and malignancies, and a Self Organizing Maps algorithm for classification and clustering of the pathway activity profiles. The analysis results allowed clearly distinguish between cancer and non-cancer lung diseases. Lung cancers were characterized by pathways implicated in cell proliferation, metabolism, while non-malignant lung diseases were characterized by deregulations in pathways involved in immune/inflammatory response and fibrotic tissue remodeling. In contrast to lung malignancies, chronic lung diseases had relatively heterogeneous pathway deregulation profiles. We identified three groups of interstitial lung diseases and showed that the development of characteristic pathological processes, such as fibrosis, can be initiated by deregulations in different signaling pathways. In conclusion, this paper describes the pathobiology of lung diseases from systems viewpoint using pathway centered high-dimensional data mining approach. Our results contribute largely to current understanding of pathological events in lung cancers and non-malignant lung diseases. Moreover, this paper provides new insight into molecular mechanisms of a number of interstitial lung diseases that have been studied to a lesser extent. PMID:27200087

  5. Vitamin D deficiency and the lung: disease initiator or disease modifier?

    PubMed

    Foong, Rachel E; Zosky, Graeme R

    2013-07-26

    Vitamin D deficiency is a global public health problem and has been associated with an increased incidence and severity of many diseases including diseases of the respiratory system. These associations have largely been demonstrated epidemiologically and have formed the basis of the justification for a large number of clinical supplementation trials with a view to improving disease outcomes. However, the trials that have been completed to date and the ongoing experimental studies that have attempted to demonstrate a mechanistic link between vitamin D deficiency and lung disease have been disappointing. This observation raises many questions regarding whether vitamin D deficiency is truly associated with disease pathogenesis, is only important in the exacerbation of disease or is simply an indirect biomarker of other disease mechanisms? In this review, we will briefly summarize our current understanding of the role of vitamin D in these processes with a focus on lung disease.

  6. Exercise-induced haemoptysis as a rare presentation of a rare lung disease.

    PubMed

    Mihalek, Andrew D; Haney, Carissa; Merino, Maria; Roy-Chowdhuri, Sinchita; Moss, Joel; Olivier, Kenneth N

    2016-09-01

    Amyloid primarily affecting the lungs is a seldom seen clinical entity. This case discusses the work-up of a patient presenting with exercise-induced haemoptysis and diffuse cystic lung disease on radiographic imaging. The common clinical and radiographic findings of diffuse cystic lung diseases as well as a brief overview of pulmonary amyloid are presented.

  7. Will chronic e-cigarette use cause lung disease?

    PubMed

    Rowell, Temperance R; Tarran, Robert

    2015-12-15

    Chronic tobacco smoking is a major cause of preventable morbidity and mortality worldwide. In the lung, tobacco smoking increases the risk of lung cancer, and also causes chronic obstructive pulmonary disease (COPD), which encompasses both emphysema and chronic bronchitis. E-cigarettes (E-Cigs), or electronic nicotine delivery systems, were developed over a decade ago and are designed to deliver nicotine without combusting tobacco. Although tobacco smoking has declined since the 1950s, E-Cig usage has increased, attracting both former tobacco smokers and never smokers. E-Cig liquids (e-liquids) contain nicotine in a glycerol/propylene glycol vehicle with flavorings, which are vaporized and inhaled. To date, neither E-Cig devices, nor e-liquids, are regulated by the Food and Drug Administration (FDA). The FDA has proposed a deeming rule, which aims to initiate legislation to regulate E-Cigs, but the timeline to take effect is uncertain. Proponents of E-Cigs say that they are safe and should not be regulated. Opposition is varied, with some opponents proposing that E-Cig usage will introduce a new generation to nicotine addiction, reversing the decline seen with tobacco smoking, or that E-Cigs generally may not be safe and will trigger diseases like tobacco. In this review, we shall discuss what is known about the effects of E-Cigs on the mammalian lung and isolated lung cells in vitro. We hope that collating this data will help illustrate gaps in the knowledge of this burgeoning field, directing researchers toward answering whether or not E-Cigs are capable of causing disease.

  8. Spatiotemporal Aeration and Lung Injury Patterns Are Influenced by the First Inflation Strategy at Birth.

    PubMed

    Tingay, David G; Rajapaksa, Anushi; Zonneveld, C Elroy; Black, Don; Perkins, Elizabeth J; Adler, Andy; Grychtol, Bartłomiej; Lavizzari, Anna; Frerichs, Inéz; Zahra, Valerie A; Davis, Peter G

    2016-02-01

    Ineffective aeration during the first inflations at birth creates regional aeration and ventilation defects, initiating injurious pathways. This study aimed to compare a sustained first inflation at birth or dynamic end-expiratory supported recruitment during tidal inflations against ventilation without intentional recruitment on gas exchange, lung mechanics, spatiotemporal regional aeration and tidal ventilation, and regional lung injury in preterm lambs. Lambs (127 ± 2 d gestation), instrumented at birth, were ventilated for 60 minutes from birth with either lung-protective positive pressure ventilation (control) or as per control after either an initial 30 seconds of 40 cm H2O sustained inflation (SI) or an initial stepwise end-expiratory pressure recruitment maneuver during tidal inflations (duration 180 s; open lung ventilation [OLV]). At study completion, molecular markers of lung injury were analyzed. The initial use of an OLV maneuver, but not SI, at birth resulted in improved lung compliance, oxygenation, end-expiratory lung volume, and reduced ventilatory needs compared with control, persisting throughout the study. These changes were due to more uniform inter- and intrasubject gravity-dependent spatiotemporal patterns of aeration (measured using electrical impedance tomography). Spatial distribution of tidal ventilation was more stable after either recruitment maneuver. All strategies caused regional lung injury patterns that mirrored associated regional volume states. Irrespective of strategy, spatiotemporal volume loss was consistently associated with up-regulation of early growth response-1 expression. Our results show that mechanical and molecular consequences of lung aeration at birth are not simply related to rapidity of fluid clearance; they are also related to spatiotemporal pressure-volume interactions within the lung during inflation and deflation.

  9. New coding in the International Classification of Diseases, Ninth Revision, for children's interstitial lung disease.

    PubMed

    Popler, Jonathan; Lesnick, Burton; Dishop, Megan K; Deterding, Robin R

    2012-09-01

    The term "children's interstitial lung disease" (chILD) refers to a heterogeneous group of rare and diffuse lung diseases associated with significant morbidity and mortality. These disorders include neuroendocrine cell hyperplasia of infancy, pulmonary interstitial glycogenosis, surfactant dysfunction mutations, and alveolar capillary dysplasia with misalignment of pulmonary veins. Diagnosis can be challenging, which may lead to a delay in recognition and treatment of these disorders. Recently, International Classifications of Diseases, Ninth Revision codes have been added for several of the chILD disorders. The purpose of this article is to give an overview of the chILD disorders and appropriate diagnostic coding.

  10. Management of Pulmonary Hypertension in Patients with Chronic Lung Disease.

    PubMed

    Barberà, Joan Albert; Blanco, Isabel

    2015-08-01

    Pulmonary hypertension (PH) is a common complication of chronic pulmonary diseases, especially in advanced disease, and is associated with greater mortality and worse clinical course. Patients with symptoms that exceed those expected by their pulmonary disease should be further evaluated by echocardiography. Confirmatory right heart catheterization is indicated in those conditions where the results of the hemodynamic assessment will determine treatment options. The treatment of choice for patients who are hypoxemic and have pulmonary hypertension associated with chronic lung disease is long-term oxygen therapy. Conventional vasodilators or drugs approved for pulmonary arterial hypertension are not recommended in patients with mild-to-moderate PH because they may impair gas exchange and because there is a lack of evidence supporting their efficacy. Patients with severe PH should be considered for referral to a center with expertise in PH and lung diseases. Ideally, these patients should be included in randomized controlled trials to determine which patients are more likely to derive benefit and which therapies are most likely to be successful.

  11. Peripleural lung disease detection based on multi-slice CT images

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

    With the development of multi-slice CT technology, obtaining accurate 3D images of lung field in a short time become possible. To support that, a lot of image processing methods need to be developed. Detection peripleural lung disease is difficult due to its existence out of lung region, because lung extraction is often performed based on threshold processing. The proposed method uses thoracic inner region extracted by inner cavity of bone as well as air region, covers peripleural lung diseased cases such as lung nodule, calcification, pleural effusion and pleural plaque. We applied this method to 50 cases including 39 peripleural lung diseased cases. This method was able to detect 39 peripleural lung disease with 2.9 false positive per case.

  12. Molecular Basis of Asbestos-Induced Lung Disease

    PubMed Central

    Liu, Gang; Cheresh, Paul; Kamp, David W.

    2013-01-01

    Asbestos causes asbestosis and malignancies by molecular mechanisms that are not fully understood. The modes of action underlying asbestosis, lung cancer, and mesothelioma appear to differ depending on the fiber type, lung clearance, and genetics. After reviewing the key pathologic changes following asbestos exposure, we examine recently identified pathogenic pathways, with a focus on oxidative stress. Alveolar epithelial cell apoptosis, which is an important early event in asbestosis, is mediated by mitochondria- and p53-regulated death pathways and may be modulated by the endoplasmic reticulum. We review mitochondrial DNA (mtDNA)-damage and -repair mechanisms, focusing on 8-oxoguanine DNA glycosylase, as well as cross talk between reactive oxygen species production, mtDNA damage, p53, OGG1, and mitochondrial aconitase. These new insights into the molecular basis of asbestos-induced lung diseases may foster the development of novel therapeutic targets for managing degenerative diseases (e.g., asbestosis and idiopathic pulmonary fibrosis), tumors, and aging, for which effective management is lacking. PMID:23347351

  13. Patterns of disease distribution of lower extremity peripheral arterial disease.

    PubMed

    Chen, Qian; Shi, Yang; Wang, Yutang; Li, Xiaoying

    2015-03-01

    Peripheral arterial disease (PAD) is a common manifestation of atherosclerosis that is associated with an increased risk of mortality and cardiovascular (CV) events. Peripheral arterial disease involves the arteries distal to the aortic bifurcation in a nonuniform manner. Studies have shown that symptoms and prognosis of patients with PAD vary according to the location and size of the affected artery. Several modalities have been used to identify the location of PAD, including noninvasive evaluations and invasive procedures. Peripheral arterial disease has a risk factor profile similar to that associated with coronary artery disease (ie, age, gender, diabetes, smoking, hypertension, and hyperlipidemia). Many studies have shown that the distribution, extent, and progression of PAD are influenced by CV risk factors but the findings are not consistent. Management strategies for PAD are different for proximal and distal PAD. The objective of this review is to discuss the patterns of diseases distribution in patients with PAD.

  14. Occupational Lung Diseases among Soldiers Deployed to Iraq and Afghanistan.

    PubMed

    Szema, Anthony M

    2013-01-01

    Military personnel deployed to Iraq and Afghanistan, from 2004 to the present, has served in a setting of unique environmental conditions. Among these are exposures to burning trash in open air "burn pits" lit on fire with jet fuel JP-8. Depending on trash burned--water bottles, styrofoam trays, medical waste, unexploded munitions, and computers--toxins may be released such as dioxins and n-hexane and benzene. Particulate matter air pollution culminates from these fires and fumes. Additional environmental exposures entail sandstorms (Haboob, Shamal, and Sharqi) which differ in direction and relationship to rain. These wars saw the first use of improvised explosive devices (roadside phosphate bombs),as well as vehicle improvised explosive devices (car bombs), which not only potentially aerosolize metals, but also create shock waves to induce lung injury via blast overpressure. Conventional mortar rounds are also used by Al Qaeda in both Iraq and Afghanistan. Outdoor aeroallergens from date palm trees are prevalent in southern Iraq by the Tigris and Euphrates rivers, while indoor aeroallergen aspergillus predominates during the rainy season. High altitude lung disease may also compound the problem, particularly in Kandahar, Afghanistan. Clinically, soldiers may present with new-onset asthma or fixed airway obstruction. Some have constrictive bronchiolitis and vascular remodeling on open lung biopsy - despite having normal spirometry and chest xrays and CT scans of the chest. Others have been found to have titanium and other metals in the lung (rare in nature). Still others have fulminant biopsy-proven sarcoidiosis. We found DNA probe-positive Mycobacterium Avium Complex in lung from a soldier who had pneumonia, while serving near stagnant water and camels and goats outside Abu Gharib. This review highlights potential exposures, clinical syndromes, and the Denver Working Group recommendations on post-deployment health.

  15. Occupational Lung Diseases among Soldiers Deployed to Iraq and Afghanistan

    PubMed Central

    Szema, Anthony M

    2013-01-01

    Military personnel deployed to Iraq and Afghanistan, from 2004 to the present, has served in a setting of unique environmental conditions. Among these are exposures to burning trash in open air “burn pits” lit on fire with jet fuel JP-8. Depending on trash burned--water bottles, styrofoam trays, medical waste, unexploded munitions, and computers--toxins may be released such as dioxins and n-hexane and benzene. Particulate matter air pollution culminates from these fires and fumes. Additional environmental exposures entail sandstorms (Haboob, Shamal, and Sharqi) which differ in direction and relationship to rain. These wars saw the first use of improvised explosive devices (roadside phosphate bombs),as well as vehicle improvised explosive devices (car bombs), which not only potentially aerosolize metals, but also create shock waves to induce lung injury via blast overpressure. Conventional mortar rounds are also used by Al Qaeda in both Iraq and Afghanistan. Outdoor aeroallergens from date palm trees are prevalent in southern Iraq by the Tigris and Euphrates rivers, while indoor aeroallergen aspergillus predominates during the rainy season. High altitude lung disease may also compound the problem, particularly in Kandahar, Afghanistan. Clinically, soldiers may present with new-onset asthma or fixed airway obstruction. Some have constrictive bronchiolitis and vascular remodeling on open lung biopsy - despite having normal spirometry and chest xrays and CT scans of the chest. Others have been found to have titanium and other metals in the lung (rare in nature). Still others have fulminant biopsy-proven sarcoidiosis. We found DNA probe–positive Mycobacterium Avium Complex in lung from a soldier who had pneumonia, while serving near stagnant water and camels and goats outside Abu Gharib. This review highlights potential exposures, clinical syndromes, and the Denver Working Group recommendations on post-deployment health. PMID:24443711

  16. Women and Lung Disease. Sex Differences and Global Health Disparities

    PubMed Central

    Harbaugh, Mary; Han, MeiLan K.; Jourdan Le Saux, Claude; Van Winkle, Laura S.; Martin, William J.; Kosgei, Rose J.; Carter, E. Jane; Sitkin, Nicole; Smiley-Jewell, Suzette M.; George, Maureen

    2015-01-01

    There is growing evidence that a number of pulmonary diseases affect women differently and with a greater degree of severity than men. The causes for such sex disparity is the focus of this Blue Conference Perspective review, which explores basic cellular and molecular mechanisms, life stages, and clinical outcomes based on environmental, sociocultural, occupational, and infectious scenarios, as well as medical health beliefs. Owing to the breadth of issues related to women and lung disease, we present examples of both basic and clinical concepts that may be the cause for pulmonary disease disparity in women. These examples include those diseases that predominantly affect women, as well as the rising incidence among women for diseases traditionally occurring in men, such as chronic obstructive pulmonary disease. Sociocultural implications of pulmonary disease attributable to biomass burning and infectious diseases among women in low- to middle-income countries are reviewed, as are disparities in respiratory health among sexual minority women in high-income countries. The implications of the use of complementary and alternative medicine by women to influence respiratory disease are examined, and future directions for research on women and respiratory health are provided. PMID:25945507

  17. Women and Lung Disease. Sex Differences and Global Health Disparities.

    PubMed

    Pinkerton, Kent E; Harbaugh, Mary; Han, MeiLan K; Jourdan Le Saux, Claude; Van Winkle, Laura S; Martin, William J; Kosgei, Rose J; Carter, E Jane; Sitkin, Nicole; Smiley-Jewell, Suzette M; George, Maureen

    2015-07-01

    There is growing evidence that a number of pulmonary diseases affect women differently and with a greater degree of severity than men. The causes for such sex disparity is the focus of this Blue Conference Perspective review, which explores basic cellular and molecular mechanisms, life stages, and clinical outcomes based on environmental, sociocultural, occupational, and infectious scenarios, as well as medical health beliefs. Owing to the breadth of issues related to women and lung disease, we present examples of both basic and clinical concepts that may be the cause for pulmonary disease disparity in women. These examples include those diseases that predominantly affect women, as well as the rising incidence among women for diseases traditionally occurring in men, such as chronic obstructive pulmonary disease. Sociocultural implications of pulmonary disease attributable to biomass burning and infectious diseases among women in low- to middle-income countries are reviewed, as are disparities in respiratory health among sexual minority women in high-income countries. The implications of the use of complementary and alternative medicine by women to influence respiratory disease are examined, and future directions for research on women and respiratory health are provided.

  18. Phanerochaete chrysosporium and granulomatous lung disease in a mulch gardener.

    PubMed

    Lanspa, Michael J; Hatton, Nathan D

    2014-03-01

    A 50-year-old woman who gardens regularly with rotting bark mulch presented with exertional dyspnea, diffusion impairment, and radiographic abnormalities (centrilobular nodules, tree-in-bud and ground glass opacities, calcified mediastinal and hilar lymph nodes) on a computed tomogram. Moderate lymphocytosis was noted on bronchoalveolar lavage. Surgical biopsy of her lung revealed granulomatous changes, and biopsies grew Phanerochaete chrysosporium, a fungus that causes white rot in tree bark. She was treated with voriconazole and instructed to avoid gardening, which led to radiographic and symptomatic improvement. She had recurrence of symptoms when she started doing yard work again. P. chrysosporium has been demonstrated to cause hypersensitivity pneumonitis in animal models. This case is the first documented report of P. chrysosporium associated with granulomatous lung disease in a human.

  19. Detection of chaotic determinism in lung cancer patients' breathing patterns and tracking of lung tumors using dMLC

    NASA Astrophysics Data System (ADS)

    Tewatia, Dinesh Kumar

    The aim of the thesis is to investigate two techniques for tracking moving lung tumors, develop a model for numerical phantom for moving tumors and analyze breathing pattern of lung cancer patients using nonlinear dynamics and chaos theory. The clinical implementation will require an electronic interface to radiation delivery machines to trigger the beam ON and hold OFF the beam once tumor goes out of the threshold window. A breathing synchronized delivery (BSD) was developed using Eclipse TM treatment planning system (Varian Medical Systems). Delivered dose calculation on 50% (maximum exhalation) phase and using shaperTM application was performed to superimpose the instantaneous average tumor displacement on the dynamic Multileaf collimator position at corresponding phase. BSD technique assumed a constant dose rate and patient is guided to reproduce the breathing pattern that was acquired during 4D CT acquisition. As BSD technique cannot directly be adapted to moving tumors in case of volumetric modulated arc therapy, we have developed a novel technique for arc-based treatments. We have demonstrated the implementation of this technique on the ADAC Pinnacle3 TM (Philips Medical Systems) treatment planning system. This technique does not require breath-hold or breath synchronization and has nearly 100% duty cycle without major hardware changes. The variation in dose accumulation due to changes in breathing pattern was studied on numerical phantom. Stereotactic body radiotherapy treatment was investigated to see the effect of changes in breathing patterns on five days of the treatment. If variation in breathing pattern is not substantial, then the total accumulated dose on that treatment day would not be significantly different from the planned dose distribution. If breathing pattern on a given day changes beyond some threshold we may partially miss the target on that day. Lung tumor motion is mainly due to breathing. No matter how robust the tumor tracking

  20. Phenotypic, immunologic, and clinical characteristics of patients with nontuberculous mycobacterial lung disease in Korea

    PubMed Central

    2013-01-01

    Background This study aimed to elucidate the phenotypic, immunologic, and clinical characteristics of Korean patients with nontuberculous mycobacterial (NTM) lung disease and compare them with non-NTM bronchiectasis (BE) patients. Methods We prospectively recruited patients between 20 and 80 years of age who had nodular BE type NTM lung disease. Phenotypic, immunologic, and clinical characteristics were evaluated through physical examination, laboratory tests, pulmonary function tests, and radiographic examinations. Questionnaires were also answered. The results of the evaluations were compared with the results of non-NTM BE patients. Results A total of 84 patients with NTM lung disease and 47 non-NTM BE patients participated in the study. Mycobacterium avium complex lung disease and M. abscessus lung disease were most common. Patients with NTM lung disease had lower body mass index than non-NTM BE patients. Scoliosis was observed more frequently in patients with NTM lung disease than in non-NTM BE patients. Conclusions Significant similarities were seen between Korean patients with NTM lung disease and patients from other countries. Differences in phenotypic and clinical characteristics between NTM lung disease and non-NTM BE patients suggest differences in the immunopathogenesis of NTM lung disease and non-NTM BE. Trial registration information ClinicalTrials.gov Registration number; NCT01616745 PMID:24274658

  1. Asymmetrical Pedaling Patterns in Parkinson's Disease Patients

    PubMed Central

    Penko, Amanda L.; Hirsch, Joshua R.; Voelcker-Rehage, Claudia; Martin, Philip E.; Blackburn, Gordon; Alberts, Jay L.

    2015-01-01

    Background Approximately 1.5 million Americans are affected by Parkinson's disease [1] which includes the symptoms of postural instability and gait dysfunction. Currently, clinical evaluations of postural instability and gait dysfunction consist of a subjective rater assessment of gait patterns using items from the Unified Parkinson's Disease Rating Scale, and assessments can be insensitive to the effectiveness of medical interventions. Current research suggests the importance of cycling for Parkinson's disease patients, and while Parkinson's gait has been evaluated in previous studies, little is known about lower extremity control during cycling. The purpose of this study is to examine the lower extremity coordination patterns of Parkinson's patients during cycling. Methods Twenty five participants, ages 44-72, with a clinical diagnosis of idiopathic Parkinson's disease participated in an exercise test on a cycle ergometer that was equipped with pedal force measurements. Crank torque, crank angle and power produced by right and left leg were measured throughout the test to calculate Symmetry Index at three stages of exercise (20 Watt, 60 Watt, maximum performance). Findings Decreases in Symmetry Index were observed for average power output in Parkinson's patients as workload increased. Maximum power Symmetry Index showed a significant difference in symmetry between performance at both the 20 Watt and 60 Watt stage and the maximal resistance stage. Minimum power Symmetry Index did not show significant differences across the stages of the test. While lower extremity asymmetries were present in Parkinson's patients during pedaling, these asymmetries did not correlate to postural instability and gait dysfunction Unified Parkinson's Disease Rating Scale scores. Interpretation This pedaling analysis allows for a more sensitive measure of lower extremity function than the Unified Parkinson's Disease Rating Scale and may help to provide unique insight into current and

  2. [Evaluation and treatment of interstitial lung disease in Argentine].

    PubMed

    Mosca, C; Quadrelli, S; Castro Zorrilla, L; Castagnino, J

    2000-01-01

    To determine the availability and usual management of interstitial lung diseases (ILD) in our country, the Section of Interstitial Lung Diseases of the Argentine Association for Respiratory Medicine (AAMR) made a survey about diagnostic methodology and treatment of ILD. A total of 115 answers were obtained (38.5%), 43% of them among physicians living in the provinces. Availability of diffusing capacity of the lung for carbon monoxide test (DLCO) is limited: 25.4% never have access to it and 35.6% can seldom use it. Availability to thoracic CT scan is wider: 85% may use if often (32.4%) or always (52.6%). Bronchoscopy is commonly available in 87.7% of the physicians either often (21.9%) or always (65.8%). However, only 20.2% perform BAL and 13.1% transbronchial biopsy in every patient. Only 16.6% perform open lung biopsy or thoracoscopic biopsy in all or most of their patients. Sixty eight percent of physicians who always have availability of DLCO perform it in every patient but only 7.1% of those who seldom have access to DLCO do so (p = 0.0003). Availability of bronchoscopy does not have any influence on the decision of performing BAL or transbronchial biopsy. Frequency of use of surgical biopsy or treatment with immunosuppressive drugs was not influenced by any variable. We conclude that there is a current trend to underuse diagnostic resources for ILD in Argentina. Limitations in availability are relevant regarding DLCO. An effort from the health authorities to centralize the management of patients with ILD would allow to study and treat them according to international recommendations.

  3. Genetics of Interstitial Lung Disease: Vol de Nuit (Night Flight)

    PubMed Central

    Furukawa, Hiroshi; Oka, Shomi; Shimada, Kota; Tsuchiya, Naoyuki; Tohma, Shigeto

    2015-01-01

    Interstitial lung disease (ILD) is a chronic, progressive fibrotic lung disease with a dismal prognosis. ILD of unknown etiology is referred to as idiopathic interstitial pneumonia (IIP), which is sporadic in the majority of cases. ILD is frequently accompanied by rheumatoid arthritis (RA), systemic sclerosis (SSc), polymyositis/dermatomyositis (PM/DM), and other autoimmune diseases, and is referred to as collagen vascular disease-associated ILD (CVD-ILD). Susceptibility to ILD is influenced by genetic and environmental factors. Recent advances in radiographic imaging techniques such as high-resolution computed tomography (CT) scanning as well as high-throughput genomic analyses have provided insights into the genetics of ILD. These studies have repeatedly revealed an association between IIP (sporadic and familial) and a single nucleotide polymorphism (SNP) in the promoter region of the mucin 5B (MUC5B). HLA-DRB1*11 alleles have been reported to correlate with ILD in European patients with SSc, whereas in Japanese patients with RA, the HLA-DR2 serological group was identified. The aim of this review is to describe the genetic background of sporadic IIP, CVD-ILD, drug-induced-ILD (DI-ILD), pneumoconiosis, and hypersensitivity pneumonitis. The genetics of ILD is still in progress. However, this information will enhance the understanding of the pathogenesis of ILD and aid the identification of novel therapeutic targets for personalized medicine in future. PMID:26056507

  4. Up-to-Date Information on Rheumatoid Arthritis-Associated Interstitial Lung Disease

    PubMed Central

    Suda, Takafumi

    2015-01-01

    Pulmonary involvement is common in rheumatoid arthritis (RA) and affects all the components of the lung. Interstitial lung disease (ILD) is the most predominant pulmonary manifestation and has been identified as the main cause of morbidity and mortality in RA. Clinically significant RA-ILD occurs in approximately 10% of RA patients. Several risk factors, such as old age, male gender, and smoking, have been reported to date. Histologically, the proportion of the usual interstitial pneumonia (UIP) pattern is higher in RA-ILD than in ILD associated with other connective tissue diseases, and RA-ILD also shows nonspecific interstitial pneumonia and organizing pneumonia patterns. High-resolution computed tomography scans are highly predictive of the histological UIP pattern with a specificity of 96%–100%. Acute exacerbation, which is the acute deterioration of the respiratory status characterized by newly developed bilateral infiltrates with unknown etiologies, has been reported in RA-ILD. Although acute exacerbation of RA-ILD has high mortality, similar to that of idiopathic pulmonary fibrosis, its incidence is lower in RA-ILD than in idiopathic pulmonary fibrosis. A consensus treatment has not yet been established. Current therapeutic regimens typically include corticosteroids with or without cytotoxic agents. Recent large longitudinal studies reported that the prognosis of RA-ILD was poor with a median survival of 2.6–3.0 years. Furthermore, histological and/or radiological patterns, such as UIP or non-UIP, have significant prognostic implications. RA-ILD patients with histological or radiological UIP patterns have poorer prognoses than those with non-UIP patterns. This review assessed the characteristics of RA-ILD by overviewing recent studies in the field and focused on the clinical significance of histological and/or radiological patterns in RA-ILD. PMID:27279757

  5. Up-to-Date Information on Rheumatoid Arthritis-Associated Interstitial Lung Disease.

    PubMed

    Suda, Takafumi

    2015-01-01

    Pulmonary involvement is common in rheumatoid arthritis (RA) and affects all the components of the lung. Interstitial lung disease (ILD) is the most predominant pulmonary manifestation and has been identified as the main cause of morbidity and mortality in RA. Clinically significant RA-ILD occurs in approximately 10% of RA patients. Several risk factors, such as old age, male gender, and smoking, have been reported to date. Histologically, the proportion of the usual interstitial pneumonia (UIP) pattern is higher in RA-ILD than in ILD associated with other connective tissue diseases, and RA-ILD also shows nonspecific interstitial pneumonia and organizing pneumonia patterns. High-resolution computed tomography scans are highly predictive of the histological UIP pattern with a specificity of 96%-100%. Acute exacerbation, which is the acute deterioration of the respiratory status characterized by newly developed bilateral infiltrates with unknown etiologies, has been reported in RA-ILD. Although acute exacerbation of RA-ILD has high mortality, similar to that of idiopathic pulmonary fibrosis, its incidence is lower in RA-ILD than in idiopathic pulmonary fibrosis. A consensus treatment has not yet been established. Current therapeutic regimens typically include corticosteroids with or without cytotoxic agents. Recent large longitudinal studies reported that the prognosis of RA-ILD was poor with a median survival of 2.6-3.0 years. Furthermore, histological and/or radiological patterns, such as UIP or non-UIP, have significant prognostic implications. RA-ILD patients with histological or radiological UIP patterns have poorer prognoses than those with non-UIP patterns. This review assessed the characteristics of RA-ILD by overviewing recent studies in the field and focused on the clinical significance of histological and/or radiological patterns in RA-ILD.

  6. Exhaled Nitric Oxide in Systemic Sclerosis Lung Disease

    PubMed Central

    Kozij, Natalie K.; Silkoff, Philip E.; Thenganatt, John; Chakravorty, Shobha

    2017-01-01

    Background. Exhaled nitric oxide (eNO) is a potential biomarker to distinguish systemic sclerosis (SSc) associated pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD). We evaluated the discriminative validity, feasibility, methods of eNO measurement, and magnitude of differences across lung diseases, disease-subsets (SSc, systemic lupus erythematosus), and healthy-controls. Methods. Consecutive subjects in the UHN Pulmonary Hypertension Programme were recruited. Exhaled nitric oxide was measured at 50 mL/s intervals using chemiluminescent detection. Alveolar and conducting airway NO were partitioned using a two-compartment model of axial diffusion (CMAD) and the trumpet model of axial diffusion (TMAD). Results. Sixty subjects were evaluated. Using the CMAD model, control subjects had lower median (IQR) alveolar NO than all PAH subjects (2.0 (1.5, 2.5) versus 3.14 ppb (2.3, 4.0), p = 0.008). SSc-ILD had significantly lower median conducting airway NO compared to controls (1009.5 versus 1342.1 ml⁎ppb/s, p = 0.04). SSc-PAH had increased median (IQR) alveolar NO compared to controls (3.3 (3.0, 5.7) versus 2.0 ppb (1.5, 2.5), p = 0.01). SSc-PAH conducting airway NO inversely correlated with DLCO (r −0.88 (95% CI −0.99, −0.26)). Conclusion. We have demonstrated feasibility, identified that CMAD modeling is preferred in SSc, and reported the magnitude of differences across cases and controls. Our data supports discriminative validity of eNO in SSc lung disease. PMID:28293128

  7. Proteomic Biomarkers for Acute Interstitial Lung Disease in Gefitinib-Treated Japanese Lung Cancer Patients

    PubMed Central

    Kawakami, Takao; Nagasaka, Keiko; Takami, Sachiko; Wada, Kazuya; Tu, Hsiao-Kun; Otsuji, Makiko; Kyono, Yutaka; Dobashi, Tae; Komatsu, Yasuhiko; Kihara, Makoto; Akimoto, Shingo; Peers, Ian S.; South, Marie C.; Higenbottam, Tim; Fukuoka, Masahiro; Nakata, Koichiro; Ohe, Yuichiro; Kudoh, Shoji; Clausen, Ib Groth; Nishimura, Toshihide; Marko-Varga, György; Kato, Harubumi

    2011-01-01

    Interstitial lung disease (ILD) events have been reported in Japanese non-small-cell lung cancer (NSCLC) patients receiving EGFR tyrosine kinase inhibitors. We investigated proteomic biomarkers for mechanistic insights and improved prediction of ILD. Blood plasma was collected from 43 gefitinib-treated NSCLC patients developing acute ILD (confirmed by blinded diagnostic review) and 123 randomly selected controls in a nested case-control study within a pharmacoepidemiological cohort study in Japan. We generated ∼7 million tandem mass spectrometry (MS/MS) measurements with extensive quality control and validation, producing one of the largest proteomic lung cancer datasets to date, incorporating rigorous study design, phenotype definition, and evaluation of sample processing. After alignment, scaling, and measurement batch adjustment, we identified 41 peptide peaks representing 29 proteins best predicting ILD. Multivariate peptide, protein, and pathway modeling achieved ILD prediction comparable to previously identified clinical variables; combining the two provided some improvement. The acute phase response pathway was strongly represented (17 of 29 proteins, p = 1.0×10−25), suggesting a key role with potential utility as a marker for increased risk of acute ILD events. Validation by Western blotting showed correlation for identified proteins, confirming that robust results can be generated from an MS/MS platform implementing strict quality control. PMID:21799770

  8. Current Status of Stem Cells and Regenerative Medicine in Lung Biology and Diseases

    PubMed Central

    Weiss, Daniel J.

