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Sample records for inflammatory lung diseases

  1. Inflammatory lung disease in Rett syndrome.

    PubMed

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

    2014-01-01

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

  2. 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

  3. The bacterial microbiota in inflammatory lung diseases.

    PubMed

    Huffnagle, Gary B; Dickson, Robert P

    2015-08-01

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

  4. 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

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

    PubMed Central

    Peters, Terence; Henry, Peter J

    2009-01-01

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

  6. Inflammatory lung disease a potential risk factor for onset of idiopathic inflammatory myopathies: results from a pilot study

    PubMed Central

    Helmers, Sevim Barbasso; Jiang, Xia; Pettersson, David; Wikman, Anna-Lis; Axelman, Pia; Lundberg, Åsa; Lundberg, Ingrid E; Alfredsson, Lars

    2016-01-01

    Objectives To assess the association between inflammatory lung disease and the risk of developing idiopathic inflammatory myopathies. Methods A population-based case–control study was conducted. Adult myositis cases, identified from the Swedish inpatient registry (diagnosed between 1995 and 1997), and randomly selected controls matched to cases on the date of birth, gender and residency, were asked to fill out a questionnaire with questions on lifestyle, environmental exposures and health. Eventually, 100 cases and 402 controls responded to the questionnaire and were included in the analyses. Exposure was defined as self-reported preceding inflammatory lung diseases (pneumonia, tuberculosis or sarcoidosis). The association between the exposure and risk of developing myositis was evaluated by calculating OR together with 95% CIs in logistic regressions. Results 42 (42%) cases and 112 (28%) controls reported preceding inflammatory lung disease. Median duration between inflammatory lung disease and first symptom of myositis was 30 years. We observed a significant association between self-reported history of lung disease at study inclusion and diagnosis of myositis (crude OR=1.8 (1.1 to 2.9); smoking adjusted OR=1.9 (1.2 to 3.1)). We further identified a modestly increased, yet non-significant, association between preceding inflammatory lung disease (prior to index year) and diagnosis of myositis (smoking adjusted OR=1.6 (0.9 to 2.8)). The association was more pronounced among the cases of myositis with concurrent interstitial lung disease (OR=3.8 (1.0 to 14.5)). Conclusions Patients with preceding inflammatory lung disease tend to have an increased risk of developing myositis compared to those without. The effect was more pronounced among patients with myositis with concurrent interstitial lung disease. Thus inflammatory lung disease may constitute a risk factor for myositis. PMID:28123774

  7. Inflammatory bowel disease of the lung: The role of infliximab?

    PubMed

    Hayek, Adam J; Pfanner, Timothy P; White, Heath D

    2015-01-01

    Pulmonary extra-intestinal manifestations (EIM) of inflammatory bowel disease are well described with a variable incidence. We present a case of Crohn's disease with pulmonary EIM including chronic bronchitis with non-resolving bilateral cavitary pulmonary nodules and mediastinal lymphadenopathy successfully treated with infliximab. Additionally, we present a case summary from a literature review on pulmonary EIM successfully treated with infliximab. Current treatment recommendations include an inhaled and/or systemic corticosteroid regimen which is largely based on case reports and expert opinion. We offer infliximab as an adjunctive therapy or alternative to corticosteroids for treatment of inflammatory bowel disease related pulmonary EIM.

  8. The nervous system of airways and its remodeling in inflammatory lung diseases.

    PubMed

    Audrit, Katrin Julia; Delventhal, Lucas; Aydin, Öznur; Nassenstein, Christina

    2017-03-01

    Inflammatory lung diseases are associated with bronchospasm, cough, dyspnea and airway hyperreactivity. The majority of these symptoms cannot be primarily explained by immune cell infiltration. Evidence has been provided that vagal efferent and afferent neurons play a pivotal role in this regard. Their functions can be altered by inflammatory mediators that induce long-lasting changes in vagal nerve activity and gene expression in both peripheral and central neurons, providing new targets for treatment of pulmonary inflammatory diseases.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2014-07-01

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

  11. Inflammatory and immune processes in the human lung in health and disease: evaluation by bronchoalveolar lavage.

    PubMed Central

    Hunninghake, G. W.; Gadek, J. E.; Kawanami, O.; Ferrans, V. J.; Crystal, R. G.

    1979-01-01

    Bronchoalveolar lavage is an invaluable means of accurately evaluating the inflammatory and immune processes of the human lung. Although lavage recovers only those cells and proteins present on the epithelial surface of the lower respiratory tract, comparison with open lung biopsies shows that these constituents are representative of the inflammatory and immune systems of the alveolar structures. With the use of these techniques, sufficient materials are obtained from normal individuals to allow characterization of not only the types of cells and proteins present but their functions as well. Such observations have been useful in defining the inflammatory and immune capabilities of the normal lung and provide a basis for the study of lung disease. Lavage methods have been used to characterize inflammatory and immune processes of the lower respiratory tract in destructive, infectious, neoplastic, and interstitial disorders. From the data already acquired, it is apparent that bronchoalveolar lavage will yield major insights into the pathogenesis, staging, and therapy decisions involved in these disorders. (Am J Pathol 97:149--206, 1979). Images Figure 9 Figure 1 Figure 2 Figure 10 Figure 7 Figure 8 Figure 4 Figure 5 Figure 6 Figure 3 PMID:495693

  12. Application of 'omics technologies to biomarker discovery in inflammatory lung diseases.

    PubMed

    Wheelock, Craig E; Goss, Victoria M; Balgoma, David; Nicholas, Ben; Brandsma, Joost; Skipp, Paul J; Snowden, Stuart; Burg, Dominic; D'Amico, Arnaldo; Horvath, Ildiko; Chaiboonchoe, Amphun; Ahmed, Hassan; Ballereau, Stéphane; Rossios, Christos; Chung, Kian Fan; Montuschi, Paolo; Fowler, Stephen J; Adcock, Ian M; Postle, Anthony D; Dahlén, Sven-Erik; Rowe, Anthony; Sterk, Peter J; Auffray, Charles; Djukanovic, Ratko

    2013-09-01

    Inflammatory lung diseases are highly complex in respect of pathogenesis and relationships between inflammation, clinical disease and response to treatment. Sophisticated large-scale analytical methods to quantify gene expression (transcriptomics), proteins (proteomics), lipids (lipidomics) and metabolites (metabolomics) in the lungs, blood and urine are now available to identify biomarkers that define disease in terms of combined clinical, physiological and patho-biological abnormalities. The aspiration is that these approaches will improve diagnosis, i.e. define pathological phenotypes, and facilitate the monitoring of disease and therapy, and also, unravel underlying molecular pathways. Biomarker studies can either select predefined biomarker(s) measured by specific methods or apply an "unbiased" approach involving detection platforms that are indiscriminate in focus. This article reviews the technologies presently available to study biomarkers of lung disease within the 'omics field. The contributions of the individual 'omics analytical platforms to the field of respiratory diseases are summarised, with the goal of providing background on their respective abilities to contribute to systems medicine-based studies of lung disease.

  13. Soluble complement receptor type 1 (CD35) in bronchoalveolar lavage of inflammatory lung diseases.

    PubMed

    Hamacher, J; Sadallah, S; Schifferli, J A; Villard, J; Nicod, L P

    1998-01-01

    Complement receptor type 1 (CR1) (CD35; C3b/C4b receptor) is a transmembrane protein of many haematopoietic cells. Once cleaved, soluble complement receptor type 1 (sCR1) exerts opposite effects as a powerful inhibitor of complement. This study addressed both the question of whether sCR1 was found in bronchoalveolar lavage (BAL) of normals and patients with various inflammatory disease, and its possible origin. In this retrospective study covering specimen and clinical data of 124 patients with acute and chronic inflammatory lung pathologies, BAL supernatants were analysed by enzyme-linked immunosorbent assay technique for sCR1. Correlations were made between the sCR1 levels obtained and the constituents of BAL. Human alveolar macrophages were cultivated in order to determine their secretory capacity of sCR1. Alveolar macrophages from normal subjects were shown to release sCR1 in vitro. In addition, sCR1 was present in BAL of normal controls and was significantly increased in acute inflammatory lung diseases such as acute respiratory distress syndrome (ARDS), bacterial and Pneumocystis carinii pneumonia, as well as in chronic inflammatory diseases such as interstitial lung fibrosis and sarcoidosis. In BAL of ARDS, bacterial, and P. carinii pneumonia, there was a good correlation between sCR1 and the absolute neutrophil counts. In sarcoidosis, a correlation was found with BAL lymphocyte counts. Serum sCR1 was not increased in patients compared to controls. Soluble complement receptor type 1 (sCR1) is found in the bronchoalveolar lavage in health as well as in acute and chronic inflammatory disease. Alveolar macrophages are capable of releasing sCR1 in vitro and may be the main physiological source of sCR1 in the alveoli. The good correlation between sCR1 and the absolute neutrophil or lymphocyte numbers in bronchoalveolar lavage of inflammatory diseases suggests a predominant role of leucocytes for the release of sCR1 in such conditions. The release of this

  14. Lung disease

    MedlinePlus

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

  15. The innate immune function of airway epithelial cells in inflammatory lung disease

    PubMed Central

    Hiemstra, Pieter S.; McCray, Paul B.; Bals, Robert

    2016-01-01

    The airway epithelium is now considered central to the orchestration of pulmonary inflammatory and immune responses, and is also key to tissue remodelling. It acts as a first barrier in the defence against a wide range of inhaled challenges, and is critically involved in the regulation of both innate and adaptive immune responses to these challenges. Recent progress in our understanding of the developmental regulation of this tissue, the differentiation pathways, recognition of pathogens and antimicrobial responses is now exploited to help understand how epithelial cell function and dysfunction contributes to the pathogenesis of a variety of inflammatory lung diseases. In the review, advances in our knowledge of the biology of airway epithelium, as well as its role and (dys)function in asthma, COPD and cystic fibrosis, are discussed. PMID:25700381

  16. 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

  17. The Role of Inflammasome in Inflammatory Macrophage in Mycobacterium Avium Complex-lung Disease and Mycobacterium Abscessus-lung Disease

    ClinicalTrials.gov

    2014-06-27

    To Investigate the Inflammasome Response of Inflammatory and Resting Macrophage; To Compare the Difference of Inflammasome Response of Inflammatory Macrophage; To Study the Diagnostic Aid From Immunological Markers in Inflammasome Response

  18. 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 ...

  19. Inflammatory bowel disease of the lung: The role of infliximab?☆

    PubMed Central

    Hayek, Adam J.; Pfanner, Timothy P.; White, Heath D.

    2015-01-01

    Pulmonary extra-intestinal manifestations (EIM) of inflammatory bowel disease are well described with a variable incidence. We present a case of Crohn's disease with pulmonary EIM including chronic bronchitis with non-resolving bilateral cavitary pulmonary nodules and mediastinal lymphadenopathy successfully treated with infliximab. Additionally, we present a case summary from a literature review on pulmonary EIM successfully treated with infliximab. Current treatment recommendations include an inhaled and/or systemic corticosteroid regimen which is largely based on case reports and expert opinion. We offer infliximab as an adjunctive therapy or alternative to corticosteroids for treatment of inflammatory bowel disease related pulmonary EIM. PMID:26236612

  20. Pleural fluid analysis of lung cancer vs benign inflammatory disease patients

    PubMed Central

    Kremer, R; Best, L A; Savulescu, D; Gavish, M; Nagler, R M

    2010-01-01

    Background: Correct diagnosis of pleural effusion (PE) as either benign or malignant is crucial, although conventional cytological evaluation is of limited diagnostic accuracy, with relatively low sensitivity rates. Methods: We identified biological markers accurately detected in a simple PE examination. We analysed data from 19 patients diagnosed with lung cancer (nine adeno-Ca, five non-small-cell Ca (not specified), four squamous-cell Ca, one large-cell Ca) and 22 patients with benign inflammatory pathologies: secondary to trauma, pneumonia or TB. Results: Pleural effusion concentrations of seven analysed biological markers were significantly lower in lung cancer patients than in benign inflammatory patients, especially in matrix metalloproteinase (MMP)-9, MMP-3 and CycD1 (lower by 65% (P<0.000003), 40% (P<0.0007) and 34% (P<0.0001), respectively), and in Ki67, ImAnOx, carbonyls and p27. High rates of sensitivity and specificity values were found for MMP-9, MMP-3 and CycD1: 80 and 100% 87 and 73% and 87 and 82%, respectively. Conclusion: Although our results are of significant merit in both the clinical and pathogenetic aspects of lung cancer, further research aimed at defining the best combination for marker analysis is warranted. The relative simplicity in analysing these markers in any routine hospital laboratory may result in its acceptance as a new diagnostic tool. PMID:20216542

  1. Inflammatory Bowel Disease

    MedlinePlus

    ... work? How does inflammatory bowel disease interfere with digestion? Who gets inflammatory bowel disease? How is inflammatory ... top How does inflammatory bowel disease interfere with digestion? When the small intestine becomes inflamed, as in ...

  2. Targeted anti-inflammatory therapeutics in asthma and chronic obstructive lung disease

    PubMed Central

    Durham, Andrew L.; Caramori, Gaetano; Chung, Kian F.; Adcock, Ian M.

    2016-01-01

    Asthma and chronic obstructive pulmonary disease (COPD) are chronic inflammatory diseases of the airway, although the drivers and site of the inflammation differ between diseases. Asthmatics with a neutrophilic airway inflammation are associated with a poor response to corticosteroids, whereas asthmatics with eosinophilic inflammation respond better to corticosteroids. Biologicals targeting the Th2-eosinophil nexus such as anti–interleukin (IL)-4, anti–IL-5, and anti–IL-13 are ineffective in asthma as a whole but are more effective if patients are selected using cellular (eg, eosinophils) or molecular (eg, periostin) biomarkers. This highlights the key role of individual inflammatory mediators in driving the inflammatory response and for accurate disease phenotyping to allow greater understanding of disease and development of patient-oriented antiasthma therapies. In contrast to asthmatic patients, corticosteroids are relatively ineffective in COPD patients. Despite stratification of COPD patients, the results of targeted therapy have proved disappointing with the exception of recent studies using CXC chemokine receptor (CXCR)2 antagonists. Currently, several other novel mediator-targeted drugs are undergoing clinical trials. As with asthma specifically targeted treatments may be of most benefit in specific COPD patient endotypes. The use of novel inflammatory mediator-targeted therapeutic agents in selected patients with asthma or COPD and the detection of markers of responsiveness or nonresponsiveness will allow a link between clinical phenotypes and pathophysiological mechanisms to be delineated reaching the goal of endotyping patients. PMID:26334389

  3. Targeted anti-inflammatory therapeutics in asthma and chronic obstructive lung disease.

    PubMed

    Durham, Andrew L; Caramori, Gaetano; Chung, Kian F; Adcock, Ian M

    2016-01-01

    Asthma and chronic obstructive pulmonary disease (COPD) are chronic inflammatory diseases of the airway, although the drivers and site of the inflammation differ between diseases. Asthmatics with a neutrophilic airway inflammation are associated with a poor response to corticosteroids, whereas asthmatics with eosinophilic inflammation respond better to corticosteroids. Biologicals targeting the Th2-eosinophil nexus such as anti-interleukin (IL)-4, anti-IL-5, and anti-IL-13 are ineffective in asthma as a whole but are more effective if patients are selected using cellular (eg, eosinophils) or molecular (eg, periostin) biomarkers. This highlights the key role of individual inflammatory mediators in driving the inflammatory response and for accurate disease phenotyping to allow greater understanding of disease and development of patient-oriented antiasthma therapies. In contrast to asthmatic patients, corticosteroids are relatively ineffective in COPD patients. Despite stratification of COPD patients, the results of targeted therapy have proved disappointing with the exception of recent studies using CXC chemokine receptor (CXCR)2 antagonists. Currently, several other novel mediator-targeted drugs are undergoing clinical trials. As with asthma specifically targeted treatments may be of most benefit in specific COPD patient endotypes. The use of novel inflammatory mediator-targeted therapeutic agents in selected patients with asthma or COPD and the detection of markers of responsiveness or nonresponsiveness will allow a link between clinical phenotypes and pathophysiological mechanisms to be delineated reaching the goal of endotyping patients.

  4. 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 ...

  5. The Th17 Pathway and Inflammatory Diseases of the Intestines, Lungs and Skin

    PubMed Central

    Weaver, Casey T.; Elson, Charles O.; Fouser, Lynette A.; Kolls, Jay K.

    2014-01-01

    The recent emergence of a new CD4+ T cell subset, Th17, has transformed our understanding of the pathogenetic basis of an increasing number of chronic immune-mediated diseases. Particularly in tissues that interface with the microbial environment — such as the intestinal and respiratory tracts, and skin — where most of the Th17 cells present in the body reside, dysregulated immunity to self, or the extended “self,” the diverse microbiota that normally colonize these tissues, can result in chronic inflammatory disease. In this review, we focus on recent advances in the biology of the Th17 pathway and genome-wide association studies (GWAS) implicating this immune pathway in human disease that are providing new insights into disease mechanisms in these and other tissues. PMID:23157335

  6. Evidences of Herbal Medicine-Derived Natural Products Effects in Inflammatory Lung Diseases

    PubMed Central

    Mernak, Márcia Isabel B.; Martins, Mílton A.; Lago, João H. G.; Tibério, Iolanda F. L. C.

    2016-01-01

    Pulmonary inflammation is a hallmark of many respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and acute respiratory syndrome distress (ARDS). Most of these diseases are treated with anti-inflammatory therapy in order to prevent or to reduce the pulmonary inflammation. Herbal medicine-derived natural products have been used in folk medicine and scientific studies to evaluate the value of these compounds have grown in recent years. Many substances derived from plants have the biological effects in vitro and in vivo, such as flavonoids, alkaloids, and terpenoids. Among the biological activities of natural products derived from plants can be pointed out the anti-inflammatory, antiviral, antiplatelet, antitumor anti-allergic activities, and antioxidant. Although many reports have evaluated the effects of these compounds in experimental models, studies evaluating clinical trials are scarce in the literature. This review aims to emphasize the effects of these different natural products in pulmonary diseases in experimental models and in humans and pointing out some possible mechanisms of action. PMID:27445433

  7. Levels of Soluble Receptor for Advanced Glycation End Products in Bronchoalveolar Lavage Fluid in Patients with Various Inflammatory Lung Diseases

    PubMed Central

    Kamo, Tetsuro; Tasaka, Sadatomo; Tokuda, Yuriko; Suzuki, Shoji; Asakura, Takanori; Yagi, Kazuma; Namkoong, Ho; Ishii, Makoto; Hasegawa, Naoki; Betsuyaku, Tomoko

    2015-01-01

    Receptor for advanced glycation end products (RAGE) is a multiligand receptor of S100/calgranulins, high-mobility group box 1, and others, and it is associated with the pathogenesis of various inflammatory and circulatory diseases. The soluble form of RAGE (sRAGE) is a decoy receptor and competitively inhibits membrane-bound RAGE activation. In this study, we measured sRAGE levels in bronchoalveolar lavage fluid (BALF) of 78 patients, including 41 with interstitial pneumonia, 11 with sarcoidosis, 9 with respiratory infection, 7 with ARDS, 5 with lung cancer, and 5 with vasculitis. Among them, sRAGE was detectable in BALF of 73 patients (94%). In patients with ARDS and vasculitis, the sRAGE levels were significantly higher than in the control subjects and those with interstitial pneumonia. The sRAGE levels were positively correlated with total cell counts in BALF and serum levels of surfactant protein-D, lactate dehydrogenase, and C-reactive protein. There was an inverse correlation between PaO2/FIO2 ratio and sRAGE levels. These results indicate that sRAGE in BALF might be considered as a biomarker of lung inflammatory disorders, especially ARDS and vasculitis. PMID:27147899

  8. 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 ...

  9. Incidental Paratracheal Air Cysts on Thoracic CT and Their Association with Chronic Inflammatory Lung Disease

    PubMed Central

    Kim, Ha Yeon; Lee, Kyung Hee; Kim, Yeo Ju; Lee, Ha Young; Kim, Ga Ram; Jeon, Yong Sun; Kim, Jung Soo; Kim, Young Sam

    2017-01-01

    Purpose. To determine the association between the progression of upper lung fibrosis and paratracheal air cysts (PACs) size. Materials and Methods. The thoracic CT images of 4573 patients were reviewed for the prevalence, size, and location of PACs and their communication with trachea. In addition, the presence of upper lung fibrosis, emphysema, and bronchiectasis was evaluated in patients with PACs and compared with a control group without PACs. Upper lung fibrosis was analyzed using a fibrosis score system. Results. The prevalence of PACs was 6.8%. Communication with tracheal lumen was demonstrated by 31.5% of patients with PACs. The prevalence of fibrosis, emphysema, and bronchiectasis in patients with PACs were 67.5%, 21.9%, and 28.3%, respectively. The prevalence of fibrosis was significantly different in the two groups by univariable and multivariable analysis (odds ratio = 2.077, P < 0.001). 140 patients with fibrosis among PAC group underwent a previous or follow-up CT; the prevalence with increase in PAC sizes was higher in patients with increase in fibrosis score than those without it (66.2% versus 17.3%, P < 0.001). Conclusions. PACs appear to be highly related to upper lung fibrosis and moderately related to bronchiectasis. In patients with fibrosis, PAC sizes tended to increase with the progression of upper lung fibrosis.

  10. 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 ...

  11. Pediatric inflammatory bowel disease

    PubMed Central

    Diefenbach, Karen A; Breuer, Christopher K

    2006-01-01

    Inflammatory bowel disease is an important cause of gastrointestinal pathology in children and adolescents. The incidence of pediatric inflammatory bowel disease is increasing; therefore, it is important for the clinician to be aware of the presentation of this disease in the pediatric population. Laboratory tests, radiology studies, and endoscopic procedures are helpful in diagnosing inflammatory bowel disease and differentiating between Crohn’s disease and ulcerative colitis. Once diagnosed, the goal of medical management is to induce remission of disease while minimizing the side effects of the medication. Specific attention needs to be paid to achieving normal growth in this susceptible population. Surgical management is usually indicated for failure of medical management, complication, or malignancy. Algorithms for diagnostic evaluation and treatment of pediatric inflammatory bowel disease are presented. The specific psychosocial issues facing these patients are also discussed in this review as are the future goals of research in the complex problem of pediatric inflammatory bowel disease. PMID:16718840

  12. Pelvic Inflammatory Disease (PID)

    MedlinePlus

    Pelvic Inflammatory Disease (PID) - CDC Fact Sheet Untreated sexually transmitted diseases (STDs) can cause pelvic inflammatory disease (PID), a ... tubal blockage; •• Ectopic pregnancy (pregnancy outside the womb); •• Infertility (inability to get pregnant); •• Long-term pelvic/abdominal ...

  13. Metal-sulfide mineral ores, Fenton chemistry and disease. Particle induced inflammatory stress response in lung cells

    DOE PAGES

    Harrington, Andrea D.; Smirnov, Alexander; Tsirka, Stella E.; ...

    2014-07-10

    The inhalation of mineral particulates and other earth materials, such as coal, can initiate or enhance disease in humans. Workers in occupations with high particulate exposure, such as mining, are particularly at risk. The ability of a material to generate an inflammatory stress response (ISR), a measure of particle toxicity, is a useful tool in evaluating said exposure risk. ISR is defined as the upregulation of cellular reactive oxygen species (ROS) normalized to cell viability. This study compares the ISR of A549 human lung epithelial cells after exposure to well-characterized common metal-sulfide ore mineral separates. The evaluation of the deleteriousmore » nature of ore minerals is based on a range of particle loadings (serial dilutions of 0.002 m2/mL stock) and exposure periods (beginning at 30 min and measured systematically for up to 24 h). There is a wide range in ISR values generated by the ore minerals. The ISR values produced by the sphalerite samples are within the range of inert materials. Arsenopyrite generated a small ISR that was largely driven by cell death. Galena showed a similar, but more pronounced response. Copper-bearing ore minerals generated the greatest ISR, both by upregulating cellular ROS and generating substantial and sustained cell death. Chalcopyrite and bornite, both containing ferrous iron, generated the greatest ISR overall. Particles containing Fenton metals as major constituents produce the highest ISR, while other heavy metals mainly generate cell death. Furthermore, this study highlights the importance of evaluating the chemistry, oxidation states and structure of a material when assessing risk management.« less

  14. Metal-sulfide mineral ores, Fenton chemistry and disease. Particle induced inflammatory stress response in lung cells

    SciTech Connect

    Harrington, Andrea D.; Smirnov, Alexander; Tsirka, Stella E.; Schoonen, Martin A. A.

    2014-07-10

    The inhalation of mineral particulates and other earth materials, such as coal, can initiate or enhance disease in humans. Workers in occupations with high particulate exposure, such as mining, are particularly at risk. The ability of a material to generate an inflammatory stress response (ISR), a measure of particle toxicity, is a useful tool in evaluating said exposure risk. ISR is defined as the upregulation of cellular reactive oxygen species (ROS) normalized to cell viability. This study compares the ISR of A549 human lung epithelial cells after exposure to well-characterized common metal-sulfide ore mineral separates. The evaluation of the deleterious nature of ore minerals is based on a range of particle loadings (serial dilutions of 0.002 m2/mL stock) and exposure periods (beginning at 30 min and measured systematically for up to 24 h). There is a wide range in ISR values generated by the ore minerals. The ISR values produced by the sphalerite samples are within the range of inert materials. Arsenopyrite generated a small ISR that was largely driven by cell death. Galena showed a similar, but more pronounced response. Copper-bearing ore minerals generated the greatest ISR, both by upregulating cellular ROS and generating substantial and sustained cell death. Chalcopyrite and bornite, both containing ferrous iron, generated the greatest ISR overall. Particles containing Fenton metals as major constituents produce the highest ISR, while other heavy metals mainly generate cell death. Furthermore, this study highlights the importance of evaluating the chemistry, oxidation states and structure of a material when assessing risk management.

  15. Metal-sulfide mineral ores, Fenton chemistry and disease--particle induced inflammatory stress response in lung cells.

    PubMed

    Harrington, Andrea D; Smirnov, Alexander; Tsirka, Stella E; Schoonen, Martin A A

    2015-01-01

    The inhalation of mineral particulates and other earth materials, such as coal, can initiate or enhance disease in humans. Workers in occupations with high particulate exposure, such as mining, are particularly at risk. The ability of a material to generate an inflammatory stress response (ISR), a measure of particle toxicity, is a useful tool in evaluating said exposure risk. ISR is defined as the upregulation of cellular reactive oxygen species (ROS) normalized to cell viability. This study compares the ISR of A549 human lung epithelial cells after exposure to well-characterized common metal-sulfide ore mineral separates. The evaluation of the deleterious nature of ore minerals is based on a range of particle loadings (serial dilutions of 0.002m(2)/mL stock) and exposure periods (beginning at 30min and measured systematically for up to 24h). There is a wide range in ISR values generated by the ore minerals. The ISR values produced by the sphalerite samples are within the range of inert materials. Arsenopyrite generated a small ISR that was largely driven by cell death. Galena showed a similar, but more pronounced response. Copper-bearing ore minerals generated the greatest ISR, both by upregulating cellular ROS and generating substantial and sustained cell death. Chalcopyrite and bornite, both containing ferrous iron, generated the greatest ISR overall. Particles containing Fenton metals as major constituents produce the highest ISR, while other heavy metals mainly generate cell death. This study highlights the importance of evaluating the chemistry, oxidation states and structure of a material when assessing risk management.

  16. Pelvic Inflammatory Disease

    MedlinePlus

    Pelvic inflammatory disease (PID) is an infection and inflammation of the uterus, ovaries, and other female reproductive organs. It causes scarring ... United States. Gonorrhea and chlamydia, two sexually transmitted diseases, are the most common causes of PID. Other ...

  17. Pelvic Inflammatory Disease

    MedlinePlus

    ... Weström, L., Joesoef, R., Reynolds, G., Hagdu, A., Thompson, S.E. (1992). Pelvic inflammatory disease and fertility. A ... Weström, L., Joesoef, R., Reynolds, G., Hagdu, A., Thompson, S.E. (1992). Pelvic inflammatory disease and fertility. A ...

  18. Childhood Interstitial Lung Disease

    MedlinePlus

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

  19. Curcumin in inflammatory diseases.

    PubMed

    Shehzad, Adeeb; Rehman, Gauhar; Lee, Young Sup

    2013-01-01

    Curcumin (diferuloylmethane), a yellow coloring agent extracted from turmeric is also used as a remedy for the treatment and prevention of inflammatory diseases. Acute and chronic inflammation is a major factor in the progression of obesity, type II diabetes, arthritis, pancreatitis, cardiovascular, neurodegenerative and metabolic diseases, as well as certain types of cancer. Turmeric has a long history of use in Ayurvedic medicine for the treatment of inflammatory disorders. Recent studies on the efficacy and therapeutic applicability of turmeric have suggested that the active ingredient of tumeric is curcumin. Further, compelling evidence has shown that curcumin has the ability to inhibit inflammatory cell proliferation, invasion, and angiogenesis through multiple molecular targets and mechanisms of action. Curcumin is safe, non-toxic, and mediates its anti-inflammatory effects through the down-regulation of inflammatory transcription factors, cytokines, redox status, protein kinases, and enzymes that all promote inflammation. In addition, curcumin induces apoptosis through mitochondrial and receptor-mediated pathways, as well as activation of caspase cascades. In the current study, the anti-inflammatory effects of curcumin were evaluated relative to various chronic inflammatory diseases. Based on the available pharmacological data obtained from in vitro and in vivo research, as well as clinical trials, an opportunity exists to translate curcumin into clinics for the prevention of inflammatory diseases in the near future.

  20. [Inflammatory pseudotumor of the lung. Case report].

    PubMed

    Santos, Nelson; Guerra, Miguel; Ferreira, Diva; Leal, Francisco; Miranda, José; Shiang, Teresa; Leal, Francisco; Vouga, Luis

    2007-01-01

    Inflammatory pseudotumor of the lung is a rare entity, of unknown etiology and variable clinical evolution. The histological variety of this entity makes the diagnosis difficult, which is generally obtained after surgical removal of the lesion. The authors report the clinical case of a 32 years old woman presenting with hemoptysis and radiologic appearance of aspergilloma. The lesion was surgically removed and the diagnosis of inflammatory pseudotumor of the lung was confirmed by pathologic and immunohistochemical analysis.

  1. Evolution of Inflammatory Diseases

    PubMed Central

    Okin, Daniel

    2013-01-01

    The association of inflammation with modern human diseases (e.g. obesity, cardiovascular disease, type 2 diabetes mellitus, cancer) remains an unsolved mystery of current biology and medicine. Inflammation is a protective response to noxious stimuli that unavoidably occurs at a cost to normal tissue function. This fundamental tradeoff between the cost and benefit of the inflammatory response has been optimized over evolutionary time for specific environmental conditions. Rapid change of the human environment due to niche construction outpaces genetic adaptation through natural selection, leading increasingly to a mismatch between the modern environment and selected traits. Consequently, multiple tradeoffs that affect human physiology are not optimized to the modern environment, leading to increased disease susceptibility. Here we examine the inflammatory response from an evolutionary perspective. We discuss unique aspects of the inflammatory response and its evolutionary history that can help explain the association between inflammation and modern human diseases. PMID:22975004

  2. Anti-inflammatory effect of prophylactic macrolides on children with chronic lung disease: a protocol for a double-blinded randomised controlled trial

    PubMed Central

    Mosquera, Ricardo A; Gomez-Rubio, Ana M; Harris, Tomika; Yadav, Aravind; McBeth, Katrina; Gonzales, Traci; Jon, Cindy; Stark, James; Avritscher, Elenir; Pedroza, Claudia; Smith, Keely; Colasurdo, Giuseppe; Wootton, Susan; Piedra, Pedro; Tyson, Jon E; Samuels, Cheryl

    2016-01-01

    Introduction Recent studies suggest that the high mortality rate of respiratory viral infections is a result of an overactive neutrophilic inflammatory response. Macrolides have anti-inflammatory properties, including the ability to downregulate the inflammatory cascade, attenuate excessive cytokine production in viral infections, and may reduce virus-related exacerbations. In this study, we will test the hypothesis that prophylactic macrolides will reduce the severity of respiratory viral illness in children with chronic lung disease by preventing the full activation of the inflammatory cascade. Methods and analysis A randomised double-blind placebo-controlled trial that will enrol 92 children to receive either azithromycin or placebo for a period of 3–6 months during two respiratory syncytial virus (RSV) seasons (2015–2016 and 2016–2017). We expect a reduction of at least 20% in the total number of days of unscheduled face-to-face encounters in the treatment group as compared with placebo group. Standard frequentist and Bayesian analyses will be performed using an intent-to-treat approach. Discussion We predict that the prophylactic use of azithromycin will reduce the morbidity associated with respiratory viral infections during the winter season in patients with chronic lung disease as evidenced by a reduction in the total number of days with unscheduled face-to-face provider encounters. Ethics and dissemination This research study was approved by the Institutional Review Board of the University of Texas Health Science Center in Houston on 9 October 2014. On completion, the results will be published. Trial registration number NCT02544984. PMID:27638496

  3. Non-small cell lung cancer is characterised by a distinct inflammatory signature in serum compared with chronic obstructive pulmonary disease

    PubMed Central

    Eide, Hanne Astrid; Halvorsen, Ann Rita; Sandhu, Vandana; Fåne, Anne; Berg, Janna; Haakensen, Vilde Drageset; Kure, Elin H; Brustugun, Odd Terje; Kiserud, Cecilie Essholt; Kyte, Jon Amund; Helland, Åslaug

    2016-01-01

    Development of lung cancer is closely related to smoking in a majority of patients. Most smokers, however, do not develop lung cancer in spite of a high mutational load accumulating in the lung tissue. Here we investigate whether a cancer-specific footprint can be revealed by investigating circulating inflammatory markers in patients with non-small cell lung cancer (NSCLC) compared with patients with chronic obstructive pulmonary disease (COPD), both cohorts characterised by similar smoking history. Serum concentrations of 57 cytokines and matrix metalloproteinases (MMPs) from 43 patients with advanced NSCLC were evaluated by multiplex immunoassays and compared with serum samples from 35 patients with COPD. Unsupervised hierarchical clustering and non-parametric analyses were performed. False discovery rate was used to adjust for multiple testing. Clustering of cytokine and MMP concentrations in the serum revealed a distinct separation of the NSCLC patients from the COPD group. Individual concentrations of thymus and activation-regulated cytokine (C-C motif chemokine ligand 17), Gro-b (C-X-C motif chemokine ligand 2 (CXCL2)), CXCL13, interleukin (IL)-1ra, IL-6, IL-8 (CXCL8), IL-16, IL-17A, macrophage migration inhibitory factor (MIF), granulocyte colony-stimulating factor, platelet-derived growth factor subunit B, MMP-2, MMP-8 and MMP-12 were significantly different in serum from NSCLC and COPD patients. Moreover, the interferon-γ/IL-10 ratio was lower in cancer patients compared with COPD patients, consistent with a cytokine milieu favouring tumour tolerance. Our results suggest that NSCLC is characterised by a distinct inflammatory signature in serum. The different cytokine profiles in NSCLC and COPD patients may represent tumour-promoting and tumour-suppressing immune responses developing in response to mucosal inflammation and mutations induced by smoking. PMID:27990285

  4. 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. ...

