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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. 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.

  5. Lung Diseases

    MedlinePlus

    ... many disorders affecting the lungs, such as asthma, COPD, infections like influenza, pneumonia and tuberculosis, lung cancer, and many other breathing problems. Some lung diseases can lead to respiratory failure. Dept. of Health and Human Services Office on Women's Health

  6. Lung disease

    MedlinePlus

    ... the lungs to take in oxygen and release carbon dioxide. People with this type of lung disorder often ... the lungs to take up oxygen and release carbon dioxide. These diseases may also affect heart function. An ...

  7. 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…

  8. 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

  9. 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 ...

  10. Enhanced Classification of Interstitial Lung Disease Patterns in HRCT Images Using Differential Lacunarity

    PubMed Central

    Vasconcelos, Verónica; Barroso, João; Marques, Luis; Silvestre Silva, José

    2015-01-01

    The analysis and interpretation of high-resolution computed tomography (HRCT) images of the chest in the presence of interstitial lung disease (ILD) is a time-consuming task which requires experience. In this paper, a computer-aided diagnosis (CAD) scheme is proposed to assist radiologists in the differentiation of lung patterns associated with ILD and healthy lung parenchyma. Regions of interest were described by a set of texture attributes extracted using differential lacunarity (DLac) and classical methods of statistical texture analysis. The proposed strategy to compute DLac allowed a multiscale texture analysis, while maintaining sensitivity to small details. Support Vector Machines were employed to distinguish between lung patterns. Training and model selection were performed over a stratified 10-fold cross-validation (CV). Dimensional reduction was made based on stepwise regression (F-test, p value < 0.01) during CV. An accuracy of 95.8 ± 2.2% in the differentiation of normal lung pattern from ILD patterns and an overall accuracy of 94.5 ± 2.1% in a multiclass scenario revealed the potential of the proposed CAD in clinical practice. Experimental results showed that the performance of the CAD was improved by combining multiscale DLac with classical statistical texture analysis. PMID:26798638

  11. Antecedents of chronic lung disease following three patterns of early respiratory disease in preterm infants

    PubMed Central

    Laughon, Matthew; Bose, Carl; Allred, Elizabeth N.; O’Shea, T. Michael; Ehrenkranz, Richard A.; Van Marter, Linda J.; Leviton, Alan

    2016-01-01

    OBJECTIVES/INTRODUCTION The incidence of chronic lung disease (CLD) varies among groups defined by their early pattern of respiratory disease. Although CLD is common among infants with continuous exposure to increased ambient oxygen throughout the first two postnatal weeks the antecedents of CLD among preterm infants without this exposure are not well understood. PATIENTS AND METHODS We examined data collected prospectively on the 1204 (out of 1506) infants born in 2002 to 2004 at 23 to 27 completed weeks of gestation who survived to 36 weeks post-menstrual age (PMA). Based on their initial respiratory presentation and need for supplemental oxygen during the first two weeks, infants were classified as having early and persistent pulmonary dysfunction (EPPD), early recovery of pulmonary function followed by deterioration (PD), or consistently good pulmonary function characterized by low FiO2 (Low FiO2). RESULTS CLD was diagnosed in 69% of infants with EPPD, in 52% with PD, and 17% in the Low FiO2 group. Risk factors for CLD varied among these groups. Birth weight z-score < -1 conveyed information about CLD risk in all three groups and was the major risk factor for infants in the Low FiO2 group (Odds Ratio [OR] 27; 95% confidence interval [CI] 7–95). Mechanical ventilation at 7 days was associated with increased risk in the pulmonary deterioration group (OR 4.2, 95% CI 2.5–6.9) and the early and persistent pulmonary dysfunction group (OR 2.7, 95% CI 1.5–4.7), but not the Low FiO2 group (OR 1.5, 95% CI 0.5–3.9). CONCLUSION Both the likelihood of a very preterm infant developing CLD and the profile of risk factors linked with CLD are related to the infant’s pattern of respiratory disease during the first two postnatal weeks. Among infants with little exposure to oxygen during this period, fetal growth restriction, not mechanical ventilation, is the factor with the strongest association with CLD. PMID:20688867

  12. 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 ... is responsible for some types of interstitial lung diseases. Specific types include Black lung disease among coal ...

  13. 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 ...

  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. 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 ...

  16. 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

  17. Childhood Interstitial Lung Disease

    MedlinePlus

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

  18. Worldwide patterns of bronchodilator responsiveness: results from the Burden of Obstructive Lung Disease study

    PubMed Central

    Vollmer, William M; Lamprecht, Bernd; Mannino, David M; Jithoo, Anamika; Nizankowska-Mogilnicka, Ewa; Mejza, Filip; Gislason, Thorarinn; Burney, Peter G J; Buist, A Sonia

    2012-01-01

    Rationale Criteria for a clinically significant bronchodilator response (BDR) are mainly based on studies in patients with obstructive lung diseases. Little is known about the BDR in healthy general populations, and even less about the worldwide patterns. Methods 10 360 adults aged 40 years and older from 14 countries in North America, Europe, Africa and Asia participated in the Burden of Obstructive Lung Disease study. Spirometry was used before and after an inhaled bronchodilator to determine the distribution of the BDR in population-based samples of healthy non-smokers and individuals with airflow obstruction. Results In 3922 healthy never smokers, the weighted pooled estimate of the 95th percentiles (95% CI) for bronchodilator response were 284 ml (263 to 305) absolute change in forced expiratory volume in 1 s from baseline (ΔFEV1); 12.0% (11.2% to 12.8%) change relative to initial value (%ΔFEV1i); and 10.0% (9.5% to 10.5%) change relative to predicted value (%ΔFEV1p). The corresponding mean changes in forced vital capacity (FVC) were 322 ml (271 to 373) absolute change from baseline (ΔFVC); 10.5% (8.9% to 12.0%) change relative to initial value (ΔFVCi); and 9.2% (7.9% to 10.5%) change relative to predicted value (ΔFVCp). The proportion who exceeded the above threshold values in the subgroup with spirometrically defined Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2 and higher (FEV1/FVC <0.7 and FEV1% predicted <80%) were 11.1%, 30.8% and 12.9% respectively for the FEV1-based thresholds and 22.6%, 28.6% and 22.1% respectively for the FVC-based thresholds. Conclusions The results provide reference values for bronchodilator responses worldwide that confirm guideline estimates for a clinically significant level of BDR in bronchodilator testing. PMID:22544896

  19. Mortality patterns from lung cancer and nonneoplastic respiratory disease among white males in the Beryllium Case Registry

    SciTech Connect

    Infante, P.F.; Wagoner, J.K.; Sprince, N.L.

    1980-02-01

    Study was undertaken of mortality patterns among white males entered into the Beryllium Case Registry (BCR) while alive with a diagnosis of beryllium-related nonneoplastic respiratory symptoms or disease. Analyses demonstrate an excessive risk of lung cancer among those subjects in the BCR who had been previously diagnosed with acute chemical pneumonitis or bronchitis secondary to short-term beryllium exposure. In the evaluation of the excessive lung cancer risk in this population, consideration should be given to the competing effects from the high case fatality rate of nonneoplastic respiratory disease. This excessive risk of lung cancer could not be explained on the basis of cigarette smoking per se. The findings of the present study utilizing subjects in the BCR are consistent with results of animal studies that over 30 years ago first demonstrated beryllium to be a carcinogen and with numerous epidemiologic studies demonstrating an increased risk of lung cancer among workers occupationally exposed to beryllium and its compounds.

  20. A Sparse Representation Based Method to Classify Pulmonary Patterns of Diffuse Lung Diseases

    PubMed Central

    Xu, Rui; Tachibana, Rie; Kido, Shoji

    2015-01-01

    We applied and optimized the sparse representation (SR) approaches in the computer-aided diagnosis (CAD) to classify normal tissues and five kinds of diffuse lung disease (DLD) patterns: consolidation, ground-glass opacity, honeycombing, emphysema, and nodule. By using the K-SVD which is based on the singular value decomposition (SVD) and orthogonal matching pursuit (OMP), it can achieve a satisfied recognition rate, but too much time was spent in the experiment. To reduce the runtime of the method, the K-Means algorithm was substituted for the K-SVD, and the OMP was simplified by searching the desired atoms at one time (OMP1). We proposed three SR based methods for evaluation: SR1 (K-SVD+OMP), SR2 (K-Means+OMP), and SR3 (K-Means+OMP1). 1161 volumes of interest (VOIs) were used to optimize the parameters and train each method, and 1049 VOIs were adopted to evaluate the performances of the methods. The SR based methods were powerful to recognize the DLD patterns (SR1: 96.1%, SR2: 95.6%, SR3: 96.4%) and significantly better than the baseline methods. Furthermore, when the K-Means and OMP1 were applied, the runtime of the SR based methods can be reduced by 98.2% and 55.2%, respectively. Therefore, we thought that the method using the K-Means and OMP1 (SR3) was efficient for the CAD of the DLDs. PMID:25821509

  1. A sparse representation based method to classify pulmonary patterns of diffuse lung diseases.

    PubMed

    Zhao, Wei; Xu, Rui; Hirano, Yasushi; Tachibana, Rie; Kido, Shoji

    2015-01-01

    We applied and optimized the sparse representation (SR) approaches in the computer-aided diagnosis (CAD) to classify normal tissues and five kinds of diffuse lung disease (DLD) patterns: consolidation, ground-glass opacity, honeycombing, emphysema, and nodule. By using the K-SVD which is based on the singular value decomposition (SVD) and orthogonal matching pursuit (OMP), it can achieve a satisfied recognition rate, but too much time was spent in the experiment. To reduce the runtime of the method, the K-Means algorithm was substituted for the K-SVD, and the OMP was simplified by searching the desired atoms at one time (OMP1). We proposed three SR based methods for evaluation: SR1 (K-SVD+OMP), SR2 (K-Means+OMP), and SR3 (K-Means+OMP1). 1161 volumes of interest (VOIs) were used to optimize the parameters and train each method, and 1049 VOIs were adopted to evaluate the performances of the methods. The SR based methods were powerful to recognize the DLD patterns (SR1: 96.1%, SR2: 95.6%, SR3: 96.4%) and significantly better than the baseline methods. Furthermore, when the K-Means and OMP1 were applied, the runtime of the SR based methods can be reduced by 98.2% and 55.2%, respectively. Therefore, we thought that the method using the K-Means and OMP1 (SR3) was efficient for the CAD of the DLDs. PMID:25821509

  2. 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 ...

  3. 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. PMID:25477529

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

    PubMed Central

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

    2015-01-01

    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. PMID:25477529

  5. Patterns of neutrophil serine protease-dependent cleavage of surfactant protein D in inflammatory lung disease.

    PubMed

    Cooley, Jessica; McDonald, Barbara; Accurso, Frank J; Crouch, Erika C; Remold-O'Donnell, Eileen

    2008-04-01

    The manuscript presents definitive studies of surfactant protein D (SP-D) in the context of inflammatory lung fluids. The extent of SP-D depletion in bronchoalveolar lavage fluid (BALF) of children affected with cystic fibrosis (CF) is demonstrated to correlate best with the presence of the active neutrophil serine protease (NSP) elastase. Novel C-terminal SP-D fragments of 27 kDa and 11 kDa were identified in patient lavage fluid in addition to the previously described N-terminal, 35-kDa fragment by the use of isoelectrofocusing, modified blotting conditions, and region-specific antibodies. SP-D cleavage sites were identified. In vitro treatment of recombinant human SP-D dodecamers with NSPs replicated the fragmentation, but unexpectedly, the pattern of SP-D fragments generated by NSPs was dependent on calcium concentration. Whereas the 35- and 11-kDa fragments were generated when incubations were performed in low calcium (200 microM CaCl(2)), incubations in physiological calcium (2 mM) with higher amounts of elastase or proteinase-3 generated C-terminal 27, 21, and 14 kDa fragments, representing cleavage within the collagen and neck regions. Studies in which recombinant SP-D cleavage by individual NSPs was quantitatively evaluated under low and high calcium conditions showed that the most potent NSP for cleaving SP-D is elastase, followed by proteinase-3, followed by cathepsin G. These relative potency findings were considered in the context of other studies that showed that active NSPs in CF BALF are in the order: elastase, followed by cathepsin G, followed by proteinase-3. The findings support a pre-eminent role for neutrophil elastase as the critical protease responsible for SP-D depletion in inflammatory lung disease. PMID:18211966

  6. Interstitial lung disease

    MedlinePlus

    Diffuse parenchymal lung disease; Alveolitis; Idiopathic pulmonary pneumonitis (IPP) ... The lungs contain tiny air sacs (alveoli), which is where oxygen is absorbed. These air sacs expand with each ...

  7. Lung Diseases

    MedlinePlus

    ... on Carcinogens: Captafol A Human Health Perspective on Climate Change (Full Report) (4MB) Certain Glass Wool Fibers (Inhalable) ( ... Environmental Public Health (PEPH) (1MB) Programs and Initiatives: Climate Change and Human Health Respiratory Disease and the Environment ( ...

  8. 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

  9. 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. PMID:26024603

  10. Lung Diseases and Conditions

    MedlinePlus

    ... Share this page from the NHLBI on Twitter. Lung Diseases and Conditions Breathing is a complex process. ... your bronchial tubes ( bronchitis ) or deep in your lungs ( pneumonia ). These infections cause a buildup of mucus ...

  11. 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.

  12. Lung Disease and Hypertension

    PubMed Central

    Imaizumi, Yuki; Eguchi, Kazuo; Kario, Kazuomi

    2014-01-01

    Chronic obstructive pulmonary disease (COPD) patients are at a high risk of developing cardiovascular diseases. Airflow limitation is a predictor of future risks of hypertension and cardiovascular events. COPD is now understood as a systemic inflammatory disease, with the focus on inflammation of the lungs. An association between inflammation and sympathetic overactivity has also been reported. In this article, we review the association between chronic lung disease and the risks of hypertension, cardiovascular morbidity, the underlying mechanisms, and the therapeutic approach to hypertension and cardiovascular diseases in patients with lung diseases. PMID:26587450

  13. 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. ...

  14. Multiple cystic lung disease.

    PubMed

    Ferreira Francisco, Flavia Angélica; Soares Souza, Arthur; Zanetti, Gláucia; Marchiori, Edson

    2015-12-01

    Multiple cystic lung disease represents a diverse group of uncommon disorders that can present a diagnostic challenge due to the increasing number of diseases associated with this presentation. High-resolution computed tomography of the chest helps to define the morphological aspects and distribution of lung cysts, as well as associated findings. The combination of appearance upon imaging and clinical features, together with extrapulmonary manifestations, when present, permits confident and accurate diagnosis of the majority of these diseases without recourse to open-lung biopsy. The main diseases in this group that are discussed in this review are lymphangioleiomyomatosis, pulmonary Langerhans cell histiocytosis and folliculin gene-associated syndrome (Birt-Hogg-Dubé); other rare causes of cystic lung disease, including cystic metastasis of sarcoma, are also discussed. Disease progression is unpredictable, and understanding of the complications of cystic lung disease and their appearance during evolution of the disease are essential for management. Correlation of disease evolution and clinical context with chest imaging findings provides important clues for defining the underlying nature of cystic lung disease, and guides diagnostic evaluation and management. PMID:26621970

  15. Interstitial lung disease

    MedlinePlus

    ... to the chest Working with or around asbestos, coal dust, cotton dust, and silica dust (called occupational ... routinely screened for lung disease. These jobs include coal mining, sand blasting, and working on a ship.

  16. Reflux and Lung Disease

    MedlinePlus

    ... Reflux and Lung Disease Proper Hydration Sodium Dangers Plant-Based Diets Why Breakfast Matters Patients & Visitors Giving For Professionals About Us Treatment & Programs Health Insights Doctors & Departments Research & Science Education & Training Make an Appointment Make a Donation ...

  17. Rheumatoid lung disease

    MedlinePlus

    ... Philadelphia, PA: Elsevier Saunders; 2016:chap 65. Lake F, Proudman S. Rheumatoid arthritis and lung disease: from mechanisms to a practical approach. Semin Respir Crit Care Med . 2014;35:222-238. PMID: 24668537 www.ncbi.nlm.nih. ...

  18. Cystic and nodular lung disease.

    PubMed

    Richards, J Caleb; Lynch, David A; Chung, Jonathan H

    2015-06-01

    Diffuse cystic and nodular lung diseases have characteristic imaging findings. The most common causes of cystic lung disease are lymphangioleiomyomatosis and Langerhans cell histiocytosis. Other less common cystic lung diseases include Birt-Hogg-Dube syndrome, lymphocytic interstitial pneumonitis, and light chain deposition disease. Computed tomography is used to differentiate cystic lung disease from emphysema, honeycombing, cavities, and bronchiectasis, which mimic cystic lung disease. Diffuse nodular lung disease are categorized as centrilobular, perilymphatic, and random types. In diffuse nodular lung disease, a specific diagnosis is achieved through a combination of history, physical examination, and imaging findings. PMID:26024606

  19. Histopathology of lung disease in the connective tissue diseases.

    PubMed

    Vivero, Marina; Padera, Robert F

    2015-05-01

    The pathologic correlates of interstitial lung disease (ILD) secondary to connective tissue disease (CTD) comprise a diverse group of histologic patterns. Lung biopsies in patients with CTD-associated ILD tend to demonstrate simultaneous involvement of multiple anatomic compartments of the lung. Certain histologic patterns tend to predominate in each defined CTD, and it is possible in many cases to confirm connective tissue-associated lung disease and guide patient management using surgical lung biopsy. This article will cover the pulmonary pathologies seen in rheumatoid arthritis, systemic sclerosis, myositis, systemic lupus erythematosus, Sjögren syndrome, and mixed CTD. PMID:25836637

  20. Inherited interstitial lung disease.

    PubMed

    Garcia, Christine Kim; Raghu, Ganesh

    2004-09-01

    This article focuses on recent advances in the identification of genes and genetic polymorphisms that have been implicated in the development of human interstitial lung diseases. It focuses on the inherited mendelian diseases in which pulmonary fibrosis is part of the clinical phenotype and the genetics of familial idiopathic pulmonary fibrosis and other rare inherited interstitial lung diseases. The article also reviews the association studies that have been published to date regarding the genetics of sporadic idiopathic pulmonary fibrosis. The reader is directed to recent reviews on human genetic predisposition of sarcoidosis, environmental-related, drug-related, connective tissue related pulmonary fibrosis, and genetic predisposition of fibrosis in animal models. PMID:15331184

  1. Immunologic lung disease

    SciTech Connect

    Harman, E.M.

    1985-07-01

    The term immunologic lung disease comprises a broad spectrum of disease. The authors have covered a few entities in which recent studies have been particularly helpful in elucidating pathophysiology though not in uncovering the inciting cause. Common to all of these entities is the problem of finding appropriate methods of defining disease activity and response to treatment. As exemplified by the improved outlook for Goodpasture's syndrome with elucidation of its underlying immunopathology, it is likely that better understanding of the immunologic basis of sarcoid and interstitial disease may be helpful in planning more effective treatment strategies. 44 references.

  2. Subclinical Interstitial Lung Disease

    PubMed Central

    Doyle, Tracy J.; Hunninghake, Gary M.

    2012-01-01

    The widespread use of high-resolution computed tomography in clinical and research settings has increased the detection of interstitial lung abnormalities (ILA) in asymptomatic and undiagnosed individuals. We reported that in smokers, ILA were present in about 1 of every 12 high-resolution computed tomographic scans; however, the long-term significance of these subclinical changes remains unclear. Studies in families affected with pulmonary fibrosis, smokers with chronic obstructive pulmonary disease, and patients with inflammatory lung disease have shown that asymptomatic and undiagnosed individuals with ILA have reductions in lung volume, functional limitations, increased pulmonary symptoms, histopathologic changes, and molecular profiles similar to those observed in patients with clinically significant interstitial lung disease (ILD). These findings suggest that, in select at-risk populations, ILA may represent early stages of pulmonary fibrosis or subclinical ILD. The growing interest surrounding this topic is motivated by our poor understanding of the inciting events and natural history of ILD, coupled with a lack of effective therapies. In this perspective, we outline past and current research focused on validating radiologic, physiological, and molecular methods to detect subclinical ILD. We discuss the limitations of the available cross-sectional studies and the need for future longitudinal studies to determine the prognostic and therapeutic implications of subclinical ILD in populations at risk of developing clinically significant ILD. PMID:22366047

  3. 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.

  4. 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

  5. Eosinophilic Lung Diseases.

    PubMed

    Cottin, Vincent

    2016-09-01

    Eosinophilic lung diseases especially comprise eosinophilic pneumonia or as the more transient Löffler syndrome, which is most often due to parasitic infections. The diagnosis of eosinophilic pneumonia is based on characteristic clinical-imaging features and the demonstration of alveolar eosinophilia, defined as at least 25% eosinophils at BAL. Peripheral blood eosinophilia is common but may be absent at presentation in idiopathic acute eosinophilic pneumonia, which may be misdiagnosed as severe infectious pneumonia. All possible causes of eosinophilia, including drug, toxin, fungus related etiologies, must be thoroughly investigated. Extrathoracic manifestations should raise the suspicion of eosinophilic granulomatosis with polyangiitis. PMID:27514599

  6. What Are Asbestos-Related Lung Diseases?

    MedlinePlus

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

  7. 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 ...

  8. Types of Childhood Interstitial Lung Disease

    MedlinePlus

    ... the NHLBI on Twitter. Types of Childhood Interstitial Lung Disease The broad term "childhood interstitial lung disease" ( ... affect are shown in the illustration below. Normal Lungs and Lung Structures Figure A shows the location ...

  9. Lung function in sickle cell disease.

    PubMed

    Koumbourlis, Anastassios C

    2014-03-01

    Although some of the most severe complications of Sickle Cell Disease (SCD) tend to be acute and severe (e.g. acute chest syndrome, stroke etc.), the chronic ones can be equally debilitating. Prominent among them is the effect that the disease has on lung growth and function. For many years the traditional teaching has been that SCD is associated with the development of a restrictive lung defect. However, there is increasing evidence that this is not a universal finding and that at least during childhood and adolescence, the majority of the patients have a normal or obstructive pattern of lung function. The following article reviews the current knowledge on the effects of SCD on lung growth and function. Special emphasis is given to the controversies among the published articles in the literature and discusses possible causes for these discrepancies. PMID:24268618

  10. Respiratory Conditions Update: Restrictive Lung Disease.

    PubMed

    Robinson, H Coleman

    2016-09-01

    Restrictive lung diseases are a heterogeneous group of conditions characterized by a restrictive pattern on spirometry and confirmed by a reduction in total lung volume. Patients with more severe symptoms may have a reduced diffusing capacity of the lung for carbon monoxide. Etiologies can be intrinsic with lung parenchymal involvement, as in interstitial lung diseases, or extrinsic to the lung, as in obesity and neuromuscular disorders. Idiopathic pulmonary fibrosis is a chronic progressive interstitial pneumonia with fibrosis for which treatment is primarily supportive with oxygen therapy, pulmonary rehabilitation, and management of comorbid conditions. Newer drugs for idiopathic pulmonary fibrosis, such as pirfenidone and nintedanib, can slow disease progression. Referral for evaluation for lung transplantation is recommended for appropriate patients. Obstructive sleep apnea and obesity hypoventilation syndrome increasingly are common health issues, with symptoms that can include snoring, daytime somnolence, difficulty concentrating, fatigue, witnessed apneas, and morning headaches. Serum bicarbonate may serve as a biomarker in screening for subclinical obesity hypoventilation syndrome. Preoperative evaluations should assess pulmonary risk in addition to cardiac risk with a thorough history, laboratory tests, and functional capacity assessments. Optimization of management may include weight loss, pulmonary rehabilitation, oxygen therapy, and respiratory support. PMID:27576233

  11. 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. PMID:26324804

  12. 7. Immunologic lung disease.

    PubMed

    Greenberger, Paul A

    2008-02-01

    The lung is an extremely complex organ and participates in initial responses to inhaled antigens, infectious agents, and irritants or as a response to exposure through the oral, parenteral, or transdermal routes. There can be constriction of the airways or involvement or even destruction of the lung parenchyma, depending on the condition. This review focuses on selected aspects of the pulmonary innate and adaptive immune responses; the new condition World Trade Center cough, which can cause an asthma-like presentation and resemble reactive airways dysfunction syndrome; and the diagnosis and treatment of various immunologic lung conditions. Innate immune responses occur in the acute respiratory distress syndrome and in transfusion-related acute lung injury. Adaptive immune responses involve specialized mucosal and systemic immune responses, lymphocytes, and antibodies and can result in CD4+ TH1 and TH2 phenotypes, such as TH1 for tuberculosis and TH2 for asthma. PMID:18241689

  13. Work-related lung diseases.

    PubMed

    Weston, Ainsley

    2011-01-01

    Work-related respiratory diseases affect people in every industrial sector, constituting approximately 60% of all disease and injury mortality and 70% of all occupational disease mortality. There are two basic types: interstitial lung diseases, that is the pneumoconioses (asbestosis, byssinosis, chronic beryllium disease, coal workers' pneumoconiosis (CWP), silicosis, flock workers' lung, and farmers' lung disease), and airways diseases, such as work-related or exacerbated asthma, chronic obstructive pulmonary disease and bronchiolitis obliterans (a disease that was recognized in the production of certain foods only 10 years ago). Common factors in the development of these diseases are exposures to dusts, metals, allergens and other toxins, which frequently cause oxidative damage. In response, the body reacts by activating primary immune response genes (i.e. cytokines that often lead to further oxidative damage), growth factors and tissue remodelling proteins. Frequently, complex imbalances in these processes contribute to the development of disease. For example, tissue matrix metalloproteases can cause the degradation of tissue, as in the development of CWP small profusions, but usually overexpression of matrix metalloproteases is controlled by serum protein inhibitors. Thus, disruption of such a balance can lead to adverse tissue damage. Susceptibility to these types of lung disease has been investigated largely through candidate gene studies, which have been characteristically small, often providing findings that have been difficult to corroborate. An important exception to this has been the finding that the HLA-DPB11(E69) allele is closely associated with chronic beryllium disease and beryllium sensitivity. Although chronic beryllium disease is only caused by exposure to beryllium, inheritance of HLA-DPB1(E69) carries an increased risk of between two- and 30-fold in beryllium exposed workers. Most, if not all, of these occupationally related diseases are

  14. Aspiration-related lung diseases.

    PubMed

    Prather, Andrew D; Smith, Tristan R; Poletto, Dana M; Tavora, Fabio; Chung, Jonathan H; Nallamshetty, Leelakrishna; Hazelton, Todd R; Rojas, Carlos A

    2014-09-01

    Aspiration is a common but underrecognized clinicopathologic entity, with varied radiographic manifestations. Aspiration represents a spectrum of diseases, including diffuse aspiration bronchiolitis, aspiration pneumonitis, airway obstruction by foreign body, exogenous lipoid pneumonia, interstitial fibrosis, and aspiration pneumonia with or without lung abscess formation. Many patients who aspirate do not present with disease, suggesting that pathophysiology is related to a variety of factors, including decreased levels of consciousness, dysphagia, impaired mucociliary clearance, composition of aspirate, and impaired host defenses. In this pictorial essay, we will review the different types of aspiration lung diseases, focusing on their imaging features and differential diagnosis. PMID:24911122

  15. 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

  16. 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

  17. CHRONIC EXPOSURE TO OZONE CAUSES RESTRICTIVE LUNG DISEASE

    EPA Science Inventory

    A chronic study to determine the progression and or/reversibility of ozone-induced lung disease was conducted. ale rats were exposed to a diurnal pattern of ozone (O3) for 1 wk, 3 wk, 3 mo, 12 mo, or 18 mo. he occurrence of chronic lung disease was determined by structural and fu...

  18. 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. PMID:19170214

  19. Agricultural lung disease.

    PubMed

    Spurzem, John R; Romberger, Debra J; Von Essen, Susanna G

    2002-12-01

    Agricultural work is associated with high rates of injury, disability, and illness. Agricultural workers are at increased risk for a variety of illnesses including respiratory disorders, dermatologic conditions, and cancer. The recognition of ODTS led to increased understanding of acute illness in farmers and grain workers. Previously, many cases of acute illness were probably erroneously called farmer's lung. The same agents that are responsible for ODTS are responsible for the high prevalence of bronchitis in certain agricultural workers. The recent description of the innate immune system is very exciting because it will lead to increased understanding of the pathogenesis of organic dust induced disorders. PMID:12512166

  20. Monitoring of Lung Involvement in Rheumatologic Disease.

    PubMed

    Paschalaki, Koralia E; Jacob, Joseph; Wells, Athol U

    2016-01-01

    The monitoring of lung involvement in patients with connective tissue diseases is central to optimal long-term management and is directed towards: (a) the detection of supervening lung involvement not present at presentation and (b) the identification of disease progression in established lung disease. For both goals, accurate surveillance requires multi-disciplinary evaluation with the integration of symptomatic change, serial pulmonary function trends and imaging data. Evaluated in isolation, each of these monitoring domains has significant limitations. Symptomatic change may be confounded by a wide variety of systemic factors. Pulmonary function tests provide the most reliable data, but are limited by measurement variability, the heterogeneity of functional patterns and the confounding effects of non-pulmonary factors. Chest radiography is insensitive to change but may provide rapid confirmation of major disease progression or alert the clinician to respiratory co-morbidities. Although high-resolution computed tomography has a central role in assessing disease severity, it should be used very selectively as a monitoring tool due to the associated radiation burden. Ancillary tests include echocardiography and exercise testing to proactively identify cases of pulmonary hypertension and worsening of oxygenation. In summary, a multi-disciplinary approach is essential for the identification of disease progression and prompt treatment of comorbidities that severely impact on the morbidity and mortality of disease. PMID:26735151

  1. 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

  2. Cilia dysfunction in lung disease.

    PubMed

    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 composed 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, to repeated chest infections, and to the 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

  3. Flavorings-Related Lung Disease

    MedlinePlus

    ... message, please visit this page: About CDC.gov . Workplace Safety & Health Topics Flavorings-Related Lung Disease Exposures to ... Pinterest Twitter YouTube NIOSH Homepage NIOSH A-Z Workplace Safety & Health Topics Publications and Products Programs Contact NIOSH ...

  4. Diet and obstructive lung diseases.

    PubMed

    Romieu, I; Trenga, C

    2001-01-01

    The results presented in this review suggest that the impact of nutrition on obstructive lung disease is most evident for antioxidant vitamins, particularly vitamin C and, to a lesser extent, vitamin E. By decreasing oxidant insults to the lung, antioxidants could modulate the development of chronic lung diseases and lung function decrement. Antioxidant vitamins could also play an important role in gene-environment interactions in complex lung diseases such as childhood asthma. Data also suggest that omega-3 fatty acids may have a potentially protective effect against airway hyperreactivity and lung function decrements; however, relevant data are still sparse. Although epidemiologic data suggest that consumption of fresh fruit may reduce risk of noncarcinogenic airway limitation, there are no clear data on which nutrients might be most relevant. While some studies evaluate daily intake of vitamin C, other studies use fruit consumption as a surrogate for antioxidant intake. Given the dietary intercorrelations among antioxidant vitamins, particularly vitamin C, beta-carotene, and flavonoids, as well as other micronutrients, it may be difficult to isolate a specific effect. Some population subgroups with higher levels of oxidative stress, such as cigarette smokers, may be more likely to benefit from dietary supplementation, since some studies have suggested that antioxidant intake may have a greater impact in this group. Studies of lung function decrement and COPD in adults suggest that daily intake of vitamin C at levels slightly exceeding the current Recommended Dietary Allowance (60 mg/day among nonsmokers and 100 mg/day among smokers) may have a protective effect (20). In the Schwartz and Weiss (85) and Britton et al. (87) studies, an increase of 40 mg/day in vitamin C intake led to an approximate 20-ml increase in FEV1. Daily mean vitamin C intakes in these studies were 66 mg and 99.2 mg, respectively, and the highest intake level (178 mg/day) was approximately

  5. Pericytes in chronic lung disease.

    PubMed

    Rowley, Jessica E; Johnson, Jill R

    2014-01-01

    Pericytes are mesenchymal cells embedded within the abluminal surface of the endothelium of microvessels such as capillaries, pre-capillary arterioles, post-capillary and collecting venules, where they maintain microvascular homeostasis and participate in angiogenesis. In addition to their roles in supporting the vasculature and facilitating leukocyte extravasation, pericytes have been recently investigated as a subpopulation of mesenchymal stem cells (MSCs) due to their capacity to differentiate into numerous cell types including the classic MSC triad, i.e. osteocytes, chondrocytes and adipocytes. Other studies in models of fibrotic inflammatory disease of the lung have demonstrated a vital role of pericytes in myofibroblast activation, collagen deposition and microvascular remodelling, which are hallmark features of chronic lung diseases such as asthma, chronic obstructive pulmonary disorder, pulmonary fibrosis and pulmonary hypertension. Further studies into the mechanisms of the pericyte-to-myofibroblast transition and migration to fibrotic foci will hopefully clarify the role of these cells in chronic lung disease and confirm the importance of pericytes in human fibrotic pulmonary disease. PMID:25034005

  6. 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. PMID:26961983

  7. 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

  8. 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

    Leidinger, Petra; Backes, Christina; Dahmke, Indra N; Galata, Valentina; Huwer, Hanno; Stehle, Ingo; Bals, Robert; Keller, Andreas; Meese, Eckart

    2014-10-15

    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

  9. An observational study of giant cell interstitial pneumonia and lung fibrosis in hard metal lung disease

    PubMed Central

    Tanaka, Junichi; Moriyama, Hiroshi; Terada, Masaki; Takada, Toshinori; Suzuki, Eiichi; Narita, Ichiei; Kawabata, Yoshinori; Yamaguchi, Tetsuo; Hebisawa, Akira; Sakai, Fumikazu; Arakawa, Hiroaki

    2014-01-01

    Background Hard metal lung disease has various pathological patterns including giant cell interstitial pneumonia (GIP) and usual interstitial pneumonia (UIP). Although the UIP pattern is considered the prominent feature in advanced disease, it is unknown whether GIP finally progresses to the UIP pattern. Objectives To clarify clinical, pathological and elemental differences between the GIP and UIP patterns in hard metal lung disease. Methods A cross-sectional study of patients from 17 institutes participating in the 10th annual meeting of the Tokyo Research Group for Diffuse Parenchymal Lung Diseases, 2009. Nineteen patients (seven female) diagnosed with hard metal lung disease by the presence of tungsten in lung specimens were studied. Results Fourteen cases were pathologically diagnosed as GIP or centrilobular inflammation/fibrosing. The other five cases were the UIP pattern or upper lobe fibrosis. Elemental analyses of lung specimens of GIP showed tungsten throughout the centrilobular fibrotic areas. In the UIP pattern, tungsten was detected in the periarteriolar area with subpleural fibrosis, but no association with centrilobular fibrosis or inflammatory cell infiltration. The GIP group was younger (43.1 vs 58.6 years), with shorter exposure duration (73 vs 285 months; p<0.01), lower serum KL-6 (398 vs 710 U/mL) and higher lymphocyte percentage in bronchoalveolar lavage fluid (31.5% vs 3.22%; p<0.05) than the fibrosis group. Conclusions The UIP pattern or upper lobe fibrosis is remarkably different from GIP in distribution of hard metal elements, associated interstitial inflammation and fibrosis, and clinical features. In hard metal lung disease, the UIP pattern or upper lobe fibrosis may not be an advanced form of GIP. PMID:24674995

  10. Restrictive lung disease in pregnancy.

    PubMed

    King, T E

    1992-12-01

    Restrictive ventilatory defects characterized by a reduction in lung volumes and an increase in the ratio of forced expiratory volume in 1 second to forced vital capacity occur when lung expansion is limited because of alterations in the lung parenchyma or because of abnormalities in the pleura, chest wall, or neuromuscular apparatus. Few studies have examined pregnant women with carefully defined restrictive lung disorders. The majority of pulmonary diseases have their onset after the childbearing years. When present, most do not alter fertility. Further, these disorders are only a relative contraindication to pregnancy because both the fetus and mother are able to survive without a high risk of increased morbidity or mortality. The clinical course of sarcoidosis is generally not altered by pregnancy. Factors indicative of a poor prognosis in sarcoidosis and pregnancy include parenchymal lesions on chest radiography, advanced roentgenologic staging, advanced maternal age, low inflammatory activity, requirement for drugs other than corticosteroids, and the presence of extrapulmonary sarcoidosis. Pregnancy seldom has a significant effect on the course of the connective tissue diseases. In PSS with significant renal involvement, pregnancy has the potential for poor fetal prognosis and the risk of maternal death due to a lethal progression of renal failure. Worsening of SLE is uncommon in pregnancy, and prophylactic therapy is generally not necessary. Most women with LAM are advised to avoid pregnancy or the use of estrogens because of the concern that it will lead to worsening of their disease. The incidence of kyphoscoliosis in pregnancy is relatively high. Premature birth rates are higher than that in the normal population. The risk of progression of the abnormal curve in a scoliotic patient appears low. However, women with unstable scolioses at the time of pregnancy can demonstrate progression of the curve with the pregnancy. Respiratory complications during

  11. Pulmonary Hypertension in Parenchymal Lung Disease

    PubMed Central

    Tsangaris, Iraklis; Tsaknis, Georgios; Anthi, Anastasia; Orfanos, Stylianos E.

    2012-01-01

    Idiopathic pulmonary arterial hypertension (IPAH) has been extensively investigated, although it represents a less common form of the pulmonary hypertension (PH) family, as shown by international registries. Interestingly, in types of PH that are encountered in parenchymal lung diseases such as interstitial lung diseases (ILDs), chronic obstructive pulmonary disease (COPD), and many other diffuse parenchymal lung diseases, some of which are very common, the available data is limited. In this paper, we try to browse in the latest available data regarding the occurrence, pathogenesis, and treatment of PH in chronic parenchymal lung diseases. PMID:23094153

  12. Functional respiratory assessment in interstitial lung disease.

    PubMed

    Miguel-Reyes, José Luis; Gochicoa-Rangel, Laura; Pérez-Padilla, Rogelio; Torre-Bouscoulet, Luis

    2015-01-01

    Interstitial lung diseases are a heterogeneous group of disorders that affect, to a greater or lesser degree, the alveolus, peripheral airway, and septal interstitium. Functional assessment in patients suspected of having an interstitial lung disease has implications for diagnosis and makes it possible to objectively analyze both response to treatment and prognosis. Recently the clinical value of lung-diffusing capacity and the six-minute walking test has been confirmed, and these are now important additions to the traditional assessment of lung function that is based on spirometry. Here we review the state-of-the-art methods for the assessment of patients with interstitial lung disease. PMID:25857578

  13. 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

  14. Infiltrative lung diseases in pregnancy.

    PubMed

    Freymond, N; Cottin, V; Cordier, J F

    2011-03-01

    Pregnancy may affect the diagnosis, management, and outcome of infiltrative lung disease (ILD). Conversely, ILD may affect pregnancy. ILD may occur as a result of drugs administered commonly or specifically during pregnancy. Most ILDs predominate in patients older than 40 years and are thus rare in pregnant women. During pregnancy ILD may arise de novo and preexisting ILD may be exacerbated or significantly worsened. Some ILDs generally do not alter the management of pregnancy, labor, or delivery. Preexisting ILD no longer contraindicates pregnancy systematically, but thorough evaluation of ILD before pregnancy is required to identify potential contraindications and adapt monitoring. PMID:21277455

  15. The UPR and lung disease.

    PubMed

    Osorio, Fabiola; Lambrecht, Bart; Janssens, Sophie

    2013-05-01

    The respiratory tract has a surface area of approximately 70 m(2) that is in direct contact with the external environment. Approximately 12,000 l of air are inhaled daily, exposing the airway epithelium to up to 25 million particles an hour. Several inhaled environmental triggers, like cigarette smoke, diesel exhaust, or allergens, are known inducers of endoplasmatic reticulum (ER) stress and cause a dysregulation in ER homeostasis. Furthermore, some epithelial cell types along the respiratory tract have a secretory function, producing large amounts of mucus or pulmonary surfactant, as well as innate host defense molecules like defensins. To keep up with their secretory demands, these cells must rely on the appropriate functioning and folding capacity of the ER, and they are particularly more vulnerable to conditions of unresolved ER stress. In the lung interstitium, triggering of ER stress pathways has a major impact on the functioning of vascular smooth muscle cells and fibroblasts, causing aberrant dedifferentiation and proliferation. Given the large amounts of foreign material inhaled, the lung is densely populated by various types of immune cells specialized in engulfing and killing pathogens and in secreting cytokines/chemokines for efficient microbial clearance. Unfolded protein response signaling cascades have been shown to intersect with the functioning of immune cells at all levels. The current review aims to highlight the role of ER stress in health and disease in the lung, focusing on its impact on different structural and inflammatory cell types. PMID:23536202

  16. Lung Cancer and Interstitial Lung Diseases: A Systematic Review

    PubMed Central

    Archontogeorgis, Kostas; Steiropoulos, Paschalis; Tzouvelekis, Argyris; Nena, Evangelia; Bouros, Demosthenes

    2012-01-01

    Interstitial lung diseases (ILDs) represent a heterogeneous group of more than two hundred diseases of either known or unknown etiology with different pathogenesis and prognosis. Lung cancer, which is the major cause of cancer death in the developed countries, is mainly attributed to cigarette smoking and exposure to inhaled carcinogens. Different studies suggest a link between ILDs and lung cancer, through different pathogenetic mechanisms, such as inflammation, coagulation, dysregulated apoptosis, focal hypoxia, activation, and accumulation of myofibroblasts as well as extracellular matrix accumulation. This paper reviews current evidence on the association between lung cancer and interstitial lung diseases such as idiopathic pulmonary fibrosis, sarcoidosis, systemic sclerosis, dermatomyositis/polymyositis, rheumatoid arthritis, systemic lupus erythematosus, and pneumoconiosis. PMID:22900168

  17. Lung Disease at High Altitude

    PubMed Central

    Stream, JO; Luks, AM; Grissom, CK

    2016-01-01

    Large numbers of people travel to high altitudes, entering an environment of hypobaric hypoxia. Exposure to low oxygen tension leads to a series of important physiologic responses that allow individuals to tolerate these hypoxic conditions. However, in some cases hypoxia triggers maladaptive responses that lead to various forms of acute and chronic high altitude illness, such as high-altitude pulmonary edema or chronic mountain sickness. Because the respiratory system plays a critical role in these adaptive and maladaptive responses, patients with underlying lung disease may be at increased risk for complications in this environment and warrant careful evaluation before any planned sojourn to higher altitudes. In this review, we describe respiratory disorders that occur with both acute and chronic exposures to high altitudes. These disorders may occur in any individual who ascends to high altitude, regardless of his/her baseline pulmonary status. We then consider the safety of high-altitude travel in patients with various forms of underlying lung disease. The available data regarding how these patients fare in hypoxic conditions are reviewed, and recommendations are provided for management prior to and during the planned sojourn. PMID:20477353

  18. Diffuse Cystic Lung Disease. Part I.

    PubMed

    Gupta, Nishant; Vassallo, Robert; Wikenheiser-Brokamp, Kathryn A; McCormack, Francis X

    2015-06-15

    The diffuse cystic lung diseases (DCLDs) are a group of pathophysiologically heterogenous processes that are characterized by the presence of multiple spherical or irregularly shaped, thin-walled, air-filled spaces within the pulmonary parenchyma. Although the mechanisms of cyst formation remain incompletely defined for all DCLDs, in most cases lung remodeling associated with inflammatory or infiltrative processes results in displacement, destruction, or replacement of alveolar septa, distal airways, and small vessels within the secondary lobules of the lung. The DCLDs can be broadly classified according to underlying etiology as those caused by low-grade or high-grade metastasizing neoplasms, polyclonal or monoclonal lymphoproliferative disorders, infections, interstitial lung diseases, smoking, and congenital or developmental defects. In the first of a two-part series, we present an overview of the cystic lung diseases caused by neoplasms, infections, smoking-related diseases, and interstitial lung diseases, with a focus on lymphangioleiomyomatosis and pulmonary Langerhans cell histiocytosis. PMID:25906089

  19. 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.