    2014-01-01

    Lung diseases remain a significant and devastating cause of morbidity and mortality worldwide. In contrast to many other major diseases, lung diseases notably chronic obstructive pulmonary diseases (COPD), including both asthma and emphysema, are increasing in prevalence and COPD is expected to become the 3rd leading cause of disease mortality worldwide by 2020. New therapeutic options are desperately needed. A rapidly growing number of investigations of stem cells and cell therapies in lung biology and diseases as well as in ex vivo lung bioengineering have offered exciting new avenues for advancing knowledge of lung biology as well as providing novel potential therapeutic approaches for lung diseases. These initial observations have led to a growing exploration of endothelial progenitor cells and mesenchymal stem (stromal) cells in clinical trials of pulmonary hypertension and chronic obstructive pulmonary disease (COPD) with other clinical investigations planned. Ex vivo bioengineering of the trachea, larynx, diaphragm, and the lung itself with both biosynthetic constructs as well as decellularized tissues have been utilized to explore engineering both airway and vascular systems of the lung. Lung is thus a ripe organ for a variety of cell therapy and regenerative medicine approaches. Current state-of-the-art progress for each of the above areas will be presented as will discussion of current considerations for cell therapy based clinical trials in lung diseases. PMID:23959715

  9. The role of oxygen free radicals in occupational and environmental lung diseases.

    PubMed Central

    Vallyathan, V; Shi, X

    1997-01-01

    Oxygen free radicals and their metabolites, collectively described as reactive oxygen species (ROS), have been implicated in the pathogenesis of many diseases. The pulmonary system is particularly vulnerable to ROS-induced injury because of its continuous exposure to toxic pollutants from a wide variety of sources in the ambient air. Additionally, lungs are exposed systemically to ROS generated from xenobiotic compounds and endogenous sources. This review describes the sources of endogenous and exogenous ROS generation in the lung. Special emphasis is given to major sources of ROS in occupational and environmental exposures to asbestos, crystalline silica, coal, chromium, herbicides, bleomycin, and cigarette smoke. ROS-induced lung injury at different target levels may contribute to similar patterns of cell injury and alterations at the molecular level by initiation, propagation, and autocatalytic chain reactions. Intracellular signalling, activation and inactivation of enzymes, stimulation, secretion, and release of proinflammatory cytokines, chemokines, and nuclear factor activation and alterations are also common events. Understanding the interactions of these intricate mechanistic events is important in the prevention and amelioration of lung injury that results from acute and chronic exposures to toxins in ambient air. PMID:9114285

  10. The role of oxygen free radicals in occupational and environmental lung diseases

    SciTech Connect

    Vallyathan, V.; Shi, Xianglin

    1997-02-01

    Oxygen free radicals and their metabolites, collectively described as reactive oxygen species (ROS), have been implicated in the pathogenesis of many diseases. The pulmonary system is particularly vulnerable to ROS-induced injury because of its continuous exposure to toxic pollutants from a wide variety of sources in the ambient air. Additionally, lungs are exposed systemically to ROS generated from xenobiotic compounds and endogenous sources. This review describes the sources of endogenous and exogenous ROS generation in the lung. Special emphasis is given to major sources of ROS in occupational and environmental exposures to asbestos, crystalline silica, coal, chromium, herbicides, bleomycin, and cigarette smoke. ROS-induced lung injury at different target levels may contribute to similar patterns of cell injury and alterations at the molecular level by initiation, propagation, and autocatalytic chain reactions. Intracellular signalling, activation and inactivation of enzymes, stimulation, secretion, and release of proinflammatory cytokines, chemokines, and nuclear factor activation and alterations are also common events. Understanding the interactions of these intricate mechanistic events is important in the prevention and amelioration of lung injury that results from acute and chronic exposures to toxins in ambient air. 147 refs., 1 fig.

  11. [Pulsed hypoxia in the treatment of obstructive lung diseases].

    PubMed

    Sil'vestrov, V P; Kovalenko, E A; Krysin, Iu S

    1993-01-01

    A new approach to the treatment of chronic nonspecific pulmonary diseases is proposed: helium-oxygen therapy combined with repeated interrupted hypoxic stimuli. Helium inclusion into hypoxic gas mixture leads to reduced air density. Gas mixture containing 10-15% of oxygen is more effective at the level of alveolocapillary membrane. When conducted in normal atmospheric pressure, the method involved no complications and produced positive responses in coronary heart disease, hypertension, alimentary diseases. The mixture of helium with oxygen (85-90% of helium, 10-15% oxygen) in combination with impulse normobaric hypoxia has been tried in 25 chronics with obstructive bronchitis and bronchial asthma. The results were indicative of the treatment efficacy: bronchial permeability improved in 67% of the cases, forced vital capacity of the lungs increased, inspiratory reserve volume grew, dyspnea and cough diminished, sputum discharge improved, general tonicity and performance status changed positively. Six-month follow-up evidenced positive shifts too.

  12. Lung carcinogenesis from chronic obstructive pulmonary disease: characteristics of lung cancer from COPD and contribution of signal transducers and lung stem cells in the inflammatory microenvironment.

    PubMed

    Sekine, Yasuo; Hata, Atsushi; Koh, Eitetsu; Hiroshima, Kenzo

    2014-07-01

    Chronic obstructive pulmonary disease (COPD) and lung cancer are closely related. The annual incidence of lung cancer arising from COPD has been reported to be 0.8-1.7 %. Treatment of lung cancer from COPD is very difficult due to low cardiopulmonary function, rapid tumor growth, and resistance to molecularly targeted therapies. Chronic inflammation caused by toxic gases can induce COPD and lung cancer. Carcinogenesis in the inflammatory microenvironment occurs during cycles of tissue injury and repair. Cellular damage can induce induction of necrotic cell death and loss of tissue integrity. Quiescent normal stem cells or differentiated progenitor cells are introduced to repair injured tissues. However, inflammatory mediators may promote the growth of bronchioalveolar stem cells, and activation of NF-κB and signal transducer and activator of transcription 3 (STAT3) play crucial roles in the development of lung cancer from COPD. Many of the protumorgenic effects of NF-κB and STAT3 activation in immune cells are mediated through paracrine signaling. NF-κB and STAT3 also contribute to epithelial-mesenchymal transition. To improve lung cancer treatment outcomes, lung cancer from COPD must be overcome. In this article, we review the characteristics of lung cancer from COPD and the mechanisms of carcinogenesis in the inflammatory microenvironment. We also propose the necessity of identifying the mechanisms underlying progression of COPD to lung cancer, and comment on the clinical implications with respect to lung cancer prevention, screening, and therapy.

  13. Chronic Suppurative Lung Disease in Children: Definition and Spectrum of Disease

    PubMed Central

    Redding, Gregory J.; Carter, Edward R.

    2017-01-01

    The most common clinical suppurative lung conditions in children are empyema, lung abscess, and bronchiectasis, and to a less often necrotizing pneumonia. Until recently, bronchiectasis was the most common form of persistent suppurative lung disease in children. Protracted bacterial bronchitis is a newly described chronic suppurative condition in children, which is less persistent but more common than bronchiectasis (1). In addition, the term “chronic suppurative lung disease” has been used recently to describe the clinical features of bronchiectasis when the radiographic features needed to make a diagnosis of bronchiectasis are absent. Webster’s New College Dictionary defines suppuration as the process of forming and/or discharging pus. Pus is a body fluid resulting from intense inflammation in response to infection that leads to neutrophil influx and apoptosis, microbial clearance, and often necrosis of nearby tissue. Pus is primarily composed of white blood cell debris. PMID:28289673

  14. Metabolomics and Its Application to Acute Lung Diseases

    PubMed Central

    Stringer, Kathleen A.; McKay, Ryan T.; Karnovsky, Alla; Quémerais, Bernadette; Lacy, Paige

    2016-01-01

    Metabolomics is a rapidly expanding field of systems biology that is gaining significant attention in many areas of biomedical research. Also known as metabonomics, it comprises the analysis of all small molecules or metabolites that are present within an organism or a specific compartment of the body. Metabolite detection and quantification provide a valuable addition to genomics and proteomics and give unique insights into metabolic changes that occur in tangent to alterations in gene and protein activity that are associated with disease. As a novel approach to understanding disease, metabolomics provides a “snapshot” in time of all metabolites present in a biological sample such as whole blood, plasma, serum, urine, and many other specimens that may be obtained from either patients or experimental models. In this article, we review the burgeoning field of metabolomics in its application to acute lung diseases, specifically pneumonia and acute respiratory disease syndrome (ARDS). We also discuss the potential applications of metabolomics for monitoring exposure to aerosolized environmental toxins. Recent reports have suggested that metabolomics analysis using nuclear magnetic resonance (NMR) and mass spectrometry (MS) approaches may provide clinicians with the opportunity to identify new biomarkers that may predict progression to more severe disease, such as sepsis, which kills many patients each year. In addition, metabolomics may provide more detailed phenotyping of patient heterogeneity, which is needed to achieve the goal of precision medicine. However, although several experimental and clinical metabolomics studies have been conducted assessing the application of the science to acute lung diseases, only incremental progress has been made. Specifically, little is known about the metabolic phenotypes of these illnesses. These data are needed to substantiate metabolomics biomarker credentials so that clinicians can employ them for clinical decision

  15. Role of CCL5 (RANTES) in viral lung disease.

    PubMed

    Culley, Fiona J; Pennycook, Alasdair M J; Tregoning, John S; Dodd, Jonathan S; Walzl, Gerhard; Wells, Timothy N; Hussell, Tracy; Openshaw, Peter J M

    2006-08-01

    CCL5/RANTES is a key proinflammatory chemokine produced by virus-infected epithelial cells and present in respiratory secretions of asthmatics. To examine the role of CCL5 in viral lung disease, we measured its production during primary respiratory syncytial virus (RSV) infection and during secondary infection after sensitizing vaccination that induces Th2-mediated eosinophilia. A first peak of CCL5 mRNA and protein production was seen at 18 to 24 h of RSV infection, before significant lymphocyte recruitment occurred. Treatment in vivo with Met-RANTES (a competitive chemokine receptor blocker) throughout primary infection decreased CD4+ and CD8+ cell recruitment and increased viral replication. In RSV-infected, sensitized mice with eosinophilic disease, CCL5 production was further augmented; Met-RANTES treatment again reduced inflammatory cell recruitment and local cytokine production. A second wave of CCL5 production occurred on day 7, attributable to newly recruited T cells. Paradoxically, mice treated with Met-RANTES during primary infection demonstrated increased cellular infiltration during reinfection. We therefore show that RSV induces CCL5 production in the lung and this causes the recruitment of RSV-specific cells, including those making additional CCL5. If this action is blocked with Met-RANTES, inflammation decreases and viral clearance is delayed. However, the exact effects of chemokine modulation depend critically on time of administration, a factor that may potentially complicate the use of chemokine blockers in inflammatory diseases.

  16. Immunosuppressive agents and interstitial lung disease: what are the risks?

    PubMed

    Meyer, Keith C

    2014-06-01

    Idiopathic pulmonary fibrosis is unlikely to respond to immunosuppressive therapies, and patients with idiopathic pulmonary fibrosis may be harmed by such therapy. In contrast, some forms of interstitial lung disease can respond well to treatment with immunosuppressive drug therapies. Such agents can, however, be associated with significant risk of adverse effects such as infection, diabetes, osteoporosis, myopathy, bone marrow suppression, hepatitis, urinary tract injury, and drug-induced pneumonitis. Treating clinicians must be aware of potential adverse reactions to any immunosuppressive drug that they prescribe for their patients, and they should implement appropriate pre-therapy screening (e.g., tuberculosis, hepatitis, renal insufficiency) and monitoring that is recommended to avoid/minimize risk during the treatment period. Some disorders (e.g., cellular non-specific interstitial pneumonia, organizing pneumonia, or sarcoidosis) may respond very well to immunosuppressive therapies including corticosteroids as monotherapy, and the use of steroid-sparing agents can minimize corticosteroid side effects and may enhance treatment efficacy for disorders such as sarcoidosis or connective tissue disease-associated forms of interstitial lung disease.

  17. OSCILLATION MECHANICS OF THE RESPIRATORY SYSTEM: APPLICATIONS TO LUNG DISEASE

    PubMed Central

    Kaczka, David W.; Dellacá, Raffaele L.

    2011-01-01

    Since its introduction in the 1950s, the forced oscillation technique (FOT) and the measurement of respiratory impedance have evolved into powerful tools for the assessment of various mechanical phenomena in the mammalian lung during health and disease. In this review, we highlight the most recent developments in instrumentation, signal processing, and modeling relevant to FOT measurements. We demonstrate how FOT provides unparalleled information on the mechanical status of the respiratory system compared to more widely-used pulmonary function tests. The concept of mechanical impedance is reviewed, as well as the various measurement techniques used to acquire such data. Emphasis is placed on the analysis of lower, physiologic frequency ranges (typically less than 10 Hz) that are most sensitive to normal physical processes as well as pathologic structural alterations. Various inverse modeling approaches used to interpret alterations in impedance are also discussed, specifically in the context of three common respiratory diseases: asthma, chronic obstructive pulmonary disease, and acute lung injury. Finally, we speculate on the potential role for FOT in the clinical arena. PMID:22011237

  18. Lymphangiogenesis and Lesion Heterogeneity in Interstitial Lung Diseases

    PubMed Central

    Yamashita, Masahiro

    2015-01-01

    The lymphatic system has several physiological roles, including fluid homeostasis and the activation of adaptive immunity by fluid drainage and cell transport. Lymphangiogenesis occurs in adult tissues during various pathologic conditions. In addition, lymphangiogenesis is closely linked to capillary angiogenesis, and the balanced interrelationship between capillary angiogenesis and lymphangiogenesis is essential for maintaining homeostasis in tissues. Recently, an increasing body of information regarding the biology of lymphatic endothelial cells has allowed us to immunohistochemically characterize lymphangiogenesis in several lung diseases. Particular interest has been given to the interstitial lung diseases. Idiopathic interstitial pneumonias (IIPs) are characterized by heterogeneity in pathologic changes and lesions, as typified by idiopathic pulmonary fibrosis/usual interstitial pneumonia. In IIPs, lymphangiogenesis is likely to have different types of localized functions within each disorder, corresponding to the heterogeneity of lesions in terms of inflammation and fibrosis. These functions include inhibitory absorption of interstitial fluid and small molecules and maturation of fibrosis by excessive interstitial fluid drainage, caused by an unbalanced relationship between capillary angiogenesis and lymphangiogenesis and trafficking of antigen-presenting cells and induction of fibrogenesis via CCL21 and CCR7 signals. Better understanding for regional functions of lymphangiogenesis might provide new treatment strategies tailored to lesion heterogeneity in these complicated diseases. PMID:26823655

  19. Fibred confocal fluorescence microscopy in the diagnosis of interstitial lung diseases

    PubMed Central

    Meng, Peng; Low, Su Ying; Takano, Angela; Ng, Yuen Li; Anantham, Devanand

    2016-01-01

    Background Accurate diagnosis is critical to both therapeutic decisions and prognostication in interstitial lung diseases (ILD). However, surgical lung biopsies carry high complication rates. Fibred confocal fluorescence microscopy (FCFM) offers an alternative as it can visualize lung tissue in vivo at the cellular level with minimal adverse events. We wanted to investigate the diagnostic utility, and safety of using FCFM for patients with ILD. Methods In patients with suspected ILD, FCFM images were obtained from multiple bronchopulmonary segments using a miniprobe inserted through the working channel of a flexible bronchoscope. The procedure was performed under moderate sedation in an outpatient setting. Morphometric measurements and fibre pattern analyses were co-related with computed tomography (CT) findings and patients’ final diagnoses based on multi-disciplinary consensus. Results One hundred and eighty four segments were imaged in 27 patients (18 males) with a median age of 67 years (range, 24–79 years). They were grouped into chronic fibrosing interstitial pneumonia (16 patients) and other ILDs. Six distinct FCFM patterns were observed: normal, increased fibres, densely packed fibres, hypercellular, thickened fibres and others/non-specific. The pattern resembling densely packed fibres was seen in at least one segment in 68.8% patients with chronic fibrosing interstitial pneumonia, but only 36.4% in other ILD (P=0.097). An association between inflammatory patterns on CT and a hypercellular pattern on FCFM was also found (P<0.001). Conclusions Our study shows the potential of FCFM in classifying ILD, but its role in further diagnosis remains limited. PMID:28149543

  20. Postnatal Infections and Immunology Affecting Chronic Lung Disease of Prematurity

    PubMed Central

    Pryhuber, Gloria S.

    2015-01-01

    Synopsis Premature infants suffer significant respiratory morbidity during infancy with long-term negative consequences on health, quality of life, and health care costs. Enhanced susceptibility to a variety of infections and inflammation play a large role in early and prolonged lung disease following premature birth, though the mechanisms of susceptibility and immune dysregulation are active areas of research. This chapter will review aspects of host-pathogen interactions and immune responses that are altered by preterm birth and that impact chronic respiratory morbidity in these children. PMID:26593074

  1. Recent Treatments of Interstitial Lung Disease with Systemic Sclerosis

    PubMed Central

    Yasuoka, Hidekata

    2015-01-01

    Systemic sclerosis (SSc) is a disorder characterized by immune dysfunction, microvascular injury, and fibrosis. Organ involvement in patients with SSc is variable; however, pulmonary involvement occurs in up to 90% of patients with SSc. Interstitial lung disease (ILD) is a major cause of mortality and, thus, a major determinant in the prognosis of patients with SSc. This review summarizes current findings about the characteristics of ILD in patients with SSc, selection of patients with SSc-ILD who are candidates for the treatment, and current treatment options. PMID:26819563

  2. Weight preserving image registration for monitoring disease progression in lung CT.

    PubMed

    Gorbunova, Vladlena; Lol, Pechin; Ashraf, Haseem; Dirksen, Asger; Nielsen, Mads; de Bruijne, Marleen

    2008-01-01

    We present a new image registration based method for monitoring regional disease progression in longitudinal image studies of lung disease. A free-form image registration technique is used to match a baseline 3D CT lung scan onto a following scan. Areas with lower intensity in the following scan compared with intensities in the deformed baseline image indicate local loss of lung tissue that is associated with progression of emphysema. To account for differences in lung intensity owing to differences in the inspiration level in the two scans rather than disease progression, we propose to adjust the density of lung tissue with respect to local expansion or compression such that the total weight of the lungs is preserved during deformation. Our method provides a good estimation of regional destruction of lung tissue for subjects with a significant difference in inspiration level between CT scans and may result in a more sensitive measure of disease progression than standard quantitative CT measures.

  3. Concise review: current status of stem cells and regenerative medicine in lung biology and diseases.

    PubMed

    Weiss, Daniel J

    2014-01-01

    Lung diseases remain a significant and devastating cause of morbidity and mortality worldwide. In contrast to many other major diseases, lung diseases notably chronic obstructive pulmonary diseases (COPDs), including both asthma and emphysema, are increasing in prevalence and COPD is expected to become the third leading cause of disease mortality worldwide by 2020. New therapeutic options are desperately needed. A rapidly growing number of investigations of stem cells and cell therapies in lung biology and diseases as well as in ex vivo lung bioengineering have offered exciting new avenues for advancing knowledge of lung biology as well as providing novel potential therapeutic approaches for lung diseases. These initial observations have led to a growing exploration of endothelial progenitor cells and mesenchymal stem (stromal) cells in clinical trials of pulmonary hypertension and COPD with other clinical investigations planned. Ex vivo bioengineering of the trachea, larynx, diaphragm, and the lung itself with both biosynthetic constructs as well as decellularized tissues have been used to explore engineering both airway and vascular systems of the lung. Lung is thus a ripe organ for a variety of cell therapy and regenerative medicine approaches. Current state-of-the-art progress for each of the above areas will be presented as will discussion of current considerations for cell therapy-based clinical trials in lung diseases.

  4. COPA mutations impair ER-Golgi transport causing hereditary autoimmune-mediated lung disease and arthritis

    PubMed Central

    Watkin, Levi B.; Jessen, Birthe; Wiszniewski, Wojciech; Vece, Timothy; Jan, Max; Sha, Youbao; Thamsen, Maike; Santos-Cortez, Regie L. P.; Lee, Kwanghyuk; Gambin, Tomasz; Forbes, Lisa; Law, Christopher S.; Stray-Petersen, Asbjørg; Cheng, Mickie H.; Mace, Emily M.; Anderson, Mark S.; Liu, Dongfang; Tang, Ling Fung; Nicholas, Sarah K.; Nahmod, Karen; Makedonas, George; Canter, Debra; Kwok, Pui-Yan; Hicks, John; Jones, Kirk D.; Penney, Samantha; Jhangiani, Shalini N.; Rosenblum, Michael D.; Dell, Sharon D.; Waterfield, Michael R.; Papa, Feroz R.; Muzny, Donna M.; Zaitlen, Noah; Leal, Suzanne M.; Gonzaga-Jauregui, Claudia; Boerwinkle, Eric; Eissa, N. Tony; Gibbs, Richard A.; Lupski, James R.; Orange, Jordan S.; Shum, Anthony K.

    2015-01-01

    Advances in genomics have allowed unbiased genetic studies of human disease with unexpected insights into the molecular mechanisms of cellular immunity and autoimmunity1. We performed whole exome sequencing (WES) and targeted sequencing in patients with an apparent Mendelian syndrome of autoimmune disease characterized by high-titer autoantibodies, inflammatory arthritis and interstitial lung disease (ILD). In five families, we identified four unique deleterious variants in the Coatomer subunit alpha (COPA) gene all located within the same functional domain. We hypothesized that mutant COPA leads to a defect in intracellular transport mediated by coat protein complex I (COPI)2–4. We show that COPA variants impair binding of proteins targeted for retrograde Golgi to ER transport and demonstrate that expression of mutant COPA leads to ER stress and the upregulation of Th17 priming cytokines. Consistent with this pattern of cytokine expression, patients demonstrated a significant skewing of CD4+ T cells toward a T helper 17 (Th17) phenotype, an effector T cell population implicated in autoimmunity5,6. Our findings uncover an unexpected molecular link between a vesicular transport protein and a syndrome of autoimmunity manifested by lung and joint disease. These findings provide a unique opportunity to understand how alterations in cellular homeostasis caused by a defect in the intracellular trafficking pathway leads to the generation of human autoimmune disease. PMID:25894502

  5. Quantification of heterogeneity in lung disease with image-based pulmonary function testing

    PubMed Central

    Stahr, Charlene S.; Samarage, Chaminda R.; Donnelley, Martin; Farrow, Nigel; Morgan, Kaye S.; Zosky, Graeme; Boucher, Richard C.; Siu, Karen K. W.; Mall, Marcus A.; Parsons, David W.; Dubsky, Stephen; Fouras, Andreas

    2016-01-01

    Computed tomography (CT) and spirometry are the mainstays of clinical pulmonary assessment. Spirometry is effort dependent and only provides a single global measure that is insensitive for regional disease, and as such, poor for capturing the early onset of lung disease, especially patchy disease such as cystic fibrosis lung disease. CT sensitively measures change in structure associated with advanced lung disease. However, obstructions in the peripheral airways and early onset of lung stiffening are often difficult to detect. Furthermore, CT imaging poses a radiation risk, particularly for young children, and dose reduction tends to result in reduced resolution. Here, we apply a series of lung tissue motion analyses, to achieve regional pulmonary function assessment in β-ENaC-overexpressing mice, a well-established model of lung disease. The expiratory time constants of regional airflows in the segmented airway tree were quantified as a measure of regional lung function. Our results showed marked heterogeneous lung function in β-ENaC-Tg mice compared to wild-type littermate controls; identified locations of airway obstruction, and quantified regions of bimodal airway resistance demonstrating lung compensation. These results demonstrate the applicability of regional lung function derived from lung motion as an effective alternative respiratory diagnostic tool. PMID:27461961

  6. Interstitial lung disease in connective tissue diseases: evolving concepts of pathogenesis and management

    PubMed Central

    2010-01-01

    Interstitial lung disease (ILD) is a challenging clinical entity associated with multiple connective tissue diseases, and is a significant cause of morbidity and mortality. Effective therapies for connective tissue disease-associated interstitial lung disease (CTD-ILD) are still lacking. Multidisciplinary clinics dedicated to the early diagnosis and improved management of patients with CTD-ILD are now being established. There is rapid progress in understanding and identifying the effector cells, the proinflammatory and profibrotic mediators, and the pathways involved in the pathogenesis of CTD-ILD. Serum biomarkers may provide new insights as risk factors for pulmonary fibrosis and as measures of disease progression. Despite these recent advances, the management of patients with CTD-ILD remains suboptimal. Further studies are therefore urgently needed to better understand these conditions, and to develop effective therapeutic interventions. PMID:20735863

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

    PubMed Central

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

    2016-01-01

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

  8. Clinical experience with pirfenidone in five patients with scleroderma-related interstitial lung disease.

    PubMed

    Miura, Yukiko; Saito, Takefumi; Fujita, Kazutaka; Tsunoda, Yoshiya; Tanaka, Toru; Takoi, Hiroyuki; Yatagai, Yohei; Rin, Shigen; Sekine, Akimasa; Hayashihara, Kenji; Nei, Takahito; Azuma, Arata

    2014-10-20

    Interstitial lung disease is the most common complication and cause of death among patients with scleroderma. Scleroderma-related interstitial lung disease has usually been treated with cyclophosphamide; however, its effect was evaluated to be modest and long-term administration of this drug is associated with adverse effects. Herein, we report our clinical experience of administering pirfenidone, which is an antifibrotic agent, in five patients with scleroderma-related interstitial lung disease. All patients demonstrated an increase in vital capacity.

  9. Novel level-set based segmentation method of the lung at HRCT images of diffuse interstitial lung disease (DILD)

    NASA Astrophysics Data System (ADS)

    Lee, Jeongjin; Seo, Joon Beom; Kim, Namkug; Park, Sang Ok; Lee, Ho; Shin, Yeong Gil; Kim, Soo-Hong

    2009-02-01

    In this paper, we propose an algorithm for reliable segmentation of the lung at HRCT of DILD. Our method consists of four main steps. First, the airway and colon are segmented and excluded by thresholding(-974 HU) and connected component analysis. Second, initial lung is identified by thresholding(-474 HU). Third, shape propagation outward the lung is performed on the initial lung. Actual lung boundaries exist inside the propagated boundaries. Finally, subsequent shape modeling level-set inward the lung from the propagated boundary can identify the lung boundary when the curvature term was highly weighted. To assess the accuracy of the proposed algorithm, the segmentation results of 54 patients are compared with those of manual segmentation done by an expert radiologist. The value of 1 minus volumetric overlap is less than 5% error. Accurate result of our method would be useful in determining the lung parenchyma at HRCT, which is the essential step for the automatic classification and quantification of diffuse interstitial lung disease.

  10. Left ventricular failure produces profound lung remodeling and pulmonary hypertension in mice: heart failure causes severe lung disease.

    PubMed

    Chen, Yingjie; Guo, Haipeng; Xu, Dachun; Xu, Xin; Wang, Huan; Hu, Xinli; Lu, Zhongbing; Kwak, Dongmin; Xu, Yawei; Gunther, Roland; Huo, Yuqing; Weir, E Kenneth

    2012-06-01

    Chronic left ventricular failure causes pulmonary congestion with increased lung weight and type 2 pulmonary hypertension. Understanding the molecular mechanisms for type 2 pulmonary hypertension and the development of novel treatments for this condition requires a robust experimental animal model and a good understanding of the nature of the resultant pulmonary remodeling. Here we demonstrate that chronic transverse aortic constriction causes massive pulmonary fibrosis and remodeling, as well as type 2 pulmonary hypertension, in mice. Thus, aortic constriction-induced left ventricular dysfunction and increased left ventricular end-diastolic pressure are associated with a ≤5.3-fold increase in lung wet weight and dry weight, pulmonary hypertension, and right ventricular hypertrophy. Interestingly, the aortic constriction-induced increase in lung weight was not associated with pulmonary edema but resulted from profound pulmonary remodeling with a dramatic increase in the percentage of fully muscularized lung vessels, marked vascular and lung fibrosis, myofibroblast proliferation, and leukocyte infiltration. The aortic constriction-induced left ventricular dysfunction was also associated with right ventricular hypertrophy, increased right ventricular end-diastolic pressure, and right atrial hypertrophy. The massive lung fibrosis, leukocyte infiltration, and pulmonary hypertension in mice after transverse aortic constriction clearly indicate that congestive heart failure also causes severe lung disease. The lung fibrosis and leukocyte infiltration may be important mechanisms in the poor clinical outcome in patients with end-stage heart failure. Thus, the effective treatment of left ventricular failure may require additional efforts to reduce lung fibrosis and the inflammatory response.

  11. Advanced sickle cell associated interstitial lung disease presenting with cor pulmonale in a Nigerian.

    PubMed

    Fawibe, Ademola Emmanuel; Kolo, Philip Manman; Ogunmodede, James Ayodele; Desalu, Olufemi Olumuyiwa; Salami, Kazeem Alakija

    2012-04-01

    Previous studies have reported abnormal pulmonary function and pulmonary hypertension among Nigerians with sickle cell disease, but there is no report of interstitial lung disease among them. We report a Nigerian sickle cell patient who presented with computed tomography proven interstitial lung disease complicated by pulmonary hypertension and cor pulmonale.

  12. Sex-specific differences in hyperoxic lung injury in mice: Implications for acute and chronic lung disease in humans

    SciTech Connect

    Lingappan, Krithika; Jiang, Weiwu; Wang, Lihua; Couroucli, Xanthi I.; Barrios, Roberto; Moorthy, Bhagavatula

    2013-10-15

    Sex-specific differences in pulmonary morbidity in humans are well documented. Hyperoxia contributes to lung injury in experimental animals and humans. The mechanisms responsible for sex differences in the susceptibility towards hyperoxic lung injury remain largely unknown. In this investigation, we tested the hypothesis that mice will display sex-specific differences in hyperoxic lung injury. Eight week-old male and female mice (C57BL/6J) were exposed to 72 h of hyperoxia (FiO{sub 2} > 0.95). After exposure to hyperoxia, lung injury, levels of 8-iso-prostaglandin F{sub 2} alpha (8-iso-PGF 2α) (LC–MS/MS), apoptosis (TUNEL) and inflammatory markers (suspension bead array) were determined. Cytochrome P450 (CYP)1A expression in the lung was assessed using immunohistochemistry and western blotting. After exposure to hyperoxia, males showed greater lung injury, neutrophil infiltration and apoptosis, compared to air-breathing controls than females. Pulmonary 8-iso-PGF 2α levels were higher in males than females after hyperoxia exposure. Sexually dimorphic increases in levels of IL-6 (F > M) and VEGF (M > F) in the lungs were also observed. CYP1A1 expression in the lung was higher in female mice compared to males under hyperoxic conditions. Overall, our results support the hypothesis that male mice are more susceptible than females to hyperoxic lung injury and that differences in inflammatory and oxidative stress markers contribute to these sex-specific dimorphic effects. In conclusion, this paper describes the establishment of an animal model that shows sex differences in hyperoxic lung injury in a temporal manner and thus has important implications for lung diseases mediated by hyperoxia in humans. - Highlights: • Male mice were more susceptible to hyperoxic lung injury than females. • Sex differences in inflammatory markers were observed. • CYP1A expression was higher in females after hyperoxia exposure.

  13. Phylogenetic tree shapes resolve disease transmission patterns

    PubMed Central

    Colijn, Caroline; Gardy, Jennifer

    2014-01-01

    Background and Objectives: Whole-genome sequencing is becoming popular as a tool for understanding outbreaks of communicable diseases, with phylogenetic trees being used to identify individual transmission events or to characterize outbreak-level overall transmission dynamics. Existing methods to infer transmission dynamics from sequence data rely on well-characterized infectious periods, epidemiological and clinical metadata which may not always be available, and typically require computationally intensive analysis focusing on the branch lengths in phylogenetic trees. We sought to determine whether the topological structures of phylogenetic trees contain signatures of the transmission patterns underlying an outbreak. Methodology: We use simulated outbreaks to train and then test computational classifiers. We test the method on data from two real-world outbreaks. Results: We show that different transmission patterns result in quantitatively different phylogenetic tree shapes. We describe topological features that summarize a phylogeny’s structure and find that computational classifiers based on these are capable of predicting an outbreak’s transmission dynamics. The method is robust to variations in the transmission parameters and network types, and recapitulates known epidemiology of previously characterized real-world outbreaks. Conclusions and implications: There are simple structural properties of phylogenetic trees which, when combined, can distinguish communicable disease outbreaks with a super-spreader, homogeneous transmission and chains of transmission. This is possible using genome data alone, and can be done during an outbreak. We discuss the implications for management of outbreaks. PMID:24916411

  14. Interstitial Lung Disease in Childhood: Clinical and Genetic Aspects

    PubMed Central

    Kitazawa, Hiroshi; Kure, Shigeo

    2015-01-01

    Interstitial lung disease (ILD) in childhood is a heterogeneous group of rare pulmonary conditions presenting chronic respiratory disorders. Many clinical features of ILD still remain unclear, making the treatment strategies mainly investigative. Guidelines may provide physicians with an overview on the diagnosis and therapeutic directions. However, the criteria used in different clinical studies for the classification and diagnosis of ILDs are not always the same, making the development of guidelines difficult. Advances in genetic testing have thrown light on some etiologies of ILD, which were formerly classified as ILDs of unknown origins. The need of genetic testing for unexplained ILD is growing, and new classification criteria based on the etiology should be adopted to better understand the disease. The purpose of this review is to give an overview of the clinical and genetic aspects of ILD in children. PMID:26512209

  15. Hypoxic pulmonary hypertension in chronic lung diseases: novel vasoconstrictor pathways.

    PubMed

    Rowan, Simon C; Keane, Michael P; Gaine, Seán; McLoughlin, Paul

    2016-03-01

    Pulmonary hypertension is a well recognised complication of chronic hypoxic lung diseases, which are among the most common causes of death and disability worldwide. Development of pulmonary hypertension independently predicts reduced life expectancy. In chronic obstructive pulmonary disease, long-term oxygen therapy ameliorates pulmonary hypertension and greatly improves survival, although the correction of alveolar hypoxia and pulmonary hypertension is only partial. Advances in understanding of the regulation of vascular smooth muscle tone show that chronic vasoconstriction plays a more important part in the pathogenesis of hypoxic pulmonary hypertension than previously thought, and that structural vascular changes contribute less. Trials of existing vasodilators show that pulmonary hypertension can be ameliorated and systemic oxygen delivery improved in carefully selected patients, although systemic hypotensive effects limit the doses used. Vasoconstrictor pathways that are selective for the pulmonary circulation can be blocked to reduce hypoxic pulmonary hypertension without causing systemic hypotension, and thus provide potential targets for novel therapeutic strategies.