  5. Pelvic inflammatory disease

    PubMed Central

    2013-01-01

    Introduction Pelvic inflammatory disease is caused by infection of the upper female genital tract and is often asymptomatic. Pelvic inflammatory disease is the most common gynaecological reason for admission to hospital in the US, and is diagnosed in approximately 1% of women aged 16 to 45 years consulting their GP in England and Wales. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: How do different antimicrobial regimens compare when treating women with confirmed pelvic inflammatory disease? What are the effects of routine antibiotic prophylaxis to prevent pelvic inflammatory disease before intrauterine contraceptive device (IUD) insertion? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2013 (Clinical Evidence reviews are updated periodically; please check our website for the most up to date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 13 RCTs or systematic reviews of RCTs that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review, we present information relating to the effectiveness and safety of the following interventions: antibiotics (oral, parenteral, different durations, different regimens) and routine antibiotic prophylaxis (before intrauterine device insertion in women at high risk or low risk). PMID:24330771

  6. Lung Diseases and Conditions

    MedlinePlus

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

  7. Pelvic inflammatory disease

    PubMed Central

    2008-01-01

    Introduction Pelvic inflammatory disease is caused by infection of the upper female genital tract and is often asymptomatic. Pelvic inflammatory disease is the most common gynaecological reason for admission to hospital in the USA and is diagnosed in almost 2% of women aged 16 to 45 years consulting their GP in England and Wales. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of empirical treatment compared with treatment delayed until the results of microbiological investigations are known? How do different antimicrobial regimens compare? What are the effects of routine antibiotic prophylaxis to prevent pelvic inflammatory disease before intrauterine contraceptive device (IUD) insertion? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2007 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found nine systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review, we present information relating to the effectiveness and safety of the following interventions: antibiotics (oral, parenteral, empirical treatment, treatment guided by test results, different durations, outpatient, inpatient), and routine antibiotic prophylaxis (before intrauterine device insertion in women at high risk or low risk). PMID:19450319

  8. Vitamin D and inflammatory diseases

    PubMed Central

    Yin, Kai; Agrawal, Devendra K

    2014-01-01

    Beyond its critical function in calcium homeostasis, vitamin D has recently been found to play an important role in the modulation of the immune/inflammation system via regulating the production of inflammatory cytokines and inhibiting the proliferation of proinflammatory cells, both of which are crucial for the pathogenesis of inflammatory diseases. Several studies have associated lower vitamin D status with increased risk and unfavorable outcome of acute infections. Vitamin D supplementation bolsters clinical responses to acute infection. Moreover, chronic inflammatory diseases, such as atherosclerosis-related cardiovascular disease, asthma, inflammatory bowel disease, chronic kidney disease, nonalcoholic fatty liver disease, and others, tend to have lower vitamin D status, which may play a pleiotropic role in the pathogenesis of the diseases. In this article, we review recent epidemiological and interventional studies of vitamin D in various inflammatory diseases. The potential mechanisms of vitamin D in regulating immune/inflammatory responses in inflammatory diseases are also discussed. PMID:24971027

  9. Indium Lung Disease

    PubMed Central

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

    2012-01-01

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

  10. Chronic inflammatory systemic diseases

    PubMed Central

    Straub, Rainer H.; Schradin, Carsten

    2016-01-01

    It has been recognized that during chronic inflammatory systemic diseases (CIDs) maladaptations of the immune, nervous, endocrine and reproductive system occur. Maladaptation leads to disease sequelae in CIDs. The ultimate reason of disease sequelae in CIDs remained unclear because clinicians do not consider bodily energy trade-offs and evolutionary medicine. We review the evolution of physiological supersystems, fitness consequences of genes involved in CIDs during different life-history stages, environmental factors of CIDs, energy trade-offs during inflammatory episodes and the non-specificity of CIDs. Incorporating bodily energy regulation into evolutionary medicine builds a framework to better understand pathophysiology of CIDs by considering that genes and networks used are positively selected if they serve acute, highly energy-consuming inflammation. It is predicted that genes that protect energy stores are positively selected (as immune memory). This could explain why energy-demanding inflammatory episodes like infectious diseases must be terminated within 3–8 weeks to be adaptive, and otherwise become maladaptive. Considering energy regulation as an evolved adaptive trait explains why many known sequelae of different CIDs must be uniform. These are, e.g. sickness behavior/fatigue/depressive symptoms, sleep disturbance, anorexia, malnutrition, muscle wasting—cachexia, cachectic obesity, insulin resistance with hyperinsulinemia, dyslipidemia, alterations of steroid hormone axes, disturbances of the hypothalamic-pituitary-gonadal (HPG) axis, hypertension, bone loss and hypercoagulability. Considering evolved energy trade-offs helps us to understand how an energy imbalance can lead to the disease sequelae of CIDs. In the future, clinicians must translate this knowledge into early diagnosis and symptomatic treatment in CIDs. PMID:26817483

  11. Inflammatory Bowel Disease

    PubMed Central

    Nasseri-Moghaddam, Siavosh

    2012-01-01

    Inflammatory bowel disease (IBD) is the term used for a group of diseases with yet unknown etiology, prevalence of which is increasing almost everywhere in the world. The disease was almost non-existent four decades ago in the east, including the middle-east, while now a days it is seen more and more. In addition to the increasing prevalence, our knowledge about its pathogenesis, clinical course, diagnosis, and treatment has changed dramatically over the past couple of decades. This has changed our concept of this group of diseases, their diagnosis, treatment, and treatment goals. Considering the vast literature on the subject, it is timely to review major topics in IBD with a look on the regional progress and knowledge as well. This essay is aimed to cover this task. PMID:24829639

  12. Inflammatory bowel disease unclassified

    PubMed Central

    Zhou, Ning; Chen, Wei-xing; Chen, Shao-hua; Xu, Cheng-fu; Li, You-ming

    2011-01-01

    Objective: Inflammatory bowel diseases (IBDs) are idiopathic, chronic, and inflammatory intestinal disorders. The two main types, ulcerative colitis (UC) and Crohn’s disease (CD), sometimes mimic each other and are not readily distinguishable. The purpose of this study was to present a series of hospitalized cases, which could not initially be classified as a subtype of IBD, and to try to note roles of the terms indeterminate colitis (IC) and inflammatory bowel disease unclassified (IBDU) when such a dilemma arises. Methods: Medical records of 477 patients hospitalized due to IBD, during the period of January 2002 to April 2009, were retrospectively studied in the present paper. All available previous biopsies from endoscopies of these patients were reanalyzed. Results: Twenty-seven of 477 IBD patients (5.7%) had been initially diagnosed as having IBDU. Of them, 23 received colonoscopy and histological examinations in our hospital. A total of 90% (9/10) and 66.7% (4/6) of patients, respectively, had a positive finding via wireless capsule endoscopy (CE) and double-balloon enteroscopy (DBE). The barium-swallow or small bowel follow-through (SBFT) was performed on 11 patients. Positive changes were observed under computer tomographic (CT) scanning in 89.5% (17/19) of patients. Reasonable treatment strategies were employed for all patients. Conclusions: Our data indicate that IBDU accounts for 5.7% of initial diagnoses of IBD. The definition of IBDU is valuable in clinical practice. For those who had no clear clinical, endoscopic, histological, or other features affording a diagnosis of either UC or CD, IBDU could be used parenthetically. PMID:21462383

  13. Pulmonary manifestations of inflammatory bowel disease

    PubMed Central

    Majewski, Sebastian

    2015-01-01

    Bronchopulmonary signs and symptoms are examples of variable extraintestinal manifestations of the inflammatory bowel diseases (IBD). These complications of Crohn's disease (CD) and ulcerative colitis (UC) seem to be underrecognized by both pulmonary physicians and gastroenterologists. The objective of the present review was to gather and summarize information on this particular matter, on the basis of available up-to-date literature. Tracheobronchial involvement is the most prevalent respiratory presentation, whereas IBD-related interstitial lung disease is less frequent. Latent and asymptomatic pulmonary involvement is not unusual. Differential diagnosis should always consider infections (mainly tuberculosis) and drug-induced lung pathology. The common link between intestinal disease and lung pathology is unknown, but many hypotheses have been proposed. It is speculated that environmental pollution, common immunological mechanisms and predisposing genetic factors may play a role. PMID:26788078

  14. Interstitial Lung Disease in Scleroderma

    PubMed Central

    Schoenfeld, Sara R.; Castelino, Flavia V.

    2015-01-01

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

  15. 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

  16. 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

  17. Adenosine deaminase 1 and concentrative nucleoside transporters 2 and 3 regulate adenosine on the apical surface of human airway epithelia: implications for inflammatory lung diseases.

    PubMed

    Hirsh, Andrew J; Stonebraker, Jaclyn R; van Heusden, Catja A; Lazarowski, Eduardo R; Boucher, Richard C; Picher, Maryse

    2007-09-11

    Adenosine is a multifaceted signaling molecule mediating key aspects of innate and immune lung defenses. However, abnormally high airway adenosine levels exacerbate inflammatory lung diseases. This study identifies the mechanisms regulating adenosine elimination from the apical surface of human airway epithelia. Experiments conducted on polarized primary cultures of nasal and bronchial epithelial cells showed that extracellular adenosine is eliminated by surface metabolism and cellular uptake. The conversion of adenosine to inosine was completely inhibited by the adenosine deaminase 1 (ADA1) inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA). The reaction exhibited Km and Vmax values of 24 microM and 0.14 nmol x min(-1) x cm(-2). ADA1 (not ADA2) mRNA was detected in human airway epithelia. The adenosine/mannitol permeability coefficient ratio (18/1) indicated a minor contribution of paracellular absorption. Adenosine uptake was Na+-dependent and was inhibited by the concentrative nucleoside transporter (CNT) blocker phloridzin but not by the equilibrative nucleoside transporter (ENT) blocker dipyridamole. Apparent Km and Vmax values were 17 microM and 7.2 nmol x min(-1) x cm(-2), and transport selectivity was adenosine = inosine = uridine > guanosine = cytidine > thymidine. CNT3 mRNA was detected throughout the airways, while CNT2 was restricted to nasal epithelia. Inhibition of adenosine elimination by EHNA or phloridzin raised apical adenosine levels by >3-fold and stimulated IL-13 and MCP-1 secretion by 6-fold. These responses were reproduced by the adenosine receptor agonist 5'-(N-ethylcarboxamido)adenosine (NECA) and blocked by the adenosine receptor antagonist, 8-(p-sulfophenyl) theophylline (8-SPT). This study shows that adenosine elimination on human airway epithelia is mediated by ADA1, CNT2, and CNT3, which constitute important regulators of adenosine-mediated inflammation.

  18. [Indium lung disease].

    PubMed

    Nakano, Makiko; Omae, Kazuyuki

    2014-02-01

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

  19. 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.

  20. [Cardiovascular disease and systemic inflammatory diseases].

    PubMed

    Cuende, José I; Pérez de Diego, Ignacio J; Godoy, Diego

    2016-01-01

    More than a century of research has shown that atherosclerosis is an inflammatory process more than an infiltrative or thrombogenic process. It has been demonstrated epidemiologically and by imaging techniques, that systemic inflammatory diseases (in particular, but not exclusively, rheumatoid arthritis and systemic lupus erythematosus) increase the atherosclerotic process, and has a demonstrated pathophysiological basis. Furthermore, treatments to control inflammatory diseases can modify the course of the atherosclerotic process. Although there are no specific scales for assessing cardiovascular risk in patients with these diseases, cardiovascular risk is high. A number of specific risk scales are being developed, that take into account specific factors such as the degree of inflammatory activity.

  1. 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.

  2. Lung disease in mice with cystic fibrosis.

    PubMed Central

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

    1997-01-01

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

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

    PubMed

    Cruse, Glenn; Bradding, Peter

    2016-05-05

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

  4. Quantitative Dual-Energy Computed Tomography Supports a Vascular Etiology of Smoking-induced Inflammatory Lung Disease

    PubMed Central

    Iyer, Krishna S.; Newell, John D.; Jin, Dakai; Fuld, Matthew K.; Saha, Punam K.; Hansdottir, Sif

    2016-01-01

    Rationale: Endothelial dysfunction is of interest in relation to smoking-associated emphysema, a component of chronic obstructive pulmonary disease (COPD). We previously demonstrated that computed tomography (CT)-derived pulmonary blood flow (PBF) heterogeneity is greater in smokers with normal pulmonary function tests (PFTs) but who have visual evidence of centriacinar emphysema (CAE) on CT. Objectives: We introduced dual-energy CT (DECT) perfused blood volume (PBV) as a PBF surrogate to evaluate whether the CAE-associated increased PBF heterogeneity is reversible with sildenafil. Methods: Seventeen PFT-normal current smokers were divided into CAE-susceptible (SS; n = 10) and nonsusceptible (NS; n = 7) smokers, based on the presence or absence of CT-detected CAE. DECT-PBV images were acquired before and 1 hour after administration of 20 mg oral sildenafil. Regional PBV and PBV coefficients of variation (CV), a measure of spatial blood flow heterogeneity, were determined, followed by quantitative assessment of the central arterial tree. Measurements and Main Results: After sildenafil administration, regional PBV-CV decreased in SS subjects but did not decrease in NS subjects (P < 0.05), after adjusting for age and pack-years. Quantitative evaluation of the central pulmonary arteries revealed higher arterial volume and greater cross-sectional area (CSA) in the lower lobes of SS smokers, which suggested arterial enlargement in response to increased peripheral resistance. After sildenafil, arterial CSA decreased in SS smokers but did not decrease in NS smokers (P < 0.01). Conclusions: These results demonstrate that sildenafil restores peripheral perfusion and reduces central arterial enlargement in normal SS subjects with little effect in NS subjects, highlighting DECT-PBV as a biomarker of reversible endothelial dysfunction in smokers with CAE. PMID:26569033

  5. Mitochondria in lung disease

    PubMed Central

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

    2016-01-01

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

  6. Mitochondria in lung disease.

    PubMed

    Cloonan, Suzanne M; Choi, Augustine M K

    2016-03-01

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

  7. Polyunsaturated fatty acids and inflammatory diseases.

    PubMed

    Gil, A

    2002-10-01

    Inflammation is overall a protective response, whose main goal is to liberate the human being of cellular lesions caused by micro-organisms, toxins, allergens, etc., as well as its consequences, and of death cells and necrotic tissues. Chronic inflammation, which is detrimental to tissues, is the basic pathogenic mechanism of hypersensitivity reactions against xenobiotics. Other frequent pathologies, for instance atherosclerosis, chronic hepatitis, inflammatory bowel disease (IBD), liver cirrhosis, lung fibrosis, psoriasis, and rheumatoid arthritis are also chronic inflammatory diseases. Chemical mediators of inflammation are derived from blood plasma or different cell-type activity. Biogenic amines, eicosanoids and cytokines are within the most important mediators of inflammatory processes. The different activities of eicosanoids derived from arachidonic acid (20:4 n-6) versus those derived from eicosapentaenoic acid (20:5 n-3) are one of the most important mechanisms to explain why n-3, or omega-3, polyunsaturated fatty acids (PUFA) exhibit anti-inflammatory properties in many inflammatory diseases. Dietary supplements ranging 1-8 g per day of n-3 PUFA have been reportedly beneficial in the treatment of IBD, eczema, psoriasis and rheumatoid arthritis. In addition, recent experimental studies in rats with experimental ulcerative colitis, induced by intrarectal injection of trinitrobenzene sulphonic acid, have documented that treatment with n-3 long-chain PUFA reduces mucosal damage as assessed by biochemical and histological markers of inflammation. Moreover, the defence antioxidant system in this model is enhanced in treated animals, provided that the n-3 PUFA supply is adequately preserved from oxidation.

  8. 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 ...

  9. Vitamin D in inflammatory diseases

    PubMed Central

    Wöbke, Thea K.; Sorg, Bernd L.; Steinhilber, Dieter

    2014-01-01

    Changes in vitamin D serum levels have been associated with inflammatory diseases, such as inflammatory bowel disease (IBD), rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis (MS), atherosclerosis, or asthma. Genome- and transcriptome-wide studies indicate that vitamin D signaling modulates many inflammatory responses on several levels. This includes (i) the regulation of the expression of genes which generate pro-inflammatory mediators, such as cyclooxygenases or 5-lipoxygenase, (ii) the interference with transcription factors, such as NF-κB, which regulate the expression of inflammatory genes and (iii) the activation of signaling cascades, such as MAP kinases which mediate inflammatory responses. Vitamin D targets various tissues and cell types, a number of which belong to the immune system, such as monocytes/macrophages, dendritic cells (DCs) as well as B- and T cells, leading to individual responses of each cell type. One hallmark of these specific vitamin D effects is the cell-type specific regulation of genes involved in the regulation of inflammatory processes and the interplay between vitamin D signaling and other signaling cascades involved in inflammation. An important task in the near future will be the elucidation of the regulatory mechanisms that are involved in the regulation of inflammatory responses by vitamin D on the molecular level by the use of techniques such as chromatin immunoprecipitation (ChIP), ChIP-seq, and FAIRE-seq. PMID:25071589

  10. Lung alveolar epithelium and interstitial lung disease.

    PubMed

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

    2009-01-01

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

  11. Biomarkers of Inflammatory Bowel Disease

    PubMed Central

    Fengming, Yi; Jianbing, Wu

    2014-01-01

    Inflammatory bowel disease (IBD) is a chronic disease mostly involved with intestine with unknown etiology. Diagnosis, evaluation of severity, and prognosis are still present as challenges for physicians. An ideal biomarker with the characters such as simple, easy to perform, noninvasive or microinvasive, cheap, rapid, and reproducible is helpful for patients and clinicians. Currently biomarkers applied in clinic include CRP, ESR, pANCA, ASCA, and fecal calprotectin. However, they are far from ideal. Lots of studies are focused on seeking for ideal biomarker for IBD. Herein, the paper reviewed recent researches on biomarkers of IBD to get advances of biomarkers in inflammatory bowel disease. PMID:24963213

  12. Macrophage polarization in inflammatory diseases.

    PubMed

    Liu, Yan-Cun; Zou, Xian-Biao; Chai, Yan-Fen; Yao, Yong-Ming

    2014-01-01

    Diversity and plasticity are two hallmarks of macrophages. M1 macrophages (classically activated macrophages) are pro-inflammatory and have a central role in host defense against infection, while M2 macrophages (alternatively activated macrophages) are associated with responses to anti-inflammatory reactions and tissue remodeling, and they represent two terminals of the full spectrum of macrophage activation. Transformation of different phenotypes of macrophages regulates the initiation, development, and cessation of inflammatory diseases. Here we reviewed the characters and functions of macrophage polarization in infection, atherosclerosis, obesity, tumor, asthma, and sepsis, and proposed that targeting macrophage polarization and skewing their phenotype to adapt to the microenvironment might hold great promise for the treatment of inflammatory diseases.

  13. Inflammatory Bowel Disease (IBD) and Pregnancy

    MedlinePlus

    ... Inflammatory Bowel Disease? Inflammatory bowel disease (IBD) includes Crohn’s disease (CD) and ulcerative colitis (UC). Symptoms include abdominal ... become pregnant? Women with ulcerative colitis and inactive Crohn’s disease are as likely to become pregnant as women ...

  14. What Are Asbestos-Related Lung Diseases?

    MedlinePlus

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

  15. Diet and Inflammatory Bowel Disease.

    PubMed

    Knight-Sepulveda, Karina; Kais, Susan; Santaolalla, Rebeca; Abreu, Maria T

    2015-08-01

    Patients with inflammatory bowel disease (IBD) are increasingly becoming interested in nonpharmacologic approaches to managing their disease. One of the most frequently asked questions of IBD patients is what they should eat. The role of diet has become very important in the prevention and treatment of IBD. Although there is a general lack of rigorous scientific evidence that demonstrates which diet is best for certain patients, several diets-such as the low-fermentable oligosaccharide, disaccharide, monosaccharide, and polyol diet; the specific carbohydrate diet; the anti-inflammatory diet; and the Paleolithic diet-have become popular. This article discusses the diets commonly recommended to IBD patients and reviews the supporting data.

  16. Diet in inflammatory bowel disease.

    PubMed

    Issa, Mazen; Saeian, Kia

    2011-04-01

    The past few years have seen a great expansion of our understanding of the pathophysiology of inflammatory bowel disease (IBD). Much of the progress has been on the genetic basis of disease as well as the role of microbiota. These findings have magnified the role of the environmental component of this rather complex process. Recent advances have emanated from more in-depth, comprehensive, and at times nontraditional inquiry into the potential role of diet through its anti-inflammatory properties and modulation of microbiota. This concise review focuses on the novel aspects of research related to the potential role of diet in IBD.

  17. Platelets protect lung from injury induced by systemic inflammatory response

    PubMed Central

    Luo, Shuhua; Wang, Yabo; An, Qi; Chen, Hao; Zhao, Junfei; Zhang, Jie; Meng, Wentong; Du, Lei

    2017-01-01

    Systemic inflammatory responses can severely injure lungs, prompting efforts to explore how to attenuate such injury. Here we explored whether platelets can help attenuate lung injury in mice resulting from extracorporeal circulation (ECC)-induced systemic inflammatory responses. Mice were subjected to ECC for 30 min, then treated with phosphate-buffered saline, platelets, the GPIIb/IIIa inhibitor Tirofiban, or the combination of platelets and Tirofiban. Blood and lung tissues were harvested 60 min later, and lung injury and inflammatory status were assessed. As expected, ECC caused systemic inflammation and pulmonary dysfunction, and platelet transfusion resulted in significantly milder lung injury and higher lung function. It also led to greater numbers of circulating platelet-leukocyte aggregates and greater platelet accumulation in the lung. Platelet transfusion was associated with higher production of transforming growth factor-β and as well as lower levels of tumour necrosis factor-α and neutrophil elastase in plasma and lung. None of these platelet effects was observed in the presence of Tirofiban. Our results suggest that, at least under certain conditions, platelets can protect lung from injury induced by systemic inflammatory responses. PMID:28155889

  18. 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.

  19. Inflammatory Bowel Disease (For Children)

    MedlinePlus

    ... be caused by a defect in the body's immune system . continue What Are the Symptoms of IBD? Inflammatory bowel disease can cause symptoms that range from mild to severe. Symptoms can include: diarrhea that happens again and again, with or without ...

  20. Gastroesophageal reflux and lung disease.

    PubMed

    Meyer, Keith C

    2015-08-01

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

  1. Therapeutic Potential of Medicinal Plants and Their Constituents on Lung Inflammatory Disorders

    PubMed Central

    Kim, Hyun Pyo; Lim, Hyun; Kwon, Yong Soo

    2017-01-01

    Acute bronchitis and chronic obstructive pulmonary diseases (COPD) are essentially lung inflammatory disorders. Various plant extracts and their constituents showed therapeutic effects on several animal models of lung inflammation. These include coumarins, flavonoids, phenolics, iridoids, monoterpenes, diterpenes and triterpenoids. Some of them exerted inhibitory action mainly by inhibiting the mitogen-activated protein kinase pathway and nuclear transcription factor-κB activation. Especially, many flavonoid derivatives distinctly showed effectiveness on lung inflammation. In this review, the experimental data for plant extracts and their constituents showing therapeutic effectiveness on animal models of lung inflammation are summarized. PMID:27956716

  2. Anaemia in inflammatory rheumatic diseases.

    PubMed

    Weiss, Günter; Schett, Georg

    2013-04-01

    Anaemia is frequently observed in patients with inflammatory rheumatic diseases. Depending on its severity, anaemia negatively affects cardiovascular performance, physical activity and the quality of life of patients. However, anaemia is considered to be a symptom of the underlying inflammatory disease and, thus, neglected as a complex medical condition that warrants specific diagnosis and treatment. Although inflammation-induced alterations in iron homeostasis and erythropoiesis have a dominant role in the pathogenesis of this type of anaemia, multiple other factors such as chronic blood loss, haemolysis, disease and treatment-associated adverse effects or vitamin deficiencies can also take part in the development of anaemia. Accordingly, the prevalence of anaemia is positively associated with the severity of the underlying disease. This Review will summarize epidemiological data on anaemia in inflammatory rheumatic diseases, along with a detailed description of underlying pathophysiological pathways, available diagnostic tools and practical diagnostic strategies. Discussion of established and newly emerging treatment regimens, as well as the need for further research in this clinically relevant field, will also be included.

  3. Inflammatory diseases modelling in zebrafish

    PubMed Central

    Morales Fénero, Camila Idelí; Colombo Flores, Alicia Angelina; Câmara, Niels Olsen Saraiva

    2016-01-01

    The ingest of diets with high content of fats and carbohydrates, low or no physical exercise and a stressful routine are part of the everyday lifestyle of most people in the western world. These conditions are triggers for different diseases with complex interactions between the host genetics, the metabolism, the immune system and the microbiota, including inflammatory bowel diseases (IBD), obesity and diabetes. The incidence of these disorders is growing worldwide; therefore, new strategies for its study are needed. Nowadays, the majority of researches are in use of murine models for understand the genetics, physiopathology and interaction between cells and signaling pathways to find therapeutic solutions to these diseases. The zebrafish, a little tropical water fish, shares 70% of our genes and conserves anatomic and physiological characteristics, as well as metabolical pathways, with mammals, and is rising as a new complementary model for the study of metabolic and inflammatory diseases. Its high fecundity, fast development, transparency, versatility and low cost of maintenance makes the zebrafish an interesting option for new researches. In this review, we offer a discussion of the existing genetic and induced zebrafish models of two important Western diseases that have a strong inflammatory component, the IBD and the obesity. PMID:26929916

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

    PubMed

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

    2014-01-01

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

  5. Linking lung function and inflammatory responses in ventilator-induced lung injury.

    PubMed

    Cannizzaro, Vincenzo; Hantos, Zoltan; Sly, Peter D; Zosky, Graeme R

    2011-01-01

    Despite decades of research, the mechanisms of ventilator-induced lung injury are poorly understood. We used strain-dependent responses to mechanical ventilation in mice to identify associations between mechanical and inflammatory responses in the lung. BALB/c, C57BL/6, and 129/Sv mice were ventilated using a protective [low tidal volume and moderate positive end-expiratory pressure (PEEP) and recruitment maneuvers] or injurious (high tidal volume and zero PEEP) ventilation strategy. Lung mechanics and lung volume were monitored using the forced oscillation technique and plethysmography, respectively. Inflammation was assessed by measuring numbers of inflammatory cells, cytokine (IL-6, IL-1β, and TNF-α) levels, and protein content of the BAL. Principal components factor analysis was used to identify independent associations between lung function and inflammation. Mechanical and inflammatory responses in the lung were dependent on ventilation strategy and mouse strain. Three factors were identified linking 1) pulmonary edema, protein leak, and macrophages, 2) atelectasis, IL-6, and TNF-α, and 3) IL-1β and neutrophils, which were independent of responses in lung mechanics. This approach has allowed us to identify specific inflammatory responses that are independently associated with overstretch of the lung parenchyma and loss of lung volume. These data provide critical insight into the mechanical responses in the lung that drive local inflammation in ventilator-induced lung injury and the basis for future mechanistic studies in this field.

  6. Interstitial Lung Disease (ILD): Treatment

    MedlinePlus

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

  7. 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.

  8. Autophagy in lung disease pathogenesis and therapeutics.

    PubMed

    Ryter, Stefan W; Choi, Augustine M K

    2015-01-01

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

  9. Interstitial lung disease

    MedlinePlus

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

  10. Diet and Inflammatory Bowel Disease

    PubMed Central

    Knight-Sepulveda, Karina; Kais, Susan; Santaolalla, Rebeca

    2015-01-01

    Patients with inflammatory bowel disease (IBD) are increasingly becoming interested in nonpharmacologic approaches to managing their disease. One of the most frequently asked questions of IBD patients is what they should eat. The role of diet has become very important in the prevention and treatment of IBD. Although there is a general lack of rigorous scientific evidence that demonstrates which diet is best for certain patients, several diets—such as the low-fermentable oligosaccharide, disaccharide, monosaccharide, and polyol diet; the specific carbohydrate diet; the anti-inflammatory diet; and the Paleolithic diet—have become popular. This article discusses the diets commonly recommended to IBD patients and reviews the supporting data. PMID:27118948

  11. Pelvic Inflammatory Disease (PID) Treatment and Care

    MedlinePlus

    ... Pelvic Inflammatory Disease (PID) STDs & Infertility STDs & Pregnancy Syphilis Trichomoniasis Other STDs See Also Pregnancy Reproductive Health ... Pelvic Inflammatory Disease (PID) STDs & Infertility STDs & Pregnancy Syphilis Trichomoniasis Other STDs See Also Pregnancy Reproductive Health ...

  12. Pelvic Inflammatory Disease (PID) Fact Sheet

    MedlinePlus

    ... Pelvic Inflammatory Disease (PID) STDs & Infertility STDs & Pregnancy Syphilis Trichomoniasis Other STDs See Also Pregnancy Reproductive Health ... Pelvic Inflammatory Disease (PID) STDs & Infertility STDs & Pregnancy Syphilis Trichomoniasis Other STDs See Also Pregnancy Reproductive Health ...

  13. Aeroparticles, Composition, and Lung Diseases

    PubMed Central

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

    2016-01-01

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

  14. Inflammatory Muscle Disease: A New Landscape.

    PubMed

    Meyer, Alain; Lannes, Béatrice; Goetz, Joëlle; Echaniz-Laguna, Andoni; Lipsker, Dan; Arnaud, Laurent; Martin, Thierry; Gottenberg, Jacques Eric; Geny, Bernard; Sibilia, Jean

    2017-03-22

    Greater accuracy in clinical descriptions combined with advances in muscle histology and immunology have established that inflammatory muscle diseases (IMDs) resemble inflammatory joint diseases in that they constitute a highly heterogeneous group of conditions. The topographic distribution, severity, and tempo of onset vary widely, and the histological findings distinguish at least five different profiles, which may reflect different pathophysiological processes. Most IMDs are connective tissue diseases that can affect multiple organs, among which the most common targets are the skin, joints, and lungs. The extramuscular manifestations may antedate the muscular involvement and should therefore suggest a diagnosis of IMD even in the absence of obvious muscle disease. About 20 different autoantibodies have been identified in patients with IMD. Some are mutually exclusive and associated with specific combinations of clinical manifestations. Following the model of antisynthetase syndrome, about 10 syndromes associated with autoantibodies specific of IMD have been identified. Thus, polymyositis is now emerging as a rare entity that is often mistaken for more recently described patterns of IMD. No consensus exists to date about the classification of IMDs. Nevertheless, the clinical manifestations, autoantibody profile, and muscle histology can be used to distinguish patient subgroups with fairly homogeneous patterns of complications, treatment responses, and outcomes. These subgroups are also characterized by specific genetic and environmental factors. The advances made in the nosology of IMDs have benefited the diagnosis, personalization of treatment strategies, and understanding of pathophysiological mechanisms. They can be expected to assist in the development of specific treatments.

  15. Inflammatory Signalings Involved in Airway and Pulmonary Diseases

    PubMed Central

    Lee, I-Ta; Yang, Chuen-Mao

    2013-01-01

    In respiratory diseases, there is an increased expression of multiple inflammatory proteins in the respiratory tract, including cytokines, chemokines, and adhesion molecules. Chemokines have been shown to regulate inflammation and immune cell differentiation. Moreover, many of the known inflammatory target proteins, such as matrix metalloproteinase-9 (MMP-9), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), cyclooxygenase-2 (COX-2), and cytosolic phospholipase A2 (cPLA2), are associated with airway and lung inflammation in response to various stimuli. Injuriously environmental stimuli can access the lung through either the airways or the pulmonary and systemic circulations. The time course and intensity of responses by resident and circulating cells may be regulated by various inflammatory signalings, including Src family kinases (SFKs), protein kinase C (PKC), growth factor tyrosine kinase receptors, nicotinamide adenine dinucleotide phosphate (NADPH)/reactive oxygen species (ROS), PI3K/Akt, MAPKs, nuclear factor-kappa B (NF-κB), activator protein-1 (AP-1), and other signaling molecules. These signaling molecules regulate both key inflammatory signaling transduction pathways and target proteins involved in airway and lung inflammation. Here, we discuss the mechanisms involved in the expression of inflammatory target proteins associated with the respiratory diseases. Knowledge of the mechanisms of inflammation regulation could lead to the pharmacological manipulation of anti-inflammatory drugs in the respiratory diseases. PMID:23690670

  16. 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

  17. The emerging role of microRNAs in regulating immune and inflammatory responses in the lung.

    PubMed

    Foster, Paul S; Plank, Maximilian; Collison, Adam; Tay, Hock L; Kaiko, Gerard E; Li, Jingjing; Johnston, Sebastian L; Hansbro, Philip M; Kumar, Rakesh K; Yang, Ming; Mattes, Joerg

    2013-05-01

    Chronic inflammatory diseases of the lung are leading causes of morbidity and mortality worldwide. Many of these disorders can be attributed to abnormal immune responses to environmental stimuli and infections. As such, understanding the innate host defense pathways and their regulatory systems will be critical to developing new approaches to treatment. In this regard, there is increasing interest in the role of microRNAs (miRNAs) in the regulation of pulmonary innate host defense responses and the inflammatory sequelae in respiratory disease. In this review, we discuss recent findings that indicate an important role for miRNAs in the regulation in mouse models of various respiratory diseases and in host defense against bacterial and viral infection. We also discuss the potential utility and limitations of targeting these molecules as anti-inflammatory strategies and also as a means to improve pathogen clearance from the lung.

  18. Sleep in patients with restrictive lung disease.

    PubMed

    Won, Christine H J; Kryger, Meir

    2014-09-01

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

  19. 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.

  20. Epidemiology and inflammatory bowel diseases.

    PubMed

    El-Tawil, Ahmed Mahmoud

    2013-03-14

    The role of alcohol in causing or aggravating the pathogenesis of inflammatory bowel disease is unclear. For finding a conclusive answer for this valuable question we conducted this review. Only two studies were identified that successfully fulfilled our inclusive criteria. Usual consumption of alcohol reduced the risk compared with less frequent use (odds ratio = 0.57, 95%CI: 0.37-0.86). Light alcoholic drinking has protective effects against development of ulcerative colitis. But this inverse association disappeared when smoking was included.

  1. Microbiota biodiversity in inflammatory bowel disease

    PubMed Central

    2014-01-01

    Gut microbiota plays a significant role in human health and energy balance, and provides protection against disease states. An altered balance between microbiota and its host (dysbiosis) would appear to contribute to the development of Inflammatory Bowel Disease (IBD), Crohn’s Disease (CD) and Ulcerative Colitis (UC). CD and UC are chronic inflammatory diseases of the gastrointestinal tes. PMID:24684926

  2. Cardiovascular disease in inflammatory rheumatic diseases.

    PubMed

    Castañeda, Santos; Nurmohamed, Michael T; González-Gay, Miguel A

    2016-10-01

    Chronic inflammatory rheumatic diseases (IRD), including rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis, are prevalent conditions worldwide, with a considerable burden on healthcare systems. They are associated with increased cardiovascular (CV) morbidity and mortality. In this review, we focused on the epidemiology, traditional CV risk factors, genetics, and the link between chronic inflammation, atherosclerosis, and CV disease. Remarkably, patients with IRD have higher vulnerability to atheromatous plaques. The risk of unstable plaques is higher in patients with rheumatoid arthritis than in controls. Active disease is a characteristic ascribed to vulnerability and rupture of plaques and a cause of thrombosis in IRD. Management of CV risk in patients with IRD includes optimal control of disease activity. CV risk stratification by applying risk charts is also essential. Imaging techniques might be useful to determine the actual CV risk of patients with IRD who are included in the category of intermediate or moderate CV risk.

  3. 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

  4. Farmer's lung disease in Somerset.

    PubMed Central

    Pether, J V; Greatorex, F B

    1976-01-01

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

  5. Cannabis for inflammatory bowel disease.

    PubMed

    Naftali, Timna; Mechulam, Raphael; Lev, Lihi Bar; Konikoff, Fred M

    2014-01-01

    The marijuana plant Cannabis sativa has been used for centuries as a treatment for a variety of ailments. It contains over 60 different cannabinoid compounds. Studies have revealed that the endocannabinoid system is involved in almost all major immune events. Cannabinoids may, therefore, be beneficial in inflammatory disorders. In murine colitis, cannabinoids decrease histologic and microscopic inflammation. In humans, cannabis has been used to treat a plethora of gastrointestinal problems, including anorexia, emesis, abdominal pain, diarrhea, and diabetic gastroparesis. Despite anecdotal reports on medical cannabis in inflammatory bowel disease (IBD), there are few controlled studies. In an observational study in 30 patients with Crohn's disease (CD), we found that medical cannabis was associated with improvement in disease activity and reduction in the use of other medications. In a more recent placebo-controlled study in 21 chronic CD patients, we showed a decrease in the CD activity index >100 in 10 of 11 subjects on cannabis compared to 4 of 10 on placebo. Complete remission was achieved in 5 of 11 subjects in the cannabis group and 1 of 10 in the placebo group. Yet, in an additional study, low-dose cannabidiol did not have an effect on CD activity. In summary, evidence is gathering that manipulating the endocannabinoid system can have beneficial effects in IBD, but further research is required to declare cannabinoids a medicine. We need to establish the specific cannabinoids, as well as appropriate medical conditions, optimal dose, and mode of administration, to maximize the beneficial effects while avoiding any potential harmful effects of cannabinoid use.