  20. 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

  1. 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.

  2. 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, ...

  3. [Interstitial lung diseases associated with smoking].

    PubMed

    Nová, Markéta; Hornychová, Helena; Matěj, Radoslav

    2016-01-01

    There are many different interstitial lung diseases associated with smoking. This short review describes officially recognized disorders (desquamative interstitial pneumonia, respiratory bronchiolitis and pulmonary Langerhans´cells histiocytosis) and entities with uncertain relationship to smoking, which have recently been published in the literature. Histopathological pictures and differential diagnosis of smoking-related diseases of the lungs are discussed. PMID:27223588

  4. [The lung in heart diseases].

    PubMed

    Sill, V

    1990-02-01

    The effects of "hypocirculation" and "hypercirculation" of the lungs are small. Hypocirculation has an influence of the ventilation/perfusion ratio, and can thus contribute to hypocapnia. In the early stages, hypercirculation--in particular via a left-to-right shung, leads to an increase in diffusion capacity; after a course of many years, a "counter-situation" occurs. Progressive pulmonary hypertension, as is exemplified for mitral stenosis, leads to measurable restrictive and obstructive impairment of function, and possible to unspecific hyper-reaction, as also, over the long-term, to a diminishement in membrane diffusion capacity. Chronic left heart failure is characterised by interstitial oedema at the level of the alveolar and bronchial capillary beds. The results are measurable restrictions in the static volumes, and in particular of the obstruction parameters and the closing volume that involve the small airways. In the individual case, no statement as to the extent of left heart failure is possible. In the passive pulmonary hypertension phase, diffusion capacity increases; in the further course of the disease, with development of interstitial and alveolar oedema, it decreases again. In acute left heart failure, the persistance and/or extent of pulmonary oedema is not determined solely by the magnitude of the pulmonary venous pressure. Permeability oedema--brought about by mediators--would appear to be significant on the basis of animal experiments. Not infrequently, left cardiac failure leads to small pleural effusions which occur in combination with substantial atelectasia, the aetiology of which is unclear. Interpretation difficulties are caused by the clinical findings and function-analytical data obtained in patients with a combination of chronic lung disease and reducted volume storage capacity of the pulmonary circulation and of the left heart failure, a common situation in the elderly patient. Diminished pulmonary function parameters that fail to

  5. Right Ventricular Dysfunction in Chronic Lung Disease

    PubMed Central

    Kolb, Todd M.; Hassoun, Paul M.

    2012-01-01

    Right ventricular dysfunction arises in chronic lung disease when chronic hypoxemia and disruption of pulmonary vascular beds contribute to increase ventricular afterload, and is generally defined by hypertrophy with preserved myocardial contractility and cardiac output. Although the exact prevalence is unknown, right ventricular hypertrophy appears to be a common complication of chronic lung disease, and more frequently complicates advanced lung disease. Right ventricular failure is rare, except during acute exacerbations of chronic lung disease or when multiple co-morbidities are present. Treatment is targeted at correcting hypoxia and improving pulmonary gas exchange and mechanics. There are presently no convincing data to support the use of pulmonary hypertension-specific therapies in patients with right ventricular dysfunction secondary to chronic lung disease. PMID:22548815

  6. Surfactant protein D in human lung diseases.

    PubMed

    Hartl, D; Griese, M

    2006-06-01

    The lung is continuously exposed to inhaled pollutants, microbes and allergens. Therefore, the pulmonary immune system has to defend against harmful pathogens, while an inappropriate inflammatory response to harmless particles must be avoided. In the bronchoalveolar space this critical balance is maintained by innate immune proteins, termed surfactant proteins. Among these, surfactant protein D (SP-D) plays a central role in the pulmonary host defence and the modulation of allergic responses. Several human lung diseases are characterized by decreased levels of bronchoalveolar SP-D. Thus, recombinant SP-D has been proposed as a therapeutical option for cystic fibrosis, neonatal lung disease and smoking-induced emphysema. Furthermore, SP-D serum levels can be used as disease activity markers for interstitial lung diseases. This review illustrates the emerging role of SP-D translated from in vitro studies to human lung diseases. PMID:16684127

  7. Imaging of occupational and environmental lung diseases

    SciTech Connect

    Akira, M.

    2008-03-15

    The chest radiograph is the basic tool for identifying occupational and environmental lung diseases; however, its sensitivity and specificity for the diagnosis of occupational and environmental lung diseases are low. High-resolution CT is the optimal method of recognizing parenchymal abnormalities in occupational and environmental disease. With the exception of pleural plaques, the CT findings of occupational and environmental lung diseases are nonspecific. Therefore, correlation of imaging features with history of exposure, other clinical features, and sometimes pathology is needed for the diagnosis of pneumoconiosis.

  8. Smoking-related interstitial lung diseases.

    PubMed

    Vassallo, Robert; Ryu, Jay H

    2012-03-01

    Cigarette smoke, a toxic collection of thousands of chemicals generated from combustion of tobacco, is recognized as the primary causative agent of certain diffuse interstitial and bronchiolar lung diseases. Most patients afflicted with these disorders are cigarette smokers, and smoking cessation has been shown to be capable of inducing disease remission and should occupy a pivotal role in the management of all smokers with these diffuse lung diseases. The role of pharmacotherapy with corticosteroids or other immunomodulating agents is not well established but may be considered in patients with progressive forms of smoking-related interstitial lung diseases. PMID:22365253

  9. Oxidants in Acute and Chronic Lung Disease

    PubMed Central

    Mannam, Praveen; Srivastava, Anup; Sugunaraj, Jaya Prakash; Lee, Patty J; Sauler, Maor

    2015-01-01

    Oxidants play an important role in homeostatic function, but excessive oxidant generation has an adverse effect on health. The manipulation of Reactive Oxygen Species (ROS) can have a beneficial effect on various lung pathologies. However indiscriminate uses of anti-oxidant strategies have not demonstrated any consistent benefit and may be harmful. Here we propose that nuanced strategies are needed to modulate the oxidant system to obtain a beneficial result in the lung diseases such as Acute Lung Injury (ALI) and Chronic Obstructive Pulmonary Disease (COPD). We identify novel areas of lung oxidant responses that may yield fruitful therapies in the future. PMID:25705575

  10. Mesenchymal stem cells and inflammatory lung diseases.

    PubMed

    Iyer, S S; Co, C; Rojas, M

    2009-03-01

    Mesenchymal stem cells (MSCs) are emerging as a therapeutic modality in various inflammatory disease states. A number of ongoing randomized Phase I/II clinical trials are evaluating the effects of allogeneic MSC infusion in patients with multiple sclerosis, graft-versus-host disease, Crohn's disease, and severe chronic myocardial ischemia. MSCs are also being considered as a potential therapy in patients with inflammatory lung diseases. Several studies, including our own, have demonstrated compelling benefits from the administration of MSCs in animal models of lung injury. These studies are leading to growing interest in the therapeutic use of MSCs in inflammatory lung diseases. In this Review, we describe how the immunoregulatory effects of MSCs can confer substantial protection in the setting of lung diseases such as acute lung injury, chronic obstructive pulmonary disease, asthma, and pulmonary hypertension. We also address potential pitfalls related to the therapeutic use of MSCs in fibrotic lung diseases such as idiopathic pulmonary fibrosis. In addition, we identify emerging areas for MSC- based therapies in modulating oxidative stress and in attenuating inflammation in alcohol-related acute lung injury. PMID:19352305

  11. Imaging of Childhood Interstitial Lung Disease

    PubMed Central

    2010-01-01

    The aphorism that children are not little adults certainly applies for the imaging of interstitial lung disease. Acquiring motion-free images of fine pulmonary structures at desired lung volumes is much more difficult in children than in adults. Several forms of interstitial lung disease are unique to children, and some forms of interstitial lung disease encountered in adults rarely, if ever, occur in children. Meticulous attention to imaging technique and specialized knowledge are required to properly perform and interpret chest imaging studies obtained for the evaluation of childhood interstitial lung disease (chILD). This review will address technique recommendations for imaging chILD, the salient imaging findings in various forms of chILD, and the efficacy of imaging in the diagnosis and management of chILD. PMID:22332031

  12. Diffuse Cystic Lung Disease. Part II.

    PubMed

    Gupta, Nishant; Vassallo, Robert; Wikenheiser-Brokamp, Kathryn A; McCormack, Francis X

    2015-07-01

    The diffuse cystic lung diseases have a broad differential diagnosis. A wide variety of pathophysiological processes spanning the spectrum from airway obstruction to lung remodeling can lead to multifocal cyst development in the lung. Although lymphangioleiomyomatosis and pulmonary Langerhans cell histiocytosis are perhaps more frequently seen in the clinic, disorders such as Birt-Hogg-Dubé syndrome, lymphocytic interstitial pneumonia, follicular bronchiolitis, and light-chain deposition disease are increasingly being recognized. Obtaining an accurate diagnosis can be challenging, and management approaches are highly disease dependent. Unique imaging features, genetic tests, serum studies, and clinical features provide invaluable clues that help clinicians distinguish among the various etiologies, but biopsy is often required for definitive diagnosis. In part II of this review, we present an overview of the diffuse cystic lung diseases caused by lymphoproliferative disorders, genetic mutations, or aberrant lung development and provide an approach to aid in their diagnosis and management. PMID:25906201

  13. [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. PMID:25708093

  14. [Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD)].

    PubMed

    Goeckenjan, G

    2003-05-01

    Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) designates interstitial lung changes in smokers, characterized histologically by bronchiolocentric accumulation of pigmented alveolar macrophages and fibrotic or cellular inflammatory changes of pulmonary interstitium. The definition is nearly identical to that of condensate pneumopathy, smoker's pneumopathy or smoker's lung, defined by accumulation of pigmented alveolar macrophages with bland alveoloseptal or peribronchial fibrosis and cellular inflammation of the bronchial wall. In addition to respiratory bronchiolitis, which is found in nearly all smokers, RB-ILD comprises a broad spectrum of varying degrees of the interstitial reaction to the exogenous injury of inhalation smoking with gradual transition to desquamative interstitial pneumonia (DIP). In most cases RB-ILD manifestations are subclinical and detected coincidentally. Radiographic features are reticulonodular and ground glass opacities of the lung. The high resolution computed tomography reveals centrilobular nodules, ground glass opacities, thickening of bronchial walls, and in some cases a reticular pattern. Mild emphysema is frequent. Lung function analysis reveals only minor restrictive or obstructive defects in most cases, often combined with hyperinflation. CO diffusing capacity is slightly to moderately impaired. Pronounced interstitial lung diseases with serious restrictive defects and arterial hypoxemia have been reported infrequently. In differential diagnosis smoking related interstitial lung diseases (DIP, Langerhans cell histiocytosis, idiopathic pulmonary fibrosis) and other interstitial lung diseases have to be excluded. In most cases diagnosis can be achieved by bronchoalveolar lavage and transbronchial lung biopsy. In cases of pronounced interstitial lung disease or assumption of an additional interstitial lung disease besides RB-ILD a thoracoscopic or open lung biopsy can be necessary. RB-ILD has a favourable

  15. Vitamin D deficiency and chronic lung disease.

    PubMed

    Gilbert, Christopher R; Arum, Seth M; Smith, Cecilia M

    2009-01-01

    Vitamin D deficiency is increasingly being recognized as a prevalent problem in the general population. Patients with chronic lung diseases such as asthma, cystic fibrosis, chronic obstructive lung disease and interstitial pneumonia appear to be at increased risk for vitamin D deficiency for reasons that are not clear. Several studies indicate that vitamin D possesses a range of anti-inflammatory properties and may be involved in processes other than the previously believed functions of calcium and phosphate homeostasis. Various cytokines, cellular elements, oxidative stress and protease/antiprotease levels appear to affect lung fibroproliferation, remodelling and function, which may be influenced by vitamin D levels. Chronic lung diseases such as asthma and chronic obstructive lung disease have also been linked to vitamin D on a genetic basis. This immune and genetic influence of vitamin D may influence the pathogenesis of chronic lung diseases. A recent observational study notes a significant association between vitamin D deficiency and decreased pulmonary function tests in a large ambulatory population. The present review will examine the current literature regarding vitamin D deficiency, its prevalence in patients with chronic lung disease, vitamin D anti-inflammatory properties and the role of vitamin D in pulmonary function. PMID:19557213

  16. Aeroparticles, Composition, and Lung Diseases.

    PubMed

    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

  17. 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

  18. 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. PMID:26846584

  19. Facts and promises on lung biomarkers in interstitial lung diseases.

    PubMed

    Campo, Ilaria; Zorzetto, Michele; Bonella, Francesco

    2015-08-01

    Interstitial lung diseases (ILDs) are a heterogeneous group of >100 pulmonary disorders. ILDs are characterized by an irreversible architectural distortion and impaired gas exchange; however, there is great variability in the clinical course. ILD diagnosis requires a combination of clinical data, radiological imaging and histological findings (when a lung biopsy is required). At the same time, successful management of ILD patients strictly depends on an accurate and confident diagnosis. In this context, the detection of reliable biomarkers able to identify ILD subtypes, avoiding lung biopsy, as well as the capacity to stratify patients and predict over time the disease course, has become a primary aim for all research studies in this field. PMID:26146183

  20. Pleuroparenchymal fibroelastosis: a pattern of chronic lung injury.

    PubMed

    Rosenbaum, Jason N; Butt, Yasmeen M; Johnson, Karen A; Meyer, Keith; Batra, Kiran; Kanne, Jeffrey P; Torrealba, José R

    2015-01-01

    Pleuroparenchymal fibroelastosis (PPFE) is a rare condition currently described as an upper lobe subpleural and interstitial proliferation of predominantly elastic fibers. The etiology is unknown, and no specific diagnostic criteria have been reported. Here we report 5 cases of PPFE, 1 man and 4 women, 3 of them diagnosed at the time autopsy, 1 diagnosed in an explanted lung, and 1 diagnosed on a surgical wedge biopsy. The average age of diagnosis among this series is 73 years, and the duration of pulmonary symptoms ranged from 14 months to at least 9 years. Two patients had been exposed to specific medications (daptomycin and dapsone) preceding the development of pulmonary symptoms, and 1 patient developed eosinophilic pneumonia in the course of the disease. Four patients had clinical evidence of fibrous interstitial pneumonia. We found evidence of diffuse parenchymal fibroelastosis involving both upper and lower lobes in all 5 cases, suggesting that the disease may be a more diffuse condition than previously reported. PPFE may actually represent a pattern of chronic lung injury rather than a specific entity and may be seen in association with a variety of clinicoradiologic conditions. Based on our findings in this series and the most recent publications of the subject, we propose the following set of diagnostic criteria for PPFE: multilobar subpleural and/or centrilobular fibrous interstitial pneumonia characterized by an extensive (>80%) proliferation of elastic fibers in nonatelectatic lung, along with absent to mild chronic inflammation, and absent to rare granulomas. PMID:25454481

  1. 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.

  2. Biomarkers in connective tissue disease-associated interstitial lung disease.

    PubMed

    Bonella, Francesco; Costabel, Ulrich

    2014-04-01

    This article reviews major biomarkers in serum and bronchoalveolar lavage fluid (BALF) with respect to their diagnostic and prognostic value in connective tissue disease-associated interstitial lung disease (CTD-ILD). In some CTD such as systemic sclerosis (SSc), the incidence of ILD is up to two-third of patients, and currently ILD represents the leading cause of death in SSc. Because of the extremely variable incidence and outcome of ILD in CTD, progress in the discovery and validation of biomarkers for diagnosis, prognosis, patients' subtyping, response to treatment, or as surrogate endpoints in clinical trials is extremely important. In contrast to idiopathic interstitial pneumonias, autoantibodies play a crucial role as biomarkers in CTD-ILD because their presence is strictly linked to the pathogenesis and tissue damage. Patterns of autoantibodies, for instance, anticitrullinated peptide antibodies in rheumatoid arthritis or aminoacyl-tRNA synthetases (ARS) in polymyositis/dermatomyositis, have been found to correlate with the presence and occasionally with the course of ILD in CTD. Besides autoantibodies, an increase in serum or BALF of a biomarker of pulmonary origin may be able to predict or reflect the development of fibrosis, the impairment of lung function, and ideally also the prognosis. Promising biomarkers are lung epithelium-derived proteins such as KL-6 (Krebs von den Lungen-6), SP-D (surfactant protein-D), SP-A (surfactant protein-A), YKL-40 (chitinase-3-like protein 1 [CHI3L1] or cytokines such as CCL18 [chemokine (C-C) motif ligand 18]). In the future, genetic/epigenetic markers, such as human leukocyte antigen (HLA) haplotypes, single nucleotide polymorphisms, and micro-RNA, may help to identify subtypes of patients with different needs of management and treatment strategies. PMID:24668534

  3. Adult stem cells for chronic lung diseases.

    PubMed

    Mora, Ana L; Rojas, Mauricio

    2013-10-01

    Idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are chronic, progressive and lethal lung diseases. The incidence of IPF and COPD increases with age, independent of exposure to common environmental risk factors. At present, there is limited understanding of the relationship between ageing and the development of chronic lung diseases. One hypothesis is that chronic injury drives to exhaustion the local and systemic repair responses in the lung. These changes are accentuated during ageing where there is a progressive accumulation of senescent cells. Recently, stem cells have emerged as a critical reparative mechanism for lung injury. In this review, we discuss the repair response of bone marrow-derived mesenchymal stem cells (B-MSC) after lung injury and how their function is affected by ageing. Our own work has demonstrated a protective role of B-MSC in several animal models of acute and chronic lung injury. We recently demonstrated the association, using animal models, between age and an increase in the susceptibility to develop severe injury and fibrosis. At the same time, we have identified functional differences between B-MSC isolated from young and old animals. Further studies are required to understand the functional impairment of ageing B-MSC, ultimately leading to a rapid stem cell depletion or fatigue, interfering with their ability to play a protective role in lung injury. The elucidation of these events will help in the development of rational and new therapeutic strategies for COPD and IPF. PMID:23648014

  4. 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...

  5. [Modern Views on Children's Interstitial Lung Disease].

    PubMed

    Boĭtsova, E V; Beliashova, M A; Ovsiannikov, D Iu

    2015-01-01

    Interstitial lung diseases (ILD, diffuse lung diseases) are a heterogeneous group of diseases in which a pathological process primarily involved alveoli and perialveolar interstitium, resulting in impaired gas exchange, restrictive changes of lung ventilation function and diffuse interstitial changes detectable by X-ray. Children's interstitial lung diseases is an topical problem ofpediatricpulmonoogy. The article presents current information about classification, epidemiology, clinical presentation, diagnostics, treatment and prognosis of these rare diseases. The article describes the differences in the structure, pathogenesis, detection of various histological changes in children's ILD compared with adult patients with ILD. Authors cite an instance of registers pediatric patients with ILD. The clinical semiotics of ILD, the possible results of objective research, the frequency of symptoms, the features of medical history, the changes detected on chest X-rays, CT semiotics described in detail. Particular attention was paid to interstitial lung diseases, occurring mainly in newborns and children during the first two years of life, such as congenital deficiencies of surfactant proteins, neuroendocrine cell hyperplasia of infancy, pulmonary interstitial glycogenosis. The diagnostic program for children's ILD, therapy options are presented in this article. PMID:26234096

  6. 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

  7. 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

  8. NOD-Like Receptors in Lung Diseases

    PubMed Central

    Chaput, Catherine; Sander, Leif Erik; Suttorp, Norbert; Opitz, Bastian

    2013-01-01

    The lung is a particularly vulnerable organ at the interface of the body and the exterior environment. It is constantly exposed to microbes and particles by inhalation. The innate immune system needs to react promptly and adequately to potential dangers posed by these microbes and particles, while at the same time avoiding extensive tissue damage. Nucleotide-binding oligomerization domain-like receptors (NLRs) represent a group of key sensors for microbes and damage in the lung. As such they are important players in various infectious as well as acute and chronic sterile inflammatory diseases, such as pneumonia, chronic obstructive pulmonary disease (COPD), acute lung injury/acute respiratory distress syndrome, pneumoconiosis, and asthma. Activation of most known NLRs leads to the production and release of pro-inflammatory cytokines, and/or to the induction of cell death. We will review NLR functions in the lung during infection and sterile inflammation. PMID:24312100

  9. 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

  10. Occupational lung disease. Part 2. Discovering the cause of diffuse parenchymal lung disease.

    PubMed

    Kuschner, Ware G; Stark, Paul

    2003-04-01

    Diffuse parenchymal lung disease (also known as interstitial lung disease) and acute irritant reactions are much less commonly managed by primary care physicians than asthma. Acute irritant reactions are typically readily recognized because of the immediate exposure-response relationship. As with asthma, a diagnosis of diffuse parenchymal lung disease should prompt a careful review of the patient's work history. Findings from history taking and radiography provide most of the data needed to establish a diagnosis of asbestosis or silicosis. A pulmonologist should be consulted about lung disease that eludes diagnosis. In cases in which a link between work and illness is strongly suspected, an occupational medicine specialist may be consulted for assistance with preparing reports for a workers' compensation claim as well as characterizing and quantifying impairment. Various government agencies provide extensive information about specific toxic exposures and occupational lung diseases by telephone and on the World Wide Web. PMID:12718237

  11. Chronic exposure to ozone causes restrictive lung disease

    SciTech Connect

    Grose, E.C.; Costa, D.L.; Hatch, G.E.; Miller, F.J.; Graham, J.A.

    1989-01-01

    A chronic study to determine the progression and/or reversibility of ozone-induced lung disease was conducted. Male rats were exposed to a diurnal pattern of ozone (O{sub 3}) for 1 week, 3 weeks, 3 months, 12 months, or 18 months. The occurrence of chronic lung disease was determined by structural and functional endpoints. Structurally, a biphasic response was observed with an initial acute inflammatory response after 1 week of exposure, a reduced acute response after 3 weeks of exposure, and an epithelial and interstitial response observed after 3 months which persisted or increased in intensity up to 18 months of exposure. Functional studies showed a persistence of decreased total lung capacity and residual volumes at 3, 12, and 18 months of exposure, a response indicative of restrictive lung disease. Biochemical changes in antioxidant metabolism were also observed after 12 and 18 months of exposure. Most significant changes were resolved after the clean-air recovery period. The study has shown that chronic exposure to O{sub 3} causes restrictive lung disease as characterized by the development of focal interstitial fibrosis.

  12. 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. PMID:23767420

  13. [Imaging features of drug-induced lung diseases].

    PubMed

    Mellot, F; Scherrer, A

    2005-05-01

    Drug-induced lung diseases are an increasingly frequent cause of morbidity. Over 350 drugs are now recognized as being implicated in drug-induced lung diseases. Early diagnosis is critical. Discontinuing the drug may result in regression of the adverse effect. Diagnosis is based on a history of drug exposure with a temporal relationship between the introduction of the drug and the onset of symptoms, histologic evidence of lung damage and exclusion of other causes of lung injury. Unfortunately there is no specific test available. Histologic and radiologic findings are often non specific and diagnosis can be difficult. Drugs can cause a constellation of distinct patterns of respiratory involvement and all anatomic compartments of the lungs may be involved. The most common patterns are: non specific interstitial pneumonia and fibrosis, pulmonary eosinophilia, hypersensitivity pneumonitis, pulmonary edema with or without diffuse alveolar damage, bronchiolitis obliterans organizing pneumonia, pulmonary hemorrhage and vasculitis. It is important to be familiar with their common radiologic appearances. PMID:16106793

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

    MedlinePlus

    ... your doctor about 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 ...

  15. 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 ...

  16. Exposure-related diffuse lung disease.

    PubMed

    Rose, Cecile S; Lynch, David A; Cool, Carlyne D

    2008-12-01

    Practicing pulmonologists are often faced with the question of whether a lung disease is related to something in the patient's workplace, home, or recreational environment. Recognizing a lung disease as exposure related creates both opportunities and obligations for clinicians. In addition to managing the patient, the obligation to consider risks to others and to prevent ongoing exposure is a challenge that requires diagnostic clarity and collaboration between multiple specialists. We present five illustrative case studies of patients with diffuse lung diseases from environmental and occupational exposures in which communication between the pulmonologist, radiologist, and pathologist was essential for both medical and public health management. Diagnostic and treatment strategies as well as social and preventive interventions are reviewed, with key points for the practicing pulmonologist. PMID:19221960

  17. Smoking-related lung disease.

    PubMed

    Galvin, Jeffrey R; Franks, Teri J

    2009-11-01

    Dyspneic smokers who come to clinical attention demonstrate varying combinations of emphysema, airway inflammation, and fibrosis in addition to the changes of pulmonary Langerhans' cell histiocytosis. There is also growing acceptance of a link between cigarette smoke and alveolar wall fibrosis. Acute eosinophilic pneumonia is a dramatic response to recent-onset smoking seen in a small number of individuals. The interconnected pathways that lead to lung inflammation and fibrosis in cigarette smokers are slowly coming into focus. PMID:19935224

  18. Management of interstitial lung disease associated with connective tissue disease.

    PubMed

    Mathai, Stephen C; Danoff, Sonye K

    2016-01-01

    The lung is a common site of complications of systemic connective tissue disease (CTD), and lung involvement can present in several ways. Interstitial lung disease (ILD) and pulmonary hypertension are the most common lung manifestations in CTD. Although it is generally thought that interstitial lung disease develops later on in CTD it is often the initial presentation ("lung dominant" CTD). ILD can be present in most types of CTD, including rheumatoid arthritis, scleroderma, systemic lupus erythematosus, polymyositis or dermatomyositis, Sjögren's syndrome, and mixed connective tissue disease. Despite similarities in clinical and pathologic presentation, the prognosis and treatment of CTD associated ILD (CTD-ILD) can differ greatly from that of other forms of ILD, such as idiopathic pulmonary fibrosis. Pulmonary hypertension (PH) can present as a primary vasculopathy in pulmonary arterial hypertension or in association with ILD (PH-ILD). Therefore, detailed history, physical examination, targeted serologic testing, and, occasionally, lung biopsy are needed to diagnose CTD-ILD, whereas both non-invasive and invasive assessments of pulmonary hemodynamics are needed to diagnose pulmonary hypertension. Immunosuppression is the mainstay of treatment for ILD, although data from randomized controlled trials (RCTs) to support specific treatments are lacking. Furthermore, treatment strategies vary according to the clinical situation-for example, the treatment of a patient newly diagnosed as having CTD-ILD differs from that of someone with an acute exacerbation of the disease. Immunosuppression is indicated only in select cases of pulmonary arterial hypertension related to CTD; more commonly, selective pulmonary vasodilators are used. For both diseases, comorbidities such as sleep disordered breathing, symptoms of dyspnea, and cough should be evaluated and treated. Lung transplantation should be considered in patients with advanced disease but is not always feasible because

  19. 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. PMID:23970508

  20. Patient-Specific Airway Wall Remodeling in Chronic Lung Disease.

    PubMed

    Eskandari, Mona; Kuschner, Ware G; Kuhl, Ellen

    2015-10-01

    Chronic lung disease affects more than a quarter of the adult population; yet, the mechanics of the airways are poorly understood. The pathophysiology of chronic lung disease is commonly characterized by mucosal growth and smooth muscle contraction of the airways, which initiate an inward folding of the mucosal layer and progressive airflow obstruction. Since the degree of obstruction is closely correlated with the number of folds, mucosal folding has been extensively studied in idealized circular cross sections. However, airflow obstruction has never been studied in real airway geometries; the behavior of imperfect, non-cylindrical, continuously branching airways remains unknown. Here we model the effects of chronic lung disease using the nonlinear field theories of mechanics supplemented by the theory of finite growth. We perform finite element analysis of patient-specific Y-branch segments created from magnetic resonance images. We demonstrate that the mucosal folding pattern is insensitive to the specific airway geometry, but that it critically depends on the mucosal and submucosal stiffness, thickness, and loading mechanism. Our results suggests that patient-specific airway models with inherent geometric imperfections are more sensitive to obstruction than idealized circular models. Our models help to explain the pathophysiology of airway obstruction in chronic lung disease and hold promise to improve the diagnostics and treatment of asthma, bronchitis, chronic obstructive pulmonary disease, and respiratory failure. PMID:25821112

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

    PubMed

    Cruse, Glenn; Bradding, Peter

    2016-05-01

    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. PMID:25959386

  2. Epigenetic contributions to the developmental origins of adult lung disease.

    PubMed

    Joss-Moore, Lisa A; Lane, Robert H; Albertine, Kurt H

    2015-04-01

    Perinatal insults, including intrauterine growth restriction, preterm birth, maternal exposure to toxins, or dietary deficiencies produce deviations in the epigenome of lung cells. Occurrence of perinatal insults often coincides with the final stages of lung development. The result of epigenome disruptions in response to perinatal insults during lung development may be long-term structural and functional impairment of the lung and development of lung disease. Understanding the contribution of epigenetic mechanisms to life-long lung disease following perinatal insults is the focus of the developmental origins of adult lung disease field. DNA methylation, histone modifications, and microRNA changes are all observed in various forms of lung disease. However, the perinatal contribution to such epigenetic mechanisms is poorly understood. Here we discuss the developmental origins of adult lung disease, the interplay between perinatal events, lung development and disease, and the role that epigenetic mechanisms play in connecting these events. PMID:25493710

  3. Diffuse Cystic Lung Diseases: Diagnostic Considerations.

    PubMed

    Xu, Kai-Feng; Feng, Ruie; Cui, Han; Tian, Xinlun; Wang, Hanping; Zhao, Jing; Huang, Hui; Zhang, Weihong; Lo, Bee Hong

    2016-06-01

    Diffuse cystic lung disease (DCLD) is a group of heterogeneous diseases that present as diffuse cystic changes in the lung on computed tomography of the chest. Most DCLD diseases are rare, although they might resemble common diseases such as emphysema and bronchiectasis. Main causes of DCLD include lymphangioleiomyomatosis, Birt-Hogg-Dubé syndrome, pulmonary Langerhans cell histiocytosis, lymphoid interstitial pneumonia, amyloidosis, light-chain deposition disease, Sjögren syndrome, and primary or metastatic neoplasm. We discuss clinical factors that are helpful in the differential diagnosis of DCLDsuch as sex and age, symptoms and signs, extrapulmonary presentations, cigarette smoking, and family history. Investigations for DCLD include high-resolution computed tomography, biochemical and histopathological studies, genetic tests, pulmonary function tests, and bronchoscopic and video-assisted thoracoscopic biopsies. A proposed diagnostic algorithm would enhance ease of diagnosing most cases of DCLD. PMID:27231867

  4. The lung in sickle cell disease.

    PubMed

    Knight, J; Murphy, T M; Browning, I

    1999-09-01

    Sickle cell disease is the most common inherited disorder in African-Americans. Although the primary defect is hematological, the changes in the erythrocytes lead to a vasculopathy with multiorgan injury. The pulmonary complications, i.e., acute chest syndrome and chronic sickle cell lung disease, are significant causes of morbidity and mortality. The pulmonary manifestations result from a unique constellation of factors which come into play in sickle cell disease. Based on the growing understanding of the molecular and cellular biology of sickle cell disease, new therapies are being developed that are likely to ameliorate the natural history of this disease and its complications. PMID:10495338

  5. Autophagy in lung disease pathogenesis and therapeutics

    PubMed Central

    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. PMID:25617802

  6. [Lung transplantation in patients with interstitial lung disease/idiopathic pulmonary fibrosis].

    PubMed

    Murer, Christian; Benden, Christian

    2016-01-01

    Lung transplantation is an established therapy for advanced lung disease. Among the common disease indications for lung transplantation, patients with interstitial lung disease, in particular, idiopathic pulmonary fibrosis (IPF), have the worst prognosis. Thus referral to a transplant center should ideally be realised at the time of diagnosis of usual interstitial pneumonitis (UIP), regardless of lung function, in order to carry out a through initial assessment and evaluation. PMID:26884220

  7. The lung in systemic vasculitis: radiological patterns and differential diagnosis.

    PubMed

    Feragalli, Beatrice; Mantini, Cesare; Sperandeo, Marco; Galluzzo, Michele; Belcaro, Giovanni; Tartaro, Armando; Cotroneo, Antonio R

    2016-05-01

    The respiratory system may be involved in all systemic vasculitides, although with a variable frequency. The aim of our review is to describe radiographic and high-resolution CT (HRCT) findings of pulmonary vasculitides and to correlate radiological findings with pathological results. Lung disease is a common feature of antineutrophil cytoplasmic autoantibody-associated small-vessel vasculitides, including granulomatosis with polyangiitis (Wegener's), eosinophilic granulomatosis with polyangiitis (Churg-Strauss) and microscopic polyangiitis. Pulmonary involvement is less frequent in immune-complex-mediated small-vessel vasculitides, such as Behçet's disease and Goodpasture's syndrome. Pulmonary involvement associated to large-vessel (gigantocellular arteritis and Takayasu's disease) or medium-vessel (nodose polyarteritis and Kawasaki's disease) vasculitides is extremely rare. The present review describes the main clinical and radiological features of pulmonary vasculitides with major purpose to correlate HRCT findings (solitary or multiple nodules, cavitary lesions, micronodules with centrilobular or peribronchial distribution, airspace consolidations, "crazy paving", tracheobronchial involvement, interstitial disease) with pathological results paying particular attention to the description of acute life-threatening manifestations. A thorough medical history, careful clinical examination and the knowledge of radiological patterns are mandatory for a correct and early diagnosis. PMID:26876879

  8. Epigenetic targets for novel therapies of lung diseases

    PubMed Central

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

    2014-01-01

    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 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. PMID:25448041

  9. 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

  10. Mucin overproduction in chronic inflammatory lung disease

    PubMed Central

    Hauber, Hans-Peter; Foley, Susan C; Hamid, Qutayba

    2006-01-01

    Mucus overproduction and hypersecretion are commonly observed in chronic inflammatory lung disease. Mucins are gel-forming glycoproteins that can be stimulated by a variety of mediators. The present review addresses the mechanisms involved in the upregulation of secreted mucins. Mucin induction by neutrophil elastase, bacteria, cytokines, growth factors, smoke and cystic fibrosis transmembrane conductance regulator malfunction are also discussed. PMID:16983448

  11. Reversing disability of irreversible lung disease.

    PubMed Central

    Tiep, B. L.

    1991-01-01

    Pulmonary rehabilitation is a comprehensive multifaceted team approach for integrating medical management, coping skills, self-management techniques, and exercise reconditioning. It provides patients with chronic lung disease the ability to adapt and live full and nearly normal lives. These changes are possible because the overall disability includes significant reversible components: Patients have bronchospasm, infection, and cor pulmonale; they respond to progressively impaired lungs by progressive inactivity, leading to physical deconditioning. Both factors contribute to dyspnea. Because patients naturally fear dyspnea, they panic easily. During panic, their work of breathing may increase and respiratory failure may result. Pulmonary rehabilitation provides good medical management; provides exercises to increase strength, endurance, and tolerance to dyspnea; and trains patients in panic control. These programs have not been shown to lengthen life span or improve static lung function. They increase exercise performance and render patients functional, independent, and subject to fewer hospital admissions. Pulmonary rehabilitation is the only approach to chronic lung disease short of lung transplantation that improves the long-term outlook for these patients. Images PMID:1866957

  12. Extracellular matrix mechanics in lung parenchymal diseases

    PubMed Central

    Suki, Béla; Bates, Jason H.T.

    2008-01-01

    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. PMID:18485836

  13. 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.

  14. Disruption of iron homeostasis and lung disease.

    PubMed

    Ghio, Andrew J

    2009-07-01

    As a result of a direct exchange with the external environment, the lungs are exposed to both iron and agents with a capacity to disrupt the homeostasis of this metal (e.g. particles). An increased availability of catalytically reactive iron can result from these exposures and, by generating an oxidative stress, this metal can contribute to tissue injury. By importing this Fe(3+) into cells for storage in a chemically less reactive form, the lower respiratory tract demonstrates an ability to mitigate both the oxidative stress presented by iron and its potential for tissue injury. This means that detoxification is accomplished by chemical reduction to Fe(2+) (e.g. by duodenal cytochrome b and other ferrireductases), iron import (e.g. by divalent metal transporter 1 and other transporters), and storage in ferritin. The metal can subsequently be exported from the cell (e.g. by ferroportin 1) in a less reactive state relative to that initially imported. Iron is then transported out of the lung via the mucociliary pathway or blood and lymphatic pathways to the reticuloendothelial system for long term storage. This coordinated handling of iron in the lung appears to be disrupted in several acute diseases on the lung including infections, acute respiratory distress syndrome, transfusion-related acute lung injury, and ischemia-reperfusion. Exposures to bleomycin, dusts and fibers, and paraquat similarly alter iron homeostasis in the lung to affect an oxidative stress. Finally, iron homeostasis is disrupted in numerous chronic lung diseases including pulmonary alveolar proteinosis, transplantation, cigarette smoking, and cystic fibrosis. PMID:19100311

  15. 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.

  16. DEPOSITION PATTERNS OF POLYDISPERSE AEROSOLS WITHIN HUMAN LUNGS

    EPA Science Inventory

    The efficacy of airborne pharmaceuticals in the treatment of lung diseases can may be improved with the selective deposition of inhaled drugs. erein, a validated mathematical model is used to examine the effects of aerosol polydispersity upon deposition in the human lung. ocalize...

  17. Potential roles of telocytes in lung diseases.

    PubMed

    Shi, Lin; Dong, Nian; Chen, Chengshui; Wang, Xiangdong

    2016-07-01

    Telocytes (TCs) are a unique type of interstitial cells with specific, extremely long prolongations named telopodes (Tps), as shown by immune-positive staining against CD34, c-kit and vimentin. They were found in many organs of mammals, with potential biological functions, including the trachea and lung, even though the exact function remains unclear. Here, we give a historical overview of the TCs research field and summarize the latest findings associated with TCs, with a special focus on the recent progress about TCs specific gene and protein profiles that has been made in understanding that TCs may play a potential, but important, role in the pathogenesis of lung diseases. PMID:26855021

  18. Gas exchange in disease: asthma, chronic obstructive pulmonary disease, cystic fibrosis, and interstitial lung disease.

    PubMed

    Young, Iven H; Bye, Peter T P

    2011-04-01

    Ventilation-perfusion (VA/Q) inequality is the underlying abnormality determining hypoxemia and hypercapnia in lung diseases. Hypoxemia in asthma is characterized by the presence of low VA/Q units, which persist despite improvement in airway function after an attack. This hypoxemia is generally attenuated by compensatory redistribution of blood flow mediated by hypoxic vasoconstriction and changes in cardiac output, however, mediator release and bronchodilator therapy may cause deterioration. Patients with chronic obstructive pulmonary disease have more complex patterns of VA/Q inequality, which appear more fixed, and changes in blood flow and ventilation have less benefit in improving gas exchange efficiency. The inability of ventilation to match increasing cardiac output limits exercise capacity as the disease progresses. Deteriorating hypoxemia during exacerbations reflects the falling mixed venous oxygen tension from increased respiratory muscle activity, which is not compensated by any redistribution of VA/Q ratios. Shunt is not a feature of any of these diseases. Patients with cystic fibrosis (CF) have no substantial shunt when managed according to modern treatment regimens. Interstitial lung diseases demonstrate impaired oxygen diffusion across the alveolar-capillary barrier, particularly during exercise, although VA/Q inequality still accounts for most of the gas exchange abnormality. Hypoxemia may limit exercise capacity in these diseases and in CF. Persistent hypercapnic respiratory failure is a feature of advancing chronic obstructive pulmonary disease and CF, closely associated with sleep disordered breathing, which is not a prominent feature of the other diseases. Better understanding of the mechanisms of hypercapnic respiratory failure, and of the detailed mechanisms controlling the distribution of ventilation and blood flow in the lung, are high priorities for future research. PMID:23737199

  19. Rare lung diseases I--Lymphangioleiomyomatosis.

    PubMed

    Juvet, Stephen C; Hwang, David; Downey, Gregory P

    2006-10-01

    The present article is the first in a series that will review selected rare lung diseases. The objective of this series is to promote a greater understanding and awareness of these unusual conditions among respirologists. Each article will begin with a case that serves as a focal point for a discussion of the pathophysiology and management of the particular condition. The first article is on lymphangioleiomyomatosis (LAM); subsequent articles will focus on pulmonary alveolar proteinosis, alpha-1-antitrypsin deficiency and primary ciliary dyskinesia. LAM is a rare, progressive and (without intervention) often fatal interstitial lung disease that predominantly affects women of childbearing age. LAM is characterized by progressive interstitial infiltration of the lung by smooth muscle cells, resulting in diffuse cystic changes of the lung parenchyma. The molecular basis of this disorder has been delineated over the past five years and LAM is now known to be a consequence of mutations in the tuberous sclerosis genes. This knowledge, combined with advances in our understanding of the signalling pathways regulated by these genes, has given rise to potential molecular therapies that hold great promise for treating this devastating disease. PMID:17036091

  20. 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. PMID:27068927

  1. [Lung Cancer as an Occupational Disease].

    PubMed

    Baur, X; Woitowitz, H-J

    2016-08-01

    Lung cancer is one of the most frequently encountered cancer types. According to the latest WHO data, about 10 % of this disease are due to occupational exposure to cancerogens. Asbestos is still the number one carcinogen. Further frequent causes include quarz and ionizing radiation (uranium mining). Probable causes of the disease can be identified only with the help of detailed occupational history taken by a medical specialist and qualified exposure assessment. Without clarifying the cause of the disease, there is neither a correct insurance procedure nor compensation for the victim, and furthermore, required preventive measures cannot be initiated. PMID:27512930

  2. Does aluminum smelting cause lung disease?

    PubMed

    Abramson, M J; Wlodarczyk, J H; Saunders, N A; Hensley, M J

    1989-04-01

    The evidence concerning a relationship between work in the aluminum industry and lung disease has been reviewed using epidemiologic criteria. Adequate data on environmental exposure are rarely presented. Case series on aluminum potroom workers over the past 50 years have identified an asthmalike syndrome that appears to be due to an irritant rather than an allergic mechanism. These studies have been supported by evidence of within shift variability of measures of lung function. However, to date, there is inadequate evidence to resolve the question of whether potroom exposure initiates asthma or merely precipitates asthmalike symptoms in a predisposed individual. Cross-sectional studies have demonstrated evidence of reduced lung function, consistent with chronic airflow limitation. In exposed aluminum smelter workers compared to unexposed control subjects. Cigarette smoking, the major potential confounding variable, has been measured and accounted for in multivariate analyses. To date, evidence is lacking from longitudinal studies about the development of disabling chronic obstructive lung disease. Exposure to coal tar pitch volatiles in the production and consumption of anodes has biologic plausibility for an association of lung cancer with work in an aluminum smelter. Although retrospective mortality studies have failed to account for the probable high prevalence of smoking in blue collar workers, the relative risk of lung cancer is very low if present at all. Pulmonary fibrosis has not been shown to be a significant problem in aluminum smelter workers. Future research in the aluminum industry needs to concentrate on longitudinal studies, preferably with an inception cohort for the investigation of potroom asthma. PMID:2648910

  3. Does aluminum smelting cause lung disease

    SciTech Connect

    Abramson, M.J.; Wlodarczyk, J.H.; Saunders, N.A.; Hensley, M.J.