  16. New insights into lung development and diseases: the role of microRNAs.

    PubMed

    Johar, Dina; Siragam, Vinayakumar; Mahood, Thomas H; Keijzer, Richard

    2015-04-01

    MicroRNAs (miRNAs) are short endogenous noncoding RNA molecules (∼ 22 nucleotides) that can regulate gene expression at the post-transcription level. Research interest in the role of miRNAs in lung biology is emerging. MiRNAs have been implicated in a range of processes such as development, homeostasis, and inflammatory diseases in lung tissues and are capable of inducing differentiation, morphogenesis, and apoptosis. In recent years, several studies have reported that miRNAs are differentially regulated in lung development and lung diseases in response to epigenetic changes, providing new insights for their versatile role in various physiological and pathological processes in the lung. In this review, we discuss the contribution of miRNAs to lung development and diseases and possible future implications in the field of lung biology.

  17. Emptying patterns of the lung studied by multiple-breath N2 washout

    NASA Technical Reports Server (NTRS)

    Lewis, S. M.

    1978-01-01

    Changes in the nitrogen concentration seen during the single-breath nitrogen washout reflect changes in relative flow (ventilation) from units with differing ventilation/volume ratios. The multiple-breath washout provides sufficient data on ventilation for units with varying ventilation/volume ratios to be plotted as a function of the volume expired. Flow from the dead space may also be determined. In young normals the emptying patterns are narrow and unimodal throughout the alveolar plateau with little or no flow from the dead space at the end of the breath. Older normals show more flow from the dead space, particularly toward the end of the breath, and some show a high ventilation/volume ratio mode early in the breath. Patients with obstructive lung disease have a high flow from the dead space which is present throughout the breath. A well ventilated mode at the end of the breath is seen in some obstructed subjects. Patients with cystic fibrosis showed a poorly ventilated mode appearing at the end of the breath as well as a very high dead space.

  18. A novel scheme for detection of diffuse lung disease in MDCT by use of statistical texture features

    NASA Astrophysics Data System (ADS)

    Wang, Jiahui; Li, Feng; Doi, Kunio; Li, Qiang

    2009-02-01

    The successful development of high performance computer-aided-diagnostic systems has potential to assist radiologists in the detection and diagnosis of diffuse lung disease. We developed in this study an automated scheme for the detection of diffuse lung disease on multi-detector computed tomography (MDCT). Our database consisted of 68 CT scans, which included 31 normal and 37 abnormal cases with three kinds of abnormal patterns, i.e., ground glass opacity, reticular, and honeycombing. Two radiologists first selected the CT scans with abnormal patterns based on clinical reports. The areas that included specific abnormal patterns in the selected CT images were then delineated as reference standards by an expert chest radiologist. To detect abnormal cases with diffuse lung disease, the lungs were first segmented from the background in each slice by use of a texture analysis technique, and then divided into contiguous volumes of interest (VOIs) with a 64×64×64 matrix size. For each VOI, we calculated many statistical texture features, including the mean and standard deviation of CT values, features determined from the run length matrix, and features from the co-occurrence matrix. A quadratic classifier was employed for distinguishing between normal and abnormal VOIs by use of a leave-one-case-out validation scheme. A rule-based criterion was employed to further determine whether a case was normal or abnormal. For the detection of abnormal VOIs, our CAD system achieved a sensitivity of 86% and a specificity of 90%. For the detection of abnormal cases, it achieved a sensitivity of 89% and a specificity of 90%. This preliminary study indicates that our CAD system would be useful for the detection of diffuse lung disease.

  19. BPD Following Preterm Birth: A Model for Chronic Lung Disease and a Substrate for ARDS in Childhood

    PubMed Central

    Bhandari, Anita; Carroll, Christopher; Bhandari, Vineet

    2016-01-01

    It has been suggested that pediatric acute respiratory distress syndrome (PARDS) may be a different entity, vis-à-vis adult acute respiratory distress syndrome (ARDS), based on its epidemiology and outcomes. A more pediatric-specific definition of PARDS to include the subgroup of patients with underlying lung (and heart) disease has been proposed. Epidemiological data suggest that up to 13% of the children with ARDS have a history of prematurity and/or underlying chronic lung disease. However, the specific contribution of bronchopulmonary dysplasia (BPD), the most common chronic lung disease in infants, to the development of PARDS is not known. BPD leads to damaged lungs with long-term consequences secondary to disordered growth and immune function. These damaged lungs could potentially act as a substrate, which given the appropriate noxious stimuli, can predispose a child to PARDS. Interestingly, similar biomarkers [KL-6, interleukin (IL)-6, IL-8, sICAM-1, angiopoietin-2, and matrix metalloproteinase-8 and -9] of pulmonary injury have been associated both with BPD and ARDS. Recognition of a unique pattern of clinical symptomatology and/or outcomes of PARDS, if present, could potentially be useful for investigating targeted therapeutic interventions. PMID:27379219

  20. Lung Nodule Image Classification Based on Local Difference Pattern and Combined Classifier

    PubMed Central

    Deng, Zhuofu

    2016-01-01

    This paper proposes a novel lung nodule classification method for low-dose CT images. The method includes two stages. First, Local Difference Pattern (LDP) is proposed to encode the feature representation, which is extracted by comparing intensity difference along circular regions centered at the lung nodule. Then, the single-center classifier is trained based on LDP. Due to the diversity of feature distribution for different class, the training images are further clustered into multiple cores and the multicenter classifier is constructed. The two classifiers are combined to make the final decision. Experimental results on public dataset show the superior performance of LDP and the combined classifier. PMID:28053650

  1. Benefit of adjunctive tacrolimus in connective tissue disease-interstitial lung disease

    PubMed Central

    Witt, Leah J.; Demchuk, Carley; Curran, James J.; Strek, Mary E.

    2016-01-01

    We evaluated the safety and effectiveness of adjunctive tacrolimus therapy with conventional immunosuppression in patients with severe connective tissue disease-related interstitial lung disease (CTD-ILD). We included patients from our interstitial lung disease (ILD) registry with CTD-ILD, in whom tacrolimus was added to corticosteroids and an additional immunosuppressive agent. Demographic data, clinical features, lung function, radiographic images, and pathologic findings were reviewed. Effectiveness was assessed by comparing pulmonary function tests (PFTs) closest to tacrolimus initiation to PFTs approximately 6–12 months later. Corticosteroid dose at these time points was also evaluated. We report adverse events attributed to tacrolimus. Seventeen patients with CTD-ILD were included in adverse event analysis; twelve were included in efficacy analysis. Length of tacrolimus therapy ranged from 6 to 110 months (mean 38.8 months ± 31.4). The mean improvement in percent predicted total lung capacity was 7.5% ± 11.7 (p=0.02). Forced vital capacity mean improvement was 7.4% ± 12.5 (p=0.06). The average decrease in corticosteroid dose at follow-up was 20.3mg ± 25.2 (p=0.02) with complete discontinuation in six patients. No patients experienced a life-threatening adverse event attributed to tacrolimus. Tacrolimus can be effective and is well tolerated as an adjunctive therapy and allows tapering of corticosteroids. PMID:26762710

  2. Silicon central pattern generators for cardiac diseases

    PubMed Central

    Nogaret, Alain; O'Callaghan, Erin L; Lataro, Renata M; Salgado, Helio C; Meliza, C Daniel; Duncan, Edward; Abarbanel, Henry D I; Paton, Julian F R

    2015-01-01

    Cardiac rhythm management devices provide therapies for both arrhythmias and resynchronisation but not heart failure, which affects millions of patients worldwide. This paper reviews recent advances in biophysics and mathematical engineering that provide a novel technological platform for addressing heart disease and enabling beat-to-beat adaptation of cardiac pacing in response to physiological feedback. The technology consists of silicon hardware central pattern generators (hCPGs) that may be trained to emulate accurately the dynamical response of biological central pattern generators (bCPGs). We discuss the limitations of present CPGs and appraise the advantages of analog over digital circuits for application in bioelectronic medicine. To test the system, we have focused on the cardio-respiratory oscillators in the medulla oblongata that modulate heart rate in phase with respiration to induce respiratory sinus arrhythmia (RSA). We describe here a novel, scalable hCPG comprising physiologically realistic (Hodgkin–Huxley type) neurones and synapses. Our hCPG comprises two neurones that antagonise each other to provide rhythmic motor drive to the vagus nerve to slow the heart. We show how recent advances in modelling allow the motor output to adapt to physiological feedback such as respiration. In rats, we report on the restoration of RSA using an hCPG that receives diaphragmatic electromyography input and use it to stimulate the vagus nerve at specific time points of the respiratory cycle to slow the heart rate. We have validated the adaptation of stimulation to alterations in respiratory rate. We demonstrate that the hCPG is tuneable in terms of the depth and timing of the RSA relative to respiratory phase. These pioneering studies will now permit an analysis of the physiological role of RSA as well as its any potential therapeutic use in cardiac disease. PMID:25433077

  3. Silicon central pattern generators for cardiac diseases.

    PubMed

    Nogaret, Alain; O'Callaghan, Erin L; Lataro, Renata M; Salgado, Helio C; Meliza, C Daniel; Duncan, Edward; Abarbanel, Henry D I; Paton, Julian F R

    2015-02-15

    Cardiac rhythm management devices provide therapies for both arrhythmias and resynchronisation but not heart failure, which affects millions of patients worldwide. This paper reviews recent advances in biophysics and mathematical engineering that provide a novel technological platform for addressing heart disease and enabling beat-to-beat adaptation of cardiac pacing in response to physiological feedback. The technology consists of silicon hardware central pattern generators (hCPGs) that may be trained to emulate accurately the dynamical response of biological central pattern generators (bCPGs). We discuss the limitations of present CPGs and appraise the advantages of analog over digital circuits for application in bioelectronic medicine. To test the system, we have focused on the cardio-respiratory oscillators in the medulla oblongata that modulate heart rate in phase with respiration to induce respiratory sinus arrhythmia (RSA). We describe here a novel, scalable hCPG comprising physiologically realistic (Hodgkin-Huxley type) neurones and synapses. Our hCPG comprises two neurones that antagonise each other to provide rhythmic motor drive to the vagus nerve to slow the heart. We show how recent advances in modelling allow the motor output to adapt to physiological feedback such as respiration. In rats, we report on the restoration of RSA using an hCPG that receives diaphragmatic electromyography input and use it to stimulate the vagus nerve at specific time points of the respiratory cycle to slow the heart rate. We have validated the adaptation of stimulation to alterations in respiratory rate. We demonstrate that the hCPG is tuneable in terms of the depth and timing of the RSA relative to respiratory phase. These pioneering studies will now permit an analysis of the physiological role of RSA as well as its any potential therapeutic use in cardiac disease.

  4. Blunted Hypoxic Pulmonary Vasoconstriction in Experimental Neonatal Chronic Lung Disease

    PubMed Central

    Rey-Parra, Gloria Juliana; Archer, Stephen L.; Bland, Richard D.; Albertine, Kurt H.; Carlton, David P.; Cho, Soo-Chul; Kirby, Beth; Haromy, Al; Eaton, Farah; Wu, Xichen; Thébaud, Bernard

    2008-01-01

    Rationale: Neonatal chronic lung disease (CLD), caused by prolonged mechanical ventilation (MV) with O2-rich gas, is the most common cause of long-term hospitalization and recurrent respiratory illness in extremely premature infants. Recurrent episodes of hypoxemia and associated ventilator adjustments often lead to worsening CLD. The mechanism that causes these hypoxemic episodes is unknown. Hypoxic pulmonary vasoconstriction (HPV), which is partially controlled by O2-sensitive voltage-gated potassium (Kv) channels, is an important adaptive response to local hypoxia that helps to match perfusion and ventilation in the lung. Objectives: To test the hypothesis that chronic lung injury (CLI) impairs HPV. Methods: We studied preterm lambs that had MV with O2-rich gas for 3 weeks and newborn rats that breathed 95%-O2 for 2 weeks, both of which resulted in airspace enlargement and pulmonary vascular changes consistent with CLD. Measurements and Main Results: HPV was attenuated in preterm lambs with CLI after 2 weeks of MV and in newborn rats with CLI after 2 weeks of hyperoxia. HPV and constriction to the Kv1.x-specific inhibitor, correolide, were preferentially blunted in excised distal pulmonary arteries (dPAs) from hyperoxic rats, whose dPAs exhibited decreased Kv1.5 and Kv2.1 mRNA and K+ current. Intrapulmonary gene transfer of Kv1.5, encoding the ion channel that is thought to trigger HPV, increased O2-sensitive K+ current in cultured smooth muscle cells from rat dPAs, and restored HPV in hyperoxic rats. Conclusions: Reduced expression/activity of O2-sensitive Kv channels in dPAs contributes to blunted HPV observed in neonatal CLD. PMID:18511704

  5. Severe pulmonary hypertension in lung disease: phenotypes and response to treatment.

    PubMed

    Brewis, Melanie J; Church, Alistair C; Johnson, Martin K; Peacock, Andrew J

    2015-11-01

    Pulmonary hypertension (PH) due to lung disease (World Health Organization (WHO) group 3) is common, but severe PH, arbitrarily defined as mean pulmonary artery pressure ≥35 mmHg is reported in only a small proportion. Whether these should be treated as patients in WHO group 1 (i.e. pulmonary arterial hypertension) with PH-targeted therapies is unknown. We compared the phenotypic characteristics and outcomes of 118 incident patients with severe PH and lung disease with 74 idiopathic pulmonary arterial hypertension (IPAH) patients, all treated with pulmonary vasodilators. Lung disease patients were older, more hypoxaemic, and had lower gas transfer, worse New York Heart Association functional class and lower 6-min walking distance (6MWD) than IPAH patients. Poorer survival in those with lung disease was driven by the interstitial lung disease (ILD) cohort. In contrast to IPAH, where significant improvements in 6MWD and N-terminal pro-brain natruiretic peptide (NT-proBNP) occurred, PH therapy in severe PH lung disease did not lead to improvement in 6MWD or functional class, but neither was deterioration seen. NT-proBNP decreased from 2200 to 1596 pg·mL(-1) (p=0.015). Response varied by lung disease phenotype, with poorer outcomes in patients with ILD and emphysema with preserved forced expiratory volume in 1 s. Further study is required to investigate whether vasodilator therapy may delay disease progression in severe PH with lung disease.

  6. Lung Transplant

    MedlinePlus

    Lung transplant Overview By Mayo Clinic Staff A lung transplant is a surgical procedure to replace a diseased or ... lung, usually from a deceased donor. A lung transplant is reserved for people who have tried other ...

  7. Advanced Therapeutic Strategies for Chronic Lung Disease Using Nanoparticle-Based Drug Delivery

    PubMed Central

    Yhee, Ji Young; Im, Jintaek; Nho, Richard Seonghun

    2016-01-01

    Chronic lung diseases include a variety of obstinate and fatal diseases, including asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), idiopathic pulmonary fibrosis (IPF), and lung cancers. Pharmacotherapy is important for the treatment of chronic lung diseases, and current progress in nanoparticles offers great potential as an advanced strategy for drug delivery. Based on their biophysical properties, nanoparticles have shown improved pharmacokinetics of therapeutics and controlled drug delivery, gaining great attention. Herein, we will review the nanoparticle-based drug delivery system for the treatment of chronic lung diseases. Various types of nanoparticles will be introduced, and recent innovative efforts to utilize the nanoparticles as novel drug carriers for the effective treatment of chronic lung diseases will also be discussed. PMID:27657144

  8. The Burden of Exposure–Related Diffuse Lung Disease

    PubMed Central

    Goldyn, Sheryl R.; Condos, Rany; Rom, William N.

    2013-01-01

    Estimating the burden of exposure-related diffuse lung disease in terms of health effects and economic burden remains challenging. Labor statistics are inadequate to define the scope of the problem, and few studies have analyzed the prevalence of exposure-related illnesses and the subsequent health care cost. Well-defined exposures, such as those associated with coal mines, asbestos mines, and stonecutting, have led to more accurate assessment of prevalence and cost. As governmental regulation of workplace exposure has increased, the prevalence of diseases such as silicosis and coal workers’ pneumoconiosis has diminished. However, the health and economic effects of diseases with long latency periods, such as asbestosis and mesothelioma, continue to increase in the short term. Newer exposures, such as those related to air pollution, nylon flock, and the World Trade Center collapse, have added to these costs. As a result, estimates of cost for occupational diseases, including respiratory illnesses, exceed $26 billion annually, and the true economic burden is likely much higher. PMID:19221957

  9. Recent Treatment of Interstitial Lung Disease with Idiopathic Inflammatory Myopathies

    PubMed Central

    Kawasumi, Hidenaga; Gono, Takahisa; Kawaguchi, Yasushi; Yamanaka, Hisashi

    2015-01-01

    Interstitial lung disease (ILD) is a prognostic factor for poor outcome in polymyositis (PM)/dermatomyositis (DM). The appropriate management of ILD is very important to improve the prognosis of patients with PM/DM. ILD activity and severity depend on the disease subtype. Therefore, clinicians should determine therapeutic strategies according to the disease subtype in each patient with PM/DM. Anti–melanoma differentiation-associated gene 5 antibody and hyperferritinemia predict the development and severity of rapidly progressive (RP) ILD, particularly in East Asian patients. Combination therapy with corticosteroids, intravenous cyclophosphamide pulse, and calcineurin inhibitors should be administered in RP-ILD. In contrast, patients with anti–aminoacyl-tRNA synthetase (ARS) show better responses to corticosteroids alone. However, ILDs with anti-ARS often display disease recurrence or become refractory to corticosteroid monotherapy. Recent studies have demonstrated that the administration of tacrolimus or rituximab in addition to corticosteroids may be considered in ILD patients with anti-ARS. Large-scale, multicenter randomized clinical trials should be conducted in the future to confirm that the aforementioned agents exhibit efficacy in ILD patients with PM/DM. The pathophysiology of ILD with PM/DM should also be elucidated in greater detail to develop effective therapeutic strategies for patients with ILD in PM/DM. PMID:26279636

  10. Speckle patterns during the spreading of lung surfactant

    NASA Astrophysics Data System (ADS)

    Llovera-González, Juan J.; Moreno-Yeras, Alfredo B.; Martínez-Muñoz, Diana M.; Ferreira, Marcia Zotti Justo; Shin Nishitani, Wagner; Almeida, Alexandre Barros; Alencar, Adriano M.; Muramatsu, Mikiya; Serra-Toledo, Rolando L.

    2013-11-01

    Pulmonary surfactant is a very important product in the medical treatment of the syndrome of insufficiency respiratory in neonates. The synthesis of this surfactant in labs need to optimize the rate of spreading in the alveolar interstitial liquid obtaining a monolayer of the phospholipids membrane base capable to maintains several of the dynamical properties of the respiratory system during breathing. The recover of theses mechanical properties has to be archived using the minimal quantities of product and with the optimal proteins composition (SP-B in special). In this paper we show our results of obtaining and process speckle pattern images of the spreading of phospholipids membrane composed the matrix of this product (DPPC) when physiologic interstitial liquid are presented.

  11. Polyamine intake, dietary pattern, and cardiovascular disease.

    PubMed

    Soda, Kuniyasu

    2010-09-01

    In addition to general lifestyle, a number of foods and dietary patterns, such as the Mediterranean diet (MD), are associated with lower incidences of chronic, age-related diseases, and mortality. We have shown that increased polyamine intake decreases age-associated pathology and increases longevity in mice. Several foods in the MD, such as fruits and legumes, are foods containing high amount of polyamines. Among age-associated conditions, cardiovascular diseases (CVD) are the leading cause of mortality worldwide, and individuals who adhere to a MD have a lower incidence of CVD. The possible contribution of increased polyamine intake to CVD prevention is discussed in this manuscript. Polyamines from food are distributed to all organs and tissues, and long-term intake increases polyamine concentration in blood. Because most polyamines are associated with red and white blood cells, they act to suppress synthesis of pro-inflammatory cytokines and of leukocyte function-associated antigen-1. Foods with anti-inflammatory properties such as n-3 polyunsaturated fatty acids are known to help prevent CVD. Additionally, suppression of de novo polyamine synthesis results from increased polyamines intake, normally synthesized from arginine. This in turn increases availability of arginine for synthesis of nitric oxide, which plays an important role in preserving normal vascular physiology.

  12. Effect of autoimmune diseases on risk and survival in histology-specific lung cancer.

    PubMed

    Hemminki, Kari; Liu, Xiangdong; Ji, Jianguang; Sundquist, Jan; Sundquist, Kristina

    2012-12-01

    Patients with autoimmune diseases are at an increased risk of cancer due to underlying dysregulation of the immune system or treatment. Data on cancer incidence, mortality and survival after autoimmune diseases would provide further information on the clinical implications. We systematically analysed data on lung cancer in patients diagnosed with 33 different autoimmune diseases. Standardised incidence ratios (SIRs), standardised mortality ratios (SMRs) and hazard ratios (HRs) were calculated for subsequent incident lung cancers or lung cancer deaths up to 2008 in patients hospitalised for autoimmune disease after 1964. Increased risks of lung cancer were recorded for SIRs after 12 autoimmune diseases, SMRs after 11 autoimmune diseases and HRs after two autoimmune diseases. The highest SIRs and SMRs, respectively, were seen after discoid lupus erythematosus (4.71 and 4.80), polymyosistis/dermatomyositis (4.20 and 4.17), systemic lupus erythematosus (2.47 and 2.69), rheumatic fever (2.07 and 2.07) and systemic sclerosis (2.19 and 1.98). Autoimmune disease did not influence survival overall but some autoimmune diseases appeared to impair survival in small cell carcinoma. All autoimmune diseases that had an SIR >2.0 are known to present with lung manifestations, suggesting that the autoimmune process contributes to lung cancer susceptibility. The data on survival are reassuring that autoimmune diseases do not influence prognosis in lung cancer.

  13. Effects of sildenafil on pulmonary hypertension and exercise tolerance in severe cystic fibrosis-related lung disease.

    PubMed

    Montgomery, Gregory S; Sagel, Scott D; Taylor, Amy L; Abman, Steven H

    2006-04-01

    Cystic fibrosis (CF) patients with advanced lung disease are at risk for developing pulmonary vascular disease and pulmonary hypertension, characterized by progressive exercise intolerance beyond the exercise-limiting effects of airways disease in CF. We report on a patient with severe CF lung disease who experienced clinically significant improvements in exercise tolerance and pulmonary hypertension without changing lung function during sildenafil therapy.

  14. DNA methylation in small cell lung cancer defines distinct disease subtypes and correlates with high expression of EZH2

    PubMed Central

    Poirier, John T.; Gardner, Eric E.; Connis, Nick; Moreira, Andre L.; de Stanchina, Elisa; Hann, Christine L.; Rudin, Charles M.

    2015-01-01

    Small cell lung cancer (SCLC) is an aggressive malignancy characterized by early metastasis, rapid development of resistance to chemotherapy, and genetic instability. This study profiles DNA methylation in SCLC, patient-derived xenografts (PDXs) and cell lines at single nucleotide resolution. DNA methylation patterns of primary samples are distinct from those of cell lines, while PDXs maintain a pattern closely consistent with primary samples. Clustering of DNA methylation and gene expression of primary SCLC revealed distinct disease subtypes among histologically indistinguishable primary patient samples with similar genetic alterations. SCLC is notable for dense clustering of high-level methylation in discrete promoter CpG islands, in a pattern clearly distinct from other lung cancers and strongly correlated with high expression of the E2F target and histone methyltransferase gene EZH2. Pharmacologic inhibition of EZH2 in a SCLC PDX markedly inhibited tumor growth. PMID:25746006

  15. DNA methylation in small cell lung cancer defines distinct disease subtypes and correlates with high expression of EZH2.

    PubMed

    Poirier, J T; Gardner, E E; Connis, N; Moreira, A L; de Stanchina, E; Hann, C L; Rudin, C M

    2015-11-26

    Small cell lung cancer (SCLC) is an aggressive malignancy characterized by early metastasis, rapid development of resistance to chemotherapy and genetic instability. This study profiles DNA methylation in SCLC, patient-derived xenografts (PDX) and cell lines at single-nucleotide resolution. DNA methylation patterns of primary samples are distinct from those of cell lines, whereas PDX maintain a pattern closely consistent with primary samples. Clustering of DNA methylation and gene expression of primary SCLC revealed distinct disease subtypes among histologically indistinguishable primary patient samples with similar genetic alterations. SCLC is notable for dense clustering of high-level methylation in discrete promoter CpG islands, in a pattern clearly distinct from other lung cancers and strongly correlated with high expression of the E2F target and histone methyltransferase gene EZH2. Pharmacologic inhibition of EZH2 in a SCLC PDX markedly inhibited tumor growth.

  16. Indoor air pollution from solid fuel use, chronic lung diseases and lung cancer in Harbin, Northeast China

    SciTech Connect

    Galeone, C.; Pelucchi, C.; La Vecchia, C.; Negri, E.; Bosetti, C.; Hu, J.F.

    2008-10-15

    In some areas of China, indoor air pollution (IAP) originating principally from the combustion of solid fuels has a relevant role in lung cancer. Most previous studies focused on the female population and only a few on both the sexes. We analyzed the relationship between IAP from solid fuel use and selected chronic lung diseases and lung cancer risk in Harbin, Northeast China, an area with a very high base line risk of lung cancer for both the sexes. We used data from a case-control study conducted between 1987 and 1990, including 218 patients with incident, histologically confirmed lung cancer and 436 controls admitted to the same hospitals as cases. We calculated an index of IAP from solid fuel use exposure using data on heating type, cooking fuel used, and house measurements. Cases reported more frequently than controls on exposure to coal fuel for house heating and/or cooking, and the odds ratio (OR) for ever versus never exposed was 2.19 (95% confidence interval (CI): 1.08-4.46). The ORs of lung cancer according to subsequent tertiles of IAP exposure index were 1.82 (95% CI: 1.14-2.89) and 1.99 (95% CI: 1.26-3.15) as compared with the lowest tertile. The ORs of lung cancer for participants with a history of chronic bronchitis and tuberculosis were 3.79 (95% CI: 2.38-6.02) and 3.82 (95% CI: 1.97-7.41), respectively. This study gives further support and quantification of the positive association between IAP, history of selected nonmalignant lung diseases, and lung cancer risk for both the sexes.

  17. Species pattern of phosphatidylinositol from lung surfactant and a comparison of the species pattern of phosphatidylinositol and phosphatidylglycerol synthesized de novo in lung microsomal fractions.

    PubMed Central

    Rüstow, B; Nakagawa, Y; Rabe, H; Waku, K; Kunze, D

    1988-01-01

    1. Phosphatidylinositol (PI) is a minor component of lung surfactant which may be able to replace the functionally important phosphatidylglycerol (PG) [Beppu, Clements & Goerke (1983) J. Appl. Physiol. 55, 496-502] without disturbing lung function. The dipalmitoyl species is one of the main species for both PI (14.4%) and PG (16.9%). Besides the C16:0--C16:0 species, the C16:0--C18:0, C16:0--C18:1, C16:0--C18:2 and C18:0--C18:1 species showed comparable proportions in the PG and PI fractions. These similarities of the species patterns and the acidic character of both phospholipids could explain why surfactant PG may be replaced by PI. 2. PI and PG were radiolabelled by incubation of microsomal fractions with [14C]glycerol 3-phosphate (Gro3P). For 11 out of 14 molecular species of PI and PG we measured comparable proportions of radioactivity. The radioactivity of these 11 species accounted together for more than 80% of the total. The addition of inositol to the incubation system decreased the incorporation in vitro of Gro3P into PG and CDP-DG (diacylglycerol) of lung microsomes (microsomal fractions), but did not change the distribution of radioactivity among the molecular species of PG. These results supported the idea that both acidic surfactant phospholipids may be synthesized de novo from a common CDP-DG pool in lung microsomes. PMID:3178759

  18. Dietary patterns of patients with advanced lung or colorectal cancer.

    PubMed

    Prado, Carla M M; Lieffers, Jessica R; Bergsten, Gabriella; Mourtzakis, Marina; Baracos, Vickie E; Reiman, Tony; Sawyer, Michael B; McCargar, Linda J

    2012-01-01

    The purpose of this study was to identify dietary patterns among patients with advanced cancer. Differences between cancer groups are described, and food groups contributing higher proportions to overall caloric intake are identified. Patients with advanced cancer (n=51) were recruited from a regional cancer centre and completed a three-day dietary record. Food items were categorized according to macronutrient content. After adjustment for body weight, substantial variation in energy intake was observed (range: 13.7 to 55.4 kcal/kg/day). For 49% of patients, protein intake was below recommendations. Overall, patients consumed the largest proportion of their calories from meat (16%), other foods (11%), dessert (9%), fruit (9%), white bread (7%), and milk (7%). Only 5% of patients consumed meal replacement supplements. The results of this descriptive study provide important insights into the dietary habits of patients with advanced cancer. These insights could be translated into the development of effective recommendations for maintaining or improving health and quality of life.

  19. Work-related lung disease surveillance report supplement 1992

    SciTech Connect

    Not Available

    1992-09-01

    The report supplements the 1991 Work Related Lung Disease Surveillance Report and contains figures and tables which expand the information provided in the 1991 document. Updated data were included for many of the figures and tables contained in the original report. Data on sex, race, geographic distribution, industry, and occupation extracted from the multiple cause of death data were presented for deaths with mention of asbestosis, malignant neoplasms of the pleura, malignant neoplasms of the peritoneum, coal workers' pneumoconiosis, silicosis, byssinosis, or hypersensitivity pneumonitis. Additionally, data from the National Hospital Discharge Survey on the number of discharges with silicosis or asbestosis, and data from the Sentinel Event Notification System for Occupational Risks program on reports of occupational asthma and silicosis were also included.

  20. Epidemiology of Lung Cancer

    PubMed Central

    Brock, Malcolm V.; Ford, Jean G.; Samet, Jonathan M.; Spivack, Simon D.

    2013-01-01

    Background: Ever since a lung cancer epidemic emerged in the mid-1900s, the epidemiology of lung cancer has been intensively investigated to characterize its causes and patterns of occurrence. This report summarizes the key findings of this research. Methods: A detailed literature search provided the basis for a narrative review, identifying and summarizing key reports on population patterns and factors that affect lung cancer risk. Results: Established environmental risk factors for lung cancer include smoking cigarettes and other tobacco products and exposure to secondhand tobacco smoke, occupational lung carcinogens, radiation, and indoor and outdoor air pollution. Cigarette smoking is the predominant cause of lung cancer and the leading worldwide cause of cancer death. Smoking prevalence in developing nations has increased, starting new lung cancer epidemics in these nations. A positive family history and acquired lung disease are examples of host factors that are clinically useful risk indicators. Risk prediction models based on lung cancer risk factors have been developed, but further refinement is needed to provide clinically useful risk stratification. Promising biomarkers of lung cancer risk and early detection have been identified, but none are ready for broad clinical application. Conclusions: Almost all lung cancer deaths are caused by cigarette smoking, underscoring the need for ongoing efforts at tobacco control throughout the world. Further research is needed into the reasons underlying lung cancer disparities, the causes of lung cancer in never smokers, the potential role of HIV in lung carcinogenesis, and the development of biomarkers. PMID:23649439

  1. Hydroxychloroquine in children with interstitial (diffuse parenchymal) lung diseases.

    PubMed

    Braun, Sarah; Ferner, Marion; Kronfeld, Kai; Griese, Matthias

    2015-04-01

    Hydroxychloroquine (HCQ) is one of the drugs frequently used for the treatment of interstitial lung disease (ILD) in children (chILD). This use is off-label and studies to analyze the effect and safety of HCQ in chILD are lacking. Therefore, a literature research on the usage of chloroquine (CQ) and HCQ in these conditions was done. Eighty-five case reports and small series in the period from 1984 to 2013 were identified in which children with different diagnoses of ILD were treated with CQ or HCQ, sometimes in combination with other medication including steroids. A favorable response to HCQ or CQ was reported in 35 cases, whereas in the other cases the effect was negative or not clear. The dose of HCQ used was between 5 and 10 mg/kg body weight/day (bw/d). No pharmacokinetic studies have been done. The side effect profile in children seemed to be similar to that in adults. Most often gastrointestinal symptoms were reported. Three patients were found developing retinal changes during the treatment with CQ, whereas in none of the patients treated with HCQ retinal changes were reported. Based on retrospective case reports and small series likely to be reported with bias, the use of HCQ in chILD might be classified as safe. As no prospective data on efficacy and safety of HCQ in chILD are available, systematic collection is necessary. This may be achieved by web-based registers like the European Management Platform for Childhood Interstitial Lung Diseases. Prospective and controlled investigations of HCQ in patients with chILD are mandatory.

  2. Recent lung cancer patterns in younger age-cohorts in Ireland

    PubMed Central

    Kabir, Zubair; Connolly, Gregory N; Clancy, Luke

    2007-01-01

    Background Smoking causes 85% of all lung cancers in males and 70% in females. Therefore, birth cohort analysis and annual-percent-changes (APC) in age-specific lung cancer mortality rates, particularly in the youngest age cohorts, can explain the beneficial impacts of both past and recent anti-smoking interventions. Methods A long-term time-trend analysis (1958-2002) in lung cancer mortality rates focusing on the youngest age-cohorts (30-49 years of age) in particular was investigated in Ireland. The rates were standardised to the World Standard Population. Lung cancer mortality data were downloaded from the WHO Cancer Mortality Database to estimate APCs in death rates, using the Joinpoint regression (version 3.0) program. A simple age-cohort modelling (log-linear Poisson model) was also done, using SAS software. Results The youngest birth cohorts (born after 1965) have almost one-fourth lower lung cancer risk relative to those born around the First World War. A more than 50% relative decline in death rates among those between 35 and 39 years of age was observed in both sexes in recent years. The youngest age-cohorts (30-39 years of age) in males also showed a significant decrease in death rates in 1998-2002 by more than 3% every five years from 1958-1962 onwards. However, death rate declines in females are slower. Conclusions The youngest birth cohorts had the lowest lung cancer risk and also showed a significant decreasing lung cancer death rate in the most recent years. Such temporal patterns indicate the beneficial impacts of both recent and past tobacco control efforts in Ireland. However, the decline in younger female cohorts is slower. A comprehensive national tobacco control program enforced on evidence-based policies elsewhere can further accelerate a decline in death rates, especially among the younger generations. PMID:17476821

  3. Correlation of Cough With Disease Activity and Treatment With Cyclophosphamide in Scleroderma Interstitial Lung Disease

    PubMed Central

    Tseng, Chi-Hong; Li, Ning; Elashoff, Robert M.; Tashkin, Donald P.