  6. Endoscopy in inflammatory bowel disease.

    PubMed

    Carter, D; Lang, A; Eliakim, R

    2013-09-01

    Small bowel imaging and endoscopy in inflammatory bowel disease (IBD) underwent a lot of change and advancement in the recent years. Modalities have shifted from gastroscopy, colonoscopy and small bowel follow through, to ileo-colonoscopy, computed tomography (CT) or magnetic resonance (MR), enteroscopy, wireless video capsule endoscopy and balloon assisted enteroscopy. Nowadays endoscopy has a major role in the diagnosis of IBD, assessing its extent, treating some of its complications (stricture, bleeding), assessing the success of various treatments (mucosal healing), and as a predictor of disease course. Wireless capsule endoscopy (WCE) is a relatively new "toy" allowing direct, patient friendly, visualization of the entire small bowel mucosa. It has gained a substantial role in the evaluation of patients with suspected Chron's Disease (CD) and indeterminate colitis. WCE has a high positive predictive value in patients with suspected CD, when one uses more than two of the International Conference on Capsule Endoscopy (ICCE) criteria, and not less important, a very high negative predictive value in patients with suspected CD. Its role in patients with known CD, assessing their disease activity and extent, its role in assessing postsurgical small bowel recurrence and its role in the evaluation of mucosal healing are still unclear. Balloon assisted enteroscopy has established its role as a complementary tool in cases where there is need of biopsies or treatment (dilatation of strictures). The present review will summarize the role of endoscopy in the diagnosis of IBD, in assessing its activity, its management, interventional endoscopy and cancer surveillance.

  7. Inflammatory bowel disease and thromboembolism

    PubMed Central

    Zezos, Petros; Kouklakis, Georgios; Saibil, Fred

    2014-01-01

    Patients with inflammatory bowel disease (IBD) have an increased risk of vascular complications. Thromboembolic complications, both venous and arterial, are serious extraintestinal manifestations complicating the course of IBD and can lead to significant morbidity and mortality. Patients with IBD are more prone to thromboembolic complications and IBD per se is a risk factor for thromboembolic disease. Data suggest that thrombosis is a specific feature of IBD that can be involved in both the occurrence of thromboembolic events and the pathogenesis of the disease. The exact etiology for this special association between IBD and thromboembolism is as yet unknown, but it is thought that multiple acquired and inherited factors are interacting and producing the increased tendency for thrombosis in the local intestinal microvasculature, as well as in the systemic circulation. Clinicians’ awareness of the risks, and their ability to promptly diagnose and manage tromboembolic complications are of vital importance. In this review we discuss how thromboembolic disease is related to IBD, specifically focusing on: (1) the epidemiology and clinical features of thromboembolic complications in IBD; (2) the pathophysiology of thrombosis in IBD; and (3) strategies for the prevention and management of thromboembolic complications in IBD patients. PMID:25320522

  8. Anemia in inflammatory bowel disease.

    PubMed

    Giannini, S; Martes, C

    2006-09-01

    Anemia is a frequent extraenteric complication of inflammatory bowel disease (IBD, Crohn's disease and ulcerative colitis). A systematic review of the literature shows that the overall prevalence of anemia ranges from 8.8% to 73.7% but differs whether in a setting of Crohn's disease or ulcerative colitis. A disabling complication of IBD, anemia worsens the patient's general condition and quality of life, and increases hospitalization rates. Different factors, including vitamin B12 and folic acid deficiency, bone marrow suppression secondary to drug therapy, autoimmune hemolytic anemia and the coexistence of myelodysplastic syndromes are involved in the pathogenesis of anemia in IBD. The main types of anemia in IBD are iron deficiency anemia and anemia accompanying chronic diseases. Correct diagnostic definition of anemia is a fundamental step in guiding the choice of therapeutic options, since the co-presence of different pathogenetic factors may sometimes require a more complex treatment plan. A review of anemia in IBD, its pathogenetic features, epidemiology, diagnosis and therapy based on evidence from recent studies is the focus of this article.

  9. New anti-inflammatory targets for chronic obstructive pulmonary disease.

    PubMed

    Barnes, Peter J

    2013-07-01

    Chronic obstructive pulmonary disease (COPD) is associated with chronic inflammation of the peripheral airways and lung parenchyma, which leads to progressive obstruction of the airways. Current management with long-acting bronchodilators does not reduce disease progression, and there are no treatments that effectively suppress chronic inflammation in COPD. An increased understanding of the inflammatory processes that are involved in the pathophysiology of COPD has identified several new therapeutic targets. This Review discusses some of the most promising of these targets, including new antioxidants, kinase inhibitors and drugs that target cellular senescence, microbial colonization, epigenetic regulation of inflammatory gene expression and corticosteroid resistance.

  10. Sex differences in the expression of lung inflammatory mediators in response to ozone.

    PubMed

    Cabello, Noe; Mishra, Vikas; Sinha, Utkarshna; DiAngelo, Susan L; Chroneos, Zissis C; Ekpa, Ndifreke A; Cooper, Timothy K; Caruso, Carla R; Silveyra, Patricia

    2015-11-15

    Sex differences in the incidence of respiratory diseases have been reported. Women are more susceptible to inflammatory lung disease induced by air pollution and show worse adverse pulmonary health outcomes than men. However, the mechanisms underlying these differences remain unknown. In the present study, we hypothesized that sex differences in the expression of lung inflammatory mediators affect sex-specific immune responses to environmental toxicants. We focused on the effects of ground-level ozone, a major air pollutant, in the expression and regulation of lung immunity genes. We exposed adult male and female mice to 2 ppm of ozone or filtered air (control) for 3 h. We compared mRNA levels of 84 inflammatory genes in lungs harvested 4 h postexposure using a PCR array. We also evaluated changes in lung histology and bronchoalveolar lavage fluid cell counts and protein content at 24 and 72 h postexposure. Our results revealed sex differences in lung inflammation triggered by ozone exposure and in the expression of genes involved in acute phase and inflammatory responses. Major sex differences were found in the expression of neutrophil-attracting chemokines (Ccl20, Cxcl5, and Cxcl2), the proinflammatory cytokine interleukin-6, and oxidative stress-related enzymes (Ptgs2, Nos2). In addition, the phosphorylation of STAT3, known to mediate IL-6-related immune responses, was significantly higher in ozone-exposed mice. Together, our observations suggest that a differential regulation of the lung immune response could be implicated in the observed increased susceptibility to adverse health effects from ozone observed in women vs. men.

  11. Immunopathogenesis of inflammatory bowel disease

    PubMed Central

    Ardid, Denis

    2010-01-01

    Inflammatory bowel disease (IBD) is a group of idiopathic, chronic and relapsing inflammatory conditions of the gastrointestinal tract. Familial and epidemiological studies have stressed the involvement of genetic factors and have also shown the critical role of environmental factors such as sanitation and hygiene in the development of IBD. However, the molecular mechanisms of intestinal inflammation in IBD have long remained unknown. In recent years, the study of susceptibility genes involved in the detection of bacterial components and in the regulation of the host immune response has shed light onto the potential role of intestinal pathogens and gut flora in IBD immunobiology. This review presents current knowledge on intestinal epithelial barrier alterations and on dysfunction of mucosal innate and acquired immune responses in IBD. The data support the etiological hypothesis which argues that pathogenic intestinal bacteria and/or infectious agents initiate and perpetuate the inflammation of the gut through disruption of tolerance towards the commensal microbiota in an individual with genetic vulnerability. PMID:21487504

  12. Hypertrophic osteoarthropathy of chronic inflammatory bowel disease

    SciTech Connect

    Oppenheimer, D.A.; Jones, H.H.

    1982-12-01

    The case of a 14-year old girl with painful periostitis and ulcerative colitis is reported. The association of chronic inflammatory bowel disease with osteoarthropathy is rare and has previously been reported in eight patients. The periosteal reaction found in association with inflammatory bowel disease is apparently related to a chronic disease course and may cause extreme localized pain.

  13. Extraintestinal Manifestations of Inflammatory Bowel Disease

    PubMed Central

    Schoepfer, Alain; Scharl, Michael; Lakatos, Peter L.; Navarini, Alexander; Rogler, Gerhard

    2015-01-01

    Abstract: Extraintestinal manifestations (EIM) in inflammatory bowel disease (IBD) are frequent and may occur before or after IBD diagnosis. EIM may impact the quality of life for patients with IBD significantly requiring specific treatment depending on the affected organ(s). They most frequently affect joints, skin, or eyes, but can also less frequently involve other organs such as liver, lungs, or pancreas. Certain EIM, such as peripheral arthritis, oral aphthous ulcers, episcleritis, or erythema nodosum, are frequently associated with active intestinal inflammation and usually improve by treatment of the intestinal activity. Other EIM, such as uveitis or ankylosing spondylitis, usually occur independent of intestinal inflammatory activity. For other not so rare EIM, such as pyoderma gangrenosum and primary sclerosing cholangitis, the association with the activity of the underlying IBD is unclear. Successful therapy of EIM is essential for improving quality of life of patients with IBD. Besides other options, tumor necrosis factor antibody therapy is an important therapy for EIM in patients with IBD. PMID:26154136

  14. Disease monitoring in inflammatory bowel disease

    PubMed Central

    Chang, Shannon; Malter, Lisa; Hudesman, David

    2015-01-01

    The optimal method for monitoring quiescent disease in patients with Crohn’s disease (CD) and ulcerative colitis is yet to be determined. Endoscopic evaluation with ileocolonoscopy is the gold standard but is invasive, costly, and time-consuming. There are many commercially available biomarkers that may be used in clinical practice to evaluate disease status in patients with inflammatory bowel disease (IBD), but the most widely adopted biomarkers are C-reactive protein (CRP) and fecal calprotectin (FC). This review summarizes the evidence for utilizing CRP and FC for monitoring IBD during clinical remission and after surgical resection. Endoscopic correlation with CRP and FC is evaluated in each disease state. Advantages and drawbacks of each biomarker are discussed with special consideration of isolated ileal CD. Fecal immunochemical testing, traditionally used for colorectal cancer screening, is mentioned as a potential new alternative assay in the evaluation of IBD. Based on a mixture of information gleaned from biomarkers, clinical status, and endoscopic evaluation, the best treatment decisions can be made for the patient with IBD. PMID:26523100

  15. The composition of cigarette smoke determines inflammatory cell recruitment to the lung in COPD mouse models

    PubMed Central

    John, Gerrit; Kohse, Katrin; Orasche, Jürgen; Reda, Ahmed; Schnelle-Kreis, Jürgen; Zimmermann, Ralf; Schmid, Otmar; Eickelberg, Oliver; Yildirim, Ali Önder

    2013-01-01

    COPD (chronic obstructive pulmonary disease) is caused by exposure to toxic gases and particles, most often CS (cigarette smoke), leading to emphysema, chronic bronchitis, mucus production and a subsequent decline in lung function. The disease pathogenesis is related to an abnormal CS-induced inflammatory response of the lungs. Similar to active (mainstream) smoking, second hand (sidestream) smoke exposure severely affects respiratory health. These processes can be studied in vivo in models of CS exposure of mice. We compared the acute inflammatory response of female C57BL/6 mice exposed to two concentrations [250 and 500 mg/m3 TPM (total particulate matter)] of sidestream and mainstream CS for 3 days and interpreted the biological effects based on physico-chemical differences in the gas and particulate phase composition of CS. BAL (bronchoalveolar lavage fluid) was obtained to perform differential cell counts and to measure cytokine release. Lung tissue was used to determine mRNA and protein expression of proinflammatory genes and to assess tissue inflammation. A strong acute inflammatory response characterized by neutrophilic influx, increased cytokine secretion [KC (keratinocyte chemoattractant), TNF-α (tumour necrosis factor α), MIP-2 (macrophage inflammatory protein 2), MIP-1α and MCP-1 (monocyte chemoattractant protein-1)], pro-inflammatory gene expression [KC, MIP-2 and MMP12 (matrix metalloproteinase 12)] and up-regulated GM-CSF (granulocyte macrophage colony-stimulating factor) production was observed in the mainstream model. After sidestream exposure there was a dampened inflammatory reaction consisting only of macrophages and diminished GM-CSF levels, most likely caused by elevated CO concentrations. These results demonstrate that the composition of CS determines the dynamics of inflammatory cell recruitment in COPD mouse models. Different initial inflammatory processes might contribute to COPD pathogenesis in significantly varying ways, thereby

  16. The composition of cigarette smoke determines inflammatory cell recruitment to the lung in COPD mouse models.

    PubMed

    John, Gerrit; Kohse, Katrin; Orasche, Jürgen; Reda, Ahmed; Schnelle-Kreis, Jürgen; Zimmermann, Ralf; Schmid, Otmar; Eickelberg, Oliver; Yildirim, Ali Önder

    2014-02-01

    COPD (chronic obstructive pulmonary disease) is caused by exposure to toxic gases and particles, most often CS (cigarette smoke), leading to emphysema, chronic bronchitis, mucus production and a subsequent decline in lung function. The disease pathogenesis is related to an abnormal CS-induced inflammatory response of the lungs. Similar to active (mainstream) smoking, second hand (sidestream) smoke exposure severely affects respiratory health. These processes can be studied in vivo in models of CS exposure of mice. We compared the acute inflammatory response of female C57BL/6 mice exposed to two concentrations [250 and 500 mg/m3 TPM (total particulate matter)] of sidestream and mainstream CS for 3 days and interpreted the biological effects based on physico-chemical differences in the gas and particulate phase composition of CS. BAL (bronchoalveolar lavage fluid) was obtained to perform differential cell counts and to measure cytokine release. Lung tissue was used to determine mRNA and protein expression of proinflammatory genes and to assess tissue inflammation. A strong acute inflammatory response characterized by neutrophilic influx, increased cytokine secretion [KC (keratinocyte chemoattractant), TNF-α (tumour necrosis factor α), MIP-2 (macrophage inflammatory protein 2), MIP-1α and MCP-1 (monocyte chemoattractant protein-1)], pro-inflammatory gene expression [KC, MIP-2 and MMP12 (matrix metalloproteinase 12)] and up-regulated GM-CSF (granulocyte macrophage colony-stimulating factor) production was observed in the mainstream model. After sidestream exposure there was a dampened inflammatory reaction consisting only of macrophages and diminished GM-CSF levels, most likely caused by elevated CO concentrations. These results demonstrate that the composition of CS determines the dynamics of inflammatory cell recruitment in COPD mouse models. Different initial inflammatory processes might contribute to COPD pathogenesis in significantly varying ways, thereby

  17. Role of β-catenin-regulated CCN matricellular proteins in epithelial repair after inflammatory lung injury

    PubMed Central

    McClendon, Jazalle; Aschner, Yael; Briones, Natalie; Young, Scott K.; Lau, Lester F.; Kahn, Michael; Downey, Gregory P.

    2013-01-01

    Repair of the lung epithelium after injury is integral to the pathogenesis and outcomes of diverse inflammatory lung diseases. We previously reported that β-catenin signaling promotes epithelial repair after inflammatory injury, but the β-catenin target genes that mediate this effect are unknown. Herein, we examined which β-catenin transcriptional coactivators and target genes promote epithelial repair after inflammatory injury. Transmigration of human neutrophils across cultured monolayers of human lung epithelial cells resulted in a fall in transepithelial resistance and the formation of discrete areas of epithelial denudation (“microinjury”), which repaired via cell spreading by 96 h. In mice treated with intratracheal (i.t.) LPS or keratinocyte chemokine, neutrophil emigration was associated with increased permeability of the lung epithelium, as determined by increased bronchoalveolar lavage (BAL) fluid albumin concentration, which decreased over 3–6 days. Activation of β-catenin/p300-dependent gene expression using the compound ICG-001 accelerated epithelial repair in vitro and in murine models. Neutrophil transmigration induced epithelial expression of the β-catenin/p300 target genes Wnt-induced secreted protein (WISP) 1 and cysteine-rich (Cyr) 61, as determined by real-time PCR (qPCR) and immunostaining. Purified neutrophil elastase induced WISP1 upregulation in lung epithelial cells, as determined by qPCR. WISP1 expression increased in murine lungs after i.t. LPS, as determined by ELISA of the BAL fluid and qPCR of whole lung extracts. Finally, recombinant WISP1 and Cyr61 accelerated repair, and Cyr61-neutralizing antibodies delayed repair of the injured epithelium in vitro. We conclude that β-catenin/p300-dependent expression of WISP1 and Cyr61 is critical for epithelial repair and represents a potential therapeutic target to promote epithelial repair after inflammatory injury. PMID:23316072

  18. Rheumatoid interstitial lung disease presenting as cor pulmonale.

    PubMed

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

    2010-10-01

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

  19. Tumor Necrosis Factor–α Overexpression in Lung Disease

    PubMed Central

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

    2005-01-01

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

  20. Cough in interstitial lung disease.

    PubMed

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

    2015-12-01

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

  1. 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

  2. Agricultural lung diseases.

    PubMed

    Kirkhorn, S R; Garry, V F

    2000-08-01

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

  3. Mucins and inflammatory bowel disease

    PubMed Central

    Shirazi, T.; Longman, R.; Corfield, A.; Probert, C.

    2000-01-01

    There is a layer of mucus lining the gastrointestinal tract, which acts as both a lubricant and as a physical barrier between luminal contents and the mucosal surface. The mucins that make up this layer consist of a protein backbone with oligosaccharides attached to specific areas of the protein core. These areas are called the variable number tandem repeat regions. The degree of glycosylation of the mucins is central to their role in the mucus barrier. The oligosaccharides are variable and complex. It has been demonstrated that the degree of sulphation and sialylation and the length of the oligosaccharide chains all vary in inflammatory bowel disease. These changes can alter the function of the mucins. Mucins are broadly divided into two groups, those that are secreted and those that are membrane bound. The major mucins present in the colorectum are MUC1, MUC2, MUC3, and MUC4.
Trefoils are a group of small peptides that have an important role in the mucus layer. Three trefoils have been demonstrated so far. They seem to play a part in mucosal protection and in mucosal repair. They may help to stabilise the mucus layer by cross linking with mucins to aid formation of stable gels. Trefoils can be expressed in the ulcer associated cell lineage, a glandular structure that can occur in the inflamed mucosa. There seem to be differences in the expression of trefoils in the colon and the small bowel, which may imply different method of mucosal repair.


Keywords: mucins; trefoil; Crohn's disease; colitis PMID:10908374

  4. Farmer's Lung Disease. A Review.

    PubMed

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

    2016-06-01

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

  5. Radiographic Differentiation of Advanced Fibrocystic Lung Diseases.

    PubMed

    Akira, Masanori

    2017-03-01

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

  6. Diet-induced obesity reprograms the inflammatory response of the murine lung to inhaled endotoxin

    SciTech Connect

    Tilton, Susan C.; Waters, Katrina M.; Karin, Norman J.; Webb-Robertson, Bobbie-Jo M.; Zangar, Richard C.; Lee, K. Monica; Bigelow, Diana J.; Pounds, Joel G.; Corley, Richard A.

    2013-03-01

    The co-occurrence of environmental factors is common in complex human diseases and, as such, understanding the molecular responses involved is essential to determine risk and susceptibility to disease. We have investigated the key biological pathways that define susceptibility for pulmonary infection during obesity in diet-induced obese (DIO) and regular weight (RW) C57BL/6 mice exposed to inhaled lipopolysaccharide (LPS). LPS induced a strong inflammatory response in all mice as indicated by elevated cell counts of macrophages and neutrophils and levels of proinflammatory cytokines (MDC, MIP-1γ, IL-12, RANTES) in the bronchoalveolar lavage fluid. Additionally, DIO mice exhibited 50% greater macrophage cell counts, but decreased levels of the cytokines, IL-6, TARC, TNF-α, and VEGF relative to RW mice. Microarray analysis of lung tissue showed over half of the LPS-induced expression in DIO mice consisted of genes unique for obese mice, suggesting that obesity reprograms how the lung responds to subsequent insult. In particular, we found that obese animals exposed to LPS have gene signatures showing increased inflammatory and oxidative stress response and decreased antioxidant capacity compared with RW. Because signaling pathways for these responses can be common to various sources of environmentally induced lung damage, we further identified biomarkers that are indicative of specific toxicant exposure by comparing gene signatures after LPS exposure to those from a parallel study with cigarette smoke. These data show obesity may increase sensitivity to further insult and that co-occurrence of environmental stressors result in complex biosignatures that are not predicted from analysis of individual exposures. - Highlights: ► Obesity modulates inflammatory markers in BAL fluid after LPS exposure. ► Obese animals have a unique transcriptional signature in lung after LPS exposure. ► Obesity elevates inflammatory stress and reduces antioxidant capacity in the lung

  7. Sexual dysfunction in inflammatory bowel disease.

    PubMed

    Ghazi, Leyla J; Patil, Seema A; Cross, Raymond K

    2015-04-01

    Sexual health is a broad term that encompasses a variety of functions including sexual thoughts, desire, arousal, intercourse, orgasm, and the impact of body image. Sexual dysfunction in individuals with inflammatory bowel disease is multifactorial including the impact of psychosocial factors, disease activity, medical therapies, surgical interventions, body image perceptions and changes, hypogonadism, and pelvic floor disorders. Providers caring for patients with inflammatory bowel disease should be cognizant of these concerns and develop management plans and techniques for earlier diagnosis and treatment.

  8. Functional and inflammatory alterations in the lung following exposure of rats to nitrogen mustard

    SciTech Connect

    Sunil, Vasanthi R.; Patel, Kinal J.; Shen, Jianliang; Reimer, David; Gow, Andrew J.; Laskin, Jeffrey D.; Laskin, Debra L.

    2011-01-01

    Nitrogen mustard is a vesicant that causes damage to the respiratory tract. In these studies, we characterized the acute effects of nitrogen mustard on lung structure, inflammatory mediator expression, and pulmonary function, with the goal of identifying mediators potentially involved in toxicity. Treatment of rats (male Wistar, 200-225 g) with nitrogen mustard (mechlorethamine hydrochloride, i.t., 0.25 mg/kg) resulted in marked histological changes in the respiratory tract, including necrotizing bronchiolitis, thickening of alveolar septa, and inflammation which was evident within 24 h. This was associated with increases in bronchoalveolar lavage protein and cells, confirming injury to alveolar epithelial regions of the lung. Nitrogen mustard administration also resulted in increased expression of inducible nitric oxide synthase and cyclooxygenase-2, pro-inflammatory proteins implicated in lung injury, in alveolar macrophages and alveolar and bronchial epithelial cells. Expression of connective tissue growth factor and matrix metalloproteinase-9, mediators regulating extracellular matrix turnover was also increased, suggesting that pathways leading to chronic lung disease are initiated early in the pathogenic process. Following nitrogen mustard exposure, alterations in lung mechanics and function were also observed. These included decreases in baseline static compliance, end-tidal volume and airway resistance, and a pronounced loss of methacholine responsiveness in resistance, tissue damping and elastance. Taken together, these data demonstrate that nitrogen mustard induces rapid structural and inflammatory changes in the lung which are associated with altered lung functioning. Understanding the nature of the injury induced by nitrogen mustard and related analogs may aid in the development of efficacious therapies for treatment of pulmonary injury resulting from exposure to vesicants.

  9. Genetics of Inflammatory Bowel Diseases.

    PubMed

    McGovern, Dermot P B; Kugathasan, Subra; Cho, Judy H

    2015-10-01

    In this review, we provide an update on genome-wide association studies (GWAS) in inflammatory bowel disease (IBD). In addition, we summarize progress in defining the functional consequences of associated alleles for coding and noncoding genetic variation. In the small minority of loci where major association signals correspond to nonsynonymous variation, we summarize studies defining their functional effects and implications for therapeutic targeting. Importantly, the large majority of GWAS-associated loci involve noncoding variation, many of which modulate levels of gene expression. Recent expression quantitative trait loci (eQTL) studies have established that the expression of most human genes is regulated by noncoding genetic variations. Significant advances in defining the epigenetic landscape have demonstrated that IBD GWAS signals are highly enriched within cell-specific active enhancer marks. Studies in European ancestry populations have dominated the landscape of IBD genetics studies, but increasingly, studies in Asian and African-American populations are being reported. Common variation accounts for only a modest fraction of the predicted heritability and the role of rare genetic variation of higher effects (ie, odds ratios markedly deviating from 1) is increasingly being identified through sequencing efforts. These sequencing studies have been particularly productive in more severe very early onset cases. A major challenge in IBD genetics will be harnessing the vast array of genetic discovery for clinical utility through emerging precision medical initiatives. In this article, we discuss the rapidly evolving area of direct-to-consumer genetic testing and the current utility of clinical exome sequencing, especially in very early onset, severe IBD cases. We summarize recent progress in the pharmacogenetics of IBD with respect to partitioning patient responses to anti-TNF and thiopurine therapies. Highly collaborative studies across research centers and

  10. Temporal complexity in clinical manifestations of lung disease.

    PubMed

    Frey, Urs; Maksym, Geoffrey; Suki, Béla

    2011-06-01

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

  11. Cystic Lung Diseases: Algorithmic Approach.

    PubMed

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

    2016-10-01

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

  12. Fluid Therapy in Lung Disease.

    PubMed

    Rozanski, Elizabeth; Lynch, Alex

    2017-03-01

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

  13. Phosphatidic acid signaling mediates lung cytokine expression and lung inflammatory injury after hemorrhage in mice.

    PubMed

    Abraham, E; Bursten, S; Shenkar, R; Allbee, J; Tuder, R; Woodson, P; Guidot, D M; Rice, G; Singer, J W; Repine, J E

    1995-02-01

    Because phosphatidic acid (PA) pathway signaling may mediate many basic reactions involving cytokine-dependent responses, we investigated the effects of CT1501R, a functional inhibitor of the enzyme lysophosphatidic acid acyltransferase (LPAAT) which converts lysophosphatidic acid (Lyso-PA) to PA. We found that CT1501R treatment not only prevented hypoxia-induced PA increases and lyso-PA consumption in human neutrophils, but also prevented neutrophil chemotaxis and adherence in vitro, and lung injury and lung neutrophil accumulation in mice subjected to hemorrhage and resuscitation. In addition, CT1501R treatment prevented increases in mRNA levels and protein production of a variety of proinflammatory cytokines in multiple lung cell populations after blood loss and resuscitation. Our results indicate the fundamental role of PA metabolism in the development of acute inflammatory lung injury after blood loss.

  14. Microbiota abnormalities in inflammatory airway diseases - Potential for therapy.

    PubMed

    Gollwitzer, Eva S; Marsland, Benjamin J

    2014-01-01

    Increasingly the development of novel therapeutic strategies is taking into consideration the contribution of the intestinal microbiota to health and disease. Dysbiosis of the microbial communities colonizing the human intestinal tract has been described for a variety of chronic diseases, such as inflammatory bowel disease, obesity and asthma. In particular, reduction of several so-called probiotic species including Lactobacilli and Bifidobacteria that are generally considered to be beneficial, as well as an outgrowth of potentially pathogenic bacteria is often reported. Thus a tempting therapeutic approach is to shape the constituents of the microbiota in an attempt to restore the microbial balance towards the growth of 'health-promoting' bacterial species. A twist to this scenario is the recent discovery that the respiratory tract also harbors a microbiota under steady-state conditions. Investigators have shown that the microbial composition of the airway flora is different between healthy lungs and those with chronic lung diseases, such as asthma, chronic obstructive pulmonary disease as well as cystic fibrosis. This is an emerging field, and thus far there is very limited data showing a direct contribution of the airway microbiota to the onset and progression of disease. However, should future studies provide such evidence, the airway microbiota might soon join the intestinal microbiota as a target for therapeutic intervention. In this review, we highlight the major advances that have been made describing the microbiota in chronic lung disease and discuss current and future approaches concerning manipulation of the microbiota for the treatment and prevention of disease.

  15. Delayed puberty associated with inflammatory bowel disease.

    PubMed

    Ballinger, Anne B; Savage, Martin O; Sanderson, Ian R

    2003-02-01

    Delayed puberty frequently complicates the clinical course of young patients with inflammatory bowel disease, more often in Crohn's disease than ulcerative colitis. Undernutrition has been thought to be the main reason for delayed puberty in these patients. However, puberty may be delayed despite a normal nutritional status. Observations in patients with inflammatory bowel disease and in rats with experimental colitis suggest that inflammatory mediators may have a direct adverse influence, independent of undernutrition, on the onset and progression of puberty. Serum androgens are consistently reported to be reduced in patients with delayed puberty and inflammatory bowel disease. This reduction is not necessarily secondary to a reduction in gonadotrophins as serum concentrations of gonadotrophins have been reported to be normal or even increased in some studies. Management of delayed puberty involves calorie supplements to correct undernutrition and treatment of inflammation. Observations in boys with delayed puberty and controlled studies in experimental models of intestinal inflammation suggest that testosterone therapy can accelerate puberty.

  16. Inflammatory Bowel Disease (For Teens)

    MedlinePlus

    ... eats. The two major types of IBD are Crohn's disease and ulcerative colitis. Crohn's disease is when the lining and wall of the intestines become inflamed and ulcers develop. Although Crohn's disease can happen in any part of the digestive ...

  17. 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.

  18. Anti-Inflammatory Effect of Apigenin on LPS-Induced Pro-Inflammatory Mediators and AP-1 Factors in Human Lung Epithelial Cells.

    PubMed

    Patil, Rajeshwari H; Babu, R L; Naveen Kumar, M; Kiran Kumar, K M; Hegde, Shubha M; Nagesh, Rashmi; Ramesh, Govindarajan T; Sharma, S Chidananda

    2016-02-01

    Apigenin is one of the plant flavonoids present in fruits and vegetables, acting as an important nutraceutical component. It is recognized as a potential antioxidant, antimicrobial, and anti-inflammatory molecule. In the present study, the mechanism of anti-inflammatory action of apigenin on lipopolysaccharide (LPS)-induced pro-inflammatory cytokines and activator protein-1 (AP-1) factors in human lung A549 cells was investigated. The anti-inflammatory activity of apigenin on LPS-induced inflammation was determined by analyzing the expression of pro-inflammatory cytokines, nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and different AP-1 factors. Apigenin significantly inhibited the LPS-induced expression of iNOS, COX-2, expression of pro-inflammatory cytokines (IL-1β, IL-2, IL-6, IL-8, and TNF-α), and AP-1 proteins (c-Jun, c-Fos, and JunB) including nitric oxide production. Study confirms the anti-inflammatory effect of apigenin by inhibiting the expression of inflammatory mediators and AP-1 factors involved in the inflammation and its importance in the treatment of lung inflammatory diseases.

  19. Inflammatory effects of inhaled sulfur mustard in rat lung

    SciTech Connect

    Malaviya, Rama; Sunil, Vasanthi R.; Cervelli, Jessica; Anderson, Dana R.; Holmes, Wesley W.; Conti, Michele L.; Gordon, Ronald E.; Laskin, Jeffrey D.; Laskin, Debra L.

    2010-10-15

    Inhalation of sulfur mustard (SM), a bifunctional alkylating agent that causes severe lung damage, is a significant threat to both military and civilian populations. The mechanisms mediating its cytotoxic effects are unknown and were investigated in the present studies. Male rats Crl:CD(SD) were anesthetized, and then intratracheally intubated and exposed to 0.7-1.4 mg/kg SM by vapor inhalation. Animals were euthanized 6, 24, 48 h or 7 days post-exposure and bronchoalveolar lavage fluid (BAL) and lung tissue collected. Exposure of rats to SM resulted in rapid pulmonary toxicity, including focal ulceration and detachment of the trachea and bronchial epithelia from underlying mucosa, thickening of alveolar septal walls and increased numbers of inflammatory cells in the tissue. There was also evidence of autophagy and apoptosis in the tissue. This was correlated with increased BAL protein content, a marker of injury to the alveolar epithelial lining. SM exposure also resulted in increased expression of markers of inflammation including cyclooxygenase-2 (COX-2), tumor necrosis factor-{alpha} (TNF{alpha}), inducible nitric oxide synthase (iNOS), and matrix metalloproteinase-9 (MMP-9), each of which has been implicated in pulmonary toxicity. Whereas COX-2, TNF{alpha} and iNOS were mainly localized in alveolar regions, MMP-9 was prominent in bronchial epithelium. In contrast, expression of the anti-oxidant hemeoxygenase, and the anti-inflammatory collectin, surfactant protein-D, decreased in the lung after SM exposure. These data demonstrate that SM-induced oxidative stress and injury are associated with the generation of cytotoxic inflammatory proteins which may contribute to the pathogenic response to this vesicant.

  20. The genetic background of inflammatory bowel disease.

    PubMed

    Yang, H; Rotter, J I

    2000-01-01

    Available evidence indicates that genetic factors are essential in providing the susceptibility to the majority of the various forms of inflammatory bowel disease occurring in man. It is also clear that the genetic susceptibility to these diseases is complex, and that more than one gene may predispose (the concept of multilocus/oligogenic inheritance), and likely in different etiologic combinations (the concept of genetic heterogeneity). Paradigms are now available that should lead to the identification of a number of these predisposing genes. These paradigms include the candidate gene approach, systematic genome wide scans, and mouse human synteny. While genome wide scans are currently limited to multiplex family linkage studies, both candidate genes and mouse human synteny can be approached in either linkage or association paradigms. Eventually whole genome association studies will be available as well. Identification of inflammatory bowel disease predisposing genes should lead to their incorporation in studies of natural history, investigation of environmental risk factors, and especially utilization of genetic markers in clinical trials. This will allow us to identify the best therapy available for the individual patient based on their unique genetic constitution. With advances in molecular technology, the search for genes influencing traits and diseases with a complex genetic background, such as the inflammatory bowel diseases, has become a realistic task. Although exogenous or infectious agents may contribute to the pathogenesis or may trigger the onset of disease, and the immune system almost certainly mediates the tissue damage, it is clear from available data that genetic factors determine the susceptibility of a given individual to inflammatory bowel disease (reviewed below). Thus, genetic studies are essential for the delineation of the basic etiologies of the various forms of inflammatory bowel disease and thus can aid in the development of radically

  1. ACUTE OZONE-INDUCED INFLAMMATORY GENE EXPRESSION IN THE RAT LUNG IS NOT RELATED TO LEVELS OF ANTIOXIDANTS IN THE LAVAGE FLUID

    EPA Science Inventory

    ABSTRACT BODY: Ozone causes oxidative stress and lung inflammation. We hypothesized that rat strains with or without genetic susceptibility to cardiovascular disease will have different antioxidant levels in alveolar lining, and that ozone induced inflammatory gene expression wil...

  2. 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

  3. Oxidative stress and inflammatory bowel disease.

    PubMed

    Almenier, Hazem A; Al Menshawy, Hazem H; Maher, Maha M; Al Gamal, Salah

    2012-01-01

    Inflammatory Bowel Disease (IBD) is a chronic relapsing and remitting inflammatory condition of the gastrointestinal tract. The exact cause of IBD remains undetermined, the condition appears to be related to a combination of genetic and environmental factors. While many gaps in our knowledge still exist, the last two decades have witnessed an unprecedented progress not only in the etiology ; but mainly in the mechanisms underlying the chronic inflammatory response, immunologic and genetic aspects. We review some recent points of research in pathogenesis with special stress on oxidative stress and its correlations with disease activity.

  4. Operative wound implantation of inflammatory sarcomatoid carcinoma of the lung.

    PubMed

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

    2014-09-01

    We describe a patient with iatrogenic chest wall implantation of inflammatory sarcomatoid carcinoma. A 43-year-old man underwent right partial lung resection for hemopneumothorax, with large bullae and an alveolar accumulation of histiocytes found on pathology. Three months later, a subcutaneous tumor appeared at a thoracoscopic port site. Needle aspiration of this tumor suggested a malignant neoplasm; therefore, a right upper lobectomy and chest wall resection were performed, and a pathologic diagnosis of sarcomatoid carcinoma was made. Pathologic reexamination of the original sample suggested that the tumor has been implanted in the patient's chest wall at the time of the first operation.