    1989-04-01

    The evidence concerning a relationship between work in the aluminum industry and lung disease has been reviewed using epidemiologic criteria. Adequate data on environmental exposure are rarely presented. Case series on aluminum potroom workers over the past 50 years have identified an asthmalike syndrome that appears to be due to an irritant rather than an allergic mechanism. These studies have been supported by evidence of within shift variability of measures of lung function. However, to date, there is inadequate evidence to resolve the question of whether potroom exposure initiates asthma or merely precipitates asthmalike symptoms in a predisposed individual. Cross-sectional studies have demonstrated evidence of reduced lung function, consistent with chronic airflow limitation. In exposed aluminum smelter workers compared to unexposed control subjects. Cigarette smoking, the major potential confounding variable, has been measured and accounted for in multivariate analyses. To date, evidence is lacking from longitudinal studies about the development of disabling chronic obstructive lung disease. Exposure to coal tar pitch volatiles in the production and consumption of anodes has biologic plausibility for an association of lung cancer with work in an aluminum smelter. Although retrospective mortality studies have failed to account for the probable high prevalence of smoking in blue collar workers, the relative risk of lung cancer is very low if present at all. Pulmonary fibrosis has not been shown to be a significant problem in aluminum smelter workers. Future research in the aluminum industry needs to concentrate on longitudinal studies, preferably with an inception cohort for the investigation of potroom asthma. 92 references.

  4. Interstitial Lung Disease due to Siderosis in a Lathe Machine Worker.

    PubMed

    Gothi, D; Satija, B; Kumar, S; Kaur, Omkar

    2015-01-01

    Since its first description in 1936, siderosis of lung has been considered a benign pneumoconiosis due to absence of significant clinical symptoms or respiratory impairment. Subsequently, authors have questioned the non-fibrogenic property of iron. However, siderosis causing interstitial lung disease with usual interstitial pneumonia (UIP) pattern has not been described in the past. We report a case of UIP on high resolution computed tomography, proven to be siderosis on transbronchial lung biopsy in a lathe machine worker. PMID:26410982

  5. Analysis of speckle patterns in phase-contrast images of lung tissue

    NASA Astrophysics Data System (ADS)

    Kitchen, M. J.; Paganin, D.; Lewis, R. A.; Yagi, N.; Uesugi, K.

    2005-08-01

    Propagation-based phase-contrast images of mice lungs have been obtained at the SPring-8 synchrotron research facility. Such images exhibit a speckled intensity pattern that bears a superficial resemblance to alveolar structures. This speckle results from focussing effects as projected air-filled alveoli form aberrated compound refractive lenses. An appropriate phase-retrieval algorithm has been utilized to reconstruct the approximate projected lung tissue thickness from single-phase-contrast mice chest radiographs. The results show projected density variations across the lung, highlighting regions of low density corresponding to air-filled regions. Potentially, this offers a better method than conventional radiography for detecting lung diseases such as fibrosis, emphysema and cancer, though this has yet to be demonstrated. As such, the approach can assist in continuing studies of lung function utilizing propagation-based phase-contrast imaging.

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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. PMID:27134484

  11. 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.

  12. Spatial pattern formation in the lung

    PubMed Central

    Donovan, Graham M.; Kritter, Thibaut

    2014-01-01

    Clustered ventilation defects are a hallmark of asthma, typically seen via imaging studies during asthma attacks. The mechanisms underlying the formation of these clusters is of great interest in understanding asthma. Because the clusters vary from event to event, many researchers believe they occur due to dynamic, rather than structural, causes. To study the formation of these clusters, we formulate and analyze a lattice-based model of the lung, considering both the role of airway bistability and a mechanism for organizing the spatial structure. Within this model we show how and why the homogeneous ventilation solution becomes unstable, and under what circumstances the resulting heterogeneous solution is a clustered solution. The size of the resulting clusters is shown to arise from structure of the eigenvalues and eigenvectors of the system, admitting not only clustered solutions but also (aphysical) checkerboard solutions. We also consider the breathing efficiency of clustered solutions in severely constricted lungs, showing that stabilizing the homogeneous solution may be advantageous in some circumstances. Extensions to hexagonal and cubic lattices are also studied. PMID:24810407

  13. 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. PMID:26059704

  14. 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

  15. Vasculitis: determinants of disease patterns.

    PubMed

    Hoffman, Gary S; Calabrese, Leonard H

    2014-08-01

    The vasculitides are a large group of heterogeneous diseases for which it has been assumed that pathogenesis is largely autoimmune. As clinicians, we distinguish one form of vasculitis from another on the basis of observed patterns of organ injury, the size of the vessels affected and histopathological findings. The terms 'small-vessel', 'medium-vessel' and 'large-vessel' vasculitis are useful clinical descriptors, but fail to inform us about why vessels of a certain calibre are favoured by one disease and not another. Classification based on vessel size also fails to consider that vessels of a specific calibre are not equally prone to injury. Distinct vulnerabilities undoubtedly relate to the fact that same-size vessels in different tissues may not be identical conduits. In fact, vessels become specialized, from the earliest stages of embryonic development, to suit the needs of different anatomical locations. Vessels of the same calibre in different locations and organs are as different as the organ parenchymal cells through which they travel. The dialogue between developing vessels and the tissues they perfuse is designed to meet special local needs. Added to the story of vascular diversity and vulnerability are changes that occur during growth, development and ageing. An improved understanding of the unique territorial vulnerabilities of vessels could form the basis of new hypotheses for the aetiopathogenesis of the vasculitides. This Review considers how certain antigens, including infectious agents, might become disease-relevant and how vascular diversity could influence disease phenotypes and the spectrum of vascular inflammatory diseases. PMID:24934189

  16. 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

  17. 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%.

  18. Macrophage polarization in interstitial lung diseases

    PubMed Central

    Mierzejewski, Michał; Osińska, Iwona; Domagała-Kulawik, Joanna

    2016-01-01

    The role of bronchoalveolar lavage fluid (BALf) examination in differential diagnosis of interstitial lung diseases (ILD) was established. Currently, functional polarization into M1 (pro-inflammatory) and M2 (anti-inflammatory) subpopulations is emphasized. The aim of our study was to compare the proportion of M1 and M2 in BALf of patients with different ILD. BALf samples were collected from 75 ILD patients: sarcoidosis (SA, 36), hypersensitivity pneumonitis (HP, 10), non-specific interstitial pneumonia (NSIP, 8), idiopathic pulmonary fibrosis (IPF, 6) and other ILD (15). Phenotyping was performed by immunocytochemistry with anti-CD40 and CD163 antibodies (for M1 and M2, respectively). For both, CD40 and CD163, three populations of cells have been specified: small cells with strong (+++), large cells with weak (+) and cells with no (–) reaction. Due to lack of statistically significant differences between patients with HP, NSIP and IPF, they were classified into a common group and compared to the group of patients with sarcoidosis. The median proportion of macrophage population was as follows: for CD40: 61%, 35%, 2% in patients with SA and 49%, 47%, 3% in patients with other ILD and for CD163: 55%, 35%, 5% in SA and 53%, 43%, 1% in ILD patients, respectively. We found a significantly higher proportion of M1 in SA when compared with other ILD. Our study showed no evidence of defined polarization of alveolar macrophages in different types of interstitial lung diseases. However, we emphasized the role of CD40 positive cells in sarcoidosis and the role of CD163 positive cells in fibrotic diffuse lung diseases. PMID:27536201

  19. 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

  20. 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

  1. 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. PMID:27231868

  2. New perspectives on basic mechanisms in lung disease. 6. Proteinase imbalance: its role in lung disease.

    PubMed Central

    Tetley, T D

    1993-01-01

    The hypothesis, some 30 years ago, that NE was the sole proteolytic agent responsible for the development of emphysema seems naive in retrospect. The availability of technology to measure NE facilitated the early research into the relationship between NE and lung disease. Despite an abundance of information on the activity of NE in the lung, it will probably require prospective studies in man with specific NE inhibitors or control at the gene level to establish a causal relationship between NE and lung disease. Parallel research has resulted in the isolation and characterisation of NE inhibitors other than PI and, indeed, alternative proteolytic enzymes that might contribute to lung disease. It is perhaps impossible now to think that a single proteinase, however omnipotent it may be, causes lung diseases as diverse as emphysema and fibrosis. An important aspect that is emerging is the interrelationship between proteolytic enzymes produced by different, or sometimes the same, cells that could potentiate tissue proteolysis. The evidence suggests that there is likely to be coordinated action between neutrophils, macrophages, and possibly mesenchymal proteinases which can activate or inactivate each other. In addition, one class of proteinases often appears able to proteolytically inactivate inhibitors of the opposite class, which presumably could amplify proteolysis if it occurred in vivo. Although the work on this aspect of proteinase activity is in its infancy, one suspects that part of the normal regulation of proteinase activity might include compartmentalisation. For example, the neutrophil stores proteinases before appropriate release and can inactivate PI to enable proteolytic action pericellularly, whereas degradation of extracellular matrix by macrophages requires interaction between the cell and matrix which is facilitated by cell receptor bound uPA. Disintegration of these "compartments" due to oedema, proteolysis, or for mechanical reasons could, firstly

  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. The Lung Microbiome, Immunity, and the Pathogenesis of Chronic Lung Disease.

    PubMed

    O'Dwyer, David N; Dickson, Robert P; Moore, Bethany B

    2016-06-15

    The development of culture-independent techniques for microbiological analysis has uncovered the previously unappreciated complexity of the bacterial microbiome at various anatomic sites. The microbiome of the lung has relatively less bacterial biomass when compared with the lower gastrointestinal tract yet displays considerable diversity. The composition of the lung microbiome is determined by elimination, immigration, and relative growth within its communities. Chronic lung disease alters these factors. Many forms of chronic lung disease demonstrate exacerbations that drive disease progression and are poorly understood. Mounting evidence supports ways in which microbiota dysbiosis can influence host defense and immunity, and in turn may contribute to disease exacerbations. Thus, the key to understanding the pathogenesis of chronic lung disease may reside in deciphering the complex interactions between the host, pathogen, and resident microbiota during stable disease and exacerbations. In this brief review we discuss new insights into these labyrinthine relationships. PMID:27260767

  5. Respiratory failure due to infliximab induced interstitial lung disease.

    PubMed

    Kakavas, Sotiris; Balis, Evangelos; Lazarou, Vasiliki; Kouvela, Marousa; Tatsis, Georgios

    2013-01-01

    Although poorly understood, interstitial lung disease has been reported as a possible complication of tumor necrosis factor alpha inhibitors. We report a case of interstitial lung disease in a 64-year-old man with psoriasis 3 weeks after the initiation of infliximab treatment. The patient had received two fortnightly infusions of infliximab following a short course of methotrexate. Thoracic computed tomography showed bilateral ground glass and interstitial infiltrates, while the results of microbiology and immunologic workup were negative. Likewise, bronchoalveolar lavage detected neither typical nor atypical pathogens. Infliximab-induced interstitial lung injury was suspected and corticosteroid therapy was administered which resulted in rapid clinical and radiological improvement. This is one of the few reported cases of interstitial lung disease due to infliximab in the psoriasis population. The patient had no pre-existing lung pathology, while his previous exposure to methotrexate was minimal and was not temporally associated with the induction of interstitial lung disease. PMID:23969008

  6. Prescribing patterns for Alzheimer disease

    PubMed Central

    Hillmer, Melinda; Krahn, Murray; Hillmer, Michael; Pariser, Pauline; Naglie, Gary

    2006-01-01

    OBJECTIVE To describe Canadian family physicians’ prescribing practices with regard to Alzheimer disease (AD). DESIGN Cross-sectional survey administered by facsimile. SETTING Four regions in Canada (British Columbia, the Prairie Provinces, Ontario, and the Atlantic Provinces). PARTICIPANTS A stratified random sample of 1000 Canadian family physicians (250 per region) chosen from the Canadian Medical Directory; 81 of whom were excluded as ineligible. MAIN OUTCOME MEASURES Prescribing practices regarding cholinesterase inhibitors (ChIs) for patients with AD. RESULTS Response rate was 36.3%. About 27% of respondents reported that ChIs were prescribed for less than 10% of their AD patients, while 12.5% reported that ChIs were prescribed for more than 90% of their AD patients. More physicians prescribed ChIs in the two regions with provincial formulary coverage (Prairie Provinces and Ontario) than in the two regions without coverage (British Columbia and Atlantic Provinces). Factors that significantly predicted lower prescribing rates included female sex, perception of ChIs’ effectiveness, and self-reported knowledge of ChIs. CONCLUSION Canadian physicians’ prescribing patterns for ChIs vary; the optimal prescribing rate is unclear. Provincial coverage of these drugs along with physicians’ sex, knowledge of ChIs, and perception of the effectiveness of ChIs appear to influence prescribing rates. PMID:16926965

  7. Chapter 17: Occupational immunologic lung disease.

    PubMed

    Sabin, Bradley R; Grammer, Leslie C

    2012-01-01

    Occupational immunologic lung disease is characterized by an immunologic response in the lung to an airborne agent inhaled in the work environment and can be subdivided into immunologically mediated occupational asthma (OA) and hypersensitivity pneumonitis (HP). Irritant-induced OA, a separate nonimmunologic entity, can be caused by chronic exposure to inhaled irritants or reactive airways dysfunction syndrome, defined as an asthma-like syndrome that persists for >3 months and occurs abruptly after a single exposure to a high concentration of an irritating industrial agent. High-risk fields for OA include farmers, printers, woodworkers, painters, plastic workers, cleaners, spray painters, electrical workers, and health care workers. OA can be triggered by high molecular weight (HMW) proteins that act as complete allergens or low molecular weight (LMW) sensitizers that act as haptens. HMW proteins (>10 kDa) are generally derived from microorganisms (such as molds and bacteria, including thermophilic actinomycetes), plants (such as latex antigens and flour proteins), or animals (such as animal dander, avian proteins, and insect scales) and are not specifically regulated by the Occupational Safety and Health Administration (OSHA). LMW haptens that bind to proteins in the respiratory mucosa include some OSHA-regulated substances such as isocyanates, anhydrides, and platinum. HP can present in an acute, a chronic, or a subacute form. The acute, subacute, and early chronic form is characterized by a CD4(+) T(H)1 and CD8(+) lymphocyte alveolitis. Classically, the bronchoalveolar lavage will show a CD4/CD8 ratio of <1. PMID:22794690

  8. Asthma-like peak flow variability in various lung diseases

    PubMed Central

    Singh, Virendra; Meena, Pradeep; Sharma, Bharat Bhushan

    2012-01-01

    Background and Objectives: Bronchodilator reversibility and diurnal peak flow variability are considered characteristic of asthma patients. Patients with chronic obstructive pulmonary disease (COPD) show poor reversibility. But reversibility and variability in other pulmonary diseases manifesting with airflow obstruction in not known. Therefore, we assessed reversibility and peak flow variability in patients with various lung diseases to recognize the pattern. Materials and Methods: Seventy consecutive patients with a diagnosis of lung diseases manifesting with airflow obstruction were recruited in the study. These included 23 patients with asthma, 11 patients with bronchiectasis, 16 patients with post-tubercular lung disease (PTLD), and 20 patients with COPD. Ten healthy matched control subjects were also selected to pair with asthmatic patients. Bronchodilator reversibility test was done initially and peak expiratory flow rate (PEFR) was measured for a duration of 1 week by patients themselves on a chart that was given to them. The mean amplitude percentage of these records were analyzed. Results: The mean values of peak flow variability were 14.73% ± 6.1% in asthmatic patients, 11.98% ± 7.5% in patients with bronchiectasis, and 10.54% ± 5.3% in PTLD. The difference in the mean values of peak flow variability between asthma and bronchiectasis, that is, 14.73 (6.1) vs 11.98 (7.5) was not statistically significant (P > 0.05). Forced expiratory volume one second (FEV1) reversibility values were 14.77% ± 26.93%, 11.24% ± 20.43%, 10.85% ± 13.02%, 16.83% ± 22.84%, and 5.47% ± 4.99% in asthma, COPD, PTLD, bronchiectasis, and healthy subjects, respectively. Conclusion: Both reversibility and diurnal peak flow variability were higher in patients with various lung diseases compared with normal healthy subjects. Although these are characteristic of asthma, some cases of bronchiectasis and PTLD patients may also manifest asthma-like PEFR variability and reversibility

  9. Intravascular laser therapy in different forms of lung diseases

    NASA Astrophysics Data System (ADS)

    Kirillov, M. N.; Reshetnikov, V. A.; Kazhekin, O. A.; Shepelenko, A. F.

    1993-06-01

    The potentions of laser intravascular therapy in elimination of pyogenic and inflammatory intoxication in cases of acute pneumonia, pyo-destructive diseases (including posttraumatic diseases) of the lungs are studied clinically.

  10. Lung Disease Caused by Mycobacterium malmoense in an Immunocompetent Patient

    PubMed Central

    Jeon, Min Kyung; Yoon, Jung A; Kim, Junhwan; Yi, Sangyoung; Sung, Heungsup; Shim, Tae Sun

    2015-01-01

    Mycobacterium malmoense is a very rare cause of lung disease in South Korea. We reported the first case of lung disease caused by M. malmoense in an immunocompetent patient. The patient was successfully treated with a 14-month course of antibiotics. PMID:26175789

  11. Blue Journal Conference. Aging and Susceptibility to Lung Disease

    PubMed Central

    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.

    2015-01-01

    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. PMID:25590812

  12. The Spectrum of Nocardia Lung Disease in Cystic Fibrosis.

    PubMed

    Mei-Zahav, Meir; Livnat, Galit; Bentur, Lea; Mussaffi, Huda; Prais, Dario; Stafler, Patrick; Bar-On, Ophir; Steuer, Guy; Blau, Hannah

    2015-08-01

    We reviewed all cases of Nocardia infection in cystic fibrosis patients at 2 centers. Eight of 200 patients had Nocardia in sputum. Four developed severe lung disease, including 3 with associated allergic bronchopulmonary aspergillosis; 4 remained clinically stable. Nocardia is often associated with significant lung disease in cystic fibrosis, possibly associated with allergic bronchopulmonary aspergillosis or steroids. PMID:25973994

  13. 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. PMID:26135330

  14. Aerosol Therapy for Obstructive Lung Diseases

    PubMed Central

    2011-01-01

    Inhaled aerosol therapies are the mainstay of treatment of obstructive lung diseases. Aerosol devices deliver drugs rapidly and directly into the airways, allowing high local drug concentrations while limiting systemic toxicity. While numerous clinical trials, literature reviews, and expert panel guidelines inform the choice of inhalational drugs, deciding which aerosol device (ie, metered-dose inhaler, nebulizer, or dry powder inhaler) best suits a given patient and clinical setting can seem arbitrary and confusing. Similar confusion regarding Current Procedural Terminology (CPT) coding for administration of aerosol therapies can lead to lost revenue from underbilling and wasted administrative effort handling denied claims. This article reviews the aerosol devices currently available, discusses their relative merits in various clinical settings, and summarizes appropriate CPT coding for aerosol therapy. PMID:21896522

  15. 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

  16. Lung epithelial ion transport in neonatal lung disease.

    PubMed

    Pitkänen, O

    2001-05-01

    Lung epithelial ion transport promotes salt and water movement across the fetal and neonatal lung epithelium. The mechanism is dependent on basolateral membrane Na-K-ATPase and the apical membrane Cl(-) and Na(+) channels. During fetal life active secretion of Cl(-) and parallel movement of Na(+) across the epithelium into the developing lung lumen induce accumulation of liquid into the future airspaces. Postnatally, however, absorption of fluid from the airspaces must start. Present evidence suggests that activation of Na(+) transport from the lumen into the basolateral direction drives fluid absorption and results in an essentially dry air-filled alveolus. In laboratory animals amiloride, a Na(+) channel blocker, induces respiratory distress and impedes lung fluid clearance. One of the epithelial amiloride-sensitive Na(+) channels, ENaC, is composed of three homologous subunits that differentially respond to glucocorticoid hormone. In newborn infants an increase in pulmonary fluid and a defective Na(+) transport associate with respiratory distress. The ontogeny, subunit composition and function of ENaC along the respiratory tract are currently under investigation. It will be interesting to find out whether the subunit composition and function of lung ENaC respond to the therapy of the critically ill newborn infant. PMID:11359039

  17. Future Directions in Early Cystic Fibrosis Lung Disease Research

    PubMed Central

    Banks-Schlegel, Susan; Accurso, Frank J.; Boucher, Richard C.; Cutting, Garry R.; Engelhardt, John F.; Guggino, William B.; Karp, Christopher L.; Knowles, Michael R.; Kolls, Jay K.; LiPuma, John J.; Lynch, Susan; McCray, Paul B.; Rubenstein, Ronald C.; Singh, Pradeep K.; Sorscher, Eric; Welsh, Michael

    2012-01-01

    Since the 1989 discovery that mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF), there has been substantial progress toward understanding the molecular basis for CF lung disease, leading to the discovery and development of new therapeutic approaches. However, the earliest impact of the loss of CFTR function on airway physiology and structure and its relationship to initial infection and inflammation are poorly understood. Universal newborn screening for CF in the United States represents an unprecedented opportunity for investigating CF clinical manifestations very early in life. Recently developed animal models with pulmonary phenotypic manifestations also provide a window into the early consequences of this genetic disorder. For these reasons, the National Heart, Lung, and Blood Institute (NHLBI) convened a working group of extramural experts, entitled “Future Research Directions in Early CF Lung Disease” on September 21–22, 2010, to identify future research directions of great promise in CF. The priority areas identified included (1) exploring pathogenic mechanisms of early CF lung disease; (2) leveraging newborn screening to elucidate the natural history of early lung disease; (3) developing a spectrum of biomarkers of early lung disease that reflects CF pathophysiology, clinical outcome, and response to treatment; (4) exploring the role of genetics/genomics (e.g., modifier genes, gene–environmental interactions, and epigenetics) in early CF pathogenesis; (5) defining early microbiological events in CF lung disease; and (6) elucidating the initial airway inflammatory, remodeling, and repair mechanisms in CF lung disease. PMID:22312017

  18. Surfactant Lipidomics in Healthy Children and Childhood Interstitial Lung Disease

    PubMed Central

    Liebisch, Gerhard; Rauch, Daniela; Stückler, Ferdinand; Schmitz, Gerd; Zarbock, Ralf

    2015-01-01

    Background Lipids account for the majority of pulmonary surfactant, which is essential for normal breathing. We asked if interstitial lung diseases (ILD) in children may disrupt alveolar surfactant and give clues for disease categorization. Methods Comprehensive lipidomics profiles of broncho-alveolar lavage fluid were generated in 115 children by electrospray ionization tandem mass spectrometry (ESI-MS/MS). Two reference populations were compared to a broad range of children with ILD. Results Class and species composition in healthy children did not differ from that in children with ILD related to diffuse developmental disorders, chronic tachypnoe of infancy, ILD related to lung vessels and the heart, and ILD related to reactive lymphoid lesions. As groups, ILDs related to the alveolar surfactant region, ILD related to unclear respiratory distress syndrome in the mature neonate, or in part ILD related to growth abnormalities reflecting deficient alveolarisation, had significant alterations of some surfactant specific phospholipids. Additionally, lipids derived from inflammatory processes were identified and differentiated. In children with ABCA3-deficiency from two ILD causing mutations saturated and monounsaturated phosphatidylcholine species with 30 and 32 carbons and almost all phosphatidylglycerol species were severely reduced. In other alveolar disorders lipidomic profiles may be of less diagnostic value, but nevertheless may substantiate lack of significant involvement of mechanisms related to surfactant lipid metabolism. Conclusions Lipidomic profiling may identify specific forms of ILD in children with surfactant alterations and characterized the molecular species pattern likely to be transported by ABCA3 in vivo. PMID:25692779

  19. International union against tuberculosis and lung disease (IUATLD): initiatives in non-tuberculous lung disease.

    PubMed

    Becklake, M R

    1995-12-01

    IUATLD initiatives in non-tuberculous lung disease developed in the late 1970s, coincident with improving tuberculosis control, and have targeted acute respiratory infections in children and chronic airways disease in adults and in children. The focus has been on methodology and the tools required to document the distribution and determinants of disease, and is illustrated in data gathered in African populations. Instruments developed include a simplified method of measuring bronchial hyper-reactivity and an asthma questionnaire Non-standard methods of questionnaire administration have also been validated, methods which are appropriate for use in the burgeoning urban communities and workforces of sub-Saharan Africa made up of rural migrants from different tribes and language groups. In addition, a review of reference values available for interpreting lung function in sub-Saharan African populations indicates a need to take into account a secular trend over the last two decades towards higher spirometric values. In the published data from Africa, not inconsiderable between-country differences are evident in the prevalence of chronic bronchitis in adults and of asthma in children. In addition, rates for childhood asthma were consistently higher in urban vs rural communities, with environmental factors playing an important role as well as being locally specific. Not only does the burden of morbidity attributable to both the chronic airway diseases reviewed justify past IUATLD initiatives in non-tuberculous lung disease, but it also argues that future initiatives should focus on investigating between- and within-country differences using a standardized methodology, with a view to identifying local environmental determinants susceptible to intervention and control. Curbing tobacco use is clearly important, not only to benefit the health of adult smokers for whom the ill-health consequences have long been recognized, but, and more important, to protect the health of

  20. 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.

  1. 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

  2. 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.

  3. 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. PMID:27086030

  4. 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. PMID:27145498

  5. [Why screen for lung cancer in patients with arterial disease?].

    PubMed

    Lederlin, M; Trédaniel, J; Priollet, P

    2015-12-01

    Lung cancer remains the leading cause of cancer death in France. Such a prognosis is explained by late diagnosis at a metastatic stage for half of the patients. Tobacco is the main risk factor for lung cancer, as it is for peripheral arterial disease. A review of literature shows that between 2.3% and 19% of patients with arterial disease also have lung cancer. When lung cancer is detected after treatment of arterial disease, it is at an advanced stage. But it can be diagnosed at an early stage when it is searched simultaneously with arterial disease treatment. There is no recommendation for lung cancer screening specifically for patients with arterial disease. However individual screening based on an annual low-dose chest scan is proposed for smokers meeting the criteria defined by the study of the National Lung Screening Trial (NLST). Such screening has two disadvantages : the high number of false positives and the irradiation induced by the accumulation of examinations. The ISET method would alternatively help to identify circulating tumor cells on a simple blood test for subjects not yet at solid tumor stage, provided this method be subject to multicentric validation. Thus one could consider that the management of a patient with arterial disease meeting NLST criteria should be accompanied with screening for lung cancer by searching for tumor cells associated with low-dose scanner. PMID:26276562

  6. 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. PMID:26974298

  7. Lung cancer screening in patients with chronic obstructive pulmonary disease.

    PubMed

    Gonzalez, Jessica; Marín, Marta; Sánchez-Salcedo, Pablo; Zulueta, Javier J

    2016-04-01

    Lung cancer and chronic obstructive pulmonary disease (COPD) are two intimately related diseases, with great impact on public health. Annual screening using low-dose computed tomography (LDCT) of the chest significantly reduces mortality due to lung cancer, and several scientific societies now recommend this technique. COPD, defined by the presence of airflow obstruction [forced expiratory volume and forced vital capacity (FVC) ratio less than 0.70], and their clinical phenotypes, namely emphysema and chronic bronchitis, have been associated with increased lung cancer risk. Several epidemiological studies, including lung cancer screening trials, have found a 2- to 4-fold increase in lung cancer risk in patients with COPD when compared to individuals without airflow obstruction. Part of the risk attributed to airflow obstruction appears to be derived from the presence of radiographic emphysema. The latter has proven to be an important lung cancer risk factor in smokers without airflow obstruction and even in never smokers. This evidence supports the idea of including patients with COPD and/or emphysema in lung cancer screening programs. There is evidence that lung cancer screening in this population is effective and can potentially reduce mortality. Specific lung cancer risk scores have been developed for patients with COPD [COPD lung cancer screening score (LUCSS) and COPD-LUCSS-diffusing capacity for carbon monoxide (DLCO)] to identify those at high risk. A multidisciplinary approach for an adequate patient selection, especially of patients with severe disease, is key to maximize benefits and reduce harms from lung cancer screening in this population. Patients with COPD included in lung cancer screening programs could also benefit from other interventions, such as smoking cessation and adequate treatment. PMID:27195278

  8. Lung cancer screening in patients with chronic obstructive pulmonary disease

    PubMed Central

    Gonzalez, Jessica; Marín, Marta; Sánchez-Salcedo, Pablo

    2016-01-01

    Lung cancer and chronic obstructive pulmonary disease (COPD) are two intimately related diseases, with great impact on public health. Annual screening using low-dose computed tomography (LDCT) of the chest significantly reduces mortality due to lung cancer, and several scientific societies now recommend this technique. COPD, defined by the presence of airflow obstruction [forced expiratory volume and forced vital capacity (FVC) ratio less than 0.70], and their clinical phenotypes, namely emphysema and chronic bronchitis, have been associated with increased lung cancer risk. Several epidemiological studies, including lung cancer screening trials, have found a 2- to 4-fold increase in lung cancer risk in patients with COPD when compared to individuals without airflow obstruction. Part of the risk attributed to airflow obstruction appears to be derived from the presence of radiographic emphysema. The latter has proven to be an important lung cancer risk factor in smokers without airflow obstruction and even in never smokers. This evidence supports the idea of including patients with COPD and/or emphysema in lung cancer screening programs. There is evidence that lung cancer screening in this population is effective and can potentially reduce mortality. Specific lung cancer risk scores have been developed for patients with COPD [COPD lung cancer screening score (LUCSS) and COPD-LUCSS-diffusing capacity for carbon monoxide (DLCO)] to identify those at high risk. A multidisciplinary approach for an adequate patient selection, especially of patients with severe disease, is key to maximize benefits and reduce harms from lung cancer screening in this population. Patients with COPD included in lung cancer screening programs could also benefit from other interventions, such as smoking cessation and adequate treatment. PMID:27195278

  9. 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.

  10. Sonic Hedgehog Signaling in the Lung. From Development to Disease

    PubMed Central

    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. PMID:25068457

  11. 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. PMID:25929952

  12. Bioactive extracellular matrix fragments in lung health and disease.

    PubMed

    Gaggar, Amit; Weathington, Nathaniel

    2016-09-01

    The extracellular matrix (ECM) is the noncellular component critical in the maintenance of organ structure and the regulation of tissue development, organ structure, and cellular signaling. The ECM is a dynamic entity that undergoes continuous degradation and resynthesis. In addition to compromising structure, degradation of the ECM can liberate bioactive fragments that cause cellular activation and chemotaxis of a variety of cells. These fragments are termed matrikines, and their cellular activities are sentinel in the development and progression of tissue injury seen in chronic lung disease. Here, we discuss the matrikines that are known to be active in lung biology and their roles in lung disease. We also consider the use of matrikines as disease markers and potential therapeutic targets in lung disease. PMID:27584731

  13. Transbronchial Lung Cryobiopsy in the Diagnosis of Fibrotic Interstitial Lung Diseases

    PubMed Central

    Cavazza, Alberto; Colby, Thomas V.; Dubini, Alessandra; Ryu, Jay H.; Carretta, Elisa; Tantalocco, Paola; Piciucchi, Sara; Ravaglia, Claudia; Gurioli, Christian; Romagnoli, Micaela; Gurioli, Carlo; Chilosi, Marco; Poletti, Venerino

    2014-01-01

    Background Histology is a key element for the multidisciplinary diagnosis of fibrotic diffuse parenchymal lung diseases (f-DPLD) when the clinical-radiological picture is nondiagnostic. Transbronchial lung cryobiopsy (TBLC) have been shown to be useful for obtaining large and well-preserved biopsies of lung parenchyma, but experience with TBLC in f-DPLD is limited. Objectives To evaluate safety, feasibility and diagnostic yield of TBLC in f-DPLD. Method Prospective study of 69 cases of TBLC using flexible cryoprobe in the clinical-radiological setting of f-DPLD with nondiagnostic high resolution computed tomography (HRCT) features. Results Safety: pneumothorax occurred in 19 patients (28%). One patient (1.4%) died of acute exacerbation. Feasibility: adequate cryobiopsies were obtained in 68 cases (99%). The median size of cryobiopsies was 43.11 mm2 (range, 11.94–76.25). Diagnostic yield: among adequate TBLC the pathologists were confident (“high confidence”) that histopathologic criteria sufficient to define a specific pattern in 52 patients (76%), including 36 of 47 with UIP (77%) and 9 nonspecific interstitial pneumonia (6 fibrosing and 3 cellular), 2 desquamative interstitial pneumonia/respiratory bronchiolitis–interstitial lung disease, 1 organizing pneumonia, 1 eosinophilic pneumonia, 1 diffuse alveolar damage, 1 hypersensitivity pneumonitis and 1 follicular bronchiolitis. In 11 diagnoses of UIP the pathologists were less confident (“low confidence”). Agreement between pathologists in the detection of UIP was very good with a Kappa coefficient of 0.83 (95% CI, 0.69–0.97). Using the current consensus guidelines for clinical-radiologic-pathologic correlation 32% (20/63) of cases were classified as Idiopathic Pulmonary Fibrosis (IPF), 30% (19/63) as possible IPF, 25% (16/63) as other f-DPLDs and 13% (8/63) were unclassifiable. Conclusions TBLC in the diagnosis of f-DPLD appears safe and feasible. TBLC has a good diagnostic yield in the clinical

  14. 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

    2013-10-01

    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. PMID:23849967

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

    PubMed

    Ryu, Yon Ju; Koh, Won-Jung; Daley, Charles L

    2016-04-01

    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

  16. Adenosine signaling and the regulation of chronic lung disease

    PubMed Central

    Zhou, Yang; Schneider, Daniel J.; Blackburn, Michael R.

    2009-01-01

    Chronic lung diseases such as asthma, chronic obstructive pulmonary disease and interstitial lung disease are characterized by inflammation and tissue remodeling processes that compromise pulmonary function. Adenosine is produced in the inflamed and damaged lung where it plays numerous roles in the regulation of inflammation and tissue remodeling. Extracellular adenosine serves as an autocrine and paracrine signaling molecule by engaging cell surface adenosine receptors. Preclinical and cellular studies suggest that adenosine plays an anti-inflammatory role in processes associated with acute lung disease, where activation of the A2AR and A2BR have promising implications for the treatment of these disorders. In contrast, there is growing evidence that adenosine signaling through the A1R, A2BR and A3R may serve pro-inflammatory and tissue remodeling functions in chronic lung diseases. This review discusses the current progress of research efforts and clinical trials aimed at understanding the complexities of this signaling pathway as they pertain to the development of treatment strategies for chronic lung diseases. PMID:19426761

  17. 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

  18. Integrin α3 Mutations with Kidney, Lung, and Skin Disease

    PubMed Central

    Has, Cristina; Spartà, Giuseppina; Kiritsi, Dimitra; Weibel, Lisa; Moeller, Alexander; Vega-Warner, Virginia; Waters, Aoife; He, Yinghong; Anikster, Yair; Esser, Philipp; Straub, Beate K.; Hausser, Ingrid; Bockenhauer, Detlef; Dekel, Benjamin; Hildebrandt, Friedhelm; Bruckner-Tuderman, Leena; Laube, Guido F.

    2012-01-01

    SUMMARY Integrin α3 is a transmembrane integrin receptor subunit that mediates signals between the cells and their microenvironment. We identified three patients with homozygous mutations in the integrin α3 gene that were associated with disrupted basement-membrane structures and compromised barrier functions in kidney, lung, and skin. The patients had a multiorgan disorder that included congenital nephrotic syndrome, interstitial lung disease, and epidermolysis bullosa. The renal and respiratory features predominated, and the lung involvement accounted for the lethal course of the disease. Although skin fragility was mild, it provided clues to the diagnosis. PMID:22512483

  19. Bleb point: mimicker of pneumothorax in bullous lung disease.

    PubMed

    Gelabert, Christopher; Nelson, Mathew

    2015-05-01

    In patients presenting with severe dyspnea, several diagnostic challenges arise in distinguishing the diagnosis of pneumothorax versus several other pulmonary etiologies like bullous lung disease, pneumonia, interstitial lung disease, and acute respiratory distress syndrome. Distinguishing between large pulmonary bullae and pneumothorax is of the utmost importance, as the acute management is very different. While multiple imaging modalities are available, plain radiographs may be inadequate to make the diagnosis and other advanced imaging may be difficult to obtain. Ultrasound has a very high specificity for pneumothorax. We present a case where a large pulmonary bleb mimics the lung point and therefore inaccurately suggests pneumothorax. PMID:25987927

  20. Inflammation in cystic fibrosis lung disease: Pathogenesis and therapy.

    PubMed

    Cantin, André M; Hartl, Dominik; Konstan, Michael W; Chmiel, James F

    2015-07-01

    Lung disease is the major cause of morbidity and mortality in patients with cystic fibrosis (CF). Although CF lung disease is primarily an infectious disorder, the associated inflammation is both intense and ineffective at clearing pathogens. Persistent high-intensity inflammation leads to permanent structural damage of the CF airways and impaired lung function that eventually results in respiratory failure and death. Several defective inflammatory responses have been linked to cystic fibrosis transmembrane conductance regulator (CFTR) deficiency including innate and acquired immunity dysregulation, cell membrane lipid abnormalities, various transcription factor signaling defects, as well as altered kinase and toll-like receptor responses. The inflammation of the CF lung is dominated by neutrophils that release oxidants and proteases, particularly elastase. Neutrophil elastase in the CF airway secretions precedes the appearance of bronchiectasis, and correlates with lung function deterioration and respiratory exacerbations. Anti-inflammatory therapies are therefore of particular interest for CF lung disease but must be carefully studied to avoid suppressing critical elements of the inflammatory response and thus worsening infection. This review examines the role of inflammation in the pathogenesis of CF lung disease, summarizes the results of past clinical trials and explores promising new anti-inflammatory options. PMID:25814049

  1. 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

  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. PMID:8465532

  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. PMID:10444954

  4. 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.

  5. Bronchial anthracofibrosis with interstitial lung disease: an association yet to be highlighted.

    PubMed

    Kunal, Shekhar; Pilaniya, Vikas; Shah, Ashok

    2016-01-01

    Bronchial anthracofibrosis (BAF), an emerging pulmonary disease due to long-standing exposure to biomass fuel smoke, is predominantly seen in females from developing nations. BAF is known to be associated with tuberculosis, pneumonia, chronic obstructive pulmonary disease and lung cancer, but the association of BAF with interstitial lung disease (ILD) is rare and yet to be highlighted. A 72-year-old woman with a 30-year history of exposure to biomass fuel smoke presented with dry cough and exertional dyspnoea. Imaging demonstrated interlobular, intralobular and peribronchovascular interstitial thickening and honeycombing adjoining the subpleural regions, suggestive of the usual interstitial pneumonia pattern. A restrictive pattern with diffusion defect was noted. Fibrebronchoscopy revealed a bluish-black anthracotic pigmentation with a narrowed and distorted left upper lobe, and apical segment of left lower lobe bronchus, confirming BAF. A diagnosis of BAF with ILD was made. To the best of our knowledge, this is the first detailed description of this association. PMID:26759407

  6. Strategies for Management of the Early Chronic Obstructive Lung Disease

    PubMed Central

    Lee, Jung Yeon; Rhee, Chin Kook; Jung, Ki Suck

    2016-01-01

    Lung function reportedly declines with age and that this decline is accelerated during disease progression. However, a recent study showed that the decline might peak in the mild and moderate stage. The prognosis of chronic obstructive pulmonary disease (COPD) can be improved if the disease is diagnosed in its early stages, prior to the peak of decline in lung function. This article reviews recent studies on early COPD and the possibility of applying the U.S. Preventive Services Task Force recommendation 2008 and 2015 for early detection of COPD in Korea. PMID:27433171

  7. [Pathophysiological approach to infiltrative lung diseases on CT].

    PubMed

    Brauner, M; Brillet, Py

    2009-11-01

    The analysis of HRCT findings of interstitial lung diseases frequently allows to predict the reversible nature of abnormalities, to recognize the involved components of the lung and to suggest the underlying pathophysiological mechanisms. Pathologic alterations in the anatomy of secondary pulmonary lobules include interlobular septal thickening or/and diseases with peripheral lobular distribution, centrilobular abnormalities, and panlobular abnormalities. Consolidations and ground glass opacities are better analyzed by taking into account the way lung responds to injury rather than anatomic distribution of lesions. The recognition of the topographic distribution of lesions and associated abnormalities, including airway diseases, pulmonary hypertension and embolus, diaphragmatic and pharyngeal dysfunctions, provides a better understanding of underlying disease mechanisms and allows a limited differential diagnosis. PMID:19953076

  8. 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.

  9. WORK-RELATED LUNG DISEASES (WORLD) SURVEILLANCE REPORT

    EPA Science Inventory

    This Work-Related Lung Disease (WoRLD) Surveillance Report is the fifth in a series of occupational respiratory disease surveillance reports (see page iv) produced by the National Institute for Occupational Safety and Health (NIOSH). It presents summary tables and figures of occu...

  10. Scintigraphic studies of inflammation in diffuse lung disease

    SciTech Connect

    Line, B.R. )

    1991-09-01

    67Ga lung scintigraphy is an established means to assess alveolar inflammation in a wide variety of diffuse lung diseases. It can be used to monitor the extent and activity of the alveolitis during the course of the disease and as a follow-up evaluation to therapy. Although the mechanism of 67Ga localization is not established firmly, the isotope appears to act as a tracer for disturbed protein and cellular fluxes within the interstitium and alveolar spaces. The radiolabeled aerosol study may also be applied to the study of these fluxes as a reflection of inflammation and injury. Although Tc-DTPA clearance studies are highly sensitive to lung injury, they may be too nonspecific to separate lung injury from other physiologic processes effectively. 117 references.

  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. Clinical approach to chronic beryllium disease and other nonpneumoconiotic interstitial lung diseases.