    2012-01-01

    Background: Cough is a significant symptom in patients with scleroderma interstitial lung disease (SSc-ILD), affecting 73% of the 158 patients enrolled in the Scleroderma Lung Study (SLS), a multicenter randomized trial of oral cyclophosphamide (CYC) vs placebo (PLA) in patients with active interstitial lung disease. Methods: We examined the correlation of cough frequency and severity and phlegm production at baseline in 156 SLS participants with other baseline variables representing SSc-ILD disease activity and the cough response to 1 year of treatment with CYC vs PLA. Results: Patients with cough at baseline had significantly lower diffusing capacity of the lung for carbon monoxide, dyspnea, the quality-of-life physical component summary, and the maximal fibrosis score on high-resolution CT imaging compared with those without cough at baseline. Cough severity and frequency correlated with FVC % predicted. After 12 months of treatment, cough frequency decreased in the CYC group compared with the PLA group and was significantly different from the PLA group at 18 months (6 months after discontinuation of CYC). However, the decreases in cough frequency did not correlate with the changes in FVC or diffusing capacity of the lung for carbon monoxide observed in the CYC group. Treatment-related improvements in cough frequency, as well as in FVC, were no longer apparent 12 months after discontinuation of CYC. Conclusions: Cough is a common symptom in SSc-ILD and correlates with the extent of fibrosis. Cough frequency decreases significantly in response to treatment with CYC but returns to baseline 1 year after withdrawal of treatment. Cough may be a symptom of ongoing fibrosis and an independent variable in assessing therapeutic response to CYC. Trial registry: ClinicalTrials.gov; No.: NCT000004563; URL: www.clinicaltrials.gov PMID:22156609

  4. Lung Transplantation in Gaucher Disease: A Learning Lesson in Trying to Avoid Both Scylla and Charybdis.

    PubMed

    de Boer, Geertje M; van Dussen, Laura; van den Toorn, Leon M; den Bakker, Michael A; Hoek, Rogier A S; Hesselink, Dennis A; Hollak, Carla E M; van Hal, Peter Th W

    2016-01-01

    Gaucher disease (GD), a lysosomal storage disorder, may result in end-stage lung disease. We report successful bilateral lung transplantation in a 49-year-old woman with GD complicated by severe pulmonary hypertension and fibrotic changes in the lungs. Before receiving the lung transplant, the patient was undergoing both enzyme replacement therapy (imiglucerase) and triple pulmonary hypertension treatment (epoprostenol, bosentan, and sildenafil). She had a history of splenectomy, severe bone disease, and renal involvement, all of which were related to GD and considered as relative contraindications for a lung transplantation. In the literature, lung transplantation has been suggested for severe pulmonary involvement in GD but has been reported only once in a child. To our knowledge, until now, no successful procedure has been reported in adults, and no reports deal with the severe potential posttransplantation complications specifically related to GD.

  5. Relative importance of cigarette smoking in occupational lung disease.

    PubMed Central

    Elmes, P C

    1981-01-01

    Since 1900 respiratory disease has remained a constant serious cause of chronic ill health and premature death in Britain. The falling importance of tuberculosis and pneumonia has been off-set by the rise in lung cancer. Bronchitis morbidity and mortality have fallen only slightly since 1935. To produce any real improvement in the future existing information as to cause must be studied. The relative contribution of occupational exposure is compared with the importance of cigarette smoking. Relevant information is scanty and has been produced to emphasise the existence of occupational diseases rather than assess their importance to the community as whole. In Britain the evidence is that within the coal mining and iron and steel industries conditions are now such that dust exposure contributes little to the morbidity or mortality compared with the workers' smoking habits. Similar results have been shown by a cross-sectional survey of many dusty occupations in Western Germany. Only in the disappearing Welsh slate industry has dust disease been at least as important as smoking. Until the current regulations were introduced conditions existed among asbestos workers such that the combined effect of cigarette smoking and dust exposure led to a loss of life expectation of over 10 years in moderate smokers. Since the new regulations were introduced the risk for asbestos workers should approximate to that for other industrial workers. While control of occupational exposure to respiratory hazards remains important, a far greater improvement to respiratory health would be produced by controlling tobacco smoking. PMID:7470398

  6. Neonatal developmental pattern of superoxide dismutase and aniline hydroxylase in rat lung

    SciTech Connect

    Kakkar, P.; Jaffery, F.N.; Viswanathan, P.N.

    1986-10-01

    The developmental biology of superoxide dismutase and aniline hydroxylase was followed in rat lungs from prenatal stage to 3 months old. Total superoxide dismutase activity as determined by spectrophotometry as well as electrophoresis was high in the prenatal rat lung, decreased in the first 24 hr postpartum, increased within 7 days, and then decreased gradually to adult levels. On polyacrylamide gel electrophoresis only two isozymic forms of superoxide dismutase were located as achromatic zones in the fetal lung. In the adult rat lung, there were three molecular forms of superoxide dismutase, two in the postmitochondrial supernatant and one in the mitochondrial fraction. Unlike superoxide dismutase, aniline hydroxylase was detectable only after 5 days of age and the activity exhibited a gradual increase afterward up to 1 month of age. The developmental pattern of superoxide dismutase and aniline hydroxylase activities in lung may be significant in understanding the mechanism of body defenses and their regulatory modulations in response to toxic air pollutants and environmental stress.

  7. Introduction of cryobiopsies in the diagnostics of interstitial lung diseases – experiences in a referral center

    PubMed Central

    Kronborg-White, Sissel; Folkersen, Birgitte; Rasmussen, Torben Riis; Voldby, Nina; Madsen, Line Bille; Rasmussen, Finn; Poletti, Venerino; Bendstrup, Elisabeth

    2017-01-01

    ABSTRACT Introduction: Transbronchial cryobiopsies (cTBB) has emerged as a new method for obtaining lung tissue biopsies in the diagnosis of interstitial lung diseases (ILDs). Until now, it has been used in a few highly specialized interventional centers and has shown promising results in obtaining a definite diagnosis of ILDs. Method: All patients undergoing a cTBB between November 2015 and June 2016 were included in this case series study. Data on patient demographics, high-resolution computed tomography patterns, size and number of biopsies, histology patterns, the contribution to a confident diagnosis and complications were registered. Results: Thirty-eight patients underwent cTBB in the period. cTBB contributed to the diagnosis in 28 (74%) of the 38 patients. Only few complications were observed; pneumothorax was the most frequent complication (10 patients, 26%). In six patients, local bleeding occurred during the procedure and was easily controlled by a Fogarty catheter balloon and in some cases tranexamic acid. Conclusion: Performing cTBB in the diagnostics of ILDs is a safe and feasible procedure. cTBB resulted in a confident diagnosis in 74% of cases. PMID:28326178

  8. [Diffuse lung disease: cause of persistent pulmonary hypertension before one year of age].

    PubMed

    Dicembrino, Manuela; Haag, Dora; Álvarez, Mariana; Díaz Cazaux, Agustina; Castaños, Claudio

    2016-06-01

    Pulmonary vascular disease in children is multifactorial and heterogeneous. While it shares some features with pulmonary hypertension in adults, there are differences in the associated comorbidities and conditions, the coexistence of genetic or developmental diseases. Interstitial lung diseases may be responsible for this entity. One is alveolar capillary dysplasia with misalignment of pulmonary veins, a rare pathology but with a mortality rate of 100%, characterized by a failure in the formation of lung tissue that eventually results in impaired gas diffusion. We present a 5-month-old patient studied due to suspected congenital heart disease with persistent hypoxemia; diagnosis was made through lung biopsy.

  9. Reproducible copy number variation patterns among single circulating tumor cells of lung cancer patients

    PubMed Central

    Ni, Xiaohui; Zhuo, Minglei; Su, Zhe; Duan, Jianchun; Gao, Yan; Wang, Zhijie; Zong, Chenghang; Bai, Hua; Chapman, Alec R.; Zhao, Jun; Xu, Liya; An, Tongtong; Ma, Qi; Wang, Yuyan; Wu, Meina; Sun, Yu; Wang, Shuhang; Li, Zhenxiang; Yang, Xiaodan; Yong, Jun; Su, Xiao-Dong; Lu, Youyong; Bai, Fan; Xie, X. Sunney; Wang, Jie

    2013-01-01

    Circulating tumor cells (CTCs) enter peripheral blood from primary tumors and seed metastases. The genome sequencing of CTCs could offer noninvasive prognosis or even diagnosis, but has been hampered by low single-cell genome coverage of scarce CTCs. Here, we report the use of the recently developed multiple annealing and looping-based amplification cycles for whole-genome amplification of single CTCs from lung cancer patients. We observed characteristic cancer-associated single-nucleotide variations and insertions/deletions in exomes of CTCs. These mutations provided information needed for individualized therapy, such as drug resistance and phenotypic transition, but were heterogeneous from cell to cell. In contrast, every CTC from an individual patient, regardless of the cancer subtypes, exhibited reproducible copy number variation (CNV) patterns, similar to those of the metastatic tumor of the same patient. Interestingly, different patients with the same lung cancer adenocarcinoma (ADC) shared similar CNV patterns in their CTCs. Even more interestingly, patients of small-cell lung cancer have CNV patterns distinctly different from those of ADC patients. Our finding suggests that CNVs at certain genomic loci are selected for the metastasis of cancer. The reproducibility of cancer-specific CNVs offers potential for CTC-based cancer diagnostics. PMID:24324171

  10. The COPD Assessment Test as a Prognostic Marker in Interstitial Lung Disease

    PubMed Central

    Someya, Fujiko; Nakagawa, Takao; Mugii, Naoki

    2016-01-01

    The chronic obstructive pulmonary disease (COPD) Assessment Test (CAT), which was developed to measure the health status of patients with COPD, was applied to patients with interstitial lung disease, aiming to examine the CAT as a predictor of outcome. Over a follow-up period of more than one year, 101 consecutive patients with interstitial lung disease were evaluated by the CAT. The CAT scores of 40 in total were categorized into four subsets according to the severity. Patients with higher (more severe) scores exhibited lower forced vital capacity and lung diffusion capacity for carbon monoxide. The survival rate was significantly lower in patients with higher scores (log-rank test, P = 0.0002), and the hazard ratios for death of the higher scores and lower lung diffusion capacity for carbon monoxide were independently significant. These findings suggest that CAT can indicate the risk of mortality in patients with interstitial lung disease. PMID:27812295

  11. [Cell senescence and pathophysiology of chronic lung diseases: role in chronic obstructive pulmonary disease].

    PubMed

    Adnot, Serge

    2014-01-01

    Knowledge of the biology of cellular senescence has improved markedly in recent years, helping us to understand the aging process. It is now clear that cellular senescence is involved in the pathogenesis of many age-related diseases, including respiratory diseases such as chronic obstructive pulmonary disease (COPD). COPD occupies a special place among chronic respiratory diseases because of its frequency and socio-economic impact. The high morbidity and mortality associated with COPD are related to multiple systemic manifestations independent of the severity of airway obstruction. COPD, although most often due to smoking, is also an aging-related respiratory disease. According to a newly developed concept, lung-cell senescence could play a key role in the pathophysiology of COPD, including remodeling of blood vessels and lung parenchyma, as well as the characteristic inflammatory process. Systemic manifestations of COPD, including cardiovascular disease, weight loss, bone demineralization and muscle dysfunction, may reflect a general process of premature aging secondary to the pulmonary changes.

  12. Respiratory rehabilitation in severe restrictive lung disease secondary to tuberculosis.

    PubMed

    Yang, G F; Alba, A; Lee, M

    1984-09-01

    There is a need for portable and less expensive devices for patients with chronic respiratory insufficiency. The case of a 44-year-old Hispanic woman is illustrative. The patient had severe restrictive lung disease secondary to right phrenic nerve crush/pneumoperitoneum and left pneumonectomy/decortication for bilateral lower lobe tuberculosis. In 1969, 12 years after her last operation, she developed dyspnea, coryza, and somnolence. She was hospitalized with a PaO2 of 30mmHg; PaCO2 of 77mmHg and a pH of 7.28. Pulmonary function tests showed alveolar hypoventilation and her resting ventilation was between 2.26 to 3.74L/min. Her vital capacity was 1130cc (37% of predicted value) and maximum breathing capacity was 36L/min (44% of predicted value). From 1969, she used a poncho (wraparound) ventilator for her long-term respiratory care and modified the poncho suit to meet her personal needs. In 1971, she discovered that a mouth intermittent positive pressure ventilation (MIPPV) method, often used by patients with neuromuscular disorders, was easier to apply. Since then, she has continued to use a Bantam Respirator with MIPPV and a lipguard/mouthpiece during the night, and the respirator with a mouthpiece for a few hours during the days. However, when she has an upper respiratory infection or feels tired, she finds that she needs the greater rest and comfort that the poncho provides. With the assistance of these two respiratory devices, she has been able to complete her education, marry, and lead a fulfilling life in the community. This patient is considered the first person with severe lung pathology to utilize MIPPV for sleep.

  13. Protease-activated receptors and prostaglandins in inflammatory lung disease

    PubMed Central

    Peters, Terence; Henry, Peter J

    2009-01-01

    Protease-activated receptors (PARs) are a novel family of G protein-coupled receptors. Signalling through PARs typically involves the cleavage of an extracellular region of the receptor by endogenous or exogenous proteases, which reveals a tethered ligand sequence capable of auto-activating the receptor. A considerable body of evidence has emerged over the past 20 years supporting a prominent role for PARs in a variety of human physiological and pathophysiological processes, and thus substantial attention has been directed towards developing drug-like molecules that activate or block PARs via non-proteolytic pathways. PARs are widely expressed within the respiratory tract, and their activation appears to exert significant modulatory influences on the level of bronchomotor tone, as well as on the inflammatory processes associated with a range of respiratory tract disorders. Nevertheless, there is debate as to whether the principal response to PAR activation is an augmentation or attenuation of airways inflammation. In this context, an important action of PAR activators may be to promote the generation and release of prostanoids, such as prostglandin E2, which have well-established anti-inflammatory effects in the lung. In this review, we primarily focus on the relationship between PARs, prostaglandins and inflammatory processes in the lung, and highlight their potential role in selected respiratory tract disorders, including pulmonary fibrosis, asthma and chronic obstructive pulmonary disease. This article is part of a themed issue on Mediators and Receptors in the Resolution of Inflammation. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009 PMID:19845685

  14. Lung cancer development in patients with connective tissue disease–related interstitial lung disease

    PubMed Central

    Enomoto, Yasunori; Inui, Naoki; Yoshimura, Katsuhiro; Nishimoto, Koji; Mori, Kazutaka; Kono, Masato; Fujisawa, Tomoyuki; Enomoto, Noriyuki; Nakamura, Yutaro; Iwashita, Toshihide; Suda, Takafumi

    2016-01-01

    Abstract Previous studies have reported that patients with idiopathic pulmonary fibrosis occasionally develop lung cancer (LC). However, in connective tissue disease (CTD)-related interstitial lung disease (ILD), there are few data regarding the LC development. The aim of the present study was to evaluate the clinical significance of LC development in patients with CTD-ILD. A retrospective review of our database of 562 patients with ILD between 2000 and 2014 identified 127 patients diagnosed with CTD-ILD. The overall and cumulative incidences of LC were calculated. In addition, the risk factors and prognostic impact of LC development were evaluated. The median age at the ILD diagnosis was 63 years (range 37–84 years), and 73 patients (57.5%) were female. The median follow-up period from the ILD diagnosis was 67.4 months (range 10.4–322.1 months). During the period, 7 out of the 127 patients developed LC (overall incidence 5.5%). The cumulative incidences at 1, 3, and 5 years were 0.0%, 1.8%, and 2.9%, respectively. The risk of LC development was significantly higher in patients with higher smoking pack-year (odds ratio [OR] 1.028; 95% confidence interval [CI] 1.008–1.049; P = 0.007) and emphysema on chest high-resolution computed tomography (OR 14.667; 95% CI 2.871–74.926; P = 0.001). The median overall survival time after developing LC was 7.0 months (95% CI 4.9–9.1 months), and the most common cause of death was LC, not ILD. According to the Cox proportional hazard model analysis with time-dependent covariates, patients who developed LC showed significantly poorer prognosis than those who did not (hazard ratio 87.86; 95% CI 19.56–394.67; P < 0.001). In CTD-ILD, clinicians should be careful with the risk of LC development in patients with a heavy smoking history and subsequent emphysema. Although not so frequent, the complication could be a poor prognostic determinant. PMID:27977621

  15. Interstitial lung disease in an adult with Fanconi anemia: Clues to the pathogenesis

    SciTech Connect

    Rubinstein, W.S.; Wenger, S.L.; Hoffman, R.M.

    1997-03-31

    We have studied a 38-year-old man with a prior diagnosis of Holt-Oram syndrome, who presented with diabetes mellitus. He had recently taken prednisone for idiopathic interstitial lung disease and trimethoprim-sulfamethoxazole for sinusitis. Thrombocytopenia progressed to pancytopenia. The patient had skeletal, cardiac, renal, cutaneous, endocrine, hepatic, neurologic, and hematologic manifestations of Fanconi anemia (FA). Chest radiographs showed increased interstitial markings at age 25, dyspnea began in his late 20s, and he stopped smoking at age 32. At age 38, computerized tomography showed bilateral upper lobe fibrosis, lower lobe honeycombing, and bronchiectasis. Pulmonary function tests, compromised at age 29, showed a moderately severe obstructive and restrictive pattern by age 38. Serum alpha-1 antitrypsin level was 224 (normal 85-213) mg/dL and PI phenotype was M1. Karyotype was 46,X-Y with a marked increase in chromosome aberrations induced in vitro by diepoxybutane. The early onset and degree of pulmonary disease in this patient cannot be fully explained by environmental or known genetic causes. The International Fanconi Anemia Registry (IFAR) contains no example of a similar pulmonary presentation. Gene-environment (ecogenetic) interactions in FA seem evident in the final phenotype. The pathogenic mechanism of lung involvement in FA may relate to oxidative injury and cytokine anomalies. 49 refs., 2 figs., 1 tab.

  16. Treatment of rheumatoid arthritis-associated interstitial lung disease: a perspective review

    PubMed Central

    Iqbal, Kundan; Kelly, Clive

    2015-01-01

    Rheumatoid arthritis (RA) is a systemic autoimmune disease affecting 0.5–1% of the worldwide population. Whilst predominantly causing chronic pain and inflammation in synovial joints, it is also associated with significant extra-articular manifestations in a large proportion of patients. Among the various pulmonary manifestations, interstitial lung disease (ILD), a progressive fibrotic disease of the lung parenchyma, is the commonest and most important, contributing significantly to increased morbidity and mortality. The most frequent patterns of RA-associated ILD (RA-ILD) are usual interstitial pneumonia and nonspecific interstitial pneumonia. New insights during the past several years have highlighted the epidemiological impact of RA-ILD and have begun to identify factors contributing to its pathogenesis. Risk factors include smoking, male sex, human leukocyte antigen haplotype, rheumatoid factor and anticyclic citrullinated protein antibodies (ACPAs). Combined with clinical information, chest examination and pulmonary function testing, high-resolution computed tomography of the chest forms the basis of investigation and allows assessment of subtype and disease extent. The management of RA-ILD is a challenge. Several therapeutic agents have been suggested in the literature but as yet no large randomized controlled trials have been undertaken to guide clinical management. Therapy is further complicated by commonly prescribed drugs of proven articular benefit such as methotrexate, leflunomide (LEF) and anti-tumour necrosis factor α agents having been implicated in both ex novo occurrence and acceleration of existing ILD. Agents that offer promise include immunomodulators such as mycophenolate and rituximab as well as newly studied antifibrotic agents. In this review, we discuss the current literature to evaluate recommendations for the management of RA-ILD and discuss key gaps in our knowledge of this important disease. PMID:26622326

  17. Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension: Pulmonary hypertension due to lung diseases and/or hypoxia.

    PubMed

    Sakkijha, Husam; Idrees, Majdy M

    2014-07-01

    Chronic lung diseases are common causes of pulmonary hypertension. It ranks second after the left heart disease. Both obstructive and restrictive lung diseases are know to cause pulmonary hypertension. The pathophysiology of the disease is complex, and includes factors affecting the blood vessels, airways, and lung parenchyma. Hypoxia and the inhalation of toxic materials are another contributing factors. Recent guidelines have further clarified the association between pulmonary hypertension and chronic lung disease and made general guidelines concerning the diagnosis and management. In this article, we will provide a detailed revision about the new classification and give general recommendations about the management of pulmonary hypertension in chronic lung diseases.

  18. Understanding nontuberculous mycobacterial lung disease: it’s been a long time coming

    PubMed Central

    Griffith, David E.; Aksamit, Timothy R.

    2016-01-01

    With a surprising predictability, most studies and reviews addressing therapy for nontuberculous mycobacterial (NTM) lung disease either start or end by mentioning the paucity of data from randomized and controlled trials. That is a legitimate criticism for NTM lung disease therapy, but it also somehow seems to influence attitudes toward all aspects of NTM investigation. Certainly the study of NTM diseases in general and NTM lung disease in particular is a recent development. Previously, NTM were viewed as minor, if inconvenient, pathogens similar to Mycobacterium tuberculosis. However, over the last three decades, NTM have emerged as increasingly important pathogens that are clearly different compared with tuberculosis. Although there has been frustratingly slow progress in the treatment of NTM diseases, in contrast there has unquestionably been impressive progress in almost every other realm of investigation into NTM disease. Our understanding of NTM lung disease a) pathophysiology, including mechanisms of organism acquisition, b) epidemiology, including estimates of disease prevalence, c) mycobacteriology, including application of molecular laboratory techniques and matrix-assisted laser desorption ionization–time of flight (MALDI–TOF) mass spectrometry, and d) even treatment strategies, including the recognition of innate drug resistance mechanisms, has immeasurably and permanently changed and advanced the landscape for NTM lung disease. It is no longer necessary to apologize for the state of NTM lung disease knowledge and understanding, but rather it is time to recognize the great distance we have travelled over the last 30 years. PMID:27990278

  19. Early rheumatoid disease. II. Patterns of joint involvement.

    PubMed Central

    Fleming, A; Benn, R T; Corbett, M; Wood, P H

    1976-01-01

    Data from the first research clinic visit (Fleming and others, 1976) have been subjected to factor analysis to identify early patterns of joint involvement. Nine patterns emerged. Two patterns, if present early, were found to have prognostic significance. An eventually more severe disease was associated with a pattern of large joint involvement (shoulder, elbow, wrist, knee) and a pattern based on metatarsophalangeal joints I and III. PMID:970995

  20. Isolated IgG4-related interstitial lung disease: unusual histological and radiological features of a pathologically proven case.

    PubMed

    Wibmer, Thomas; Kropf-Sanchen, Cornelia; Rüdiger, Stefan; Blanta, Ioanna; Stoiber, Kathrin M; Rottbauer, Wolfgang; Schumann, Christian

    2013-03-19

    IgG4-related lung disease is commonly associated with autoimmune pancreatitis. Recently, isolated IgG4-related interstitial lung disease (ILD) without other organ involvement has newly been reported in two cases with clinical features of nonspecific interstitial pneumonitis (NSIP).We report the first case of an isolated IgG4-related ILD in a 78-year-old man with dry cough and dyspnea, whose clinical findings proved to be different from NSIP. Serum IgG4 levels were increased. Chest CT scan revealed bilateral consolidations especially in the lower lobes, enlarged mediastinal and hilar lymph nodes and pleural effusions. Video-assisted thoracoscopic (VATS) lung biopsy revealed a pattern similar to usual interstitial pneumonia (UIP) and an abundant IgG4-positive plasma cell infiltration. He was effectively treated by steroid therapy.Increasing recognition of IgG4 related diseases has led to a growing number of new entities. The novel concept of isolated IgG4-related ILD as a pulmonary manifestation of a systemic IgG4-related disorder should be taken into account as a possible differential diagnosis of ILD and mass-forming lesions, even when no other organ manifestation is clinically apparent at the time of diagnosis. Lung specific diagnostic criteria and algorithms are required to enhance diagnostic accuracy in cases of possible IgG4-related ILD.

  1. Isolated IgG4-related interstitial lung disease: unusual histological and radiological features of a pathologically proven case

    PubMed Central

    2013-01-01

    IgG4-related lung disease is commonly associated with autoimmune pancreatitis. Recently, isolated IgG4-related interstitial lung disease (ILD) without other organ involvement has newly been reported in two cases with clinical features of nonspecific interstitial pneumonitis (NSIP). We report the first case of an isolated IgG4-related ILD in a 78-year-old man with dry cough and dyspnea, whose clinical findings proved to be different from NSIP. Serum IgG4 levels were increased. Chest CT scan revealed bilateral consolidations especially in the lower lobes, enlarged mediastinal and hilar lymph nodes and pleural effusions. Video-assisted thoracoscopic (VATS) lung biopsy revealed a pattern similar to usual interstitial pneumonia (UIP) and an abundant IgG4-positive plasma cell infiltration. He was effectively treated by steroid therapy. Increasing recognition of IgG4 related diseases has led to a growing number of new entities. The novel concept of isolated IgG4-related ILD as a pulmonary manifestation of a systemic IgG4-related disorder should be taken into account as a possible differential diagnosis of ILD and mass-forming lesions, even when no other organ manifestation is clinically apparent at the time of diagnosis. Lung specific diagnostic criteria and algorithms are required to enhance diagnostic accuracy in cases of possible IgG4-related ILD. PMID:23509921

  2. Inadequate Palliative Care in Chronic Lung Disease. An Issue of Health Care Inequality

    PubMed Central

    Jecker, Nancy S.

    2016-01-01

    Patients with chronic lung diseases suffer higher symptom burden, lower quality of life, and greater social isolation compared with patients with other diagnoses, such as cancer. These conditions may be alleviated by palliative care, yet palliative care is used less by patients with chronic lung disease compared with patients with cancer. Underuse is due, in part, to poor implementation of primary palliative care and inadequate referral to specialty palliative care. Lack of primary and specialty palliative care in patients with chronic lung disease falls short of the minimum standard of competent health care, and represents a disparity in health care and a social injustice. We invoke the ethical principles of justice and sufficiency to highlight the importance of this issue. We identify five barriers to implementing palliative care in patients with chronic lung disease: uncertainty in prognosis; lack of provider skill to engage in discussions about palliative care; fear of using opioids among patients with chronic lung disease; fear of diminishing hope; and perceived and implicit bias against patients with smoking-related lung diseases. We propose mechanisms for improving implementation of palliative care for patients with chronic lung disease with the goal of enhancing justice in health care. PMID:26730490

  3. Bronchocentric granulomatosis with extensive cystic lung disease in tuberculosis: An unusual presentation

    PubMed Central

    Periwal, Pallavi; Khanna, Arjun; Gothi, Rajesh; Talwar, Deepak

    2016-01-01

    Tuberculosis is known to cause both cystic lung disease and bronchocentric granulomatosis (BCG). However, both are rare manifestations of this common disease. We report a case of BCG with extensive cystic lung disease in a young female who presented with fever, weight loss, and recurrent pneumothoraces with respiratory failure. Early diagnosis and treatment are imperative, as appropriate therapy may be life-saving in such cases. PMID:27185999

  4. Branching patterns emerge in a mathematical model of the dynamics of lung development.

    PubMed

    Guo, Yina; Chen, Ting-Hsuan; Zeng, Xingjuan; Warburton, David; Boström, Kristina I; Ho, Chih-Ming; Zhao, Xin; Garfinkel, Alan

    2014-01-15

    Recent experimental work has described an elegant pattern of branching in the development of the lung. Multiple forms of branching have been identified, including side branching and tip bifurcation. A particularly interesting feature is the phenomenon of 'orthogonal rotation of the branching plane'. The lung must fill 3D space with the essentially 2D phenomenon of branching. It accomplishes this by rotating the branching plane by 90° with each generation. The mechanisms underlying this rotation are not understood. In general, the programmes that underlie branching have been hypothetically attributed to genetic 'subroutines' under the control of a 'global master routine' to invoke particular subroutines at the proper time and location, but the mechanisms of these routines are not known. Here, we demonstrate that fundamental mechanisms, the reaction and diffusion of biochemical morphogens, can create these patterns. We used a partial differential equation model that postulates three morphogens, which we identify with specific molecules in lung development. We found that cascades of branching events, including side branching, tip splitting and orthogonal rotation of the branching plane, all emerge immediately from the model, without further assumptions. In addition, we found that one branching mode can be easily switched to another, by increasing or decreasing the values of key parameters. This shows how a 'global master routine' could work by the alteration of a single parameter. Being able to simulate cascades of branching events is necessary to understand the critical features of branching, such as orthogonal rotation of the branching plane between successive generations, and branching mode switch during lung development. Thus, our model provides a paradigm for how genes could possibly act to produce these spatial structures. Our low-dimensional model gives a qualitative understanding of how generic physiological mechanisms can produce branching phenomena, and how

  5. Pathologic and Radiologic Correlation of Adult Cystic Lung Disease: A Comprehensive Review

    PubMed Central

    Parimi, Vamsi; Taddonio, Michale; Kane, Joshua Robert; Yeldandi, Anjana

    2017-01-01

    The presence of pulmonary parenchymal cysts on computed tomography (CT) imaging presents a significant diagnostic challenge. The diverse range of possible etiologies can usually be differentiated based on the clinical setting and radiologic features. In fact, the advent of high-resolution CT has facilitated making a diagnosis solely on analysis of CT image patterns, thus averting the need for a biopsy. While it is possible to make a fairly specific diagnosis during early stages of disease evolution by its characteristic radiological presentation, distinct features may progress to temporally converge into relatively nonspecific radiologic presentations sometimes necessitating histological examination to make a diagnosis. The aim of this review study is to provide both the pathologist and the radiologist with an overview of the diseases most commonly associated with cystic lung lesions primarily in adults by illustration and description of pathologic and radiologic features of each entity. Brief descriptions and characteristic radiologic features of the various disease entities are included and illustrative examples are provided for the common majority of them. In this article, we also classify pulmonary cystic disease with an emphasis on the pathophysiology behind cyst formation in an attempt to elucidate the characteristics of similar cystic appearances seen in various disease entities. PMID:28270943

  6. Intensive care unit (ICU) readmission after major lung resection: Prevalence, patterns, and mortality

    PubMed Central

    Jung, Jae Jun; Cho, Jong Ho; Hong, Tae Hee; Kim, Hong Kwan; Choi, Yong Soo; Kim, Jhingook; Shim, Young Mog

    2016-01-01

    Background The aim of this study was to identify risk factors associated with mortality in patients re‐admitted to an intensive care unit (ICU) after initial recovery from major lung resection. Methods We retrospectively reviewed the case records of all patients who underwent major lung resection between February 2011 and May 2013. A total of 1916 patients underwent major resection surgery for various lung diseases, 63 (3.3%) of which required ICU admission after initial recovery. We analyzed preoperative and perioperative data, including ICU factors and outcomes. Results The patient group included 57 men (90.5%) with a mean age of 65.3 years. Pathologic diagnosis was malignancy in 92.1% of patients, while 7.9% had benign disease. Open thoracotomy was performed in 84.1%, whereas minimally invasive approaches were performed in 15.9%. In‐hospital mortality occurred in 16 (25.4%) patients. Patients were classified as either survivors (n = 47, 74.6%) or non‐survivors (n = 16, 25.4%). The most common reason for ICU readmission was pulmonary complication (n = 50, 79.4%). Thirty‐one patients (49.2%) required mechanical ventilation, seven (11.1%) required extracorporeal membrane oxygenation, and three (4.8%) required renal support. Multivariate analysis showed that acute respiratory distress syndrome (ARDS) and delirium were independent risk factors for in‐hospital mortality. In addition, delirium frequently occurred in patients with ARDS. Conclusion ARDS and delirium were independent risk factors for in‐hospital mortality in patients who were readmitted to the ICU after major lung resection. Future studies are needed to determine if the prevention of delirium and ARDS can improve postoperative outcomes for patients with lung cancer. PMID:27925393

  7. Pulmonary hypertension in the course of diffuse parenchymal lung diseases - state of art and future considerations.

    PubMed

    Szturmowicz, Monika; Kacprzak, Aneta; Błasińska-Przerwa, Katarzyna; Kuś, Jan

    2015-01-01

    Lung diseases are one of the most frequent causes of pulmonary hypertension (PH). The development of PH influences the course of lung disease, worsening the clinical symptoms and prognosis. According to the most recent publications, PH in the course of lung diseases develops as a result of both "parenchymal" and vascular pathology, in the patients with genetic predisposition. Prolonged infection (especially viral one) may be an additional promoting factor. Right heart catheterization (RHC), which is an invasive procedure, is the only objective method of diagnosing PH. According to the latest recommendations, the management algorithm of PH and coexisting interstitial lung disease is based on RHC and the results of pulmonary function tests. Majority of the patients develop mild PH in the course of advanced lung disease. Best treatment of underlying lung pathology combined with long term oxygen treatment is recommended in this group. In case of severe PH (mean resting pulmonary artery pressure (mPAP) ≥ 35 mm Hg) the alternate cause of PH has to be sought. PAH-specific drugs use should be limited to patients with severe PH participating in clinical trials. In this review, the value of various non-invasive methods (echocardiography, radiological examination, exercise capacity and brain natriuretic peptides assessment) in the process of screening for PH is presented, and the results of recent randomized clinical trials with PAH-specific drugs in patients with diffuse parenchymal lung diseases are discussed.