  5. The Gut Microbiota in Inflammatory Bowel Disease.

    PubMed

    Sheehan, Donal; Shanahan, Fergus

    2017-03-01

    Genes, bacteria, and immunity contribute to the pathogenesis of inflammatory bowel disease. Most genetic risk relates to defective sensing of microbes and their metabolites or defective regulation of the host response to the microbiota. Because the composition of the microbiota shapes the developing immune system and is determined in early life, the prospect of therapeutic manipulation of the microbiota in adulthood after the onset of disease is questionable. However, the microbiota may be a marker of risk and a modifier of disease activity and a contributor to extraintestinal manifestations and associations in some patients with inflammatory bowel disease.

  6. 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.

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

    PubMed Central

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

    2012-01-01

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

  8. Neurotrophins in lung health and disease

    PubMed Central

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

    2010-01-01

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

  9. Nocardia infections among immunomodulated inflammatory bowel disease patients: A review

    PubMed Central

    Abreu, Cândida; Rocha-Pereira, Nuno; Sarmento, António; Magro, Fernando

    2015-01-01

    Human nocardiosis, caused by Nocardia spp., an ubiquitous soil-borne bacteria, is a rare granulomatous disease close related to immune dysfunctions. Clinically can occur as an acute life-threatening disease, with lung, brain and skin being commonly affected. The infection was classically diagnosed in HIV infected persons, organ transplanted recipients and long term corticosteroid treated patients. Currently the widespread use of immunomodulators and immunossupressors in the treatment of inflammatory diseases changed this scenario. Our purpose is to review all published cases of nocardiosis in immunomodulated patients due to inflammatory diseases and describe clinical and laboratory findings. We reviewed the literature concerning human cases of nocardiosis published between 1980 and 2014 in peer reviewed journals. Eleven cases of nocardiosis associated with anti-tumor necrosis factor (TNF) prescription (9 related with infliximab and 2 with adalimumab) were identified; 7 patients had inflammatory bowel disease (IBD), 4 had rheumatological conditions; nocardia infection presented as cutaneous involvement in 3 patients, lung disease in 4 patients, hepatic in one and disseminated disease in 3 patients. From the 10 cases described in IBD patients 7 were associated with anti-TNF and 3 with steroids and azathioprine. In conclusion, nocardiosis requires high levels of clinical suspicion and experience of laboratory staff, in order to establish a timely diagnosis and by doing so avoid worst outcomes. Treatment for long periods tailored by the susceptibility of the isolated species whenever possible is essential. The safety of restarting immunomodulators or anti-TNF after the disease or the value of prophylaxis with cotrimoxazole is still debated. PMID:26074688

  10. The role of substance P in inflammatory disease.

    PubMed

    O'Connor, Terence M; O'Connell, Joseph; O'Brien, Darren I; Goode, Triona; Bredin, Charles P; Shanahan, Fergus

    2004-11-01

    The diffuse neuroendocrine system consists of specialised endocrine cells and peptidergic nerves and is present in all organs of the body. Substance P (SP) is secreted by nerves and inflammatory cells such as macrophages, eosinophils, lymphocytes, and dendritic cells and acts by binding to the neurokinin-1 receptor (NK-1R). SP has proinflammatory effects in immune and epithelial cells and participates in inflammatory diseases of the respiratory, gastrointestinal, and musculoskeletal systems. Many substances induce neuropeptide release from sensory nerves in the lung, including allergen, histamine, prostaglandins, and leukotrienes. Patients with asthma are hyperresponsive to SP and NK-1R expression is increased in their bronchi. Neurogenic inflammation also participates in virus-associated respiratory infection, non-productive cough, allergic rhinitis, and sarcoidosis. SP regulates smooth muscle contractility, epithelial ion transport, vascular permeability, and immune function in the gastrointestinal tract. Elevated levels of SP and upregulated NK-1R expression have been reported in the rectum and colon of patients with inflammatory bowel disease (IBD), and correlate with disease activity. Increased levels of SP are found in the synovial fluid and serum of patients with rheumatoid arthritis (RA) and NK-1R mRNA is upregulated in RA synoviocytes. Glucocorticoids may attenuate neurogenic inflammation by decreasing NK-1R expression in epithelial and inflammatory cells and increasing production of neutral endopeptidase (NEP), an enzyme that degrades SP. Preventing the proinflammatory effects of SP using tachykinin receptor antagonists may have therapeutic potential in inflammatory diseases such as asthma, sarcoidosis, chronic bronchitis, IBD, and RA. In this paper, we review the role that SP plays in inflammatory disease.

  11. Inflammatory signaling in Alzheimer disease and depression.

    PubMed

    Barber, Robert

    2011-08-01

    To help define the relationships among inflammation, Alzheimer disease, and depression, the Texas Alzheimer's Research Consortium analyzed an array of inflammatory biomarkers in a cohort of patients with Alzheimer disease and in controls. Inflammation severity was highly correlated with earlier age at onset of Alzheimer disease and was also associated with cognitive decline. The relationship between inflammation and depression was not as clear, and it varied with aspects of depression, gender, and the presence of Alzheimer disease.

  12. Types of Childhood Interstitial Lung Disease

    MedlinePlus

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

  13. 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, ...

  14. Characterization of TLR-induced inflammatory responses in COPD and control lung tissue explants

    PubMed Central

    Pomerenke, Anna; Lea, Simon R; Herrick, Sarah; Lindsay, Mark A; Singh, Dave

    2016-01-01

    Purpose Viruses are a common cause of exacerbations in chronic obstructive pulmonary disease (COPD). They activate toll-like receptors (TLRs) 3, 7, and 8, leading to a pro-inflammatory response. We have characterized the responses of TLR3 and TLR7/8 in lung tissue explants from COPD patients and control smokers. Methods We prepared lung whole tissue explants (WTEs) from patients undergoing surgery for confirmed or suspected lung cancer. In order to mimic the conditions of viral infection, we used poly(I:C) for TLR3 stimulation and R848 for TLR7/8 stimulation. These TLR ligands were used alone and in combination. The effects of tumor necrosis factor α (TNFα) neutralization and dexamethasone on TLR responses were examined. Inflammatory cytokine release was measured by enzyme-linked immunosorbent assay and gene expression by quantitative real-time polymerase chain reaction. Results WTEs from COPD patients released higher levels of pro-inflammatory cytokines compared with WTEs from smokers. Activation of multiple TLRs led to a greater than additive release of TNFα and CCL5. TNFα neutralization and dexamethasone treatment decreased cytokine release. Conclusion This WTE model shows an enhanced response of COPD compared with controls, suggesting an increased response to viral infection. There was amplification of innate immune responses with multiple TLR stimulation. PMID:27729782

  15. Managing Pain in Inflammatory Bowel Disease

    PubMed Central

    Jones, R. Carter W.; Wallace, Mark S.

    2011-01-01

    Pain is a common complaint in inflammatory bowel disease, and it has significant consequences for patients' quality of life. A thorough evaluation to determine the source of patients' pain should include clinical, laboratory, radiologic, and endoscopic assessments as indicated. Differentiating among active inflammation, secondary complications, and functional pain can be complicated. Even when all active disease is adequately treated, clinicians are often left with the difficulty of managing chronic pain. This paper will review the benefits and limitations of several commonly used treatments and promising future therapies. A suggested treatment algorithm will provide some guidance in this challenging area of inflammatory bowel disease management. PMID:22298998

  16. New pharmaceuticals in inflammatory bowel disease.

    PubMed

    Łodyga, Michał; Eder, Piotr; Bartnik, Witold; Gonciarz, Maciej; Kłopocka, Maria; Linke, Krzysztof; Małecka-Panas, Ewa; Radwan, Piotr; Rydzewska, Grażyna

    2015-01-01

    This paper complements the previously published Guidelines of the Working Group of the Polish Society of Gastroenterology and former National Consultant in Gastroenterology regarding the management of patients with Crohn's disease and ulcerative colitis. Attention was focused on the new pharmaceutical recently registered for inflammatory bowel disease treatment.

  17. Extraintestinal Manifestations of Inflammatory Bowel Disease

    PubMed Central

    Burakoff, Robert

    2011-01-01

    Extraintestinal manifestations of inflammatory bowel disease are prevalent in both ulcerative colitis and Crohn's disease. The most common manifestations involve the musculoskeletal and dermatologic systems. Other manifestations involve the hepatopan-creatobiliary system (eg, primary sclerosing cholangitis) as well as the ocular, renal, and pulmonary systems. A multidisciplinary team approach is often needed for effective management, and emergency situations require prompt evaluation. PMID:21857821

  18. [Chronic inflammatory bowel diseases and nutrition].

    PubMed

    Meier, R

    1996-01-01

    The etiology of inflammatory bowel disease is still unknown. Several potential mechanisms are discussed. The etiological and therapeutic importance of nutrition is controversial. Though changes in dietary habits and incidence of inflammatory bowel disease during the last century were in parallel, no specific nutritional factor has been isolated. No dietary prophylaxis of inflammatory bowel disease is yet known; all dietary therapies in inflammatory bowel disease aim to improve nutritional support and to diminish inflammation by bowel rest. Children and adolescents gain in weight and height. Total parenteral nutrition will not substantially reduce disease activity and operation rates. Total parenteral nutrition can only be recommended in ulcerative colitis patients with severe disease in the initial phase and in Crohn's patients with severe malnutrition and intestinal complications. Enteral nutrition support is less effective in ulcerative colitis than in Crohn's disease. Reported remission rates on enteral nutrition are 25% for ulcerative colitis and up to 80% for Crohn. However, in active Crohn's disease enteral nutrition is less effective than standard therapy with methylprednisolone and sulfasalizine. It is generally believed that nutrition therapy in combination with drugs is the best treatment modality. There is no evidence to support the importance of any combination of the formula diets such as elemental, oligopeptide, or polymeric formulations. Administration of formula diets by nasogastric tubes all show similar remission rates. Whether newer diets supplemented with arginine, glutamine, omega-3-fatty acids or short chain fatty acids increase remission rates is not known. Further studies in this field are warranted.

  19. Proteomics and chronic inflammatory bowel diseases.

    PubMed

    Felley-Bosco, Emanuela; André, Muriel

    2004-01-01

    Inflammatory bowel diseases (IBD) are relatively frequent in developed countries. Physiopathological events involved in the etiology of IBDs include activation of immune, mesenchymal and epithelial cells. This review gives an overview of the currently applied proteomics technologies. It describes metabolic changes and goes into the approaches using this methodology to understand the molecular mechanisms implicated in the development of the disease.

  20. The hookworm pharmacopoeia for inflammatory diseases.

    PubMed

    Navarro, Severine; Ferreira, Ivana; Loukas, Alex

    2013-03-01

    In the developed world, declining prevalence of parasitic infections correlates with increased incidence of allergic and autoimmune disorders. Current treatments for these chronic inflammatory conditions have little to no effect on their prevalence and are referred to as "controllers" rather than cures. There has been limited success in therapeutically targeting allergic and autoimmune pathways, leaving an unmet need for development of effective anti-inflammatories. We discuss the benefit of hookworm infections and the parasite's ability to condition the immune system to prevent allergic asthma and inflammatory bowel diseases. We then examine the immunomodulatory properties of selected hookworm-derived proteins in these two models of inflammation. While hookworm protein therapy has yet to be fully exploited, the identification of these proteins and the mechanisms by which they skew the immune system will provide new avenues for controlling and optimally reversing key pathological processes important in allergic and inflammatory bowel diseases.

  1. Inflammatory Bowel Disease (For Children)

    MedlinePlus

    ... bowel disease (or IBD ). IBD most often affects people between 15 and 35 years old, but has even been found in children as ... don't think that IBD is caused by emotional stress or specific foods. You ... in families. About 20% of people with the disease also have a relative who ...

  2. Preferential expansion of pro-inflammatory Tregs in human non-small cell lung cancer

    PubMed Central

    Phillips, Joseph D.; Blatner, Nichole R.; Haghi, Leila; DeCamp, Malcolm M.; Meyerson, Shari L.; Heiferman, Michael J.; Heiferman, Jeffrey R.; Gounari, Fotini; Bentrem, David J.; Khazaie, Khashayarsha

    2016-01-01

    Objectives Lung cancer is the leading cause of cancer-related death in the USA. Regulatory T cells (Tregs) normally function to temper immune responses and decrease inflammation. Previous research has demonstrated different subsets of Tregs with contrasting anti- or pro-inflammatory properties. This study aimed to determine Treg subset distributions and characteristics present in non-small cell lung cancer (NSCLC) patients. Methods Peripheral blood was collected from healthy controls (HC) and NSCLC patients preceding surgical resection, and mononuclear cells were isolated, stained, and analyzed by flow cytometry. Tregs were defined by expression of CD4 and CD25 and classified into CD45RA+Foxp3int (naïve, Fr. I) or CD45RA−Foxp3hi (activated Fr. II). Activated conventional T cells were CD4+CD45RA−Foxp3int (Fr. III). Results Samples from 23 HC and 26 NSCLC patients were collected. Tregs isolated from patients with NSCLC were found to have enhanced suppressive function on naive T cells. Cancer patients had significantly increased frequencies of activated Tregs (fraction II: FrII), 17.5 versus 3.2 % (P < 0.001). FrII Tregs demonstrated increased RORγt and IL17 expression and decreased IL10 expression compared to Tregs from HC, indicating pro-inflammatory characteristics. Conclusions This study demonstrates that a novel subset of Tregs with pro-inflammatory characteristics preferentially expand in NSCLC patients. This Treg subset appears identical to previously reported pro-inflammatory Tregs in human colon cancer patients and in mouse models of polyposis. We expect the pro-inflammatory Tregs in lung cancer to contribute to the immune pathogenesis of disease and propose that targeting this Treg subset may have protective benefits in NSCLC. PMID:26047578

  3. Pharmacological nutrition in inflammatory bowel diseases.

    PubMed

    Campos, F G; Waitzberg, D L; Teixeira, M G; Mucerino, D R; Kiss, D R; Habr-Gama, A

    2003-01-01

    Inflammatory Bowel Diseases--ulcerative colitis and Crohn's disease--are chronic gastrointestinal inflammatory diseases of unknown etiology. Decreased oral intake, malabsorption, accelerated nutrient losses, increased requirements, and drug-nutrient interactions cause nutritional and functional deficiencies that require proper correction by nutritional therapy. The goals of the different forms of nutritional therapy are to correct nutritional disturbances and to modulate inflammatory response, thus influencing disease activity. Nutritional intervention may improve outcome in certain individuals; however, because of the costs and complications of such therapy, careful selection is warranted. Total parenteral nutrition has been used to correct and prevent nutritional disturbances and to promote bowel rest during active disease, mainly in cases of digestive fistulae with a high output. Its use should be reserved for patients who cannot tolerate enteral nutrition. Enteral nutrition is effective in inducing clinical remission of disease in adults and promoting growth in children. Recent research has focused on the use of specific nutrients as primary treatment agents. Although some reports have indicated that glutamine, short-chain fatty acids, antioxidants and immunonutrition with omega-3 fatty acids are an important therapeutic alternative in the management of inflammatory bowel diseases, the beneficial reported effects have yet to be translated into the clinical practice. The real efficacy of these nutrients still need further evaluation through prospective and randomized trials.

  4. IL-18 and Cutaneous Inflammatory Diseases

    PubMed Central

    Lee, Ji hyun; Cho, Dae Ho; Park, Hyun Jeong

    2015-01-01

    Interleukin (IL)-18, an IL-1 family cytokine, is a pleiotropic immune regulator. IL-18 plays a strong proinflammatory role by inducing interferon (IFN)-γ. Previous studies have implicated IL-18 in the pathogenesis of various diseases. However, it is not well understood biologic activities of IL-18 in the diverse skin diseases. Here, we have reviewed the expression and function of IL-18 in skin diseases including inflammatory diseases. This article provides an evidence-based understanding of the role of IL-18 in skin diseases and its relationship with disease activities. PMID:26690141

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

    PubMed

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

    2017-01-27

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

  6. Outcome measures in inflammatory rheumatic diseases

    PubMed Central

    2009-01-01

    Inflammatory rheumatic diseases are generally multifaceted disorders and, therefore, measurement of multiple outcomes is relevant to most of these diseases. Developments in outcome measures in the rheumatic diseases are promoted by the development of successful treatments. Outcome measurement will increasingly deal with measurement of low levels of disease activity and avoidance of disease consequences. It is an advantage for patient management and knowledge transfer if the same outcomes are used in practice and in trials. Continuous measures of change are generally the most powerful and, therefore, are preferred as primary outcomes in trials. For daily clinical practice, outcome measures should reflect the patients' state and have to be easily derivable. The objective of this review is to describe recent developments in outcome measures for inflammatory rheumatic diseases for trials and clinical practice, with an emphasis on rheumatoid arthritis. PMID:19849821

  7. The inflammatory cytokine interleukin-23 is elevated in lung cancer, particularly small cell type

    PubMed Central

    Cam, Caner; Muftuoglu, Tuba; Bigi, Oguz; Emirzeoglu, Levent; Celik, Serkan; Ozgun, Alpaslan; Tuncel, Tolga; Top, Cihan

    2016-01-01

    Aim of the study Interleukin (IL)-17 and IL-23 play roles in inflammation and autoimmunity. The function of the IL-17/IL-23 pathway has not been completely evaluated in cancer patients. We aimed to investigate serum IL-17 and IL-23 levels and their relationship with clinicopathological and biochemical parameters in lung cancer patients. Material and methods Forty-five lung cancer patients and 46 healthy volunteers were included in the study. IL-17 and IL-23 measurements were made with the ELISA method. The ages of patients (53–84 years) and healthy subjects (42–82 years) were similar. Results Serum IL-23 levels were higher in lung cancer patients than in healthy subjects (491.27 ±1263.38 pg/ml vs. 240.51 ±233.18 pg/ml; p = 0.032). IL-23 values were higher in small cell lung cancer (SCLC) patients than in non-small cell lung cancer (NSCLC) patients (1325.30 ±2478.06 pg/ml vs. 229.15 ±103.22 pg/ml; p = 0.043). Serum IL-17 levels were lower in the patients, but the difference was not statistically significant (135.94 ±52.36 pg/ml vs. 171.33 ±133.51 pg/ml; p = 0.124). Presence of comorbid disease (diabetes mellitus, hypertension or chronic obstructive lung disease) did not have any effect on the levels of IL-17 or IL-23. Erythrocyte sedimentation rate values were positively correlated with cytokine levels, but serum albumin levels were negatively correlated. Conclusions Serum IL-23 levels are elevated in lung cancer patients, particularly those with SCLC. IL-17 and IL-23 values are correlated with inflammatory markers in the patients. PMID:27647985

  8. Pelvic Inflammatory Disease (For Teens)

    MedlinePlus

    ... getting a sexually transmitted disease (STD) , such as chlamydia or gonorrhea. Girls who have sex with different ... look for signs of infection, including STDs like chlamydia and gonorrhea. Sometimes doctors need an ultrasound or ...

  9. Pelvic Inflammatory Disease (For Teens)

    MedlinePlus

    ... sexually transmitted disease (STD) , such as chlamydia or gonorrhea. Girls who have sex with different partners or ... signs of infection, including STDs like chlamydia and gonorrhea. Sometimes doctors need an ultrasound or CAT scan ...

  10. The Immunological Basis of Inflammatory Bowel Disease

    PubMed Central

    Silva, Francesca A. R.; Rodrigues, Bruno L.; Ayrizono, Maria de Lourdes S.

    2016-01-01

    Inflammatory bowel diseases (IBDs) are chronic ailments, Crohn's disease and ulcerative colitis being the most important. These diseases present an inflammatory profile and they differ according to pathophysiology, the affected area in the gastrointestinal tract, and the depth of the inflammation in the intestinal wall. The immune characteristics of IBD arise from abnormal responses of the innate and adaptive immune system. The number of Th17 cells increases in the peripheral blood of IBD patients, while Treg cells decrease, suggesting that the Th17/Treg proportion plays an important role in the development and maintenance of inflammation. The purpose of this review was to determine the current state of knowledge on the immunological basis of IBD. Many studies have shown the need for further explanation of the development and maintenance of the inflammatory process. PMID:28070181

  11. Inflammatory Cutaneous Diseases in Renal Transplant Recipients

    PubMed Central

    Savoia, Paola; Cavaliere, Giovanni; Zavattaro, Elisa; Veronese, Federica; Fava, Paolo

    2016-01-01

    Kidney transplant recipients frequently suffer from skin infections and malignancies, possibly due to the effects of long-term immunosuppressive therapy. While the relationships between immunosuppression and these pathological conditions have been widely investigated, little is known about the relative incidence and characteristics of inflammatory skin diseases in this type of patient. In this study, we analyze the incidence of a number of inflammatory cutaneous diseases in a cohort of patients who underwent kidney transplantation. Although our study shows a relatively low incidence of these pathologies in transplanted patients—in agreement with the general action of immunosuppressant therapies in reducing inflammation—we scored a different efficacy of the various immunosuppressive regimens on inflammatory and autoimmune skin diseases. This information can be key for designing immunosuppressive regimens and devising accurate follow-up protocols. PMID:27548160

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

    PubMed

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

    2015-06-01

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

  13. Tyrosine kinases in inflammatory dermatologic disease

    PubMed Central

    Paniagua, Ricardo T.; Fiorentino, David; Chung, Lorinda; Robinson, William H.

    2010-01-01

    Tyrosine kinases are enzymes that catalyze the phosphorylation of tyrosine residues on protein substrates. They are key components of signaling pathways that drive an array of cellular responses including proliferation, differentiation, migration, and survival. Specific tyrosine kinases have recently been identified as critical to the pathogenesis of several autoimmune and inflammatory diseases. Small-molecule inhibitors of tyrosine kinases are emerging as a novel class of therapy that may provide benefit in certain patient subsets. In this review, we highlight tyrosine kinase signaling implicated in inflammatory dermatologic diseases, evaluate strategies aimed at inhibiting these aberrant signaling pathways, and discuss prospects for future drug development. PMID:20584561

  14. Fecal biomarkers in inflammatory bowel disease.

    PubMed

    Lopez, Robert N; Leach, Steven T; Lemberg, Daniel A; Duvoisin, Gilles; Gearry, Richard B; Day, Andrew S

    2017-03-01

    Over the last two decades, knowledge on fecal biomarkers has substantially increased. Nowadays, these non-invasive markers of inflammation have significant clinical utility in the management of inflammatory bowel disease. Their use informs the decision to perform endoscopy before diagnosis is made right through to influencing therapeutic choices and the need for interval endoscopic assessment. In this review, the roles of two S100 proteins, calprotectin, and S100A12 are described along with that of lactoferrin, in the context of inflammatory bowel disease.

  15. 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.

  16. 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

  17. Pelvic Inflammatory Disease (PID) Statistics

    MedlinePlus

    ... cdc.gov/std/stats15/appendixa.htm) for more information on other data sources and Table 44 (http://www.cdc.gov/std/stats15/tables/44.htm) . SOURCE: National Disease and Therapeutic Index, IMS Health, Integrated Promotional Services™, IMS Health Report, 1966–2014. The ...

  18. Endothelial Response to Glucocorticoids in Inflammatory Diseases

    PubMed Central

    Zielińska, Karolina A.; Van Moortel, Laura; Opdenakker, Ghislain; De Bosscher, Karolien; Van den Steen, Philippe E.

    2016-01-01

    The endothelium plays a crucial role in inflammation. A balanced control of inflammation requires the action of glucocorticoids (GCs), steroidal hormones with potent cell-specific anti-inflammatory properties. Besides the classic anti-inflammatory effects of GCs on leukocytes, recent studies confirm that endothelial cells also represent an important target for GCs. GCs regulate different aspects of endothelial physiology including expression of adhesion molecules, production of pro-inflammatory cytokines and chemokines, and maintenance of endothelial barrier integrity. However, the regulation of endothelial GC sensitivity remains incompletely understood. In this review, we specifically examine the endothelial response to GCs in various inflammatory diseases ranging from multiple sclerosis, stroke, sepsis, and vasculitis to atherosclerosis. Shedding more light on the cross talk between GCs and endothelium will help to improve existing therapeutic strategies and develop new therapies better tailored to the needs of patients. PMID:28018358

  19. Lung contusion: inflammatory mechanisms and interaction with other injuries.

    PubMed

    Raghavendran, Krishnan; Notter, Robert H; Davidson, Bruce A; Helinski, Jadwiga D; Kunkel, Steven L; Knight, Paul R

    2009-08-01

    This article reviews current animal models and laboratory studies investigating the pathophysiology of lung contusion (LC), a common and severe condition in patients with blunt thoracic trauma. Emphasis is on studies elucidating cells, mediators, receptors, and processes important in the innate pulmonary inflammatory response that contribute to LC injury. Surfactant dysfunction in the pathogenesis of LC is also discussed, as is the potential role of epithelial cell or neutrophil apoptosis. Studies examining combination injuries where LC is exacerbated by secondary insults such as gastric aspiration in trauma patients are also noted. The need for continuing mechanism-based research to further clarify the pathophysiology of LC injury, and to define and test potential therapeutic interventions targeting specific aspects of inflammation or surfactant dysfunction to improve clinical outcomes in patients with LC, is also emphasized.

  20. [Inflammatory bowel disease: importance of nutrition today].

    PubMed

    Jorquera Plaza, F; Espinel Díez, J; Olcoz Goñi, J L

    1997-01-01

    Malnutrition is a very common situation in patients inflammatory with intestinal disease (IID), which can be caused by a multitude of factors. It has been shown that nutritional support not only improves the nutritional condition of the patients, but in Crohn's disease it also has an effect on the activity of the disease, although this effect is smaller than that of steroids. Elemental diets are no more efficient than polymeric diets except under very special circumstances, but they are more expensive and patients tolerate them worse. A digestive pause is not recommended unless there is an absolute contraindication for the use of the digestive tract. Therefore, parenteral nutrition, which is more expensive and can cause serious complications, will be reserved for very specific indications. The use of fish oil supplements, either because it competes with arachidonic acid and prevents the initiation of the inflammatory cascade, or because it decreases the production of cytokines, has shown to be potentially useful in inflammatory intestinal disease, and this must be confirmed by further studies. Short chain fatty acids enemas have shown promising results in distal ulcerative colitis but the lack of homogeneity in the studies makes it necessary for these results to be consolidated in new studies. Nutritional support is especially interesting in children with inflammatory intestinal disease given that the growth retardation which is often seen in severe cases, can be controlled by adequate enteral or parenteral diets.

  1. Minimally Invasive Surgery for Inflammatory Bowel Disease

    PubMed Central

    Holder-Murray, Jennifer; Marsicovetere, Priscilla

    2015-01-01

    Abstract: Surgical management of inflammatory bowel disease is a challenging endeavor given infectious and inflammatory complications, such as fistula, and abscess, complex often postoperative anatomy, including adhesive disease from previous open operations. Patients with Crohn's disease and ulcerative colitis also bring to the table the burden of their chronic illness with anemia, malnutrition, and immunosuppression, all common and contributing independently as risk factors for increased surgical morbidity in this high-risk population. However, to reduce the physical trauma of surgery, technologic advances and worldwide experience with minimally invasive surgery have allowed laparoscopic management of patients to become standard of care, with significant short- and long-term patient benefits compared with the open approach. In this review, we will describe the current state-of the-art for minimally invasive surgery for inflammatory bowel disease and the caveats inherent with this practice in this complex patient population. Also, we will review the applicability of current and future trends in minimally invasive surgical technique, such as laparoscopic “incisionless,” single-incision laparoscopic surgery (SILS), robotic-assisted, and other techniques for the patient with inflammatory bowel disease. There can be no doubt that minimally invasive surgery has been proven to decrease the short- and long-term burden of surgery of these chronic illnesses and represents high-value care for both patient and society. PMID:25989341

  2. Scrotal inflammatory disease: color Doppler US findings.

    PubMed

    Horstman, W G; Middleton, W D; Melson, G L

    1991-04-01

    A study of 45 patients with 51 cases of hemiscrotal inflammatory disease was done to determine the color Doppler ultrasonographic appearance of scrotal inflammatory disorders. The diagnosis was ultimately established by means of appropriate response to antibiotic treatment (47 cases) or surgery (four cases). In all cases, there was evidence of hyperemia: an increased number and concentration of detectable vessels in the affected portion of the scrotum. In 17 cases, the gray scale images were normal, and the only evidence of inflammation was the presence of hypervascularity. Abnormally decreased epididymal vascular resistance was detected in 14 cases of epididymitis; abnormally decreased testicular vascular resistance was detected in six cases of orchitis. Spontaneous venous flow was present in 18 patients. The authors conclude that color Doppler can demonstrate the hyperemic response to scrotal inflammatory disease and that, in the proper clinical setting, it can supplement the gray scale findings and increase diagnostic confidence.

  3. Kinetics of lung lesion development and pro-inflammatory cytokine response in pigs with vaccine-associated enhanced respiratory disease induced by challenge with pandemic (2009) A/H1N1 influenza virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this report was to characterize the enhanced clinical disease and lung lesions observed in pigs vaccinated with inactivated H1N2 swine delta-cluster influenza A virus and challenged with pandemic 2009 A/H1N1 human influenza virus. Eighty-four, six-week-old, crossbred pigs were rand...

  4. [Medical treatment of inflammatory intestinal diseases].

    PubMed

    Järnerot, G

    1991-01-01

    What possible treatments are there for inflammatory intestinal diseases, and on what scientific grounds do we treat these patients? A survey shows that the considerable decline in mortality which has occurred as regards ulcerous colitis ensued rather via trial and error than as a result of regular clinical tests.

  5. 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.

  6. Animal Models of Fibrotic Lung Disease

    PubMed Central

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

    2013-01-01

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

  7. Cystic fibrosis lung disease in adult patients.

    PubMed

    Vender, Robert L

    2008-04-01

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

  8. Tight junctions in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer

    PubMed Central

    Landy, Jonathan; Ronde, Emma; English, Nick; Clark, Sue K; Hart, Ailsa L; Knight, Stella C; Ciclitira, Paul J; Al-Hassi, Hafid Omar

    2016-01-01

    Inflammatory bowel diseases are characterised by inflammation that compromises the integrity of the epithelial barrier. The intestinal epithelium is not only a static barrier but has evolved complex mechanisms to control and regulate bacterial interactions with the mucosal surface. Apical tight junction proteins are critical in the maintenance of epithelial barrier function and control of paracellular permeability. The characterisation of alterations in tight junction proteins as key players in epithelial barrier function in inflammatory bowel diseases is rapidly enhancing our understanding of critical mechanisms in disease pathogenesis as well as novel therapeutic opportunities. Here we give an overview of recent literature focusing on the role of tight junction proteins, in particular claudins, in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer. PMID:27003989

  9. Pancreatic disorders in inflammatory bowel disease

    PubMed Central

    Antonini, Filippo; Pezzilli, Raffaele; Angelelli, Lucia; Macarri, Giampiero

    2016-01-01

    An increased incidence of pancreatic disorders either acute pancreatitis or chronic pancreatitis has been recorded in patients with inflammatory bowel disease (IBD) compared to the general population. Although most of the pancreatitis in patients with IBD seem to be related to biliary lithiasis or drug induced, in some cases pancreatitis were defined as idiopathic, suggesting a direct pancreatic damage in IBD. Pancreatitis and IBD may have similar presentation therefore a pancreatic disease could not be recognized in patients with Crohn’s disease and ulcerative colitis. This review will discuss the most common pancreatic diseases seen in patients with IBD. PMID:27574565

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

    PubMed

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

    2015-04-01

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

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

    PubMed

    Hansell, David M

    2013-09-01

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

  12. IL-17A attracts inflammatory cells in murine lung infection with P. aeruginosa.

    PubMed

    Wonnenberg, Bodo; Jungnickel, Christopher; Honecker, Anja; Wolf, Lisa; Voss, Meike; Bischoff, Markus; Tschernig, Thomas; Herr, Christian; Bals, Robert; Beisswenger, Christoph

    2016-11-01

    IL-17A-dependent immunity is of importance in the protection against extracellular bacterial pathogens. However, IL-17A is also suggested to mediate the pathogenesis of lung diseases, such as acute respiratory distress syndrome. Here, we studied the role of IL-17A in a mouse model of acute pneumonia. IL-17A mediated the expression of keratinocyte-derived chemokine (KC) and the recruitment of inflammatory cells in mice infected with a sub-lethal dose of Pseudomonas aeruginosa. IL-17A deficiency protected mice from lethal P. aeruginosa lung infection. A sub-lethal infection with Streptococcus pneumoniae resulted in increased bacterial burden associated with increased pulmonary inflammation. Thus, the type of infectious bacteria seemed to influence the way in which IL-17A functions during pulmonary infection. Reducing pulmonary inflammation by targeting IL-17A may be a therapeutic option in acute P. aeruginosa pneumonia.

  13. [Smoking-related interstitial lung diseases].

    PubMed

    Marten, Katharina

    2007-03-01

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

  14. Inflammatory bowel diseases: principles of nutritional therapy.

    PubMed

    Campos, Fábio Guilherme; Waitzberg, Dan L; Teixeira, Magaly Gemio; Mucerino, Donato Roberto; Habr-Gama, Angelita; Kiss, Desidério R

    2002-01-01

    Inflammatory Bowel Diseases - ulcerative colitis and Crohn's disease- are chronic gastrointestinal inflammatory diseases of unknown etiology. Decreased oral intake, malabsorption, accelerated nutrient losses, increased requirements, and drug-nutrient interactions cause nutritional and functional deficiencies that require proper correction by nutritional therapy. The goals of the different forms of nutritional therapy are to correct nutritional disturbances and to modulate inflammatory response, thus influencing disease activity. Total parenteral nutrition has been used to correct and to prevent nutritional disturbances and to promote bowel rest during active disease, mainly in cases of digestive fistulae with high output. Its use should be reserved for patients who cannot tolerate enteral nutrition. Enteral nutrition is effective in inducing clinical remission in adults and promoting growth in children. Due to its low complication rate and lower costs, enteral nutrition should be preferred over total parenteral nutrition whenever possible. Both present equal effectiveness in primary therapy for remission of active Crohn's disease. Nutritional intervention may improve outcome in certain individuals; however, because of the costs and complications of such therapy, careful selection is warranted, especially in patients presumed to need total parenteral nutrition. Recent research has focused on the use of nutrients as primary treatment agents. Immunonutrition is an important therapeutic alternative in the management of inflammatory bowel diseases, modulating the inflammation and changing the eicosanoid synthesis profile. However, beneficial reported effects have yet to be translated into the clinical practice. The real efficacy of these and other nutrients (glutamine, short-chain fatty acids, antioxidants) still need further evaluation through prospective and randomized trials.

  15. [Alveolar hemorrhage associated with intestinal inflammatory disease and Hashimoto thyroiditis].

    PubMed

    Rabec, C; Barcat, J; Rey, D

    2003-06-01

    Diffuse alveolar hemorrhage (DAH) is characterized by diffuse bleeding into alveolar spaces. Three histopathological patterns may be seen: 1) pulmonary capillaritis due to immunological aggression to the membrane, 2) diffuse alveolar damage within the context of acute respiratory distress syndrome, and 3) and "bland" DAH without alveolar or capillary damage. In the first two groups, pulmonary damage usually occurs within the context of a systemic disease. In the last, injury is usually found only in the lung, an entity called pulmonary hemosiderosis. We present a case of DAH with neither capillaritis nor diffuse alveolar damage in association with inflammatory bowel disease and Hashimoto thyroiditis. The case is interesting both because the association has not yet been described in the literature and because the presence of alveolar bleeding without evident tissue damage within the context of known autoimmune diseases may extend the field to include a new pathophysiological mechanism of pulmonary hemorrhage.

  16. Multiphoton microscopy and microspectroscopy for diagnostics of inflammatory and neoplastic lung

    NASA Astrophysics Data System (ADS)

    Pavlova, Ina; Hume, Kelly R.; Yazinski, Stephanie A.; Flanders, James; Southard, Teresa L.; Weiss, Robert S.; Webb, Watt W.