    PubMed

    Maier, Lisa A

    2002-10-01

    Exposures in the workplace result in a diverse set of diseases ranging from the pneumoconiosis to other interstitial lung diseases to acute lung injury. Physician awareness of the potential disease manifestations associated with specific exposures is important in defining these diseases and in preventing additional disease. Most occupational diseases mimic other forms of lung disease, including pulmonary fibrosis, sarcoidosis, adult respiratory distress syndrome (ARDS), and bronchiolitis. A "sarcoidosis"-like syndrome, usually limited to the lungs, may result from exposure to bioaerosols and a number of metals. Exposure to beryllium in the workplace produces a granulomatous lung disease clinically indistinguishable from sarcoidosis, chronic beryllium disease (CBD). Beryllium's ability to produce a beryllium-specific immune response is used in the beryllium lymphocyte proliferation tests to confirm a diagnosis of CBD and exclude sarcoidosis. Exposure to other metals must also be considered in the differential diagnosis of sarcoidosis. When an individual presents acutely with ARDS or acute lung injury, an acute inhalational exposure must be considered. Exposure to a number of irritant substances at high levels may cause a "chemical pneumonitis" or acute lung injury, depending on the solubility and physicochemical properties of the substance. Some of the most notable agents include nitrogen and sulfur oxides, phosgene, and smoke breakdown products. Ingestion of paraquat may also result in an ARDS syndrome, with pulmonary fibrosis eventually resulting. Bronchiolitis is a rare manifestation of inhalational exposures but must also be considered in the clinical evaluation of inhalational exposure. PMID:12362066

  13. Stem cell therapy: the great promise in lung disease.

    PubMed

    Siniscalco, Dario; Sullo, Nikol; Maione, Sabatino; Rossi, Francesco; D'Agostino, Bruno

    2008-06-01

    Lung injuries are leading causes of morbidity and mortality worldwide. Pulmonary diseases such as asthma or chronic obstructive pulmonary disease characterized by loss of lung elasticity, small airway tethers, and luminal obstruction with inflammatory mucoid secretions, or idiopathic pulmonary fibrosis characterized by excessive matrix deposition and destruction of the normal lung architecture, have essentially symptomatic treatments and their management is costly to the health care system.Regeneration of tissue by stem cells from endogenous, exogenous, and even genetically modified cells is a promising novel therapy. The use of adult stem cells to help with lung regeneration and repair could be a newer technology in clinical and regenerative medicine. In fact, different studies have shown that bone marrow progenitor cells contribute to repair and remodeling of lung in animal models of progressive pulmonary hypertension.Therefore, lung stem cell biology may provide novel approaches to therapy and could represent a great promise for the future of molecular medicine. In fact, several diseases can be slowed or even blocked by stem cell transplantation. PMID:19124369

  14. 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. PMID:27316904

  15. Rheumatoid lung disease. (A clinical, physiological and histological study in 33 patients).

    PubMed

    Danieli, G; Corvetta, A; Mariuzzi, G M; Beltrami, C A; Osculati, F; Cinti, S; Massei, V; Sanguinetti, C M

    1980-01-01

    Clinical, physiological and histological investigations on lung involvement are reported in 33 rheumatoid patients. The clinico-pathological patterns of rheumatoid lung disease observed in 19/27 non-smoking female patients were characterized radiologically by diffuse interstitial opacities, functionally by V/Q inequality and microscopically by peribronchiolar and/or alveolar fibrosis. Emphasis is placed on the ventilation/perfusion relationship as well as histopathological studies for a more accurate diagnosis of lung disease in RA. Patients with pulmonary nodules and pleural opacities were also observed. A possible immunological aetiology is suggested on the basis of the simultaneous finding of IgG, complement and fibrinogen in the pulmonary tissue. PMID:7209294

  16. 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.

  17. 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

  18. Noninfectious lung pathology in patients with Crohn's disease.

    PubMed

    Casey, Mary B; Tazelaar, Henry D; Myers, Jeffrey L; Hunninghake, Gary W; Kakar, Sanjay; Kalra, Sanjay X; Ashton, Rendell; Colby, Thomas V

    2003-02-01

    Lung involvement in Crohn's disease is not well characterized. We reviewed our experience with 11 lung biopsies (seven wedge and four transbronchial) from patients with Crohn's disease to study this association further. Negative cultures, special stains for organisms Gomori-methenamine-silver [GMS], acid fast), and polymerase chain reaction for (four cases) were required for inclusion. The group included five women and six men with a mean age of 47 years (range 13-84 years). A diagnosis of Crohn's disease preceded the lung disease in nine patients. In two patients the diagnosis of Crohn's disease followed the diagnosis of their pulmonary disease 1 and 15 months later. Radiologically, eight patients had diffuse infiltrates, two had bilateral nodular infiltrates, and one had a mass. Chronic bronchiolitis with nonnecrotizing granulomatous inflammation was present in four patients, one of whom was taking mesalamine. Two patients had an acute bronchiolitis associated with a neutrophil-rich bronchopneumonia with suppuration and vague granulomatous features. One patient on mesalamine had cellular interstitial pneumonia with rare giant cells. Four patients demonstrated organizing pneumonia with focal granulomatous features, two of whom were taking mesalamine, and one of these two responded to infliximab (anti-tumor necrosis factor) monoclonal antibody therapy. Noninfectious pulmonary disease in patients with Crohn's disease has variable histologic appearances, including granulomatous inflammation and airway-centered disease resembling that seen in patients with ulcerative colitis. Drugs may contribute to pulmonary disease in some patients. PMID:12548168

  19. Pemetrexed for advanced non-small cell lung cancer patients with interstitial lung disease

    PubMed Central

    2014-01-01

    Background Non-small cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) need to be approached carefully given the high incidence of pulmonary toxicity. Pemetrexed (PEM) is the key drug for the treatment of NSCLC. However, its safety, especially with respect to the exacerbation of ILD, and efficacy in NSCLC patients with ILD have yet to be established. Method We investigated the safety and efficacy of PEM monotherapy in NSCLC patients with or without idiopathic interstitial pneumonia (IIPs). The medical charts of these patients were retrospectively reviewed. Results Twenty-five patients diagnosed as having IIPs (IIPs group) and 88 patients without ILD (non-ILD group) were treated with PEM monotherapy at Juntendo University Hospital between 2009 and 2013. In the IIPs group, 12 patients were found to have usual interstitial pneumonitis (UIP) on chest computed tomography (CT) (UIP group) and the other 13 patients showed a non-UIP pattern on chest CT (non-UIP IIPs group). Three patients in the IIPs group (2 in the UIP group and 1 in the non-UIP IIPs group) and 1 in the non-ILD group developed pulmonary toxicity during treatment (3.5% overall, 12.0% in the IIPs group versus 1.1% in the non-ILD group). Moreover, all 3 patients in the IIPs group died of pulmonary toxicity. Overall survival tended to be longer in the non-ILD group than in the IIPs group (p = 0.08). Multivariate analyses demonstrated that IIPs was the only significant independent risk factor for PEM-related pulmonary toxicity. Conclusion We found that the incidence of PEM-related pulmonary toxicity was significantly higher amongst NSCLC patients with IIPs than among those without IIPs. Particular care must be taken when administering PEM to treat NSCLC patients with IIPs. PMID:25012241

  20. 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.

  1. 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

  2. Promotion of Lung Health: NHLBI Workshop on the Primary Prevention of Chronic Lung Diseases

    PubMed Central

    Budinger, G. R. Scott; Escobar, Gabriel J.; Hansel, Nadia N.; Hanson, Corrine K.; Huffnagle, Gary B.; Buist, A. Sonia

    2014-01-01

    Lung-related research primarily focuses on the etiology and management of diseases. In recent years, interest in primary prevention has grown. However, primary prevention also includes “health promotion” (actions in a population that keep an individual healthy). We encourage more research on population-based (public health) strategies that could not only maximize lung health but also mitigate “normal” age-related declines—not only for spirometry but across multiple measures of lung health. In developing a successful strategy, a “life course” approach is important. Unfortunately, we are unable to achieve the full benefit of this approach until we have better measures of lung health and an improved understanding of the normal trajectory, both over an individual’s life span and possibly across generations. We discuss key questions in lung health promotion, with an emphasis on the upper (healthier) end of the distribution of lung functioning and resiliency and briefly summarize the few interventions that have been studied to date. We conclude with suggestions regarding the most promising future research for this important, but largely neglected, area of lung research. PMID:24754821

  3. 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

  4. 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. PMID:26585429

  5. Mast cells and their activation in lung disease.

    PubMed

    Virk, Harvinder; Arthur, Greer; Bradding, Peter

    2016-08-01

    Mast cells and their activation contribute to lung health via innate and adaptive immune responses to respiratory pathogens. They are also involved in the normal response to tissue injury. However, mast cells are involved in disease processes characterized by inflammation and remodeling of tissue structure. In these diseases mast cells are often inappropriately and chronically activated. There is evidence for activation of mast cells contributing to the pathophysiology of asthma, pulmonary fibrosis, and pulmonary hypertension. They may also play a role in chronic obstructive pulmonary disease, acute respiratory distress syndrome, and lung cancer. The diverse mechanisms through which mast cells sense and interact with the external and internal microenvironment account for their role in these diseases. Newly discovered mechanisms of redistribution and interaction between mast cells, airway structural cells, and other inflammatory cells may offer novel therapeutic targets in these disease processes. PMID:26845625

  6. Mesenchymal Stromal Cells from Neonatal Tracheal Aspirates Demonstrate a Pattern of Lung-Specific Gene Expression

    PubMed Central

    Bozyk, Paul D.; Popova, Antonia P.; Bentley, John Kelley; Goldsmith, Adam M.; Linn, Marisa J.; Weiss, Daniel J.

    2011-01-01

    We have previously isolated mesenchymal stromal cells (MSCs) from the tracheal aspirates of premature neonates with respiratory distress. Although isolation of MSCs correlates with the development of bronchopulmonary dysplasia, the physiologic role of these cells remains unclear. To address this, we further characterized the cells, focusing on the issues of gene expression, origin, and cytokine expression. Microarray comparison of early passage neonatal lung MSC gene expression to cord blood MSCs and human fetal and neonatal lung fibroblast lines demonstrated that the neonatal lung MSCs differentially expressed 971 gene probes compared with cord blood MSCs, including the transcription factors Tbx2, Tbx3, Wnt5a, FoxF1, and Gli2, each of which has been associated with lung development. Compared with lung fibroblasts, 710 gene probe transcripts were differentially expressed by the lung MSCs, including IL-6 and IL-8/CXCL8. Differential chemokine expression was confirmed by protein analysis. Further, neonatal lung MSCs exhibited a pattern of Hox gene expression distinct from cord blood MSCs but similar to human fetal lung fibroblasts, consistent with a lung origin. On the other hand, limiting dilution analysis showed that fetal lung fibroblasts form colonies at a significantly lower rate than MSCs, and fibroblasts failed to undergo differentiation along adipogenic, osteogenic, and chondrogenic lineages. In conclusion, MSCs isolated from neonatal tracheal aspirates demonstrate a pattern of lung-specific gene expression, are distinct from lung fibroblasts, and secrete pro-inflammatory cytokines. PMID:21341990

  7. [Chronic interstitial lung disease in children: Diagnostic approach and management].

    PubMed

    Fuger, M; Clair, M-P; El Ayoun Ibrahim, N; L'Excellent, S; Nizery, L; O'Neill, C; Tabone, L; Truffinet, O; Yakovleff, C; de Blic, J

    2016-05-01

    Chronic interstitial lung disease (ILD) in children is a heterogeneous group of rare lung disorders characterized by an inflammatory process of the alveolar wall and the pulmonary interstitium that induces gas exchange disorders. The diagnostic approach to an ILD involves three essential steps: recognizing the ILD, appreciating the impact, and identifying the cause. The spectrum of clinical findings depends to a large extent on age. In the newborn, the beginning is often abrupt (neonatal respiratory distress), whereas there is a more gradual onset in infants (failure to thrive, tachypnea, indrawing of the respiratory muscles). In older children, the onset is insidious and the diagnosis can only be made at an advanced stage of the disease. The diagnosis is based on noninvasive methods (clinical history, respiratory function tests, chest X-ray, and high-resolution CT scan) and invasive techniques (bronchoalveolar lavage, transbronchial biopsy, video-assisted thoracoscopic biopsy, and open lung biopsy). The treatment of interstitial lung disease in children depends on the nature of the underlying pathology. The most common therapeutic approach involves the use of corticosteroids and immunosuppressive agents for their anti-inflammatory and antifibrotic effects. Children with ILD also need support therapy (oxygen therapy, nutritional support, treatment of pulmonary arterial hypertension, vaccination). Lung transplantation is discussed in patients with severe respiratory failure. PMID:27021883

  8. Lung microbiota across age and disease stage in cystic fibrosis.

    PubMed

    Coburn, Bryan; Wang, Pauline W; Diaz Caballero, Julio; Clark, Shawn T; Brahma, Vijaya; Donaldson, Sylva; Zhang, Yu; Surendra, Anu; Gong, Yunchen; Elizabeth Tullis, D; Yau, Yvonne C W; Waters, Valerie J; Hwang, David M; Guttman, David S

    2015-01-01

    Understanding the significance of bacterial species that colonize and persist in cystic fibrosis (CF) airways requires a detailed examination of bacterial community structure across a broad range of age and disease stage. We used 16S ribosomal RNA sequencing to characterize the lung microbiota in 269 CF patients spanning a 60 year age range, including 76 pediatric samples from patients of age 4-17, and a broad cross-section of disease status to identify features of bacterial community structure and their relationship to disease stage and age. The CF lung microbiota shows significant inter-individual variability in community structure, composition and diversity. The core microbiota consists of five genera - Streptococcus, Prevotella, Rothia, Veillonella and Actinomyces. CF-associated pathogens such as Pseudomonas, Burkholderia, Stenotrophomonas and Achromobacter are less prevalent than core genera, but have a strong tendency to dominate the bacterial community when present. Community diversity and lung function are greatest in patients less than 10 years of age and lower in older age groups, plateauing at approximately age 25. Lower community diversity correlates with worse lung function in a multivariate regression model. Infection by Pseudomonas correlates with age-associated trends in community diversity and lung function. PMID:25974282

  9. Lung microbiota across age and disease stage in cystic fibrosis

    PubMed Central

    Coburn, Bryan; Wang, Pauline W.; Diaz Caballero, Julio; Clark, Shawn T.; Brahma, Vijaya; Donaldson, Sylva; Zhang, Yu; Surendra, Anu; Gong, Yunchen; Elizabeth Tullis, D.; Yau, Yvonne C. W.; Waters, Valerie J.; Hwang, David M.; Guttman, David S.

    2015-01-01

    Understanding the significance of bacterial species that colonize and persist in cystic fibrosis (CF) airways requires a detailed examination of bacterial community structure across a broad range of age and disease stage. We used 16S ribosomal RNA sequencing to characterize the lung microbiota in 269 CF patients spanning a 60 year age range, including 76 pediatric samples from patients of age 4–17, and a broad cross-section of disease status to identify features of bacterial community structure and their relationship to disease stage and age. The CF lung microbiota shows significant inter-individual variability in community structure, composition and diversity. The core microbiota consists of five genera - Streptococcus, Prevotella, Rothia, Veillonella and Actinomyces. CF-associated pathogens such as Pseudomonas, Burkholderia, Stenotrophomonas and Achromobacter are less prevalent than core genera, but have a strong tendency to dominate the bacterial community when present. Community diversity and lung function are greatest in patients less than 10 years of age and lower in older age groups, plateauing at approximately age 25. Lower community diversity correlates with worse lung function in a multivariate regression model. Infection by Pseudomonas correlates with age-associated trends in community diversity and lung function. PMID:25974282

  10. Endothelium-platelet interactions in inflammatory lung disease.

    PubMed

    Tabuchi, Arata; Kuebler, Wolfgang M

    2008-01-01

    In addition to their established role in hemostasis, recent studies have identified platelets as key regulators of inflammatory reactions. Upon activation, platelets interact with both endothelial cells and circulating leukocytes. By receptor-mediated activation of interacting cell types and by release of mitogenic, pro-inflammatory and -coagulatory mediators, platelets contribute crucially to the initiation and propagation of pathological conditions and processes such as inflammatory bowel disease or atherosclerosis. In inflammatory lung disease, platelets play a critical role in the recruitment of neutrophils, eosinophils and lymphocytes as shown in experimental models of acute lung injury and allergic airway inflammation. Circulating platelet-leukocyte aggregates have been detected in patients with allergic asthma and cystic fibrosis, and in experimental lung injury. Here, we discuss the molecular mechanisms regulating the interaction of platelets with leukocytes, endothelial cells, and the subendothelial matrix with special regard to platelet kinetics in pulmonary microvessels and the putative role of platelets in inflammatory lung disorders. In light of the existing data from experimental and clinical studies it is conceivable that platelet adhesion molecules and platelet mediators provide promising targets for novel therapeutic strategies in inflammatory lung diseases. PMID:18625343

  11. Outcome Measures for Clinical Trials in Interstitial Lung Diseases

    PubMed Central

    Lammi, Matthew R.; Baughman, Robert P.; Birring, Surinder S.; Russell, Anne-Marie; Ryu, Jay H.; Scholand, Marybeth; Distler, Oliver; LeSage, Daphne; Sarver, Catherine; Antoniou, Katerina; Highland, Kristin B.; Kowal-Bielecka, Otylia; Lasky, Joseph A.; Wells, Athol U.; Saketkoo, Lesley Ann

    2015-01-01

    The chronic fibrosing idiopathic interstitial pneumonias (IIPs) are a group of heterogeneous pulmonary parenchymal disorders described by radiologic and histological patterns termed usual interstitial pneumonia (UIP) and non-specific interstitial pneumonia (NSIP). These include idiopathic pulmonary fibrosis (IPF) and those related to connective tissue disease (CTD) and are associated with substantial morbidity and mortality. Beyond the importance of establishing an appropriate diagnosis, designing optimal clinical trials for IIPs has been fraught with difficulties in consistency of clinical endpoints making power analyses, and the establishment of efficacy and interpretation of results across trials challenging. Preliminary recommendations, developed by rigorous consensus methods, proposed a minimum set of outcome measures, a ‘core set’, to be incorporated into future clinical trials (Saketkoo et al, THORAX. 2014.). This paper sets out to examine the candidate instruments for each domain (Dyspnea, Cough, Health Related Quality of Life, Imaging, Lung Physiology and Function, Mortality). Candidate measures that were not selected as well as measures that were not available for examination at the time of the consensus process will also be discussed. PMID:27019654

  12. Interstitial lung disease: state of the clinical art.

    PubMed

    Perez, R L; Staton, G W

    1991-10-01

    Interstitial lung diseases pose a great challenge to the clinician because of the indolent and variably active nature of these disorders and the limited number of therapeutic options. Adjunctive therapy includes supplemental oxygen in hypoxic patients, bronchodilators in patients with an obstructive lung component, and aggressive use of antibiotics in febrile patients on potent immunosuppressive therapy and suspected or confirmed infections. In younger patients who present late in their illness or deteriorate on therapy, lung transplantation is the only option. Recent advances in our knowledge of the cellular and molecular mechanisms operating in ILD and techniques which include gene amplification and cloning promise to yield more effective treatments for these diseases which currently produce a high incidence of morbidity and mortality. PMID:1744519

  13. Fibrocytes in the Pathogenesis of Chronic Fibrotic Lung Disease

    PubMed Central

    Loomis-King, Hillary; Moore, Bethany B.

    2016-01-01

    Fibrocytes were initially described in 1999 and since that time there has been a growing body of literature to suggest their importance in a number of chronic lung diseases. It is now well established that fibrocytes derive from the bone marrow and circulate within the peripheral blood. However, when injury occurs, fibrocytes can travel to the site of damage via chemokine-mediated recruitment. Recent studies suggest that fibrocyte numbers increase within the lung or circulation during numerous disease processes. Although fibrocytes readily differentiate into fibroblasts in vitro, whether they do so in vivo is still unknown. The variety of pro-fibrotic mediators that are secreted by fibrocytes makes it likely that they act via paracrine functions to influence the behavior of resident lung cells. This review summarizes recent insights regarding fibrocytes in asthma, scleroderma and IPF.

  14. 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

  15. Childhood wheezing, asthma, allergy, atopy, and lung function: different socioeconomic patterns for different phenotypes.

    PubMed

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

    2015-11-01

    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

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

    PubMed

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

    2016-08-01

    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

  17. 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

  18. Fitness to fly in patients with lung disease.

    PubMed

    Nicholson, Trevor T; Sznajder, Jacob I

    2014-12-01

    Patients with chronic lung disease may have mild hypoxemia at sea level. Some of these cases may go unrecognized, and even among those who are known to be hypoxemic, some do not use supplemental oxygen. During air travel in a hypobaric hypoxic environment, compensatory pulmonary mechanisms may be inadequate in patients with lung disease despite normal sea-level oxygen requirements. In addition, compensatory cardiovascular mechanisms may be less effective in some patients who are unable to increase cardiac output. Air travel also presents an increased risk of venous thromboembolism. Patients with cystic lung disease may also be at increased risk of pneumothorax. Although overall this risk appears to be relatively low, should a pneumothorax occur, it could present a significant challenge to the patient with chronic lung disease, particularly if hypoxemia is already present. As such, a thorough assessment of patients with chronic lung disease and cardiac disease who are contemplating air travel should be performed. The duration of the planned flight, the anticipated levels of activity, comorbid illnesses, and the presence of risk factors for venous thromboembolism are important considerations. Hypobaric hypoxic challenge testing reproduces an environment most similar to that encountered during actual air travel; however, it is not widely available. Assessment for hypoxia is otherwise best performed using a normobaric hypoxic challenge test. Patients in need of supplemental oxygen need to contact the airline and request this accommodation during flight. They should also be advised on arranging portable oxygen concentrators before air travel, and a discussion of the potential risks of travel should take place. PMID:25393882

  19. 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.

  20. DOES CHRONIC OZONE EXPOSURE LEAD TO LUNG DISEASE?

    EPA Science Inventory

    The potential role of ozone in the induction of chronic lung diseases remains unclear. sing an ambient profile adopted from aerometric data from the Southwest Air Basin, rats were exposed to O3 for up to 18 months before assessments of pulmonary structure, function and biochemist...

  1. Recent Advances and Future Needs in Interstitial Lung Diseases.

    PubMed

    Jones, Mark G; Richeldi, Luca

    2016-06-01

    Interstitial lung diseases (ILDs) are a diverse range of conditions affecting the lung interstitium. The prototypic ILD, idiopathic pulmonary fibrosis (IPF), is a chronic progressive fibrotic lung disease with a median survival of only 3 years from the time of diagnosis. Recently significant progress has been made in both our understanding of the pathogenesis and of the therapeutic targeting of IPF. This culminated in the worldwide approval of the first antifibrotic therapies nintedanib and pirfenidone. While an important first step, patients continue to progress and better therapies are urgently required. The aim of this article is to highlight some of the recent advances that have been made in our understanding of genetics, disease classification, clinical trial design, and novel antifibrotic therapy in IPF. It discusses future priorities if we are to continue to increase the length and quality of life of patients with IPF, and considers possible approaches to translate the progress made in IPF to other progressive fibrotic lung diseases where our understanding remains limited. PMID:27231869

  2. Mediterranean dietary pattern and chronic diseases.

    PubMed

    Panico, Salvatore; Mattiello, Amalia; Panico, Camilla; Chiodini, Paolo

    2014-01-01

    The study of the relationship between the Mediterranean way of eating and the occurrence of diseases typical of the economically developed countries has been considered the starting point of nutritional epidemiology. From the Seven Countries Study in the 1950s to the recent European EPIC collaboration, the evaluation of the components of diet-affecting chronic diseases such as cardiovascular disease and cancer has been crucially based on the analysis of foods and nutrients characterizing the Mediterranean dietary habits. This long research history has been marked by a consistency of data over time when either single nutrients/food groups or more complex dietary patterns have been analyzed: The Mediterranean way of eating is a protective tool from cardiovascular diseases and many cancers. Italy has been a natural point of observation, starting from cardiovascular disease in the mid-1950s and continuing with major cancers. In spite of unfavorable lifestyle changes in the Italian population mostly due to globalization of unhealthy habits (richer diet and lower levels of physical activity), those individuals still close to the Mediterranean style are significantly protected. The very recent Italian data derived from the observation of about 50,000 individuals, participating in the Italian cohorts of the EPIC study, confirm these findings and are consistent with results from other European populations and in some cases also from North American populations. Moreover, several dietary trials suggest that such a way of eating improves both the metabolic risk condition for chronic disease and the occurrence of those diseases. In conclusion, a way of eating inspired by a Mediterranean dietary pattern is not only based on evidence but is also a palatable style that has contributed to protection from the epidemic of chronic diseases. PMID:24114475

  3. Lung clearance index in the assessment of airways disease.

    PubMed

    Horsley, Alex

    2009-06-01

    In the last few years there has been a growing interest in lung clearance index (LCI), a measure of lung physiology derived from multiple breath washout tests. This resurgence of interest was initially driven by the recognition that such assessments were capable of detecting early airways disease in children, and are more sensitive and easier to perform in this population than conventional lung function tests [Aurora P, Kozlowska W, Stocks J. Gas mixing efficiency from birth to adulthood measured by multiple-breath washout. Respir Physiol Neurobiol, 2005;148(1-2):125-39]. With an appreciation of the importance of earlier identification of airways dysfunction, and prevention of irreversible structural airway changes, methods of following airways disease in these "silent years" are especially important. LCI has now been reported in studies involving all age groups, from infants to adults [Lum S, Gustafsson P, Ljungberg H, Hulskamp G, Bush A, Carr SB, et al. Early detection of cystic fibrosis lung disease: multiple-breath washout versus raised volume tests. Thorax, 2007;62(4):341-7; Horsley AR, Gustafsson PM, Macleod K, Saunders CJ, Greening AP, Porteous D, et al. Lung clearance index is a sensitive, repeatable and practical measure of airways disease in adults with cystic fibrosis. Thorax, 2008;63:135-40], and has a narrow range of normal over this wide age range, making it especially suitable for long-term follow-up studies. In cystic fibrosis (CF) particularly, there is a pressing need for sensitive and repeatable clinical endpoints for therapeutic interventions [Rosenfeld M. An overview of endpoints for cystic fibrosis clinical trials: one size does not fit all. Proc Am Thorac Soc, 2007;4(4):299-301], and LCI has been proposed as an outcome measure in future CF gene therapy studies [Davies JC, Cunningham S, Alton EW, Innes JA. Lung clearance index in CF: a sensitive marker of lung disease severity. Thorax, 2008;63(2):96-7]. This review will consider how LCI is

  4. Gene therapy for lung inflammatory diseases: not so far away?

    PubMed Central

    Sallenave, J. M.; Porteous, D. J.; Haslett, C.

    1997-01-01

    The lung is a readily accessible target organ for gene therapy. To date, therapeutic gene delivery has largely focused on introducing functional, corrective genes in lung diseases arising from single gene defects such as cystic fibrosis. More recently interest has centred on gene therapy as a potential therapeutic tool in modulating complex pathological processes such as pulmonary inflammation. Genetic modification of critical components of the inflammatory process may be beneficial-for example, overexpressing anti-elastase genes may circumvent elastase mediated lung damage in emphysema. With the development of improved viral and liposome vectors and the evolution of effective adjuvant immunosuppression to obviate host immune responses-- for example, using selective cytokines and blockers of T cell surface activation--the potential exists to target therapeutic doses of transgene to deficient or dysregulated cells. Furthermore, increased understanding of tissue-specific promoter regions and of mechanisms controlling regulation of gene expression offer the potential for close control of therapeutic gene expression within the lung. Continuing refinements in these technologies will provide new therapeutic strategies in inflammatory lung disease. 


 PMID:9337837

  5. Gene therapy for lung inflammatory diseases: not so far away?

    PubMed

    Sallenave, J M; Porteous, D J; Haslett, C

    1997-08-01

    The lung is a readily accessible target organ for gene therapy. To date, therapeutic gene delivery has largely focused on introducing functional, corrective genes in lung diseases arising from single gene defects such as cystic fibrosis. More recently interest has centred on gene therapy as a potential therapeutic tool in modulating complex pathological processes such as pulmonary inflammation. Genetic modification of critical components of the inflammatory process may be beneficial-for example, overexpressing anti-elastase genes may circumvent elastase mediated lung damage in emphysema. With the development of improved viral and liposome vectors and the evolution of effective adjuvant immunosuppression to obviate host immune responses--for example, using selective cytokines and blockers of T cell surface activation--the potential exists to target therapeutic doses of transgene to deficient or dysregulated cells. Furthermore, increased understanding of tissue-specific promoter regions and of mechanisms controlling regulation of gene expression offer the potential for close control of therapeutic gene expression within the lung. Continuing refinements in these technologies will provide new therapeutic strategies in inflammatory lung disease. PMID:9337837

  6. Current Status of Gene Therapy for Inherited Lung Diseases

    PubMed Central

    Driskell, Ryan R.; Engelhardt, John F.

    2007-01-01

    Gene therapy as a treatment modality for pulmonary disorders has attracted significant interest over the past decade. Since the initiation of the first clinical trials for cystic fibrosis lung disease using recombinant adenovirus in the early 1990s, the field has encountered numerous obstacles including vector inflammation, inefficient delivery, and vector production. Despite these obstacles, enthusiasm for lung gene therapy remains high. In part, this enthusiasm is fueled through the diligence of numerous researchers whose studies continue to reveal great potential of new gene transfer vectors that demonstrate increased tropism for airway epithelia. Several newly identified serotypes of adeno-associated virus have demonstrated substantial promise in animal models and will likely surface soon in clinical trials. Furthermore, an increased understanding of vector biology has also led to the development of new technologies to enhance the efficiency and selectivity of gene delivery to the lung. Although the promise of gene therapy to the lung has yet to be realized, the recent concentrated efforts in the field that focus on the basic virology of vector development will undoubtedly reap great rewards over the next decade in treating lung diseases. PMID:12524461

  7. Interstitial lung disease induced by alectinib (CH5424802/RO5424802).

    PubMed

    Ikeda, Satoshi; Yoshioka, Hiroshige; Arita, Machiko; Sakai, Takahiro; Sone, Naoyuki; Nishiyama, Akihiro; Niwa, Takashi; Hotta, Machiko; Tanaka, Tomohiro; Ishida, Tadashi

    2015-02-01

    A 75-year-old woman with anaplastic lymphoma kinase (ALK)-rearranged Stage IV lung adenocarcinoma was administered the selective anaplastic lymphoma kinase inhibitor, alectinib, as a third-line treatment in a Phase 1-2 study. On the 102nd day, chest computed tomography showed diffuse ground glass opacities. Laboratory data revealed high serum levels of KL-6, SP-D and lactate dehydrogenase without any clinical symptoms. There was no evidence of infection. Marked lymphocytosis was seen in bronchoalveolar lavage fluid analysis, and transbronchial lung biopsy showed mild thickening of alveolar septa and lymphocyte infiltration. Interstitial lung disease was judged to be related to alectinib based on improvements in imaging findings and serum biomarkers after discontinuation of alectinib. To our knowledge, this is the first reported case of alectinib-induced interstitial lung disease. Alectinib is a promising drug for ALK-rearranged non-small cell lung cancer. Clinical trials of this selective anaplastic lymphoma kinase inhibitor will facilitate the meticulous elucidation of its long-term safety profile. PMID:25398579

  8. 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

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

    PubMed Central

    2014-01-01

    Asthma and chronic obstructive pulmonary disease (COPD) are characterized by airway obstruction and airflow limitation 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 current

  10. [Clinical study on development of nontuberculous mycobacterial lung disease].

    PubMed

    Kurashima, Atsuyuki

    2004-12-01

    DEVELOPEMENT OF MAC LUNG DISEASE: An increase of nodular bronchiectatic type of MAC lung disease becomes a problem among respiratory physician today. The reason is still unknown, but it seems to be globally recognized that this type of MAC disease is developing particularly in middle-aged woman. Some papers mentioned the existence of such type of MAC lung disease already early in the 70s, in Japan. Yamamoto described that 17 cases of middle lobe type lung disease out of 154 non-photochoromogen cases, and 76.5% were female, in 1970. Shimoide also pointed such type of 39 cases out of 240 MAC lung disease and 84.6% were female, in 1980. Prince reported MAC lung disease seen in old and middle age female of 21 cases including lethality example of 4 cases without a precedent disease in 1989. After his report, the international consensus of this peculiar type of MAC lung disease seems to be spread. In 1989, we compared 72 cases of nodular bronchiectatic type of MAC lung disease and 56 cases of diffuse panbronchiolitis (DPB) that was a most typical chronic airway disease at that time in Japan. The average age of disease onset of DPB group was 37.0 +/- 16.3 years old and that of MAC group was 54.5 +/- 16.3 years old. The percentage of female was 32% in DPB group and 87.5% in MAC group. It was highly possible that two groups belong different parent population. We could grasp that nodular bronchiectatic type of MAC lung disease patients is a unique group. We observed the serial films of 21 cases of nodular bronchiectatic MAC lung disease, and divide the progression of the disease to sequential 7 steps as Fig. 1. Small nodules progress to cavities in mean about 10 years. However, why is MAC which is opportunistic pathogen with weak virulence, able to form a lesion at unimpaired lung parenchyma? Is there really normal site? Why dose it start from lingula? Why is MAC seen a lot in woman? While it is extremely pathognomonic clinical picture, and, is an extremely interesting

  11. 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%.

  12. Probiotics in the Management of Lung Diseases

    PubMed Central

    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. PMID:23737654

  13. Fatal obstructive lung disease after haploidentical sibling cord blood transplantation.

    PubMed

    Ohnuma, K; Toyoda, Y; Ishida, Y; Honda, K; Nagao, T; Ijiri, R; Tanaka, Y; Goto, K; Hiroki, K; Kigasawa, H; Nishihira, H

    1998-05-01

    We report the case of a patient with fatal obstructive lung disease after an HLA-haploidentical sibling cord blood transplant (CBT), with severe acute GVHD. A 2-year-old girl developed expiratory air trapping gradually with acute and chronic GVHD after CBT for the treatment of ALL. Anti-CMV and immunosuppressive therapy were ineffective, and the patient died of progressive respiratory acidosis. Necropsy of the lung revealed severe bronchiolitis obliterans with cytomegalic inclusion cells in the granulation tissues of the bronchiolitis. Thus, immunologic and GVHD problems can occur even in CBT. PMID:9613788

  14. Lung clearance index for monitoring early lung disease in alpha-1-antitrypsin deficiency.

    PubMed

    Fuchs, Susanne I; Schwerk, Nicolaus; Pittschieler, Klaus; Ahrens, Frank; Baden, Winfried; Bals, Robert; Fähndrich, Sebastian; Gleiber, Wolfgang; Griese, Matthias; Hülskamp, Georg; Köhnlein, Thomas; Reckling, Ludmilla; Rietschel, Ernst; Staab, Doris; Gappa, Monika

    2016-07-01

    Patients with alpha-1-antitrypsin deficiency (AATD) and a PI-ZZ genotype are at high risk to develop severe emphysema during adulthood. However, little is known about early stages of emphysema and disease manifestation in other PI-types. Spirometry is commonly used for monitoring although early manifestation of emphysema is suspected within the peripheral airways that are not accessible by forced expiratory manoeuvres. We hypothesized that the Lung Clearance Index (LCI) derived from multiple breath nitrogen-washout (N2-washout) is useful to bridge this diagnostic gap. Patients from age 4 years onward and different PI-types performed N2-washout and spirometry. Results were compared to controls. 193 patients (4-79 years, 75% PI-ZZ) and 33 controls (8-60 years) were included. Mean (SD) LCI in patients was 9.1 (3.1) and 6.3 (0.6) in controls (p ≤ 0.001). 47% of adult patients with other than PI-ZZ genotypes and 39% of all patients with normal spirometry had abnormal LCIs. The LCI measured by N2-washout discriminates between patients with AATD and controls, reflects AATD related lung disease in all stages and appears to identify early peripheral lung changes in younger age than spirometry. We conclude that a normal spirometry does not exclude presence of AATD related lung disease even in genotypes other than PI-ZZ. PMID:27296827

  15. Autophagy: a potential therapeutic target in lung diseases

    PubMed Central

    Nakahira, Kiichi

    2013-01-01

    Macroautophagy (hereafter referred to as autophagy) is an evolutionally conserved intracellular process to maintain cellular homeostasis by facilitating the turnover of protein aggregates, cellular debris, and damaged organelles. During autophagy, cytosolic constituents are engulfed into double-membrane-bound vesicles called “autophagosomes,” which are subsequently delivered to the lysosome for degradation. Accumulated evidence suggests that autophagy is critically involved not only in the basal physiological states but also in the pathogenesis of various human diseases. Interestingly, a diverse variety of clinically approved drugs modulate autophagy to varying extents, although they are not currently utilized for the therapeutic purpose of manipulating autophagy. In this review, we highlight the functional roles of autophagy in lung diseases with focus on the recent progress of the potential therapeutic use of autophagy-modifying drugs in clinical medicine. The purpose of this review is to discuss the merits, and the pitfalls, of modulating autophagy as a therapeutic strategy in lung diseases. PMID:23709618

  16. 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

  17. DEPOSITION PATTERNS OF AEROSOLIZED DRUGS WITHIN HUMAN LUNGS: EFFECTS OF VENTILATORY PARAMETERS

    EPA Science Inventory

    An analytical model is used to study the effects of ventilatory parameters on particle deposition patterns within the human lung. ased upon fluid dynamics considerations (Reynolds numbers), an original method of partitioning the lung is presented. he model is validated by compari...

  18. 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

  19. Pathogenesis of Interstitial Lung Disease in Children and Adults.

    PubMed

    Glasser, Stephan W; Hardie, William D; Hagood, James S

    2010-03-01

    Interstitial lung diseases (ILDs) occur across the lifespan, from birth to advanced age. However, the causes, clinical manifestations, histopathology, and management of ILD differ greatly among infants, older children, and adults. The historical approach of classifying childhood ILD (chILD) using adult classification schemes may therefore have done more harm than good. Nevertheless, identification of novel forms of chILD in the past decade, such as surfactant metabolism dysfunction disorders and neuroendocrine cell hyperplasia of infancy (NEHI), as well as genomic analysis of adult ILDs, has taught us that identical genotypes may result in distinct phenotypes at different ages and developmental stages, and that lung developmental pathways and cellular phenotypes are often recapitulated in adult ILDs. Thus comparison of the pathophysiology of ILD in children and adults in the context of lung development is useful in understanding the pathogenesis of these disorders, and may lead to novel therapeutic interventions for ILDs at all ages. PMID:22087431

  20. 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

  1. β2-agonist therapy in lung disease.

    PubMed

    Cazzola, Mario; Page, Clive P; Rogliani, Paola; Matera, M Gabriella

    2013-04-01

    β2-Agonists are effective bronchodilators due primarily to their ability to relax airway smooth muscle (ASM). They exert their effects via their binding to the active site of β2-adrenoceptors on ASM, which triggers a signaling cascade that results in a number of events, all of which contribute to relaxation of ASM. There are some differences between β2-agonists. Traditional inhaled short-acting β2-agonists albuterol, fenoterol, and terbutaline provide rapid as-needed symptom relief and short-term prophylactic protection against bronchoconstriction induced by exercise or other stimuli. The twice-daily β2-agonists formoterol and salmeterol represent important advances. Their effective bronchodilating properties and long-term improvement in lung function offer considerable clinical benefits to patients. More recently, a newer β2-agonist (indacaterol) with a longer pharmacodynamic half-life has been discovered, with the hopes of achieving once-daily dosing. In general, β2-agonists have an acceptable safety profile, although there is still controversy as to whether long-acting β2-agonists may increase the risk of asthma mortality. In any case, they can induce adverse effects, such as increased heart rate, palpitations, transient decrease in PaO2, and tremor. Desensitization of β2-adrenoceptors that occurs during the first few days of regular use of β2-agonist treatment may account for the commonly observed resolution of the majority of these adverse events after the first few doses. Nevertheless, it can also induce tolerance to bronchoprotective effects of β2-agonists and has the potential to reduce bronchodilator sensitivity to them. Some novel once-daily β2-agonists (olodaterol, vilanterol, abediterol) are under development, mainly in combination with an inhaled corticosteroid or a long-acting antimuscarinic agent. PMID:23348973

  2. 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

  3. Classification of Impulse Oscillometric Patterns of Lung Function in Asthmatic Children using Artificial Neural Networks.