  8. Relationship Between Diseased Lung Tissues on Computed Tomography and Motion of Fiducial Marker Near Lung Cancer

    SciTech Connect

    Onodera, Yuya; Nishioka, Noriko; Yasuda, Koichi; Fujima, Noriyuki; Torres, Mylin; Kamishima, Tamotsu; Ooyama, Noriko; Onimaru, Rikiya; Terae, Satoshi; Ooizumi, Satoshi; Nishimura, Masaharu; Shirato, Hiroki

    2011-04-01

    Purpose: For lung cancer patients with poor pulmonary function because of emphysema or fibrosis, it is important to predict the amplitude of internal tumor motion to minimize the irradiation of the functioning lung tissue before undergoing stereotactic body radiotherapy. Methods and Materials: Two board-certified diagnostic radiologists independently assessed the degree of pulmonary emphysema and fibrosis on computed tomography scans in 71 patients with peripheral lung tumors before real-time tumor-tracking radiotherapy. The relationships between the computed tomography findings of the lung parenchyma and the motion of the fiducial marker near the lung tumor were investigated. Of the 71 patients, 30 had normal pulmonary function, and 29 had obstructive pulmonary dysfunction (forced expiratory volume in 1 s/forced vital capacity ratio of <70%), 6 patients had constrictive dysfunction (percentage of vital capacity <80%), and 16 had mixed dysfunction. Results: The upper region was associated with smaller tumor motion, as expected (p = .0004), and the presence of fibrosis (p = .088) and pleural tumor contact (p = .086) were weakly associated with tumor motion. The presence of fibrotic changes in the lung tissue was associated with smaller tumor motion in the upper region (p <.05) but not in the lower region. The findings of emphysema and pulmonary function tests were not associated with tumor motion. Conclusion: Tumors in the upper lung region with fibrotic changes have smaller motion than those in the upper region of the lungs without fibrotic changes. The tumor motion in the lower lung region was not significantly different between patients with and without lung fibrosis. Emphysema was not associated with the amplitude of tumor motion.

  9. Drug-induced interstitial lung disease: mechanisms and best diagnostic approaches.

    PubMed

    Matsuno, Osamu

    2012-05-31

    Drug-induced interstitial lung disease (DILD) is not uncommon and has many clinical patterns, ranging from benign infiltrates to life-threatening acute respiratory distress syndrome. There are two mechanisms involved in DILD, which are probably interdependent: one is direct, dose-dependent toxicity and the other is immune-mediated. Cytotoxic lung injury may result from direct injury to pneumocytes or the alveolar capillary endothelium. Drugs can induce all types of immunological reactions described by Gell and Coombs; however, most reactions in immune-mediated DILD may be T cell-mediated. DILD can be difficult to diagnose; diagnosis is often possible by exclusion alone. Identifying the causative drug that induces an allergy or cytotoxicity is essential for preventing secondary reactions. One method to confirm the diagnosis of a drug-induced disease is re-exposure or re-test of the drug. However, clinicians are reluctant to place patients at further risk of illness, particularly in cases with severe drug-induced diseases. Assessment of cell-mediated immunity has recently increased, because verifying the presence or absence of drug-sensitized lymphocytes can aid in confirmation of drug-induced disease. Using peripheral blood samples from drug-allergic patients, the drug-induced lymphocyte stimulation test (DLST) and the leukocyte migration test (LMT) can detect the presence of drug-sensitized T cells. However, these tests do not have a definite role in the diagnosis of DILD. This study explores the potential of these new tests and other similar tests in the diagnosis of DILD and provides a review of the relevant literature on this topic.

  10. Asbestos-induced lung disease in small-scale clutch manufacturing workers

    PubMed Central

    Gothi, Dipti; Gahlot, Tanushree; Sah, Ram B.; Saxena, Mayank; Ojha, U. C.; Verma, Anand K.; Spalgais, Sonam

    2016-01-01

    Background: The crocidolite variety of asbestos is banned. However, chrysotile, which is not prohibited, is still used in developing countries in making products such as clutch plate. Fourteen workers from a small-scale clutch plate-manufacturing factory were analyzed for asbestos-induced lung disease as one of their colleagues had expired due to asbestosis. Aims: This study was conducted to evaluate the awareness of workers, the prevalence and type of asbestos-induced lung disease, and the sensitivity and specificity of diffusion test. Materials and Methods: History, examination, chest radiograph, spirometry with diffusion, and high resolution computed tomography (HRCT) thorax was performed in all the workers. The diagnosis of asbestos-induced lung disease was suspected on the basis of HRCT. This was subsequently confirmed on transbronchial lung biopsy (TBLB). Results: None of the workers had detailed information about asbestos and its ill effects. Eleven out of 14 (71.42%) workers had asbestos-induced lung disease. All 11 had small airway disease (SAD). Three had SAD alone, 6 had additional interstitial lung disease (ILD), and 2 patients had additional ILD and chronic obstructive pulmonary disease. Sensitivity and specificity of residual volume (RV) or total lung capacity (TLC) for detecting SAD was 90% and 100%, respectively, and that of diffusion capacity of lung for carbon monoxide (DLCO) for detecting ILD was 100%. Conclusion: The awareness about asbestos in small-scale clutch-plate manufacturing industry is poor. The usage of chrysotile should be strictly regulated as morbidity and mortality is high. DLCO and RV/TLC are sensitive and specific in detecting nonmalignant asbestos induced lung disease. PMID:28194083

  11. Biomarkers and Autoantibodies of Interstitial Lung Disease with Idiopathic Inflammatory Myopathies

    PubMed Central

    Yoshifuji, Hajime

    2015-01-01

    Various autoantibodies are seen in idiopathic inflammatory myopathies. Among myositis-specific antibodies, anti-aminoacyl-tRNA synthetase and anti-melanoma differentiation-associated protein 5 (MDA5) antibodies are associated with interstitial lung disease (ILD). Anti-MDA5 antibodies are associated with dermatomyositis (DM) or clinically amyopathic DM complicated with rapidly progressive ILD. In anti-MDA5-positive patients, a random ground-glass attenuation pattern is a characteristic finding of ILD in chest high-resolution computed tomography. Conversely, anti-aminoacyl-tRNA synthetase antibodies are not associated with rapidly progressive ILD but with chronic ILD. DM or clinically amyopathic DM patients with anti-MDA5, and characteristic high-resolution computed tomography findings are highly likely to have devastating ILD and need aggressive treatment. PMID:27081322

  12. Metabolomics provide new insights on lung cancer staging and discrimination from chronic obstructive pulmonary disease.

    PubMed

    Deja, Stanislaw; Porebska, Irena; Kowal, Aneta; Zabek, Adam; Barg, Wojciech; Pawelczyk, Konrad; Stanimirova, Ivana; Daszykowski, Michal; Korzeniewska, Anna; Jankowska, Renata; Mlynarz, Piotr

    2014-11-01

    Chronic obstructive pulmonary disease (COPD) and lung cancer are widespread lung diseases. Cigarette smoking is a high risk factor for both the diseases. COPD may increase the risk of developing lung cancer. Thus, it is crucial to be able to distinguish between these two pathological states, especially considering the early stages of lung cancer. Novel diagnostic and monitoring tools are required to properly determine lung cancer progression because this information directly impacts the type of the treatment prescribed. In this study, serum samples collected from 22 COPD and 77 lung cancer (TNM stages I, II, III, and IV) patients were analyzed. Then, a collection of NMR metabolic fingerprints was modeled using discriminant orthogonal partial least squares regression (OPLS-DA) and further interpreted by univariate statistics. The constructed discriminant models helped to successfully distinguish between the metabolic fingerprints of COPD and lung cancer patients (AUC training=0.972, AUC test=0.993), COPD and early lung cancer patients (AUC training=1.000, AUC test=1.000), and COPD and advanced lung cancer patients (AUC training=0.983, AUC test=1.000). Decreased acetate, citrate, and methanol levels together with the increased N-acetylated glycoproteins, leucine, lysine, mannose, choline, and lipid (CH3-(CH2)n-) levels were observed in all lung cancer patients compared with the COPD group. The evaluation of lung cancer progression was also successful using OPLS-DA (AUC training=0.811, AUC test=0.904). Based on the results, the following metabolite biomarkers may prove useful in distinguishing lung cancer states: isoleucine, acetoacetate, and creatine as well as the two NMR signals of N-acetylated glycoproteins and glycerol.

  13. Occupational lung diseases: from old and novel exposures to effective preventive strategies.

    PubMed

    Cullinan, Paul; Muñoz, Xavier; Suojalehto, Hille; Agius, Raymond; Jindal, Surinder; Sigsgaard, Torben; Blomberg, Anders; Charpin, Denis; Annesi-Maesano, Isabella; Gulati, Mridu; Kim, Yangho; Frank, Arthur L; Akgün, Metin; Fishwick, David; de la Hoz, Rafael E; Moitra, Subhabrata

    2017-01-06

    Occupational exposure is an important, global cause of respiratory disease. Unlike many other non-communicable lung diseases, the proximal causes of many occupational lung diseases are well understood and they should be amenable to control with use of established and effective approaches. Therefore, the risks arising from exposure to silica and asbestos are well known, as are the means of their prevention. Although the incidence of occupational lung disease has decreased in many countries, in parts of the world undergoing rapid economic transition and population growth-often with large informal and unregulated workforces-occupational exposures continue to impose a heavy burden of disease. The incidence of interstitial and malignant lung diseases remains unacceptably high because control measures are not implemented or exposures arise in novel ways. With the advent of innovative technologies, new threats are continually introduced to the workplace (eg, indium compounds and vicinal diketones). In developed countries, work-related asthma is the commonest occupational lung disease of short latency. Although generic control measures to reduce the risk of developing or exacerbating asthma are well recognised, there is still uncertainty, for example, with regards to the management of workers who develop asthma but remain in the same job. In this Review, we provide recommendations for research, surveillance, and other action for reducing the burden of occupational lung diseases.

  14. Is air travel safe for those with lung disease?

    PubMed

    Coker, R K; Shiner, R J; Partridge, M R

    2007-12-01

    Airlines commonly report respiratory in-flight emergencies; flight outcomes have not been examined prospectively in large numbers of respiratory patients. The current authors conducted a prospective, observational study of flight outcomes in this group. UK respiratory specialists were invited to recruit patients planning air travel. Centres undertook their usual pre-flight assessment. Within 2 weeks of returning, patients completed a questionnaire documenting symptoms, in-flight oxygen use and unscheduled healthcare use. In total, 616 patients were recruited. Of these, 500 (81%) returned questionnaires. The most common diagnoses were airway (54%) and diffuse parenchymal lung disease (23%). In total, 12 patients died, seven before flying and five within 1 month. Pre-flight assessment included oximetry (96%), spirometry (95%), hypoxic challenge (45%) and walk test (10%). Of the patients, 11% did not fly. In those who flew, unscheduled respiratory healthcare use increased from 9% in the 4 weeks prior to travel to 19% in the 4 weeks after travel. However, when compared with self-reported data during the preceding year, medical consultations increased by just 2%. In patients flying after careful respiratory specialist assessment, commercial air travel appears generally safe.

  15. Ethics and decision making in end stage lung disease.

    PubMed

    Simonds, A K

    2003-03-01

    Most physicians believe they do more good than harm, and these duties of helping and not harming the patient are rooted in the Hippocratic oath, the good Samaritan tradition, and the Order of the Knight Hospitallers founded in the 11th century to care for pilgrims and those wounded in the Crusades.(1) In recent times the simple principles of beneficence and non-maleficence have been augmented and sometimes challenged by a rising awareness of patient/consumer rights, and the public expectation of greater involvement in medical, social and scientific affairs which affect them. In a publicly funded healthcare system in which rationing (explicit or otherwise) is inevitable, the additional concepts of utility and distributive justice can easily come into conflict with the individual's right to autonomy. Possible treatment options for end stage lung disease include transplantation and long term invasive ventilation which are challenging in resource terms. Other interventions such as pulmonary rehabilitation and palliative care are relatively low cost but not uniformly accessible.

  16. Rat models of asthma and chronic obstructive lung disease.

    PubMed

    Martin, James G; Tamaoka, Meiyo

    2006-01-01

    The rat has been extensively used to model asthma and somewhat less extensively to model chronic obstructive pulmonary disease (COPD). The features of asthma that have been successfully modeled include allergen-induced airway constriction, eosinophilic inflammation and allergen-induced airway hyperresponsiveness. T-cell involvement has been directly demonstrated using adoptive transfer techniques. Both CD4+ and CD8+ T cells are activated in response to allergen challenge in the sensitized rat and express Thelper2 cytokines (IL-4, IL-5 and IL-13). Repeated allergen exposure causes airway remodeling. Dry gas hyperpnea challenge also evokes increases in lung resistance, allowing exercise-induced asthma to be modeled. COPD is modeled using elastase-induced parenchymal injury to mimic emphysema. Cigarette smoke-induced airspace enlargement occurs but requires months of cigarette exposure. Inflammation and fibrosis of peripheral airways is an important aspect of COPD that is less well modeled. Novel approaches to the treatment of COPD have been reported including treatments aimed at parenchymal regeneration.

  17. Nanoparticle diffusion in respiratory mucus from humans without lung disease

    PubMed Central

    Schuster, Benjamin S.; Suk, Jung Soo; Woodworth, Graeme F.; Hanes, Justin

    2013-01-01

    A major role of respiratory mucus is to trap inhaled particles, including pathogens and environmental particulates, to limit body exposure. Despite the tremendous health implications, how particle size and surface chemistry affect mobility in respiratory mucus from humans without lung disease is not known. We prepared polymeric nanoparticles densely coated with low molecular weight polyethylene glycol (PEG) to minimize muco-adhesion, and compared their transport to that of uncoated particles in human respiratory mucus, which we collected from the endotracheal tubes of surgical patients with no respiratory comorbidities. We found that 100 and 200 nm diameter PEG-coated particles rapidly penetrated respiratory mucus, at rates exceeding their uncoated counterparts by approximately 15- and 35-fold, respectively. In contrast, PEG-coated particles ≥ 500 nm in diameter were sterically immobilized by the mucus mesh. Thus, even though respiratory mucus is a viscoelastic solid at the macroscopic level (as measured using a bulk rheometer), nanoparticles that are sufficiently small and muco-inert can penetrate the mucus as if it were primarily a viscous liquid. These findings help elucidate the barrier properties of respiratory mucus and provide design criteria for therapeutic nanoparticles capable of penetrating mucus to approach the underlying airway epithelium. PMID:23384790

  18. Alpha-1-Antitrypsin Deficiency in Serbian Adults with Lung Diseases

    PubMed Central

    Stankovic, Marija; Divac-Rankov, Aleksandra; Petrovic-Stanojevic, Natasa; Mitic-Milikic, Marija; Nagorni-Obradovic, Ljudmila; Radojkovic, Dragica

    2012-01-01

    Aim: Alpha-1-antitrypsin (A1AT) is the main inhibitor of neutrophil elastase, and severe alpha-1-antitrypsin deficiency (A1ATD) is a genetic risk factor for early-onset emphysema. Despite the relatively high prevalence of A1ATD, this condition is frequently underdiagnosed. Our aim was to determine the distribution of the A1ATD phenotypes/alleles in patients with lung diseases as well as in the Serbian population. Methods: The study included the adults with chronic obstructive pulmonary disease (COPD) (n=348), asthma (n=71), and bronchiectasis (n=35); the control was 1435 healthy blood donors. The A1ATD variants were identified by isoelectric focusing or polymerase chain reaction-mediated site-directed mutagenesis. Results: PiMZ heterozygotes, PiZZ homozygotes, and Z allele carriers are associated with significantly higher risk of developing COPD than healthy individuals (odds ratios 3.43, 42.42, and 5.49 respectively). The calculated prevalence of PiZZ, PiMZ, and PiSZ was higher in patients with COPD (1:202, 1:8, and 1:1243) than in the Serbian population (1:5519, 1:38, and 1:5519). Conclusion: The high prevalence of A1ATD phenotypes/allele in our population has confirmed the necessity of screening for A1ATD in patients with COPD. On the other hand, on the basis of the estimated number of those with A1ATD among the COPD patients, it is possible to assess the diagnostic efficiency of A1ATD in the Serbian population. PMID:22971141

  19. A prospective cohort study among new Chinese coal miners: the early pattern of lung function change

    PubMed Central

    Wang, M; Wu, Z; Du, Q; Petsonk, E; Peng, K; Li, Y; Li, S; Han, G; Atffield, M

    2005-01-01

    Aims: To investigate the early pattern of longitudinal change in forced expiratory volume in 1 second (FEV1) among new Chinese coal miners, and the relation between coal mine dust exposure and the decline of lung function. Methods: The early pattern of lung function changes in 317 newly hired Chinese underground coal miners was compared to 132 referents. This three year prospective cohort study involved a pre-employment and 15 follow up health surveys, including a questionnaire and spirometry tests. Twice a month, total and respirable dust area sampling was done. The authors used a two stage analysis and a linear mixed effects model approach to analyse the longitudinal spirometry data, and to investigate the changes in FEV1 over time, controlling for age, height, pack years of smoking, mean respirable dust concentration, the room temperature during testing, and the groupxtime interaction terms. Results: FEV1 change over time in new miners is non-linear. New miners experience initial rapid FEV1 declines, primarily during the first year of mining, little change during the second year, and partial recovery during the third year. Both linear and quadratic time trends in FEV1 change are highly significant. Smoking miners lost more FEV1 than non-smokers. Referents, all age less than 20 years, showed continued lung growth, whereas the miners who were under age 20 exhibited a decline in FEV1. Conclusion: Dust and smoking affect lung function in young, newly hired Chinese coal miners. FEV1 change over the first three years of employment is non-linear. The findings have implications for both methods and interpretation of medical screening in coal mining and other dusty work: during the first several years of employment more frequent testing may be desirable, and caution is required in interpreting early FEV1 declines. PMID:16234407

  20. Elemental analysis of occupational and environmental lung diseases by electron probe microanalyzer with wavelength dispersive spectrometer.

    PubMed

    Takada, Toshinori; Moriyama, Hiroshi; Suzuki, Eiichi

    2014-01-01

    Occupational and environmental lung diseases are a group of pulmonary disorders caused by inhalation of harmful particles, mists, vapors or gases. Mineralogical analysis is not generally required in the diagnosis of most cases of these diseases. Apart from minerals that are encountered rarely or only in specific occupations, small quantities of mineral dusts are present in the healthy lung. As such when mineralogical analysis is required, quantitative or semi-quantitative methods must be employed. An electron probe microanalyzer with wavelength dispersive spectrometer (EPMA-WDS) enables analysis of human lung tissue for deposits of elements by both qualitative and semi-quantitative methods. Since 1993, we have analyzed 162 cases of suspected occupational and environmental lung diseases using an EPMA-WDS. Our institute has been accepting online requests for elemental analysis of lung tissue samples by EPMA-WDS since January 2011. Hard metal lung disease is an occupational interstitial lung disease that primarily affects workers exposed to the dust of tungsten carbide. The characteristic pathological findings of the disease are giant cell interstitial pneumonia (GIP) with centrilobular fibrosis, surrounded by mild alveolitis with giant cells within the alveolar space. EPMA-WDS analysis of biopsied lung tissue from patients with GIP has demonstrated that tungsten and/or cobalt is distributed in the giant cells and centrilobular fibrosing lesion in GIP. Pneumoconiosis, caused by amorphous silica, and acute interstitial pneumonia, associated with the giant tsunami, were also elementally analyzed by EPMA-WDS. The results suggest that commonly found elements, such as silicon, aluminum, and iron, may cause occupational and environmental lung diseases.

  1. [Epidemiological, clinical and evolutionary peculiarities of interstitial lung disease in systemic sclerosis].

    PubMed

    Aydi, Z; Rachdi, I; Ben Dhaou, B; Dridi, M; Daoud, F; Baili, L; Boussema, F

    2016-04-01

    Pulmonary involvement during systemic sclerosis (SS) is dominated by interstitial lung disease and arterial pulmonary hypertension. It is about a retrospective study analyzing 65 cases of SS over a period of 13 years. We compared cases with and without interstitial lung disease. The diagnosis of SS was retained according to American College of Rheumatology (ACR)/EULAR 2013 criteria. The diagnosis of interstitial lung disease was retained in TDM and EFR. Pulmonary hypertension is defined by a pulmonary arterial pression higher than 25 mmHg. The mean delay of diagnosis of interstitial lung disease and the diagnosis was of 48 months (extremes 0-78 months). The comparison between both groups according to average age of the patients, prevalence of pulmonary hypertension, frequency of Raynaud phenomenon and trophic disorders did not find any significant difference. Lung involvement was associated with an esophageal involvement in 71% of the cases (P=0.059). Antibodies anti-Scl 70 were noted more frequently in patient's with interstitial lung disease (79% of the cases, P=0.001). Patients were treated with colchicine and vitamin E. A corticotherapy had been indicated at a single patient. The evolution of SS was marked by the stabilisation of the restrictive syndrome in 71.8% of the cases and a worsening in 25% of the cases. Early and appropriate diagnosis of SS and screening of lung involvement are essential for a early care.

  2. Breath analysis system for early detection of lung diseases based on multi-sensor array

    NASA Astrophysics Data System (ADS)

    Jeon, Jin-Young; Yu, Joon-Boo; Shin, Jeong-Suk; Byun, Hyung-Gi; Lim, Jeong-Ok

    2013-05-01

    Expiratory breath contains various VOCs(Volatile Organic Compounds) produced from the human. When a certain disease exists, the exhalation has specific VOCs which may be generated from diseases. Many researchers have been actively working to find different types of biomarkers which are characteristic for particular diseases. Research regarding the identification of specific diseases from exhalation is still in progress. The aim of this research is to implement early detection of lung disease such as lung cancer and COPD(Chronic Obstructive Pulmonary Disease), which was nominated on the 6th of domestic death rate in 2010, based on multi-sensor array system. The system has been used to acquire sampled expiratory gases data and PCA(Principle Component Analysis) technique was applied to analyze signals from multi-sensor array. Throughout the experimental trials, a clearly distinguishable difference between lung disease patients and healthy controls was found from the measurement and analysis of their respective expiratory gases.

  3. Role of macrophage migration inhibitory factor in age-related lung disease.

    PubMed

    Sauler, Maor; Bucala, Richard; Lee, Patty J

    2015-07-01

    The prevalence of many common respiratory disorders, including pneumonia, chronic obstructive lung disease, pulmonary fibrosis, and lung cancer, increases with age. Little is known of the host factors that may predispose individuals to such diseases. Macrophage migration inhibitory factor (MIF) is a potent upstream regulator of the immune system. MIF is encoded by variant alleles that occur commonly in the population. In addition to its role as a proinflammatory cytokine, a growing body of literature demonstrates that MIF influences diverse molecular processes important for the maintenance of cellular homeostasis and may influence the incidence or clinical manifestations of a variety of chronic lung diseases. This review highlights the biological properties of MIF and its implication in age-related lung disease.

  4. Assessment of interstitial lung disease in Sjögren's syndrome by lung ultrasound: a pilot study of correlation with high-resolution chest tomography.

    PubMed

    Vasco, Pablo Guisado; de Luna Cardenal, Gonzalo; Garrido, Isabel Martín; Pinilla, José Manuel Luque; Rodríguez, Guadalupe Fraile; Mateo, Juan José Nava; Ruiz, Daniel Carnevalli

    2016-11-29

    The background of this study is to assess the accuracy of lung ultrasound (LUS) to diagnose interstitial lung disease (ILD) in Sjögren's syndrome (Sjs), in patients who have any alterations in pulmonary function tests (PFT) or respiratory symptoms. LUS was correlated with chest tomography (hrCT), considering it as the imaging gold standard technique to diagnose ILD. This is a pilot, multicenter, cross-sectional, and consecutive-case study. The inclusion criteria are ≥18 years old, Signs and symptoms: according to ACEG 2002 criteria, respiratory symptoms (dyspnea, cough), or any alterations in PFR. LUS was done following the International Consensus Conference on Lung Ultrasound protocol for interstitial syndrome (B pattern). Of the 50 patients in follow-up, 13 (26%) met the inclusion criteria. All were women with age 63.62 years (range 39-88). 78.6% of the cases had primary Sjs (SLE, RA, n = 2). The intra-rater reliability k is 1, according to Gwet's Ac1 and GI index (probability to concordance-e(K)-, by Cohen, of 0.52). LUS has a sensitivity of 1 (95% CI 0.398-1.0), specificity of 0.89 (95% CI 0.518-0.997), and a positive probability reason of 9.00 (95% CI 7.1-11.3) to detect ILD. The correlation of Pearson is r = 0.84 (p < 0.001). To check the accuracy of LUS to diagnose ILD, a completely bilateral criterion of yes/no for interstitial pattern was chosen, AUC reaches significance, 0.94 (0.07) (95% CI 0.81-1.0, p = 0.014). LUS reaches an excellent correlation to hrCT in Sjs affected with ILD, and might be a useful technique in daily clinical practice for the assessment of pulmonary disease in the sicca syndrome.

  5. Prenatal and Perinatal Determinants of Lung Health and Disease in Early Life: A National Heart, Lung, and Blood Institute Workshop Report.

    PubMed

    Manuck, Tracy A; Levy, Philip T; Gyamfi-Bannerman, Cynthia; Jobe, Alan H; Blaisdell, Carol J

    2016-05-02

    Human lung growth and development begins with preconception exposures and continues through conception and childhood into early adulthood. Numerous environmental exposures (both positive and negative) can affect lung health and disease throughout life. Infant lung health correlates with adult lung function, but significant knowledge gaps exist regarding the influence of preconception, perinatal, and postnatal exposures on general lung health throughout life. On October 1 and 2, 2015, the National Heart, Lung, and Blood Institute convened a group of extramural investigators to develop their recommendations for the direction(s) for future research in prenatal and perinatal determinants of lung health and disease in early life and to identify opportunities for scientific advancement. They identified that future investigations will need not only to examine abnormal lung development, but also to use developing technology and resources to better define normal and/or enhanced lung health. Birth cohort studies offer key opportunities to capture the important influence of preconception and obstetric risk factors on lung health, development, and disease. These studies should include well-characterized obstetrical data and comprehensive plans for prospective follow-up. The importance of continued basic science, translational, and animal studies for providing mechanisms to explain causality using new methods cannot be overemphasized. Multidisciplinary approaches involving obstetricians, neonatologists, pediatric and adult pulmonologists, and basic scientists should be encouraged to design and conduct comprehensive and impactful research on the early stages of normal and abnormal human lung growth that influence adult outcome.

  6. Dietary influences on chronic obstructive lung disease and asthma: a review of the epidemiological evidence.

    PubMed

    Smit, H A; Grievink, L; Tabak, C

    1999-05-01

    The epidemiological evidence for a relationship between diet and indicators of asthma and chronic obstructive pulmonary disease (COPD) is evaluated. The review focuses on the intake of Na, n-3 fatty acids, and antioxidant vitamins as well as fruit and vegetables. Experimental studies suggest that a high-Na diet has a small adverse effect on airway reactivity in asthma patients. However, observational studies provide no clear evidence that high Na intake has adverse effects on airway reactivity or asthma symptoms in open populations. n-3 Polyunsaturated fatty acids, which are present in fish oils, are metabolized into less broncho-constricting and inflammatory mediators than n-6 polyunsaturated fatty acids. Studies in the general adult population suggest that a high fish intake has a beneficial effect on lung function, but the relationship with respiratory symptoms and clinically-manifest asthma or COPD is less evident. Also, experimental studies in asthma patients have not demonstrated an improvement in asthma severity after supplementations with fish oil. Several studies showed a beneficial association between fruit and vegetable intake and lung function, but the relationship with respiratory symptoms and the clinically-manifest disease was less convincing. A similar pattern was found for vitamin C in relation to indicators of asthma and COPD, but there are still conflicting results with respect to vitamin E and beta-carotene. In conclusion, the epidemiological evidence for a beneficial effect on indicators of asthma and COPD of eating fish, fruit and vegetables is increasing. However, the effectiveness of dietary supplementation in open-population samples is often not demonstrated. Several unresolved questions are raised, which should be addressed in future studies on the relationship between diet and respiratory disease.

  7. Comorbidity Patterns in Patients with Chronic Diseases in General Practice

    PubMed Central

    García-Olmos, Luis; Salvador, Carlos H.; Alberquilla, Ángel; Lora, David; Carmona, Montserrat; García-Sagredo, Pilar; Pascual, Mario; Muñoz, Adolfo; Monteagudo, José Luis; García-López, Fernando

    2012-01-01

    Introduction Healthcare management is oriented toward single diseases, yet multimorbidity is nevertheless the rule and there is a tendency for certain diseases to occur in clusters. This study sought to identify comorbidity patterns in patients with chronic diseases, by reference to number of comorbidities, age and sex, in a population receiving medical care from 129 general practitioners in Spain, in 2007. Methods A cross-sectional study was conducted in a health-area setting of the Madrid Autonomous Region (Comunidad Autónoma), covering a population of 198,670 individuals aged over 14 years. Multiple correspondences were analyzed to identify the clustering patterns of the conditions targeted. Results Forty-two percent (95% confidence interval [CI]: 41.8–42.2) of the registered population had at least one chronic condition. In all, 24.5% (95% CI: 24.3–24.6) of the population presented with multimorbidity. In the correspondence analysis, 98.3% of the total information was accounted for by three dimensions. The following four, age- and sex-related comorbidity patterns were identified: pattern B, showing a high comorbidity rate; pattern C, showing a low comorbidity rate; and two patterns, A and D, showing intermediate comorbidity rates. Conclusions Four comorbidity patterns could be identified which grouped diseases as follows: one showing diseases with a high comorbidity burden; one showing diseases with a low comorbidity burden; and two showing diseases with an intermediate comorbidity burden. PMID:22359665

  8. Therapeutic prospects to treat skeletal muscle wasting in COPD (chronic obstructive lung disease).

    PubMed

    Hansen, Michelle J; Gualano, Rosa C; Bozinovski, Steve; Vlahos, Ross; Anderson, Gary P

    2006-01-01

    Chronic obstructive pulmonary disease (COPD) is an incurable group of lung diseases characterised by progressive airflow limitation and loss of lung function, which lead to profound disability. It is mostly caused by cigarette smoke. Although COPD is one of the most prevalent diseases worldwide and its incidence is increasing, current therapies do little to improve the condition. Much current research focuses on strategies to halt the accelerated rate of decline in lung function that occurs in the disease. However, as most symptoms occur when the lungs are already extensively and irreversibly damaged, it is uncertain whether an agent able to slow or halt decline in lung function would actually provide relief to COPD patients. As lung function worsens, systemic comorbidities contribute markedly to disability. Loss of lean body mass (skeletal muscle) has recently been identified as a major determinant of disability in COPD and an independent predictor of mortality. In contrast to lung structure damage, skeletal muscle retains regenerative capacity in COPD. In this review, we discuss mechanisms of wasting in COPD, focusing on therapeutic strategies that might improve the health and productive life expectancy of COPD patients by improving skeletal muscle mass and function. Single or combination approaches exploiting the suppression of procatabolic inflammatory mediators, inhibition of ubiquitin ligases, repletion of anabolic hormones and growth factors, inhibition of myoblast apoptosis, remediation of systemic oxidative stress and promotion of repair, and regeneration via stimulation of satellite cell differentiation hold considerable therapeutic promise.

  9. Ganciclovir-resistant, cytomegalic interstitial lung disease in a patient with systemic lupus erythematosus.

    PubMed

    Finger, Eduardo; Romaldini, Helio; Lewi, David Salomão; Scheinberg, Morton Aaron

    2007-10-01

    A patient with systemic lupus erythematosus developed interstitial lung disease initially felt to be a manifestation of the disease but that, on further workup, proved to be a manifestation of cytomegalic disease resistant to ganciclovir. Treatment with foscarnet was associated with prompt improvement.