    2012-03-01

    Limitations of current medical procedures for detecting early lung cancers inspire the need for new diagnostic imaging modalities for the direct microscopic visualization of lung nodules. Multiphoton microscopy (MPM) provides for subcellular resolution imaging of intrinsic fluorescence from unprocessed tissue with minimal optical attenuation and photodamage. We demonstrate that MPM detects morphological and spectral features of lung tissue and differentiates between normal, inflammatory and neoplastic lung. Ex vivo MPM imaging of intrinsic two-photon excited fluorescence was performed on mouse and canine neoplastic, inflammatory and tumor-free lung sites. Results showed that MPM detected microanatomical differences between tumor-free and neoplastic lung tissue similar to standard histopathology but without the need for tissue processing. Furthermore, inflammatory sites displayed a distinct red-shifted fluorescence compared to neoplasms in both mouse and canine lung, and adenocarcinomas displayed a less pronounced fluorescence emission in the 500 to 550 nm region compared to adenomas in mouse models of lung cancer. These spectral distinctions were also confirmed by two-photon excited fluorescence microspectroscopy. We demonstrate the feasibility of applying MPM imaging of intrinsic fluorescence for the differentiation of lung neoplasms, inflammatory and tumor-free lung, which motivates the application of multiphoton endoscopy for the in situ imaging of lung nodules.

  17. 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.

  18. Zinc absorption in inflammatory bowel disease

    SciTech Connect

    Valberg, L.S.; Flanagan, P.R.; Kertesz, A.; Bondy, D.C.

    1986-07-01

    Zinc absorption was measured in 29 patients with inflammatory bowel disease and a wide spectrum of disease activity to determine its relationship to disease activity, general nutritional state, and zinc status. Patients with severe disease requiring either supplementary oral or parenteral nutrition were excluded. The mean 65ZnCl2 absorption, in the patients, determined using a 65Zn and 51Cr stool-counting test, 45 +/- 17% (SD), was significantly lower than the values, 54 +/- 16%, in 30 healthy controls, P less than 0.05. Low 65ZnCl2 absorption was related to undernutrition, but not to disease activity in the absence of undernutrition or to zinc status estimated by leukocyte zinc measurements. Mean plasma zinc or leukocyte zinc concentrations in patients did not differ significantly from controls, and only two patients with moderate disease had leukocyte zinc values below the 5th percentile of normal. In another group of nine patients with inflammatory bowel disease of mild-to-moderate severity and minimal nutritional impairment, 65Zn absorption from an extrinsically labeled turkey test meal was 31 +/- 10% compared to 33 +/- 7% in 17 healthy controls, P greater than 0.1. Thus, impairment in 65ZnCl2 absorption in the patients selected for this study was only evident in undernourished persons with moderate or severe disease activity, but biochemical evidence of zinc deficiency was uncommon, and clinical features of zinc depletion were not encountered.

  19. Polymicrobial synergy and dysbiosis in inflammatory disease

    PubMed Central

    Lamont, Richard J.; Hajishengallis, George

    2014-01-01

    Uncontrolled inflammation of the periodontal area may arise when complex microbial communities transition from a commensal to a pathogenic entity. Communication among constituent species leads to polymicrobial synergy among metabolically compatible organisms that acquire functional specialization within the developing community. Keystone pathogens, even at low abundance, elevate community virulence and the resulting dysbiotic community targets specific aspects of host immunity to further disable immune surveillance while promoting an overall inflammatory response. Inflammophilic organisms benefit from proteinaceous substrates derived from inflammatory tissue breakdown. Inflammation and dysbiosis reinforce each other and the escalating environmental changes further select for a pathobiotic community. We have synthesized the polymicrobial synergy and dysbiotic components of the process into a new model for inflammatory diseases. PMID:25498392

  20. Polymicrobial synergy and dysbiosis in inflammatory disease.

    PubMed

    Lamont, Richard J; Hajishengallis, George

    2015-03-01

    Uncontrolled inflammation of the periodontal area may arise when complex microbial communities transition from a commensal to a pathogenic entity. Communication among constituent species leads to polymicrobial synergy between metabolically compatible organisms that acquire functional specialization within the developing community. Keystone pathogens, even at low abundance, elevate community virulence, and the resulting dysbiotic community targets specific aspects of host immunity to further disable immune surveillance while promoting an overall inflammatory response. Inflammophilic organisms benefit from proteinaceous substrates derived from inflammatory tissue breakdown. Inflammation and dysbiosis reinforce each other, and the escalating environmental changes further select for a pathobiotic community. We have synthesized the polymicrobial synergy and dysbiotic components of the process into a new model for inflammatory diseases.

  1. Natural killer cells in inflammatory heart disease.

    PubMed

    Ong, SuFey; Rose, Noel R; Čiháková, Daniela

    2017-02-01

    Despite of a multitude of excellent studies, the regulatory role of natural killer (NK) cells in the pathogenesis of inflammatory cardiac disease is greatly underappreciated. Clinical abnormalities in the numbers and functions of NK cells are observed in myocarditis and inflammatory dilated cardiomyopathy (DCMi) as well as in cardiac transplant rejection [1-6]. Because treatment of these disorders remains largely symptomatic in nature, patients have little options for targeted therapies [7,8]. However, blockade of NK cells and their receptors can protect against inflammation and damage in animal models of cardiac injury and inflammation. In these models, NK cells suppress the maturation and trafficking of inflammatory cells, alter the local cytokine and chemokine environments, and induce apoptosis in nearby resident and hematopoietic cells [1,9,10]. This review will dissect each protective mechanism employed by NK cells and explore how their properties might be exploited for their therapeutic potential.

  2. 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.

  3. Predictors of Aggressive Inflammatory Bowel Disease

    PubMed Central

    Yarur, Andres J.; Strobel, Sebastian G.; Deshpande, Amar R.

    2011-01-01

    Inflammatory bowel disease comprises a group of conditions characterized by idiopathic inflammation of the gastrointestinal tract. The natural course of disease can range from an indolent course with prolonged periods of remission to aggressive, incapacitating disease. Predicting which patients are more susceptible to developing severe disease is important, especially when choosing therapeutic agents and treatment strategies. This paper reviews current evidence on the main demographic, clinical, endoscopic, histologic, serologic, and genetic markers that predict aggressive inflammatory bowel disease. In ulcerative colitis, we considered disease to be aggressive when patients had a high relapse rate, need for admission and/or surgery, development of colon cancer, or extraintestinal manifestations. We defined aggressive Crohn's disease as having a high relapse rate, development of penetrating disease, need for repeat surgery, or multiple admissions for flares. In Crohn's disease, involvement of the upper gastrointestinal tract and ileum, penetrating disease, early age at diagnosis, smoking, extensive ulceration of the mucosa, high titers of serum antibodies, and mutations of the NOD2 gene are markers of aggressive disease. In ulcerative colitis, patients with more extensive involvement of the colon (pancolitis) have more symptomatology and are at higher risk for needing a colectomy and developing colon cancer. Also, plasmocytic infiltration of the colonic mucosa and crypt atrophy predict treatment failure. As with diagnosis, no single method can predict disease aggressiveness. Multiple serologic and genetic tests are being developed to refine the accuracy of prediction. Endoscopic findings can also predict the future course of disease. At present, clinical manifestations are the most useful way to make therapeutic decisions. PMID:22298958

  4. Targeting mast cells in inflammatory diseases.

    PubMed

    Reber, Laurent L; Frossard, Nelly

    2014-06-01

    Although mast cells have long been known to play a critical role in anaphylaxis and other allergic diseases, they also participate in some innate immune responses and may even have some protective functions. Data from the study of mast cell-deficient mice have facilitated our understanding of some of the molecular mechanisms driving mast cell functions during both innate and adaptive immune responses. This review presents an overview of the biology of mast cells and their potential involvement in various inflammatory diseases. We then discuss some of the current pharmacological approaches used to target mast cells and their products in several diseases associated with mast cell activation.

  5. (Auto)antibodies in inflammatory bowel diseases.

    PubMed

    Vermeire, Severine; Vermeulen, Nathalie; Van Assche, Gert; Bossuyt, Xavier; Rutgeerts, Paul

    2008-06-01

    Patients who have inflammatory bowel diseases (IBD) express strong antibody responses to a variety of epitopes. A number of (auto)antibodies have been described in patients who have Crohn's disease or ulcerative colitis. These markers reflect a loss of tolerance toward bacterial and fungal flora and have been studied for their clinical value in IBD patients. However, currently, they have no place in the diagnostic work up. Their real promise may lie in their use as surrogate markers of complicated aggressive disease as shown in various retrospective studies, but prospective data are lacking.

  6. Architecture and inflammatory cell composition of the feline lung with special consideration of eosinophil counts.

    PubMed

    Shibly, S; Klang, A; Galler, A; Schwendenwein, I; Christian, M; Guija, A; Tichy, A; Hirt, R A

    2014-05-01

    An increase in the number of eosinophils in bronchoalveolar lavage fluid (BALF) is a hallmark of feline asthma; however, a wide range in the percentage of eosinophils in BALF has been documented in healthy cats. In this study, BALF and lung tissue were collected from 15 cats without respiratory disease, BALF was taken from 15 cats with asthma and lung tissue was collected from six different asthmatic cats. Total nucleated cell count (TNCC) and inflammatory cell percentages were measured in BALF and lung tissue was evaluated microscopically. Asthmatic cats had a significantly higher eosinophil count in lung tissue, but BALF TNCC did not differ significantly between groups. Cats without respiratory signs had significantly more numerous macrophages and lymphocytes in BALF than asthmatics, but significantly lower percentages of eosinophils (4.2 ± 7.8% versus 49.4 ± 20.6%, P <0.001). In healthy feline airways a BALF eosinophil percentage of <5% can be expected. Dominant microscopical findings in feline asthma include high eosinophil counts, airway remodelling and inflammation. There is good correlation between the findings in BALF and tissue in feline asthma.

  7. Microbiome, Metabolome and Inflammatory Bowel Disease

    PubMed Central

    Ahmed, Ishfaq; Roy, Badal C.; Khan, Salman A.; Septer, Seth; Umar, Shahid

    2016-01-01

    Inflammatory Bowel Disease (IBD) is a multifactorial disorder that conceptually occurs as a result of altered immune responses to commensal and/or pathogenic gut microbes in individuals most susceptible to the disease. During Crohn’s Disease (CD) or Ulcerative Colitis (UC), two components of the human IBD, distinct stages define the disease onset, severity, progression and remission. Epigenetic, environmental (microbiome, metabolome) and nutritional factors are important in IBD pathogenesis. While the dysbiotic microbiota has been proposed to play a role in disease pathogenesis, the data on IBD and diet are still less convincing. Nonetheless, studies are ongoing to examine the effect of pre/probiotics and/or FODMAP reduced diets on both the gut microbiome and its metabolome in an effort to define the healthy diet in patients with IBD. Knowledge of a unique metabolomic fingerprint in IBD could be useful for diagnosis, treatment and detection of disease pathogenesis. PMID:27681914

  8. Changes in ion transport in inflammatory disease.

    PubMed

    Eisenhut, Michael

    2006-03-29

    Ion transport is essential for maintenance of transmembranous and transcellular electric potential, fluid transport and cellular volume. Disturbance of ion transport has been associated with cellular dysfunction, intra and extracellular edema and abnormalities of epithelial surface liquid volume. There is increasing evidence that conditions characterized by an intense local or systemic inflammatory response are associated with abnormal ion transport. This abnormal ion transport has been involved in the pathogenesis of conditions like hypovolemia due to fluid losses, hyponatremia and hypokalemia in diarrhoeal diseases, electrolyte abnormalities in pyelonephritis of early infancy, septicemia induced pulmonary edema, and in hypersecretion and edema induced by inflammatory reactions of the mucosa of the upper respiratory tract. Components of membranous ion transport systems, which have been shown to undergo a change in function during an inflammatory response include the sodium potassium ATPase, the epithelial sodium channel, the Cystic Fibrosis Transmembrane Conductance Regulator and calcium activated chloride channels and the sodium potassium chloride co-transporter. Inflammatory mediators, which influence ion transport are tumor necrosis factor, gamma interferon, interleukins, transforming growth factor, leukotrienes and bradykinin. They trigger the release of specific messengers like prostaglandins, nitric oxide and histamine which alter ion transport system function through specific receptors, intracellular second messengers and protein kinases. This review summarizes data on in vivo measurements of changes in ion transport in acute inflammatory conditions and in vitro studies, which have explored the underlying mechanisms. Potential interventions directed at a correction of the observed abnormalities are discussed.

  9. Dietary inflammatory index is related to asthma risk, lung function and systemic inflammation in asthma

    PubMed Central

    Wood, Lisa G; Shivappa, Nitin; Berthon, Bronwyn S; Gibson, Peter G; Hebert, James R

    2014-01-01

    Background Asthma prevalence has increased in recent years and evidence suggests that diet may be a contributing factor. Increased use of processed foods has led to a decrease in diet quality, which may be creating a pro-inflammatory environment, thereby leading to the development and/or progression of various chronic inflammatory diseases and conditions. Recently, the Dietary Inflammatory Index (DII) has been developed and validated to assess the inflammatory potential of individual diets. Objective This study aimed to examine the DII in subjects with asthma compared to healthy controls and to relate the DII to asthma risk, lung function and systemic inflammation. Methods Subjects with asthma (n=99) and healthy controls (n=61) were recruited. Blood was collected and spirometry was performed. The DII was calculated from food frequency questionnaires administered to study subjects. Results The mean DII score for the asthmatics was higher than the DII score for healthy controls (−1.40 versus −1.86, p=0.04), indicating their diets were more pro-inflammatory. For every 1 unit increase in DII score the odds of having asthma increased by 70% (OR: 1.70, 95% CI: 1.03, 2.14; p=0.040). FEV1 was significantly associated with DII score (β=−3.44, 95% CI: −6.50,−0.39; p=0.020), indicating that for every 1 unit increase in DII score, FEV1 decreased by 3.44 times. Furthermore, plasma IL-6 concentrations were positively associated with DII score (β=0.13, 95% CI: 0.05, 0.21;p=0.002). Conclusion and clinical relevance As assessed using the DII score, the usual diet consumed by asthmatics in this study was pro-inflammatory relative to the diet consumed by the healthy controls. The DII score was associated with increased systemic inflammation and lower lung function. Hence, consumption of pro-inflammatory foods may contribute to worse asthma status and targeting an improvement in DII in asthmatics, as an indicator of suitable dietary intake, might be a useful strategy for

  10. Video capsule endoscopy in inflammatory bowel disease

    PubMed Central

    Collins, Paul D

    2016-01-01

    Video capsule endoscopy (VCE) has evolved to become an important tool for the non-invasive examination of the small bowel, which hitherto had been relatively inaccessible to direct visualisation. VCE has been shown to play a role in monitoring the activity of small bowel Crohn’s disease and can be used to assess the response to anti-inflammatory treatment in Crohn’s disease. For those patients with Crohn’s disease who have undergone an intestinal resection, VCE has been assessed as a tool to detect post-operative recurrence. VCE may also aid in the reclassification of patients with a diagnosis of Inflammatory Bowel Disease Unclassified to Crohn’s disease. The evolution of colon capsule endoscopy (CCE) has expanded the application of this technology further. The use of CCE to assess the activity of ulcerative colitis has been described. This advance in capsule technology has also fuelled interest in its potential role as a minimally invasive tool to assess the whole of GI tract opening the possibility of its use for the panenteric assessment of Crohn’s disease. VCE is a safe procedure. However, the risk of a retained capsule is higher in patients with suspected or confirmed Crohn’s disease compared with patients having VCE examination for other indications. A retained video capsule is rare after successful passage of a patency capsule which may be utilised to pre-screen patients undergoing VCE. This paper describes the use of VCE in the assessment of inflammatory bowel disease. PMID:27499830

  11. CT evaluation of the colon: inflammatory disease.

    PubMed

    Horton, K M; Corl, F M; Fishman, E K

    2000-01-01

    Computed tomography (CT) is valuable for detection and characterization of many inflammatory conditions of the colon. At CT, a dilated, thickened appendix is suggestive of appendicitis. A 1-4-cm, oval, fatty pericolic lesion with surrounding mesenteric inflammation is diagnostic of epiploic appendagitis. The key to distinguishing diverticulitis from other inflammatory conditions of the colon is the presence of diverticula in the involved segment. In typhlitis, CT demonstrates cecal distention and circumferential thickening of the cecal wall, which may have low attenuation secondary to edema. In radiation colitis, the clinical history is the key to suggesting the diagnosis because the CT findings can be nonspecific. The location of the involved segment and the extent and appearance of wall thickening may help distinguish Crohn disease and ulcerative colitis. In ischemic colitis, CT typically demonstrates circumferential, symmetric wall thickening with fold enlargement. CT findings of graft-versus-host disease include small bowel and colonic wall thickening, which may result in luminal narrowing and separation of bowel loops. In infectious colitis, the site and thickness of colon affected may suggest a specific organism. The amount of wall thickening in pseudomembranous colitis is typically greater than in any other inflammatory disease of the colon except Crohn disease.

  12. Hydrogen Sulfide and Inflammatory Joint Diseases.

    PubMed

    Burguera, Elena Fernandez; Meijide-Failde, Rosa; Blanco, Francisco J

    2016-08-29

    Rheumatoid arthritis (RA) and osteoarthritis (OA) are widespread rheumatic diseases characterized by persistent inflammation and joint destruction. Hydrogen sulfide (H2S) is an endogenous gas with important physiologic functions in the brain, vasculature and other organs. Recent studies have found H2S to be a mediator in inflammatory joint diseases. H2S exhibited anti-inflammatory, anti-catabolic and/or anti-oxidant effects in rodent models of acute arthritis and in in vitro models using human synoviocytes and articular chondrocytes from RA and OA tissues. These findings suggest that exogenous supplementation of H2S may provide a viable therapeutic option for these diseases. The earliest studies used fast-dissolving salts, such as NaSH, but GYY4137, which produces H2S more physiologically, shortly appeared. More recently still, new H2S-forming compounds that target mitochondria have been synthesized. These compounds open exciting opportunities for investigating the role of H2S in cell bioenergetics, typically altered in arthritides. Positive results have been also obtained when H2S is administered as a sulphurous water bath, an option meriting further study. This review summarizes the recent literature concerning H2S and inflammatory joint diseases, highlighting relevant developments.

  13. [Inflammatory bowel diseases: an immunological approach].

    PubMed

    Sepúlveda, Sofía E; Beltrán, Caroll J; Peralta, Alexis; Rivas, Paola; Rojas, Néstor; Figueroa, Carolina; Quera, Rodrigo; Hermoso, Marcela A

    2008-03-01

    Inflammatory bowel diseases (IBD) are inflammatory diseases with a multifactorial component that involve the intestinal tract. The two relevant IBD syndromes are Crohn's disease (CD) and ulcerative colitis (UC). One factor involved in IBD development is a genetic predisposition, associated to NOD2/CARD15 and Toll-like receptor 4 (TLR4) polymorphisms that might favor infectious enterocolitis that is possibly associated to the development of IBD. The identification of specific immunologic alterations in IBD and their relationship to the etiology of the disease is a relevant research topic. The role of intra and extracellular molecules, such as transcription factors and cytokines that are involved in the inflammatory response, needs to be understood. The relevance of immunologic molecules that might drive the immune response to a T helper (Th) 1, Th 2 or the recently described Th 17 phenotype, has been demonstrated in animal models and clinical studies with IBD patients. CD and UC predominantly behave with a Th 1 and Th 2 immune phenotype, respectively. Recently, an association between CD and Th 17 has been reported. The knowledge acquired from immunologic and molecular research will help to develop accurate diagnostic methods and efficient therapies.

  14. Developmental origins of inflammatory and immune diseases.

    PubMed

    Chen, Ting; Liu, Han-Xiao; Yan, Hui-Yi; Wu, Dong-Mei; Ping, Jie

    2016-08-01

    Epidemiological and experimental animal studies show that suboptimal environments in fetal and neonatal life exert a profound influence on physiological function and risk of diseases in adult life. The concepts of the 'developmental programming' and Developmental Origins of Health and Diseases (DOHaD) have become well accepted and have been applied across almost all fields of medicine. Adverse intrauterine environments may have programming effects on the crucial functions of the immune system during critical periods of fetal development, which can permanently alter the immune function of offspring. Immune dysfunction may in turn lead offspring to be susceptible to inflammatory and immune diseases in adulthood. These facts suggest that inflammatory and immune disorders might have developmental origins. In recent years, inflammatory and immune disorders have become a growing health problem worldwide. However, there is no systematic report in the literature on the developmental origins of inflammatory and immune diseases and the potential mechanisms involved. Here, we review the impacts of adverse intrauterine environments on the immune function in offspring. This review shows the results from human and different animal species and highlights the underlying mechanisms, including damaged development of cells in the thymus, helper T cell 1/helper T cell 2 balance disturbance, abnormal epigenetic modification, effects of maternal glucocorticoid overexposure on fetal lymphocytes and effects of the fetal hypothalamic-pituitary-adrenal axis on the immune system. Although the phenomena have already been clearly implicated in epidemiologic and experimental studies, new studies investigating the mechanisms of these effects may provide new avenues for exploiting these pathways for disease prevention.

  15. Inflammatory oral cavity diseases of the cat.

    PubMed

    Pedersen, N C

    1992-11-01

    There is a great deal of frustration among veterinarians about the diagnosis and treatment of inflammatory diseases of the oral cavity of the cat. This frustration is due to both the high frequency of feline oral inflammatory lesions and our poor understanding of their causes. This poor understanding can be blamed on several things: (1) a rapidly emerging, but still relatively poor, understanding of feline diseases in general and nutrition in particular; (2) a tendency to lump rather than separate specific oral inflammations; (3) a tendency not to use a thorough and systematic approach to diagnosing oral cavity disease; and (4) the reluctance of veterinarians to apply what is already known about human oral cavity diseases to cats. When problems 2 through 4 are adequately addressed, it becomes apparent that we really know more about oral cavity disease in the cat than we thought we knew and that great progress has been made. The task ahead is to define, in precise medical terms, those remaining disease entities of the oral cavity that pose the greatest health risk to cats, to apply what has been already been discovered from human disease counterparts, and to study them systematically.

  16. Pro-inflammatory phenotype of COPD fibroblasts not compatible with repair in COPD lung.

    PubMed

    Zhang, Jing; Wu, Lian; Qu, Jie-ming; Bai, Chun-xue; Merrilees, Mervyn J; Black, Peter N

    2012-07-01

    Chronic obstructive pulmonary disease (COPD) is characterized by loss of elastic fibres from small airways and alveolar walls, with the decrease in elastin increasing with disease severity. It is unclear why there is a lack of repair of elastic fibres. We have examined fibroblasts cultured from lung tissue from subjects with or without COPD to determine if the secretory profile explains lack of tissue repair. In this study, fibroblasts were cultured from lung parenchyma of patients with mild COPD [Global initiative for chronic Obstructive Lung Disease (GOLD) 1, n= 5], moderate to severe COPD (GOLD 2-3, n= 12) and controls (non-COPD, n= 5). Measurements were made of proliferation, senescence-associated β-galactosidase-1, mRNA expression of IL-6, IL-8, MMP-1, tropoelastin and versican, and protein levels for IL-6, IL-8, PGE(2,) tropoelastin, insoluble elastin, and versican. GOLD 2-3 fibroblasts proliferated more slowly (P < 0.01), had higher levels of senescence-associated β-galactosidase-1 (P < 0.001) than controls and showed significant increases in mRNA and/or protein for IL-6 (P < 0.05), IL-8 (P < 0.01), MMP-1 (P < 0.05), PGE(2) (P < 0.05), versican (P < 0.05) and tropoelastin (P < 0.05). mRNA expression and/or protein levels of tropoelastin (P < 0.01), versican (P < 0.05), IL-6 (P < 0.05) and IL-8 (P < 0.05) were negatively correlated with FEV1% of predicted. Insoluble elastin was not increased. In summary, fibroblasts from moderate to severe COPD subjects display a secretory phenotype with up-regulation of inflammatory molecules including the matrix proteoglycan versican, and increased soluble, but not insoluble, elastin. Versican inhibits assembly of tropoelastin into insoluble elastin and we conclude that the pro-inflammatory phenotype of COPD fibroblasts is not compatible with repair of elastic fibres.

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

    PubMed

    Delzell, John E

    2013-06-01

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

  18. Surgical strategies in paediatric inflammatory bowel disease

    PubMed Central

    Baillie, Colin T; Smith, Jennifer A

    2015-01-01

    Inflammatory bowel disease (IBD) comprises two distinct but related chronic relapsing inflammatory conditions affecting different parts of the gastrointestinal tract. Crohn’s disease is characterised by a patchy transmural inflammation affecting both small and large bowel segments with several distinct phenotypic presentations. Ulcerative colitis classically presents as mucosal inflammation of the rectosigmoid (distal colitis), variably extending in a contiguous manner more proximally through the colon but not beyond the caecum (pancolitis). This article highlights aspects of the presentation, diagnosis, and management of IBD that have relevance for paediatric practice with particular emphasis on surgical considerations. Since 25% of IBD cases present in childhood or teenage years, the unique considerations and challenges of paediatric management should be widely appreciated. Conversely, we argue that the organizational separation of the paediatric and adult healthcare worlds has often resulted in late adoption of new approaches particularly in paediatric surgical practice. PMID:26034347

  19. Extraluminal factors contributing to inflammatory bowel disease

    PubMed Central

    Batra, Arvind; Stroh, Thorsten; Siegmund, Britta

    2011-01-01

    Many identified and yet unknown factors contribute to the pathogenesis of inflammatory bowel disease (IBD). The genome-wide association studies clearly support the earlier developed concept that IBD occurs in genetically predisposed individuals who are exposed to distinct environmental factors, which together result in dysregulation of the mucosal immune system. Thus, the majority of previous studies have focused on the immune response within the intestinal wall. The present review aims to emphasize the contribution of three extraluminal structures to this inflammatory process, namely the mesenteric fat tissue, the lymphatics and the microvasculature. Broadening our view across the intestinal wall will not only facilitate our understanding of the disease, but will also us to identify future therapeutic targets. PMID:21350706

  20. Mucosal cytokine network in inflammatory bowel disease

    PubMed Central

    Andoh, Akira; Yagi, Yuhki; Shioya, Makoto; Nishida, Atsushi; Tsujikawa, Tomoyuki; Fujiyama, Yoshihide

    2008-01-01

    Inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn’s disease (CD) are characterized by ongoing mucosal inflammation in which dysfunction of the host immunologic response against dietary factors and commensal bacteria is involved. The chronic inflammatory process leads to disruption of the epithelial barrier, and the formation of epithelial ulceration. This permits easy access for the luminal microbiota and dietary antigens to cells resident in the lamina propria, and stimulates further pathological immune cell responses. Cytokines are essential mediators of the interactions between activated immune cells and non-immune cells, including epithelial and mesenchymal cells. The clinical efficacy of targeting TNF-α clearly indicates that cytokines are the therapeutic targets in IBD patients. In this manuscript, we focus on the biological activities of recently-reported cytokines [Interleukin (IL)-17 cytokine family, IL-31 and IL-32], which might play a role through interaction with TNF-α in the pathophysiology of IBD. PMID:18777592

  1. Systemic complications of inflammatory bowel disease.

    PubMed

    Baillie, J; Soltis, R D

    1985-02-01

    Radiologic assessment of the sacroiliac joints should be part of every inflammatory bowel disease patient's workup; ankylosing spondylitis is 10 to 20 times more common in ulcerative colitis patients than in normal persons. Iritis, which occurs in 10 to 20% of ulcerative colitis patients, often precedes bowel symptoms. It may be necessary to use long-term, low-dose steroid therapy to control frequently recurring iritis.

  2. [Histopathological differential diagnosis in inflammatory bowel diseases].

    PubMed

    Fociani, P; Carsana, L; Zerbi, P; Ferri, A; Sampietro, G M; Vago, G

    2003-01-01

    In front of the suspicious diagnosis of an inflammatory bowel disease (IBD), the pathologist must have adequate and complete clinical, anamnestic, instrumental informations and, if possible, the previous histopathologic examinations. This is necessary because: the diagnosis of IBD is made with exclusion criteria, different pathologic entities may have similar macroscopic and microscopic findings and the characteristic lesions are often present in little number. The authors consider in this paper the problem of the differential diagnosis of IBD.

  3. 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

  4. Interplay between Cellular and Molecular Inflammatory Mediators in Lung Cancer

    PubMed Central

    Orozco-Morales, Mario; Soca-Chafre, Giovanny; Barrios-Bernal, Pedro; Hernández-Pedro, Norma; Arrieta, Oscar

    2016-01-01

    Inflammation is a component of the tumor microenvironment and represents the 7th hallmark of cancer. Chronic inflammation plays a critical role in tumorigenesis. Tumor infiltrating inflammatory cells mediate processes associated with progression, immune suppression, promotion of neoangiogenesis and lymphangiogenesis, remodeling of extracellular matrix, invasion and metastasis, and, lastly, the inhibition of vaccine-induced antitumor T cell response. Accumulating evidence indicates a critical role of myeloid cells in the pathophysiology of human cancers. In contrast to the well-characterized tumor-associated macrophages (TAMs), the significance of granulocytes in cancer has only recently begun to emerge with the characterization of tumor-associated neutrophils (TANs). Recent studies show the importance of CD47 in the interaction with macrophages inhibiting phagocytosis and promoting the migration of neutrophils, increasing inflammation which can lead to recurrence and progression in lung cancer. Currently, therapies are targeted towards blocking CD47 and enhancing macrophage-mediated phagocytosis. However, antibody-based therapies may have adverse effects that limit its use. PMID:26941482

  5. Interaction of obesity and inflammatory bowel disease

    PubMed Central

    Harper, Jason W; Zisman, Timothy L

    2016-01-01

    Inflammatory bowel disease (IBD) is a chronic inflammatory condition of unknown etiology that is thought to result from a combination of genetic, immunologic and environmental factors. The incidence of IBD has been increasing in recent decades, especially in developing and developed nations, and this is hypothesized to be in part related to the change in dietary and lifestyle factors associated with modernization. The prevalence of obesity has risen in parallel with the rise in IBD, suggesting a possible shared environmental link between these two conditions. Studies have shown that obesity impacts disease development and response to therapy in patients with IBD and other autoimmune conditions. The observation that adipose tissue produces pro-inflammatory adipokines provides a potential mechanism for the observed epidemiologic links between obesity and IBD, and this has developed into an active area of investigative inquiry. Additionally, emerging evidence highlights a role for the intestinal microbiota in the development of both obesity and IBD, representing another potential mechanistic connection between the two conditions. In this review we discuss the epidemiology of obesity and IBD, possible pathophysiologic links, and the clinical impact of obesity on IBD disease course and implications for management. PMID:27672284

  6. Reflectance Confocal Microscopy for Inflammatory Skin Diseases.

    PubMed

    Agozzino, M; Gonzalez, S; Ardigò, M

    2016-10-01

    In vivo reflectance confocal microscopy (RCM) is a relatively novel non-invasive tool for microscopic evaluation of the skin used prevalently for diagnosis and management of skin tumour. Its axial resolution, its non-invasive and easy clinical application represents the goals for a large diffusion of this technique. During the last 15 years, RCM has been demonstrated to be able to increase the sensibility and sensitivity of dermoscopy in the diagnosis of skin tumours integrating in real time clinic, dermoscopic and microscopic information useful for the definition of malignancy. Despite to date, no large comparative studies on inflammatory skin diseases has been published in the literature, several papers already showed that RCM has a potential for the evaluation of the descriptive features of the most common inflammatory skin diseases as psoriasis, lupus erythematosus, contact dermatitis and others. The aim of the application of this technique in non-neoplastic skin diseases has been prevalently focused on the possibility of clinical diagnosis confirmation, as well as therapeutic management. Moreover, the use of RCM as driver for an optimised skin biopsy has been also followed in order to reduce the number of unsuccessful histopathological examination. In this review article we describe the confocal features of the major groups of inflammatory skin disorders focusing on psoriasiform dermatitis, interface dermatitis and spongiotic dermatitis.

  7. 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

  8. Pulmonary Hypertension in Diffuse Parenchymal Lung Diseases.

    PubMed

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

    2017-01-01

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

  9. Therapeutic Potential of Traditional Chinese Medicine on Inflammatory Diseases

    PubMed Central

    Tsai, Wen-Hsin; Yang, Chih-Ching; Li, Ping-Chia; Chen, Wang-Chuan; Chien, Chiang-Ting

    2013-01-01

    Increased oxidative stress induces inflammation to several tissues/organs leading to cell death and long-term injury. Traditional Chinese Medicine (TCM) with antioxidant, anti-inflammatory, anti-apoptotic, and autophagic regulatory functions has been widely used as preventive or therapeutic strategy in modern medicine. Oxidative stress and inflammation have been widely reported to contribute to cigarette smoke-induced lung inflammation, hepatotoxicity, or sympathetic activation-induced liver inflammation, lipopolysaccharide-induced renal inflammation, and substance P-mediated neurogenic hyperactive bladder based on clinical findings. In this review, we introduce several evidences for TCM treatment including Monascus adlay (MA) produced by inoculating adlay (Cois lachrymal-jobi L. var. ma-yuen Stapf) with Monascus purpureus on lung injury, Amla (Emblica officinalis Gaertn. of Euphorbiaceae family) on hepatotoxin-induced liver inflammation, Virgate Wormwood Decoction (Yīn Chén Hāo tāng) and its active component genipin on sympathetic activation–induced liver inflammation, and green tea extract and its active components, catechins, or a modified TCM formula Five Stranguries Powder (Wǔ Lén Sǎn) plus Crataegi Fructus (Shān Zhā) on hyperactive bladder. The pathophysiologic and molecular mechanisms of TCM on ameliorating inflammatory diseases are discussed in the review. PMID:24716170

  10. Therapeutic potential of traditional chinese medicine on inflammatory diseases.

    PubMed

    Tsai, Wen-Hsin; Yang, Chih-Ching; Li, Ping-Chia; Chen, Wang-Chuan; Chien, Chiang-Ting

    2013-07-01

    Increased oxidative stress induces inflammation to several tissues/organs leading to cell death and long-term injury. Traditional Chinese Medicine (TCM) with antioxidant, anti-inflammatory, anti-apoptotic, and autophagic regulatory functions has been widely used as preventive or therapeutic strategy in modern medicine. Oxidative stress and inflammation have been widely reported to contribute to cigarette smoke-induced lung inflammation, hepatotoxicity, or sympathetic activation-induced liver inflammation, lipopolysaccharide-induced renal inflammation, and substance P-mediated neurogenic hyperactive bladder based on clinical findings. In this review, we introduce several evidences for TCM treatment including Monascus adlay (MA) produced by inoculating adlay (Cois lachrymal-jobi L. var. ma-yuen Stapf) with Monascus purpureus on lung injury, Amla (Emblica officinalis Gaertn. of Euphorbiaceae family) on hepatotoxin-induced liver inflammation, Virgate Wormwood Decoction (Yīn Chén Hāo tāng) and its active component genipin on sympathetic activation-induced liver inflammation, and green tea extract and its active components, catechins, or a modified TCM formula Five Stranguries Powder (Wǔ Lén Sǎn) plus Crataegi Fructus (Shān Zhā) on hyperactive bladder. The pathophysiologic and molecular mechanisms of TCM on ameliorating inflammatory diseases are discussed in the review.

  11. Downregulation of Mcl-1 has anti-inflammatory pro-resolution effects and enhances bacterial clearance from the lung.

    PubMed

    Lucas, C D; Dorward, D A; Tait, M A; Fox, S; Marwick, J A; Allen, K C; Robb, C T; Hirani, N; Haslett, C; Duffin, R; Rossi, A G

    2014-07-01

    Phagocytes not only coordinate acute inflammation and host defense at mucosal sites, but also contribute to tissue damage. Respiratory infection causes a globally significant disease burden and frequently progresses to acute respiratory distress syndrome, a devastating inflammatory condition characterized by neutrophil recruitment and accumulation of protein-rich edema fluid causing impaired lung function. We hypothesized that targeting the intracellular protein myeloid cell leukemia 1 (Mcl-1) by a cyclin-dependent kinase inhibitor (AT7519) or a flavone (wogonin) would accelerate neutrophil apoptosis and resolution of established inflammation, but without detriment to bacterial clearance. Mcl-1 loss induced human neutrophil apoptosis, but did not induce macrophage apoptosis nor impair phagocytosis of apoptotic neutrophils. Neutrophil-dominant inflammation was modelled in mice by either endotoxin or bacteria (Escherichia coli). Downregulating inflammatory cell Mcl-1 had anti-inflammatory, pro-resolution effects, shortening the resolution interval (Ri) from 19 to 7 h and improved organ dysfunction with enhanced alveolar-capillary barrier integrity. Conversely, attenuating drug-induced Mcl-1 downregulation inhibited neutrophil apoptosis and delayed resolution of endotoxin-mediated lung inflammation. Importantly, manipulating lung inflammatory cell Mcl-1 also accelerated resolution of bacterial infection (Ri; 50 to 16 h) concurrent with enhanced bacterial clearance. Therefore, manipulating inflammatory cell Mcl-1 accelerates inflammation resolution without detriment to host defense against bacteria, and represents a target for treating infection-associated inflammation.