    PubMed

    Barua, Miroslava; Nazeran, Homer; Nava, Patricia; Diong, Bill; Goldman, Michael

    2005-01-01

    Impulse Oscillometry (IOS) is an innovative patient-friendly pulmonary testing technique which measures the respiratory system impedance (Z) by using the spectral components of pressure to flow ratio which yields resistance and reactance values at different frequencies. The high dimensionality of IOS measurement data makes the analysis of this information difficult. Artificial Neural Networks (ANNs) are mathematical models composed of a large number of highly interconnected neurons that are able to learn and generalize from data. An ANN-based approach to the analysis of IOS data can potentially provide an efficient and automatic method to recognize and classify pulmonary diseases. This would help characterize major respiratory illnesses such as asthma based on IOS measurements. Asthma can be difficult to diagnose, because the symptoms are sometimes similar to other lung conditions. A data set composed of 361 impulse oscillometric patterns from asthmatic children was used in this study. The ANN was capable of distinguishing between relatively constricted and nonconstricted airway conditions in these patients. Using all of the 361 patterns during training as well as in the feed-forward stage, a classification accuracy of 95.01% was obtained for validation. When the ANN was presented with only 60% of the original 361 patterns in the data set during training and with the remaining 40% as unseen patterns, the generalization stage, a classification accuracy of 98.61% was achieved. PMID:17282180

  4. Mycobacterial Lung Disease Complicating HIV Infection.

    PubMed

    Haas, Michelle K; Daley, Charles L

    2016-04-01

    Mycobacterial infections have caused enormous morbidity and mortality in people living with human immunodeficiency virus (HIV) infection. Of these, the most devastating has been tuberculosis (TB), the leading cause of death among HIV-positive persons globally. TB has killed more people living with HIV than any other infection. Diagnosis of latent TB infection (LTBI) is critical as treatment can prevent emergence of TB disease. Bacteriologic confirmation of TB disease should be sought whenever possible as well as drug susceptibility testing. When detected early, drug susceptible TB is curable. Similar to TB, nontuberculous mycobacteria (NTM) can also produce pulmonary and extrapulmonary infections including disseminated disease that can be fatal. Diagnosis through accurate identification of the pathogenic organism will greatly inform treatment. Depending on the NTM identified, treatment may not be curable. Ultimately, preventive strategies such as initiation of antiretroviral drugs and treatment of LTBI are interventions expected to have significant impacts on control of TB and NTM in the setting of HIV. This chapter will review the impact of pulmonary mycobacterial infections on HIV-positive individuals. PMID:26974300

  5. Organoids as a model system for studying human lung development and disease.

    PubMed

    Nadkarni, Rohan R; Abed, Soumeya; Draper, Jonathan S

    2016-05-01

    The lung is a complex organ comprising multiple cell types that perform a variety of vital processes, including immune defense and gas exchange. Diseases of the lung, such as chronic obstructive pulmonary disease, asthma and lung cancer, together represent one of the largest causes of patient suffering and mortality. Logistical barriers that hamper access to embryonic, normal adult or diseased lung tissue currently hinder the study of lung disease. In vitro lung modeling represents an attractive and accessible avenue for investigating lung development, function and disease pathology, but accurately modeling the lung in vitro requires a system that recapitulates the structural features of the native lung. Organoids are stem cell-derived three-dimensional structures that are supported by an extracellular matrix and contain multiple cell types whose spatial arrangement and interactions mimic those of the native organ. Recently, organoids representative of the respiratory system have been generated from adult lung stem cells and human pluripotent stem cells. Ongoing studies are showing that organoids may be used to model human lung development, and can serve as a platform for interrogating the function of lung-related genes and signalling pathways. In a therapeutic context, organoids may be used for modeling lung diseases, and as a platform for screening for drugs that alleviate respiratory disease. Here, we summarize the organoid-forming capacity of respiratory cells, current lung organoid technologies and their potential use in future therapeutic applications. PMID:26721435

  6. 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

  7. 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

  8. Epigenetics and Chromatin Remodeling Play a Role in Lung Disease

    PubMed Central

    Mortaz, Esmaeil; Masjedi, Mohammad Reza; Barnes, Peter J

    2011-01-01

    Epigenetics is defined as heritable changes that affect gene expression without altering the DNA sequence. Epigenetic regulation of gene expression is facilitated through different mechanisms such as DNA methylation, histone modifications and RNA-associated silencing by small non-coding RNAs. All these mechanisms are crucial for normal development, differentiation and tissue-specific gene expression. These three systems interact and stabilize one another and can initiate and sustain epigenetic silencing, thus determining heritable changes in gene expression. Histone acetylation regulates diverse cellular functions including inflammatory gene expression, DNA repair and cell proliferation. Transcriptional coactivators possess intrinsic histone acetyltransferase activity and this activity drives inflammatory gene expression. Eleven classical histone deacetylases (HDACs) act to regulate the expression of distinct subsets of inflammatory/immune genes. Thus, loss of HDAC activity or the presence of HDAC inhibitors can further enhance inflammatory gene expression by producing a gene-specific change in HAT activity. For example, HDAC2 expression and activity are reduced in lung macrophages, biopsy specimens, and blood cells from patients with severe asthma and smoking asthmatics, as well as in patients with chronic obstructive pulmonary disease (COPD). This may account, at least in part, for the enhanced inflammation and reduced steroid responsiveness seen in these patients. Other proteins, particularly transcription factors, are also acetylated and are targets for deacetylation by HDACs and sirtuins, a related family of 7 predominantly protein deacetylases. Thus the acetylation/deacetylation status of NF-κB and the glucocorticoid receptor can also affect the overall expression pattern of inflammatory genes and regulate the inflammatory response. Understanding and targeting specific enzymes involved in this process might lead to new therapeutic agents, particularly in

  9. 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

  10. 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. PMID:23992090

  11. ABCA3 lung disease in an ex 27 week preterm infant responsive to systemic glucocorticosteroids.

    PubMed

    Tan, Jason Kg; Murray, Conor; Schultz, Andre

    2016-01-01

    We present a case of an infant born at almost 28 weeks gestation, found to be homozygous for a missense mutation of ABCA3, with diffuse lung disease that has continued throughout infancy. The patient's clinical course and chest imaging was highly suggestive of diffuse lung disease of infancy, and not of chronic lung disease of prematurity. The lung disease proved to be highly responsive to systemic corticosteroids. This is a case of ABCA3 lung disease that demonstrated improvement after systemic glucocorticosteroid administration. PMID:26222203

  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 surfactant homeostasis associated genetic abnormalities and lung diseases].

    PubMed

    Jiang, Xiaojing; Sun, Xiuzhu; Du, Weihua; Hao, Haisheng; Zhao, Xueming; Wang, Dong; Zhu, Huabin; Liu, Yan

    2016-08-10

    Pulmonary surfactant (PS) is synthesized and secreted by alveolar epithelial type II (AEII) cells, which is a complex compound formed by proteins and lipids. Surfactant participates in a range of physiological processes such as reducing the surface tension, keeping the balance of alveolar fluid, maintaining normal alveolar morphology and conducting host defense. Genetic disorders of the surfactant homeostasis genes may result in lack of surfactant or cytotoxicity, and lead to multiple lung diseases in neonates, children and adults, including neonatal respiratory distress syndrome, interstitial pneumonia, pulmonary alveolar proteinosis, and pulmonary fibrosis. This paper has provided a review for the functions and processes of pulmonary surfactant metabolism, as well as the connection between disorders of surfactant homeostasis genes and lung diseases. PMID:27455022

  14. 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. PMID:27104378

  15. Pulmonary rehabilitation improves sleep quality in chronic lung disease.

    PubMed

    Soler, Xavier; Diaz-Piedra, Carolina; Ries, Andrew L

    2013-04-01

    Sleep-related disorders are common in patients with chronic obstructive pulmonary disease (COPD) and, possibily, other lung disorders. Exercise has been shown to improve sleep disturbances. In patients with COPD, pulmonary rehabilitation (PR) produces important health benefits with improvement in symptoms, exercise tolerance, and quality of life. However, the effect of PR on sleep quality remains unknown. The aim of this observational study was to evaluate sleep quality in patients with chronic lung disease and the role of PR as a non-pharmacologic treatment to improve sleep. Sixty-four patients with chronic lung disease enrolled in an 8-week comprehensive PR program, and completed the study (48% male; obstructive [72%], restrictive [20%], mixed [8%]; 44% on supplemental oxygen). Baseline spirometry [mean (SD)]: FEV1% pred = 48.9 (17.4), FVC% pred = 72.5 (18.1), and FEV1/FVC% = 53.1 (18.9). Exercise tolerance and questionnaires related to symptoms, health-related quality of life (HRQL), and sleep quality using the Pittsburgh Sleep Quality Index (PSQI) were obtained before and after PR. 58% reported poor sleep quality (PSQI > 5) at baseline. Sleep quality improved by 19% (p = 0.017) after PR, along with significant improvements in dyspnea, exercise tolerance, self-efficacy, and HRQL. Sleep quality in patients with chronic lung disease was poor. In addition to expected improvements in symptoms, exercise tolerance, and HRQL after PR, the subgroup of patients with COPD had a significant improvement in sleep quality. These findings suggest that PR may be an effective, non-pharmacologic treatment option for sleep problems in patients with COPD. PMID:23514215

  16. State-of-the-Art Imaging of the Lung for Connective Tissue Disease (CTD).

    PubMed

    Ohno, Yoshiharu; Koyama, Hisanobu; Yoshikawa, Takeshi; Seki, Shinichiro

    2015-12-01

    Involvement of the respiratory system is common in connective tissue diseases (CTDs), and the resultant lung injury can affect every part of the lung: the pleura, alveoli, interstitium, vasculature, lymphatic tissue, and large and/or small airways. Most of the parenchymal manifestations of CTD are similar to those found in interstitial lung diseases (ILDs), especially idiopathic interstitial pneumonias, and can be classified using the same system. Although there is some overlap, each CTD is associated with a characteristic pattern of pulmonary involvement. For this reason, thin-section CT as well as pulmonary function tests and serum markers are utilized for diagnosis, disease severity assessment, and therapeutic efficacy evaluation of ILD associated with CTD. In addition, newly developed pulmonary magnetic resonance imaging (MRI) procedures have been recommended as useful alternative imaging options for patients with CTD. This review article will (1) address radiological findings for chest radiography and conventional or thin-section CT currently used for six major types of CTD, rheumatoid arthritis, scleroderma (progressive systemic sclerosis), polymyositis/dermatomyositis, systemic lupus erythematosus, Sjögren syndrome and mixed connective tissue disease; (2) briefly deal with radiation dose reduction for thin-section CT examination; and (3) discuss clinically applicable or state-of-the-art MR imaging for CTD patients. PMID:26483318

  17. 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

  18. Pulmonary Hypertension and Right Heart Dysfunction in Chronic Lung Disease

    PubMed Central

    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. PMID:25165714

  19. Large ABCA3 and SFTPC Deletions Resulting in Lung Disease

    PubMed Central

    Henderson, Lindsay B.; Melton, Kristin; Wert, Susan; Couriel, Jonathan; Bush, Andrew; Ashworth, Michael

    2013-01-01

    Rationale: Mutations in genes encoding proteins important in the function and metabolism of pulmonary surfactant are recognized causes of lung disease. Clinical genetic testing is available for these disorders, but children with phenotypes consistent with surfactant dysfunction and no identifiable mutations in the known causative genes have been reported. Objectives: To identify the mechanism(s) for lung disease in two children with the phenotype of surfactant dysfunction who had negative testing in clinical laboratories for gene mutations causing surfactant dysfunction. Methods: Amplicons spanning multiple exons of candidate genes were generated by polymerase chain reaction and sequenced. Measurements and Main Results: A 4,335-base deletion that included all of exon 12 of the gene encoding member A3 of the adenosine triphosphate–binding cassette transporter was identified in a full-term infant with respiratory failure. A 333-base deletion involving part of exon 4 and the adjacent intron of the gene encoding surfactant protein C was identified in a child with interstitial lung disease. Conclusions: Large deletions are a cause of surfactant dysfunction disorders and may need to be sought for specifically in children whose phenotypes suggest these syndromes but in whom clinical genetic testing is unrevealing. PMID:24024739

  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. 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

  2. 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

  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. PMID:27200087

  4. Mesenchymal stem cell therapy and lung diseases.

    PubMed

    Akram, Khondoker M; Samad, Sohel; Spiteri, Monica; Forsyth, Nicholas R

    2013-01-01

    Mesenchymal stem cells (MSCs), a distinct population of adult stem cells, have amassed significant interest from both medical and scientific communities. An inherent multipotent differentiation potential offers a cell therapy option for various diseases, including those of the musculoskeletal, neuronal, cardiovascular and pulmonary systems. MSCs also secrete an array of paracrine factors implicated in the mitigation of pathological conditions through anti-inflammatory, anti-apoptotic and immunomodulatory mechanisms. The safety and efficacy of MSCs in human application have been confirmed through small- and large-scale clinical trials. However, achieving the optimal clinical benefit from MSC-mediated regenerative therapy approaches is entirely dependent upon adequate understanding of their healing/regeneration mechanisms and selection of appropriate clinical conditions. MSC-mediated acute alveolar injury repair. A cartoon depiction of an injured alveolus with associated inflammation and AEC apoptosis. Proposed routes of MSC delivery into injured alveoli could be by either intratracheal or intravenous routes, for instance. Following delivery a proposed mechanism of MSC action is to inhibit/reduce alveolar inflammation by abrogation of IL-1_-depenedent Tlymphocyte proliferation and suppression of TNF-_ secretion via macrophage activation following on from stimulation by MSC-secreted IL-1 receptor antagonist (IL-1RN). The inflammatory environment also stimulates MSC to secrete prostaglandin-E2 (PGE2) which can stimulate activated macrophages to secrete the anti-inflammatory cytokine IL-10. Inhibition of AEC apoptosis following injury can also be promoted via MSC stimulated up-regulation of the anti-apoptotic Bcl-2 gene. MSC-secreted KGF can stimulate AECII proliferation and migration propagating alveolar epithelial restitution. Alveolar structural engraftment of MSC is a rare event. PMID:22772131

  5. The intersection of obstructive lung disease and sleep apnea.

    PubMed

    Khatri, Sumita B; Ioachimescu, Octavian C

    2016-02-01

    Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) have synergistic detrimental effects. Their comorbid association leads to compromised gas exchange (hypoxia and hypercapnia) and higher rates of morbidity and death. As our understanding of the pathophysiologic processes of sleep evolves, the relationship between OSA and obstructive lung diseases such as COPD ("overlap syndrome") or asthma ("alternative overlap syndrome") has become more apparent. The pathophysiology of the combined conditions and optimal management are still being defined, but the effect on quality of life and morbidity underscore the importance of proper diagnosis and appropriately tailored management in these patients. PMID:26871389

  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. PMID:27272655

  7. The heterogeneity of lung macrophages in the susceptibility to disease.

    PubMed

    Morales-Nebreda, Luisa; Misharin, Alexander V; Perlman, Harris; Budinger, G R Scott

    2015-09-01

    Alveolar macrophages are specialised resident phagocytes in the alveolus, constituting the first line of immune cellular defence in the lung. As the lung microenvironment is challenged and remodelled by inhaled pathogens and air particles, so is the alveolar macrophage pool altered by signals that maintain and/or replace its composition. The signals that induce the recruitment of circulating monocytes to the injured lung, as well as their distinct gene expression profile and susceptibility to epigenetic reprogramming by the local environment remain unclear. In this review, we summarise the unique characteristics of the alveolar macrophage pool ontogeny, phenotypic heterogeneity and plasticity during homeostasis, tissue injury and normal ageing. We also discuss new evidence arising from recent studies where investigators described how the epigenetic landscape drives the specific gene expression profile of alveolar macrophages. Altogether, new analysis of macrophages by means of "omic" technologies will allow us to identify key pathways by which these cells contribute to the development and resolution of lung disease in both mice and humans. PMID:26324812

  8. Somatic growth and lung function in sickle cell disease.

    PubMed

    Catanzaro, Tina; Koumbourlis, Anastassios C

    2014-03-01

    Somatic growth is a key indicator of overall health and well-being with important prognostic implications in the management of chronic disease. Worldwide studies of growth in children and adults with SCD have predominantly shown delayed growth (especially in terms of body weight) that is gradual and progressive in nature. However, more recent studies have shown that a substantial number of patients with SCD have normal weight gain whereas some are even obese. Height in patients with SCD is not universally affected even among those with suboptimal weight gain, whereas some achieve the same or greater height than healthy controls. The relationship between somatic growth and lung function in SCD is not yet clearly defined. As a group, patients with SCD tend to have lower lung volumes compared with healthy controls. These findings are similar across the age spectrum and across ethnic/racial lines regardless of the differences in body weight. Several mechanisms and risk factors have been proposed to explain these findings. These include malnutrition, racial differences and socioeconomic status. In addition, there are structural changes of the thorax (specifically the anterio-posterior chest diameter and anterio-posterior to lateral chest ratio) specific to sickle cell disease, that potentially interfere with normal lung growth. Although, caloric and protein intake have been shown to improve both height and weight, the composition of an optimal diet remains unclear. The following article reviews the current knowledge and controversies regarding somatic growth and its relationship with lung function in sickle cell disease (SCD) as well as the role of specific deficiencies of certain micronutrients. PMID:24268619

  9. Image-based diagnostic aid for interstitial lung disease with secondary data integration

    NASA Astrophysics Data System (ADS)

    Depeursinge, Adrien; Müller, Henning; Hidki, Asmâa; Poletti, Pierre-Alexandre; Platon, Alexandra; Geissbuhler, Antoine

    2007-03-01

    Interstitial lung diseases (ILDs) are a relatively heterogeneous group of around 150 illnesses with often very unspecific symptoms. The most complete imaging method for the characterisation of ILDs is the high-resolution computed tomography (HRCT) of the chest but a correct interpretation of these images is difficult even for specialists as many diseases are rare and thus little experience exists. Moreover, interpreting HRCT images requires knowledge of the context defined by clinical data of the studied case. A computerised diagnostic aid tool based on HRCT images with associated medical data to retrieve similar cases of ILDs from a dedicated database can bring quick and precious information for example for emergency radiologists. The experience from a pilot project highlighted the need for detailed database containing high-quality annotations in addition to clinical data. The state of the art is studied to identify requirements for image-based diagnostic aid for interstitial lung disease with secondary data integration. The data acquisition steps are detailed. The selection of the most relevant clinical parameters is done in collaboration with lung specialists from current literature, along with knowledge bases of computer-based diagnostic decision support systems. In order to perform high-quality annotations of the interstitial lung tissue in the HRCT images an annotation software and its own file format is implemented for DICOM images. A multimedia database is implemented to store ILD cases with clinical data and annotated image series. Cases from the University & University Hospitals of Geneva (HUG) are retrospectively and prospectively collected to populate the database. Currently, 59 cases with certified diagnosis and their clinical parameters are stored in the database as well as 254 image series of which 26 have their regions of interest annotated. The available data was used to test primary visual features for the classification of lung tissue patterns

  10. 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

  11. 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. PMID:25945507

  12. 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.

  13. 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

  14. Nanomedicine for the management of lung and blood diseases.

    PubMed

    Buxton, Denis B

    2009-04-01

    Nanotechnology provides a broad range of opportunities to develop new solutions for clinical problems. For the pulmonary field, nanotechnology promises better delivery of drugs and nucleic acid-based therapeutics to disease sites. Administration of therapeutics via inhalation provides the opportunity for direct delivery to the lung epithelium, the lining of the respiratory tract. By appropriate selection of particle size, deep lung delivery can be obtained with control of phagocytic uptake, the removal of particles by resident macrophages. Nanotechnology can also help in pulmonary therapies administered by intravenous and oral routes through targeting specific cell types and controlling bioavailability and release kinetics. In the hematology field, nanotechnology can counter multiple drug resistance in leukemia by blocking drug efflux from cancer cells, and provide effective delivery of siRNA into lymphocytes to block apoptosis in sepsis. Controlling the surface properties of materials on devices such as valves and stents promises improved biocompatibility by inhibition of thrombosis, the formation of blood clots, and regulating cell adhesion and activation. Nanoparticle-based thrombolytic agents have the potential to improve the effectiveness of clot removal. Treatment of both lung and blood diseases is also likely to benefit from nano-scaffold-based methods for controlling the differentiation and proliferation of stem and progenitor cells. PMID:19331540

  15. 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. PMID:27279757

  16. 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

  17. 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

  18. 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. PMID:24443711

  19. The Lung Tissue Microbiome in Chronic Obstructive Pulmonary Disease

    PubMed Central

    Sze, Marc A.; Dimitriu, Pedro A.; Hayashi, Shizu; Elliott, W. Mark; McDonough, John E.; Gosselink, John V.; Cooper, Joel; Sin, Don D.; Mohn, William W.

    2012-01-01

    Rationale: Based on surface brushings and bronchoalveolar lavage fluid, Hilty and coworkers demonstrated microbiomes in the human lung characteristic of asthma and chronic obstructive pulmonary disease (COPD), which have now been confirmed by others. Objectives: To extend these findings to human lung tissue samples. Methods: DNA from lung tissue samples was obtained from nonsmokers (n = 8); smokers without COPD (n = 8); patients with very severe COPD (Global Initiative for COPD [GOLD] 4) (n = 8); and patients with cystic fibrosis (CF) (n = 8). The latter served as a positive control, with sterile water as a negative control. All bacterial community analyses were based on polymerase chain reaction amplifying 16S rRNA gene fragments. Total bacterial populations were measured by quantitative polymerase chain reaction and bacterial community composition was assessed by terminal restriction fragment length polymorphism analysis and pyrotag sequencing. Measurement and Main Results: Total bacterial populations within lung tissue were small (20–1,252 bacterial cells per 1,000 human cells) but greater in all four sample groups versus the negative control group (P < 0.001). Terminal restriction fragment length polymorphism analysis and sequencing distinguished three distinct bacterial community compositions: one common to the nonsmoker and smoker groups, a second to the GOLD 4 group, and the third to the CF-positive control group. Pyrotag sequencing identified greater than 1,400 unique bacterial sequences and showed an increase in the Firmicutes phylum in GOLD 4 patients versus all other groups (P < 0.003) attributable to an increase in the Lactobacillus genus (P < 0.0007). Conclusions: There is a detectable bacterial community within human lung tissue that changes in patients with very severe COPD. PMID:22427533

  20. 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

  1. 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. PMID:25433077

  2. [Aluminum lung as an occupational disease. Case reports].

    PubMed

    Avolio, G; Galietti, F; Iorio, M; Oliaro, A

    1989-04-01

    The cases are examined of 13 males, mean age 53, granted disability pensions by the Turin I.N.A.I.L. in 1975-86 as suffering from lung disease caused by the inhalation of dust and exhalation of aluminium. The patients had worked in bauxite smelting for Al2O3 production and the preparation of synthetic abrasives (8 cases), in milling using synthetic abrasives (1 case) in the cold grinding of aluminium for paint production (3 cases) and in the electrolytic processing of aluminium (1 case). In line with the latest reports in the literature the present series confirms the possibility that interstitial fibrosis can be caused by exposure to aluminium in industries other than bauxite processing. The relatively benign character of modern aluminium lung is also confirmed. PMID:2657501

  3. Successful alectinib treatment after crizotinib-induced interstitial lung disease.

    PubMed

    Fujiuchi, Satoru; Fujita, Yuka; Sasaki, Takaaki; Ohsaki, Yoshinobu

    2016-05-01

    A 70-year-old woman with lung adenocarcinoma, harbouring anaplastic lymphoma kinase gene rearrangement, was treated with crizotinib as third-line chemotherapy. After 2 months, crizotinib was discontinued because of the development of crizotinib-induced interstitial lung disease (ILD). Steroid treatment was then introduced and tapered off. Following complete resolution of the interstitial shadow, cytotoxic chemotherapy was initiated, and continued for over 2 years, until new intrapulmonary lesions developed. Although there was a risk of drug-induced interstitial pneumonia, alectinib was initiated as the fifth-line therapy, without steroid supplementation, as there was no alternative treatment. No recurrence of ILD was noted at 10 months. To our knowledge, this is the first report of successful alectinib treatment after the development of crizotinib-induced ILD without the use of prednisolone. PMID:27516885

  4. Successful alectinib treatment after crizotinib‐induced interstitial lung disease

    PubMed Central

    Fujita, Yuka; Sasaki, Takaaki; Ohsaki, Yoshinobu

    2016-01-01

    Abstract A 70‐year‐old woman with lung adenocarcinoma, harbouring anaplastic lymphoma kinase gene rearrangement, was treated with crizotinib as third‐line chemotherapy. After 2 months, crizotinib was discontinued because of the development of crizotinib‐induced interstitial lung disease (ILD). Steroid treatment was then introduced and tapered off. Following complete resolution of the interstitial shadow, cytotoxic chemotherapy was initiated, and continued for over 2 years, until new intrapulmonary lesions developed. Although there was a risk of drug‐induced interstitial pneumonia, alectinib was initiated as the fifth‐line therapy, without steroid supplementation, as there was no alternative treatment. No recurrence of ILD was noted at 10 months. To our knowledge, this is the first report of successful alectinib treatment after the development of crizotinib‐induced ILD without the use of prednisolone. PMID:27516885

  5. Aerosol-Based Cell Therapy for Treatment of Lung Diseases.

    PubMed

    Kardia, Egi; Halim, Nur Shuhaidatul Sarmiza Abdul; Yahaya, Badrul Hisham

    2016-01-01

    Aerosol-based cell delivery technique via intratracheal is an effective route for delivering transplant cells directly into the lungs. An aerosol device known as the MicroSprayer(®) Aerosolizer is invented to transform liquid into an aerosol form, which then can be applied via intratracheal administration for drug delivery. The device produces a uniform and concentrated distribution of aerosolized liquid. Using the capability of MicroSprayer(®) Aerosolizer to transform liquid into aerosol form, our group has designed a novel method of cell delivery using an aerosol-based technique. We have successfully delivered skin-derived fibroblast cells and airway epithelial cells into the airway of a rabbit with minimum risk of cell loss and have uniformly distributed the cells into the airway. This chapter illustrates the application of aerosol device to deliver any type of cells for future treatment of lung diseases. PMID:27062596

  6. A canine model of beryllium-induced granulomatous lung disease

    SciTech Connect

    Haley, P.J.; Finch, G.L.; Mewhinney, J.A.; Harmsen, A.G.; Hahn, F.F.; Hoover, M.D.; Muggenburg, B.A.; Bice, D.E. )

    1989-08-01

    Groups of beagle dogs were exposed by inhalation to attain either low or high initial lung burdens (ILB) of BeO calcined at 500 degrees or 1000 degrees C. Dogs were killed at 8, 32, 64, 180, and 365 days after exposure for evaluation of beryllium tissue burdens and histopathologic examination. Histologic lesions were characterized by perivascular and peribronchiolar infiltrates of lymphocytes and macrophages 8 days after exposure. These lesions progressed to distinct microgranulomas accompanied by patchy granulomatous pneumonia. Lesions were more severe in dogs exposed to 500 degrees C BeO. Additional dogs were sampled by bronchoalveolar lavage at 3, 6, 7, 11, 15, 18, and 22 months after exposure for characterization of lung cytology and lung immune responses. Lymphocyte percentages and numbers were increased in lavage samples 3 months after exposure in dogs with both the high and low ILB of 500 degrees C. Values for both parameters decreased rapidly thereafter. Dogs with either low or high ILB of 1000 degrees C-treated BeO displayed negligible to low and variable changes in both lymphocyte percentages and numbers. In vitro lymphocyte stimulation by beryllium was increased 180 and 210 days after exposure in dogs with the high ILB 500 degrees C BeO only. A marked degree of individual variation in both histologic lesions and lymphocyte responses among dogs was noted. Less soluble 1000 degrees C-treated BeO was retained in the lung longer than the more soluble 500 degrees C-treated material that was cleared almost entirely by 1 year after exposure. Because these changes are similar to those reported in humans with chronic beryllium disease, these data suggest that the beagle represents a good model to study histologic and immunologic aspects of this disease syndrome.

  7. 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. PMID:26186685

  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. [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. PMID:8059397

  10. 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

  11. Metabolomics and Its Application to Acute Lung Diseases.

    PubMed

    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-making and

  12. 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

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

    PubMed

    Vallyathan, V; Shi, X

    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. PMID:9114285

  14. 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

  15. Surfactant Proteins in Smoking-Related Lung Disease.

    PubMed

    Papaioannou, Andriana I; Papiris, Spyridon; Papadaki, Georgia; Manali, Effrosyni D; Roussou, Aneza; Spathis, Aris; Karakitsos, Petros; Kostikas, Konstantinos

    2016-01-01

    Pulmonary surfactant is a highly surface-active mixture of proteins and lipids that is synthesized and secreted in the alveoli by type II epithelial cells and is found in the fluid lining the alveolar surface. The protein part of surfactant constitutes two hydrophilic proteins (SP-A and SP-D) that regulate surfactant metabolism and have immunologic functions, and two hydrophobic proteins (SP-B and SP-C), which play a direct role in the organization of the surfactant structure in the interphase and in the stabilization of the lipid layers during the respiratory cycle. Several studies have shown that cigarette smoke seems to affect, in several ways, both surfactant homeostasis and function. The alterations in surfactants' biophysical properties caused by cigarette smoking, contribute to the development of several smoking related lung diseases. In this review we provide information on biochemical and physiological aspects of the pulmonary surfactant and on its possible association with the development of two major chronic diseases of the lung known to be related to smoking, i.e. chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Additional information on the possible role of surfactant protein alterations and/or dysfunction in the combination of these two conditions, recently described as combined pulmonary fibrosis and emphysema (CPFE) are also provided. PMID:26420367

  16. 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

  17. Lung Transplant

    MedlinePlus

    ... the NHLBI on Twitter. What Is a Lung Transplant? A lung transplant is surgery to remove a person's diseased lung ... a healthy lung from a deceased donor. Lung transplants are used for people who are likely to ...

  18. A Histomorphological Pattern Analysis of Pulmonary Tuberculosis in Lung Autopsy and Surgically Resected Specimens

    PubMed Central

    Lobo, Flora D.; Adiga, Deepa Sowkur Anandarama

    2016-01-01

    Background. Tuberculosis (TB) is a major cause of morbidity and mortality globally. Many cases are diagnosed on autopsy and a subset of patients may require surgical intervention either due to the complication or sequelae of TB. Materials and Methods. 40 cases of resected lung specimens following surgery or autopsy in which a diagnosis of pulmonary tuberculosis was made were included. Histopathological pattern analysis of pulmonary tuberculosis along with associated nonneoplastic changes and identification of Mycobacterium tuberculosis bacilli was done. Results. The mean age of diagnosis was 41 years with male predominance (92.5%). Tuberculosis was suspected in only 12.1% of cases before death. Seven cases were operated upon due to associated complications or suspicion of malignancy. Tubercular consolidation was the most frequent pattern followed by miliary tuberculosis. The presence of necrotizing granulomas was seen in 33 cases (82.5%). Acid fast bacilli were seen in 57.5% cases on Ziehl-Neelsen stain. Conclusion. Histopathology remains one of the most important methods for diagnosing tuberculosis, especially in TB prevalent areas. It should be considered in the differential diagnosis of all respiratory diseases because of its varied clinical presentations and manifestations. PMID:27088035

  19. 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

  20. Respiratory and lower limb muscle function in interstitial lung disease.

    PubMed

    Panagiotou, Marios; Polychronopoulos, Vlasis; Strange, Charlie

    2016-05-01

    Growing evidence suggests that respiratory and limb muscle function may be impaired in patients with interstitial lung disease (ILD). Importantly, muscle dysfunction could promote dyspnoea, fatigue and functional limitation all of which are cardinal features of ILD. This article examines the risk factors for skeletal muscle dysfunction in ILD, reviews the current evidence on overall respiratory and limb muscle function and focuses on the occurrence and implications of skeletal muscle dysfunction in ILD. Research limitations and pathways to address the current knowledge gaps are highlighted. PMID:26768011

  1. Targeting mitochondrial dysfunction in lung diseases: emphasis on mitophagy

    PubMed Central

    Sureshbabu, Angara; Bhandari, Vineet

    2013-01-01

    During mild stressful conditions, cells activate a multitude of mechanisms in an attempt to repair or re-establish homeostasis. One such mechanism is autophagic degradation of mitochondria or mitophagy to dispose damaged mitochondria. However, if stress persists beyond recovery then dysfunctional mitochondria can ignite cell death. This review article summarizes recent studies highlighting the molecular pathways that facilitate mitochondria to alter its morphological dynamics, coordinate stress responses, initiate mitophagy and activate cell death in relevance to pulmonary pathologies. Thorough understanding of how these signaling mechanisms get disrupted may aid in designing new mitochondria-based therapies to combat lung diseases. PMID:24421769

  2. 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

  3. EMT and Interstitial Lung Disease: A Mysterious Relationship

    PubMed Central

    Kage, Hidenori; Borok, Zea

    2014-01-01

    Purpose of review Pathogenesis of interstitial lung diseases (ILD) has largely been investigated in the context of the most frequent ILD, idiopathic pulmonary fibrosis (IPF). We review studies of epithelial to mesenchymal transition (EMT) and discuss its potential contribution to collagen-producing (myo)fibroblasts in IPF. Recent findings Endoplasmic reticulum (ER) stress leading to epithelial apoptosis has been reported as a potential etiologic factor in fibrosis. Recent studies further suggest EMT as a link between ER stress and fibrosis. Combinatorial interactions among Smad3, β-catenin and other transcriptional co-activators at the α-smooth muscle actin (α-SMA) promoter provide direct evidence for crosstalk between transforming growth factor-β (TGFβ) and β-catenin pathways during EMT. Lineage tracing yielded conflicting results, with two recent studies supporting and one opposing a role for EMT in lung fibrosis. Summary Advances have been made in elucidating causes and mechanisms of EMT, potentially leading to new treatment options, although contributions of EMT to lung fibrosis in vivo remain controversial. In addition to EMT providing a direct source of (myo)fibroblasts, expression of mesenchymal markers may reflect epithelial injury, in which case inhibition of EMT might be deleterious. EMT-derived cells may also contribute to aberrant epithelial-mesenchymal crosstalk that promotes fibrogenesis. PMID:22854509

  4. 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. PMID:23959715

  5. 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. PMID:18982686

  6. 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

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

    PubMed

    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

  8. The First Successful Heart-Lung Transplant in a Korean Child with Humidifier Disinfectant-Associated Interstitial Lung Disease

    PubMed Central

    Kim, Yong-Hee; Hong, Sang-Bum

    2016-01-01

    From 2006 to 2011, an outbreak of a particular type of childhood interstitial lung disease occurred in Korea. The condition was intractable and progressed to severe respiratory failure, with a high mortality rate. Moreover, in several familial cases, the disease affected young women and children simultaneously. Epidemiologic, animal, and post-interventional studies identified the cause as inhalation of humidifier disinfectants. Here, we report a 4-year-old girl who suffered from severe progressive respiratory failure. She could survive by 100 days of extracorporeal membrane oxygenation support and finally, underwent heart-lung transplantation. This is the first successful pediatric heart-lung transplantation carried out in Korea. PMID:27134508

  9. The First Successful Heart-Lung Transplant in a Korean Child with Humidifier Disinfectant-Associated Interstitial Lung Disease.

    PubMed

    Jhang, Won Kyoung; Park, Seong Jong; Lee, Eun; Yang, Song I; Hong, Soo Jong; Seo, Ju-Hee; Kim, Hyung-Young; Park, Jeong-Jun; Yun, Tae-Jin; Kim, Hyeong Ryul; Kim, Yong-Hee; Kim, Dong Kwan; Park, Seung-Il; Lee, Sang-Oh; Hong, Sang-Bum; Shim, Tae-Sun; Choi, In-Cheol; Yu, Jinho

    2016-05-01

    From 2006 to 2011, an outbreak of a particular type of childhood interstitial lung disease occurred in Korea. The condition was intractable and progressed to severe respiratory failure, with a high mortality rate. Moreover, in several familial cases, the disease affected young women and children simultaneously. Epidemiologic, animal, and post-interventional studies identified the cause as inhalation of humidifier disinfectants. Here, we report a 4-year-old girl who suffered from severe progressive respiratory failure. She could survive by 100 days of extracorporeal membrane oxygenation support and finally, underwent heart-lung transplantation. This is the first successful pediatric heart-lung transplantation carried out in Korea. PMID:27134508

  10. Patterns of airway involvement in inflammatory bowel diseases

    PubMed Central

    Papanikolaou, Ilias; Kagouridis, Konstantinos; Papiris, Spyros A

    2014-01-01

    Extraintestinal manifestations occur commonly in inflammatory bowel diseases (IBD). Pulmonary manifestations (PM) of IBD may be divided in airway disorders, interstitial lung disorders, serositis, pulmonary vasculitis, necrobiotic nodules, drug-induced lung disease, thromboembolic lung disease and enteropulmonary fistulas. Pulmonary involvement may often be asymptomatic and detected solely on the basis of abnormal screening tests. The common embryonic origin of the intestine and the lungs from the primitive foregut, the co-existence of mucosa associated lymphoid tissue in both organs, autoimmunity, smoking and bacterial translocation from the colon to the lungs may all be involved in the pathogenesis of PM in IBD. PM are mainly detected by pulmonary function tests and high-resolution computed tomography. This review will focus on the involvement of the airways in the context of IBD, especially stenoses of the large airways, tracheobronchitis, bronchiectasis, bronchitis, mucoid impaction, bronchial granulomas, bronchiolitis, bronchiolitis obliterans syndrome and the co-existence of IBD with asthma, chronic obstructive pulmonary disease, sarcoidosis and a1-antitrypsin deficiency. PMID:25400999

  11. Acute kidney injury in critically ill patients with lung disease: kidney-lung crosstalk

    PubMed Central

    de Abreu, Krasnalhia Lívia Soares; da Silva Junior, Geraldo Bezerra; Muniz, Thalita Diógenes; Barreto, Adller Gonçalves Costa; Lima, Rafael Siqueira Athayde; Holanda, Marcelo Alcântara; Pereira, Eanes Delgado Barros; Libório, Alexandre Braga; Daher, Elizabeth de Francesco

    2013-01-01

    Objective To examine the factors associated with acute kidney injury and outcome in patients with lung disease. Methods A prospective study was conducted with 100 consecutive patients admitted to a respiratory intensive care unit in Fortaleza (CE), Brazil. The risk factors for acute kidney injury and mortality were investigated in a group of patients with lung diseases. Results The mean age of the study population was 57 years, and 50% were male. The incidence of acute kidney injury was higher in patients with PaO2/FiO2<200 mmHg (54% versus 23.7%; p=0.02). Death was observed in 40 cases and the rate of mortality of the acute kidney injury group was higher (62.8% versus 27.6%; p=0.01). The independent factor that was found to be associated with acute kidney injury was PaO2/FiO2<200 mmHg (p=0.01), and the independent risk factors for death were PEEP at admission (OR: 3.6; 95%CI: 1.3-9.6; p=0.009) and need for hemodialysis (OR: 7.9; 95%CI: 2.2-28.3; p=0.001). Conclusion There was a higher mortality rate in the acute kidney injury group. Increased mortality was associated with mechanical ventilation, high PEEP, urea and need for dialysis. Further studies must be performed to better establish the relationship between kidney and lung injury and its impact on patient outcome. PMID:23917978

  12. 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. PMID:26895650

  13. 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

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

    PubMed

    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. Rituximab-induced interstitial lung disease: five case reports.

    PubMed

    Naqibullah, Matiuallah; Shaker, Saher B; Bach, Karen S; Bendstrup, Elisabeth

    2015-01-01

    Rituximab (RTX), a mouse/human chimeric anti-CD20 IgG1 monoclonal antibody has been effectively used as a single agent or in combination with chemotherapy regimen to treat lymphoma since 1997. In addition, it has been used to treat idiopathic thrombocytopenic purpura, systemic lupus erythematous, rheumatoid arthritis, and autoimmune hemolytic anemia. Recently, RTX has also been suggested for the treatment of certain connective tissue disease-related interstitial lung diseases (ILD) and hypersensitivity pneumonitis. Rare but serious pulmonary adverse reactions are reported. To raise awareness about this serious side effect of RTX treatment, as the indication for its use increases with time, we report five cases of probable RTX-ILD and discuss the current literature on this potentially lethal association. PMID:26557260

  16. Platelets in Pulmonary Immune Responses and Inflammatory Lung Diseases.

    PubMed

    Middleton, Elizabeth A; Weyrich, Andrew S; Zimmerman, Guy A

    2016-10-01

    Platelets are essential for physiological hemostasis and are central in pathological thrombosis. These are their traditional and best known activities in health and disease. In addition, however, platelets have specializations that broaden their functional repertoire considerably. These functional capabilities, some of which are recently discovered, include the ability to sense and respond to infectious and immune signals and to act as inflammatory effector cells. Human platelets and platelets from mice and other experimental animals can link the innate and adaptive limbs of the immune system and act across the immune continuum, often also linking immune and hemostatic functions. Traditional and newly recognized facets of the biology of platelets are relevant to defensive, physiological immune responses of the lungs and to inflammatory lung diseases. The emerging view of platelets as blood cells that are much more diverse and versatile than previously thought further predicts that additional features of the biology of platelets and of megakaryocytes, the precursors of platelets, will be discovered and that some of these will also influence pulmonary immune defenses and inflammatory injury. PMID:27489307

  17. Artificial intelligence-assisted occupational lung disease diagnosis.

    PubMed

    Harber, P; McCoy, J M; Howard, K; Greer, D; Luo, J

    1991-08-01

    An artificial intelligence expert-based system for facilitating the clinical recognition of occupational and environmental factors in lung disease has been developed in a pilot fashion. It utilizes a knowledge representation scheme to capture relevant clinical knowledge into structures about specific objects (jobs, diseases, etc) and pairwise relations between objects. Quantifiers describe both the closeness of association and risk, as well as the degree of belief in the validity of a fact. An independent inference engine utilizes the knowledge, combining likelihoods and uncertainties to achieve estimates of likelihood factors for specific paths from work to illness. The system creates a series of "paths," linking work activities to disease outcomes. One path links a single period of work to a single possible disease outcome. In a preliminary trial, the number of "paths" from job to possible disease averaged 18 per subject in a general population and averaged 25 per subject in an asthmatic population. Artificial intelligence methods hold promise in the future to facilitate diagnosis in pulmonary and occupational medicine. PMID:1864103

  18. Three-dimensional velocity mapping of lung motion using vessel bifurcation pattern matching

    SciTech Connect

    Tashiro, Mutsumi; Minohara, Shinichi; Kanai, Tatsuaki; Yusa, Ken; Sakurai, Hideyuki; Nakano, Takashi

    2006-06-15

    We present a new quantification technique for three-dimensional (3D) lung motion by means of tracking the anatomical features inside the lung using a set of sequential 3D-CT images (a 4D-CT image). The method is based on the conservation of topology, such as connections and junctions of vessels, during the motion. Lung CT images are used to do lung volume modeling, lung vessel extracting and thinning, and coordinates of vessel bifurcations are derived as feature points. Such feature points are tracked in a series of 3D-CT images, i.e., the points are individually tracked between two successive 3D-CT images, in which the lung is deformed. Consequently, 3D displacement vectors are obtained. The feature point tracking is carried out using point pattern matching with a probabilistic relaxation method. We examined this technique using a lung 3D-CT image and artificially deformed one, and separately scanned CT images for a rigid bifurcation phantom. The studies estimated that the error of the vectors is within {approx}1 voxel, i.e., 1 mm or less. Therefore, the accuracy is expected to be high enough for radiation therapy. This technique enables us to quantify realistic 3D organ motion without any fiducial markers. It can be applied to the quantification of tumor (target volume) deformation by gridding interpolation into all voxels. We expect it to be useful for dose estimation in mobile organs and for 4D treatment planning in radiation therapy.

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

    PubMed

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

    2016-02-01

    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 20.3 mg ± 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

  20. 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.

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

    PubMed

    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

  2. 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

  3. Factors Associated with Lung Function Decline in Patients with Non-Tuberculous Mycobacterial Pulmonary Disease

    PubMed Central

    Lee, Meng-Rui; Yang, Ching-Yao; Chang, Kai-Ping; Keng, Li-Ta; Yen, David Hung-Tsang; Wang, Jann-Yuan; Wu, Huey-Dong; Lee, Li-Na; Yu, Chong-Jen

    2013-01-01

    Background There is paucity of risk factors on lung function decline among patients with non-tuberculous mycobacteria (NTM) pulmonary disease in literature. Methods Patients with NTM pulmonary disease between January 2000 and April 2011 were retrospectively selected. Sixty-eight patients had at least two pulmonary function tests within a mean follow-up period of 47 months. Results Sixty-eight patients were included. They had a median age of 65 years and 65% had impaired lung function (Forced expiratory volume in 1 second [FEV1] <80% of predicted value). The mean FEV1 decline was 48 ml/year. By linear regression, younger age (beta: 0.472, p<0.001), initial FEV1>50% of predicted value (beta: 0.349, p = 0.002), male sex (beta: 0.295, p = 0.018), bronchiectasis pattern (beta: 0.232, p = 0.035), and radiographic score >3 (beta: 0.217, p = 0.049) were associated with greater FEV1 decline. Initial FEV1>50% of predicted value (beta: 0.263, p = 0.032) was also associated with greater FVC annual decline, whereas M. kansasii pulmonary disease was marginally associated with greater annual FVC decline (beta: 0.227, p = 0.062). Conclusions NTM pulmonary disease is associated with greater decline in lung function in patients who are young, male, with bronchiectasis, and with a high radiographic score. Special attention should be given to patients with these risk factors. PMID:23483998

  4. 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

  5. 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

  6. PRENATAL DEXAMETHASONE ADMINISTRATION DISRUPTS THE PATTERN OF CELLULAR DEVELOPMENT IN RAT LUNG

    EPA Science Inventory

    To examine whether prenatal exposure to glucocorticoids could adversely affect subsequent cellular development of the lung, we administered 0.2 mg/kg of dexamethasone to pregnant rats on gestational days 17, 18, and 19. ungs of the offspring were then examined for patterns of cel...