  10. Vitamin D and Chronic Lung Disease: A Review of Molecular Mechanisms and Clinical Studies12

    PubMed Central

    Finklea, James D.; Grossmann, Ruth E.; Tangpricha, Vin

    2011-01-01

    Vitamin D is classically recognized for its role in calcium homeostasis and skeletal metabolism. Over the last few decades, vitamin D deficiency has increased in prevalence in adults and children. Potential extraskeletal effects of vitamin D have been under investigation for several diseases. Several cross-sectional studies have associated lower vitamin D status with decreased lung function. This finding has prompted investigators to examine the association of vitamin D deficiency with several chronic lung diseases. One major focus has been the link between maternal vitamin D status and childhood asthma. Vitamin D deficiency has also been associated with increased risk of respiratory infection from influenza A and Mycobacterium tuberculosis. Other chronic respiratory diseases associated with vitamin D deficiency include cystic fibrosis, interstitial lung disease, and chronic obstructive pulmonary disease. This review will examine the current clinical literature and potential mechanisms of vitamin D in various pulmonary diseases. PMID:22332056

  11. Prognostic Factors for Myositis-Associated Interstitial Lung Disease

    PubMed Central

    Fujisawa, Tomoyuki; Hozumi, Hironao; Kono, Masato; Enomoto, Noriyuki; Hashimoto, Dai; Nakamura, Yutaro; Inui, Naoki; Yokomura, Koshi; Koshimizu, Naoki; Toyoshima, Mikio; Shirai, Toshihiro; Yasuda, Kazumasa; Hayakawa, Hiroshi; Suda, Takafumi

    2014-01-01

    Background Interstitial lung disease (ILD) is a common manifestation of polymyositis (PM), dermatomyositis (DM), and clinically amyopathic dermatomyositis (CADM); however, little is known about the factors influencing the prognosis for PM/DM/CADM-associated ILD. (PM/DM/CADM-ILD). The aim of the present study is to assess prognostic factors for PM/DM/CADM-ILD. Methods The clinical features and survival of 114 consecutive patients diagnosed with PM/DM/CADM-ILD (39 men and 75 women; median age, 56 years) were analyzed retrospectively. Results The study group included 30 PM-associated ILD, 41 DM-associated ILD, and 43 CADM-associated ILD cases. The clinical presentation of ILD was acute/subacute form in 59 patients (51.8%) and chronic form in 55 patients (48.2%). The major pulmonary symptoms were dyspnea, cough, and fever. High-resolution computed tomography frequently revealed ground-glass opacities, traction bronchiectasis, and consolidation. Most of the patients were treated with corticosteroids or corticosteroids in combination with immunosuppressive agents. The all-cause mortality was 27.2%. Acute/subacute form, % forced vital capacity (FVC), age, % of neutrophils in bronchoalveolar lavage (BAL) fluid, and a diagnosis of CADM (vs. PM) were significantly associated with poor outcome in univariate Cox proportional hazards models. Multivariate Cox proportional hazards analysis validated acute/subacute ILD, %FVC, age, and diagnosis of CADM (vs. PM) as significant predictors of overall mortality. Patients with acute/subacute ILD had a much lower survival rate than those with the chronic form (p<0.001). Patients with CADM-ILD had a lower survival rate than those with PM-ILD (p = 0.034). Conclusions Acute/subacute form, older age, lower level of FVC and diagnosis of CADM predict poor outcome in PM/DM/CADM-ILD. PMID:24905449

  12. Chest physiotherapy in preterm infants with lung diseases

    PubMed Central

    2010-01-01

    Background In neonatology the role of chest physiotherapy is still uncertain because of the controversial outcomes. Methods The aim of this study was to test the applicability in preterm infants of 'reflex rolling', from the Vojta method, in preterm neonates with lung pathology, with particular attention to the effects on blood gases and oxygen saturation, on the spontaneous breathing, on the onset of stress or pain. The study included 34 preterm newborns with mean gestational age of 30.5 (1.6) weeks - mean (DS) - and birth weight of 1430 (423) g - mean (DS) -, who suffered from hyaline membrane disease, under treatment with nasal CPAP (continuous positive airways pressure), or from pneumonia, under treatment with oxygen-therapy. The neonates underwent phase 1 of 'reflex rolling' according to Vojta method three times daily. Respiratory rate, SatO2, transcutaneous PtcCO2 e PtcO2 were monitored; in order to evaluate the onset of stress or pain following the stimulations, the NIPS score and the PIPP score were recorded; cerebral ultrasound scans were performed on postnatal days 1-3-5-7, and then weekly. Results In this population the first phase of Vojta's 'reflex rolling' caused an increase of PtcO2 and SatO2 values. No negative effects on PtcCO2 and respiratory rate were observed, NIPS and PIPP stress scores remained unmodified during the treatment; in no patient the intraventricular haemorrhage worsened in time and none of the infants developed periventricular leucomalacia. Conclusions Our experience, using the Vojta method, allows to affirm that this method is safe for preterm neonates, but further investigations are necessary to confirm its positive effects and to evaluate long-term respiratory outcomes. PMID:20868518

  13. Prenatal predictors of chronic lung disease in very preterm infants

    PubMed Central

    Henderson‐Smart, D J; Hutchinson, J L; Donoghue, D A; Evans, N J; Simpson, J M; Wright, I

    2006-01-01

    Objective To identify prenatal risk factors for chronic lung disease (CLD) at 36 weeks postmenstrual age in very preterm infants. Population Data were collected prospectively as part of the ongoing audit of the Australian and New Zealand Neonatal Network (ANZNN) of all infants born at less than 32 weeks gestation admitted to all tertiary neonatal intensive care units in Australia and New Zealand. Methods Prenatal factors up to 1 minute of age were examined in the subset of infants born at gestational ages 22–31 weeks during 1998–2001, and who survived to 36 weeks postmenstrual age (n = 11 453). Factors that were significantly associated with CLD at 36 weeks were entered into a multivariate logistic regression model. Results After adjustment, low gestational age was the dominant risk factor, with an approximate doubling of the odds with each week of decreasing gestational age from 31 to less than 25 weeks (trend p<0.0001). Birth weight for gestational age also had a dose‐response effect: the lower the birth weight for gestational age, the greater the risk, with infants below the third centile having 5.67 times greater odds of CLD than those between the 25th and 75th centile (trend p<0.0001). There was also a significantly increased risk for male infants (odds ratio 1.51 (95% confidence interval 1.36 to 1.68), p<0.0001). Conclusions These population based data show that the prenatal factors low gestational age, low birth weight for gestational age, and male sex significantly predict the development of chronic respiratory insufficiency in very preterm infants and may assist clinical decision about delivery. PMID:16131530

  14. Stem cells, cell therapies, and bioengineering in lung biology and diseases. Comprehensive review of the recent literature 2010-2012.

    PubMed

    Weiss, Daniel J

    2013-10-01

    A conference, "Stem Cells and Cell Therapies in Lung Biology and Lung Diseases," was held July 25 to 28, 2011 at the University of Vermont to review the current understanding of the role of stem and progenitor cells in lung repair after injury and to review the current status of cell therapy and ex vivo bioengineering approaches for lung diseases. These are rapidly expanding areas of study that provide further insight into and challenge traditional views of mechanisms of lung repair after injury and pathogenesis of several lung diseases. The goals of the conference were to summarize the current state of the field, to discuss and debate current controversies, and to identify future research directions and opportunities for basic and translational research in cell-based therapies for lung diseases. The goal of this article, which accompanies the formal conference report, is to provide a comprehensive review of the published literature in lung regenerative medicine from the last conference report through December 2012.

  15. Automated Measurement of Heterogeneity in CT Images of Healthy and Diseased Rat Lungs using Variogram Analysis of an Octree Decomposition

    SciTech Connect

    Jacob, Rick E.; Carson, James P.

    2014-01-01

    Elastase dosed mice, whole lung and single lobe groups. Combines octree image decomposition with variogram-based analysis Results in promising novel approach for characterizing and measuring lung disease at different stages

  16. Fungal diseases mimicking primary lung cancer: radiologic-pathologic correlation.

    PubMed

    Gazzoni, Fernando F; Severo, Luiz Carlos; Marchiori, Edson; Irion, Klaus L; Guimarães, Marcos D; Godoy, Myrna C; Sartori, Ana P G; Hochhegger, Bruno

    2014-04-01

    A variety of fungal pulmonary infections can produce radiologic findings that mimic lung cancers. Distinguishing these infectious lesions from lung cancer remains challenging for radiologists and clinicians. In such cases, radiographic findings and clinical manifestations can be highly suggestive of lung cancer, and misdiagnosis can significantly delay the initiation of appropriate treatment. Likewise, the findings of imaging studies cannot replace the detection of a species as the aetiological agent. A biopsy is usually required to diagnose the infectious nature of the lesions. In this article, we review the clinical, histologic and radiologic features of the most common fungal infections that can mimic primary lung cancers, including paracoccidioidomycosis, histoplasmosis, cryptococcosis, coccidioidomycosis, aspergillosis, mucormycosis and blastomycosis.

  17. Development of a Three-Dimensional Bioengineering Technology to Generate Lung Tissue for Personalized Disease Modeling.

    PubMed

    Wilkinson, Dan C; Alva-Ornelas, Jackelyn A; Sucre, Jennifer M S; Vijayaraj, Preethi; Durra, Abdo; Richardson, Wade; Jonas, Steven J; Paul, Manash K; Karumbayaram, Saravanan; Dunn, Bruce; Gomperts, Brigitte N

    2017-02-01

    Stem cell technologies, especially patient-specific, induced stem cell pluripotency and directed differentiation, hold great promise for changing the landscape of medical therapies. Proper exploitation of these methods may lead to personalized organ transplants, but to regenerate organs, it is necessary to develop methods for assembling differentiated cells into functional, organ-level tissues. The generation of three-dimensional human tissue models also holds potential for medical advances in disease modeling, as full organ functionality may not be necessary to recapitulate disease pathophysiology. This is specifically true of lung diseases where animal models often do not recapitulate human disease. Here, we present a method for the generation of self-assembled human lung tissue and its potential for disease modeling and drug discovery for lung diseases characterized by progressive and irreversible scarring such as idiopathic pulmonary fibrosis (IPF). Tissue formation occurs because of the overlapping processes of cellular adhesion to multiple alveolar sac templates, bioreactor rotation, and cellular contraction. Addition of transforming growth factor-β1 to single cell-type mesenchymal organoids resulted in morphologic scarring typical of that seen in IPF but not in two-dimensional IPF fibroblast cultures. Furthermore, this lung organoid may be modified to contain multiple lung cell types assembled into the correct anatomical location, thereby allowing cell-cell contact and recapitulating the lung microenvironment. Our bottom-up approach for synthesizing patient-specific lung tissue in a scalable system allows for the development of relevant human lung disease models with the potential for high throughput drug screening to identify targeted therapies. Stem Cells Translational Medicine 2017;6:622-633.

  18. Development of a Three-Dimensional Bioengineering Technology to Generate Lung Tissue for Personalized Disease Modeling.

    PubMed

    Wilkinson, Dan C; Alva-Ornelas, Jackelyn A; Sucre, Jennifer M S; Vijayaraj, Preethi; Durra, Abdo; Richardson, Wade; Jonas, Steven J; Paul, Manash K; Karumbayaram, Saravanan; Dunn, Bruce; Gomperts, Brigitte N

    2016-09-15

    : Stem cell technologies, especially patient-specific, induced stem cell pluripotency and directed differentiation, hold great promise for changing the landscape of medical therapies. Proper exploitation of these methods may lead to personalized organ transplants, but to regenerate organs, it is necessary to develop methods for assembling differentiated cells into functional, organ-level tissues. The generation of three-dimensional human tissue models also holds potential for medical advances in disease modeling, as full organ functionality may not be necessary to recapitulate disease pathophysiology. This is specifically true of lung diseases where animal models often do not recapitulate human disease. Here, we present a method for the generation of self-assembled human lung tissue and its potential for disease modeling and drug discovery for lung diseases characterized by progressive and irreversible scarring such as idiopathic pulmonary fibrosis (IPF). Tissue formation occurs because of the overlapping processes of cellular adhesion to multiple alveolar sac templates, bioreactor rotation, and cellular contraction. Addition of transforming growth factor-β1 to single cell-type mesenchymal organoids resulted in morphologic scarring typical of that seen in IPF but not in two-dimensional IPF fibroblast cultures. Furthermore, this lung organoid may be modified to contain multiple lung cell types assembled into the correct anatomical location, thereby allowing cell-cell contact and recapitulating the lung microenvironment. Our bottom-up approach for synthesizing patient-specific lung tissue in a scalable system allows for the development of relevant human lung disease models with the potential for high throughput drug screening to identify targeted therapies.

  19. The changing pattern of ischemic heart disease

    PubMed Central

    Anderson, T. W.

    1973-01-01

    Male and female death rates from all the major forms of cardiovascular disease were approximately equal until about 1920. Since that time the male:female ratio in fatal ischemic heart disease (IHD) has risen dramatically, but some closely related diseases such as cerebrovascular disease and uncomplicated angina pectoris have maintained sex ratios close to unity. It is difficult to reconcile this divergent trend in the sex ratio of IHD with a simple stenotic-thrombotic view of myocardial infarction (MI) and it is suggested that the modern epidemic of MI in men may be the result of a disorder of muscle metabolism (“vulnerable myocardium”) superimposed on a relatively stable background of stenotic-thrombotic arterial disease. The proposed mechanism would also help to explain the selective action of some modern “coronary risk factors” (such as cigarette smoking and physical inactivity) which increase the risk of MI but have little or no effect on the risk of developing cerebrovascular disease or uncomplicated angina pectoris. PMID:4714875

  20. Lung transplant

    MedlinePlus

    ... in the arteries of the lungs ( pulmonary hypertension ) Sarcoidosis Lung transplant may not be done for people ... Chronic Cystic fibrosis Idiopathic pulmonary fibrosis Lung disease Sarcoidosis Review Date 4/13/2015 Updated by: Dale ...

  1. Overview and Recommendations for Medical Screening and Diagnostic Evaluation of Postdeployment Lung Disease in Returning US Warfighters

    DTIC Science & Technology

    2012-06-01

    nonspecific, and disease is difficult to distinguish from more common obstruc- tive lung diseases such as chronic asthma and emphysema . Constric- tive... emphysema , chronic obstructive pulmonary disease, bronchiolitis, new interstitial lung disease, AEP (as is already being done at Landstuhl Regional

  2. Longitudinal micro-CT provides biomarkers of lung disease that can be used to assess the effect of therapy in preclinical mouse models, and reveal compensatory changes in lung volume.

    PubMed

    Vande Velde, Greetje; Poelmans, Jennifer; De Langhe, Ellen; Hillen, Amy; Vanoirbeek, Jeroen; Himmelreich, Uwe; Lories, Rik J

    2016-01-01

    In vivo lung micro-computed tomography (micro-CT) is being increasingly embraced in pulmonary research because it provides longitudinal information on dynamic disease processes in a field in which ex vivo assessment of experimental disease models is still the gold standard. To optimize the quantitative monitoring of progression and therapy of lung diseases, we evaluated longitudinal changes in four different micro-CT-derived biomarkers [aerated lung volume, lung tissue (including lesions) volume, total lung volume and mean lung density], describing normal development, lung infections, inflammation, fibrosis and therapy. Free-breathing mice underwent micro-CT before and repeatedly after induction of lung disease (bleomycin-induced fibrosis, invasive pulmonary aspergillosis, pulmonary cryptococcosis) and therapy (imatinib). The four lung biomarkers were quantified. After the last time point, we performed pulmonary function tests and isolated the lungs for histology. None of the biomarkers remained stable during longitudinal follow-up of adult healthy mouse lungs, implying that biomarkers should be compared with age-matched controls upon intervention. Early inflammation and progressive fibrosis led to a substantial increase in total lung volume, which affects the interpretation of aerated lung volume, tissue volume and mean lung density measures. Upon treatment of fibrotic lung disease, the improvement in aerated lung volume and function was not accompanied by a normalization of the increased total lung volume. Significantly enlarged lungs were also present in models of rapidly and slowly progressing lung infections. The data suggest that total lung volume changes could partly reflect a compensatory mechanism that occurs during disease progression in mice. Our findings underscore the importance of quantifying total lung volume in addition to aerated lung or lesion volumes to accurately document growth and potential compensatory mechanisms in mouse models of lung

  3. A novel mechanical lung model of pulmonary diseases to assist with teaching and training

    PubMed Central

    Chase, J Geoffrey; Yuta, Toshinori; Mulligan, Kerry J; Shaw, Geoffrey M; Horn, Beverley

    2006-01-01

    Background A design concept of low-cost, simple, fully mechanical model of a mechanically ventilated, passively breathing lung is developed. An example model is built to simulate a patient under mechanical ventilation with accurate volumes and compliances, while connected directly to a ventilator. Methods The lung is modelled with multiple units, represented by rubber bellows, with adjustable weights placed on bellows to simulate compartments of different superimposed pressure and compliance, as well as different levels of lung disease, such as Acute Respiratory Distress Syndrome (ARDS). The model was directly connected to a ventilator and the resulting pressure volume curves recorded. Results The model effectively captures the fundamental lung dynamics for a variety of conditions, and showed the effects of different ventilator settings. It was particularly effective at showing the impact of Positive End Expiratory Pressure (PEEP) therapy on lung recruitment to improve oxygenation, a particulary difficult dynamic to capture. Conclusion Application of PEEP therapy is difficult to teach and demonstrate clearly. Therefore, the model provide opportunity to train, teach, and aid further understanding of lung mechanics and the treatment of lung diseases in critical care, such as ARDS and asthma. Finally, the model's pure mechanical nature and accurate lung volumes mean that all results are both clearly visible and thus intuitively simple to grasp. PMID:16919173

  4. Hyper IgM syndrome presenting as chronic suppurative lung disease.

    PubMed

    Montella, Silvia; Maglione, Marco; Giardino, Giuliana; Di Giorgio, Angela; Palamaro, Loredana; Mirra, Virginia; Ursini, Matilde Valeria; Salerno, Mariacarolina; Pignata, Claudio; Caffarelli, Carlo; Santamaria, Francesca

    2012-09-19

    The Hyper-immunoglobulin M syndromes (HIGM) are a heterogeneous group of genetic disorders resulting in defects of immunoglobulin class switch recombination. Affected patients show humoral immunodeficiency and high susceptibility to opportunistic infections. Elevated serum IgM levels are the hallmark of the disease, even though in few rare cases they may be in the normal range. Hyper IgM is associated with low to undetectable levels of serum IgG, IgA, and IgE. In some cases, alterations in different genes may be identified. Mutations in five genes have so far been associated to the disease, which can be inherited with an X-linked (CD40 ligand, and nuclear factor-kB essential modulator defects) or an autosomal recessive (CD40, activation-induced cytidine deaminase, and uracil-DNA glycosylase mutation) pattern. The patient herein described presented with recurrent upper and lower respiratory infections and evidence of suppurative lung disease at the conventional chest imaging. The presence of low serum IgG and IgA levels, elevated IgM levels, and a marked reduction of in vivo switched memory B cells led to a clinical and functional diagnosis of HIGM although the genetic cause was not identified.

  5. Hyper IgM syndrome presenting as chronic suppurative lung disease

    PubMed Central

    2012-01-01

    The Hyper-immunoglobulin M syndromes (HIGM) are a heterogeneous group of genetic disorders resulting in defects of immunoglobulin class switch recombination. Affected patients show humoral immunodeficiency and high susceptibility to opportunistic infections. Elevated serum IgM levels are the hallmark of the disease, even though in few rare cases they may be in the normal range. Hyper IgM is associated with low to undetectable levels of serum IgG, IgA, and IgE. In some cases, alterations in different genes may be identified. Mutations in five genes have so far been associated to the disease, which can be inherited with an X-linked (CD40 ligand, and nuclear factor-kB essential modulator defects) or an autosomal recessive (CD40, activation-induced cytidine deaminase, and uracil-DNA glycosylase mutation) pattern. The patient herein described presented with recurrent upper and lower respiratory infections and evidence of suppurative lung disease at the conventional chest imaging. The presence of low serum IgG and IgA levels, elevated IgM levels, and a marked reduction of in vivo switched memory B cells led to a clinical and functional diagnosis of HIGM although the genetic cause was not identified. PMID:22992442

  6. Fibrocytes Regulate Wilms’ Tumor 1-Positive Cell Accumulation in Severe Fibrotic Lung Disease

    PubMed Central

    Sontake, Vishwaraj; Shanmukhappa, Shiva K.; DiPasquale, Betsy A.; Reddy, Geereddy B.; Medvedovic, Mario; Hardie, William D.; White, Eric S.; Madala, Satish K.

    2015-01-01

    Collagen-producing myofibroblast transdifferentiation is considered a crucial determinant in the formation of scar tissue in the lungs of patients with idiopathic pulmonary fibrosis (IPF). Multiple resident pulmonary cell types and bone marrow-derived fibrocytes have been implicated as contributors to fibrotic lesions due to the transdifferentiation potential of these cells into myofibroblasts. In this study, we assessed the expression of Wilms’ tumor 1 (WT1), a known marker of mesothelial cells, in various cell types in normal and fibrotic lungs. We demonstrate that WT1 is expressed by both mesothelial and mesenchymal cells in IPF lungs, but has limited or no expression in normal human lungs. We also demonstrate that WT1-positive cells accumulate in fibrotic lung lesions, using two different mouse models of pulmonary fibrosis and WT1 promoter-driven fluorescent reporter mice. Reconstitution of bone-marrow cells into a transforming growth factor-α transgenic-mouse model demonstrated that fibrocytes do not transform into WT1-positive mesenchymal cells, but do augment accumulation of WT1-positive cells in severe fibrotic lung disease. Importantly, the number of WT1-positive cells in fibrotic lesions were correlated with severity of lung disease as assessed by changes in lung function, histology, and hydroxyproline levels in mice. Finally, inhibition of WT1 expression was sufficient to attenuate collagen and other extracellular-matrix gene production by mesenchymal cells from both murine and human fibrotic lungs. Thus, the results of this study demonstrate a novel association between fibrocyte-driven WT1-positive cell accumulation and severe fibrotic lung disease. PMID:26371248

  7. Successful EGFR-TKI rechallenge of leptomeningeal carcinomatosis after gefitinib-induced interstitial lung disease.

    PubMed

    Nakamichi, Shinji; Kubota, Kaoru; Horinouchi, Hidehito; Kanda, Shintaro; Fujiwara, Yutaka; Nokihara, Hiroshi; Yamamoto, Noboru; Tamura, Tomohide

    2013-04-01

    We report the case of a 49-year-old non-smoking Japanese woman with backache and difficulty in walking. She was diagnosed as having advanced lung adenocarcinoma, and an epithelial growth factor receptor mutation (in-frame deletions in exon 19) was found. After radiation therapy of bone metastases with spinal cord compression and brain metastases, gefitinib was administered. On day 2, she developed acute interstitial lung disease. Gefitinib therapy was discontinued and treatment with high-dose steroid therapy improved the interstitial lung disease. Cisplatin plus pemetrexed was initiated as second-line chemotherapy, but she was hospitalized again for leptomeningeal carcinomatosis. Considering the poor prognosis of leptomeningeal carcinomatosis, we decided that erlotinib was our only choice of treatment. As a third-line treatment, erlotinib was administered after informing the patient about the high risk of interstitial lung disease. Neurological symptoms were improved within a week and interstitial lung disease did not recur. The patient has received erlotinib successfully for 18 months without the recurrence of leptomeningeal carcinomatosis. Erlotinib rechallenge after gefitinib-induced interstitial lung disease must be carefully chosen based on the balance of a patient's risk and benefit.

  8. Spectrum of high-resolution computed tomography imaging in occupational lung disease

    PubMed Central

    Satija, Bhawna; Kumar, Sanyal; Ojha, Umesh Chandra; Gothi, Dipti

    2013-01-01

    Damage to the lungs caused by dusts or fumes or noxious substances inhaled by workers in certain specific occupation is known as occupational lung disease. Recognition of occupational lung disease is especially important not only for the primary worker, but also because of the implications with regard to primary and secondary disease prevention in the exposed co-workers. Although many of the disorders can be detected on chest radiography, high-resolution computed tomography (HRCT) is superior in delineating the lung architecture and depicting pathology. The characteristic radiological features suggest the correct diagnosis in some, whereas a combination of clinical features, occupational history, and radiological findings is essential in establishing the diagnosis in others. In the presence of a history of exposure and consistent clinical features, the diagnosis of even an uncommon occupational lung disease can be suggested by the characteristic described HRCT findings. In this article, we briefly review the HRCT appearance of a wide spectrum of occupational lung diseases. PMID:24604929

  9. Patterns of Mixing in the Alveolar Region of the Human Lungs

    NASA Astrophysics Data System (ADS)

    Kumar, Haribalan; Lin, Ching-Long; Tawhai, Merryn H.; McLennan, Geoffrey; Hoffman, Eric A.

    2007-11-01

    The air-flow characteristics in the alveolar region of the human lungs is investigated to understand the mixing patterns at low Reynolds number and their relationship to transport and deposition of pharmaceutical and pollutant particles. 2D and 3D realistic honeycomb-like polygonal geometries are constructed to represent alveolar sacs. An in-house characteristic-Galerkin finite element code in an ALE framework is utilized to simulate flow in the acinar airways ranging from the 17^th to 23^rd generation (with Re=1-0.01). The flow is unsteady and is driven by physiologically rhythmic wall motion. Lagrangian-based numerical visualization is used to provide a complete description of the dynamics. Results in the form of material advection (dye or blob) and stretch rate are presented. Time averaged mixing estimates are used to analyze different breathing frequencies and patterns.

  10. Epidemiology of Nontuberculous Mycobacterial Lung Disease and Tuberculosis, Hawaii, USA

    PubMed Central

    Frankland, Timothy B.; Daida, Yihe G.; Honda, Jennifer R.; Olivier, Kenneth N.; Zelazny, Adrian; Honda, Stacey; Prevots, D. Rebecca

    2017-01-01

    Previous studies found Hawaiians and Asian-Americans/Pacific Islanders to be independently at increased risk for nontuberculous mycobacterial pulmonary disease (NTMPD) and tuberculosis (TB). To better understand NTM infection and TB risk patterns in Hawaii, USA, we evaluated data on a cohort of patients in Hawaii for 2005–2013. Period prevalence of NTMPD was highest among Japanese, Chinese, and Vietnamese patients (>300/100,000 persons) and lowest among Native Hawaiians and Other Pacific Islanders (50/100,000). Japanese patients were twice as likely as all other racial/ethnic groups to have Mycobacterium abscessus isolated (adjusted odds ratio 2.0, 95% CI 1.2–3.2) but were not at increased risk for infection with other mycobacteria species. In contrast, incidence of TB was stable and was lowest among Japanese patients (no cases) and highest among Filipino, Korean, and Vietnamese patients (>50/100,000). Substantial differences exist in the epidemiology of NTMPD by race/ethnicity, suggesting behavioral and biologic factors that affect disease susceptibility. PMID:28221128

  11. Increasing Prevalence of Chronic Lung Disease in Veterans of the Wars in Iraq and Afghanistan.

    PubMed

    Pugh, Mary Jo; Jaramillo, Carlos A; Leung, Kar-Wei; Faverio, Paola; Fleming, Nicholas; Mortensen, Eric; Amuan, Megan E; Wang, Chen-Pin; Eapen, Blessen; Restrepo, Marcos; Morris, Michael J

    2016-05-01

    Research from the wars in Afghanistan and Iraq have focused on traumatic brain injury (TBI) and mental health conditions; however, it is becoming clear that other health concerns, such as respiratory illnesses, warrant further scientific inquiry. Early reports from theater and postdeployment health assessments suggested an association with deployment-related exposures (e.g., sand, burn pits, chemical, etc.) and new-onset respiratory symptoms. We used data from Veterans Affairs medical encounters between fiscal years 2003 and 2011 to identify trends in chronic obstructive pulmonary disease, asthma, and interstitial lung disease in veterans. We used data from Veterans Affairs and Department of Defense sources to identify sociodemographic (age, sex, race), military (e.g., service branch, multiple deployments) and clinical characteristics (TBI, smoking) of individuals with and without chronic lung diseases. Generalized estimating equations found significant increases over time for chronic obstructive pulmonary disease and asthma in both unadjusted and adjusted analyses. Trends for interstitial lung disease were significant only in adjusted analyses. Age, smoking, and TBI were also significantly associated with chronic lung diseases; however, multiple deployments were not associated. Research is needed to identify which characteristics of deployment-related exposures are linked with chronic lung disease.

  12. Antisynthetase syndrome: An under-recognized cause of interstitial lung disease

    PubMed Central

    Maturu, Venkata Nagarjuna; Lakshman, Arjun; Bal, Amanjit; Dhir, Varun; Sharma, Aman; Garg, Mandeep; Saikia, Biman; Agarwal, Ritesh

    2016-01-01

    Background: Antisynthetase syndrome (AS) is an uncommon and under-recognised connective tissue disease characterized by the presence of antibodies to anti-aminoacyl t-RNA synthetase along with features of interstitial lung disease (ILD), myositis and arthritis. The aim of the current study is to describe our experience with management of AS. Materials and Methods: This was a 2-year (2013-2014) retrospective analysis of patients diagnosed with anti-Jo-1-related AS. The presence of anti-Jo-1 antibody was tested by the immunoblot assay. All patients underwent high-resolution computed tomography of the chest, transthoracic echocardiography and evaluation for inflammatory myositis. Transbronchial lung biopsies and muscle biopsies were obtained when clinically indicated. Results: Nine patients (mean age: 43.8 years) were diagnosed with anti-Jo-1-related AS. The median duration of symptoms before diagnosis of AS was 6 months. All patients were negative for antinuclear antibodies by indirect immunofluorescence. The prevalence of ILD, myositis and arthritis at presentation was 100%, 77.8% and 55.6%, respectively. The most common ILD pattern was non-specific interstitial pneumonia (n = 6) followed by organizing pneumonia (n = 2) and usual interstitial pneumonia (n = 1). ILD was the sole manifestation in two patients and was subclinical in two patients. Six patients had pleuropericardial effusions, three patients had pulmonary artery hypertension and two patients had venous thromboembolism. Eight of the nine patients improved after treatment with steroids and other immunosuppressants. Conclusion: Antisynthetase syndrome is an important and a treatable cause of ILD. Strong clinical suspicion is needed to achieve an early diagnosis. PMID:26933302

  13. Patterns of cortical thinning in nondemented Parkinson's disease patients

    PubMed Central

    Uribe, Carme; Segura, Barbara; Baggio, Hugo Cesar; Abos, Alexandra; Marti, Maria Jose; Valldeoriola, Francesc; Compta, Yaroslau; Bargallo, Nuria

    2016-01-01

    ABSTRACT Background Clinical variability in the Parkinson's disease phenotype suggests the existence of disease subtypes. We investigated whether distinct anatomical patterns of atrophy can be identified in Parkinson's disease using a hypothesis‐free, data‐driven approach based on cortical thickness data. Methods T1‐weighted 3‐tesla MRI and a comprehensive neuropsychological assessment were performed in a sample of 88 nondemented Parkinson's disease patients and 31 healthy controls. We performed a hierarchical cluster analysis of imaging data using Ward's linkage method. A general linear model with cortical thickness data was used to compare clustering groups. Results We observed 3 patterns of cortical thinning in patients when compared with healthy controls. Pattern 1 (n = 30, 34.09%) consisted of cortical atrophy in bilateral precentral gyrus, inferior and superior parietal lobules, cuneus, posterior cingulate, and parahippocampal gyrus. These patients showed worse cognitive performance when compared with controls and the other 2 patterns. Pattern 2 (n = 29, 32.95%) consisted of cortical atrophy involving occipital and frontal as well as superior parietal areas and included patients with younger age at onset. Finally, in pattern 3 (n = 29, 32.95%), there was no detectable cortical thinning. Patients in the 3 patterns did not differ in disease duration, motor severity, dopaminergic medication doses, or presence of mild cognitive impairment. Conclusions Three cortical atrophy subtypes were identified in nondemented Parkinson's disease patients: (1) parieto‐temporal pattern of atrophy with worse cognitive performance, (2) occipital and frontal cortical atrophy and younger disease onset, and (3) patients without detectable cortical atrophy. These findings may help identify prognosis markers in Parkinson's disease. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement

  14. Crohn's disease-associated interstitial lung disease mimicking sarcoidosis: a case report and review of the literature.

    PubMed

    Thao, Choua; Lagstein, Amir; Allen, Tadashi; Dincer, Huseyin Erhan; Kim, Hyun Joo

    2016-10-07

    Respiratory involvement in Crohn's disease (CD) is a rare manifestation known to involve the large and small airways, lung parenchyma, and pleura. The clinical presentation is nonspecific, and diagnostic tests can mimic other pulmonary diseases, posing a diagnostic challenge and delay in treatment. We report a case of a 60-year-old female with a history of CD and psoriatic arthritis who presented with dyspnea, fever, and cough with abnormal radiological findings. Diagnostic testing revealed an elevated CD4:CD8 ratio in the bronchoalveolar lavage fluid, and cryoprobe lung biopsy results showed non-necrotizing granulomatous inflammation. We describe here the second reported case of pulmonary involvement mimicking sarcoidosis in Crohn's disease and a review of the literature on the approaches to making a diagnosis of CD-associated interstitial lung disease.