  12. The Changing Phenotype of Inflammatory Bowel Disease

    PubMed Central

    Sheehan, Donal; Shanahan, Fergus

    2016-01-01

    It is widely known that there have been improvements in patient care and an increased incidence of Inflammatory Bowel Disease (IBD) worldwide in recent decades. However, less well known are the phenotypic changes that have occurred; these are discussed in this review. Namely, we discuss the emergence of obesity in patients with IBD, elderly onset disease, mortality rates, colorectal cancer risk, the burden of medications and comorbidities, and the improvement in surgical treatment with a decrease in surgical rates in recent decades. PMID:28050166

  13. MR colonography in inflammatory bowel disease.

    PubMed

    Rimola, Jordi; Ordás, Ingrid

    2014-02-01

    MR colonography has a high diagnostic accuracy for detecting Crohn disease (CD) activity and determining the extent and severity of lesions. In the setting of stricturing CD, MR colonography can provide a detailed map of the lesions, which is useful for clinical decision making. MR colonography can be used as an alternative to conventional colonoscopy in the setting of CD, or as a complementary tool in selected patients with ulcerative colitis. This article reviews the spectrum of MR colonography findings in colonic inflammatory bowel disease and discusses the potential applications and limitations of MR colonography.

  14. Trefoil factors in inflammatory bowel disease

    PubMed Central

    Aamann, Luise; Vestergaard, Else Marie; Grønbæk, Henning

    2014-01-01

    Inflammatory bowel disease (IBD), which comprises ulcerative colitis and Crohn’s disease, is characterized by inflammation of the gastrointestinal tract. The trefoil factors 1, 2, and 3 (TFF1-3) are a family of peptides that play important roles in the protection and repair of epithelial surfaces, including the gastrointestinal tract. TFFs may be involved in IBD pathogenesis and are a potential treatment option. In the present review, we describe the TFF family and their potential role in IBD by summarizing the current knowledge of their expression, possible function and pharmacological role in IBD. PMID:24696606

  15. Preventive health measures in inflammatory bowel disease

    PubMed Central

    Abegunde, Ayokunle T; Muhammad, Bashir H; Ali, Tauseef

    2016-01-01

    We aim to review the literature and provide guidance on preventive health measures in inflammatory bowel disease (IBD). Structured searches were performed in PubMed, MEDLINE, EMBASE, Web of Science and Cochrane Library from January 1976 to June 2016 using the following keywords: (inflammatory bowel disease OR Crohn’s disease OR ulcerative colitis) AND (health maintenance OR preventive health OR health promotion). Abstracts of the articles selected from each of these multiple searches were reviewed, and those meeting the inclusion criteria (that is, providing data regarding preventive health or health maintenance in IBD patients) were recorded. Reference lists from the selected articles were manually reviewed to identify further relevant studies. Patients with IBD are at increased risk of developing adverse events related to the disease course, therapeutic interventions, or non-adherence to medication. Recent studies have suggested that IBD patients do not receive preventive services with the same thoroughness as patients with other chronic diseases. Preventive health measures can avert morbidity and improve the quality of life of patients with IBD. Gastroenterologists and primary care physicians (PCPs) should have an up to date working knowledge of preventive health measures for IBD patients. A holistic approach and better communication between gastroenterologists and PCPs with explicit clarification of roles will prevent duplication of services and streamline care. PMID:27678347

  16. Molecular diagnosis of orbital inflammatory disease.

    PubMed

    Rosenbaum, James T; Choi, Dongseok; Wilson, David J; Grossniklaus, Hans E; Sibley, Cailin H; Harrington, Christina A; Planck, Stephen R

    2015-04-01

    Orbital inflammatory diseases include thyroid eye disease (TED), granulomatosis with polyangiitis (GPA), sarcoidosis, and nonspecific orbital inflammation (NSOI). Histopathological diagnosis usually relies on the clinical context and is not always definitive. Gene expression profiling provides diagnostic and therapeutic information in several malignancies, but its role in evaluating nonmalignant disease is relatively untested. We hypothesized that gene expression profiling could provide diagnostic information for NSOI. We collected formalin-fixed, paraffin-embedded orbital biopsies from 10 institutions and 83 subjects including 25 with thyroid eye disease, 25 nonspecific orbital inflammation, 20 healthy controls, 6 with granulomatosis with polyangiitis, and 7 with sarcoidosis. Tissues were divided into discovery and validation sets. Gene expression was quantified using Affymetrix U133 Plus 2.0 microarrays. A random forest statistical algorithm based on data from 39 probe sets identified controls, GPA, or TED with an average accuracy of 76% (p=0.02). Random forest analysis indicated that 52% of tissues from patients with nonspecific inflammation were consistent with a diagnosis of GPA. Molecular diagnosis by gene expression profiling will augment clinical data and histopathology in differentiating forms of orbital inflammatory disease.

  17. [Inflammatory bowel diseases--imaging diagnostics].

    PubMed

    Gil, Jerzy; Wojtuń, Stanisław; Stec-Michalska, Krystyna; Chojnacki, Cezary

    2004-01-01

    The basic diagnostic procedure in ulcerative colitis is an endoscopy of gastrointestinal tract. It allows the macroscopic evaluation as well as the specimen taking for histological assessment what is the basis for ultimate diagnosis. In case of Crohn's disease the radiological diagnostics is of equal importance as endoscope evaluation. The imaging of inflammatory changes in Crohn's disease still poses some difficulties, especially, that located in the small intestine. Lately, the range of accessible examinations has been wider. We have in disposal the ultrasonography, the computed tomography, the magnetic resonance imaging and the capsular endoscopy. All of them are of great use in the diagnosis of Crohn's disease. In case of microscopic colitis all the imaging diagnostics has no use. The only one mean to establish the diagnosis is a histological assessment. What is more, in the period of remission the colon tissue could be normal. In this paper we discussed the traditional and contemporary intestine imaging methods in inflammatory bowel diseases. The conclusion is that the further progress in science offers a better imaging and, what is even more important, the more efficient diagnostics and treatment of these diseases.

  18. Preventive health measures in inflammatory bowel disease.

    PubMed

    Abegunde, Ayokunle T; Muhammad, Bashir H; Ali, Tauseef

    2016-09-14

    We aim to review the literature and provide guidance on preventive health measures in inflammatory bowel disease (IBD). Structured searches were performed in PubMed, MEDLINE, EMBASE, Web of Science and Cochrane Library from January 1976 to June 2016 using the following keywords: (inflammatory bowel disease OR Crohn's disease OR ulcerative colitis) AND (health maintenance OR preventive health OR health promotion). Abstracts of the articles selected from each of these multiple searches were reviewed, and those meeting the inclusion criteria (that is, providing data regarding preventive health or health maintenance in IBD patients) were recorded. Reference lists from the selected articles were manually reviewed to identify further relevant studies. Patients with IBD are at increased risk of developing adverse events related to the disease course, therapeutic interventions, or non-adherence to medication. Recent studies have suggested that IBD patients do not receive preventive services with the same thoroughness as patients with other chronic diseases. Preventive health measures can avert morbidity and improve the quality of life of patients with IBD. Gastroenterologists and primary care physicians (PCPs) should have an up to date working knowledge of preventive health measures for IBD patients. A holistic approach and better communication between gastroenterologists and PCPs with explicit clarification of roles will prevent duplication of services and streamline care.

  19. Inflammatory bowel diseases: a burden in pediatrics

    PubMed Central

    Mărginean, Cristina Oana; Meliţ, Lorena Elena; Mocanu, Simona; Mărginean, Maria Oana

    2017-01-01

    Abstract Introduction: Inflammatory bowel disease is a chronic condition of the gastrointestinal tract, comprising mainly Crohn disease (CD) and ulcerative colitis (UC). Both of them are frequently encountered in children, being multifactorial conditions, with an unclear etiology. Patients concerns: We present 4 cases of inflammatory bowel disease (IBD) in children in order to underline the variable evolution depending on the patient's particularities. Diagnosis, interventions and outcomes: The first case, a 13-year-old male patient, with a history of Henoch–Schonlein purpura, was admitted for rectal bleeding and weight loss, with normal laboratory parameters. The colonoscopy and the histopathological examination established the diagnosis of UC. The evolution was initially favorable under corticosteroids and sulfasalazine, but with 3 relapses in 2 years. The second case, a 16-year-old male patient, with a history of lactose intolerance and constipation, was admitted for bloody, diarrheic stools, the laboratory tests pointing out only leukocytosis with neutrophilia. The colonoscopy and histopathological examination established the diagnosis of UC. The patient's evolution was slowly favorable. The third case, a 9-year old male patient, with emotional disorders and babbling, admitted for semiconsistent, bloody stools, with increased inflammatory tests, whose colonoscopy pointed out diffuse edema and hemorrhages, the histopathological examination establishing the diagnosis of CD. The evolution was initially favorable, but with 5 relapses in 3 years. The last case, a 12-year-old male patient, was admitted with diarrheic, bloody stools, refractory to antibiotics, and weight loss, with increased inflammatory tests. The colonoscopy pointed out ulcerations, hemorrhages, and disseminated puss deposits. The histopathological examination established the diagnosis of CD. The patient's evolution was favorable, with only 1 relapse in 3 years. Conclusions: The adequate

  20. Fecal Microbiota Transplantation in Inflammatory Bowel Disease.

    PubMed

    Reinisch, Walter

    2017-01-01

    The etiology of inflammatory bowel disease (IBD) is unknown, but it is thought to arise from an aberrant immune response to a change in colonic environment in a genetically susceptible individual. The intestinal microbiota are located at the complex interface of the epithelial barrier and are sensitive to changes in environmental factors, such as diets, drugs or smoking and signals derived from the intestinal immune system and the gut-brain axis. In patients with IBD, an imbalance in the structural and/or functional configuration of the intestinal microbiota leading to the disruption of the host-microorganism homeostasis (dysbiosis) has been reproducibly reported. As animal models of IBD require gut bacteria to induce inflammation, it is hypothesized that the dysbiosis observed in patients is not only a surrogate of changes at the intestinal barrier but also a potential cause or at least enhancer of the mucosal inflammatory process. That burgeoning notion has stimulated thoughts to modify the intestinal microbiota and rekindled interest in previous work on the efficacy of antibiotics in patients with IBD. The feasibility and tremendous success of fecal microbiota transplantation (FMT) to treat antibiotic resistant Clostridium difficile has finally paved the way to embark into the unchartered territory of IBD using FMT. Different routes and number of administrations, choices of donors, disease status and permitted therapies might have contributed to mixed results, particularly from the so far published randomized controlled trials. However, microbiome analysis suggests that a durable transplantation of donor bacteria to the host appears feasible and might be associated with a higher likelihood of response. On the other hand, this raises the concern of transplanting not only anti-inflammatory active bacteria and their products, but also not-yet-known dispositions for other diseases including cancer. Attempts are being made to better characterize those components of

  1. Inflammatory Mechanisms Linking Periodontal Diseases to Cardiovascular Diseases

    PubMed Central

    Schenkein, Harvey A.; Loos, Bruno G.

    2015-01-01

    Aims In this paper, inflammatory mechanisms that link periodontal diseases to cardiovascular diseases (CVD) are reviewed. Materials and Methods and Results This paper is a literature review. Studies in the literature implicate a number of possible mechanisms that could be responsible for increased inflammatory responses in atheromatous lesions due to periodontal infections. These include increased systemic levels of inflammatory mediators stimulated by bacteria and their products at sites distant from the oral cavity, elevated thrombotic and hemostatic markers that promote a prothrombotic state and inflammation, cross-reactive systemic antibodies that promote inflammation and interact with the atheroma, promotion of dyslipidemia with consequent increases in proinflammatory lipid classes and subclasses, and common genetic susceptibility factors present in both disease leading to increased inflammatory responses. Conclusions Such mechanisms may be thought to act in concert to increase systemic inflammation in periodontal disease and to promote or exacerbate atherogenesis. However, proof that the increase in systemic inflammation attributable to periodontitis impacts inflammatory responses during atheroma development, thrombotic events, or myocardial infarction or stroke is lacking. PMID:23627334

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

    MedlinePlus

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

  3. 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 ...

  4. Diet-induced obesity reprograms the inflammatory response of the murine lung to inhaled endotoxin.

    PubMed

    Tilton, Susan C; Waters, Katrina M; Karin, Norman J; Webb-Robertson, Bobbie-Jo M; Zangar, Richard C; Lee, K Monica; Bigelow, Diana J; Pounds, Joel G; Corley, Richard A

    2013-03-01

    The co-occurrence of environmental factors is common in complex human diseases and, as such, understanding the molecular responses involved is essential to determine risk and susceptibility to disease. We have investigated the key biological pathways that define susceptibility for pulmonary infection during obesity in diet-induced obese (DIO) and regular weight (RW) C57BL/6 mice exposed to inhaled lipopolysaccharide (LPS). LPS induced a strong inflammatory response in all mice as indicated by elevated cell counts of macrophages and neutrophils and levels of proinflammatory cytokines (MDC, MIP-1γ, IL-12, RANTES) in the bronchoalveolar lavage fluid. Additionally, DIO mice exhibited 50% greater macrophage cell counts, but decreased levels of the cytokines, IL-6, TARC, TNF-α, and VEGF relative to RW mice. Microarray analysis of lung tissue showed over half of the LPS-induced expression in DIO mice consisted of genes unique for obese mice, suggesting that obesity reprograms how the lung responds to subsequent insult. In particular, we found that obese animals exposed to LPS have gene signatures showing increased inflammatory and oxidative stress response and decreased antioxidant capacity compared with RW. Because signaling pathways for these responses can be common to various sources of environmentally induced lung damage, we further identified biomarkers that are indicative of specific toxicant exposure by comparing gene signatures after LPS exposure to those from a parallel study with cigarette smoke. These data show obesity may increase sensitivity to further insult and that co-occurrence of environmental stressors result in complex biosignatures that are not predicted from analysis of individual exposures.

  5. Diet-Induced Obesity Reprograms the Inflammatory Response of the Murine Lung to Inhaled Endotoxin

    SciTech Connect

    Tilton, Susan C.; Waters, Katrina M.; Karin, Norman J.; Webb-Robertson, Bobbie-Jo M.; Zangar, Richard C.; Lee, Monika K.; Bigelow, Diana J.; Pounds, Joel G.; Corley, Richard A.

    2013-03-01

    The co-occurrence of environmental factors is common in complex human diseases and, as such, understanding the molecular responses involved is essential to determine risk and susceptibility to disease. We have investigated the key biological pathways that define susceptibility for pulmonary infection during obesity in diet-induced obese (DIO) and regular weight (RW) C57BL/6 mice exposed to inhaled lipopolysaccharide (LPS). LPS induced a strong inflammatory response in all mice as indicated by elevated cell counts of macrophages and neutrophils and levels of proinflammatory cytokines (MDC, MIP-1γ, IL-12, RANTES) in the bronchoalveolar lavage fluid. Additionally, DIO mice exhibited 50% greater macrophage cell counts, but decreased levels of the cytokines, IL-6, TARC, TNF-α, and VEGF relative to RW mice. Microarray analysis of lung tissue showed over half of the LPS-induced expression in DIO mice consisted of genes unique for obese mice, suggesting that obesity reprograms how the lung responds to subsequent insult. In particular, we found that obese animals exposed to LPS have gene signatures showing increased inflammatory and oxidative stress response and decreased antioxidant capacity compared with RW. Because signaling pathways for these responses can be common to various sources of environmentally induced lung damage, we further identified biomarkers that are indicative of specific toxicant exposure by comparing gene signatures after LPS exposure to those from a parallel study with cigarette smoke. These data show obesity may increase sensitivity to further insult and that co-occurrence of environmental stressors result in complex biosignatures that are not predicted from analysis of individual exposures.

  6. Pancreatic function in chronic inflammatory bowel disease.

    PubMed

    Angelini, G; Cavallini, G; Bovo, P; Brocco, G; Castagnini, A; Lavarini, E; Merigo, F; Tallon, N; Scuro, L A

    1988-03-01

    This study was prospectively carried out to evaluate the frequency and clinical significance of pancreatic impairment in the course of chronic inflammatory bowel disease (CIBD). Twenty-seven patients affected by ulcerative colitis or Crohn's disease were submitted to a secretin-cerulein test, oral glucose test (OGT) and to indirect immunofluorescence (IFL) for detection of autoantibodies against exocrine and endocrine tissue. A bicarbonate plus enzyme or only an enzyme insufficiency was found in 11/27 patients, whereas isolated lipase decrease was observed in 18 subjects. In the results of the OGT and the indirect IFL test there was no difference between patients and controls. These data demonstrate that pancreatic impairment is a far more frequent occurrence than generally recognized in clinical practice. The decrease of lipase secretion could worsen the consequences of malabsorption in Crohn's disease of the small intestine. Therefore we think that a pancreatic assessment is advisable, at least in Crohn's disease patients with steatorrhea.

  7. 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

  8. Oral pathology in inflammatory bowel disease

    PubMed Central

    Muhvić-Urek, Miranda; Tomac-Stojmenović, Marija; Mijandrušić-Sinčić, Brankica

    2016-01-01

    The incidence of inflammatory bowel diseases (IBD) - Crohn’s disease (CD) and ulcerative colitis (UC) - has been increasing on a global scale, and progressively, more gastroenterologists will be included in the diagnosis and treatment of IBD. Although IBD primarily affects the intestinal tract, extraintestinal manifestations of the disease are often apparent, including in the oral cavity, especially in CD. Specific oral manifestations in patients with CD are as follows: indurate mucosal tags, cobblestoning and mucogingivitis, deep linear ulcerations and lip swelling with vertical fissures. The most common non-specific manifestations, such as aphthous stomatitis and angular cheilitis, occur in both diseases, while pyostomatitis vegetans is more pronounced in patients with UC. Non-specific lesions in the oral cavity can also be the result of malnutrition and drugs. Malnutrition, followed by anemia and mineral and vitamin deficiency, affects the oral cavity and teeth. Furthermore, all of the drug classes that are applied to the treatment of inflammatory bowel diseases can lead to alterations in the oral cavity due to the direct toxic effects of the drugs on oral tissues, as well as indirect immunosuppressive effects with a risk of developing opportunistic infections or bone marrow suppression. There is a higher occurrence of malignant diseases in patients with IBD, which is related to the disease itself and to the IBD-related therapy with a possible oral pathology. Treatment of oral lesions includes treatment of the alterations in the oral cavity according to the etiology together with treatment of the primary intestinal disease, which requires adequate knowledge and a strong cooperation between gastroenterologists and specialists in oral medicine. PMID:27433081

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

    PubMed

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

    2017-01-01

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

  10. Can Probiotics Cure Inflammatory Bowel Diseases?

    PubMed

    Korada, Siva Kumar; Yarla, Nagendra Sastry; Bishayee, Anupam; Aliev, Gjumrakch; Aruna Lakshmi, K; Arunasree, M K; Dananajaya, B L; Mishra, Vijendra

    2016-01-01

    Gastrointestinal (GI) disorders, especially microbial dysbiosis play role in several GI ailments such as irritable bowel syndrome, colorectal cancer, inflammatory bowel diseases, and antibiotic-associated diarrhoea. Role of inflammatory bowel disease (IBD) is multifactorial as it involves loss of maintaining intestinal epithelial barrier integrity, increased release of pro-inflammatory molecules, and microbial dysbiosis in gut microflora. Some specific pathogens also play a key role in the IBD development. The origin and causation are still in unfathomable condition and the exact root cause is unknown. Recently probiotic studies have been gaining importance because of their positive responses in their IBD experimental results. According to joint Food and Agricultural Organisation/World Health Organisation working group, probiotics are defined as live microorganisms which when administered in adequate amount confer health benefit on the host. These live beneficial microorganisms are considered helpful in improving gut colonization and perseverance thereby improves prophylactic effect. In the direction of IBD research, a number of studies are needed to standardize its methodology and its applicability on human usage. The particular review presents an overview of gut microflora and its impact on host health, types of IBD and existing therapies to treat this disorder, mechanism of several probiotic actions, role of probiotics in IBD prevention with their supporting evidences.

  11. Host-microorganism interactions in lung diseases.

    PubMed

    Marsland, Benjamin J; Gollwitzer, Eva S

    2014-12-01

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

  12. Skin Manifestations of Inflammatory Bowel Disease

    PubMed Central

    Huang, Brian L.; Chandra, Stephanie; Shih, David Quan

    2012-01-01

    Inflammatory bowel disease (IBD) is a disease that affects the intestinal tract via an inflammatory process. Patients who suffer from IBD often have diseases that affect multiple other organ systems as well. These are called extraintestinal manifestations and can be just as, if not more debilitating than the intestinal inflammation itself. The skin is one of the most commonly affected organ systems in patients who suffer from IBD. The scientific literature suggests that a disturbance of the equilibrium between host defense and tolerance, and the subsequent over-activity of certain immune pathways are responsible for the cutaneous disorders seen so frequently in IBD patients. The purpose of this review article is to give an overview of the types of skin diseases that are typically seen with IBD and their respective pathogenesis, proposed mechanisms, and treatments. These cutaneous disorders can manifest as metastatic lesions, reactive processes to the intestinal inflammation, complications of IBD itself, or side effects from IBD treatments; these can be associated with IBD via genetic linkage, common autoimmune processes, or other mechanisms that will be discussed in this article. Ultimately, it is important for healthcare providers to understand that skin manifestations should always be checked and evaluated for in patients with IBD. Furthermore, skin disorders can predate gastrointestinal symptoms and thus may serve as important clinical indicators leading physicians to earlier diagnosis of IBD. PMID:22347192

  13. Kinetics of lung lesion development and pro-inflammatory cytokine response in pigs with vaccine-associated enhanced respiratory disease induced by challenge with pandemic (2009) A/H1N1 influenza virus.

    PubMed

    Gauger, P C; Vincent, A L; Loving, C L; Henningson, J N; Lager, K M; Janke, B H; Kehrli, M E; Roth, J A

    2012-11-01

    The objective of this report was to characterize the enhanced clinical disease and lung lesions observed in pigs vaccinated with inactivated H1N2 swine δ-cluster influenza A virus and challenged with pandemic 2009 A/H1N1 human influenza virus. Eighty-four, 6-week-old, cross-bred pigs were randomly allocated into 3 groups of 28 pigs to represent vaccinated/challenged (V/C), non-vaccinated/challenged (NV/C), and non-vaccinated/non-challenged (NV/NC) control groups. Pigs were intratracheally inoculated with pH1N1 and euthanized at 1, 2, 5, and 21 days post inoculation (dpi). Macroscopically, V/C pigs demonstrated greater percentages of pneumonia compared to NV/C pigs. Histologically, V/C pigs demonstrated severe bronchointerstitial pneumonia with necrotizing bronchiolitis accompanied by interlobular and alveolar edema and hemorrhage at 1 and 2 dpi. The magnitude of peribronchiolar lymphocytic cuffing was greater in V/C pigs by 5 dpi. Microscopic lung lesion scores were significantly higher in the V/C pigs at 2 and 5 dpi compared to NV/C and NV/NC pigs. Elevated TNF-α, IL-1β, IL-6, and IL-8 were detected in bronchoalveolar lavage fluid at all time points in V/C pigs compared to NV/C pigs. These data suggest H1 inactivated vaccines followed by heterologous challenge resulted in potentiated clinical signs and enhanced pulmonary lesions and correlated with an elevated proinflammatory cytokine response in the lung. The lung alterations and host immune response are consistent with the vaccine-associated enhanced respiratory disease (VAERD) clinical outcome observed reproducibly in this swine model.

  14. Impaired Clearance of Apoptotic Cells in Chronic Inflammatory Diseases: Therapeutic Implications

    PubMed Central

    Szondy, Zsuzsa; Garabuczi, Éva; Joós, Gergely; Tsay, Gregory J.; Sarang, Zsolt

    2014-01-01

    In healthy individuals, billions of cells die by apoptosis every day. Removal of the dead cells by phagocytosis (a process called efferocytosis) must be efficient to prevent secondary necrosis and the consequent release of pro-inflammatory cell contents that damages the tissue environment and provokes autoimmunity. In addition, detection and removal of apoptotic cells generally induces an anti-inflammatory response. As a consequence improper clearance of apoptotic cells, being the result of either genetic anomalies and/or a persistent disease state, contributes to the establishment and progression of a number of human chronic inflammatory diseases such as autoimmune and neurological disorders, inflammatory lung diseases, obesity, type 2 diabetes, or atherosclerosis. During the past decade, our knowledge about the mechanism of efferocytosis has significantly increased, providing therapeutic targets through which impaired phagocytosis of apoptotic cells and the consequent inflammation could be influenced in these diseases. PMID:25136342

  15. Airway Epithelial Cell Cilia and Obstructive Lung Disease

    PubMed Central

    Yaghi, Asma; Dolovich, Myrna B.

    2016-01-01

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

  16. Genetic therapies for cystic fibrosis lung disease.

    PubMed

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

    2011-04-15

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

  17. Increased Prevalence of Methanosphaera stadtmanae in Inflammatory Bowel Diseases

    PubMed Central

    Blais Lecours, Pascale; Marsolais, David; Cormier, Yvon; Berberi, Marie; Haché, Chantal; Bourdages, Raymond; Duchaine, Caroline

    2014-01-01

    Background The gut microbiota is associated with the modulation of mucosal immunity and the etiology of inflammatory bowel diseases (IBD). Previous studies focused on the impact of bacterial species on IBD but seldom suspected archaea, which can be a major constituent of intestinal microbiota, to be implicated in the diseases. Recent evidence supports that two main archaeal species found in the digestive system of humans, Methanobrevibacter smithii (MBS) and Methanosphaera stadtmanae (MSS) can have differential immunogenic properties in lungs of mice; with MSS but not MBS being a strong inducer of the inflammatory response. We thus aimed at documenting the immunogenic potential of MBS and MSS in humans and to explore their association with IBD. Methods To validate the immunogenicity of MBS and MSS in humans, peripheral blood mononuclear cells from healthy subjects were stimulated with these two microorganisms and the production of inflammatory cytokine TNF was measured by ELISA. To verify MBS and MSS prevalence in IBD, stool samples from 29 healthy control subjects and 29 patients suffering from IBD were collected for DNA extraction. Plasma was also collected from these subjects to measure antigen-specific IgGs by ELISA. Quantitative PCR was used for bacteria, methanogens, MBS and MSS quantification. Results Mononuclear cells stimulated with MSS produced higher concentrations of TNF (39.5 ng/ml) compared to MBS stimulation (9.1 ng/ml). Bacterial concentrations and frequency of MBS-containing stools were similar in both groups. However, the number of stool samples positive for the inflammatory archaea MSS was higher in patients than in controls (47% vs 20%). Importantly, only IBD patients developed a significant anti-MSS IgG response. Conclusion The prevalence of MSS is increased in IBD patients and is associated with an antigen-specific IgG response. PMID:24498365

  18. α1-Antitrypsin Activates Protein Phosphatase 2A to Counter Lung Inflammatory Responses

    PubMed Central

    Geraghty, Patrick; Eden, Edward; Pillai, Manju; Campos, Michael; McElvaney, Noel G.

    2014-01-01

    Rationale: α1-Antitrypsin (A1AT) was identified as a plasma protease inhibitor; however, it is now recognized as a multifunctional protein that modulates immunity, inflammation, proteostasis, apoptosis, and cellular senescence. Like A1AT, protein phosphatase 2A (PP2A), a major serine-threonine phosphatase, regulates similar biologic processes and plays a key role in chronic obstructive pulmonary disease. Objectives: Given their common effects, this study investigated whether A1AT acts via PP2A to alter tumor necrosis factor (TNF) signaling, inflammation, and proteolytic responses in this disease. Methods: PP2A activity was measured in peripheral blood neutrophils from A1AT-deficient (PiZZ) and healthy (PiMM) individuals and in alveolar macrophages from normal (60 mg/kg) and high-dose (120 mg/kg) A1AT-treated PiZZ subjects. PP2A activation was assessed in human neutrophils, airway epithelial cells, and peripheral blood monocytes treated with plasma purified A1AT protein. Similarly, lung PP2A activity was measured in mice administered intranasal A1AT. PP2A was silenced in lung epithelial cells treated with A1AT and matrix metalloproteinase and cytokine production was then measured following TNF-α stimulation. Measurements and Main Results: PP2A was significantly lower in neutrophils isolated from PiZZ compared with PiMM subjects. A1AT protein activated PP2A in human alveolar macrophages, monocytes, neutrophils, airway epithelial cells, and in mouse lungs. This activation required functionally active A1AT protein and protein tyrosine phosphatase 1B expression. A1AT treatment acted via PP2A to prevent p38 and IκBα phosphorylation and matrix metalloproteinase and cytokine induction in TNF-α–stimulated epithelial cells. Conclusions: Together, these data indicate that A1AT modulates PP2A to counter inflammatory and proteolytic responses induced by TNF signaling in the lung. PMID:25341065

  19. Autophagy in pulmonary macrophages mediates lung inflammatory injury via NLRP3 inflammasome activation during mechanical ventilation.

    PubMed

    Zhang, Yang; Liu, Gongjian; Dull, Randal O; Schwartz, David E; Hu, Guochang

    2014-07-15

    The inflammatory response is a primary mechanism in the pathogenesis of ventilator-induced lung injury. Autophagy is an essential, homeostatic process by which cells break down their own components. We explored the role of autophagy in the mechanisms of mechanical ventilation-induced lung inflammatory injury. Mice were subjected to low (7 ml/kg) or high (28 ml/kg) tidal volume ventilation for 2 h. Bone marrow-derived macrophages transfected with a scrambled or autophagy-related protein 5 small interfering RNA were administered to alveolar macrophage-depleted mice via a jugular venous cannula 30 min before the start of the ventilation protocol. In some experiments, mice were ventilated in the absence and presence of autophagy inhibitors 3-methyladenine (15 mg/kg ip) or trichostatin A (1 mg/kg ip). Mechanical ventilation with a high tidal volume caused rapid (within minutes) activation of autophagy in the lung. Conventional transmission electron microscopic examination of lung sections showed that mechanical ventilation-induced autophagy activation mainly occurred in lung macrophages. Autophagy activation in the lungs during mechanical ventilation was dramatically attenuated in alveolar macrophage-depleted mice. Selective silencing of autophagy-related protein 5 in lung macrophages abolished mechanical ventilation-induced nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome activation and lung inflammatory injury. Pharmacological inhibition of autophagy also significantly attenuated the inflammatory responses caused by lung hyperinflation. The activation of autophagy in macrophages mediates early lung inflammation during mechanical ventilation via NLRP3 inflammasome signaling. Inhibition of autophagy activation in lung macrophages may therefore provide a novel and promising strategy for the prevention and treatment of ventilator-induced lung injury.

  20. Extraintestinal manifestations in inflammatory bowel disease

    PubMed Central

    Danese, Silvio; Semeraro, Stefano; Papa, Alfredo; Roberto, Italia; Scaldaferri, Franco; Fedeli, Giuseppe; Gasbarrini, Giovanni; Gasbarrini, Antonio

    2005-01-01

    Inflammatory bowel diseases (IBD) can be really considered to be systemic diseases since they are often associated with extraintestinal manifestations, complications, and other autoimmune disorders. Indeed, physicians who care for patients with ulcerative colitis and Crohn’s disease, the two major forms of IBD, face a new clinical challenge every day, worsened by the very frequent rate of extraintestinal complications. The goal of this review is to provide an overview and an update on the extraintestinal complications occurring in IBD. Indeed, this paper highlights how virtually almost every organ system can be involved, principally eyes, skin, joints, kidneys, liver and biliary tracts, and vasculature (or vascular system) are the most common sites of systemic IBD and their involvement is dependent on different mechanisms. PMID:16437620

  1. Important cutaneous manifestations of inflammatory bowel disease

    PubMed Central

    Trost, L; McDonnell, J

    2005-01-01

    Inflammatory bowel disease (IBD) has many extraintestinal manifestations. Cutaneous manifestations are usually related to the activity of the bowel disease but may have an independent course. Anyone presenting with IBD should be examined for cutaneous manifestations. Pyoderma gangrenosum is a severe painful ulcerating disease that requires moist wound management and, in the absence of secondary infection, systemic corticosteroids, cyclosporine, or both. Infliximab may also be used. Erythema nodosum is a common cause of tender red nodules of the shins. Management includes leg elevation, NSAIDs, and potassium iodide. Oral manifestations of IBD include aphthous stomatitis, mucosal nodularity (cobblestoning), and pyostomatitis vegetans. Treatment should be directed both at the cutaneous lesions and at the underlying systemic condition. PMID:16143688

  2. Newer treatments for inflammatory bowel disease.

    PubMed

    Stotland, B R; Lichtenstein, G R

    1998-02-01

    Inflammatory bowel disease represents chronic idiopathic disorders which involve either the colon exclusively (ulcerative colitis) of any part of the gastrointestinal tract (Crohn's disease). The course of these entities is typified by periods of symptomatic exacerbation interspersed with clinical remissions. Management is based upon regimens which decrease mucosal inflammation. Colonic disease distal to the splenic flexure may be treated with topical therapy, but other regions generally necessitate oral therapy. Currently used medications include the aminosalicylates, glucocorticoids, antibiotics and immunomodulators. The immunomodulator class of medications includes azathioprine, 6-mercaptopurine, cyclosporine A and methotrexate. Newer agents include short-chain fatty acids, omega-3 fatty acids and antibodies directed to tumor necrosis factor. Medical management also occasionally involves optimizing nutritional status with the addition of elemental diets or total parenteral nutrition. Management of specific clinical presentations is discussed.