  7. Diffuse Cystic Lung Disease as the Presenting Manifestation of Sjögren Syndrome.

    PubMed

    Gupta, Nishant; Wikenheiser-Brokamp, Kathryn A; Fischer, Aryeh; McCormack, Francis X

    2016-03-01

    Interstitial lung diseases, especially lymphoproliferative disorders such as follicular bronchiolitis and lymphoid interstitial pneumonia, are commonly seen in association with Sjögren syndrome. Although the predominant computed tomographic (CT) findings in patients with lymphoid interstitial pneumonia/follicular bronchiolitis include poorly defined centrilobular nodules and ground-glass attenuation, cystic changes can be seen in approximately two-thirds of these patients. The objective of this study was to define the clinical, radiological, and histopathological features of cyst-predominant lymphoid interstitial pneumonia/follicular bronchiolitis in patients with Sjögren syndrome. We present four patients who were referred to our institution with diffuse cystic changes on chest CT imaging. All four had a presumptive diagnosis of lymphangioleiomyomatosis but were subsequently found to have Sjögren syndrome. The diagnosis was established based on the clinical symptoms of xerostomia and xerophthalmia along with serologic detection of antinuclear antibodies, rheumatoid factor, anti-Sjögren's syndrome-related antigen A (SSA)/Ro antibodies, and anti-Sjögren's syndrome-related antigen B (SSB)/La antibodies. The cystic pattern associated with Sjögren syndrome had a characteristic appearance on chest CT images. Typical features included a wide variation in cyst size, internal structure within cysts, geographic simplification of parenchymal architecture producing a "dissolving lung appearance," perivascular and often basilar-predominant distribution, and frequent association with ground-glass opacities and nodules. In a compatible clinical context, we submit that these findings can be sufficiently distinctive to obviate the need for lung biopsy, even in the absence of confirmatory serological studies or lip biopsy. Clinicians should consider occult Sjögren syndrome in the differential diagnosis of patients presenting with idiopathic diffuse cystic lung disease. PMID

  8. 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

  9. Influence of Pulmonary Rehabilitation on Lung Function Changes After the Lung Resection for Primary Lung Cancer in Patients with Chronic Obstructive Pulmonary Disease.

    PubMed

    Mujovic, Natasa; Mujovic, Nebojsa; Subotic, Dragan; Ercegovac, Maja; Milovanovic, Andjela; Nikcevic, Ljubica; Zugic, Vladimir; Nikolic, Dejan

    2015-11-01

    Influence of physiotherapy on the outcome of the lung resection is still controversial. Study aim was to assess the influence of physiotherapy program on postoperative lung function and effort tolerance in lung cancer patients with chronic obstructive pulmonary disease (COPD) that are undergoing lobectomy or pneumonectomy. The prospective study included 56 COPD patients who underwent lung resection for primary non small-cell lung cancer after previous physiotherapy (Group A) and 47 COPD patients (Group B) without physiotherapy before lung cancer surgery. In Group A, lung function and effort tolerance on admission were compared with the same parameters after preoperative physiotherapy. Both groups were compared in relation to lung function, effort tolerance and symptoms change after resection. In patients with tumors requiring a lobectomy, after preoperative physiotherapy, a highly significant increase in FEV1, VC, FEF50 and FEF25 of 20%, 17%, 18% and 16% respectively was registered with respect to baseline values. After physiotherapy, a significant improvement in 6-minute walking distance was achieved. After lung resection, the significant loss of FEV1 and VC occurred, together with significant worsening of the small airways function, effort tolerance and symptomatic status. After the surgery, a clear tendency existed towards smaller FEV1 loss in patients with moderate to severe, when compared to patients with mild baseline lung function impairment. A better FEV1 improvement was associated with more significant loss in FEV1. Physiotherapy represents an important part of preoperative and postoperative treatment in COPD patients undergoing a lung resection for primary lung cancer. PMID:26618048

  10. Interstitial Lung Disease in Children Younger Than 2 Years.

    PubMed

    Spagnolo, Paolo; Bush, Andrew

    2016-06-01

    Childhood interstitial lung disease (chILD) represents a highly heterogeneous group of rare disorders associated with substantial morbidity and mortality. Although our understanding of chILD remains limited, important advances have recently been made, the most important being probably the appreciation that disorders that present in early life are distinct from those occurring in older children and adults, albeit with some overlap. chILD manifests with diffuse pulmonary infiltrates and nonspecific respiratory signs and symptoms, making exclusion of common conditions presenting in a similar fashion an essential preliminary step. Subsequently, a systematic approach to diagnosis includes a careful history and physical examination, computed tomography of the chest, and some or all of bronchoscopy with bronchoalveolar lavage, genetic testing, and if diagnostic uncertainty persists, lung biopsy. This review focuses on chILD presenting in infants younger than 2 years of age and discusses recent advances in the classification, diagnostic approach, and management of chILD in this age range. We describe novel genetic entities, along with initiatives that aim at collecting clinical data and biologic samples from carefully characterized patients in a prospective and standardized fashion. Early referral to expert centers and timely diagnosis may have important implications for patient management and prognosis, but effective therapies are often lacking. Following massive efforts, international collaborations among the key stakeholders are finally starting to be in place. These have allowed the setting up and conducting of the first randomized controlled trial of therapeutic interventions in patients with chILD. PMID:27245831

  11. Sex-specific Differences in Hyperoxic Lung Injury in Mice: Implications for Acute and Chronic Lung Disease in Humans

    PubMed Central

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

    2014-01-01

    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 (FiO2>0.95). After exposure to hyperoxia, lung injury, levels of 8-iso-prostaglandin F2 alpha (8-iso-PGF 2α) (LC-MS/MS), apoptosis (TUNEL) and inflammatory markers (suspension bead array) were determined. CytochromeP450 (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. PMID:23792423

  12. 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.

  13. Identification of Neutrophil Activation Markers as Novel Surrogate Markers of CF Lung Disease

    PubMed Central

    Hage, Lisa; Kügler, Marion; Menendez, Katrin; Naehrlich, Lutz; Schulz, Richard; Roderfeld, Martin; Roeb, Elke

    2014-01-01

    Background and aims Cystic Fibrosis (CF) lung disease is characterized by progressively declining lung function and represents a major factor contributing to the high morbidity and mortality associated with CF. However, apart from spirometry, respiratory disease surrogate markers reliably indicating CF lung disease and the occurrence of pulmonary exacerbations (PEx) are still lacking. Within this study, we aimed to identify new experimental biomarkers for the detection of CF lung disease. Methods 54 adult and 26 pediatric CF patients were included in the study and serum concentrations of MMP-1, -2, -8, -9, -13, TIMP-1, TIMP-2, YKL-40, hyaluronic acid, procollagen III peptide were quantified by ELISA. CF lung disease was diagnosed by lung function test, PEx was defined based on a clinical scoring established by Rosenfeld in 2001. Results Adults and children with moderate to severe CF lung disease exhibited significantly increased serum expression of MMP-8, MMP-9, YKL-40 and TIMP-1. Further, MMP-8, MMP-9 and YKL-40 were significantly increased in adult CF patients suffering from PEx compared to those without clinical signs of respiratory exacerbation. MMP-8, MMP-9, YKL-40, and TIMP-1 serum levels were unaffected by the presence or absence of CF liver disease or pancreatic insufficiency. Conclusions MMP-8, MMP-9, and YKL-40 might serve as novel non-invasive biomarkers of CF lung disease and PEx. PMID:25545245

  14. Statin Use Is Associated with Reduced Mortality in Patients with Interstitial Lung Disease

    PubMed Central

    2015-01-01

    Introduction We hypothesized that statin use begun before the diagnosis of interstitial lung disease is associated with reduced mortality. Methods We studied all patients diagnosed with interstitial lung disease in the entire Danish population from 1995 through 2009, comparing statin use versus no statin use in a nested 1:2 matched study. Results The cumulative survival as a function of follow-up time from the date of diagnosis of interstitial lung disease (n = 1,786+3,572) and idiopathic lung fibrosis (n = 261+522) was higher for statin users versus never users (log-rank: P = 7·10−9 and P = 0.05). The median survival time in patients with interstitial lung disease was 3.3 years in statin users and 2.1 years in never users. Corresponding values in patients with idiopathic lung fibrosis were 3.4 versus 2.4 years. After multivariable adjustment, the hazard ratio for all-cause mortality for statin users versus never users was 0.73 (95% confidence interval, 0.68 to 0.79) in patients with interstitial lung disease and 0.76 (0.62 to 0.93) in patients with idiopathic lung fibrosis. Results were robust in all sensitivity analyses. Conclusion Among patients with interstitial lung disease statin use was associated with reduced all-cause mortality. PMID:26473476

  15. The Immediate Pulmonary Disease Pattern following Exposure to High Concentrations of Chlorine Gas

    PubMed Central

    Balte, Pallavi P.; Clark, Kathleen A.; Mohr, Lawrence C.; Karmaus, Wilfried J.; Van Sickle, David; Svendsen, Erik R.

    2013-01-01

    Background. Classification of pulmonary disease into obstructive, restrictive, and mixed patterns is based on 2005 ATS/ERS guidelines and modified GOLD criteria by Mannino et al. (2003), but these guidelines are of limited use for simple spirometry in situations involving mass casualties. Aim. The purpose of this study was to apply these guidelines to patients who underwent simple spirometry following high concentration of chlorine gas inhalation after a train derailment in Graniteville, South Carolina. Methods. We retrospectively investigated lung functions in ten patients. In order to classify pulmonary disease pattern, we used 2005 ATS/ERS guidelines and modified GOLD criteria along with our own criteria developed using available simple spirometry data. Results. We found predominant restrictive pattern in our patients with both modified GOLD and our criteria, which is in contrast to other chlorine exposure studies where obstructive pattern was more common. When compared to modified GOLD and our criteria, 2005 ATS/ERS guidelines underestimated the frequency of restrictive disease. Conclusion. Diagnosis of pulmonary disease patterns is of importance after irritant gas inhalation. Acceptable criteria need to be developed to evaluate pulmonary disease through simple spirometry in events leading to mass casualty and patient surge in hospitals. PMID:24386566

  16. Carboplatin plus paclitaxel in combination with bevacizumab for the treatment of adenocarcinoma with interstitial lung diseases

    PubMed Central

    SUZUKI, HIDEKAZU; HIRASHIMA, TOMONORI; KOBAYASHI, MASASHI; OKAMOTO, NORIO; MATSUURA, YUKA; TAMIYA, MOTOHIRO; MORISHITA, NAOKO; OKAFUJI, KOHEI; SHIROYAMA, TAKAYUKI; MORIMURA, OSAMU; MORITA, SATOMU; KAWASE, ICHIRO

    2013-01-01

    Interstitial lung diseases (ILDs) are frequently associated with lung cancer. The safety of carboplatin plus paclitaxel in combination with bevacizumab (CP-B) in patients with ILD and lung cancer (ILD-LC) remains to be clarified. In the present study, the safety and efficacy of CP-B treatment in ILD-LC patients were retrospectively investigated. Four patients, who completed CP-B therapy, were included in this study. The dose of carboplatin was the area under the curve 5, paclitaxel was 200 mg/m2 and bevacizumab was 15 mg/kg at treatment initiation. The patients were males, had histologically confirmed adenocarcinoma, were smokers and demonstrated non-usual interstitial pneumonia (non-UIP) patterns on computed tomography (CT). Patients received 1–6 cycles of CP-B therapy. Three of the four patients received maintenance bevacizumab therapy for 3–10 cycles. Only one patient demonstrated a partial response. Neutropenia was the most frequent adverse event. One patient experienced gut perforation during the first course of CP-B. No pulmonary toxicity was observed. Thus, treatment of ILD-LC patients with CP-B was not associated with pulmonary toxicity, however, this study population appeared to be at a low risk. PMID:24649195

  17. AB017. Interstitial lung disease patient diagnostic journey (intensity)

    PubMed Central

    Lederer, David J.; Bianchi, Pauline; Loboda, Jeanne; Danese, Sherry; Cosgrove, Gregory P.

    2016-01-01

    Background Interstitial lung disease (ILD) is complicated to diagnose because its signs and symptoms mimic a wide range of common medical conditions. The objective of the INTENSITY survey was to advance the understanding of respondents’ diagnostic experiences with ILDs, including idiopathic pulmonary fibrosis (IPF). The survey was designed to trace the path that respondents took to diagnosis, identify obstacles they faced, and gauge the emotional impact of their journey. Results from the INTENSITY survey will help us more fully understand respondents’ diagnostic experiences so we can further our efforts to improve timely diagnosis and treatment of ILDs. Methods We administered a 25-minute quantitative online survey from August 14–26, 2015. Of the 1,152 respondents screened to ensure they were US residents, and had been diagnosed with an interstitial lung disease, 600 met criteria and completed the survey. Recruitment was accomplished through two channels: email invitations sent to 16,000 Pulmonary Fibrosis Foundation (PFF) members and an open invitation to participate through the pulmonary fibrosis community website Results Shortness of breath (77%) and cough (53%) were the most common early symptoms in ILD patients. Twenty-five percent of respondents saw their primary care physician once before being referred to a specialist, however 61% of respondents saw their primary care physician >2 times before referral to a pulmonologist. Misdiagnosis occurred in 55% of respondents. The median time from symptom onset to correct diagnosis was 11 months, however 49% of respondents carried an incorrect diagnosis for 1 to 10 years. Thirty-eight percent were misdiagnosed more than twice, most frequently with asthma, pneumonia, bronchitis, and allergies. An accurate diagnosis was achieved after a median of 6 months and a median of 3 physician visits. The majority underwent an invasive diagnostic procedure. Fourteen percent of respondents saw more than 6 physicians before

  18. Expression of aquaporins in bronchial tissue and lung parenchyma of patients with chronic obstructive pulmonary disease

    PubMed Central

    2014-01-01

    Background Aquaporins AQP1 and AQP5 are highly expressed in the lung. Recent studies have shown that the expression of these proteins may be mechanistically involved in the airway inflammation and in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate the expression of AQP1 and AQP5 in the bronchial tissue and the lung parenchyma of patients with COPD and COPD-resistant smokers. Methods Using a case–control design, we selected a group of 15 subjects with COPD and 15 resistant smokers (smokers without COPD) as a control, all of whom were undergoing lung resection surgery due to a lung neoplasm. We studied the expression of AQP1 and AQP5 in the bronchial tissue and the lung parenchyma by means of immunohistochemistry and reverse-transcription real-time polymerase chain reaction. Tissue expression of AQP1 and AQP5 was semi-quantitatively assessed in terms of intensity and expression by immunohistochemistry using a 4-point scale ranging from 0 (none) to 3 (maximum). Results There were no significant differences in gene expression between COPD patients and resistant smokers both in the bronchial tissue and in the lung parenchyma. However, AQP1 gene expression was 2.41-fold higher in the parenchyma of smokers with COPD compared to controls, whereas the AQP5 gene showed the opposite pattern, with a 7.75-fold higher expression in the bronchus of smokers with COPD compared with controls. AQP1 and AQP5 proteins were preferentially expressed in endothelial cells, showing a higher intensity for AQP1 (66.7% of cases with an intensity of 3, and 93.3% of subjects with an extension of 3 among patients with COPD). Subtle interstitial disease was associated with type II pneumocyte hyperplasia and an increased expression of AQP1. Conclusions This study provides pilot observations on the differences in AQP1 and AQP5 expression between COPD patients and COPD-resistant smokers. Our findings suggest a potential role for AQP1 in the

  19. Patterns of Respiratory Disease During the First 2 Postnatal Weeks in Extremely Premature Infants

    PubMed Central

    Laughon, Matthew; Allred, Elizabeth N.; Bose, Carl; O'Shea, T. Michael; Van Marter, Linda J.; Ehrenkranz, Richard A.; Leviton, Alan

    2009-01-01

    Background Pulmonary disease among infants of <28 weeks' gestation (extremely low gestational age newborns) often has the following pattern: the infant starts out with little need for supplemental oxygen and ventilatory support in the first postnatal week but then has pulmonary deterioration in the second postnatal week, with an increased need for supplemental oxygen and respiratory support. We evaluated the antecedents and correlates of patterns of early lung disease, with particular emphasis on pulmonary deterioration, in a large cohort study (the Extremely Low Gestational Age Newborn [ELGAN] study). Patients and Methods We examined data collected prospectively on 1340 infants born between 2002 and 2004 at 23 to 27 completed weeks of gestation and who survived to 14 days. Pulmonary deterioration was defined as receipt of fraction of inspired oxygen <0.23 on any day between days 3 and 7 and receipt of fraction of inspired oxygen ≥ 0.25 on day 14. Results One fifth (20%) of the infants had consistently low fraction of inspired oxygen, approximately two fifths (38%) had pulmonary deterioration, and the remaining approximately two fifths (43%) had consistently high fraction of inspired oxygen (early and persistent lung dysfunction). Compared with infants who had consistently low fraction of inspired oxygen, infants who experienced pulmonary deterioration had lower gestational ages and lower birth weights, had higher scores for neonatal acute physiology, and received more intensive modes of respiratory support. Gender, multifetal pregnancy, cesarean delivery, antenatal steroids, chorioamnionitis, and funisitis were not associated with pulmonary deterioration. The incidence of chronic lung disease, defined as oxygen therapy at 36 weeks' postmenstrual age, was 17% in the consistently low fraction of inspired oxygen group, 51% in the pulmonary deterioration group, and 67% in the early and persistent pulmonary dysfunction group. The incidence of death in these 3 groups

  20. Ventilation patterns of the songbird lung/air sac system during different behaviors

    PubMed Central

    Mackelprang, Rebecca; Goller, Franz

    2013-01-01

    SUMMARY Unidirectional, continuous airflow through the avian lung is achieved through an elaborate air sac system with a sequential, posterior to anterior ventilation pattern. This classical model was established through various approaches spanning passively ventilated systems to mass spectrometry analysis of tracer gas flow into various air sacs during spontaneous breathing in restrained ducks. Information on flow patterns in other bird taxa is missing, and these techniques do not permit direct tests of whether the basic flow pattern can change during different behaviors. Here we use thermistors implanted into various locations of the respiratory system to detect small pulses of tracer gas (helium) to reconstruct airflow patterns in quietly breathing and behaving (calling, wing flapping) songbirds (zebra finch and yellow-headed blackbird). The results illustrate that the basic pattern of airflow in these two species is largely consistent with the model. However, two notable differences emerged. First, some tracer gas arrived in the anterior set of air sacs during the inspiration during which it was inhaled, suggesting a more rapid throughput through the lung than previously assumed. Second, differences in ventilation between the two anterior air sacs emerged during calling and wing flapping, indicating that adjustments in the flow pattern occur during dynamic behaviors. It is unclear whether this modulation in ventilation pattern is passive or active. This technique for studying ventilation patterns during dynamic behaviors proves useful for establishing detailed timing of airflow and modulation of ventilation in the avian respiratory system. PMID:23788706

  1. Role of Innate Lymphoid Cells in Lung Disease.

    PubMed

    Marashian, Sayed Mehran; Mortaz, Esmaeil; Jamaati, Hamid Reza; Alavi-Moghaddam, Mostafa; Kiani, Arda; Abedini, Atefeh; Garssen, Johan; Adcock, Ian M; Velayati, Ali Akbar

    2015-08-01

    Innate lymphoid cells (ILCs) are identified as novel population of hematopoietic cells which protect the body by coordinating the innate immune response against a wide range of threats including infections, tissue damages and homeostatic disturbances. ILCs, particularly ILC2 cells, are found throughout the body including the brain. ILCs are morphologically similar to lymphocytes, express and release high levels of T-helper (Th)1, Th2 and Th17 cytokines but do not express classical cell-surface markers that are associated with other immune cell lineages. Three types of ILCs (ILC1, 2 & 3) have been reported depending upon the cytokines produced. ILC1 cells encompass natural killer (NK) cells and interferon (IFN)-g releasing cells; ILC2 cells release the Th2 cytokines, IL-5, IL-9 and IL-13 in response to IL-25 and IL-33; and ILC3 cells which release IL-17 and IL-22. ILC2 cells have been implicated inmucosal reactions occurring in animal models of allergic asthma and virus-induced lung disorders resulting in the regulation of airway remodeling and tissue homeostasis. There is evidence for increased ILC2 cell numbers in allergic responses in man but little is known about the role of ILCs in chronic obstructive pulmonary disease (COPD). Further understanding of the characteristics of ILCs such as their origin, location and phenotypes and function would help to clarify the role of these cells in the pathogenesis of various lung diseases. In this review we will focus on the role of ILC2 cells and consider their origin, function,location and possible role in the pathogenesis of the chronic inflammatory disorders such as asthma and COPD. PMID:26547702

  2. Age, Sexual Dimorphism, and Disease Associations in the Developing Human Fetal Lung Transcriptome.

    PubMed

    Kho, Alvin T; Chhabra, Divya; Sharma, Sunita; Qiu, Weiliang; Carey, Vincent J; Gaedigk, Roger; Vyhlidal, Carrie A; Leeder, J Steven; Tantisira, Kelan G; Weiss, Scott T

    2016-06-01

    The fetal origins of disease hypothesis suggests that variations in the course of prenatal lung development may affect life-long pulmonary function growth, decline, and pathobiology. Many studies support the existence of differences in the developing lung trajectory in males and females, and sex-specific differences in the prevalence of chronic lung diseases, such as asthma and bronchopulmonary dysplasia. The objectives of this study were to investigate the early developing fetal lung for transcriptomic correlates of postconception age (maturity) and sex, and their associations with chronic lung diseases. We analyzed whole-lung transcriptome profiles of 61 females and 78 males at 54-127 days postconception (dpc) from nonsmoking mothers using unsupervised principal component analysis and supervised linear regression models. We identified dominant transcriptomic correlates for postconception age and sex with corresponding gene sets that were enriched for developing lung structural and functional ontologies. We observed that the transcriptomic sex difference was not a uniform global time shift/lag, rather, lungs of males appear to be more mature than those of females before 96 dpc, and females appear to be more mature than males after 96 dpc. The age correlate gene set was consistently enriched for asthma and bronchopulmonary dysplasia genes, but the sex correlate gene sets were not. Despite sex differences in the developing fetal lung transcriptome, postconception age appears to be more dominant than sex in the effect of early fetal lung developments on disease risk during this early pseudoglandular phase of development. PMID:26584061

  3. Patterns of symptom distress in adults receiving treatment for lung cancer.

    PubMed

    Cooley, Mary E; Short, Thomas H; Moriarty, Helene J

    2002-01-01

    Knowledge of the patterns of symptom distress in adults receiving treatment for lung cancer is an important first step in developing interventions that can potentially lessen symptom distress. The purposes of this secondary analysis were to describe the changes in patterns of symptom distress over time in adults receiving treatment for lung cancer, and to examine the relationship of selected demographic and clinical characteristics to symptom distress. Complete data were available for 117 patients. The patterns of symptom distress in adults receiving treatment for lung cancer varied between treatment groups and over time. Symptom distress scores were moderate to high on entry into the study, indicating that symptom management in newly diagnosed lung cancer patients is essential and should begin early in the course of illness. Moreover, clinical interventions should be tailored to the type of treatment. Various demographic and clinical variables were weak and inconsistent predictors of symptom distress, underscoring the importance of examining the role of psychosocial factors in mediating symptom distress. PMID:12418365

  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. PMID:26757299

  5. Impact of lung disease on respiratory impedance in young children with cystic fibrosis.

    PubMed

    Ramsey, Kathryn A; Ranganathan, Sarath C; Gangell, Catherine L; Turkovic, Lidija; Park, Judy; Skoric, Billy; Stick, Stephen M; Sly, Peter D; Hall, Graham L

    2015-12-01

    This study aimed to evaluate the ability of the forced oscillation technique (FOT) to detect underlying lung disease in preschool children with cystic fibrosis (CF) diagnosed following newborn screening.184 children (aged 3-6 years) with CF underwent lung function testing on 422 occasions using the FOT to assess respiratory resistance and reactance at the time of their annual bronchoalveolar lavage collection and chest computed tomography scan. We examined associations between FOT outcomes and the presence and progression of respiratory inflammation, infection and structural lung disease.Children with CF who had pronounced respiratory disease, including free neutrophil elastase activity, infection with pro-inflammatory pathogens and structural lung abnormalities had similar FOT outcomes to those children without detectable lung disease. In addition, the progression of lung disease over 1 year was not associated with worsening FOT outcomes.We conclude that the forced oscillation technique is relatively insensitive to detect underlying lung disease in preschool children with CF. However, FOT may still be of value in improving our understanding of the physiological changes associated with early CF lung disease. PMID:26405283

  6. Future directions in early cystic fibrosis lung disease research: an NHLBI workshop report.

    PubMed

    Ramsey, Bonnie W; Banks-Schlegel, Susan; Accurso, Frank J; Boucher, Richard C; Cutting, Garry R; Engelhardt, John F; Guggino, William B; Karp, Christopher L; Knowles, Michael R; Kolls, Jay K; LiPuma, John J; Lynch, Susan; McCray, Paul B; Rubenstein, Ronald C; Singh, Pradeep K; Sorscher, Eric; Welsh, Michael

    2012-04-15

    Since the 1989 discovery that mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF), there has been substantial progress toward understanding the molecular basis for CF lung disease, leading to the discovery and development of new therapeutic approaches. However, the earliest impact of the loss of CFTR function on airway physiology and structure and its relationship to initial infection and inflammation are poorly understood. Universal newborn screening for CF in the United States represents an unprecedented opportunity for investigating CF clinical manifestations very early in life. Recently developed animal models with pulmonary phenotypic manifestations also provide a window into the early consequences of this genetic disorder. For these reasons, the National Heart, Lung, and Blood Institute (NHLBI) convened a working group of extramural experts, entitled "Future Research Directions in Early CF Lung Disease" on September 21-22, 2010, to identify future research directions of great promise in CF. The priority areas identified included (1) exploring pathogenic mechanisms of early CF lung disease; (2) leveraging newborn screening to elucidate the natural history of early lung disease; (3) developing a spectrum of biomarkers of early lung disease that reflects CF pathophysiology, clinical outcome, and response to treatment; (4) exploring the role of genetics/genomics (e.g., modifier genes, gene-environmental interactions, and epigenetics) in early CF pathogenesis; (5) defining early microbiological events in CF lung disease; and (6) elucidating the initial airway inflammatory, remodeling, and repair mechanisms in CF lung disease. PMID:22312017

  7. 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.

  8. A Healthy Dietary Pattern Reduces Lung Cancer Risk: A Systematic Review and Meta-Analysis

    PubMed Central

    Sun, Yanlai; Li, Zhenxiang; Li, Jianning; Li, Zengjun; Han, Jianjun

    2016-01-01

    Background: Diet and nutrients play an important role in cancer development and progress; a healthy dietary pattern has been found to be associated with several types of cancer. However, the association between a healthy eating pattern and lung cancer risk is still unclear. Objective: Therefore, we conducted a systematic review with meta-analysis to evaluate whether a healthy eating pattern might reduce lung cancer risk. Methods: We identified relevant studies from the PubMed and Embase databases up to October 2015, and the relative risks were extracted and combined by the fixed-effects model when no substantial heterogeneity was observed; otherwise, the random-effects model was employed. Subgroup and publication bias analyses were also performed. Results: Finally, eight observational studies were included in the meta-analysis. The pooled relative risk of lung cancer for the highest vs. lowest category of healthy dietary pattern was 0.81 (95% confidence interval, CI: 0.75–0.86), and no significant heterogeneity was detected. The relative risks (RRs) for non-smokers, former smokers and current smokers were 0.89 (95% CI: 0.63–1.27), 0.74 (95% CI: 0.62–0.89) and 0.86 (95% CI: 0.79–0.93), respectively. The results remained stable in subgroup analyses by other confounders and sensitivity analysis. Conclusions: The results of our meta-analysis suggest that a healthy dietary pattern is associated with a lower lung cancer risk, and they provide more beneficial evidence for changing the diet pattern in the general population. PMID:26959051

  9. Neutrophil elastase and matrix metalloproteinase 12 in cystic fibrosis lung disease.

    PubMed

    Wagner, Claudius J; Schultz, Carsten; Mall, Marcus A

    2016-12-01

    Chronic lung disease remains the major cause of morbidity and mortality in patients with cystic fibrosis (CF). Recent studies in young children with CF diagnosed by newborn screening identified neutrophil elastase (NE), a major product released from neutrophils in inflamed airways, as a key risk factor for the onset and early progression of CF lung disease. However, the understanding of how NE and potentially other proteases contribute to the complex in vivo pathogenesis of CF lung disease remains limited. In this review, we summarize recent progress in this area based on studies in βENaC-overexpressing (βENaC-Tg) mice featuring CF-like lung disease and novel protease-specific Förster resonance energy transfer (FRET) sensors for localization and quantification of protease activity in the lung. These studies demonstrated that NE is implicated in several key features of CF lung disease such as neutrophilic airway inflammation, mucus hypersecretion, and structural lung damage in vivo. Furthermore, these studies identified macrophage elastase (matrix metalloproteinase 12 (MMP12)) as an additional protease contributing to early lung damage in βENaC-Tg mice. Collectively, these results suggest that NE and MMP12 released from activated neutrophils and macrophages in mucus-obstructed airways play important pathogenetic roles and may serve as potential therapeutic targets to prevent and/or delay irreversible structural lung damage in patients with CF. PMID:27456476

  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. 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

  12. [A nonlinear multi-compartment lung model for optimization of breathing airflow pattern].

    PubMed

    Cai, Yongming; Gu, Lingyan; Chen, Fuhua

    2015-02-01

    It is difficult to select the appropriate ventilation mode in clinical mechanical ventilation. This paper presents a nonlinear multi-compartment lung model to solve the difficulty. The purpose is to optimize respiratory airflow patterns and get the minimum of the work of inspiratory phrase and lung volume acceleration, minimum of the elastic potential energy and rapidity of airflow rate changes of expiratory phrase. Sigmoidal function is used to smooth the respiratory function of nonlinear equations. The equations are established to solve nonlinear boundary conditions BVP, and finally the problem was solved with gradient descent method. Experimental results showed that lung volume and the rate of airflow after optimization had good sensitivity and convergence speed. The results provide a theoretical basis for the development of multivariable controller monitoring critically ill mechanically ventilated patients. PMID:25997262

  13. [A case of occupational lung disease (welder lung) in a mechanical worker].

    PubMed

    Di Lorenzo, L; Trabucco, S; Massola, A; Corfiati, M; Bello, A; Soleo, L

    2007-01-01

    A case of welder's lung is reported in a male hard smoker who had worked as welder-carpenter for almost 30 years. In order to establish an etiologic diagnosis, given the informed consent from the worker, open lung biopsy was performed that allowed to obtain sufficiently large specimens of affected lung to make histological, immunohistochemical and mineralogical examination. In such a way the pathologic features were accurately defined and a multidisciplinary approach was applied to differential diagnosis. The worker is recommended to undergo a strict health surveillance because of the reported association of welder's lung with lung cancer, especially in smokers. PMID:18409991

  14. 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

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

    PubMed

    Iqbal, Kundan; Kelly, Clive

    2015-12-01

    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

  16. Limited-disease small-cell lung cancer.

    PubMed

    Zimmermann, Frank B; Bamberg, Michael; Molls, Michael; Jeremic, Branislav

    2003-01-01

    Substantial improvements in treatment outcome for limited-disease small-cell lung cancer (LD SCLC) have been achieved in the last two decades owing to the introduction of chemotherapy (CHT) consisting of cisplatin and etoposide (PE), and the understanding that thoracic radiation therapy (TRT) is an essential component in improving treatment outcome. In addition, a recent metaanalysis confirmed the importance of prophylactic cranial irradiation (PCI) in general treatment plans for patients who show a complete response to treatment. However, numerous questions remain unanswered regarding this disease. While TRT/PE/PCI is considered to be the standard treatment in the majority of centers worldwide, the emergence of new and effective drugs (e.g., topoisomerase I inhibitors and paclitaxel) for the treatment of LD SCLC will likely affect therapy strategies in the near future. Important issues regarding optimal doses and fractionation regimens, as well as the timing of TRT, remain to be resolved. While most centers currently use b.i.d. fractionation as a result of the Intergroup findings, high-dose standard TRT may also be beneficial. TRT volumes are also considered an important issue, since they likely relate to the incidence of both local failure and toxicity. Finally, the optimization of PCI (total dose, fractionation regimen, and timing) is already under way. The value of surgery is limited to peripheral tumors and poorly responding cancer, and to confirm histology or improve local control and survival. PMID:14508848

  17. 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.

  18. Characterization of free breathing patterns with 5D lung motion model

    SciTech Connect

    Zhao Tianyu; Lu Wei; Yang Deshan; Mutic, Sasa; Noel, Camille E.; Parikh, Parag J.; Bradley, Jeffrey D.; Low, Daniel A.

    2009-11-15

    Purpose: To determine the quiet respiration breathing motion model parameters for lung cancer and nonlung cancer patients. Methods: 49 free breathing patient 4DCT image datasets (25 scans, cine mode) were collected with simultaneous quantitative spirometry. A cross-correlation registration technique was employed to track the lung tissue motion between scans. The registration results were applied to a lung motion model: X-vector=X-vector{sub 0}+{alpha}-vector{beta}-vector f, where X-vector is the position of a piece of tissue located at reference position X-vector{sub 0} during a reference breathing phase (zero tidal volume v, zero airflow f). {alpha}-vector is a parameter that characterizes the motion due to air filling (motion as a function of tidal volume v) and {beta}-vector is the parameter that accounts for the motion due to the imbalance of dynamical stress distributions during inspiration and exhalation that causes lung motion hysteresis (motion as a function of airflow f). The parameters {alpha}-vector and {beta}-vector together provide a quantitative characterization of breathing motion that inherently includes the complex hysteresis interplay. The {alpha}-vector and {beta}-vector distributions were examined for each patient to determine overall general patterns and interpatient pattern variations. Results: For 44 patients, the greatest values of |{alpha}-vector| were observed in the inferior and posterior lungs. For the rest of the patients, |{alpha}-vector| reached its maximum in the anterior lung in three patients and the lateral lung in two patients. The hysteresis motion {beta}-vector had greater variability, but for the majority of patients, |{beta}-vector| was largest in the lateral lungs. Conclusions: This is the first report of the three-dimensional breathing motion model parameters for a large cohort of patients. The model has the potential for noninvasively predicting lung motion. The majority of patients exhibited similar |{alpha}-vector| maps

  19. Maternal and fetal origins of lung disease in adulthood.

    PubMed

    Harding, Richard; Maritz, Gert

    2012-04-01

    This review focuses on genetic and environmental influences that result in long term alterations in lung structure and function. Environmental factors operating during fetal and early postnatal life can have persistent effects on lung development and so influence lung function and respiratory health throughout life. Common factors affecting the quality of the intrauterine environment that can alter lung development include fetal nutrient and oxygen availability leading to intrauterine growth restriction, fetal intrathoracic space, intrauterine infection or inflammation, maternal tobacco smoking and other drug exposures. Similarly, factors that operate during early postnatal life, such as mechanical ventilation and high FiO(2) in the case of preterm birth, undernutrition, exposure to tobacco smoke and respiratory infections, can all lead to persistent alterations in lung structure and function. Greater awareness of the many prenatal and early postnatal factors that can alter lung development will help to improve lung development and hence respiratory health throughout life. PMID:22277111

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

    PubMed Central

    Sakkijha, Husam; Idrees, Majdy M.

    2014-01-01

    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. PMID:25076998

  1. Bedside Lung Ultrasound During Acute Chest Syndrome in Sickle Cell Disease

    PubMed Central

    Razazi, Keyvan; Deux, Jean-François; de Prost, Nicolas; Boissier, Florence; Cuquemelle, Elise; Galactéros, Frédéric; Rahmouni, Alain; Maître, Bernard; Brun-Buisson, Christian; Mekontso Dessap, Armand

    2016-01-01

    Abstract Lung ultrasound (LU) is increasingly used to assess pleural and lung disease in intensive care unit (ICU) and emergency unit at the bedside. We assessed the performance of bedside chest radiograph (CR) and LU during severe acute chest syndrome (ACS), using computed tomography (CT) as the reference standard. We prospectively explored 44 ACS episodes (in 41 patients) admitted to the medical ICU. Three imaging findings were evaluated (consolidation, ground-glass opacities, and pleural effusion). A score was used to quantify and compare loss of lung aeration with each technique and assess its association with outcome. A total number of 496, 507, and 519 lung regions could be assessed by CT scan, bedside CR, and bedside LU, respectively. Consolidations were the most common pattern and prevailed in lung bases (especially postero-inferior regions). The agreement with CT scan patterns was significantly higher for LU as compared to CR (κ coefficients of 0.45 ± 0.03 vs 0.30 ± 0.03, P < 0.01 for the parenchyma, and 0.73 ± 0.08 vs 0.06 ± 0.09, P < 0.001 for pleural effusion). The Bland and Altman analysis showed a nonfixed bias of −1.0 (P = 0.12) between LU score and CT score whereas CR score underestimated CT score with a fixed bias of −5.8 (P < 0.001). The specificity for the detection of consolidated regions or pleural effusion (using CT scan as the reference standard) was high for LU and CR, whereas the sensitivity was high for LU but low for CR. As compared to others, ACS patients with an LU score above the median value of 11 had a larger volume of transfused and exsanguinated blood, greater oxygen requirements, more need for mechanical ventilation, and a longer ICU length of stay. LU outperformed CR for the diagnosis of consolidations and pleural effusion during ACS. Higher values of LU score identified patients at risk of worse outcome. PMID:26886600

  2. 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.

  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. Burden of Obstructive Lung Disease Study in Tehran: Research Design and Lung Spirometry Protocol

    PubMed Central

    Sharifi, Hooman; Masjedi, Mohammad Reza; Emami, Habib; Ghanei, Mostafa; Buist, Sonia

    2014-01-01

    Background: Chronic obstructive pulmonary diseases (COPD) are planned to rank fifth in burden of disease and third with respect to mortality by 2020. Carrying out research regarding different aspects of COPD is mentioned as important health priorities by academic institutions and governments. The burden of lung disease (BOLD) Initiative was designed a decade ago to develop robust models that can be used to estimate the prevalence and current and future economic burden of COPD. The goal of the present project is to describe the prevalence and determining the causes and risk factors of COPD in the population of Tehran city. Methods: This cross-sectional study follows a stratified cluster sampling strategy with proportional allocation within strata. The target population is all noninstitutionalized inhabitants, aged 18-40 in one group and over 40 in another, who inhabit in Tehran city. The stratification of the sample according to the 22 municipal districts of Tehran is incorporated in the sampling process. Proportional to the number of households in the 22 districts, the appropriate number of clusters is weighted according to each district. For each cluster, a team of three members approaches the index household, which is specified through the aforementioned random selection of clusters, and continues the enumeration in 10 neighbor households in a systematic manner. Results: As a study protocol, there are no specific results to present; our purpose is to share our design with the scientific body. Conclusions: We expect that findings from the BOLD study in Tehran will show the status of COPD and its causes in the community. PMID:25538840

  5. Expression of a human surfactant protein C mutation associated with interstitial lung disease disrupts lung development in transgenic mice.