  15. A Single US Center Experience of Transbronchial Lung Cryobiopsy for Diagnosing Interstitial Lung Disease With a 2-Scope Technique

    PubMed Central

    Aragaki, Alejandro; Baughman, Robert; Wikenheiser-Brokamp, Kathryn; Khanna, Gaurav; Tanase, Daniel; Kirschner, Michelle; Benzaquen, Sadia

    2017-01-01

    Background: Transbronchial lung cryobiopsy (TBLC) has been used to establish the diagnosis of interstitial lung disease (ILD) in recent years. The technique and diagnostic yield vary among institutions. We report a new 2-scope technique and the results of TBLC in our institution. Methods: This is a retrospective chart review of patients who underwent TBLC for evaluation of ILD. Bronchoscopy with TBLC was performed by a board-certified interventional pulmonologist with a 2-scope technique under general anesthesia. Results: A total of 74 patients underwent TBLC with a 2-scope technique. Their mean age was 54±14 years. The mean tissue surface area was 63.54±6.76 mm2. The average anesthesia time was 80.66 minutes. The diagnostic yield was 87.84%. The most common diagnosis was sarcoidosis pneumothorax, which occurred in 5 cases (7%). There was 1 case with bronchoscopic-related respiratory failure associated with significant bleeding. Death occurred in 3 cases (4%), which is comparable to recent mortality data for “elective” surgical lung biopsy for ILD (1.7% to 4.2%). Conclusion: TBLC with a 2-scope technique could be an alternative method for diagnosing various types of ILD in patients unfit for surgical lung biopsy. Further prospective studies should clarify its role in the diagnostic armamentarium for undiagnosed ILDs. PMID:28323726

  16. Effect of a single nucleotide polymorphism in miR-146a on COX-2 protein expression and lung function in smokers with chronic obstructive pulmonary disease

    PubMed Central

    Wang, Ran; Li, Min; Zhou, Sijing; Zeng, Daxiong; Xu, Xuan; Xu, Rui; Sun, Gengyun

    2015-01-01

    Objective To evaluate the effect of a single nucleotide polymorphism (rs2910164) in the miR-146a precursor on the expression level of miR-146a, cyclooxygenase-2 (COX2), and production of prostaglandin E2 (PGE2) in lung tissue harvested from smokers with chronic obstructive pulmonary disease, as well as the lung function and disease stages from the same patient population. Methods and results One-hundred and sixty-eight smokers with diagnosed chronic obstructive pulmonary disease were recruited. The patients were genotyped for rs2910164 polymorphism using Sanger sequencing, and their lung function/disease stages were evaluated following Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. Meanwhile, messenger ribonucleic acid and protein expression levels of miR-146a and COX2 as well as PGE2 production were determined in 66 lung tissue samples collected in the patients who received surgical treatment. We confirmed that COX2 is a validated target of miR-146a in human fibroblast cells, and identified the differential expression patterns of miR-146a and COX2 in each rs2910164 genotype group. We observed a significant association between rs2910164 in miR-146a and the levels of either COX2 or PGE2 using real-time polymerase chain reaction and Western blot. Consistently, we were able to demonstrate that the rs2910164 single nucleotide polymorphism has a functional effect on the baseline lung function in the study population. Conclusion In the present study, the rs2910164 CC and GC genotype was found to be associated with an improved lung function and milder disease stages, at least partially, mediated by its ability to increase in COX2 expression and PGE2 production. PMID:25767384

  17. Diffuse Parenchymal Lung Diseases with Clinicoradiological Discordance: Role of Transbronchial Lung Biopsy as a Diagnostic Tool - An Observational Study

    PubMed Central

    Narayan, Kiran Vishnu; Edakalavan, Jyothi; Kumar, Neethu Kesava

    2016-01-01

    Introduction The diagnosis of Diffuse Parenchymal Lung Disease (DPLD) requires a multidisciplinary approach with reconciliation of clinicoradiological and histopathological data. But when the preliminary clinicoradiological profile fails to suggest a diagnosis, an adequate lung biopsy specimen with meticulous histological examination and a multidisciplinary approach usually yields results. There is also a high chance of sampling error due to patchy and heterogeneous involvement of the disease process and due to the small volume of tissue taken. As seen in our study, Trans-Bronchial Lung Biopsy (TBLB) if performed by an experienced bronchoscopist can be done as an outpatient procedure yielding adequate specimens for diagnosis and guide effective treatment in these patients. Aim To study the utility and diagnostic yield of TBLB in DPLD patients when there is clinicoradiological discordance. Materials and Methods The current retrospective observational study was undertaken in the Institute of Chest Diseases, Government Medical College, Kozhikode, Kerala, India, from January 2012 to December 2014. Out of 169 DPLD patients who attended the tertiary care centre, 66 patients without a definite diagnosis by clinicoradiological assessment were included in the study. They underwent TBLB using a fibre-optic video bronchoscope. An open lung biopsy was advised if the TBLB did not yield a definite diagnosis. Results Among the 66 patients, histopathological confirmation was obtained in 51 patients, 39 of which were by TBLB (59%). Few diagnoses like invasive adenocarcinoma, Pneumocystis jirovecii pneumonia and Aspergillus infection were least expected. Conclusion TBLB if performed correctly can be an effective intervening modality in establishing the diagnosis of DPLD before going for an invasive surgical biopsy. PMID:28050417

  18. The trend and the disease prediction of vascular endothelial growth factor and placenta growth factor in nontuberculous mycobacterial lung disease

    PubMed Central

    Lin, Chou-Han; Shu, Chin-Chung; Hsu, Chia-Lin; Cheng, Shih-Lung; Wang, Jann-Yuan; Yu, Chong-Jen; Lee, Li-Na

    2016-01-01

    Nontuberculous mycobacteria (NTM)-lung disease (LD) is an increasing health problem worldwide. The diagnosis of this disease remains difficult, however the application of placenta growth factor (PlGF) and vascular endothelial growth factor (VEGF) has not yet been studied. We screened patients with Mycobacterium avium complex or M. abscessus isolated from sputum, and enrolled 32 patients with NTM-LD and 93 with NTM pulmonary colonization. The NTM-LD group had a lower body mass index, higher proportion of bronchiectasis, more respiratory symptoms and pulmonary lesions, and higher titers of sputum acid-fast stain than the NTM pulmonary colonization group. The plasma level of PlGF was lower in the NTM-LD group than in the NTM colonization group, whereas the level of VEGF was higher in the NTM-LD group. In multivariable logistic regression analysis excluding NTM cultures, the predictive model for NTM-LD included sputum AFS titer, a nodular-bronchiectasis radiographic pattern, plasma VEGF/PlGF ratio, and chest radiographic score (VEGF/P1GF ratio became not significant as a factor in multivariable generalized linear model). The four-factor predictive index had good positive likelihood ratio and negative likelihood ratio for predicting NTM-LD in the patients with NTM in their sputum. PMID:27876856

  19. Chronic obstructive lung disease and posttraumatic stress disorder: current perspectives

    PubMed Central

    Abrams, Thad E; Blevins, Amy; Weg, Mark W Vander

    2015-01-01

    Background Several studies have reported on the co-occurrence of chronic obstructive pulmonary disease (COPD) and psychiatric conditions, with the most robust evidence base demonstrating an impact of comorbid anxiety and depression on COPD-related outcomes. In recent years, research has sought to determine if there is a co-occurrence between COPD and posttraumatic stress disorder (PTSD) as well as for associations between PTSD and COPD-related outcomes. To date, there have been no published reviews summarizing this emerging literature. Objectives The primary objective of this review was to determine if there is adequate evidence to support a co-occurrence between PTSD and COPD. Secondary objectives were to: 1) determine if there are important clinical considerations regarding the impact of PTSD on COPD management, and 2) identify targeted areas for further research. Methods A structured review was performed using a systematic search strategy limited to studies in English, addressing adults, and to articles that examined: 1) the co-occurrence of COPD and PTSD and 2) the impact of PTSD on COPD-related outcomes. To be included, articles must have addressed some type of nonreversible obstructive lung pathology. Results A total of 598 articles were identified for initial review. Upon applying the inclusion and exclusion criteria, n=19 articles or abstracts addressed our stated objectives. Overall, there is inconclusive evidence to support the co-occurrence between PTSD and COPD. Studies finding a significant co-occurrence generally had inferior methods of identifying COPD; in contrast, studies that utilized more robust COPD measures (such as a physician exam) generally failed to find a relationship. Among studies that examined the impact of PTSD on COPD-related outcomes, there was more consistent evidence that PTSD affects the perception of respiratory symptom burden and management. In addition, methods for measuring an important confounder (smoking) were generally

  20. Expression of the Epstein-Barr virus in lymphoproliferative diseases of the lung.

    PubMed

    Shimakage, Misuzu; Sakamoto, Haruhiko; Harada, Shizuko; Sasagawa, Toshiyuki; Kodama, Ken

    2007-06-01

    There have been few studies regarding the etiology of lymphoproliferative disorders of the lung. To examine the possible involvement of the Epstein-Barr virus (EBV) in these diseases, EBV mRNAs, proteins and DNA, were detected. Two non-Hodgkin's lymphomas (NHL) originating in the lung, 5 mucosal-associated lymphoid tissue lymphomas (MALT lymphoma) of the lung, 1 lymphoid hyperplasia of the lung and 1 lymphoid interstitial pneumonia (LIP), were subjected to mRNA in situ hybridization, indirect immunofluorescence staining and PCR. mRNA in situ hybridization using BamHIW, BamHIY1Y2, the Epstein-Barr virus nuclear antigen (EBNA) and the EBV encoded small non-polyadenylated RNA (EBER1) probe revealed signals in all the examined samples, although some samples showed weak signals by using the EBER1 probe. Indirect immunofluorescence staining using the anti-leader protein, anti-EBNA2, the anti-latent member protein-1 and anti-BamHIZ coding leftward reading frame-1 antibodies showed definitive fluorescence. PCR also revealed EBV DNA in these specimens. EBV infected all the lymphoproliferative diseases of the lung irrespective of the histological or clinical stages. Furthermore, EBV infected not only the atypical lymphocytes but also the macrophages in the tissues of these diseases. These results suggest that the expression of EBV could be involved in the pathogenesis of many lymphoproliferative diseases of the lung.

  1. Correlated Variability in the Breathing Pattern and End-Expiratory Lung Volumes in Conscious Humans

    PubMed Central

    Dellaca, Raffaele L.; Aliverti, Andrea; Lo Mauro, Antonella; Lutchen, Kenneth R.; Pedotti, Antonio; Suki, Bela

    2015-01-01

    In order to characterize the variability and correlation properties of spontaneous breathing in humans, the breathing pattern of 16 seated healthy subjects was studied during 40 min of quiet breathing using opto-electronic plethysmography, a contactless technology that measures total and compartmental chest wall volumes without interfering with the subjects breathing. From these signals, tidal volume (VT), respiratory time (TTOT) and the other breathing pattern parameters were computed breath-by-breath together with the end-expiratory total and compartmental (pulmonary rib cage and abdomen) chest wall volume changes. The correlation properties of these variables were quantified by detrended fluctuation analysis, computing the scaling exponentα. VT, TTOT and the other breathing pattern variables showed α values between 0.60 (for minute ventilation) to 0.71 (for respiratory rate), all significantly lower than the ones obtained for end-expiratory volumes, that ranged between 1.05 (for rib cage) and 1.13 (for abdomen) with no significant differences between compartments. The much stronger long-range correlations of the end expiratory volumes were interpreted by a neuromechanical network model consisting of five neuron groups in the brain respiratory center coupled with the mechanical properties of the respiratory system modeled as a simple Kelvin body. The model-based α for VT is 0.57, similar to the experimental data. While the α for TTOT was slightly lower than the experimental values, the model correctly predicted α for end-expiratory lung volumes (1.045). In conclusion, we propose that the correlations in the timing and amplitude of the physiological variables originate from the brain with the exception of end-expiratory lung volume, which shows the strongest correlations largely due to the contribution of the viscoelastic properties of the tissues. This cycle-by-cycle variability may have a significant impact on the functioning of adherent cells in the

  2. Correlated variability in the breathing pattern and end-expiratory lung volumes in conscious humans.

    PubMed

    Dellaca, Raffaele L; Aliverti, Andrea; Lo Mauro, Antonella; Lutchen, Kenneth R; Pedotti, Antonio; Suki, Bela

    2015-01-01

    In order to characterize the variability and correlation properties of spontaneous breathing in humans, the breathing pattern of 16 seated healthy subjects was studied during 40 min of quiet breathing using opto-electronic plethysmography, a contactless technology that measures total and compartmental chest wall volumes without interfering with the subjects breathing. From these signals, tidal volume (VT), respiratory time (TTOT) and the other breathing pattern parameters were computed breath-by-breath together with the end-expiratory total and compartmental (pulmonary rib cage and abdomen) chest wall volume changes. The correlation properties of these variables were quantified by detrended fluctuation analysis, computing the scaling exponenta. VT, TTOT and the other breathing pattern variables showed α values between 0.60 (for minute ventilation) to 0.71 (for respiratory rate), all significantly lower than the ones obtained for end-expiratory volumes, that ranged between 1.05 (for rib cage) and 1.13 (for abdomen) with no significant differences between compartments. The much stronger long-range correlations of the end expiratory volumes were interpreted by a neuromechanical network model consisting of five neuron groups in the brain respiratory center coupled with the mechanical properties of the respiratory system modeled as a simple Kelvin body. The model-based α for VT is 0.57, similar to the experimental data. While the α for TTOT was slightly lower than the experimental values, the model correctly predicted α for end-expiratory lung volumes (1.045). In conclusion, we propose that the correlations in the timing and amplitude of the physiological variables originate from the brain with the exception of end-expiratory lung volume, which shows the strongest correlations largely due to the contribution of the viscoelastic properties of the tissues. This cycle-by-cycle variability may have a significant impact on the functioning of adherent cells in the

  3. A role for cell adhesion in beryllium-mediated lung disease

    SciTech Connect

    Hong-geller, Elizabeth

    2008-01-01

    Chronic beryllium disease (CBD) is a debilitating lung disorder in which exposure to the lightweight metal beryllium (Be) causes the accumulation of beryllium-specific CD4+ T cells in the lung and formation of noncaseating pulmonary granulomas. Treatment for CBD patients who exhibit progressive pulmonary decline is limited to systemic corticosteroids, which suppress the severe host inflammatory response. Studies in the past several years have begun to highlight cell-cell adhesion interactions in the development of Be hypersensitivity and CBD. In particular, the high binding affinity between intercellular adhesion molecule 1 (I-CAM1) on lung epithelial cells and the {beta}{sub 2} integrin LFA-1 on migrating lymphocytes and macrophages regulates the concerted rolling of immune cells to sites of inflammation in the lung. In this review, we discuss the evidence that implicates cell adhesion processes in onset of Be disease and the potential of cell adhesion as an intervention point for development of novel therapies.

  4. Lung Cancer Workshop XI: Tobacco-Induced Disease: Advances in Policy, Early Detection and Management.

    PubMed

    Mulshine, James L; Avila, Rick; Yankelevitz, David; Baer, Thomas M; Estépar, Raul San Jose; Ambrose, Laurie Fenton; Aldigé, Carolyn R

    2015-05-01

    The Prevent Cancer Foundation Lung Cancer Workshop XI: Tobacco-Induced Disease: Advances in Policy, Early Detection and Management was held in New York, NY on May 16 and 17, 2014. The two goals of the Workshop were to define strategies to drive innovation in precompetitive quantitative research on the use of imaging to assess new therapies for management of early lung cancer and to discuss a process to implement a national program to provide high quality computed tomography imaging for lung cancer and other tobacco-induced disease. With the central importance of computed tomography imaging for both early detection and volumetric lung cancer assessment, strategic issues around the development of imaging and ensuring its quality are critical to ensure continued progress against this most lethal cancer.

  5. Interstitial lung disease more than 40 years after a 5 year occupational exposure to talc.

    PubMed

    Gysbrechts, C; Michiels, E; Verbeken, E; Verschakelen, J; Dinsdale, D; Nemery, B; Demedts, M

    1998-06-01

    A 62 yr old woman was initially diagnosed with sarcoidosis until a thoracoscopic biopsy revealed the presence of numerous birefringent particles in fibrotic areas of the centrilobular lung zones. These particles were examined by electron microscopy and X-ray spectrometry and characterized as impure talc. Further inquiry into her occupational history revealed that she had worked from the age of 14-18 yrs in a factory making rubber hoses, where she had had an intense exposure to talc. There was no evidence of silicosis or asbestosis, and other significant causes of interstitial lung disease were excluded. This case emphasizes the importance of a thorough occupational history, which may reveal a remote and forgotten exposure to a significant cause of interstitial lung disease. Although this presentation of talcosis is unusual, this case suggests that even a relatively short, but presumably intense exposure to talc more than 40 yrs previously may be a cause of progressive lung fibrosis.

  6. Stability and Change in Patterns of Coping with Parkinson's Disease

    ERIC Educational Resources Information Center

    Frazier, Leslie D.

    2002-01-01

    This study examined how Parkinson's disease patients cope with disease-related stressors over time. Of interest was whether patterns of coping would support a dispositional model of coping (i.e., stability) or a contextual model of coping (i.e., change). The influence of stability and change in coping on mental and physical health outcomes was…

  7. Statistical signal processing technique for identification of different infected sites of the diseased lungs.

    PubMed

    Abbas, Ali

    2012-06-01

    Accurate Diagnosis of lung disease depends on understanding the sounds emanating from lung and its location. Lung sounds are of significance as they supply precise and important information on the health of the respiratory system. In addition, correct interpretation of breath sounds depends on a systematic approach to auscultation; it also requires the ability to describe the location of abnormal finding in relation to bony structures and anatomic landmark lines. Lungs consist of number of lobes; each lung lobe is further subdivided into smaller segments. These segments are attached to each other. Knowledge of the position of the lung segments is useful and important during the auscultation and diagnosis of the lung diseases. Usually the medical doctors give the location of the infection a segmental position reference. Breath sounds are auscultated over the anterior chest wall surface, the lateral chest wall surfaces, and posterior chest wall surface. Adventitious sounds from different location can be detected. It is common to seek confirmation of the sound detection and its location using invasive and potentially harmful imaging diagnosis techniques like x-rays. To overcome this limitation and for fast, reliable, accurate, and inexpensive diagnose a technique is developed in this research for identifying the location of infection through a computerized auscultation system.

  8. The Lung Microbiome in Moderate and Severe Chronic Obstructive Pulmonary Disease

    PubMed Central

    Pragman, Alexa A.; Kim, Hyeun Bum; Reilly, Cavan S.; Wendt, Christine; Isaacson, Richard E.

    2012-01-01

    Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder characterized by incompletely reversible airflow obstruction. Bacterial infection of the lower respiratory tract contributes to approximately 50% of COPD exacerbations. Even during periods of stable lung function, the lung harbors a community of bacteria, termed the microbiome. The role of the lung microbiome in the pathogenesis of COPD remains unknown. The COPD lung microbiome, like the healthy lung microbiome, appears to reflect microaspiration of oral microflora. Here we describe the COPD lung microbiome of 22 patients with Moderate or Severe COPD compared to 10 healthy control patients. The composition of the lung microbiomes was determined using 454 pyrosequencing of 16S rDNA found in bronchoalveolar lavage fluid. Sequences were analyzed using mothur, Ribosomal Database Project, Fast UniFrac, and Metastats. Our results showed a significant increase in microbial diversity with the development of COPD. The main phyla in all samples were Actinobacteria, Firmicutes, and Proteobacteria. Principal coordinate analyses demonstrated separation of control and COPD samples, but samples did not cluster based on disease severity. However, samples did cluster based on the use of inhaled corticosteroids and inhaled bronchodilators. Metastats analyses demonstrated an increased abundance of several oral bacteria in COPD samples. PMID:23071781

  9. Nebulised liposomal amphotericin B for Aspergillus lung diseases: case series and literature review.

    PubMed

    Godet, Cendrine; Goudet, Véronique; Laurent, François; Le Moal, Gwenaël; Gounant, Valérie; Frat, Jean-Pierre; Cateau, Estelle; Roblot, France; Cadranel, Jacques

    2015-03-01

    Over the past 10 years the incidence of Aspergillus spp. has significantly increased, and it is now the most widespread air transmission fungal pathogen in developed countries. Whatever the clinical expression of the pulmonary disease and despite recent progress in antifungal drug therapy, morbidity and mortality related to aspergillosis lung disease still constitute a serious threat for immunosuppressed or mildly immunocompromised patients. Moreover, the treatments currently used have many limitations due to adverse effects and drug interactions. Finally, subjects exposed to azoles present an increased risk of Aspergillus-resistant strain emergence. We have reported five cases with aspergillosis lung diseases that were either difficult to control or in which patients had a contra-indication to triazole therapy, but which showed durable improvement following the administration of nebulised liposomal amphotericin B. Our alternative strategy could be of interest for patients with aspergillosis lung disease who otherwise cannot be conventionally treated by triazoles.

  10. [Diagnosis of predisposition to chronic cor pulmonale formation in occupational lung diseases caused by dust].

    PubMed

    Panev, N I; Korotenko, O Iu; Zakharenkov, V V; Korchagina, Iu S; Gafarov, N I

    2014-01-01

    Study covered 426 miners aged 40-54 years with previously diagnosed occupational respiratory diseases due to dust (246 patients with chronic occupational obstructive bronchitis, 98 with anthracosilicosis and 82 with chronic dust nonobstructive bronchitis). 315 (73.9%) examinees out of 426 with lung diseases due to dust demonstrated chronic cor pulnmonale. Considering high share of this complication, the authors used Bayes method to create a method to diagnose predisposition towards chronic cor pulmonale in patients with dust lung diseases through respiratory failure, concomitant coronary heart disease and arterial hypertension, blood groups ABO, MN and P, some structural and functional parameters of heart: myocardium weight index, relative wall thickness index and left ventricle sphericity index, average lung artery pressure. Increasing number of analyzed factors that directly influence chronic cor pulmonale development and selecting additional markers help to improve forecasting of the complication.

  11. Mortality from lung cancer and chronic obstructive pulmonary disease in New Mexico, 1958-82.

    PubMed

    Samet, J M; Wiggins, C L; Key, C R; Becker, T M

    1988-09-01

    We examined mortality from lung cancer and from chronic obstructive pulmonary disease in Hispanic White, Other White, and Native American residents of New Mexico during the period 1958-82. Age-specific mortality was calculated by combining death certificate data with population estimates based on the 1960, 1970, and 1980 censuses that were adjusted for inconsistencies in the designation of race and ethnicity. In Other Whites, age-adjusted mortality rates from lung cancer and from chronic obstructive pulmonary disease increased progressively in males and females. Mortality rates for both diseases also increased in Hispanics during the study period, but the most recent rates for Hispanics were well below those for Other Whites. Age-specific mortality rates for lung cancer declined for more recently born Hispanic women at older ages. In Native Americans, rates for both diseases were low throughout the study period and did not show consistent temporal trends.

  12. Management of Systemic Sclerosis-Associated Interstitial Lung Disease (SSc-ILD)

    PubMed Central

    Silver, Katherine Culp

    2015-01-01

    Although scleroderma-associated interstitial lung disease (SSc-ILD) is a significant contributor to both morbidity and mortality, its pathogenesis is largely unclear. Pulmonary function tests (PFTs) and high resolution CT (HRCT) scanning continue to be the most effective tools to screen for lung involvement and to monitor for disease progression. More research and better biomarkers are needed to identify patients most at risk for developing SSc-ILD as well as to recognize which of these patients will progress to more severe disease. While immunosuppression remains the mainstay of treatment, anti-fibrotic agents may offer new avenues of treatment for patients with SSc-ILD in the future. PMID:26210128

  13. Acute exacerbation of preexisting interstitial lung disease after administration of etanercept for rheumatoid arthritis.

    PubMed

    Hagiwara, Kiyofumi; Sato, Takeo; Takagi-Kobayashi, Shoko; Hasegawa, Shunsuke; Shigihara, Nayumi; Akiyama, Osamu

    2007-05-01

    A 70-year-old woman with a 6-year history of seropositive rheumatoid arthritis (RA) and asymptomatic interstitial lung disease (ILD) began taking etanercept for ongoing arthritis despite treatment with methotrexate (MTX) and bucillamine. MTX was discontinued before introduction of etanercept. She developed lung injury 8 weeks after starting etanercept. Etanercept was discontinued and oral prednisolone 40 mg/day was begun, and her clinical findings gradually improved. Lung injury, although rare, is a recently noticed, potentially fatal adverse effect of all 3 licensed biological anti-tumor necrosis factor (TNF) agents. We recommend caution in the use of anti-TNF agents in elderly RA patients with preexisting ILD.

  14. Reversal of diffuse patchy pattern in lung perfusion scan in a case of severe pulmonary arterial hypertension.

    PubMed

    Kodama, Yoshihiko; Abe, Kohtaro; Hosokawa, Kazuya; Ohtani, Kisho; Nagao, Michinobu; Hirooka, Yoshitaka; Sunagawa, Kenji

    2015-01-01

    A diffuse patchy pattern in the perfusion scan of the lung is a hallmark of severe pulmonary arterial hypertension (PAH). However, the mechanisms of this unique pattern remain uncertain. We here present the case of a 19-year-old woman with severe PAH who demonstrated reversal of the diffuse patchy pattern with improvement of pulmonary blood flow within a month after upfront triple combination therapy. Our case is a first report showing reversibility of diffuse patchy pattern by a short-term treatment in severe PAH. These findings suggest the possibility that the mechanisms underlying the diffuse patchy pattern may involve reversible vasoconstriction in addition to remodeling of small pulmonary arteries.

  15. Systems Medicine for Lung Diseases: Phenotypes and Precision Medicine in Cancer, Infection, and Allergy.

    PubMed

    Schmeck, Bernd; Bertrams, Wilhelm; Lai, Xin; Vera, Julio

    2016-01-01

    Lung diseases cause an enormous socioeconomic burden. Four of them are among the ten most important causes of deaths worldwide: Pneumonia has the highest death toll of all infectious diseases, lung cancer kills the most people of all malignant proliferative disorders, chronic obstructive pulmonary disease (COPD) ranks third in mortality among the chronic noncommunicable diseases, and tuberculosis is still one of the most important chronic infectious diseases. Despite all efforts, for example, by the World Health Organization and clinical and experimental researchers, these diseases are still highly prevalent and harmful. This is in part due to the specific organization of tissue homeostasis, architecture, and immunity of the lung. Recently, several consortia have formed and aim to bring together clinical and molecular data from big cohorts of patients with lung diseases with novel experimental setups, biostatistics, bioinformatics, and mathematical modeling. This "systems medicine" concept will help to match the different disease modalities with adequate therapeutic and possibly preventive strategies for individual patients in the sense of precision medicine.

  16. The Role of School Health Education in Preventing Heart, Lung, and Blood Diseases.

    ERIC Educational Resources Information Center

    Kolbe, Lloyd J.; Newman, Ian M.

    1984-01-01

    This article reviews the scope and dynamics of heart, lung, and blood diseases and explains the need for research on primary prevention programs for children. Suggestions for school health education programs that contribute to disease prevention are delineated. (Author/DF)

  17. Pathway Reconstruction of Airway Remodeling in Chronic Lung Diseases: A Systems Biology Approach

    PubMed Central

    Najafi, Ali; Masoudi-Nejad, Ali; Ghanei, Mostafa; Nourani, Mohamad-Reza; Moeini, Ali

    2014-01-01

    Airway remodeling is a pathophysiologic process at the clinical, cellular, and molecular level relating to chronic obstructive airway diseases such as chronic obstructive pulmonary disease (COPD), asthma and mustard lung. These diseases are associated with the dysregulation of multiple molecular pathways in the airway cells. Little progress has so far been made in discovering the molecular causes of complex disease in a holistic systems manner. Therefore, pathway and network reconstruction is an essential part of a systems biology approach to solve this challenging problem. In this paper, multiple data sources were used to construct the molecular process of airway remodeling pathway in mustard lung as a model of airway disease. We first compiled a master list of genes that change with airway remodeling in the mustard lung disease and then reconstructed the pathway by generating and merging the protein-protein interaction and the gene regulatory networks. Experimental observations and literature mining were used to identify and validate the master list. The outcome of this paper can provide valuable information about closely related chronic obstructive airway diseases which are of great importance for biologists and their future research. Reconstructing the airway remodeling interactome provides a starting point and reference for the future experimental study of mustard lung, and further analysis and development of these maps will be critical to understanding airway diseases in patients. PMID:24978043

  18. Disease transmission promotes evolution of host spatial patterns

    PubMed Central

    Bull, James C.; Keeling, Matthew J.

    2016-01-01

    Ecological dynamics can produce a variety of striking patterns. On ecological time scales, pattern formation has been hypothesized to be due to the interaction between a species and its local environment. On longer time scales, evolutionary factors must be taken into account. To examine the evolutionary robustness of spatial pattern formation, we construct a spatially explicit model of vegetation in the presence of a pathogen. Initially, we compare the dynamics for vegetation parameters that lead to competition induced spatial patterns and those that do not. Over ecological time scales, banded spatial patterns dramatically reduced the ability of the pathogen to spread, lowered its endemic density and hence increased the persistence of the vegetation. To gain an evolutionary understanding, each plant was given a heritable trait defining its resilience to competition; greater competition leads to lower vegetation density but stronger spatial patterns. When a disease is introduced, the selective pressure on the plant's resilience to the competition parameter is determined by the transmission of the disease. For high transmission, vegetation that has low resilience to competition and hence strong spatial patterning is an evolutionarily stable strategy. This demonstrates a novel mechanism by which striking spatial patterns can be maintained by disease-driven selection. PMID:27628172

  19. Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas

    PubMed Central

    Campbell, Joshua D.; Alexandrov, Anton; Kim, Jaegil; Wala, Jeremiah; Berger, Alice H.; Pedamallu, Chandra Sekhar; Shukla, Sachet A.; Guo, Guangwu; Brooks, Angela N.; Murray, Bradley A.; Imielinski, Marcin; Hu, Xin; Ling, Shiyun; Akbani, Rehan; Rosenberg, Mara; Cibulskis, Carrie; Ramachandran, Aruna; Collisson, Eric A.; Kwiatkowski, David J.; Lawrence, Michael S.; Weinstein, John N.; Verhaak, Roel G. W.; Wu, Catherine J.; Hammerman, Peter S.; Cherniack, Andrew D.; Getz, Gad; Artyomov, Maxim N.; Schreiber, Robert; Govindan, Ramaswamy; Meyerson, Matthew

    2016-01-01

    To compare lung adenocarcinoma (ADC) and lung squamous cell carcinoma (SqCC) and to identify new drivers of lung carcinogenesis, we examined exome sequences and copy number profiles of 660 lung ADC and 484 lung SqCC tumor/normal pairs. Recurrent alterations in lung SqCCs were more similar to other squamous carcinomas than to lung ADCs. Novel significantly mutated genes included PPP3CA, DOT1L, and FTSJD1 in lung ADC, RASA1 in lung SqCC, and KLF5, EP300, and CREBBP in both tumor types. Novel amplification peaks encompassed MIR21 in lung ADC, MIR205 in lung SqCC, and MAPK1 in both. Lung ADCs lacking receptor tyrosine kinase/Ras/Raf alterations revealed mutations in SOS1, VAV1, RASA1, and ARHGAP35. Regarding neoantigens, 47% of the lung ADC and 53% of the lung SqCC tumors had at least 5 predicted neoepitopes. While targeted therapies for lung ADC and lung SqCC are largely distinct, immunotherapies may aid in treatment for both subtypes. PMID:27158780

  20. Pneumovirus-Induced Lung Disease in Mice Is Independent of Neutrophil-Driven Inflammation

    PubMed Central

    Lutter, René; Boon, Louis; Bem, Reinout A.; van Woensel, Job B. M.

    2016-01-01

    The human pneumovirus respiratory syncytial virus (RSV) is the most common pathogen causing lower respiratory tract disease in young children worldwide. A hallmark of severe human RSV infection is the strong neutrophil recruitment to the airways and lungs. Massive neutrophil activation has been proven detrimental in numerous diseases, yet in RSV the contribution of neutrophils to disease severity, and thereby, the relevance of targeting them, is largely unknown. To determine the relevance of potential neutrophil targeting therapies, we implemented antibody-mediated neutrophil depletion in a mouse pneumonia virus of mice (PVM) model. PVM is a host specific murine pneumovirus closely related to human RSV, which reproduces many of the features of RSV infection, such as high viral replication and neutrophil recruitment. Clinical disease and markers of lung inflammation and injury were studied in PVM-infected mice treated with either depleting or isotype control antibodies. To confirm our results we performed all experiments in two mice strains: C57Bl6 and BALBc mice. Neutrophil depletion in blood and lungs was efficient throughout the disease. Remarkably, in both mouse strains we found no difference in clinical disease severity between neutrophil-depleted and control arms. In line with this observation, we found no differences between groups in histopathological lung injury and lung viral loads. In conclusion, our study shows that in mice neutrophil recruitment to the lungs does not affect disease outcome or viral clearance during severe PVM infection. As such, this model does not support the notion that neutrophils play a key role in mouse pneumovirus disease. PMID:28005954

  1. AGER -429T/C Is Associated with an Increased Lung Disease Severity in Cystic Fibrosis

    PubMed Central

    Beucher, Julie; Boëlle, Pierre-Yves; Busson, Pierre-François; Muselet-Charlier, Céline; Clement, Annick; Corvol, Harriet; Abely, M.; Belleguic, C.; Bellon, G.; Bessaci, K.; Bonnel, A.S.; Brémont, F.; Brouard, J.; Bui, S.; Chiron, R.; Chumbi-Flores, R.; Clement, A.; Corvol, H.; Dalphin, J.C.; Dalphin, M.L.; David, V.; de Miranda, S.; Derelle, J.; Domblides, P.; Dominique, S.; Dubus, J.C.; Durieu, I.; Dury, S.; Ellaffi, M.; Epaud, R.; Fanton, A.; Fayon, M.; Fleurence, E.; Foucaud, P.; Ginies, J.L.; Godbert, B.; Grenet, D.; Guillot, M.; Héraud, M. C.; Housset, B.; Hubert, D.; Huet, F.; Kessler, R.; Labbé, A.; Laurans, M.; le Bourgeois, M.; le Roux, P.; Llerena, C.; Loeuille, G.A.; Marguet, C.; Mely, L.; Moisan-Petit, V.; Munck, A.; Murris-Espin, M.; Nove Josserand, R.; Pautard, J.C.; Pin, I.; Pramil, S.; Prevotat, A.; Rault, G.; Reix, P.; Remus, N.; Renouil, M.; Reynaud-Gaubert, M.; Richaud Thiriez, B.; Roussey, M.; Sermet-Gaudelus, I.; Stremler, N.; Uffredi, M.L.; Urban, T.; Vigneron, P.; Wallaert, B.; Weiss, L.

    2012-01-01

    The clinical course of cystic fibrosis (CF) varies between patients bearing identical CFTR mutations, suggesting the involvement of modifier genes. We assessed the association of lung disease severity with the variant AGER -429 T/C, coding for RAGE, a pro-inflammatory protein, in CF patients from the French CF Gene Modifier Study. We analyzed the lung function of 967 CF patients p.Phe508del homozygous. FEV1 was analyzed as CF-specific percentile adjusted on age, height and mortality. AGER -429T/C polymorphism was genotyped and its function was evaluated in vitro by measurement of the luciferase activity. AGER -429 minor allele (C) was associated with poorer lung function (p = 0.03). In vitro, the promoter activity was higher in cells transfected with AGER -429C compared to cells transfected with the AGER -429T allele (p = 0.016 in BEAS-2B cells). AGER seems to be a modifier gene of lung disease severity in CF, and could be an interesting biomarker of CF airway inflammation. The functional promoter AGER -429C variant is associated with an increased RAGE expression that can lead to an increased lung inflammation and a more severe lung disease. PMID:22860029

  2. AGER -429T/C is associated with an increased lung disease severity in cystic fibrosis.

    PubMed

    Beucher, Julie; Boëlle, Pierre-Yves; Busson, Pierre-François; Muselet-Charlier, Céline; Clement, Annick; Corvol, Harriet

    2012-01-01

    The clinical course of cystic fibrosis (CF) varies between patients bearing identical CFTR mutations, suggesting the involvement of modifier genes. We assessed the association of lung disease severity with the variant AGER -429 T/C, coding for RAGE, a pro-inflammatory protein, in CF patients from the French CF Gene Modifier Study. We analyzed the lung function of 967 CF patients p.Phe508del homozygous. FEV(1) was analyzed as CF-specific percentile adjusted on age, height and mortality. AGER -429T/C polymorphism was genotyped and its function was evaluated in vitro by measurement of the luciferase activity. AGER -429 minor allele (C) was associated with poorer lung function (p = 0.03). In vitro, the promoter activity was higher in cells transfected with AGER -429C compared to cells transfected with the AGER -429T allele (p = 0.016 in BEAS-2B cells). AGER seems to be a modifier gene of lung disease severity in CF, and could be an interesting biomarker of CF airway inflammation. The functional promoter AGER -429C variant is associated with an increased RAGE expression that can lead to an increased lung inflammation and a more severe lung disease.