  3. Fibronectin Matrix Remodeling in the Regulation of the Inflammatory Response within the Lung: An Early Step in Lung Cancer Progression

    DTIC Science & Technology

    2011-09-01

    such as that which occurs in chronic obstructive pulmonary disease (COPD) and emphysema , is associated with increased risk of lung cancer. These...the mechanical properties of lung tissue are seen in a number of disease states including cancer, COPD, asthma and emphysema , where changes in the

  4. Biomarkers in Paediatric Cystic Fibrosis Lung Disease.

    PubMed

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

    2015-09-01

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

  5. Fecal Microbiota Transplantation for Inflammatory Bowel Disease

    PubMed Central

    Lopez, Joanna

    2016-01-01

    The gut bacterial microbiome, particularly its role in disease and inflammation, has gained international attention with the successful use of fecal microbiota transplantation (FMT) in the treatment of Clostridium difficile infection. This success has led to studies exploring the role of FMT in other conditions, including inflammatory bowel disease (IBD). Both Crohn’s disease and ulcerative colitis are chronic inflammatory conditions of the gastrointestinal system that have multifactorial etiologies. A shift in gut microbial composition in genetically susceptible individuals, an altered immune system, and environmental factors are all hypothesized to have a role in the pathogenesis of IBD. While numerous case reports and cohort studies have described the use of FMT in patients with IBD over the last 2 decades, the development of new sequencing techniques and results from 2 recent randomized, controlled trials have allowed for a better understanding of the relationship between the microbiome and the human host. However, despite these efforts, knowledge remains limited and the role of FMT in the management of IBD remains uncertain. Further investigation is necessary before FMT joins the current armamentarium of treatment options in clinical practice. PMID:27493597

  6. Osteoporosis in patients with inflammatory bowel disease.

    PubMed Central

    Compston, J E; Judd, D; Crawley, E O; Evans, W D; Evans, C; Church, H A; Reid, E M; Rhodes, J

    1987-01-01

    Bone mineral content in spinal trabecular and peripheral cortical bone was measured in 75 unselected patients with small and/or large intestinal inflammatory bowel disease. Osteoporosis, defined as a bone mineral content greater than 2 SD below the age and sex matched normal mean value was present in 23 patients (30.6%). Three amenorrhoeic females aged 34, 38, and 42 years had severe clinical osteoporosis and a further three patients had one or more vertebral crush fractures. Eighteen of the 23 patients with osteoporosis had small intestinal disease with one or more resections and the mean lifetime steroid dose in those with osteoporosis was significantly higher than in those with normal bone mineral content. Bone mineral content in spinal trabecular bone showed significant negative correlations with lifetime steroid dose and serum alkaline phosphatase and a significant positive correlation with serum albumin. Peripheral cortical bone mineral content was positively correlated with body weight, height and body mass index. We conclude that the prevalence of osteoporosis is increased in patients with inflammatory bowel disease, severe clinical osteoporosis developing in some relatively young patients. The pathogenesis of this bone loss is probably multifactorial; steroid therapy is likely to be an important contributory factor. PMID:3583068

  7. Interleukin-6 blockade in ocular inflammatory diseases

    PubMed Central

    Mesquida, M; Leszczynska, A; Llorenç, V; Adán, A

    2014-01-01

    Interleukin-6 (IL-6) is a key cytokine featuring redundancy and pleiotropic activity. It plays a central role in host defence against environmental stress such as infection and injury. Dysregulated, persistent interleukin (IL)-6 production has been implicated in the development of various autoimmune, chronic inflammatory diseases and even cancers. Significant elevation of IL-6 has been found in ocular fluids derived from refractory/chronic uveitis patients. In experimental autoimmune uveitis models with IL-6 knock-out mice, IL-6 has shown to be essential for inducing inflammation. IL-6 blockade can suppress acute T helper type 17 (Th17) responses via its differentiation and, importantly, can ameliorate chronic inflammation. Tocilizumab, a recombinant humanized anti-IL-6 receptor antibody, has been shown to be effective in several autoimmune diseases, including uveitis. Herein, we discuss the basic biology of IL-6 and its role in development of autoimmune conditions, focusing particularly on non-infectious uveitis. It also provides an overview of efficacy and safety of tocilizumab therapy for ocular inflammatory diseases. PMID:24528300

  8. Nutrition and chronic inflammatory rheumatic disease.

    PubMed

    Semerano, Luca; Julia, Chantal; Aitisha, Ouidade; Boissier, Marie-Christophe

    2016-11-30

    Nutrition is a major environmental influence on human health. Epidemiological and interventional studies suggest a pathophysiological or therapeutic role, respectively, for nutrition in inflammatory rheumatic diseases (IRDs). Nevertheless, the associations between nutrition and IRDs are often weak and inconsistent, and the available clinical trials on nutrition are methodologically flawed. Experimental evidence is accumulating that micronutrients in the diet may influence intestinal and systemic immune responses via complex interactions involving the gut microbiota. Micronutrients may, therefore, contribute to the pathogenesis of inflammatory diseases. No interventions targeting these interactions for diagnostic, prophylactic, or therapeutic purposes have been developed to date. Moreover, the relevance to human disease of experimental results obtained in animals or in vitro is unclear. Novel high-throughput technologies (-omics) may prove useful for a systems biology approach to these results that takes the complexity of the interactions into account. Concomitant cohort studies combining clinical and laboratory data collected over time may provide new impetus to research into the connections between nutrition and IRDs.

  9. The aged gut in inflammatory bowel diseases.

    PubMed

    Ardesia, M; Villanacci, V; Fries, W

    2015-12-01

    Senescence is accompanied by various anatomical and functional alterations starting from mastication and deglutition and consequent modifications of nutrition. In addition, the widespread use of proton pump inhibitors and non-steroidal anti-inflammatory drugs in aged subjects weakens the gastric barrier, thus contributing to easier entry of microbes into the gastrointestinal tract. The microbiota of the elderly is less stable than that of younger adults, therefore, gut dysbiosis is more frequent. Dysbiosis represents a key factor for infections, e.g. Clostridium difficile, especially after antibiotic treatment, but also represents an important step for the development of inflammatory bowel diseases (IBD). IBD onset in the elderly needs careful evaluation in order to distinguish this entity from other pathologies that may affect the gut in senescence. Colitis associated with diverticula, drug-induced, ischemic, and microscopic colitides are among the possible diseases and, therefore, a careful macroscopic and histologic evaluation is mandatory. Finally, late onset IBD represents an important challenge for physicians since it occurs in subjects with frequent comorbidities and relative concomitant treatments. Although there is some evidence that disease course of elderly-onset IBD follows a milder course, overall morbidity, hospitalization rates and even mortality, the latter mostly due to comorbidities, are increased, especially in emergency settings.

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

    PubMed

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

    2006-08-01

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

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

    PubMed

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

    2012-06-01

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

  12. Gut Microbiota in Inflammatory Bowel Disease

    PubMed Central

    2013-01-01

    The gut mucosal barrier plays an important role in maintaining a delicate immune homeostasis. The pathogenesis of inflammatory bowel disease (IBD) is considered to involve a defective mucosal immunity along with a genetic predisposition. Recent views have suggested an excessive response to components of the gut microbiota in IBD. A condition of "dysbiosis", with alterations of the gut microbial composition, has been observed in patients with IBD. In this article, the author review recent studies of gut microbiota in IBD, particularly the importance of the gut microbiota in the pathogenesis of pediatric IBD. PMID:24010101

  13. 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

  14. Risk of cardiovascular disease in inflammatory bowel disease

    PubMed Central

    Wu, Ping; Jia, Fangyuan; Zhang, Bao; Zhang, Peiying

    2017-01-01

    Cardiovascular disease (CVD) can arise because of chronic inflammation and inflammatory bowel disease (IBD) is one such disease where the risk for CVD and eventual heart failure is increased considerably. The incidence of IBD, which refers to both ulcerative colitis and Crohn's disease, has been on the increase in several countries and is a potential risk factor for CVD. Although IBD can potentially cause venous thromboembolism, its significance in arterial stiffening, atherosclerosis, ischemic heart disease and myocardial infarction is only being realized now and it is currently under debate. However, several studies with large groups of patients have demonstrated the association of IBD with heart disease. It has been suggested that systemic inflammation as observed in IBD patients leads to oxidative stress and elevated levels of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), which lead to phenotypic changes in smooth muscle cells and sets into motion a series of events that culminate in atherosclerosis and CVD. Besides the endogenous factors and cytokines, it has been suggested that due to the compromised intestinal mucosal barrier, endotoxins and bacterial lipopolysaccharides produced by intestinal microflora can enter into circulation and activate inflammatory responses that lead to atherosclerosis. Therapeutic management of IBD-associated heart diseases cannot be achieved with simple anti-inflammatory drugs such as corticosteroids and anti-TNF-α antibodies. Treatment with existing medications for CVDs, aspirin, platelet aggregation inhibitors and statins is found to be acceptable and safe. Nevertheless, further research is needed to assess their efficacy in IBD patients suffering from heart disease. PMID:28352306

  15. Interstitial Lung Disease Induced by Pazopanib Treatment

    PubMed Central

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

    2017-01-01

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

  16. Dexmedetomidine attenuates inflammatory reaction in the lung tissues of septic mice by activating cholinergic anti-inflammatory pathway.

    PubMed

    Liu, Zhaoguo; Wang, Yueping; Wang, Yaoqi; Ning, Qiaoqing; Zhang, Yong; Gong, Chunzhi; Zhao, Wenxiang; Jing, Guangjian; Wang, Qianqian

    2016-06-01

    Dexmedetomidine (Dex) is a highly selective α2-adrenergic receptor agonist that is widely used for sedation in intensive care units and in clinical anesthesia. Dex has also been shown to possess anti-inflammatory benefits. However, the underlying mechanism by which Dex relieves the inflammatory reaction in the lung tissues of septic mice has not been fully elucidated. In this study, we aimed to evaluate the protective effects and possible mechanism of Dex on the sepsis-induced lung inflammatory response in mice. Sepsis was induced in mice models through the intraperitoneal injection of lipopolysaccharide (LPS). The preemptive administration of Dex substantially abated sepsis-induced pulmonary edema, pulmonary histopathological changes, and NF-κB p65 activity. The production of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) at both the mRNA and protein levels was also reduced. Moreover, these effects were significantly blocked by the α7 nicotinic acetylcholine receptor (α7nAChR) antagonist α-bungarotoxin (α-Bgt). α-Bgt aggravated pulmonary edema and pulmonary histopathological changes, as well as increased NF-κB p65 activity and TNF-α and IL-6 expression at both the mRNA and protein levels. The overall results demonstrate that Dex inhibits the LPS-induced inflammatory reaction in the lung tissues of septic mice partly through the α7nAChR-dependent cholinergic anti-inflammatory pathway.

  17. Interstitial lung disease probably caused by imipramine.

    PubMed

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

    2014-01-01

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

  18. Lymphomatoid granulomatosis mimicking interstitial lung disease.

    PubMed

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

    2008-11-01

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

  19. The Lung Microbiome and Airway Disease.

    PubMed

    Lynch, Susan V

    2016-12-01

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

  20. 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.

  1. 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

  2. Extracellular matrix mechanics in lung parenchymal diseases.

    PubMed

    Suki, Béla; Bates, Jason H T

    2008-11-30

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

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

    PubMed

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

    2016-04-01

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

  4. Proteomics and metabolomics in inflammatory bowel disease.

    PubMed

    Yau, Yunki; Leong, Rupert W; Zeng, Ming; Wasinger, Valerie C

    2013-07-01

    Genome-wide studies in inflammatory bowel disease (IBD) have allowed us to understand Crohn's disease and ulcerative colitis as forms of related autoinflammatory disorders that arise from a multitude of pathogenic origins. Proteomics and metabolomics are the offspring of genomics that possess unprecedented possibilities to characterize unknown pathogenic pathways. It has been about a decade since proteomics was first applied to IBD, and 5 years for metabolomics. These techniques have yielded novel and potentially important findings, but turning these results into beneficial patient outcomes remains challenging. This review recounts the history and context of clinical IBD developments before and after proteomics and metabolomics IBD in this field, discusses the challenges in consolidating high complexity data with physiological understanding, and provides an outlook on the emerging principles that will help interface the bioanalytical laboratory with IBD prognosis.

  5. Vaccinating Patients With Inflammatory Bowel Disease

    PubMed Central

    Reich, Jason; Wasan, Sharmeel

    2016-01-01

    Patients with inflammatory bowel disease (IBD) are not vaccinated at the same rate as general medical patients. IBD places patients at increased risk for developing vaccine-preventable illnesses, and this risk is further exacerbated by immunosuppressive therapy. Therefore, gastroenterologists should familiarize themselves with health maintenance measures pertaining to patients with IBD. This article highlights the vaccinations required for patients with IBD, especially those who are immunosuppressed: influenza; pneumococcal pneumonia; hepatitis A and B viruses; human papilloma virus; meningococcal disease; tetanus, diphtheria, and pertussis; measles, mumps, and rubella; varicella zoster; and herpes zoster. This article also discusses issues regarding patients with IBD who travel outside of the United States, as well as highlights and provides suggestions for areas of quality improvement that are needed in the field. PMID:27917091

  6. Management of inflammatory bowel disease in pregnancy

    PubMed Central

    Smith, M A; Sanderson, J D

    2010-01-01

    Inflammatory bowel disease (IBD) affects body image, relationships, family planning, fertility and pregnancy outcomes. However, the common misconception that IBD is a contraindication, or serious concern, in pregnancy is essentially a myth. Most patients with IBD can expect to have uneventful pregnancies. We present an overview of the management of IBD during pregnancy, including management in those planning pregnancy, the suitability of relevant medication during pregnancy and breast feeding, investigation and monitoring of IBD during pregnancy, surgical management and considerations relating to delivery. While there are some definite alterations required in the management of IBD during pregnancy, management is essentially unchanged. With close attention to aspects such as nutrition and smoking cessation, and optimal disease control in the run-up to and during pregnancy, we have an opportunity to help our patients with IBD achieve good pregnancy outcomes. PMID:27582844

  7. Report: impact of inflammatory bowel disease.

    PubMed

    Wilhelm, Sheila M

    2016-03-01

    Inflammatory bowel disease (IBD) includes ulcerative colitis (UC) and Crohn's disease (CD), 2 conditions characterized by chronic inflammation. Approximately 1.17 million people in the United States are affected by these 2 conditions. It is theorized that a genetic susceptibility coupled with environmental factors, such as smoking, antibiotics, oral contraceptives, appendectomy, or diet, may influence the development of IBD. Patients with UC and CD may exhibit similar symptoms, and the conditions are often misclassified, as there is a lack of standard criteria for diagnosing IBD. Therefore, it is important for clinicians to rule out any diarrhea-related conditions for an accurate diagnosis. UC and CD typically manifest in early adulthood, and the chronic nature of these conditions greatly impacts a patient's perception, body image, and quality of life. The inability to participate in social activities due to UC and CD impacts not only patients, but also those with whom they have close relationships.

  8. GENETICS AND PATHOGENESIS OF INFLAMMATORY BOWEL DISEASE

    PubMed Central

    Liu, Ta-Chiang; Stappenbeck, Thaddeus S.

    2016-01-01

    We are currently in an exciting time where our understanding of genetic underpinnings of inflammatory bowel disease (IBD) has undergone a revolution, based in large part by novel genotyping and sequencing technologies. With >160 susceptible loci identified for IBD, the goals now are to understand at a fundamental level, the function of these susceptibility alleles. Clinical relevance of how these susceptible genes shape the development of IBD is also a high priority. The main challenge is to understand how the environment and microbiome play a role in triggering disease in genetically susceptible individual, as the interactions may be complex. To advance the field, novel in vitro and mouse models that are designed to interrogate complex genetics and be able to functionally test hypotheses are needed. Ultimately, the goal of genetics studies will be to translate genetics to the patients with IBD and improve their care. PMID:26907531

  9. [Nutritional therapy in inflammatory bowel disease].

    PubMed

    Piquet, Marie-Astrid; Gloro, Romain; Justum, Anne-Marie; Reimund, Jean-Marie

    2006-02-01

    Protein-energy malnutrition and specific nutrient deficiencies are common in inflammatory bowel diseases (IBD), more particularly in Crohn's disease. In adults, the use of artificial nutrition is indicated in the event of malnutrition, short bowel syndrome, or IBD refractory to all other treatments. In children, enteral nutrition has a place as first-line treatment to avoid side effects of corticosteroids on growth. The use, as a therapeutic tool, of specific nutrients (n-3 fatty acids, glutamine, antioxydant vitamins and minerals, TGF-beta, probiotics...) seems interesting at the pathophysiological level. Nevertheless, these nutrients are still under evaluation and there are not enough available studies to recommend them in clinical routine. A very promising solution is the use of probiotics for the treatment of refractory pouchitis.

  10. Hormonal contraception and pelvic inflammatory disease.

    PubMed

    Henry-Suchet, J

    1997-12-01

    Estrogen-progestogen contraception (OC) is significantly associated with a high prevalence of Chlamydia trachomatis in the lower genital tracts of young women. In contrast, pelvic inflammatory disease is less frequent and is associated with milder pelvic lesions in OC users than in non-users. A recent study suggests that OC use can be associated with silent endometritis and salpingitis. The usual clinical, biological and laparoscopic signs of acute and chronic pelvic inflammatory disease are described. As shown tby several cost-benefit analyses, C. trachomatis detection in family planning centers is cost-effective and the eradication of bacteria is obtained in 90% of cases by a new treatment: azithromycin (1 g for 1 day). Although the data clearly show that C. trachomatis screening is cost-effective, selection of the diagnostic laboratory tests used in such screening programs should be carefully evaluated relative to cost, feasibility, specificity and sensitivity, and should be adapted to the presumed prevalence in screened populations. A systematic screening is indicated in populations susceptible to a prevalence of 5% or more.

  11. Innate immune dysfunction in inflammatory bowel disease.

    PubMed

    Gersemann, M; Wehkamp, J; Stange, E F

    2012-05-01

    The pathogenetic mechanisms that cause the two types of inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC), are still under investigation. Nevertheless, there is broad agreement that luminal microbes are of particular relevance in the development of these conditions. In recent years, increasing evidence has shown that defects in the innate immunity are at the centre of both types of IBD. The innate intestinal barrier is provided by the epithelium which secretes antimicrobial peptides (so-called defensins) that are retained in the mucus layer. In ileal CD, the alpha-defensins are lacking owing to several Paneth cell defects. In colonic CD, the expression of beta-defensins is inadequate. This may be related to downregulation of the transcription factor peroxisome proliferator-activated receptor-gamma and in some cohorts is associated with a reduced HBD2 gene copy number. In UC, the mucus layer, which protects the host from the enormous amounts of luminal microbes, is defective. This is accompanied by an insufficient differentiation from intestinal stem cells towards goblet cells. All these disturbances in the gut barrier shift the balance from epithelial defence towards bacterial offence. The current treatment for CD and UC is based on suppression of this secondary inflammatory process. In future, patients may benefit from new therapeutic approaches stimulating the protective innate immune system.

  12. Biologic Agents in Inflammatory Eye Disease

    PubMed Central

    Posarelli, Chiara; Arapi, Ilir; Figus, Michele; Neri, Piergiorgio

    2011-01-01

    Non-infectious uveitis is a potentially sight threatening disease. Along the years, several therapeutic strategies have been proposed as a means to its treatment, including local and systemic steroids, immunosuppressives and more recently, biologic agents. The introduction of biologics can be defined as a new era: biologic therapies provide new options for patients with refractory and sight threatening inflammatory disorders. The availability of such novel treatment modalities has markedly improved the therapy of uveitis and considerably increased the possibility of long-term remissions. This article provides a review of current literature on biologic agents, such as tumor necrosis factor blockers, anti-interleukins and other related biologics, such as interferon alpha, for the treatment of uveitis. Several reports describe the efficacy of biologics in controlling a large number of refractory uveitides, suggesting a central role in managing ocular inflammatory diseases. However, there is still lack of randomized controlled trials to validate most of their applications. Biologics are promising drugs for the treatment of uveitis, showing a favorable safety and efficacy profile. On the other hand, lack of evidence from randomized controlled studies limits our understanding as to when commence treatment, which agent to choose, and how long to continue therapy. In addition, high cost and the potential for serious and unpredictable complications have very often limited their use in uveitis refractory to traditional immunosuppressive therapy. PMID:22454752

  13. Biologic agents in inflammatory eye disease.

    PubMed

    Posarelli, Chiara; Arapi, Ilir; Figus, Michele; Neri, Piergiorgio

    2011-10-01

    Non-infectious uveitis is a potentially sight threatening disease. Along the years, several therapeutic strategies have been proposed as a means to its treatment, including local and systemic steroids, immunosuppressives and more recently, biologic agents. The introduction of biologics can be defined as a new era: biologic therapies provide new options for patients with refractory and sight threatening inflammatory disorders. The availability of such novel treatment modalities has markedly improved the therapy of uveitis and considerably increased the possibility of long-term remissions. This article provides a review of current literature on biologic agents, such as tumor necrosis factor blockers, anti-interleukins and other related biologics, such as interferon alpha, for the treatment of uveitis. Several reports describe the efficacy of biologics in controlling a large number of refractory uveitides, suggesting a central role in managing ocular inflammatory diseases. However, there is still lack of randomized controlled trials to validate most of their applications. Biologics are promising drugs for the treatment of uveitis, showing a favorable safety and efficacy profile. On the other hand, lack of evidence from randomized controlled studies limits our understanding as to when commence treatment, which agent to choose, and how long to continue therapy. In addition, high cost and the potential for serious and unpredictable complications have very often limited their use in uveitis refractory to traditional immunosuppressive therapy.

  14. Epithelial Transport in Inflammatory Bowel Diseases

    PubMed Central

    Ghishan, Fayez K.; Kiela, Pawel R.

    2014-01-01

    The epithelium of the gastrointestinal tract is one of the most versatile tissues in the organism, responsible for providing a tight barrier between dietary and bacterial antigens and the mucosal and systemic immune system, while maintaining efficient digestive and absorptive processes to ensure adequate nutrient and energy supply. Inflammatory Bowel Diseases (IBD; Crohn’s disease and ulcerative colitis) are associated with a breakdown of both functions, which in some cases are clearly interrelated. In this updated literature review, we focus on the effects of intestinal inflammation and the associated immune mediators on selected aspects of the transepithelial transport of macro- and micronutrients. The mechanisms responsible for nutritional deficiencies are not always clear and could be related to decreased intake, malabsorption and excess losses. We summarize the known causes of nutrient deficiencies and the mechanism of IBD-associated diarrhea. We also overview the consequences of impaired epithelial transport, which infrequently transcend its primary purpose to affect the gut microbial ecology and epithelial integrity. While some of those regulatory mechanisms are relatively well established, more work needs to be done to determine how inflammatory cytokines can alter the transport process of nutrients across the gastrointestinal and renal epithelia. PMID:24691115

  15. Resolvins and omega three polyunsaturated fatty acids: Clinical implications in inflammatory diseases and cancer.

    PubMed

    Moro, Kazuki; Nagahashi, Masayuki; Ramanathan, Rajesh; Takabe, Kazuaki; Wakai, Toshifumi

    2016-07-16

    Inflammation is a central process in several disorders and contributes to cancer progression. Inflammation involves a complex cascade of pro-inflammatory and anti-inflammatory signaling events with protein and lipid mediators. Recent advances in lipid detection have revealed the importance of lipid mediators in inflammation. Omega three polyunsaturated fatty acids (ω-3 PUFA) are found naturally in fish oil and have been extensively studied in multiple inflammatory diseases with improved outcomes. Resolvins are thought to be the active metabolites of ω-3 PUFA, and are responsible for facilitating the resolving phase of acute inflammation. Clinically, resolvins have been associated with resolution of acute kidney injury and acute lung injury, micro and macro vascular response to injury, and inhibition of microglia-activated inflammation in neurodegenerative disorders. In addition to inflammatory diseases, ω-3 PUFA and resolvins appear to modulate cancer progression. ω-3 PUFA intake has been associated with reduced inflammation in colorectal cancer, and favorable phenotype in breast cancer. Resolvins offer promising therapeutic potential as they may modulate inflammation with minimal side-effects, in contrast to currently available anti-inflammatory medications. This review describes the roles of ω-3 PUFA and resolvins in the inflammatory cascade, various inflammatory diseases, and specific cancers. Additionally, it will discuss the clinical therapeutic potential of resolvins as targets in inflammatory diseases and cancers.

  16. Mitochondrial dysfunction in inflammatory bowel disease

    PubMed Central

    Novak, Elizabeth A.; Mollen, Kevin P.

    2015-01-01

    Inflammatory Bowel Disease (IBD) represents a group of idiopathic disorders characterized by chronic or recurring inflammation of the gastrointestinal tract. While the exact etiology of disease is unknown, IBD is recognized to be a complex, multifactorial disease that results from an intricate interplay of genetic predisposition, an altered immune response, changes in the intestinal microbiota, and environmental factors. Together, these contribute to a destruction of the intestinal epithelial barrier, increased gut permeability, and an influx of immune cells. Given that most cellular functions as well as maintenance of the epithelial barrier is energy-dependent, it is logical to assume that mitochondrial dysfunction may play a key role in both the onset and recurrence of disease. Indeed several studies have demonstrated evidence of mitochondrial stress and alterations in mitochondrial function within the intestinal epithelium of patients with IBD and mice undergoing experimental colitis. Although the hallmarks of mitochondrial dysfunction, including oxidative stress and impaired ATP production are known to be evident in the intestines of patients with IBD, it is as yet unclear whether these processes occur as a cause of consequence of disease. We provide a current review of mitochondrial function in the setting of intestinal inflammation during IBD. PMID:26484345

  17. Non-Inflammatory Destructive Periodontal Disease

    PubMed Central

    José Ricardo Kina; Yumi Umeda Suzuki, Thaís; Fumico Umeda Kina, Eunice; Kina, Juliana; Kina, Mônica

    2016-01-01

    Background: Non-Inflammatory Destructive Periodontal Disease (NIDPD), is a severe destructive periodontal disease, that is characterized by the attachment loss and alveolar bone loss, without signs of the gingival inflammation, and the periodontal pocket development. Objective: Despite the fact that various cases of NIDPD have been reported; their etiology and disease evolution is still indefinite, and therefore, are open for discussion. Method: An NIDPD case was studied in order to demonstrate features of the disease, and discuss the possible etiology and treatment. Results: In this clinical case, the etiology of NIDPD seems to be an association of endogenous opportunist bacteria with anatomical aspects, occlusion pattern, emotional stress and mouth breathing condition. Conclusion: In spite of all cases described in the literature are comparable and may have similar etiology as related in this clinical case, additional research is needed to identify and clarify the role of the etiologic factors which determine the disease. PMID:27053968

  18. Inflammatory mechanisms in patients with chronic obstructive pulmonary disease.

    PubMed

    Barnes, Peter J

    2016-07-01

    Chronic obstructive pulmonary disease (COPD) is associated with chronic inflammation affecting predominantly the lung parenchyma and peripheral airways that results in largely irreversible and progressive airflow limitation. This inflammation is characterized by increased numbers of alveolar macrophages, neutrophils, T lymphocytes (predominantly TC1, TH1, and TH17 cells), and innate lymphoid cells recruited from the circulation. These cells and structural cells, including epithelial and endothelial cells and fibroblasts, secrete a variety of proinflammatory mediators, including cytokines, chemokines, growth factors, and lipid mediators. Although most patients with COPD have a predominantly neutrophilic inflammation, some have an increase in eosinophil counts, which might be orchestrated by TH2 cells and type 2 innate lymphoid cells though release of IL-33 from epithelial cells. These patients might be more responsive to corticosteroids and bronchodilators. Oxidative stress plays a key role in driving COPD-related inflammation, even in ex-smokers, and might result in activation of the proinflammatory transcription factor nuclear factor κB (NF-κB), impaired antiprotease defenses, DNA damage, cellular senescence, autoantibody generation, and corticosteroid resistance though inactivation of histone deacetylase 2. Systemic inflammation is also found in patients with COPD and can worsen comorbidities, such as cardiovascular diseases, diabetes, and osteoporosis. Accelerated aging in the lungs of patients with COPD can also generate inflammatory protein release from senescent cells in the lung. In the future, it will be important to recognize phenotypes of patients with optimal responses to more specific therapies, and development of biomarkers that identify the therapeutic phenotypes will be important.

  19. Cold stress aggravates inflammatory responses in an LPS-induced mouse model of acute lung injury

    NASA Astrophysics Data System (ADS)

    Joo, Su-Yeon; Park, Mi-Ju; Kim, Kyun-Ha; Choi, Hee-Jung; Chung, Tae-Wook; Kim, Yong Jin; Kim, Joung Hee; Kim, Keuk-Jun; Joo, Myungsoo; Ha, Ki-Tae

    2016-08-01

    Although the relationship between environmental cold temperature and susceptibility to respiratory infection is generally accepted, the effect of ambient cold temperature on host reactivity in lung inflammation has not been fully studied. To examine the function of ambient cold temperature on lung inflammation, mice were exposed to 4 °C for 8 h each day for 14 days. In the lungs of mice exposed to cold stress, inflammatory cells in bronchoalveolar lavage (BAL) fluid and lung tissues were slightly increased by about twofold. However, the structures of pulmonary epithelial cells were kept within normal limits. Next, we examined the effect of cold stress on the inflammatory responses in a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. The infiltration of neutrophils and inflammation of lung tissue determined by histology were significantly increased by exposure to ambient cold temperature. In addition, the production of pro-inflammatory cytokines including interleukin (IL)-12, IL-17, and monokine induced by gamma interferon (MIG) was elevated by exposure to cold stress. Therefore, we suggest that cold stress is a factor that exacerbates lung inflammation including ALI. To our knowledge, this is the first report on the relationship between cold stress and severity of lung inflammation.

  20. Vapors Produced by Electronic Cigarettes and E-Juices with Flavorings Induce Toxicity, Oxidative Stress, and Inflammatory Response in Lung Epithelial Cells and in Mouse Lung

    PubMed Central

    Lerner, Chad A.; Sundar, Isaac K.; Yao, Hongwei; Gerloff, Janice; Ossip, Deborah J.; McIntosh, Scott; Robinson, Risa; Rahman, Irfan

    2015-01-01

    Oxidative stress and inflammatory response are the key events in the pathogenesis of chronic airway diseases. The consumption of electronic cigarettes (e-cigs) with a variety of e-liquids/e-juices is alarmingly increasing without the unrealized potential harmful health effects. We hypothesized that electronic nicotine delivery systems (ENDS)/e-cigs pose health concerns due to oxidative toxicity and inflammatory response in lung cells exposed to their aerosols. The aerosols produced by vaporizing ENDS e-liquids exhibit oxidant reactivity suggesting oxidants or reactive oxygen species (OX/ROS) may be inhaled directly into the lung during a “vaping” session. These OX/ROS are generated through activation of the heating element which is affected by heating element status (new versus used), and occurs during the process of e-liquid vaporization. Unvaporized e-liquids were oxidative in a manner dependent on flavor additives, while flavors containing sweet or fruit flavors were stronger oxidizers than tobacco flavors. In light of OX/ROS generated in ENDS e-liquids and aerosols, the effects of ENDS aerosols on tissues and cells of the lung were measured. Exposure of human airway epithelial cells (H292) in an air-liquid interface to ENDS aerosols from a popular device resulted in increased secretion of inflammatory cytokines, such as IL-6 and IL-8. Furthermore, human lung fibroblasts exhibited stress and morphological change in response to treatment with ENDS/e-liquids. These cells also secrete increased IL-8 in response to a cinnamon flavored e-liquid and are susceptible to loss of cell viability by ENDS e-liquids. Finally, exposure of wild type C57BL/6J mice to aerosols produced from a popular e-cig increase pro-inflammatory cytokines and diminished lung glutathione levels which are critical in maintaining cellular redox balance. Thus, exposure to e-cig aerosols/juices incurs measurable oxidative and inflammatory responses in lung cells and tissues that could lead to

  1. Preventing infective complications in inflammatory bowel disease

    PubMed Central

    Mill, Justine; Lawrance, Ian C

    2014-01-01

    Over the past decade there has been a dramatic change in the treatment of patients with Crohn’s disease and ulcerative colitis, which comprise the inflammatory bowel diseases (IBD). This is due to the increasing use of immunosuppressives and in particular the biological agents, which are being used earlier in the course of disease, and for longer durations, as these therapies result in better clinical outcomes for patients. This, however, has the potential to increase the risk of opportunistic and serious infections in these patients, most of which are preventable. Much like the risk for potential malignancy resulting from the use of these therapies long-term, a balance needs to be struck between medication use to control the disease with minimization of the risk of an opportunistic infection. This outcome is achieved by the physician’s tailored use of justified therapies, and the patients’ education and actions to minimize infection risk. The purpose of this review is to explore the evidence and guidelines available to all physicians managing patients with IBD using immunomodulating agents and to aid in the prevention of opportunistic infections. PMID:25110408

  2. Preventing infective complications in inflammatory bowel disease.

    PubMed

    Mill, Justine; Lawrance, Ian C

    2014-08-07

    Over the past decade there has been a dramatic change in the treatment of patients with Crohn's disease and ulcerative colitis, which comprise the inflammatory bowel diseases (IBD). This is due to the increasing use of immunosuppressives and in particular the biological agents, which are being used earlier in the course of disease, and for longer durations, as these therapies result in better clinical outcomes for patients. This, however, has the potential to increase the risk of opportunistic and serious infections in these patients, most of which are preventable. Much like the risk for potential malignancy resulting from the use of these therapies long-term, a balance needs to be struck between medication use to control the disease with minimization of the risk of an opportunistic infection. This outcome is achieved by the physician's tailored use of justified therapies, and the patients' education and actions to minimize infection risk. The purpose of this review is to explore the evidence and guidelines available to all physicians managing patients with IBD using immunomodulating agents and to aid in the prevention of opportunistic infections.

  3. Iron deficiency anemia in inflammatory bowel disease

    PubMed Central

    Kaitha, Sindhu; Bashir, Muhammad; Ali, Tauseef

    2015-01-01

    Anemia is a common extraintestinal manifestation of inflammatory bowel disease (IBD) and is frequently overlooked as a complication. Patients with IBD are commonly found to have iron deficiency anemia (IDA) secondary to chronic blood loss, and impaired iron absorption due to tissue inflammation. Patients with iron deficiency may not always manifest with signs and symptoms; so, hemoglobin levels in patients with IBD must be regularly monitored for earlier detection of anemia. IDA in IBD is associated with poor quality of life, necessitating prompt diagnosis and appropriate treatment. IDA is often associated with inflammation in patients with IBD. Thus, commonly used laboratory parameters are inadequate to diagnose IDA, and newer iron indices, such as reticulocyte hemoglobin content or percentage of hypochromic red cells or zinc protoporphyrin, are required to differentiate IDA from anemia of chronic disease. Oral iron preparations are available and are used in patients with mild disease activity. These preparations are inexpensive and convenient, but can produce gastrointestinal side effects, such as abdominal pain and diarrhea, that limit their use and patient compliance. These preparations are partly absorbed due to inflammation. Non-absorbed iron can be toxic and worsen IBD disease activity. Although cost-effective intravenous iron formulations are widely available and have improved safety profiles, physicians are reluctant to use them. We present a review of the pathophysiologic mechanisms of IDA in IBD, improved diagnostic and therapeutic strategies, efficacy, and safety of iron replacement in IBD. PMID:26301120

  4. Diagnostic difficulties in inflammatory bowel disease pathology.

    PubMed

    Yantiss, R K; Odze, R D

    2006-01-01

    This review summarizes some of the common diagnostic problems encountered by pathologists when evaluating patients with chronic colitis and in whom inflammatory bowel disease (IBD) is either suspected or within the differential diagnosis. Both ulcerative colitis (UC) and Crohn's disease (CD) show characteristic, but non-specific, pathological features that may overlap and result in a diagnosis of 'indeterminate colitis' (IC). However, other reasons why pathologists may entertain a diagnosis of IC include failure to recognize or accept certain 'hardcore' histological features as indicative of CD, an attempt to classify cases of chronic colitis based on mucosal biopsy material or in the absence of adequate clinical and radiographic information, and the presence of other disease processes that mask, or mimic, IBD. In addition, some cases of UC may show unusual CD-like features, such as discontinuous or patchy disease, ileal inflammation, extracolonic inflammation, granulomatous inflammation in response to ruptured crypts, aphthous ulcers, or transmural inflammation. Furthermore, other forms of colitis, such as microscopic colitis, diverticulitis and diversion colitis may, on occasion, also show IBD-like changes. The clinical and pathological features that aid in the distinction between these entities, and others, are covered in detail in this review.

  5. Challenges and Current Efforts in the Development of Biomarkers for Chronic Inflammatory and Remodeling Conditions of the Lungs.

    PubMed

    Grunig, Gabriele; Baghdassarian, Aram; Park, Sung-Hyun; Pylawka, Serhiy; Bleck, Bertram; Reibman, Joan; Berman-Rosenzweig, Erika; Durmus, Nedim

    2015-01-01

    This review discusses biomarkers that are being researched for their usefulness to phenotype chronic inflammatory lung diseases that cause remodeling of the lung's architecture. The review focuses on asthma, chronic obstructive pulmonary disease (COPD), and pulmonary hypertension. Bio-markers of environmental exposure and specific classes of biomarkers (noncoding RNA, metabolism, vitamin, coagulation, and microbiome related) are also discussed. Examples of biomarkers that are in clinical use, biomarkers that are under development, and biomarkers that are still in the research phase are discussed. We chose to present examples of the research in biomarker development by diseases, because asthma, COPD, and pulmonary hypertension are distinct entities, although they clearly share processes of inflammation and remodeling.