    PubMed

    Bridges, James P; Wert, Susan E; Nogee, Lawrence M; Weaver, Timothy E

    2003-12-26

    Surfactant Protein C (SP-C) is a secreted transmembrane protein that is exclusively expressed by alveolar type II epithelial cells of the lung. SP-C associates with surfactant lipids to reduce surface tension within the alveolus, maintaining lung volume at end expiration. Mutations in the gene encoding SP-C (SFTPC) have recently been linked to chronic lung disease in children and adults. The goal of this study was to determine whether a disease-linked mutation in SFTPC causes lung disease in transgenic mice. The SFTPC mutation, designated g.1728 G --> A, results in the deletion of exon4, generating a truncated form of SP-C (SP-C(Deltaexon4)). cDNA encoding SP-C(Deltaexon4) was constitutively expressed in type II epithelial cells of transgenic mice. Viable F0 transgene-positive mice were not generated after two separate rounds of pronuclear injections. Histological analysis of lung tissue harvested from embryonic day 17.5 F0 transgene-positive fetuses revealed that SP-C(Deltaexon4) caused a dose-dependent disruption in branching morphogenesis of the lung associated with epithelial cell cytotoxicity. Transient expression of SP-C(Deltaexon4) in isolated type II epithelial cells or HEK293 cells resulted in incomplete processing of the mutant proprotein, a dose-dependent increase in BiP transcription, trapping of the proprotein in the endoplasmic reticulum, and rapid degradation via a proteasome-dependent pathway. Taken together, these data suggest that the g.1728 G --> A mutation causes misfolding of the SP-C proprotein with subsequent induction of the unfolded protein response and endoplasmic reticulum-associated degradation pathways ultimately resulting in disrupted lung morphogenesis. PMID:14525980

  6. Aging and Lung Disease. Clinical Impact and Cellular and Molecular Pathways.

    PubMed

    Rojas, Mauricio; Mora, Ana L; Kapetanaki, Maria; Weathington, Nathaniel; Gladwin, Mark; Eickelberg, Oliver

    2015-12-01

    With the expected rapid growth of the aging population worldwide, there is a clear need to understand the complex process of aging to develop interventions that might extend the health span in this group of patients. Aging is associated with increased susceptibility to a variety of chronic diseases, and lung pathologies are no exception. The prevalence of lung diseases such as idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease has been found to increase considerably with age. In October 2014, the Division of Pulmonary, Allergy, and Critical Care of the University of Pittsburgh cohosted the Pittsburgh-Munich Lung Conference focused in aging and lung disease with the Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Ludwig-Maximilians University and Helmholtz Zentrum Munich Germany. The purpose of the conference was to disseminate novel concepts in aging mechanisms that have an impact in lung physiology and pathogenesis of pulmonary diseases that commonly occur in older populations. The conference included 28 presentations on diverse topics, which are summarized in this report. The participants identified priorities for future basic and translational investigations that will assist in the identification of molecular insights involved in the pathogenesis of age-related pulmonary diseases and the design of therapeutic interventions for these lung conditions. PMID:26653202

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

    PubMed

    Brown, Crystal E; Jecker, Nancy S; Curtis, J Randall

    2016-03-01

    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

  8. CXCR1 and CXCR2 haplotypes synergistically modulate cystic fibrosis lung disease.

    PubMed

    Kormann, Michael S D; Hector, Andreas; Marcos, Veronica; Mays, Lauren E; Kappler, Matthias; Illig, Thomas; Klopp, Norman; Zeilinger, Sonja; Carevic, Melanie; Rieber, Nikolaus; Eickmeier, Olaf; Zielen, Stefan; Gaggar, Amit; Moepps, Barbara; Griese, Matthias; Hartl, Dominik

    2012-06-01

    Cystic fibrosis (CF) lung disease severity is largely independent on the CF transmembrane conductance regulator (CFTR) genotype, indicating the contribution of genetic modifiers. The chemokine receptors CXCR1 and CXCR2 have been found to play essential roles in the pathogenesis of CF lung disease. Here, we determine whether genetic variation of CXCR1 and CXCR2 influences CF lung disease severity. Genomic DNA of CF patients in Germany (n = 442) was analysed for common variations in CXCR1 and CXCR2 using a single-nucleotide polymorphism (SNP) tagging approach. Associations of CXCR1 and CXCR2 SNPs and haplotypes with CF lung disease severity, CXCR1 and CXCR2 expression, and neutrophil effector functions were assessed. Four SNPs in CXCR1 and three in CXCR2 strongly correlated with age-adjusted lung function in CF patients. SNPs comprising haplotypes CXCR1_Ha and CXCR2_Ha were in high linkage disequilibrium and patients heterozygous for the CXCR1-2 haplotype cluster (CXCR1-2_Ha) had lower lung function compared with patients with homozygous wild-type alleles (forced expiratory volume in 1 s ≤ 70% predicted, OR 7.24; p = 2.30 × 10(-5)). CF patients carrying CXCR1-2_Ha showed decreased CXCR1 combined with increased CXCR2 mRNA and protein expression, and displayed disturbed antibacterial effector functions. CXCR1 and CXCR2 genotypes modulate lung function and antibacterial host defence in CF lung disease. PMID:22088968

  9. 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

  10. Influence of breathing pattern and lung inflation on impulse oscillometry measurements in horses.

    PubMed

    Van Erck, E; Votion, D; Kirschvink, N; Genicot, B; Lindsey, J; Art, T; Lekeux, P

    2004-11-01

    The objective of this paper was to determine if changes in ventilation patterns could influence the outcome of respiratory function measurements performed with our impulse oscillometry system (IOS) in horses. In a first study, IOS tests were performed in vitro on six isolated equine lungs. Lung inflation levels were controlled by modifying depressurisation inside an artificial thorax and different ventilation patterns were imposed. In a second in vivo study, transient variations in breathing pattern were evaluated both with the IOS and a current reference technique (CRT) in five healthy mature horses after an intravenous (i.v.) injection of lobeline hydrochloride. In both studies, respiratory rate (RR, range: 7-42 breaths/min.) and tidal volume (V(T), range: 0.4-25 L) had minor or no influence on IOS parameters. The influence of lung inflation, most marked for resistance at 5 Hz (R(5 Hz)), was limited for the considered physiological range. In vivo, statistical models indicated that maximal changes in pleural pressure (Max Delta Ppl) and peak flows were the main determinants of the variability of the resistance (R(rs)) and the reactance (X(rs)) of the respiratory system. The fourfold increase in baseline Max Delta Ppl and peak flows obtained during hyperpnoea caused a significant increase in R(rs) at 5 and 10 Hz and a decrease in X(rs) at all frequencies. We conclude that IOS parameters are not influenced by tachypnoea, but will reflect alterations in respiratory mechanics caused by hyperpnoeic breathing. PMID:15501143

  11. Lung hyperinflation in chronic obstructive pulmonary disease: mechanisms, clinical implications and treatment.

    PubMed

    Langer, Daniel; Ciavaglia, Casey E; Neder, J Alberto; Webb, Katherine A; O'Donnell, Denis E

    2014-12-01

    Lung hyperinflation is highly prevalent in patients with chronic obstructive pulmonary disease and occurs across the continuum of the disease. A growing body of evidence suggests that lung hyperinflation contributes to dyspnea and activity limitation in chronic obstructive pulmonary disease and is an important independent risk factor for mortality. In this review, we will summarize the recent literature on pathogenesis and clinical implications of lung hyperinflation. We will outline the contribution of lung hyperinflation to exercise limitation and discuss its impact on symptoms and physical activity. Finally, we will examine the physiological rationale and efficacy of selected pharmacological and non-pharmacological 'lung deflating' interventions aimed at improving symptoms and physical functioning. PMID:25159007

  12. 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

  13. Perseverant, non-indicated treatment of obese patients for obstructive lung disease

    PubMed Central

    2013-01-01

    Background Bronchodilators are a mainstay of treatment for patients with airflow obstruction. We hypothesized that patients with obesity and no objective documentation of airflow obstruction are inappropriately treated with bronchodilators. Methods Spirometric results and medical records of all patients with body mass index >30 kg/m2 who were referred for testing between March 2010 and August 2011 were analyzed. Results 155 patients with mean age of 52.6 ± (SE)1.1 y and BMI of 38.7 ± 0.7 kg/m2 were studied. Spirometry showed normal respiratory mechanics in 62 (40%), irreversible airflow obstruction in 36 (23.2%), flows suggestive of restriction in 35 (22.6%), reversible obstruction, suggestive of asthma in 11 (7.1%), and mixed pattern (obstructive and restrictive) in 6 (3.9%). Prior to testing, 45.2% (28 of 62) of patients with normal spirometry were being treated with medications for obstructive lung diseases and 33.9% (21 of 62) continued them despite absence of airflow obstruction on spirometry. 60% (21 of 35) of patients with a restrictive pattern in their spirometry received treatment for obstruction prior to spirometry and 51.4% (18 of 35) continued bronchodilator therapy after spirometric testing. There was no independent association of non-indicated treatment with spirometric results, age, BMI, co-morbidities or smoking history. All patients with airflow obstruction on testing who were receiving bronchodilators before spirometry continued to receive them after testing. Conclusion A substantial proportion of patients with obesity referred for pulmonary function testing did not have obstructive lung disease, but were treated nonetheless, before and after spirometry demonstrating absence of airway obstruction. PMID:24266961

  14. [Methods of nutritional assessment in chronic obstructive lung diseases].

    PubMed

    Doré, M F; Laaban, J P

    1999-06-01

    A poor nutritional state is often encountered in the course of chronic obstructive lung disease (COLD) and worsens the prognosis. The methods used to assess nutritional status proposed in the literature vary greatly. We detail here the methods used in clinical practice and in research, describing results obtained in patients with COLD. Appropriate routine tests are discussed. Body weight should be followed in this population, but weight loss may be masked by sodium-water retention. Bioelectric impedancemetry or biphotonic absorptiometry are used to define body composition in patients with COLD. Lean mass can be measured with the creatinine/height index but is difficult in the ambulatory patient. Plasma levels of visceral proteins are often normal and do not appear to be useful markers in these patients. Immunology tests (delayed hypersensitivity, total lymphocyte counts) are not sensitive screening tests. An evaluation of skeletal muscle function using the walking test or an exercise test is recommended before starting a renutrition program and to evaluate its efficacy. PMID:10486837

  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. PMID:12612311

  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. PMID:16337418

  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. 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.

  19. 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. PMID:24388365

  20. Effect of lung transplantation on diaphragmatic function in patients with chronic obstructive pulmonary disease.

    PubMed Central

    Wanke, T.; Merkle, M.; Formanek, D.; Zifko, U.; Wieselthaler, G.; Zwick, H.; Klepetko, W.; Burghuber, O. C.

    1994-01-01

    BACKGROUND--To date there are no data on the effects of lung transplantation on diaphragmatic function in patients with end stage chronic obstructive pulmonary disease (COPD). It is not known whether the relation between the transdiaphragmatic pressure (PDI) and lung volume is altered in recipients after transplantation as a result of changes in diaphragmatic structure caused by chronic hyperinflation. The effect of lung transplantation on diaphragmatic strength was determined in patients with COPD and the relation between postoperative PDI and lung volume analysed. METHODS--Diaphragmatic strength was assessed in eight double lung transplant recipients, six single lung transplant recipients, and in 14 patients with COPD whose lung function was similar to those of the transplant recipients preoperatively. PDI obtained during unilateral and bilateral phrenic nerve stimulation at 1 Hz (twitch PDI) at functional residual capacity (FRC) and during maximal sniff manoeuvres (sniff PDI) at various levels of inspiratory vital capacity (VCin) served as parameters for diaphragmatic strength. Sniff PDI assessed at the various VCin levels were used to analyse the PDI/lung volume relation. RESULTS--Lung transplantation caused a reduction in lung volume, especially in the double lung transplant recipients. As a consequence sniff PDI was higher in the double lung transplant recipients than in the patients with COPD at all levels of VCin analysed. However, sniff PDI values analysed at comparable intrathoracic gas volumes were not reduced in the patients with COPD when compared with those who underwent lung transplantation. Bilateral twitch PDI values were similar in the patients with COPD and in the lung transplant recipients. In the single lung transplant recipients unilateral twitch PDI values were similar on the transplanted and the non-transplanted side. The relation between PDI and lung volume was similar in the patients with COPD and in the lung transplant recipients

  1. Accumulation of BDCA1+ Dendritic Cells in Interstitial Fibrotic Lung Diseases and Th2-High Asthma

    PubMed Central

    Greer, Alexandra M.; Matthay, Michael A.; Kukreja, Jasleen; Bhakta, Nirav R.; Nguyen, Christine P.; Wolters, Paul J.; Woodruff, Prescott G.; Fahy, John V.; Shin, Jeoung-Sook

    2014-01-01

    Dendritic cells (DCs) significantly contribute to the pathology of several mouse lung disease models. However, little is known of the contribution of DCs to human lung diseases. In this study, we examined infiltration with BDCA1+ DCs of human lungs in patients with interstitial lung diseases or asthma. Using flow cytometry, we found that these DCs increased by 5∼6 fold in the lungs of patients with idiopathic pulmonary fibrosis or hypersensitivity pneumonitis, which are both characterized by extensive fibrosis in parenchyma. The same DC subset also significantly increased in the lung parenchyma of patients with chronic obstructive pulmonary disease, although the degree of increase was relatively modest. By employing immunofluorescence microscopy using FcεRI and MHCII as the specific markers for BDCA1+ DCs, we found that the numbers of BDCA1+ DCs also significantly increased in the airway epithelium of Th2 inflammation-associated asthma. These findings suggest a potential contribution of BDCA1+ DCs in human lung diseases associated with interstitial fibrosis or Th2 airway inflammation. PMID:24915147

  2. [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. PMID:26651932

  3. Different dietary patterns and reduction of lung cancer risk: A large case-control study in the U.S.

    PubMed Central

    Tu, Huakang; Heymach, John V.; Wen, Chi-Pang; Ye, Yuanqing; Pierzynski, Jeanne A.; Roth, Jack A.; Wu, Xifeng

    2016-01-01

    Reducing lung cancer risk by modifying diet is highly desirable. We investigated whether different U.S. dietary patterns were associated with lung cancer risk. Dietary patterns were derived using exploratory factor analysis for 2139 non-small cell lung cancer (NSCLC) cases and 2163 frequency-matched controls. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Highest adherence (highest vs. lowest quintile) to the “Tex-Mex”, “fruits and vegetables”, and “American/Western” patterns was associated with a 55% reduced (OR = 0.45; 95% CI = 0.37–0.56; P < 0.001), 32% reduced (OR = 0.68; 95% CI = 0.55–0.85; P = 0.001), and 45% increased (OR = 1.45; 95% CI = 1.18–1.78; P < 0.001) risk of lung cancer, respectively. The effects were stronger for squamous cell carcinoma and ever smokers for the “fruits and vegetables” pattern, and stronger for other non-small cell lung cancer and never smokers for the “American/Western” pattern. Among six genome-wide association (GWA) studies-identified lung cancer susceptibility loci assessed, a variant (rs2808630) of the C-reactive protein gene modified the associations for the “fruits and vegetables” (P for interaction = 0.03) and “American/Western” (P for interaction = 0.02) patterns. Our study first showed that the “Tex-Mex” dietary pattern was associated with a reduced lung cancer risk. Also, the “fruits and vegetables” and “American/Western” patterns affected lung cancer risk, and the effects were further modified by host genetic background. PMID:27230571

  4. Different dietary patterns and reduction of lung cancer risk: A large case-control study in the U.S.

    PubMed

    Tu, Huakang; Heymach, John V; Wen, Chi-Pang; Ye, Yuanqing; Pierzynski, Jeanne A; Roth, Jack A; Wu, Xifeng

    2016-01-01

    Reducing lung cancer risk by modifying diet is highly desirable. We investigated whether different U.S. dietary patterns were associated with lung cancer risk. Dietary patterns were derived using exploratory factor analysis for 2139 non-small cell lung cancer (NSCLC) cases and 2163 frequency-matched controls. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Highest adherence (highest vs. lowest quintile) to the "Tex-Mex", "fruits and vegetables", and "American/Western" patterns was associated with a 55% reduced (OR = 0.45; 95% CI = 0.37-0.56; P < 0.001), 32% reduced (OR = 0.68; 95% CI = 0.55-0.85; P = 0.001), and 45% increased (OR = 1.45; 95% CI = 1.18-1.78; P < 0.001) risk of lung cancer, respectively. The effects were stronger for squamous cell carcinoma and ever smokers for the "fruits and vegetables" pattern, and stronger for other non-small cell lung cancer and never smokers for the "American/Western" pattern. Among six genome-wide association (GWA) studies-identified lung cancer susceptibility loci assessed, a variant (rs2808630) of the C-reactive protein gene modified the associations for the "fruits and vegetables" (P for interaction = 0.03) and "American/Western" (P for interaction = 0.02) patterns. Our study first showed that the "Tex-Mex" dietary pattern was associated with a reduced lung cancer risk. Also, the "fruits and vegetables" and "American/Western" patterns affected lung cancer risk, and the effects were further modified by host genetic background. PMID:27230571

  5. 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.

  6. Genome-scale long noncoding RNA expression pattern in squamous cell lung cancer

    PubMed Central

    Wang, Ying; Qian, Chen-Yue; Li, Xiang-Ping; Zhang, Yu; He, Hui; Wang, Jing; Chen, Juan; Cui, Jia-Jia; Liu, Rong; Zhou, Hui; Xiao, Lin; Xu, Xiao-Jing; Zheng, Yi; Fu, Yi-Lan; Chen, Zi-Yu; Chen, Xiang; Zhang, Wei; Ye, Cheng-Cheng; Zhou, Hong-Hao; Yin, Ji-Ye; Liu, Zhao-Qian

    2015-01-01

    In this study, we aimed to explore the long noncoding RNA expression pattern in squamous cell lung cancer (SQCC) on a genome-wide scale. Total RNAs were extracted from 16 lung SQCC patients’ normal and matched lung cancer tissues by Trizol reagent. The expression level of genome-wide scale lncRNA and mRNA was determined by microarray. qRT-PCR was used to validate the lncRNA expression level in 47 patients. Data analyses were performed using R and Bioconductor. A total of 2,748 up and 852 down regulated probes were identified to be significantly and differentially expressed in tumor tissues. The annotation result of their co-expressed mRNAs showed that the most significantly related category of GO analysis was development and differentiation, while the most significantly related pathway was cell cycle. Subgroup analysis identified that 46 and 18 probes were specifically differentially expressed in smoking and moderately differentiated tumors, respectively. Our study indicated that clusters of lncRNAs were significantly and differentially expressed in SQCC compared with normal tissues in the same subject. They may exert a significant role in lung cancer development and could be potential targets for future treatment of SQCC. PMID:26159226

  7. Extracting regional brain patterns for classification of neurodegenerative diseases

    NASA Astrophysics Data System (ADS)

    Pulido, Andrea; Rueda, Andrea; Romero, Eduardo

    2013-11-01

    In structural Magnetic Resonance Imaging (MRI), neurodegenerative diseases generally present complex brain patterns that can be correlated with di erent clinical onsets of this pathologies. An objective method that aims to determine both global and local changes is not usually available in clinical practice, thus the interpretation of these images is strongly dependent on the radiologist's skills. In this paper, we propose a strategy which interprets the brain structure using a framework that highlights discriminant brain patterns for neurodegenerative diseases. This is accomplished by combining a probabilistic learning technique, which identi es and groups regions with similar visual features, with a visual saliency method that exposes relevant information within each region. The association of such patterns with a speci c disease is herein evaluated in a classi cation task, using a dataset including 80 Alzheimer's disease (AD) patients and 76 healthy subjects (NC). Preliminary results show that the proposed method reaches a maximum classi cation accuracy of 81.39%.

  8. 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. PMID:25957294

  9. Older Adults with Chronic Lung Disease Report Less Limitation Compared with Younger Adults with Similar Lung Function Impairment

    PubMed Central

    Han, Meilan K.; Thompson, Bruce; Limper, Andrew H.; Martinez, Fernando J.; Schwarz, Marvin I.; Sciurba, Frank C.; Criner, Gerald J.; Wise, Robert A.

    2015-01-01

    Rationale: Disability guidelines are often based on pulmonary function testing, but factors other than lung function influence how an individual experiences physiologic impairment. Age may impact the perception of impairment in adults with chronic lung disease. Objectives: To determine if self-report of physical functional impairment differs between older adults with chronic lung disease compared with younger adults with similar degrees of lung function impairment. Methods: The Lung Tissue Research Consortium provided data on 981 participants with chronic obstructive pulmonary disease and interstitial lung disease who were well characterized with clinical, radiological, and pathological diagnoses. We used multiple logistic regression to determine if responses to health status questions (from the Short Form-12 and St. George’s Respiratory Questionnaire) related to perception of impairment differed in older adults (age ≥ 65 yr, n = 427) compared with younger adults (age < 65 yr, n = 393). Measurements and Main Results: Pulmonary function was higher in older adults (median FEV1 %, 70) compared with younger adults (median FEV1 %, 62) (P < 0.001), whereas the median 6-minute-walk distance was similar between groups (372 m vs. 388 m, P = 0.21). After adjusting for potential confounders, older adults were less likely to report that their health limited them significantly in performing moderate activities (odds ratio [OR], 0.36; 95% confidence interval [CI], 0.22–0.58) or climbing several flights of stairs (OR, 0.51; 95% CI, 0.34–0.77). The odds of reporting that their physical health limited the kinds of activities they performed were reduced by 63% in older adults (OR, 0.37; 95% CI, 0.24–0.58), and, similarly, the odds of reporting that their health caused them to accomplish less than they would like were also lower in older adults (OR, 0.39; 95% CI, 0.25–0.60). The OR for reporting that their breathing problem stops them from doing most

  10. Cured Meat Consumption, Lung Function, and Chronic Obstructive Pulmonary Disease among United States Adults

    PubMed Central

    Jiang, Rui; Paik, David C.; Hankinson, John L.; Barr, R. Graham

    2007-01-01

    Rationale: Cured meats are high in nitrites. Nitrites generate reactive nitrogen species that may cause nitrative and nitrosative damage to the lung resulting in emphysema. Objective: To test the hypothesis that frequent consumption of cured meats is associated with lower lung function and increased odds of chronic obstructive pulmonary disease (COPD). Methods: Cross-sectional study of 7,352 participants in the Third National Health and Nutrition Examination Survey, 45 years of age or more, who had adequate measures of cured meat, fish, fruit, and vegetable intake, and spirometry. Results: After adjustment for age, smoking, and multiple other potential confounders, frequency of cured meat consumption was inversely associated with FEV1 and FEV1/FVC but not FVC. The adjusted differences in FEV1 between individuals who did not consume cured meats and those who consumed cured meats 1 to 2, 3 to 4, 5 to 13, and 14 or more times per month were −37.6, −11.5, −42.0, and −110 ml, respectively (p for trend < 0.001). Corresponding differences for FEV1/FVC were −0.91, −0.54, −1.13, and −2.13% (p for trend = 0.001). These associations were not modified by smoking status. The multivariate odds ratio for COPD (FEV1/FVC ⩽ 0.7 and FEV1 < 80% predicted) was 1.78 (95% confidence interval, 1.29–2.47) comparing the highest with the lowest category of cured meat consumption. The corresponding odds ratios for mild, moderate, and severe COPD were 1.11, 1.46, and 2.41, respectively. Conclusions: Frequent cured meat consumption was associated independently with an obstructive pattern of lung function and increased odds of COPD. Additional studies are required to determine if cured meat consumption is a causal risk factor for COPD. PMID:17255565

  11. Castleman's disease presenting in the lungs: A report of two cases

    PubMed Central

    CAO, WEIJUN; LIANG, SHUO; LIU, JINMING; BAI, JIUWU; LI, HUIPING

    2015-01-01

    Castleman's disease (CD) is a rare disease that most commonly occurs in the mediastinum. The lung is a rare site in which CD may occur. The current study reported 2 cases of CD localized in the lungs. Computed tomography imaging identified a high-density mass in the lungs of the two patients. Biopsy and pathological examinations indicated that one case presented features of two CD types (hyaline-vascular and plasma cell types), while the other case suffered from multicentric CD. The present study highlighted the typical clinical features of CD in the lungs. In addition, it is proposed that a diagnosis of CD should be considered for certain patients with masses in the lungs, and a biopsy should be performed to facilitate diagnosis and treatment. PMID:26622622

  12. Spectrum of Smoking-related Lung Diseases: Imaging Review and Update.

    PubMed

    Madan, Rachna; Matalon, Shanna; Vivero, Marina

    2016-03-01

    There is increased awareness of smoking-related lung diseases other than lung cancer and chronic obstructive pulmonary disease. Concurrently, there is general acceptance that there is difficulty in establishing a specific diagnosis of smoking-related interstitial lung disease (ILD), as many patients may not undergo biopsy to facilitate a specific histopathologic diagnosis. Cases that do proceed to biopsy may demonstrate multiple abnormalities, and histologic overlap between different disease processes may confound the picture. This review outlines the key aspects of smoking-related lung disease, including entities secondary to smoking-related lung inflammation such as respiratory bronchiolitis-ILD, desquamative idiopathic pneumonia, and pulmonary Langerhans cell histiocytosis, as well as chronic fibrosing lung diseases strongly associated with cigarette smoke including idiopathic pulmonary fibrosis, combined pulmonary fibrosis and emphysema, nonspecific interstitial pneumonia, and rheumatoid arthritis-ILD. The focus will be on incorporation of clinical findings, key pulmonary function testing parameters, high-resolution computer tomography (HRCT) findings, and pathologic correlates in refining the differential diagnosis and differentiating between the various entities. PMID:26479130

  13. The importance of balanced pro-inflammatory and anti-inflammatory mechanisms in diffuse lung disease

    PubMed Central

    Keane, Michael P; Strieter, Robert M

    2002-01-01

    The lung responds to a variety of insults in a remarkably consistent fashion but with inconsistent outcomes that vary from complete resolution and return to normal to the destruction of normal architecture and progressive fibrosis. Increasing evidence indicates that diffuse lung disease results from an imbalance between the pro-inflammatory and anti-inflammatory mechanisms, with a persistent imbalance that favors pro-inflammatory mediators dictating the development of chronic diffuse lung disease. This review focuses on the mediators that influence this imbalance. PMID:11806840

  14. Autotaxin-LPA receptor axis in the pathogenesis of lung diseases

    PubMed Central

    Chu, Xiangpeng; Wei, Xiaojie; Lu, Shaolin; He, Peijian

    2015-01-01

    Lysophosphatidic acid (LPA) is a small lipid which mediates a variety of cellular functions via the activation of LPA receptors. LPA is generated from lysophosphatidylcholine by the extracellular enzyme, autotaxin (ATX). Elevated ATX expression, LPA production and their signaling pathways have been reported in multiple pathological conditions of lung tissue, including inflammation, fibrosis and cancer. Emerging evidence has highlighted the importance of ATX and LPA receptors in the pathogenesis of lung diseases. Here, we briefly review the current knowledge of different roles of the ATX-LPA receptor axis in lung diseases focusing on inflammation, fibrosis and cancer. PMID:26770305

  15. Digging our own graves: coal miners and the struggle over black lung disease. Doctoral thesis (final)

    SciTech Connect

    Smith, B.E.

    1981-05-01

    The report analyzes the controversy over black lung disease among U.S. coal miners, situated within the recent struggle over industrial relations in bituminous coal. Summaries of the postwar coal industry and the changing medical approach to black lung provide the historical backdrop to the recent controversy. The development of the black lung movement is reconstructed primarily through material from oral interviews with its participants. The movement is viewed essentially as a class conflict between miners and operators over who would bear the burden of occupational disease: miners, by continuing to be disabled and without compensation; or the operators, by reducing dust levels in the mines and financing benefits for disabled workers.

  16. 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

  17. BPIFB1 (LPLUNC1) is upregulated in cystic fibrosis lung disease.

    PubMed

    Bingle, Lynne; Wilson, Kirsty; Musa, Maslinda; Araujo, Bianca; Rassl, Doris; Wallace, William A; LeClair, Elizabeth E; Mauad, Thais; Zhou, Zhe; Mall, Marcus A; Bingle, Colin D

    2012-11-01

    Although the biology the PLUNC (recently renamed BPI fold, BPIF) family of secreted proteins is poorly understood, multiple array based studies have suggested that some are differentially expressed in lung diseases. We have examined the expression of BPIFB1 (LPLUNC1), the prototypic two-domain containing family member, in lungs from CF patients and in mouse models of CF lung disease. BPIFB1 was localized in CF lung samples along with BPIFA1, MUC5AC, CD68 and NE and directly compared to histologically normal lung tissues and that of bacterial pneumonia. We generated novel antibodies to mouse BPIF proteins to conduct similar studies on ENaC transgenic (ENaC-Tg) mice, a model for CF-like lung disease. Small airways in CF demonstrated marked epithelial staining of BPIFB1 in goblet cells but staining was absent from alveolar regions. BPIFA1 and BPIFB1 were not co-localised in the diseased lungs. In ENaC-Tg mice there was strong staining of both proteins in the airways and luminal contents. This was most marked for BPIFB1 and was noted within 2 weeks of birth. The two proteins were present in distinct cells within epithelium. BPIFB1 was readily detected in BAL from ENaC-Tg mice but was absent from wild-type mice. Alterations in the expression of BPIF proteins is associated with CF lung disease in humans and mice. It is unclear if this elevation of protein production, which results from phenotypic alteration of the cells within the diseased epithelium, plays a role in the pathogenesis of the disease. PMID:22767025

  18. 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

  19. 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

    2016-05-01

    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. PMID:26953657

  20. Spatial and Temporal Emergence Pattern of Lyme Disease in Virginia

    PubMed Central

    Li, Jie; Kolivras, Korine N.; Hong, Yili; Duan, Yuanyuan; Seukep, Sara E.; Prisley, Stephen P.; Campbell, James B.; Gaines, David N.

    2014-01-01

    The emergence of infectious diseases over the past several decades has highlighted the need to better understand epidemics and prepare for the spread of diseases into new areas. As these diseases expand their geographic range, cases are recorded at different geographic locations over time, making the analysis and prediction of this expansion complicated. In this study, we analyze spatial patterns of the disease using a statistical smoothing analysis based on areal (census tract level) count data of Lyme disease cases in Virginia from 1998 to 2011. We also use space and space–time scan statistics to reveal the presence of clusters in the spatial and spatiotemporal distribution of Lyme disease. Our results confirm and quantify the continued emergence of Lyme disease to the south and west in states along the eastern coast of the United States. The results also highlight areas where education and surveillance needs are highest. PMID:25331806

  1. Relationship Between Lung Function Impairment and Health-Related Quality of Life in COPD and Interstitial Lung Disease

    PubMed Central

    Berry, Cristine E.; Drummond, M. Bradley; Han, MeiLan K.; Li, Daner; Fuller, Cathy; Limper, Andrew H.; Martinez, Fernando J.; Schwarz, Marvin I.; Sciurba, Frank C.

    2012-01-01

    Background: Health-related quality-of-life (HRQL) measures have been correlated with lung function in patients with COPD and interstitial lung disease (ILD). However, different pathophysiologic mechanisms may influence how these distinct diseases affect HRQL, resulting in differing HRQL by pulmonary diagnosis among patients with similar severity of ventilatory impairment. Methods: The National Heart, Lung, and Blood Institute Lung Tissue Research Consortium provided data on well-characterized participants with COPD (n = 576) and ILD (n = 405) at four clinical sites. Using multiple linear regression, we examined the effects of FEV1 (% predicted) and diagnosis (ILD vs COPD) on HRQL scores, including total St. George Respiratory Questionnaire (SGRQ) scores and Short Form-12 (SF-12) physical component summary (PCS) and mental component summary (MCS) scores. Results: Participants with ILD had, on average, higher SGRQ scores (15.33 points; 95% CI, 12.46-18.19; P <.001) and lower SF-12 PCS scores ( − 4.73 points; 95% CI, − 6.31 to − 3.14; P <.001) compared with patients with COPD with similar FEV1 % predicted values, indicating worse HRQL. The specific diagnosis also modified the effect of FEV1 on the total SGRQ score (P = .003) and the SF-12 PCS score (P = .03). There was no relationship between lung function and SF-12 MCS scores. Conclusions: HRQL scores were worse for patients with ILD compared with patients with COPD with similar degrees of ventilatory impairment. Differences in dyspnea mechanism or in the rate of disease progression may account for these differences in HRQL. PMID:22576634

  2. The emerging role of myeloid-derived suppressor cells in lung diseases.

    PubMed

    Kolahian, Saeed; Öz, Hasan Halit; Zhou, Benyuan; Griessinger, Christoph M; Rieber, Nikolaus; Hartl, Dominik

    2016-03-01

    Myeloid-derived suppressor cells (MDSCs) are innate immune cells characterised by their potential to control T-cell responses and to dampen inflammation. While the role of MDSCs in cancer has been studied in depth, our understanding of their relevance for infectious and inflammatory disease conditions has just begun to evolve. Recent studies highlight an emerging and complex role for MDSCs in pulmonary diseases. In this review, we discuss the potential contribution of MDSCs as biomarkers and therapeutic targets in lung diseases, particularly lung cancer, tuberculosis, chronic obstructive pulmonary disease, asthma and cystic fibrosis. PMID:26846830

  3. Interactive high-resolution computed tomography digital atlas of interstitial lung disease.

    PubMed

    Walker, Christopher M; Chung, Jonathan H; Wall, Corey; Pipavath, Sudhakar N; Chapman, Teresa; Reddy, Gautham P; Stern, Eric J; Godwin, J David; Weinberger, Ed

    2011-11-01

    High-resolution computed tomography is a necessary tool used in the diagnosis of interstitial lung disease. The interpretation of high-resolution computed tomography can be difficult given the wide spectrum of imaging appearances within the same disease and among different diseases. The authors provide a new educational method to learn about the spectrum of idiopathic interstitial lung disease through the use of a free online digital atlas and review article. This atlas can be downloaded at http://www.seattlechildrens.org/radiologyeducation/ILD. PMID:21889896

  4. Peribronchiolar metaplasia: a common histologic lesion in diffuse lung disease and a rare cause of interstitial lung disease: clinicopathologic features of 15 cases.

    PubMed

    Fukuoka, Junya; Franks, Teri J; Colby, Thomas V; Flaherty, Kevin R; Galvin, Jeffrey R; Hayden, Dennis; Gochuico, Bernadette R; Kazerooni, Ella A; Martinez, Fernando; Travis, William D

    2005-07-01

    Peribronchiolar metaplasia (PBM) is a histologic lesion consisting of peribronchiolar metaplasia (PBM) of bronchiolar-type epithelium. Although widely recognized, PBM has received little attention in the pathologic literature and is not known to have clinical significance. We identified 15 cases in which PBM was the only major histologic finding in surgical lung biopsies from patients with interstitial lung disease (PBM-ILD), and we reviewed the clinical, imaging, and pathologic findings. The mean age was 57 years (range, 44-74 years) with 13 females and 2 males. One patient had been a welder with fume and asbestos exposure; another had pigeon exposure. Smoking history was available for 13 patients: three current smokers, one cocaine user, two former smokers, and seven never smokers. Three patients had collagen vascular disease. One had elevated serum antinuclear antibody titers. Pulmonary function data were available for 10 patients: one obstructive, five restrictive, two mixed obstructive and restrictive, and two normal. Computerized tomography in 7 patients showed mosaic attenuation in 3 patients and air trapping in 1 patient; no bronchiectasis, septal lines, or honeycombing were seen in any cases. All 11 patients with available follow-up are alive; 4 of them have experienced symptomatic improvement (follow-up, 0.6-6.9 years; mean, 2.4 years). PBM was found focally in other interstitial lung diseases, which were assessed for this lesion: 59% of usual interstitial pneumonia (17 of 29), 50% of nonspecific interstitial pneumonia (10 of 20), desquamative interstitial pneumonia (3 of 6), hypersensitivity pneumonitis (9 of 18), and 11% of respiratory bronchiolitis (2 of 18). In summary, PBM is a common histologic finding in various interstitial lung disorders. It is rarely the sole major lung biopsy finding in patients presenting with interstitial lung disease (PBM-ILD). Patients are mostly older women, with mild symptoms and CT findings. Survival appears to be

  5. 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

  6. Iodine-131 uptake in inflammatory lung disease: a potential pitfall in treatment of thyroid carcinoma

    SciTech Connect

    Hoeschl, R.C.; Choy, D.H.; Gandevia, B.

    1988-05-01

    A mixed differentiated thyroid carcinoma was found in a small asymptomatic nodule in a 44-yr-old woman with recurrent chest infections and bronchiectasis. After total thyroidectomy and 162 mCi (6 GBq) radioiodine ablation there was uptake in the thyroid remnant and in both lungs, interpreted as lung metastases. In 2 years she received further three 162 mCi (6 GBq) doses of /sup 131/I, as scans showed very similar lung activity. Another scan, during thyroxin suppression, showed again activity in the lungs. A 47-yr-old male patient with similar respiratory disease and no history of thyroid disorder volunteered to undergo radioiodine scan while on triiodothyronine suppression. His scan, too, showed concentration in the lungs. The female patient died 7 years after the diagnosis of lung thyroid metastases was made. No metastasis was found at autopsy. Radioiodine lung uptake may occur in patients with chronic inflammatory lung disease, presenting a potential diagnostic pitfall in patients with differentiated thyroid carcinoma.

  7. Clinical impacts of a micropapillary pattern in lung adenocarcinoma: a review

    PubMed Central

    Cao, Ying; Zhu, Li-Zhen; Jiang, Meng-Jie; Yuan, Ying

    2016-01-01

    Lung adenocarcinoma with a micropapillary pattern (MPPAC) has recently drawn increased attention among researchers. Micropapillary-predominant adenocarcinoma (MPA), which is defined by micropapillary pattern (MPP), is the primary histological pattern observed semiquantitatively in 5% increments on resection specimens, and MPA was formally determined to be a new histological subtype according to the new multidisciplinary classification in 2011. According to published studies, MPPAC is most common in males and nonsmokers and is associated with lymphatic invasion, pleural invasion, and lymph node metastases. MPPAC often presents as part-solid and lobulated nodules in computed tomography scans. MPP tends to have a higher maximum standardized uptake value as determined by fluorodeoxyglucose positron emission tomography combined with computed tomography, indicating a high risk of recurrence. Molecular markers, including vimentin, napsin A, phosphorylated c-Met, cytoplasmic maspin, Notch-1, MUC1, and tumoral CD10, may have higher expression in MPPAC than other subtypes; conversely, markers such as MUC4 and surfactant apoprotein A have lower expression in MPPAC. MPPAC with EGFR mutations can benefit from treatment with EGFR tyrosine kinase inhibitors. Furthermore, a complete lobectomy may be more suitable than limited resection for MPPAC because of the low sensitivity of intraoperative frozen sections and the high risk of lymph node metastasis. MPA benefits more from adjuvant chemotherapy than do other histological subtypes, whereas MPA does not benefit from adjuvant radiotherapy. Of note, MPP is associated with poor prognosis in early-stage lung adenocarcinoma, but the prognostic value of MPP is controversial in advanced-stage lung adenocarcinoma. PMID:26770064

  8. Characteristic features of tacrolimus-induced lung disease in rheumatoid arthritis patients.

    PubMed

    Sasaki, Takanori; Nakamura, Wataru; Inokuma, Shigeko; Matsubara, Erika

    2016-02-01

    This paper aims to study the background and clinical characteristics of tacrolimus (TAC)-induced lung disease. A case of a rheumatoid arthritis (RA) patient who developed TAC-induced interstitial lung disease (TAC-ILD) is reported. The Japanese Pharmaceuticals and Medical Devices Agency (PMDA) website was searched for cases of TAC-ILD and its prevalence among all cases of TAC-related adverse events. As for cases of TAC-ILD, its underlying disease, preexisting lung diseases, and fatal outcome were also searched. Literature review of TAC-ILD cases was added. A 65-year-old female RA patient with preexisting bronchiectasis developed near-fatal TAC-ILD. Amelioration of RA, ground-glass opacities in the upper, anterior, and central lung fields, and decrease in peripheral blood lymphocyte count were the major findings in this patient. A search of the PMDA website revealed the following: the prevalence of TAC-ILD was 3 % of all cases of TAC-related adverse events, 56 out of 85 RA cases (66 %), and one out of 15 other cases had a preexisting lung disease; the prevalences of fatal outcome in RA and other cases were 24 and 38 %, respectively. A few cases in the literature had preexisting ILD and developed diffuse alveolar damage. In our case, preexisting bronchiectasis, arthritis remission, newly developed ground-glass opacities (GGOs) in the upper, anterior, and central lung fields, and decrease in peripheral blood lymphocyte count were the major findings. From the search of the PMDA website, about one fourth of the cases with TAC-related lung injury had a fatal outcome, and among RA patients, two thirds had preexisting lung diseases. PMID:25644583

  9. 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. PMID:27136656

  10. 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

  11. Cystic fibrosis pigs develop lung disease and exhibit defective bacterial eradication at birth.

    PubMed

    Stoltz, David A; Meyerholz, David K; Pezzulo, Alejandro A; Ramachandran, Shyam; Rogan, Mark P; Davis, Greg J; Hanfland, Robert A; Wohlford-Lenane, Chris; Dohrn, Cassie L; Bartlett, Jennifer A; Nelson, George A; Chang, Eugene H; Taft, Peter J; Ludwig, Paula S; Estin, Mira; Hornick, Emma E; Launspach, Janice L; Samuel, Melissa; Rokhlina, Tatiana; Karp, Philip H; Ostedgaard, Lynda S; Uc, Aliye; Starner, Timothy D; Horswill, Alexander R; Brogden, Kim A; Prather, Randall S; Richter, Sandra S; Shilyansky, Joel; McCray, Paul B; Zabner, Joseph; Welsh, Michael J

    2010-04-28

    Lung disease causes most of the morbidity and mortality in cystic fibrosis (CF). Understanding the pathogenesis of this disease has been hindered, however, by the lack of an animal model with characteristic features of CF. To overcome this problem, we recently generated pigs with mutated CFTR genes. We now report that, within months of birth, CF pigs spontaneously developed hallmark features of CF lung disease, including airway inflammation, remodeling, mucus accumulation, and infection. Their lungs contained multiple bacterial species, suggesting that the lungs of CF pigs have a host defense defect against a wide spectrum of bacteria. In humans, the temporal and causal relations between inflammation and infection have remained uncertain. To investigate these processes, we studied newborn pigs. Their lungs showed no inflammation but were less often sterile than controls. Moreover, after introduction of bacteria into their lungs, pigs with CF failed to eradicate bacteria as effectively as wild-type pigs. These results suggest that impaired bacterial elimination is the pathogenic event that initiates a cascade of inflammation and pathology in CF lungs. Our finding that pigs with CF have a host defense defect against bacteria within hours of birth provides an opportunity to further investigate CF pathogenesis and to test therapeutic and preventive strategies that could be deployed before secondary consequences develop. PMID:20427821

  12. Vitamin d and susceptibility of chronic lung diseases: role of epigenetics.

    PubMed

    Sundar, Isaac K; Rahman, Irfan

    2011-01-01

    Vitamin D deficiency is linked to accelerated decline in lung function, increased inflammation, and reduced immunity in chronic lung diseases. Epidemiological studies have suggested that vitamin D insufficiency is associated with low lung function in susceptible subjects who are exposed to higher levels of environmental agents (airborne particulates). Recent studies have highlighted the role of vitamin D and vitamin D receptor (VDR) in regulation of several genes that are involved in inflammation, immunity, cellular proliferation, differentiation, and apoptosis. Vitamin D has also been implicated in reversal of steroid resistance and airway remodeling, which are the hallmarks of chronic obstructive pulmonary disease (COPD) and severe asthma. VDR protein level is decreased in lungs of patients with COPD. VDR deficient mice develop an abnormal lung phenotype with characteristics of COPD, such as airspace enlargement and decline in lung function associated with increased lung inflammatory cellular influx, and immune-lymphoid aggregates formation. Dietary vitamin D may regulate epigenetic events, in particular on genes which are responsible for COPD susceptibility. Active metabolite of vitamin D, 1,25-dihydroxyvitamin D(3) plays an essential role in cellular metabolism and differentiation via its nuclear receptor (VDR) that cooperates with several other chromatin modification enzymes (histone acetyltransferases and histone deacetylases), thereby mediating complex epigenetic events in vitamin D signaling and metabolism. This review provides an update on the current knowledge and understanding on vitamin D, and susceptibility of chronic lung diseases in relation to the possible role of epigenetics in its molecular action. Understanding the molecular epigenetic mechanism of vitamin D/VDR would provide rationale for dietary vitamin D-mediated intervention in prevention and management of chronic lung diseases linked with vitamin D deficiency. PMID:21941510

  13. 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 Central

    Vande Velde, Greetje; Poelmans, Jennifer; De Langhe, Ellen; Hillen, Amy; Vanoirbeek, Jeroen; Himmelreich, Uwe; Lories, Rik J.

    2016-01-01

    ABSTRACT 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

  14. CDC42 is required for structural patterning of the lung during development.

    PubMed

    Wan, Huajing; Liu, Caijun; Wert, Susan E; Xu, Wei; Liao, Yong; Zheng, Yi; Whitsett, Jeffrey A

    2013-02-01

    The formation of highly branched epithelial structures is critical for the development of many essential organs, including lung, liver, pancreas, kidney and mammary glands. Elongation and branching of these structures require precise control of complex morphogenetic processes that are dependent upon coordinate regulation of cell shape, apical-basal polarity, proliferation, migration, and interactions among multiple cell types. Herein, we demonstrate that temporal-spatial regulation of epithelial cell polarity by the small GTPase, CDC42, is essential for branching morphogenesis of the developing lung. Epithelial cell-specific deletion of CDC42 in fetal mice disrupted epithelial cell polarity, the actin cytoskeleton, intercellular contacts, directional trafficking of proteins, proliferation and mitotic spindle orientation, impairing the organization and patterning of the developing respiratory epithelium and adjacent mesenchyme. Transition from a pseudostratified to a simple columnar epithelium was impaired, consistent with coordinate dysregulation of epithelial cell polarity, mitotic spindle orientation, and repositioning of mitotic cells within the epithelium during cell cycle progression. Expression of sonic hedgehog and its receptor, patched-1, was decreased, while fibroblast growth factor 10 expression in the mesenchyme was expanded, resulting in disruption of branching morphogenesis and bronchiolar smooth muscle formation in this model. CDC42 is required for spatial positioning of proliferating epithelial cells, as well as signaling interactions between the epithelium and mesenchyme and is, therefore, essential for formation and maintenance of the respiratory tract during morphogenesis of the fetal lung. PMID:23219958

  15. CDC42 is Required for Structural Patterning of the Lung During Development

    PubMed Central

    Wan, Huajing; Liu, Caijun; Wert, Susan E.; Wei, Xu; Liao, Yong; Zheng, Yi; Whitsett, Jeffrey A.