  3. Lichenoid exanthema mimicking graft-versus-host disease associated with obstructive lung disease in a non-transplanted patient.

    PubMed

    Eberle, Franziska Carola; Holland, Angelique; Hörster, Stefan; Vogelmeier, Claus; Hertl, Michael

    2010-01-01

    Lichenoid graft-versus-host disease (GVHD) is commonly observed in patients who have received donor lymphocyte infusions or allogeneic bone marrow transplantation (BMT). Here we report a striking case of lichenoid GVH-like exanthema in a young woman without any history of blood transfusions or BMT. A polymorphous, multiforme-like exanthema was observed after systemic antibiotic therapy of bronchitis and was initially diagnosed as drug eruption. Later on, disseminated lichenoid papules were noticed on the trunk and extremities with all histologic and clinical characteristics of lichenoid GVHD. Cutaneous GVH-like disease developed, as did obstructive lung disease. Pulmonary as well as skin disease were both refractory to various immunosuppressive therapies. The immune pathogenesis that caused the skin and lung disease in this patient remains unclear. Multiple pregnancies with two abortions with the potential induction of microchimerism may play a role in the disease pathogenesis.

  4. Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas.

    PubMed

    Campbell, Joshua D; Alexandrov, Anton; Kim, Jaegil; Wala, Jeremiah; Berger, Alice H; Pedamallu, Chandra Sekhar; Shukla, Sachet A; Guo, Guangwu; Brooks, Angela N; Murray, Bradley A; Imielinski, Marcin; Hu, Xin; Ling, Shiyun; Akbani, Rehan; Rosenberg, Mara; Cibulskis, Carrie; Ramachandran, Aruna; Collisson, Eric A; Kwiatkowski, David J; Lawrence, Michael S; Weinstein, John N; Verhaak, Roel G W; Wu, Catherine J; Hammerman, Peter S; Cherniack, Andrew D; Getz, Gad; Artyomov, Maxim N; Schreiber, Robert; Govindan, Ramaswamy; Meyerson, Matthew

    2016-06-01

    To compare lung adenocarcinoma (ADC) and lung squamous cell carcinoma (SqCC) and to identify new drivers of lung carcinogenesis, we examined the exome sequences and copy number profiles of 660 lung ADC and 484 lung SqCC tumor-normal pairs. Recurrent alterations in lung SqCCs were more similar to those of other squamous carcinomas than to alterations in lung ADCs. New significantly mutated genes included PPP3CA, DOT1L, and FTSJD1 in lung ADC, RASA1 in lung SqCC, and KLF5, EP300, and CREBBP in both tumor types. New amplification peaks encompassed MIR21 in lung ADC, MIR205 in lung SqCC, and MAPK1 in both. Lung ADCs lacking receptor tyrosine kinase-Ras-Raf pathway alterations had mutations in SOS1, VAV1, RASA1, and ARHGAP35. Regarding neoantigens, 47% of the lung ADC and 53% of the lung SqCC tumors had at least five predicted neoepitopes. Although targeted therapies for lung ADC and SqCC are largely distinct, immunotherapies may aid in treatment for both subtypes.

  5. [Humidifier lung].

    PubMed

    Gerber, P; de Haller, R; Pyrozynski, W J; Sturzenegger, E R; Brändli, O

    1981-02-07

    Breathing air from a humidifier or an air conditioning unit contaminated by various microorganisms can cause an acute lung disease involving fever, cough and dyspnea, termed "humidifier fever". This type of hypersensitivity pneumonitis was first described in 1959 by PESTALOZZI in the Swiss literature and subsequently by BANASZAK et al. in the Anglo-American. Here a chronic form of this disease which led to pulmonary fibrosis is described: A 37-year-old woman who works in a cheese shop presented with dyspnea which had been progressive over two years, weight loss, a diffuse reticular pattern radiographically and a severe restrictive defect in lung function tests. Open lung biopsy revealed chronic interstitial and alveolar inflammation with non-caseating granulomas and fibrotic changes. Circulating immune complexes and precipitins against the contaminated humidifier water and cheese mites were found, but no antibodies suggesting legionnaires' disease. Two out of five otherwise healthy employees of this cheese shop, where a new humidifying system had been installed 7 years earlier, also had precipitins against the contaminated water from the humidifier and the cheese mites. Despite ending of exposure and longterm steroid and immunosuppressive therapy, the signs and symptoms of pulmonary fibrosis persisted. Contrary to the acute disease, this chronic form is termed "humidifier lung". The importance is stressed of investigating the possibility of exposure to contaminated humidifiers or air conditioning units in all cases of newly detected pulmonary fibrosis.

  6. Application of 'omics technologies to biomarker discovery in inflammatory lung diseases.

    PubMed

    Wheelock, Craig E; Goss, Victoria M; Balgoma, David; Nicholas, Ben; Brandsma, Joost; Skipp, Paul J; Snowden, Stuart; Burg, Dominic; D'Amico, Arnaldo; Horvath, Ildiko; Chaiboonchoe, Amphun; Ahmed, Hassan; Ballereau, Stéphane; Rossios, Christos; Chung, Kian Fan; Montuschi, Paolo; Fowler, Stephen J; Adcock, Ian M; Postle, Anthony D; Dahlén, Sven-Erik; Rowe, Anthony; Sterk, Peter J; Auffray, Charles; Djukanovic, Ratko

    2013-09-01

    Inflammatory lung diseases are highly complex in respect of pathogenesis and relationships between inflammation, clinical disease and response to treatment. Sophisticated large-scale analytical methods to quantify gene expression (transcriptomics), proteins (proteomics), lipids (lipidomics) and metabolites (metabolomics) in the lungs, blood and urine are now available to identify biomarkers that define disease in terms of combined clinical, physiological and patho-biological abnormalities. The aspiration is that these approaches will improve diagnosis, i.e. define pathological phenotypes, and facilitate the monitoring of disease and therapy, and also, unravel underlying molecular pathways. Biomarker studies can either select predefined biomarker(s) measured by specific methods or apply an "unbiased" approach involving detection platforms that are indiscriminate in focus. This article reviews the technologies presently available to study biomarkers of lung disease within the 'omics field. The contributions of the individual 'omics analytical platforms to the field of respiratory diseases are summarised, with the goal of providing background on their respective abilities to contribute to systems medicine-based studies of lung disease.

  7. Hierarchical Bayesian modeling of spatio-temporal patterns of lung cancer incidence risk in Georgia, USA: 2000-2007

    NASA Astrophysics Data System (ADS)

    Yin, Ping; Mu, Lan; Madden, Marguerite; Vena, John E.

    2014-10-01

    Lung cancer is the second most commonly diagnosed cancer in both men and women in Georgia, USA. However, the spatio-temporal patterns of lung cancer risk in Georgia have not been fully studied. Hierarchical Bayesian models are used here to explore the spatio-temporal patterns of lung cancer incidence risk by race and gender in Georgia for the period of 2000-2007. With the census tract level as the spatial scale and the 2-year period aggregation as the temporal scale, we compare a total of seven Bayesian spatio-temporal models including two under a separate modeling framework and five under a joint modeling framework. One joint model outperforms others based on the deviance information criterion. Results show that the northwest region of Georgia has consistently high lung cancer incidence risk for all population groups during the study period. In addition, there are inverse relationships between the socioeconomic status and the lung cancer incidence risk among all Georgian population groups, and the relationships in males are stronger than those in females. By mapping more reliable variations in lung cancer incidence risk at a relatively fine spatio-temporal scale for different Georgian population groups, our study aims to better support healthcare performance assessment, etiological hypothesis generation, and health policy making.

  8. The NF-kappaB signaling in cystic fibrosis lung disease: pathophysiology and therapeutic potential.

    PubMed

    Bodas, Manish; Vij, Neeraj

    2010-04-01

    Lung disease is the major cause of morbidity and mortality of cystic fibrosis (CF), an autosomal recessive disease caused by mutations in CF transmembrane-conductance regulator (CFTR) gene. In CF, elevated levels of interleukin-8 (IL-8) signaling mediated by the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) result in chronic infection, neutrophilic inflammation, and progressive airway destruction. The most frequent mutation in the CFTR gene is the deletion of phenylalanine 508 (DeltaF508), which results in its endoplasmic reticulum associated degradation (ERAD) by the ubiquitin-proteasome system. The inability of DeltaF508-CFTR to reach cell surface leads to inherently high levels of NF-kappaB. Severity of CF lung disease depends on the levels of functional CFTR on cell surface that control its chloride transport and NF-kappaB mediated innate immune response functions. NF-kappaB mediated chronic inflammation is a prominent feature of CF lung disease and the mechanism(s) by which CFTR regulates these inflammatory signaling pathways is becoming apparent. Recent data suggest that CFTR localization to lipid-rafts is critical for regulating NF-kappaB mediated innate immune response and chronic CF lung disease. We anticipate that targeting the pathways, which facilitates CFTR's rescue to the cell surface and lipid-rafts, will not only restore CFTR channel function but also control NF-kappaB mediated chronic inflammation, although the level of correction may be a critical factor for therapeutic efficacy. We discuss here the mechanisms of NF-kappaB induction in CF, pathogenesis of CF lung disease, and novel therapeutic strategies that may help in reversing the chronic CF lung disease.

  9. The NFκB Signaling in Cystic Fibrosis Lung Disease: Pathophysiology and Therapeutic Potential

    PubMed Central

    Bodas, Manish; Vij, Neeraj

    2010-01-01

    Lung disease is the major cause of morbidity and mortality of cystic fibrosis (CF), an autosomal recessive disease caused by mutations in CF transmembrane-conductance regulator (CFTR) gene. In CF, elevated levels of interleukin-8 (IL-8) signaling mediated by the nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) result in chronic infection, neutrophilic inflammation, and progressive airway destruction. The most frequent mutation in the CFTR gene is the deletion of phenylalanine 508 (ΔF508), which results in its endoplasmic reticulum associated degradation (ERAD) by the ubiquitin-proteasome system. The inability of ΔF508-CFTR to reach cell surface leads to inherently high levels of NFκB. Severity of CF lung disease depends on the levels of functional CFTR on cell surface that control its chloride transport and NFκB mediated innate immune response functions. NFκB mediated chronic inflammation is a prominent feature of CF lung disease and the mechanism(s) by which CFTR regulates these inflammatory signaling pathways is becoming apparent. Recent data suggest that CFTR localization to lipid-rafts is critical for regulating NFκB mediated innate immune response and chronic CF lung disease. We anticipate that targeting the pathways, which facilitates CFTR’s rescue to the cell surface and lipid-rafts, will not only restore CFTR channel function but also control NFκB mediated chronic inflammation, although the level of correction may be a critical factor for therapeutic efficacy. We discuss here the mechanisms of NFκB induction in CF, pathogenesis of CF lung disease, and novel therapeutic strategies that may help in reversing the chronic CF lung disease. PMID:20423679

  10. Integrative analysis of lung development-cancer expression associations reveals the roles of signatures with inverse expression patterns.

    PubMed

    Zhang, Chunlong; Li, Chunquan; Xu, Yanjun; Feng, Li; Shang, Desi; Yang, Xinmiao; Han, Junwei; Sun, Zeguo; Li, Yixue; Li, Xia

    2015-05-01

    Recent studies have focused on exploring the associations between organ development and malignant tumors; however, the clinical relevance of the development signatures was inadequately addressed in lung cancer. In this study, we explored the associations between lung development and lung cancer progression by analyzing a total of two development and seven cancer datasets. We identified representative expression patterns (continuously up- and down-regulated) from development and cancer profiles, and inverse pattern associations were observed at both the gene and functional levels. Furthermore, we dissected the biological processes dominating the associations, and found that proliferation and immunity were respectively involved in the two inverse development-cancer expression patterns. Through sub-pathway analysis of the signatures with inverse expression patterns, we finally identified a 13-gene risk signature from the cell cycle sub-pathway, and evaluated its predictive performance for lung cancer patient clinical outcome using independent cohorts. Our findings indicated that the integrative analysis of development and cancer expression patterns provided a framework for identifying effective molecular signatures for clinical utility.

  11. Quantitative consensus of supervised learners for diffuse lung parenchymal HRCT patterns

    NASA Astrophysics Data System (ADS)

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

    2013-03-01

    Automated lung parenchymal classification usually relies on supervised learning of expert chosen regions representative of the visually differentiable HRCT patterns specific to different pathologies (eg. emphysema, ground glass, honey combing, reticular and normal). Considering the elusiveness of a single most discriminating similarity measure, a plurality of weak learners can be combined to improve the machine learnability. Though a number of quantitative combination strategies exist, their efficacy is data and domain dependent. In this paper, we investigate multiple (N=12) quantitative consensus approaches to combine the clusters obtained with multiple (n=33) probability density-based similarity measures. Our study shows that hypergraph based meta-clustering and probabilistic clustering provides optimal expert-metric agreement.

  12. Experimental chronic kidney disease attenuates ischemia-reperfusion injury in an ex vivo rat lung model

    PubMed Central

    Huang, Kun-Lun; Lan, Chou-Chin; Hsu, Yu-Juei; Wu, Geng-Chin; Peng, Chia-Hui

    2017-01-01

    Lung ischemia reperfusion injury (LIRI) is one of important complications following lung transplant and cardiopulmonary bypass. Although patients on hemodialysis are still excluded as lung transplant donors because of the possible effects of renal failure on the lungs, increased organ demand has led us to evaluate the influence of chronic kidney disease (CKD) on LIRI. A CKD model was induced by feeding Sprague-Dawley rats an adenine-rich (0.75%) diet for 2, 4 and 6 weeks, and an isolated rat lung in situ model was used to evaluate ischemia reperfusion (IR)-induced acute lung injury. The clinicopathological parameters of LIRI, including pulmonary edema, lipid peroxidation, histopathological changes, immunohistochemistry changes, chemokine CXCL1, inducible nitric oxide synthase (iNOS), proinflammatory and anti-inflammatory cytokines, heat shock protein expression, and nuclear factor-κB (NF-κB) activation were determined. Our results indicated that adenine-fed rats developed CKD as characterized by increased blood urea nitrogen and creatinine levels and the deposition of crystals in the renal tubules and interstitium. IR induced a significant increase in the pulmonary arterial pressure, lung edema, lung injury scores, the expression of CXCL1 mRNA, iNOS level, and protein concentration of the bronchial alveolar lavage fluid (BALF). The tumor necrosis factor-α levels in the BALF and perfusate; the interleukin-10 level in the perfusate; and the malondialdehyde levels in the lung tissue and perfusate were also significantly increased by LIRI. Counterintuitively, adenine-induced CKD significantly attenuated the severity of lung injury induced by IR. CKD rats exhibited increased heat shock protein 70 expression and decreased activation of NF-κB signaling. In conclusion, adenine-induced CKD attenuated LIRI by inhibiting the NF-κB pathway. PMID:28291795

  13. Ultrahigh resolution optical coherence tomography imaging of diseased rat lung using Gaussian shaped super continuum sources

    NASA Astrophysics Data System (ADS)

    Nishizawa, N.; Ishida, S.; Kitatsuji, M.; Ohshima, H.; Hasegawa, Y.; Matsushima, M.; Kawabe, T.

    2012-02-01

    We have been investigating ultrahigh resolution optical coherence tomography (UHR-OCT) imaging of lung tissues using fiber super continuum sources. The high power, low-noise, Gaussian shaped supercontinuum generated with ultrashort pulses and optical fibers at several wavelengths were used as the broadband light sources for UHR-OCT. For the 800 nm wavelength region, the axial resolution was 3.0 um in air and 2.0 um in tissue. Since the lung consists of tiny alveoli which are separated by thin wall, the UHR-OCT is supposed to be effective for lung imaging. The clear images of alveoli of rat were observed with and without index matching effects by saline. In this work, we investigated the UHR-OCT imaging of lung disease model. The lipopolysaccharide (LPS) induced acute lung injury / acute respiratory distress syndrome (ALI/ARDS) model of rat was prepared as the sample with disease and the UHR-OCT imaging of the disease part was demonstrated. The increment of signal intensity by pleural thickening was observed. The accumulation of exudative fluid in alveoli was also observed for two samples. By the comparison with normal lung images, we can obviously show the difference in the ALI/ARDS models. Since the lung consists of alveolar surrounded by capillary vessels, the effect of red-blood cells (RBC) is considered to be important. In this work, ex-vivo UHR-OCT imaging of RBC was demonstrated. Each RBC was able to be observed individually using UHR-OCT. The effect of RBC was estimated with the rat lung perfused with PBS.

  14. Lung function and six-minute walk test performance in individuals with sickle cell disease

    PubMed Central

    Ohara, Daniela G.; Ruas, Gualberto; Walsh, Isabel A. P.; Castro, Shamyr S.; Jamami, Mauricio

    2014-01-01

    Background Sickle Cell Disease (SCD), which is characterized by a mutation in the gene encoding beta hemoglobin, causes bodily dysfunctions such as impaired pulmonary function and reduced functional capacity. Objective To assess changes in pulmonary function and functional capacity in patients with SCD and to identify the relationships between these variables. Method We evaluated sociodemographic, anthropometric, lung function (spirometry), respiratory (manovacuometer), peripheral muscle strength (Handgrip strength - HS) and functional capacity (i.e., the six-minute walk test) parameters in 21 individuals with SCD (average age of 29±6 years). Shapiro-Wilk, paired Student's, Wilcoxon, Pearson and Spearman correlation tests were used for statistical analyses, and the significance threshold was set at p<0.05. Results A total of 47.6% of the study subjects exhibited an altered ventilation pattern, 42.8% had a restrictive ventilatory pattern (RVP) and 4.8% exhibited a mixed ventilatory pattern (MVP). The observed maximal inspiratory pressure (MIP) values were below the predicted values for women (64 cmH2O), and the maximum expiratory pressure (MEP) values, HS values and distance walked during the 6MWT were below the predicted values for both men (103 cmH2O, 39 Kgf and 447 m, respectively) and women (64 cmH2O; 27 Kgf; 405 m, respectively). Positive correlations were observed between maximum voluntary ventilation (MVV) and MEP (r=0.4; p=0.046); MVV and BMI (r=0.6; p=0.003); and between HS and MIP (r=0.7; p=0.001), MEP (r=0.6; p=0.002), MVV (r=0.5; p=0.015), distance walked in the 6MWT (r=0.4; p=0.038) and BMI (r=0.6; p=0.004). Conclusions SCD promoted changes in lung function and functional capacity, including RVPs and a reduction in the distance walked in the 6MWT when compared to the predictions. In addition, significant correlations between the variables were observed. PMID:24675916

  15. Reperfusion edema after thromboendarterectomy: radiographic patterns of disease.

    PubMed

    Miller, W T; Osiason, A W; Langlotz, C P; Palevsky, H I

    1998-07-01

    In patients with chronic pulmonary embolism, pulmonary thromboendarterectomy may result in a unique form of noncardiogenic pulmonary edema termed reperfusion edema. This report reviews the authors' experience after pulmonary thromboendarterectomy with particular emphasis on the radiographic manifestations of reperfusion edema. The clinical and radiographic record of 25 patients who underwent pulmonary thromboendarterectomy at the University of Pennsylvania from 1985 through 1995 were reviewed. The zonal distribution of radiographic opacity, time to maximal opacity, and the time to clearance of reperfusion edema were determined. The relationship of these radiographic manifestations to clinical severity of disease and clinical outcome was examined. Reperfusion edema, characterized by patchy bilateral perihilar alveolar opacities, occurred in all but one patient. There is a lower lung zone predominance of opacities, but in individual cases, striking unilateral or haphazard arrangements of opacities may be seen. In this small sample of patients, no association between preoperative pulmonary arterial pressures and radiographic appearance or clinical outcome was found. However, severity of radiographic opacities, as measured by the extent of involved lung, correlated with disease severity, as measured by time to extubation and time to discharge. Pneumonia, defined as a radiographic opacity that evolves discordantly with the reperfusion edema opacities, occurred in 20% of cases. Reperfusion edema is a common consequence of pulmonary thromboendarterectomy. The severity of radiographic manifestations and clinical severity of disease are related. This characteristically appears as perihilar alveolar opacities.

  16. Bench-to-bedside review: Damage-associated molecular patterns in the onset of ventilator-induced lung injury

    PubMed Central

    2011-01-01

    Mechanical ventilation (MV) has the potential to worsen pre-existing lung injury or even to initiate lung injury. Moreover, it is thought that injurious MV contributes to the overwhelming inflammatory response seen in patients with acute lung injury or acute respiratory distress syndrome. Ventilator-induced lung injury (VILI) is characterized by increased endothelial and epithelial permeability and pulmonary inflammation, in which the innate immune system plays a key role. A growing body of evidence indicates that endogenous danger molecules, also termed damage-associated molecular patterns (DAMPs), are released upon tissue injury and modulate the inflammatory response. DAMPs activate pattern recognition receptors, may induce the release of proinflammatory cytokines and chemokines, and have been shown to initiate or propagate inflammation in non-infectious conditions. Experimental and clinical studies demonstrate the presence of DAMPs in bronchoalveolar lavage fluid in patients with VILI and the upregulation of pattern recognition receptors in lung tissue by MV. The objective of the present article is to review research in the area of DAMPs, their recognition by the innate immune system, their role in VILI, and the potential utility of blocking DAMP signaling pathways to reduce VILI in the critically ill. PMID:22216838

  17. Endothelial dysfunction and lung capillary injury in cardiovascular diseases.

    PubMed

    Guazzi, Marco; Phillips, Shane A; Arena, Ross; Lavie, Carl J

    2015-01-01

    Cardiac dysfunction of both systolic and diastolic origins leads to increased left atrial pressure, lung capillary injury and increased resistance to gas transfer. Acutely, pressure-induced trauma disrupts the endothelial and alveolar anatomical configuration and definitively causes an impairment of cellular pathways involved in fluid-flux regulation and gas exchange efficiency, a process well identified as stress failure of the alveolar-capillary membrane. In chronic heart failure (HF), additional stimuli other than pressure may trigger the true remodeling process of capillaries and small arteries characterized by endothelial dysfunction, proliferation of myofibroblasts, fibrosis and extracellular matrix deposition. In parallel there is a loss of alveolar gas diffusion properties due to the increased path from air to blood (thickening of extracellular matrix) and loss of fine molecular mechanism involved in fluid reabsorption and clearance. Deleterious changes in gas transfer not only reflect the underlying lung tissue damage but also portend independent prognostic information and may play a role in the pathogenesis of exercise limitation and ventilatory abnormalities observed in these patients. Few currently approved treatments for chronic HF have the potential to positively affect structural remodeling of the lung capillary network; angiotensin-converting enzyme inhibitors are one of the few currently established options. Recently, more attention has been paid to novel therapies specifically targeting the nitric oxide pathway as a suitable target to improve endothelial function and permeability as well as alveolar gas exchange properties.

  18. Clinical application of exhaled nitric oxide measurement in pediatric lung diseases

    PubMed Central

    2012-01-01

    Summary Fractional exhaled nitric oxide (FeNO) is a non invasive method for assessing the inflammatory status of children with airway disease. Different ways to measure FeNO levels are currently available. The possibility of measuring FeNO levels in an office setting even in young children, and the commercial availability of portable devices, support the routine use of FeNO determination in the daily pediatric practice. Although many confounding factors may affect its measurement, FeNO is now widely used in the management of children with asthma, and seems to provide significantly higher diagnostic accuracy than lung function or bronchial challenge tests. The role of FeNO in airway infection (e.g. viral bronchiolitis and common acquired pneumonia), in bronchiectasis, or in cases with diffuse lung disease is less clear. This review focuses on the most recent advances and the current clinical applications of FeNO measurement in pediatric lung disease. PMID:23273317

  19. Circulating Aneuploid Cells Detected in the Blood of Patients with Infectious Lung Diseases

    PubMed Central

    Kim, Hongsun; Cho, Jong Ho; Sonn, Chung-Hee; Kim, Jae-Won; Choi, Yul; Lee, Jinseon; Kim, Jhingook

    2017-01-01

    The identification of circulating tumor cells (CTCs) is clinically important for diagnosing cancer. We have previously developed a size-based filtration platform followed by epithelial cell adhesion molecule immunofluorescence staining for detecting CTCs. To characterize CTCs independently of cell surface protein expression, we incorporated a chromosomal fluorescence in situ hybridization (FISH) assay to detect abnormal copy numbers of chromosomes in cells collected from peripheral blood samples by the size-based filtration platform. Aneuploid cells were detected in the peripheral blood of patients with lung cancer. Unexpectedly, aneuploid cells were also detected in the control group, which consisted of peripheral blood samples from patients with benign lung diseases, such as empyema necessitatis and non-tuberculous mycobacterial lung disease. These findings suggest that chromosomal abnormalities are observed not only in tumor cells, but also in benign infectious diseases. Thus, our findings present new considerations and bring into light the possibility of false positives when using FISH for cancer diagnosis. PMID:28382274

  20. A Cytophaga species endotoxin as a putative agent of occupation-related lung disease.

    PubMed Central

    Flaherty, D K; Deck, F H; Hood, M A; Liebert, C; Singleton, F; Winzenburger, P; Bishop, K; Smith, L R; Bynum, L M; Witmer, W B

    1984-01-01

    A previous study suggested that a biologically active bacterial endotoxin was a putative agent of lung disease in a textile-producing facility. The endotoxin was isolated from the biomass growing in a chilled-water spray air humidification system. The bacterial flora of the air humidification system were isolated and taxonomically identified to the genus level. By using indirect immunofluorescence assays, a serologically reactive Cytophaga species was identified. A serologically reactive, biologically active (Limulus assay) endotoxin was purified from phenol extracts of the Cytophaga species. The endotoxin contained sugars, hexosamines, and lipids identical to those found in the humidifier biomass endotoxin. All subjects with biopsy-proven and suspected lung disease had antibodies directed toward the purified Cytophaga endotoxin. The data suggest that the Cytophaga endotoxin is the putative agent of lung disease in the textile facility. PMID:6360896

  1. A case of solely lung-involved IgG4-related disease mimicking tuberculosis.

    PubMed

    Tan, Hongyi; Li, Haitao; Hu, Yongbing; Niu, Ruichao; Pan, Pinhua; Hu, Chengping

    2015-01-01

    IgG4-related disease (IgG4-RD) is a chronic progressive autoimmune disease. Solely lung involved IgG4-RD is extremely rare. Herein, we reported a case of IgG4-related disease as mimicking tuberculosis. A 52-year-old male patient was admitted due to cough and hemoptysis for two months and fever for 1 month. The pre-admission diagnosis in another hospital was secondary pulmonary tuberculosis, but the quadruple anti-tuberculosis therapy was ineffective and the disease condition continued to deteriorate. The percutaneous lung biopsy was carried out after admission and the pathological diagnosis was IgG4-related disease. The patient's disease condition was improved following hormonal therapy.

  2. Restrictive lung disease is an independent predictor of exercise intolerance in the adult with congenital heart disease

    PubMed Central

    Ginde, Salil; Bartz, Peter J.; Hill, Garick D.; Danduran, Michael J.; Biller, Julie; Sowinski, Jane; Tweddell, James S.; Earing, Michael G.

    2016-01-01

    Background/Objectives Following repair of congenital heart disease (CHD), adult patients are at risk for reduced exercise capacity. Restrictive lung disease (RLD) may contribute to reduced exercise capacity in this population. The aim of this study was to determine the prevalence of RLD and its impact on exercise tolerance in the adult with congenital heart disease. Methods One hundred consecutive adult patients with CHD, who underwent routine cardiopulmonary exercise testing with spirometry, were evaluated. Clinical data was obtained by retrospective chart review. Results Patients from 10 major diagnostic groups were identified. The median age for the cohort was 31 years (range 18–63) and included 43 males and 57 females. Most patients, 79%, had at least one previous surgical procedure. Based on spirometry and flow/volume loops, 50 patients were classified as normal pulmonary function, 44 patients had patterns suggestive of RLD, 4 suggestive of mixed (obstructive and restrictive), and 2 indeterminate. Risk factors associated with RLD include history of multiple thoracotomies (odds ratio=9.01, p=0.05) and history of atrial arrhythmias (odd ratio=4.25, p=0.05). Overall, 56% of the patients had abnormal exercise capacity. Spirometry suggestive of RLD was a significant risk factor for decreased exercise capacity (odds ratio=3.65, p=0.03). Patients with spirometry suggesting RLD also had lower exercise duration (p=0.004) and a higher New York Heart Association Functional Class (p=0.02). History of previous surgery and decreased heart rate reserve were also significant risk factors for decreased exercise capacity. Conclusion Abnormal spirometry suggestive of RLD is common in the adult with CHD and is a significant risk factor for decreased exercise tolerance in this population. Further studies, are needed to evaluate the relationship between RLD and exercise intolerance and its relationship to mortality in the adult with CHD. PMID:23075089

  3. Identification of genes differentially regulated by vitamin D deficiency that alter lung pathophysiology and inflammation in allergic airways disease.

    PubMed

    Foong, Rachel E; Bosco, Anthony; Troy, Niamh M; Gorman, Shelley; Hart, Prue H; Kicic, Anthony; Zosky, Graeme R

    2016-09-01

    Vitamin D deficiency is associated with asthma risk. Vitamin D deficiency may enhance the inflammatory response, and we have previously shown that airway remodeling and airway hyperresponsiveness is increased in vitamin D-deficient mice. In this study, we hypothesize that vitamin D deficiency would exacerbate house dust mite (HDM)-induced inflammation and alterations in lung structure and function. A BALB/c mouse model of vitamin D deficiency was established by dietary manipulation. Responsiveness to methacholine, airway smooth muscle (ASM) mass, mucus cell metaplasia, lung and airway inflammation, and cytokines in bronchoalveolar lavage (BAL) fluid were assessed. Gene expression patterns in mouse lung samples were profiled by RNA-Seq. HDM exposure increased inflammation and inflammatory cytokines in BAL, baseline airway resistance, tissue elastance, and ASM mass. Vitamin D deficiency enhanced the HDM-induced influx of lymphocytes into BAL, ameliorated the HDM-induced increase in ASM mass, and protected against the HDM-induced increase in baseline airway resistance. RNA-Seq identified nine genes that were differentially regulated by vitamin D deficiency in the lungs of HDM-treated mice. Immunohistochemical staining confirmed that protein expression of midline 1 (MID1) and adrenomedullin was differentially regulated such that they promoted inflammation, while hypoxia-inducible lipid droplet-associated, which is associated with ASM remodeling, was downregulated. Protein expression studies in human bronchial epithelial cells also showed that addition of vitamin D decreased MID1 expression. Differential regulation of these genes by vitamin D deficiency could determine lung inflammation and pathophysiology and suggest that the effect of vitamin D deficiency on HDM-induced allergic airways disease is complex.

  4. Correlation of spicule sign on computed tomography scans with peripheral lung cancers associated with interstitial lung disease and chronic obstructive pulmonary disease.

    PubMed

    Chen, L; Gao, L; Wu, W L

    2015-03-27

    The objective of this study was to investigate the correlation between spicular signs on computed tomography (CT) scans and peripheral lung cancer (PLC) that is associated with interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD). We analyzed clinical data from 96 PLC cases and grouped patients based on whether they had interstitial pneumonia into either ILD/COPD group or non-ILD/COPD group. The occurrence rate of spicule sign was 90.3% in the ILD/COPD group and 61.8% in the non-ILD/COPD group, respectively. There was a significant difference between these groups (P < 0.05). There were no significant differences in the occurrence rate of spicular signs among patients with different pathological types of PLC. The severity of ILD affected the spicular morphology on CT scans directly. There was a significant correlation between the appearance of spicule sign on CT scans and PLC that was associated with ILD/COPD.

  5. Lung cancer and its association with chronic obstructive pulmonary disease: update on nexus of epigenetics

    PubMed Central

    Sundar, Isaac K.; Mullapudi, Nandita; Yao, Hongwei; Spivack, Simon D.; Rahman, Irfan

    2013-01-01

    Purpose of review Chronic obstructive pulmonary disease (COPD) and lung cancer are the leading causes of morbidity and mortality worldwide. The current research is focused on identifying the common and disparate events involved in epigenetic modifications that concurrently occur during the pathogenesis of COPD and lung cancer. The purpose of this review is to describe the current knowledge and understanding of epigenetic modifications in pathogenesis of COPD and lung cancer. Recent findings This review provides an update on advances of how epigenetic modifications are linked to COPD and lung cancer, and their commonalities and disparities. The key epigenetic modification enzymes (e.g. DNA methyltransferases – CpG methylation, histone acetylases/deacetylases and histone methyltransferases/demethylases) that are identified to play an important role in COPD and lung tumorigenesis and progression are described in this review. Summary Distinct DNA methyltransferases and histone modification enzymes are differentially involved in pathogenesis of lung cancer and COPD, although some of the modifications are common. Understanding the epigenetic modifications involved in pathogenesis of lung cancer or COPD with respect to common and disparate mechanisms will lead to targeting of epigenetic therapies against these disorders. PMID:21537190

  6. Ventilation/perfusion lung scan in pulmonary veno-occlusive disease.

    PubMed

    Seferian, Andrei; Helal, Badia; Jaïs, Xavier; Girerd, Barbara; Price, L