    2012-01-01

    The formation of highly branched epithelial structures is critical for the development of many essential organs, including lung, liver, pancreas, kidney and mammary glands. Elongation and branching of these structures require precise control of complex morphogenetic processes that are dependent upon coordinate regulation of cell shape, apical-basal polarity, proliferation, migration, and interactions among multiple cell types. Herein, we demonstrate that temporal-spatial regulation of epithelial cell polarity by the small GTPase, CDC42, is essential for branching morphogenesis of the developing lung. Epithelial cell-specific deletion of CDC42 in fetal mice disrupted epithelial cell polarity, the actin cytoskeleton, intercellular contacts, directional trafficking of proteins, proliferation and mitotic spindle orientation, impairing the organization and patterning of the developing respiratory epithelium and adjacent mesenchyme. Transition from a pseudostratified to a simple columnar epithelium was impaired, consistent with coordinate dysregulation of epithelial cell polarity, mitotic spindle orientation, and repositioning of mitotic cells within the epithelium during cell cycle progression. Expression of sonic hedgehog and its receptor, patched-1, was decreased, while fibroblast growth factor 10 expression in the mesenchyme was expanded, resulting in disruption of branching morphogenesis and bronchiolar smooth muscle formation in this model. CDC42 is required for spatial positioning of proliferating epithelial cells, as well as signaling interactions between the epithelium and mesenchyme and is, therefore, essential for formation and maintenance of the respiratory tract during morphogenesis of the fetal lung. PMID:23219958

  16. 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

  17. Scintigraphic patterns of veno-occlusive disease in liver transplantation.

    PubMed

    Bernstine, Hanna; Mor, Eytan; Ben Ari, Ziv; Belinki, Alexander; Hardoff, Ruth

    2004-05-01

    Venous vascular complications in liver transplant recipients are rare. Diagnosis is usually based on clinical criteria and typical findings on liver biopsy. The scintigraphic patterns of posttransplant liver veno-occlusive disease are described, and the value of follow-up studies is suggested. The authors present 2 patients who developed posttransplantation hepatic veno-occlusive disease. The first patient had a severe form of the disease and a fatal outcome. The second patient had a mild to moderate form of this disorder with complete resolution following treatment. PMID:15069326

  18. Nitric oxide synthase polymorphisms, gene expression and lung function in chronic obstructive pulmonary disease

    PubMed Central

    2013-01-01

    Background Due to the pleiotropic effects of nitric oxide (NO) within the lungs, it is likely that NO is a significant factor in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of this study was to test for association between single nucleotide polymorphisms (SNPs) in three NO synthase (NOS) genes and lung function, as well as to examine gene expression and protein levels in relation to the genetic variation. Methods One SNP in each NOS gene (neuronal NOS (NOS1), inducible NOS (NOS2), and endothelial NOS (NOS3)) was genotyped in the Lung Health Study (LHS) and correlated with lung function. One SNP (rs1800779) was also analyzed for association with COPD and lung function in four COPD case–control populations. Lung tissue expression of NOS3 mRNA and protein was tested in individuals of known genotype for rs1800779. Immunohistochemistry of lung tissue was used to localize NOS3 expression. Results For the NOS3 rs1800779 SNP, the baseline forced expiratory volume in one second in the LHS was significantly higher in the combined AG + GG genotypic groups compared with the AA genotypic group. Gene expression and protein levels in lung tissue were significantly lower in subjects with the AG + GG genotypes than in AA subjects. NOS3 protein was expressed in the airway epithelium and subjects with the AA genotype demonstrated higher NOS3 expression compared with AG and GG individuals. However, we were not able to replicate the associations with COPD or lung function in the other COPD study groups. Conclusions Variants in the NOS genes were not associated with lung function or COPD status. However, the G allele of rs1800779 resulted in a decrease of NOS3 gene expression and protein levels and this has implications for the numerous disease states that have been associated with this polymorphism. PMID:24192154

  19. Update on host-pathogen interactions in cystic fibrosis lung disease.

    PubMed

    Hector, Andreas; Frey, Nina; Hartl, Dominik

    2016-12-01

    Bacterial and fungal infections are hallmarks of cystic fibrosis (CF) lung disease. In the era of long-term inhaled antibiotics and increasing CF patient survival, new "emerging" pathogens are detected in CF airways, yet their pathophysiological disease relevance remains largely controversial and incompletely defined. As a response to chronic microbial triggers, innate immune cells, particularly neutrophils, are continuously recruited into CF airways where they combat pathogens but also cause tissue injury through release of oxidants and proteases. The coordinated interplay between host immune cell activation and pathogens is essential for the outcome of CF lung disease. Here, we provide a concise overview and update on host-pathogen interactions in CF lung disease. PMID:26905568

  20. Mortality from lung cancer and chronic obstructive pulmonary disease in New Mexico, 1958-82.

    PubMed Central

    Samet, J M; Wiggins, C L; Key, C R; Becker, T M

    1988-01-01

    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. PMID:3407816

  1. [50 years WATL (Scientific Working Group for the Therapy of Lung Diseases)].

    PubMed

    Wirtz, H; Kropp, R; Behr, J; Costabel, U; Bonnet, R; Schönfeld, N; Prasse, A; Kardos, P; Seehausen, V; Loddenkemper, R

    2014-03-01

    On the occasion of the 50th anniversary of the Scientific Working Group for the Therapy of Lung Diseases (WATL) the history is described from its foundation to the present situation. Research topics during this long period are specified and the studies are briefly outlined. In the beginning, WATL was engaged mainly in studies on tuberculosis, later on, the spectrum of WATL was broadened considerably to diseases like sarcoidosis, pulmonary Langerhans' cell histiocytosis, pulmonary emphysema due to α1-antitrypsin deficiency, chronic obstructive bronchitis and bronchial asthma as well as nontuberculous mycobacterioses. Finally, realising that the methodological capabilities of WATL were not sufficient to conduct large trials in classical lung diseases considering current requirements, WATL has begun to acquire competence in rare lung diseases such as lymphangioleiomyomatosis and alveolar proteinosis. In addition, WATL is dedicated to educative aims by organising conferences on topics which are not part of main stream respiratory medicine. PMID:24595854

  2. Exercise testing and training in chronic lung disease and pulmonary arterial hypertension.

    PubMed

    Arena, Ross

    2011-01-01

    Research examining the clinical value of exercise testing and training in patients with chronic lung disease and pulmonary arterial hypertension (PAH) is less robust compared with cardiac populations but nevertheless highly supportive. Functional limitations are common in these patients, and exercise testing provides important information pertaining to the degree of this limitation, disease severity, and prognosis. Moreover, exercise testing, particularly in conjunction with ventilatory expired gas analysis, serves as a valuable diagnostic tool when the mechanism of the functional limitation and abnormal exertional symptoms is uncertain. Most work with respect to the benefits of exercise training has been performed in chronic obstructive lung disease cohorts and is used to support pulmonary rehabilitation. Emerging data indicate that exercise training is likewise beneficial in patients with interstitial lung disease and PAH. This review summarizes the evidence supporting the value of exercise testing and training and provides recommendations for clinical practice. PMID:21545932

  3. 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

  4. 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)

  5. 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.

  6. 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. PMID:25898957

  7. Pattern of Skin Diseases in a Tertiary Institution in Kolkata

    PubMed Central

    Kar, Chinmay; Das, Sudip; Roy, Alok Kumar

    2014-01-01

    Background: There are very little elaborative studies in India about various patterns of skin diseases and various factors those influence the diseases in a tertiary institution. Aims: To find out the various patterns of skin diseases in relation to age, sex, occupation, and socio-economic status. To find out the magnitude of skin diseases and compare with other similar studies. Materials and Methods: Collection of data of all new skin cases in a specified period of one year and put on proforma for diagnosis. Few investigations were done for correct diagnosis. Results: It was found that skin OPD patients (new) were 4.16% of total new OPD patients, and male female ratio was 1.1:1. Among all patients (12910), infection was commonest (39.54%), followed by allergic skin disorder (29.20%). 25.05% patients were housewives, followed by students (23.21%). Study showed that 33.28% patients had per capita income of ` 361-720/month, and 22.35% patients were educated and/or studied up to class V. Conclusion: Pattern of skin diseases are mostly depend not only on environmental factors but also on occupation, socio-economic status, literacy, and age of the patients. PMID:24700954

  8. Joint Modeling of Transitional Patterns of Alzheimer's Disease

    PubMed Central

    Liu, Wei; Zhang, Bo; Zhang, Zhiwei; Zhou, Xiao-Hua

    2013-01-01

    While the experimental Alzheimer's drugs recently developed by pharmaceutical companies failed to stop the progression of Alzheimer's disease, clinicians strive to seek clues on how the patients would be when they visit back next year, based upon the patients' current clinical and neuropathologic diagnosis results. This is related to how to precisely identify the transitional patterns of Alzheimer's disease. Due to the complexities of the diagnosis of Alzheimer's disease, the condition of the disease is usually characterized by multiple clinical and neuropathologic measurements, including Clinical Dementia Rating (CDRGLOB), Mini-Mental State Examination (MMSE), a score derived from the clinician judgement on neuropsychological tests (COGSTAT), and Functional Activities Questionnaire (FAQ). In this research article, we investigate a class of novel joint random-effects transition models that are used to simultaneously analyze the transitional patterns of multiple primary measurements of Alzheimer's disease and, at the same time, account for the association between the measurements. The proposed methodology can avoid the bias introduced by ignoring the correlation between primary measurements and can predict subject-specific transitional patterns. PMID:24073268

  9. 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

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

    PubMed Central

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

    2014-01-01

    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

  11. MSC Microvesicles for the Treatment of Lung Disease: A New Paradigm for Cell-Free Therapy

    PubMed Central

    Sdrimas, Konstantinos

    2014-01-01

    Abstract Significance: Bronchopulmonary dysplasia (BPD), also known as chronic lung disease of infancy, is a major complication of preterm birth that, despite improvements in neonatal respiratory support and perinatal care, remains an important cause of morbidity and mortality, often with severe adverse neurodevelopmental sequelae. Even with major advances in our understanding of the pathogenesis of this disease, BPD remains essentially without adequate treatment. Recent Advances: Cell-based therapies arose as a promising treatment for acute and chronic lung injury in many experimental models of disease. Currently, more than 3000 human clinical trials employing cell therapy for the treatment of diverse diseases, including cardiac, neurologic, immune, and respiratory conditions, are ongoing or completed. Among the treatments, mesenchymal stem cells (MSCs) are the most studied and have been extensively tested in experimental models of BPD, pulmonary hypertension, pulmonary fibrosis, and acute lung injury. Critical Issues: Despite the promising potential, MSC therapy for human lung disease still remains at an experimental stage and optimal transplantation conditions need to be determined. Although the mechanism of MSC action can be manifold, accumulating evidence suggests a predominant paracrine, immunomodulatory, and cytoprotective effect. Future Directions: The current review summarizes the effect of MSC treatment in models of lung injury, including BPD, and focuses on the MSC secretome and, specifically, MSC-derived microvesicles as potential key mediators of therapeutic action that can be the focus of future therapies. Antioxid. Redox Signal. 21, 1905–1915. PMID:24382303

  12. 12. Patterns of Adrenal Gland Involvement from Lung Cancer Shown by 18F-Fluorodeoxyglucose Positron Emission Tomography Compared to Computed Tomography and Magnetic Resonance Imaging.

    PubMed

    Zubeldia; Abou-Zied; Nabi

    2000-07-01

    Purpose: The frequency of adrenal metastases from non-small cell lung cancer (NSCLC) varies between 4 to 25%. Adrenal metastases are frequently missed (78%) by Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). The purpose of this study was to characterize the patterns of adrenal gland involvement from lung cancer by 18-F-Fluorodeoxyglucose Positron Emission Tomography (18FDG-PET).Methods: Retrospective review of patients evaluated for known or suspected lung carcinoma. Results of 18FDG-PET, CT, MRI, and scans were compared.Results: From February 1996 to May 2000, 91 patients with known (85 patients) or suspected (6 patients) lung cancer were evaluated with 18FDG-PET scan. Twenty-two patients (mean age 63, range 38-88 years) had abnormal adrenal glands by either 18FDG-PET (16 patients), CT (12 patients) or MRI (1 patient). In 13 cases 18FDG-PET scan was ordered to clarify CT or MRI findings. Only 7 patients showed adrenal gland involvement: 5 patients (5.5%) with unilateral disease and 2 patients (2.2%) with bilateral disease. PET depicted unsuspected findings in 9 patients: 8 patients (8.8%) with unilateral disease and 1 patient (1.1%) with bilateral disease.(18)FDG-PET upstaged 9 patients from limited (N1M0) to widespread disease (M1), thus obviating surgical intervention.Conclusion: This study demonstrates the potential of 18FDG-PET scanning in revealing unsuspected adrenal metastases in patients with early stages of NSCLC as well as characterizing CT or MRI equivocal adrenal masses. PMID:11150769

  13. Role of surfactant protein A in non-infectious lung diseases.

    PubMed

    Goto, Hisatsugu; Mitsuhashi, Atsushi; Nishioka, Yasuhiko

    2014-01-01

    Surfactant protein A (SP-A) is a large multimeric protein found in the airways and alveoli of the lungs. SP-A is a member of the collectin family of proteins, characterized by NH2-terminal collagen-like regions and COOH-terminal lectin domains. Although other surfactant proteins such as SP-B function to reduce surface tension in the lungs, SP-A as well as SP-D regulates the pulmonary immune response. To date, a number of studies have shown the immunoregulatory function of SP-A, mainly in the field of infectious diseases. By binding to a wide variety of pathogens, SP-A opsonizes and enhances pathogen uptake by phagocytes. In addition to the effect on pathogens, recent studies have shown that SP-A also modulates lung immune system in the area of non-infectious lung diseases. In this review, the potential role of SP-A in the multiple aspects of pulmonary host defense will be discussed, focusing mainly on non-infectious lung diseases such as acute and chronic pulmonary fibrosis and lung cancer. J. Med. Invest. 61: 1-6, February, 2014. PMID:24705741

  14. Expression of Carcinoembryonic Cell Adhesion Molecule 6 and Alveolar Epithelial Cell Markers in Lungs of Human Infants with Chronic Lung Disease.

    PubMed

    Gonzales, Linda W; Gonzalez, Robert; Barrette, Anne Marie; Wang, Ping; Dobbs, Leland; Ballard, Philip L

    2015-12-01

    The membrane protein carcinoembryonic antigen cell adhesion molecule (CEACAM6) is expressed in the epithelium of various tissues, participating in innate immune defense, cell proliferation and differentiation, with overexpression in gastrointestinal tract, pancreatic and lung tumors. It is developmentally and hormonally regulated in fetal human lung, with an apparent increased production in preterm infants with respiratory failure. To further examine the expression and cell localization of CEACAM6, we performed immunohistochemical and biochemical studies in lung specimens from infants with and without chronic lung disease. CEACAM6 protein and mRNA were increased ~4-fold in lungs from infants with chronic lung disease as compared with controls. By immunostaining, CEACAM6 expression was markedly increased in the lung parenchyma of infants and children with a variety of chronic lung disorders, localizing to hyperplastic epithelial cells with a ~7-fold elevated proliferative rate by PCNA staining. Some of these cells also co-expressed membrane markers of both type I and type II cells, which is not observed in normal postnatal lung, suggesting they are transitional epithelial cells. We suggest that CEACAM6 is both a marker of lung epithelial progenitor cells and a contributor to the proliferative response after injury due to its anti-apoptotic and cell adhesive properties. PMID:26374831

  15. Chagas Disease, Migration and Community Settlement Patterns in Arequipa, Peru

    PubMed Central

    Gilman, Robert H.; Cornejo del Carpio, Juan G.; Naquira, Cesar; Bern, Caryn; Levy, Michael Z.

    2009-01-01

    Background Chagas disease is one of the most important neglected tropical diseases in the Americas. Vectorborne transmission of Chagas disease has been historically rare in urban settings. However, in marginal communities near the city of Arequipa, Peru, urban transmission cycles have become established. We examined the history of migration and settlement patterns in these communities, and their connections to Chagas disease transmission. Methodology/Principal Findings This was a qualitative study that employed focus group discussions and in-depth interviews. Five focus groups and 50 in-depth interviews were carried out with 94 community members from three shantytowns and two traditional towns near Arequipa, Peru. Focus groups utilized participatory methodologies to explore the community's mobility patterns and the historical and current presence of triatomine vectors. In-depth interviews based on event history calendars explored participants' migration patterns and experience with Chagas disease and vectors. Focus group data were analyzed using participatory analysis methodologies, and interview data were coded and analyzed using a grounded theory approach. Entomologic data were provided by an ongoing vector control campaign. We found that migrants to shantytowns in Arequipa were unlikely to have brought triatomines to the city upon arrival. Frequent seasonal moves, however, took shantytown residents to valleys surrounding Arequipa where vectors are prevalent. In addition, the pattern of settlement of shantytowns and the practice of raising domestic animals by residents creates a favorable environment for vector proliferation and dispersal. Finally, we uncovered a phenomenon of population loss and replacement by low-income migrants in one traditional town, which created the human settlement pattern of a new shantytown within this traditional community. Conclusions/Significance The pattern of human migration is therefore an important underlying determinant of

  16. The Significance of Mycobacterium abscessus Subspecies abscessus Isolation During Mycobacterium avium Complex Lung Disease Therapy

    PubMed Central

    Philley, Julie V.; Brown-Elliott, Barbara A.; Benwill, Jeana L.; Shepherd, Sara; York, Deanna; Wallace, Richard J.

    2015-01-01

    BACKGROUND: Isolation of Mycobacterium abscessus subspecies abscessus (MAA) is common during Mycobacterium avium complex (MAC) lung disease therapy, but there is limited information about the clinical significance of the MAA isolates. METHODS: We identified 53 of 180 patients (29%) treated for MAC lung disease who had isolation of MAA during MAC lung disease therapy. Patients were divided into those without (group 1) and those with (group 2) MAA lung disease. RESULTS: There were no significant demographic differences between patients with and without MAA isolation or between groups 1 and 2. Group 1 and 2 patients had similar total sputum cultures obtained (P = .7; 95% CI, −13.4 to 8.6) and length of follow-up (P = .8; 95% CI, −21.5 to 16.1). Group 2 patients had significantly more total positive cultures for MAA (mean±SD, 15.0 ± 11.1 vs 1.2 ± 0.4; P < .0001; 95% CI, −17.7 to −9.9), were significantly more likely to develop new or enlarging cavitary lesions while on MAC therapy (P > .0001), and were significantly more likely to meet all three American Thoracic Society diagnostic criteria for nontuberculous mycobacterial disease (21 of 21 [100%] vs 0 of 32 [0%]; P < .0001) compared with group 1 patients. Group 1 patients were significantly more likely to have single, positive MAA cultures than group 2 patients (25 of 31 vs 0 of 21; P < .0001). CONCLUSIONS: Microbiologic and clinical follow-up after completion of MAC lung disease therapy is required to determine the significance of MAA isolated during MAC lung disease therapy. Single MAA isolates are not likely to be clinically significant. PMID:25357074

  17. Lung disease in a global context. A call for public health action.

    PubMed

    Schluger, Neil W; Koppaka, Ram

    2014-03-01

    As described in a recently released report of the Forum of International Respiratory Societies, four of the leading causes of death in the world are chronic obstructive pulmonary disease, acute respiratory tract infections, lung cancer, and tuberculosis. A fifth, asthma, causes enormous global morbidity. Not enough progress has been made in introducing new therapies and reducing disease burden for these illnesses in the last few decades, despite generous investments and some notable progress in biomedical research. Four external and modifiable drivers are responsible for a substantial percentage of the disease burden represented by the major lung diseases: tobacco, outdoor air pollution, household air pollution, and occupational exposures to lung toxins. Especially in low- and middle-income countries, but in highly developed economies as well, pressures for economic development and lax regulation are contributing to the continued proliferation of these drivers. Public health approaches to the most common lung diseases could have enormous effects on reducing morbidity and mortality. There must be increased advocacy from and mobilization of civil society to bring attention to the drivers of lung diseases in the world. The World Health Organization should negotiate accords similar to the Framework Convention on Tobacco Control to address air pollution and occupational exposures. Large increases in funding by government agencies and nongovernmental organizations around the world are needed to identify technologies that will reduce health risks while allowing populations to enjoy the benefits of economic development. This paradigm, focused more on public health than on individual medical treatment, has the best chance of substantial reduction in the burden of lung disease around the world in the next several years. PMID:24673697

  18. AB029. Clinical utility of a molecular diagnostic in evaluation of interstitial lung disease

    PubMed Central

    Wu, Xiaoping; Rosenbluth, Michael; Choi, Yoonha; Danese, Sherry; Bianchi, Pauline; Flaherty, Kevin; Martinez, Fernando

    2016-01-01

    Background The accurate diagnosis of idiopathic pulmonary fibrosis (IPF) continues to be challenging due to its overlapping features with other interstitial lung diseases (ILDs). With the approval of pirfenidone and nintedanib for treatment of IPF, there is greater urgency to identify patients with IPF without requiring surgical lung biopsy (SLB). In this study, we evaluated the clinical utility of a genomic classifier under development to identify usual interstitial pneumonia (UIP), the pathology pattern associated with IPF, using bronchoscopically collected samples. Methods A national survey was conducted from March 17–20, 2015 among 76 pulmonologists from ILD centers and non-specialty clinics. The survey described a genomic test with high precision for detecting UIP pattern using bronchoscopically collected samples. Physicians were asked about diagnostic/treatment next steps on four ILD patient cases representing confident UIP, possible UIP, possible UIP vs. hypersensitivity pneumonitis (HP), and connective tissue disease related ILD and how the genomic test would alter management. Results Physicians’ likelihood of using the genomic test varied with the method of sampling. Ninety-one percent of physicians reported they would likely use the test if it required bronchoalveolar lavage (BAL), compared with 85% for transbronchial biopsy (TBB), and 63% for SLB. Across four clinical scenarios, a positive genomic test result significantly increased treatment with pirfenidone/nintedanib and reduced biopsies. The largest impact occurred in the possible UIP cases with an increase in treatment from 11% to 46% (P<0.001) and a decrease in biopsies from 59% to 26% (P<0.001). A positive test in the setting of confident UIP raised treatment recommendation from 47% to 70% (P<0.001) and decreased biopsies from 42% to 18% (P<0.001), suggesting its utility even in cases with high pre-test probability for UIP. A negative test result was less impactful on management than a

  19. 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

  20. 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

  1. Local and systemic neutrophilic inflammation in patients with lung cancer and chronic obstructive pulmonary disease

    PubMed Central

    2013-01-01

    Background Recent investigations suggest that neutrophils play an important role in the immune response to lung cancer as well as chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate the amount of neutrophils and markers of their activity in lung cancer and COPD and in coexistence of these two diseases. Methods In total, 267 persons were included in the study: 139 patients with lung cancer, 55 patients with lung cancer and COPD, 40 patients with COPD, and 33 healthy subjects. Peripheral blood and BAL fluid samples were obtained for cell count analysis and determination of NE, MPO levels and ROS production. NE and MPO levels in the serum and BAL fluid were determined by ELISA. ROS production was analyzed by flow cytometer. Results The percentage, cell count of neutrophils and neutrophil to lymphocyte ratio in the peripheral blood were significantly higher in lung cancer patients with or without COPD compared to COPD patients or healthy individuals (P < 0.05). The percentage and cell count of neutrophils in BAL fluid were significantly lower in patients with lung cancer with or without COPD than in patients with COPD (P < 0.05). However, BAL fluid and serum levels of both NE and MPO were significantly higher in patients with lung cancer than COPD patients or healthy individuals (P < 0.05). Neutrophils produced higher amounts of ROS in patients with lung cancer with or without COPD compared with COPD patients or healthy individuals (P < 0.05). Conclusions The results from this study demonstrate higher degree of local and systemic neutrophilic inflammation in patients with lung cancer (with or without COPD) than in patients with COPD. PMID:23919722

  2. 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.

  3. Audience interest in mass media messages about lung disease in Vermont.

    PubMed Central

    Worden, J K; Sweeney, R R; Waller, J A

    1978-01-01

    This study pretested audience interest in 25 potential message concepts to be used in a mass media campaign designed to change knowledge, attitudes, and behavior regarding lung disease. A group of 150 respondents reflecting specific target audiences (smokers, older persons, etc.) rated each concept on the basis of a two-sentence description using Haskins' 0--100 scale. Results indicated that older persons were most interested in message concepts suggesting ways to deal with various lung disease symptoms, and smokers showed highest interest in concepts offering positive and straightforward advice on how to quit smoking, rather than concepts that were negative, cute, or satirical in approach. Recommendations based on audience interest were made for the design of future lung disease media campaigns. PMID:645984

  4. Application of Clinico-Radiologic-Pathologic Diagnosis of Diffuse Parenchymal Lung Diseases in Children in China

    PubMed Central

    Xu, Dan; Chen, Zhimin; Chen, Huizhong; Huang, Rongyan; Zhao, Shunying; Liu, Xiuyun; Zhou, Chunju; Peng, Yun; Yuan, Xinyu; Zou, Jizhen; Zhang, Hailing; Zhao, Deyu; Liu, Enmei; Zheng, Yuejie; Zhong, Lili; Lu, Min; Lu, Jirong; Nong, Guangmin

    2015-01-01

    Diffuse parenchymal lung diseases in children (chDPLD) or interstitial lung diseases in children (chILD) represent a heterogeneous group of respiratory disorders that are mostly chronic and associated with high morbidity and mortality. However, the incidence of chDPLD is so low that most pediatricians lack sufficient knowledge of chDPLD, especially in China. Based on the clinico- radiologic- pathologic (CRP) diagnosis, we tried to describe (1) the characteristics of chDPLD and (2) the ratio of each constituent of chDPLD in China. Data were evaluated, including clinical, radiographic, and pathologic results from lung biopsies. We collected 25 cases of chDPLD, 18 boys and 7 girls with a median age of 6.0 years, from 16 hospitals in China. The most common manifestations included cough (n = 24), dyspnea (n = 21), and fever (n = 4). There were three cases of exposure-related interstitial lung disease (ILD), three cases of systemic disease-associated ILD, nineteen cases of alveolar structure disorder-associated ILD, and no cases of ILD specific to infancy. Non-specific interstitial pneumonia (n = 9) was the two largest groups. Conclusion: Non-specific interstitial pneumonia is the main categories of chDPLD in China. Lung biopsy is always a crucial step in the final diagnosis. However, clinical and imaging studies should be carefully evaluated for their value in indicating a specific chDPLD. PMID:25569558

  5. Long-term IL-33–producing epithelial progenitor cells in chronic obstructive lung disease

    PubMed Central

    Byers, Derek E.; Alexander-Brett, Jennifer; Patel, Anand C.; Agapov, Eugene; Dang-Vu, Geoffrey; Jin, Xiaohua; Wu, Kangyun; You, Yingjian; Alevy, Yael; Girard, Jean-Philippe; Stappenbeck, Thaddeus S.; Patterson, G. Alexander; Pierce, Richard A.; Brody, Steven L.; Holtzman, Michael J.

    2013-01-01

    Chronic obstructive lung disease is characterized by persistent abnormalities in epithelial and immune cell function that are driven, at least in part, by infection. Analysis of parainfluenza virus infection in mice revealed an unexpected role for innate immune cells in IL-13–dependent chronic lung disease, but the upstream driver for the immune axis in this model and in humans with similar disease was undefined. We demonstrate here that lung levels of IL-33 are selectively increased in postviral mice with chronic obstructive lung disease and in humans with very severe chronic obstructive pulmonary disease (COPD). In the mouse model, IL-33/IL-33 receptor signaling was required for Il13 and mucin gene expression, and Il33 gene expression was localized to a virus-induced subset of airway serous cells and a constitutive subset of alveolar type 2 cells that are both linked conventionally to progenitor function. In humans with COPD, IL33 gene expression was also associated with IL13 and mucin gene expression, and IL33 induction was traceable to a subset of airway basal cells with increased capacities for pluripotency and ATP-regulated release of IL-33. Together, these findings provide a paradigm for the role of the innate immune system in chronic disease based on the influence of long-term epithelial progenitor cells programmed for excess IL-33 production. PMID:23945235

  6. Impact of Coexisting Pulmonary Diseases on Survival of Patients With Lung Adenocarcinoma

    PubMed Central

    Jian, Zhi-Hong; Huang, Jing-Yang; Ko, Pei-Chieh; Jan, Shiou-Rung; Nfor, Oswald Ndi; Lung, Chia-Chi; Ku, Wen-Yuan; Ho, Chien-Chang; Pan, Hui-Hsien; Liaw, Yung-Po

    2015-01-01

    Abstract Asthma, chronic obstructive pulmonary disease (COPD), and pulmonary tuberculosis (TB) are common pulmonary diseases associated with lung cancer. Besides, smoking is more prevalent in Taiwanese men. This study evaluated gender disparities in coexisting pulmonary diseases on survival of patients with lung adenocarcinoma. Patients newly diagnosed with lung cancer between 2003 and 2008 were identified from Taiwan National Health Insurance Research Database. Cases with lung adenocarcinoma were further confirmed using the Cancer Registry Database and followed up until the end of 2010. Cox proportional hazard regression was used to calculate the hazard ratio (HR) of coexisting asthma, COPD, and/or TB to estimate all-cause mortality risk. During the study period, 13,399 cases of lung adenocarcinoma were identified. The HRs of adenocarcinoma in men and women were 1.20 (95% confidence interval [CI], 1.10–1.30) and 1.05 (95% CI, 0.95–1.16), respectively, for individuals with asthma, 1.32 (95% CI, 1.16–1.51) and 0.97 (95% CI, 0.89–1.05), respectively, for COPD, and 0.99 (95% CI, 0.93–1.06) and 1.06 (95% CI, 0.86–1.32), respectively, for individuals with TB. Specifically, among men with coexisting pulmonary diseases, the HRs were 1.63 (95% CI, 1.25–2.13), 1.31 (95% CI, 1.08–1.59), and 1.23 (95% CI, 1.11–1.36) for individuals with asthma + COPD + TB, asthma + COPD, and COPD + TB, respectively. However, there was no increase risk of mortality among women with coexisting pulmonary diseases. Coexisting pulmonary diseases are at an elevated risk of mortality among male patients with lung adenocarcinoma. Such patients deserve greater attention while undergoing cancer treatment. PMID:25634179

  7. Group III Pulmonary Hypertension: Pulmonary Hypertension Associated with Lung Disease: Epidemiology, Pathophysiology, and Treatments.

    PubMed

    Klinger, James R

    2016-08-01

    Pulmonary hypertension (PH) associated with chronic lung disease (WHO group 3) is the second leading cause of PH and is associated with increased morbidity and mortality. Elevation of pulmonary arterial pressure (PAP) is usually moderate and correlates with severity of lung disease. In a small minority, PAP may approach that seen in WHO group 1 pulmonary arterial hypertension (PAH). Current medications for treating PAH have not shown benefit in controlled trials of group 3 PH and their routine use is discouraged. Patients with severe group 3 PH should be considered for referral to expert centers or entry into clinical trials. PMID:27443138

  8. History of lung disease and risk of lung cancer in a population with high household fuel combustion exposures in rural China

    PubMed Central

    Hosgood, H. Dean; Chapman, Robert S.; He, Xingzhou; Wei, Hu; Tian, Linwei; Liu, Larry Z.; Lai, Hong; Chen, Wei; Rothman, Nathaniel; Lan, Qing

    2013-01-01

    History of chronic lung diseases and household coal use for heating and cooking are established risk factors of lung cancer; however, few studies have been able to explore these risk factors simultaneously. Xuanwei, China, has some of the highest rates of lung cancer in China and most residents experience substantial in-home coal smoke exposures. Using a population-based case-control study of 498 lung cancer cases and 498 age-matched controls, we evaluated the risk of lung cancer in relation to coal smoke exposure and history of chronic lung diseases, including chronic obstructive pulmonary disease (COPD), asthma, tuberculosis (TB), chronic bronchitis, and emphysema. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by conditional logistic regression adjusting for potential confounders. We observed an increased risk of lung cancer with history of any chronic lung disease among males (OR=14.2; 95%CI =4.3 to 46.9), females (OR=2.6; 95%CI =1.1 to 6.3), smokers (OR=12.7; 95%CI =3.5 to 45.8), and nonsmokers (OR=2.6; 95%CI =1.1 to 6.4). Specifically, TB (OR=83.7; 95%CI =11.0 to 634.7), COPD (OR=3.2; 95%CI =1.7 to 6.0), and emphysema and chronic bronchitis (OR=3.3; 95%CI =1.7 to 6.4) were associated with increased risks. These findings suggest that history of chronic lung diseases may also increase risk of lung cancer in populations with indoor coal smoke exposures. PMID:23891511

  9. Using Fractal And Morphological Criteria For Automatic Classification Of Lung Diseases

    NASA Astrophysics Data System (ADS)

    Vehel, Jacques Levy

    1989-11-01

    Medical Images are difficult to analyze by means of classical image processing tools because they are very complex and irregular. Such shapes are obtained for instance in Nuclear Medecine with the spatial distribution of activity for organs such as lungs, liver, and heart. We have tried to apply two different theories to these signals: - Fractal Geometry deals with the analysis of complex irregular shapes which cannot well be described by the classical Euclidean geometry. - Integral Geometry treats sets globally and allows to introduce robust measures. We have computed three parameters on three kinds of Lung's SPECT images: normal, pulmonary embolism and chronic desease: - The commonly used fractal dimension (FD), that gives a measurement of the irregularity of the 3D shape. - The generalized lacunarity dimension (GLD), defined as the variance of the ratio of the local activity by the mean activity, which is only sensitive to the distribution and the size of gaps in the surface. - The Favard length that gives an approximation of the surface of a 3-D shape. The results show that each slice of the lung, considered as a 3D surface, is fractal and that the fractal dimension is the same for each slice and for the three kind of lungs; as for the lacunarity and Favard length, they are clearly different for normal lungs, pulmonary embolisms and chronic diseases. These results indicate that automatic classification of Lung's SPECT can be achieved, and that a quantitative measurement of the evolution of the disease could be made.

  10. Theoretical modeling of the interaction between alveoli during inflation and deflation in normal and diseased lungs.

    PubMed

    Schirrmann, Kerstin; Mertens, Michael; Kertzscher, Ulrich; Kuebler, Wolfgang M; Affeld, Klaus

    2010-04-19

    Alveolar recruitment is a central strategy in the ventilation of patients with acute lung injury and other lung diseases associated with alveolar collapse and atelectasis. However, biomechanical insights into the opening and collapse of individual alveoli are still limited. A better understanding of alveolar recruitment and the interaction between alveoli in intact and injured lungs is of crucial relevance for the evaluation of the potential efficacy of ventilation strategies. We simulated human alveolar biomechanics in normal and injured lungs. We used a basic simulation model for the biomechanical behavior of virtual single alveoli to compute parameterized pressure-volume curves. Based on these curves, we analyzed the interaction and stability in a system composed of two alveoli. We introduced different values for surface tension and tissue properties to simulate different forms of lung injury. The data obtained predict that alveoli with identical properties can coexist with both different volumes and with equal volumes depending on the pressure. Alveoli in injured lungs with increased surface tension will collapse at normal breathing pressures. However, recruitment maneuvers and positive endexpiratory pressure can stabilize those alveoli, but coexisting unaffected alveoli might be overdistended. In injured alveoli with reduced compliance collapse is less likely, alveoli are expected to remain open, but with a smaller volume. Expanding them to normal size would overdistend coexisting unaffected alveoli. The present simulation model yields novel insights into the interaction between alveoli and may thus increase our understanding of the prospects of recruitment maneuvers in different forms of lung injury. PMID:20031137

  11. Lung transplantation in chronic obstructive pulmonary disease: patient selection and special considerations.

    PubMed

    Lane, C Randall; Tonelli, Adriano R

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality and morbidity. Lung transplantation is one of the few treatments available for end-stage COPD with the potential to improve survival and quality of life. The selection of candidates and timing of listing present challenges, as COPD tends to progress fairly slowly, and survival after lung transplantation remains limited. Though the natural course of COPD is difficult to predict, the use of assessments of functional status and multivariable indices such as the BODE index can help identify which patients with COPD are at increased risk for mortality, and hence which are more likely to benefit from lung transplantation. Patients with COPD can undergo either single or bilateral lung transplantation. Although many studies suggest better long-term survival with bilateral lung transplant, especially in younger patients, this continues to be debated, and definitive recommendations about this cannot be made. Patients may be more susceptible to particular complications of transplant for COPD, including native lung hyperinflation, and development of lung cancer. PMID:26491282

  12. 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

  13. Lung volumes, chest wall configuration, and pattern of breathing in microgravity.

    PubMed

    Paiva, M; Estenne, M; Engel, L A

    1989-10-01

    We studied the changes in functional residual capacity (FRC), thoracoabdominal volume (Vw), and chest wall configuration in five normal subjects seated in an aircraft flying parabolic trajectories resulting in 20-s periods of microgravity. We measured vital capacity (VC), inspiratory capacity, and tidal volume by integrating airflow at the mouth and changes in rib cage and abdominal volume (delta Vrc and delta Vab, respectively, where delta Vrc + delta Vab = delta Vw) using induction plethysmography. During microgravity (0 Gz) FRC decreased by 413 +/- 70 (SE) ml and VC by 0.37 liter. The decrease in Vw did not differ from that in FRC and was entirely the result of reduction of Vab, the Vrc showing no significant change. During tidal breathing the abdominal contribution (delta Vab/delta Vw) increased from 0.39 +/- 0.08 at 1 Gz to 0.57 +/- 0.08 at 0 Gz. During brief periods of hypergravity (approximately 1.8 Gz) all changes were opposite in sign and relatively smaller. Limited data during "roller coaster" flight patterns suggested that, in contrast to configurational changes, the temporal pattern of breathing was uninfluenced by changes in Gz. We conclude that at the onset of weightlessness there are substantial changes in lung volume and thoracoabdominal configuration. Abdominal contribution to tidal excursions increases but the temporal pattern of breathing is unchanged. PMID:2793756

  14. Cell Therapy for Lung Diseases. Report from an NIH–NHLBI Workshop, November 13–14, 2012

    PubMed Central

    Matthay, Michael A.; Anversa, Piero; Bhattacharya, Jahar; Burnett, Bruce K.; Chapman, Harold A.; Hare, Joshua M.; Hei, Derek J.; Hoffman, Andrew M.; Kourembanas, Stella; McKenna, David H.; Ortiz, Luis A.; Ott, Harald C.; Tente, William; Thébaud, Bernard; Trapnell, Bruce C.; Weiss, Daniel J.; Yuan, Jason X.-J.

    2013-01-01

    The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health convened the Cell Therapy for Lung Disease Working Group on November 13–14, 2012, to review and formulate recommendations for future research directions. The workshop brought together investigators studying basic mechanisms and the roles of cell therapy in preclinical models of lung injury and pulmonary vascular disease, with clinical trial experts in cell therapy for cardiovascular diseases and experts from the NHLBI Production Assistance for Cell Therapy program. The purpose of the workshop was to discuss the current status of basic investigations in lung cell therapy, to identify some of the scientific gaps in current knowledge regarding the potential roles and mechanisms of cell therapy in the treatment of lung diseases, and to develop recommendations to the NHLBI and the research community on scientific priorities and practical steps that would lead to first-in-human trials of lung cell therapy. PMID:23713908

  15. Expression pattern of FGFR2, Grb2 and Plcγ1 acts as a novel prognostic marker of recurrence recurrence-free survival in lung adenocarcinoma

    PubMed Central

    Timsah, Zahra; Berrout, Jonathan; Suraokar, Milind; Behrens, Carmen; Song, Juhee; Lee, J Jack; Ivan, Cristina; Gagea, Mihai; Shires, Michael; Hu, Xin; Vallien, Courtney; Kingsley, Charles V; Wistuba, IgnacioI; Ladbury, John E

    2015-01-01

    Lung adenocarcinoma is characterized by complex biology involving alterations at the genomic and protein expression levels. FGFR2 mutation and/or amplification are key drivers of disease progression and drug resistance in lung adenocarcinoma patients. These genetic alterations drive oncogenic downstream signalling due to the deregulated activity of the receptor. We have previously reported that wild type FGFR2 provides a binding site for which two proteins, Grb2 and Plcγ1, compete in a concentration-dependent manner. Metastasis and invasion ensue when Plcγ1 prevails on the receptor giving rise to oncogenic outcome in the absence of gene mutation/deletion. The effect of this signalling mechanism on FGFR2-driven lung adenocarcinoma has not previously been considered. In this study we show that fluctuation in the combinatorial expression levels of FGFR2, Grb2 and Plcγ1 modulates cell invasive properties, tumor formation and is linked to recurrence-free survival in 150 lung adenocarcinoma patients. High levels of expression of FGFR2 and Plcγ1 in a low background of Grb2 significantly correlates with poor prognosis. On the other hand, low levels of expression of FGFR2 and Plcγ1 in a high background of Grb2 correlates with favourable prognosis. This study defines the expression pattern of FGFR2, Plcγ1 and Grb2 as a novel prognostic marker in human lung adenocarcinoma. Thus, consideration of the Grb2 and Plcγ1-mediated mechanism of FGFR2 regulation will enhance the therapeutic targeting of aberrant FGFR2 activity to provide the much-needed improvement to the treatment regimen of this high mortality disease. PMID:26693065

  16. Epidemiologic studies of inorganic dust-related lung diseases in The Netherlands

    SciTech Connect

    Meijers, J.M.; Swaen, G.M.; van Vliet, K.; Borm, P.J. )

    1990-01-01

    The results of two epidemiologic investigations on dust-related lung diseases are presented. The two studies had different aims and designs. A cross-sectional study was done to investigate the silicosis prevalence in Dutch fine ceramic workers. In the small ceramic workshops in the Gouda region, simple pneumoconiosis is still commonly present (13.3%), whereas the silicosis prevalence in the highly mechanized industries is low (1.7%). Furthermore, heavy smoking seems to enhance the risk for silicosis after long-term exposure to quartz. A case-control study was performed to analyze the relation between dust exposure in the fine ceramic and coal mining industries and lung cancer. No relation between a work history in the dusty trades and lung cancer emerged, and a correlation with a specific histologic tumor cell type could not be demonstrated. Apparently, workers in the Dutch fine ceramic or coal mining industry have no increased risk of developing lung malignancies.

  17. Cysteine cathepsins and cystatins: from ancillary tasks to prominent status in lung diseases.

    PubMed

    Lalmanach, Gilles; Saidi, Ahlame; Marchand-Adam, Sylvain; Lecaille, Fabien; Kasabova, Mariana

    2015-02-01

    Human cysteine cathepsins (family C1, clan CA) have long been regarded as ubiquitous household enzymes, primarily involved in the recycling and degradation of proteins in lysosomes. This opinion has changed considerably during recent decades, however, with the demonstration of their involvement in various physiological processes. A growing body of evidence supports the theory that cathepsins play specific functions in lung homeostasis and pathophysiological events such as asthma, lung fibrosis (including idiopathic pulmonary fibrosis), chronic obstructive pulmonary disease (embracing emphysema and chronic bronchitis), silicosis, bronchopulmonary dysplasia or tumor invasion. The objective of this review is to provide an update on the current knowledge of the role of these enzymes in the lung. Particular attention has been paid to the understanding of the role of these proteases and their natural inhibitors, cystatins (family I25, clan IH), in TGF-β1-driven fibrotic processes with an emphasis on lung fibrosis. PMID:25178906