  6. Flavorings-Related Lung Disease

    MedlinePlus

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

  7. Risk of lung cancer in Parkinson's disease

    PubMed Central

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

    2016-01-01

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

  8. Rheumatic manifestations of inflammatory bowel disease.

    PubMed

    Rodríguez-Reyna, Tatiana Sofía; Martínez-Reyes, Cynthia; Yamamoto-Furusho, Jesús Kazúo

    2009-11-28

    This article reviews the literature concerning rheumatic manifestations of inflammatory bowel disease (IBD), including common immune-mediated pathways, frequency, clinical course and therapy. Musculoskeletal complications are frequent and well-recognized manifestations in IBD, and affect up to 33% of patients with IBD. The strong link between the bowel and the osteo-articular system is suggested by many clinical and experimental observations, notably in HLA-B27 transgenic rats. The autoimmune pathogenic mechanisms shared by IBD and spondyloarthropathies include genetic susceptibility to abnormal antigen presentation, aberrant recognition of self, the presence of autoantibodies against specific antigens shared by the colon and other extra-colonic tissues, and increased intestinal permeability. The response against microorganisms may have an important role through molecular mimicry and other mechanisms. Rheumatic manifestations of IBD have been divided into peripheral arthritis, and axial involvement, including sacroiliitis, with or without spondylitis, similar to idiopathic ankylosing spondylitis. Other periarticular features can occur, including enthesopathy, tendonitis, clubbing, periostitis, and granulomatous lesions of joints and bones. Osteoporosis and osteomalacia secondary to IBD and iatrogenic complications can also occur. The management of the rheumatic manifestations of IBD consists of physical therapy in combination with local injection of corticosteroids and nonsteroidal anti-inflammatory drugs; caution is in order however, because of their possible harmful effects on intestinal integrity, permeability, and even on gut inflammation. Sulfasalazine, methotrexate, azathioprine, cyclosporine and leflunomide should be used for selected indications. In some cases, tumor necrosis factor-alpha blocking agents should be considered as first-line therapy.

  9. Chlamydia trachomatis in pelvic inflammatory disease.

    PubMed

    Shrikhande, S N; Joshi, S G; Zodpey, S P; Saoji, A M

    1995-04-01

    The prevalence of genital Chlamydia trachomatis infection and some epidemiologic factors associated with it were studied in 273 pelvic inflammatory disease (PID) patients attending Gynaecologic clinic, Government Medical College, Nagpur. For detection of chlamydial antigen Pharmacia Diagnostics Chlamydia EIA test was used. This study revealed an overall positivity rate of 33% for C. trachomatis infection in PID patients. Of the hypothesised risk factors low socioeconomic status, history of sexual contacts with multiple partners and use of intrauterine devices (IUD) were significantly associated with C. trachomatis infections. However, use of oral contraceptives, barrier contraceptives and increasing age were found to be protective factors for C. trachomatis infection. Thus considering the significant contribution of C. trachomatis in etiology of PID and its independent association with some epidemiologic risk factors, extensive epidemiologic measures are recommended for prevention of these infections.

  10. [Enteric microflora in inflammatory bowel disease patients].

    PubMed

    Rahmouni, Oumaira; Dubuquoy, Laurent; Desreumaux, Pierre; Neut, Christel

    2016-11-01

    During the last years, the importance of a well equilibrated intestinal microbiota (eubiosis) has become more and more obvious in human health. Dysbiosis is now a well-recognized feature associated with IBD (inflammatory bowel disease). Rupture of the normal microbiota can occur through different mechanisms: (1) by a typical Western diet rich in fat and low in fiber, (2) by an acute disruption of the microbiota (by an acute gastroenteritis or by intake of antibiotics) or (3) by a combination of event in early childhood avoiding the establishment of eubiosis (the hygiene hypothesis). Risk factors for IBD are stated for each disruption mechanism. Dysbiosis can also induce colonization by several pathobionts able to aggravate inflammation. Among the potential candidates in IBD, most attention has been paid on AIEC during the last years.

  11. Flavonoids in Inflammatory Bowel Disease: A Review

    PubMed Central

    Vezza, Teresa; Rodríguez-Nogales, Alba; Algieri, Francesca; Utrilla, Maria Pilar; Rodriguez-Cabezas, Maria Elena; Galvez, Julio

    2016-01-01

    Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the intestine that compromises the patients’ life quality and requires sustained pharmacological and surgical treatments. Since their etiology is not completely understood, non-fully-efficient drugs have been developed and those that have shown effectiveness are not devoid of quite important adverse effects that impair their long-term use. In this regard, a growing body of evidence confirms the health benefits of flavonoids. Flavonoids are compounds with low molecular weight that are widely distributed throughout the vegetable kingdom, including in edible plants. They may be of great utility in conditions of acute or chronic intestinal inflammation through different mechanisms including protection against oxidative stress, and preservation of epithelial barrier function and immunomodulatory properties in the gut. In this review we have revised the main flavonoid classes that have been assessed in different experimental models of colitis as well as the proposed mechanisms that support their beneficial effects. PMID:27070642

  12. Neurological disorders and inflammatory bowel diseases

    PubMed Central

    Casella, Giovanni; Tontini, Gian Eugenio; Bassotti, Gabrio; Pastorelli, Luca; Villanacci, Vincenzo; Spina, Luisa; Baldini, Vittorio; Vecchi, Maurizio

    2014-01-01

    Extraintestinal manifestations occur in about one-third of patients living with inflammatory bowel disease (IBD) and may precede the onset of gastrointestinal symptoms by many years. Neurologic disorders associated with IBD are not frequent, being reported in 3% of patients, but they often represent an important cause of morbidity and a relevant diagnostic issue. In addition, the increasing use of immunosuppressant and biological therapies for IBD may also play a pivotal role in the development of neurological disorders of different type and pathogenesis. Hence, we provide a complete and profound review of the main features of neurological complications associated with IBD, with particular reference to those related to drugs and with a specific focus on their clinical presentation and possible pathophysiological mechanisms. PMID:25083051

  13. Does bacterial vaginosis cause pelvic inflammatory disease?

    PubMed

    Taylor, Brandie DePaoli; Darville, Toni; Haggerty, Catherine L

    2013-02-01

    Pelvic inflammatory disease (PID), the infection and inflammation of the female genital tract, results in serious reproductive morbidity including infertility and ectopic pregnancy. Bacterial vaginosis (BV) is a complex alteration of the vaginal flora that has been implicated in PID. The role of BV in the etiology and pathogenesis of PID has not been studied extensively. Our objective was to extensively review data related to the relationship between BV and PID (n = 19 studies). Several studies found a link between BV and cervicitis, endometritis, and salpingitis. Furthermore, it seems that some BV-associated organisms are associated with PID, whereas others are not. However, studies demonstrating an independent association between BV-associated organisms and PID are sparse. In addition, a causal association between BV and PID has not been established. Prospective studies are needed to further delineate the role of BV in PID, with particular focus on individual BV-associated organisms.

  14. Hard metal lung disease: a case series

    PubMed Central

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

    2016-01-01

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

  15. Nutritional considerations in pediatric inflammatory bowel disease.

    PubMed

    Conklin, Laurie S; Oliva-Hemker, Maria

    2010-06-01

    Nutrition is a critical part of the management of inflammatory bowel disease (IBD) in children and adults. Malnutrition and micronutrient deficiencies are common at the time of diagnosis and may persist throughout the course of the disease. There are a number of similarities with regards to the nutritional complications and the approach to nutritional management in IBD in both children and adults, but there are also important differences. Growth failure, pubertal delay and the need for corticosteroid-sparing regimens are of higher importance in pediatrics. In the pediatric population, exclusive enteral nutrition may be equivalent to corticosteroids in inducing remission in acute Crohn's disease, and may have benefits over corticosteroids in children. Adherence with exclusive enteral nutrition is better in children than in adults. Iron deficiency anemia is an important problem for adults and children with IBD. Intravenous iron administration may be superior to oral iron supplementation. Ensuring adequate bone health is another critical component of nutritional management in IBD, but guidelines for screening and therapeutic interventions for low bone mineral density are lacking in children.

  16. Inflammatory diseases of the central nervous system in dogs.

    PubMed

    Thomas, W B

    1998-08-01

    Inflammatory diseases of the central nervous system (CNS) are important causes of seizures in dogs. Specific diseases include canine distemper, rabies, cryptococcosis, coccidioidomycosis, toxoplasmosis, neosporosis, Rocky Mountain spotted fever, ehrlichiosis, granulomatous meningoencephalomyelitis, and pug dog encephalitis. Inflammatory disorders should be considered when a dog with seizures has persistent neurological deficits, suffers an onset of seizures at less than 1 or greater than 5 years of age, or exhibits signs of systemic illness. A thorough history, examination, and analysis of cerebrospinal fluid are important in the diagnosis of inflammatory diseases. However, even with extensive diagnostic testing, a specific etiology is identified in less than two thirds of dogs with inflammatory diseases of the CNS.

  17. 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.

  18. Inflammatory bowel disease and celiac disease: overlaps and differences.

    PubMed

    Pascual, Virginia; Dieli-Crimi, Romina; López-Palacios, Natalia; Bodas, Andrés; Medrano, Luz María; Núñez, Concepción

    2014-05-07

    Recent findings demonstrate the common genetic basis for many immune-mediated diseases, and consequently, the partially shared pathogenesis. We collected these findings and reviewed the extension of these overlaps to other disease characteristics. Two autoimmune diseases were selected that also share the specific target organ, the bowel. The etiology and immunopathogenesis of both conditions characterized by chronic intestinal inflammation, inflammatory bowel disease (IBD) and celiac disease (CeD), are not completely understood. Both are complex diseases with genetics and environment contributing to dysregulation of innate and adaptive immune responses, leading to chronic inflammation and disease. CeD constitutes a particular disease because the main environmental and genetic triggers are largely known. IBD comprises two main clinical forms, Crohn's disease and ulcerative colitis, which most likely involve a complex interplay between some components of the commensal microbiota and other environmental factors in their origin. These multifactorial diseases encompass a broad spectrum of clinical phenotypes and ages of onset, although the clinical presentation often differs depending on childhood or adult onset, with greater heterogeneity commonly observed in adults.

  19. Inflammatory bowel disease and celiac disease: Overlaps and differences

    PubMed Central

    Pascual, Virginia; Dieli-Crimi, Romina; López-Palacios, Natalia; Bodas, Andrés; Medrano, Luz María; Núñez, Concepción

    2014-01-01

    Recent findings demonstrate the common genetic basis for many immune-mediated diseases, and consequently, the partially shared pathogenesis. We collected these findings and reviewed the extension of these overlaps to other disease characteristics. Two autoimmune diseases were selected that also share the specific target organ, the bowel. The etiology and immunopathogenesis of both conditions characterized by chronic intestinal inflammation, inflammatory bowel disease (IBD) and celiac disease (CeD), are not completely understood. Both are complex diseases with genetics and environment contributing to dysregulation of innate and adaptive immune responses, leading to chronic inflammation and disease. CeD constitutes a particular disease because the main environmental and genetic triggers are largely known. IBD comprises two main clinical forms, Crohn’s disease and ulcerative colitis, which most likely involve a complex interplay between some components of the commensal microbiota and other environmental factors in their origin. These multifactorial diseases encompass a broad spectrum of clinical phenotypes and ages of onset, although the clinical presentation often differs depending on childhood or adult onset, with greater heterogeneity commonly observed in adults. PMID:24803796

  20. [Medical therapy of inflammatory bowel diseases: Crohn's disease].

    PubMed

    Lakatos, László; Lakatos, Péter László

    2007-06-17

    The therapy of inflammatory bowel diseases is based on 5-aminosalicylates (5-ASAs) that are the forefront of treatment of mild-to-moderate active disease and maintenance; steroids are used for the treatment of moderate-to-severe active disease; immunosuppressives and sometimes antibiotics in moderate-to-severe disease; maintenance and for the treatment of selected complications. The last few years have witnessed a significant change in the treatment of Crohn's disease. Based on evidence from new clinical studies and recent meta-analyses, the role of and indications for conventional therapy have been reassessed. The 5-ASAs are nowadays less frequently used in both active disease and maintenance therapy. Instead, budesonide has been introduced in the treatment of mild-to-moderate ileal disease. Besides the modest use of 5-ASAs, steroids are prescribed for active colonic disease. Immunosuppressives, especially azathioprine, are more commonly used in moderate-to-severe disease as well as in maintenance. The preferred maintenance regimen following medically- and surgically-induced remission, in addition to relationship between medical and surgical therapies, has also changed. The recent introduction of new "biological" therapy represents a major, promising change in the therapy of resistant and penetrating disease.

  1. Baclofen, a GABABR agonist, ameliorates immune-complex mediated acute lung injury by modulating pro-inflammatory mediators.

    PubMed

    Jin, Shunying; Merchant, Michael L; Ritzenthaler, Jeffrey D; McLeish, Kenneth R; Lederer, Eleanor D; Torres-Gonzalez, Edilson; Fraig, Mostafa; Barati, Michelle T; Lentsch, Alex B; Roman, Jesse; Klein, Jon B; Rane, Madhavi J

    2015-01-01

    Immune-complexes play an important role in the inflammatory diseases of the lung. Neutrophil activation mediates immune-complex (IC) deposition-induced acute lung injury (ALI). Components of gamma amino butyric acid (GABA) signaling, including GABA B receptor 2 (GABABR2), GAD65/67 and the GABA transporter, are present in the lungs and in the neutrophils. However, the role of pulmonary GABABR activation in the context of neutrophil-mediated ALI has not been determined. Thus, the objective of the current study was to determine whether administration of a GABABR agonist, baclofen would ameliorate or exacerbate ALI. We hypothesized that baclofen would regulate IC-induced ALI by preserving pulmonary GABABR expression. Rats were subjected to sham injury or IC-induced ALI and two hours later rats were treated intratracheally with saline or 1 mg/kg baclofen for 2 additional hours and sacrificed. ALI was assessed by vascular leakage, histology, TUNEL, and lung caspase-3 cleavage. ALI increased total protein, tumor necrosis factor α (TNF-α and interleukin-1 receptor associated protein (IL-1R AcP), in the bronchoalveolar lavage fluid (BALF). Moreover, ALI decreased lung GABABR2 expression, increased phospho-p38 MAPK, promoted IκB degradation and increased neutrophil influx in the lung. Administration of baclofen, after initiation of ALI, restored GABABR expression, which was inhibited in the presence of a GABABR antagonist, CGP52432. Baclofen administration activated pulmonary phospho-ERK and inhibited p38 MAPK phosphorylation and IκB degradation. Additionally, baclofen significantly inhibited pro-inflammatory TNF-α and IL-1βAcP release and promoted BAL neutrophil apoptosis. Protective effects of baclofen treatment on ALI were possibly mediated by inhibition of TNF-α- and IL-1β-mediated inflammatory signaling. Interestingly, GABABR2 expression was regulated in the type II pneumocytes in lung tissue sections from lung injured patients, further suggesting a

  2. Genetic therapies for cystic fibrosis lung disease

    PubMed Central

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

    2011-01-01

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

  3. Lung and Heart Disease Secondary to Liver Disease

    PubMed Central

    Goldberg, David S.; Fallon, Michael B.

    2015-01-01

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

  4. Asbestos-induced lung diseases: an update

    PubMed Central

    KAMP, DAVID W.

    2009-01-01

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

  5. Genetics of Crohn disease, an archetypal inflammatory barrier disease.

    PubMed

    Schreiber, Stefan; Rosenstiel, Philip; Albrecht, Mario; Hampe, Jochen; Krawczak, Michael

    2005-05-01

    Chronic inflammatory disorders such as Crohn disease, atopic eczema, asthma and psoriasis are triggered by hitherto unknown environmental factors that function on the background of some polygenic susceptibility. Recent technological advances have allowed us to unravel the genetic aetiology of these and other complex diseases. Using Crohn disease as an example, we show how the discovery of susceptibility genes furthers our understanding of the underlying disease mechanisms and how it will, ultimately, give rise to new therapeutic developments. The long-term goal of such endeavours is to develop targeted prophylactic strategies. These will probably target the molecular interaction on the mucosal surface between the products of the genome and the microbial metagenome of a patient.

  6. Nano-based theranostics for chronic obstructive lung diseases: challenges and therapeutic potential.

    PubMed

    Vij, Neeraj

    2011-09-01

    The major challenges in the delivery and therapeutic efficacy of nano-delivery systems in chronic obstructive airway conditions are airway defense, severe inflammation and mucous hypersecretion. Chronic airway inflammation and mucous hypersecretion are hallmarks of chronic obstructive airway diseases, including asthma, COPD (chronic obstructive pulmonary disease) and CF (cystic fibrosis). Distinct etiologies drive inflammation and mucous hypersecretion in these diseases, which are further induced by infection or components of cigarette smoke. Controlling chronic inflammation is at the root of treatments such as corticosteroids, antibiotics or other available drugs, which pose the challenge of sustained delivery of drugs to target cells or tissues. In spite of the wide application of nano-based drug delivery systems, very few are tested to date. Targeted nanoparticle-mediated sustained drug delivery is required to control inflammatory cell chemotaxis, fibrosis, protease-mediated chronic emphysema and/or chronic lung obstruction in COPD. Moreover, targeted epithelial delivery is indispensable for correcting the underlying defects in CF and targeted inflammatory cell delivery for controlling other chronic inflammatory lung diseases. We propose that the design and development of nano-based targeted theranostic vehicles with therapeutic, imaging and airway-defense penetrating capability, will be invaluable for treating chronic obstructive lung diseases. This paper discusses a novel nano-theranostic strategy that we are currently evaluating to treat the underlying cause of CF and COPD lung disease.

  7. Intravenous iron in inflammatory bowel disease.

    PubMed

    Muñoz, Manuel; Gómez-Ramírez, Susana; García-Erce, José Antonio

    2009-10-07

    The prevalence of anemia across studies on patients with inflammatory bowel disease (IBD) is high (30%). Both iron deficiency (ID) and anemia of chronic disease contribute most to the development of anemia in IBD. The prevalence of ID is even higher (45%). Anemia and ID negatively impact the patient's quality of life. Therefore, together with an adequate control of disease activity, iron replacement therapy should start as soon as anemia or ID is detected to attain a normal hemoglobin (Hb) and iron status. Many patients will respond to oral iron, but compliance may be poor, whereas intravenous (i.v.) compounds are safe, provide a faster Hb increase and iron store repletion, and presents a lower rate of treatment discontinuation. Absolute indications for i.v. iron treatment should include severe anemia, intolerance or inappropriate response to oral iron, severe intestinal disease activity, or use of an erythropoietic stimulating agent. Four different products are principally used in clinical practice, which differ in their pharmacokinetic properties and safety profiles: iron gluconate and iron sucrose (lower single doses), and iron dextran and ferric carboxymaltose (higher single doses). After the initial resolution of anemia and the repletion of iron stores, the patient's hematological and iron parameters should be carefully and periodically monitored, and maintenance iron treatment should be provided as required. New i.v. preparations that allow for giving 1000-1500 mg in a single session, thus facilitating patient management, provide an excellent tool to prevent or treat anemia and ID in this patient population, which in turn avoids allogeneic blood transfusion and improves their quality of life.

  8. Transition of Care in Inflammatory Bowel Disease

    PubMed Central

    Abraham, Bincy P

    2014-01-01

    The management of patients with chronic conditions, such as inflammatory bowel disease (IBD), requires specific attention and careful planning during the transition from pediatric to adult care. Early education about the transition process and the acquisition of self-management skills are crucial to fostering independent adolescents and young adults who have the knowledge and tools to manage life with a chronic disease. A growing body of literature describes the challenges and barriers to providing adolescent and transition care. Potential barriers to effective transition include the following: differences between adult- and pediatric-onset IBD; patients’ lack of developmental maturity and readiness, self-efficacy, and knowledge of the disease; poor adherence to therapy; adolescent anxiety and depression; differences between pediatric and adult IBD care; and parental and provider reluctance to transition. Despite our ability to identify barriers and challenges, there remain significant gaps in our knowledge about how they should be addressed. Outcomes data on adolescents with IBD are limited, and there are even fewer data on how the transition of care affects long-term treatment and outcomes. More research is needed to truly understand the best way to facilitate care during transition and improve outcomes. Current research and transition guidelines acknowledge that providing support and guidance to patients and their families and establishing clear goals can ultimately equip patients with the skills needed to cope with a chronic disease as adults and can improve their long-term care. This paper provides an overview of the transition from pediatric to adult IBD care, a discussion of challenges and barriers, and recommendations and resources that can help patients, parents, and providers navigate this important process. PMID:27540335

  9. 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

  10. [Pulmonary hypertension in chronic lung diseases].

    PubMed

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

    2014-10-01

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

  11. Relationship of Acute Lung Inflammatory Injury to Fas/FasL System

    PubMed Central

    Neff, Thomas A.; Guo, Ren-Feng; Neff, Simona B.; Sarma, J. Vidya; Speyer, Cecilia L.; Gao, Hongwei; Bernacki, Kurt D.; Huber-Lang, Markus; McGuire, Stephanie; Hoesel, L. Marco; Riedemann, Niels C.; Beck-Schimmer, Beatrice; Zetoune, Firas S.; Ward, Peter A.

    2005-01-01

    There is mounting evidence that apoptosis plays a significant role in tissue damage during acute lung injury. To evaluate the role of the apoptosis mediators Fas and FasL in acute lung injury, Fas (lpr)- or FasL (gld)-deficient and wild-type mice were challenged with intrapulmonary deposition of IgG immune complexes. Lung injury parameters (125I-albumin leak, accumulation of myeloperoxidase, and wet lung weights) were measured and found to be consistently reduced in both lpr and gld mice. In wild-type mice, lung injury was associated with a marked increase in Fas protein in lung. Inflamed lungs of wild-type mice showed striking evidence of activated caspase-3, which was much diminished in inflamed lungs from lpr mice. Intratracheal administration of a monoclonal Fas-activating antibody (Jo2) in wild-type mice induced MIP-2 and KC production in bronchoalveolar lavage fluids, and a murine alveolar macrophage cell line (MH-S) showed significantly increased MIP-2 production after incubation with this antibody. Bronchoalveolar lavage fluid content of MIP-2 and KC was substantially reduced in lpr mice after lung injury when compared to levels in wild-type mice. These data suggest that the Fas/FasL system regulates the acute lung inflammatory response by positively affecting CXC-chemokine production, ultimately leading to enhanced neutrophil influx and tissue damage. PMID:15743781

  12. Obstructive lung disease models: what is valid?

    PubMed

    Ferdinands, Jill M; Mannino, David M

    2008-12-01

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

  13. Transitional Care in Inflammatory Bowel Disease

    PubMed Central

    2011-01-01

    Transitional care is an organized effort to provide pediatric patients with the tools and resources they need to assume personal responsibility for their medical care while facilitating their transfer from a pediatrician to an adult practitioner. Since inflammatory bowel disease (IBD) is usually chronic and up to 25% of IBD patients are diagnosed before the age of 18 years, transitional care is an important consideration for adolescent and young adult patients. The importance of transitional care for chronic diseases that begin in childhood has been recognized in a number of published recommendations. However, most of these recommendations arise from intuitive reasoning, as physicians lack information regarding the need for transitional care, optimal delivery protocols, and the efficacy of transition programs. Even fewer studies have been published regarding transitional care in IBD. Current guidelines stress the importance of providing patients with educational resources to help them develop the skills they need to manage their care as independent adults, introducing the concept of transfer to adult care in advance of the actual transfer, and developing routes of communication to facilitate the transfer from pediatric to adult care providers. Future studies should aim to elucidate which programs are effective and how they should be implemented. PMID:21346849

  14. Home hyperalimentation for inflammatory bowel disease.

    PubMed

    Bodzin, J H

    1992-04-01

    Total parenteral nutrition (TPN) has become a useful tool in the management of patients with inflammatory bowel disease (IBD). In the past, it was felt that TPN would have a therapeutic role in IBD, but experience has shown that it functions more as an adjunct to other therapeutic interventions. The specific roles of TPN in IBD include: (1) nutritional maintenance in the short bowel syndrome, (2) TPN as adjunctive therapy in jejunoileitis of Crohn's disease, (3) home TPN (HTPN) in Crohn's colitis, and (4) preoperative repletion of significantly depleted patients going to surgery. The adaptation of hospital techniques to the home situation has allowed patients to carry out long-term TPN therapy at home. Patients with IBD on HTPN are subject to the same mechanical and metabolic problems as are other patients on HTPN and, in addition, have a higher infection rate. When carried out appropriately, however, HTPN is a valuable technique in the management of patients with IBD and may provide an improved quality of life.

  15. Faecal calprotectin: Management in inflammatory bowel disease

    PubMed Central

    Benítez, José Manuel; García-Sánchez, Valle

    2015-01-01

    Inflammatory bowel disease (IBD) is a chronic and relapsing disorder which leads to an inflammation of the gastrointestinal tract. A tailored therapy to achieve mucosal healing with the less adverse events has become a key issue in the management of IBD. In the past, the clinical remission was the most important factor to consider for adapting diagnostic procedures and therapeutic strategies. However, there is no a good correlation between symptoms and intestinal lesions, so currently the goals of treatment are to achieve not only the control of symptoms, but deep remission, which is related with a favourable prognosis. Thus, the determination of biological markers or biomarkers of intestinal inflammation play a crucial role. Many biomarkers have been extensively evaluated in IBD showing significant correlation with endoscopic lesions, risk of recurrence and response to treatment. One of the most important markers is faecal calprotectin (FC). Despite calprotectin limitations, this biomarker represents a reliable and noninvasive alternative to reduce the need for endoscopic procedures. FC has demonstrated its performance for regular monitoring of IBD patients, not only to the diagnosis for discriminating IBD from non-IBD diagnosis, but for assessing disease activity, relapse prediction and response to therapy. Although, FC provides better results than other biomarkers such as C-reactive protein and erythrocyte sedimentation rate, these surrogate markers of intestinal inflammation should not be used isolation but in combination with other clinical, endoscopic, radiological or/and histological parameters enabling a comprehensive assessment of IBD patients. PMID:26600978

  16. Infertility in men with inflammatory bowel disease

    PubMed Central

    Shin, Takeshi; Okada, Hiroshi

    2016-01-01

    Inflammatory bowel disease (IBD) predominantly affects young adults. Fertility-related issues are therefore important in the management of patients with IBD. However, relatively modest attention has been paid to reproductive issues faced by men with IBD. To investigate the effects of IBD and its treatment on male fertility, we reviewed the current literature using a systematic search for published studies. A PubMed search were performed using the main search terms “IBD AND male infertility”, “Crohn’s disease AND male infertility”, “ulcerative colitis AND male infertility”. References in review articles were used if relevant. We noted that active inflammation, poor nutrition, alcohol use, smoking, medications, and surgery may cause infertility in men with IBD. In surgery such as proctocolectomy with ileal pouch-anal anastomosis, rectal incision seems to be associated with sexual dysfunction. Of the medications used for IBD, sulfasalazine reversibly reduces male fertility. No other medications appear to affect male fertility significantly, although small studies suggested some adverse effects. There are limited data on the effects of drugs for IBD on male fertility and pregnancy outcomes; however, patients should be informed of the possible effects of paternal drug exposure. This review provides information on fertility-related issues in men with IBD and discusses treatment options. PMID:27602237

  17. Infertility in men with inflammatory bowel disease.

    PubMed

    Shin, Takeshi; Okada, Hiroshi

    2016-08-06

    Inflammatory bowel disease (IBD) predominantly affects young adults. Fertility-related issues are therefore important in the management of patients with IBD. However, relatively modest attention has been paid to reproductive issues faced by men with IBD. To investigate the effects of IBD and its treatment on male fertility, we reviewed the current literature using a systematic search for published studies. A PubMed search were performed using the main search terms "IBD AND male infertility", "Crohn's disease AND male infertility", "ulcerative colitis AND male infertility". References in review articles were used if relevant. We noted that active inflammation, poor nutrition, alcohol use, smoking, medications, and surgery may cause infertility in men with IBD. In surgery such as proctocolectomy with ileal pouch-anal anastomosis, rectal incision seems to be associated with sexual dysfunction. Of the medications used for IBD, sulfasalazine reversibly reduces male fertility. No other medications appear to affect male fertility significantly, although small studies suggested some adverse effects. There are limited data on the effects of drugs for IBD on male fertility and pregnancy outcomes; however, patients should be informed of the possible effects of paternal drug exposure. This review provides information on fertility-related issues in men with IBD and discusses treatment options.

  18. Glucocorticoids limit acute lung inflammation in concert with inflammatory stimuli by induction of SphK1

    PubMed Central

    Vettorazzi, Sabine; Bode, Constantin; Dejager, Lien; Frappart, Lucien; Shelest, Ekaterina; Klaßen, Carina; Tasdogan, Alpaslan; Reichardt, Holger M.; Libert, Claude; Schneider, Marion; Weih, Falk; Henriette Uhlenhaut, N.; David, Jean-Pierre; Gräler, Markus; Kleiman, Anna; Tuckermann, Jan P.

    2015-01-01

    Acute lung injury (ALI) is a severe inflammatory disease for which no specific treatment exists. As glucocorticoids have potent immunosuppressive effects, their application in ALI is currently being tested in clinical trials. However, the benefits of this type of regimen remain unclear. Here we identify a mechanism of glucocorticoid action that challenges the long-standing dogma of cytokine repression by the glucocorticoid receptor. Contrarily, synergistic gene induction of sphingosine kinase 1 (SphK1) by glucocorticoids and pro-inflammatory stimuli via the glucocorticoid receptor in macrophages increases circulating sphingosine 1-phosphate levels, which proves essential for the inhibition of inflammation. Chemical or genetic inhibition of SphK1 abrogates the therapeutic effects of glucocorticoids. Inflammatory p38 MAPK- and mitogen- and stress-activated protein kinase 1 (MSK1)-dependent pathways cooperate with glucocorticoids to upregulate SphK1 expression. Our findings support a critical role for SphK1 induction in the suppression of lung inflammation by glucocorticoids, and therefore provide rationales for effective anti-inflammatory therapies. PMID:26183376

  19. Mechanical Ventilation Induces an Inflammatory Response in Preinjured Lungs in Late Phase of Sepsis.

    PubMed

    Xuan, Wei; Zhou, Quanjun; Yao, Shanglong; Deng, Qingzhu; Wang, Tingting; Wu, Qingping

    2015-01-01

    Mechanical ventilation (MV) may amplify the lung-specific inflammatory response in preinjured lungs by elevating cytokine release and augmenting damage to the alveolar integrity. In this study, we test the hypothesis that MV exerts different negative impacts on inflammatory response at different time points of postlung injury. Basic lung injury was induced by cecal ligation and puncture (CLP) surgery in rats. Physiological indexes including blood gases were monitored during MV and samples were assessed following each experiment. Low V T (tidal volume) MV caused a slight increase in cytokine release and tissue damage at day 1 and day 4 after sepsis induced lung injury, while cytokine release from the lungs in the two moderately ventilated V T groups was amplified. Interestingly, in the two groups where rats received low V T MV, we found that infiltration of inflammatory cells was only profound at day 4 after CLP. Marked elevation of protein leakage indicated a compromise in alveolar integrity in rats that received moderate V T MV at day 4 following CLP, correlating with architectural damage to the alveoli. Our study indicates that preinjured lungs are more sensitive to mechanical MV at later phases of sepsis, and this situation may be a result of differing immune status.

  20. Mck2-dependent infection of alveolar macrophages promotes replication of MCMV in nodular inflammatory foci of the neonatal lung.

    PubMed

    Stahl, F R; Keyser, K A; Heller, K; Bischoff, Y; Halle, S; Wagner, K; Messerle, M; Förster, R

    2015-01-01

    Infection with cytomegalovirus (CMV) shows a worldwide high prevalence with only immunocompromised individuals or newborns to become symptomatic. The host's constitution and the pathogen's virulence determine whether disease occurs after infection. Mouse CMV (MCMV) is an appreciated pathogen for in vivo investigation of host-pathogen interactions. It has recently been reported that a single base pair deletion can spontaneously occur in the open reading frame of MCMV-encoded chemokine 2 (MCK2), preventing the expression of the full-length gene product. To study the consequences of this mutation, we compared the Mck2-defective reporter virus MCMV-3D with the newly generated repaired Mck2(+) mutant MCMV-3DR. Compared with MCMV-3D, neonatal mice infected with MCMV-3DR showed severe viral disease after lung infection. Viral disease coincided with high viral activity in multiple organs and increased virus replication in previously described nodular inflammatory foci (NIF) in the lung. Notably, MCMV-3DR showed tropism for alveolar macrophages in vitro and in vivo, whereas MCMV-3D did not infect this cell type. Moreover, in vivo depletion of alveolar macrophages reduced MCMV-3DR replication in the lung. We proposed an Mck2-mediated mechanism by which MCMV exploits alveolar macrophages to increase replication upon first encounter with the host's lung mucosa.

  1. Inflammatory Bowel Disease: Historical Perspective, Epidemiology, and Risk Factors.

    PubMed

    Malik, Talha A

    2015-12-01

    Inflammatory bowel disease (IBD) describes a group of closely related yet heterogeneous predominantly intestinal disease processes that are a result of an uncontrolled immune mediated inflammatory response. It is estimated that approximately one and a half million persons in North America have IBD. Pathogenesis of IBD involves an uncontrolled immune mediated inflammatory response in genetically predisposed individuals to a still unknown environmental trigger that interacts with the intestinal flora. There continues to be an enormous amount of information emanating from epidemiological studies providing expanded insight into the occurrence, distribution, determinants, and mechanisms of inflammatory bowel disease.

  2. Inflammatory myofibroblastic tumour of the lung: a reactive lesion or a true neoplasm?

    PubMed Central

    Panagiotopoulos, Nikolaos; Gvinianidze, Lasha; Woo, Wen Ling; Borg, Elaine; Lawrence, David

    2015-01-01

    Inflammatory myofibroblastic tumour (IMT) of the lung represents an extremely rare type of inflammatory pseudo tumor that appears most commonly in children and young individuals. There has been an ongoing controversy whether an IMT is a reactive lesion or a true neoplasm making the further management extremely challenging. Purpose of the paper is through a literature review to highlight the existence of this rare tumour along with its key features and the management options available. PMID:26101648

  3. Pulmonary hypertension in chronic interstitial lung diseases.

    PubMed

    Caminati, Antonella; Cassandro, Roberto; Harari, Sergio

    2013-09-01

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

  4. 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

  5. Diagnostic Utility of Auto-Antibodies in Inflammatory Muscle Diseases.

    PubMed

    Allenbach, Y; Benveniste, O

    2015-01-01

    To date, there are four main groups of idiopathic inflammatory myopathies (IIM): polymyositis (PM), dermatomyositis (DM), immune-mediated necrotizing myopathy (IMNM) and sporadic inclusion body myositis; based on clinical presentation and muscle pathology. Nevertheless, important phenotypical differences (either muscular and/or extra-muscular manifestations) within a group persist. In recent years, the titration of different myositis-specific (or associated) auto-antibodies as a diagnostic tool has increased. This is an important step forward since it may facilitate, at a viable cost, the differential diagnosis between IIM and other myopathies. We have now routine access to assays for the detection of different antibodies. For example, IMNM are related to the presence of anti-SRP or anti-HMGCR. PM is associated with anti-synthetase antibodies (anti-Jo-1, PL-7, PL-12, OJ, and EJ) and DM with anti-Mi-2, anti-SAE, anti-TIF-1-γ and anti-NXP2 (both associated with cancer) or anti-MDA5 antibodies (associated with interstitial lung disease). Today, over 30 myositis specific and associated antibodies have been characterised, and all groups of myositis may present one of those auto-antibodies. Most of them allow identification of homogenous patient groups, more precisely than the classical international classifications of myositis. This implies that classification criteria could be modified accordingly, since these auto-antibodies delineate groups of patients suffering from myositis with consistent clinical phenotype (muscular and extra-muscular manifestations), common prognostic (cancer association, presence of interstitial lung disease, mortality and risk of relapse) and treatment responses. Nevertheless, since numerous auto-antibodies have been recently characterised, the exact prevalence of myositis specific antibodies remains to be documented, and research of new auto-antibodies in the remaining seronegative group is still needed.

  6. Inflammatory pouch disease: The spectrum of pouchitis

    PubMed Central

    Zezos, Petros; Saibil, Fred

    2015-01-01

    Restorative proctocolectomy with ileal-pouch anal anastomosis (IPAA) is the operation of choice for medically refractory ulcerative colitis (UC), for UC with dysplasia, and for familial adenomatous polyposis (FAP). IPAA can be a treatment option for selected patients with Crohn’s colitis without perianal and/or small bowel disease. The term “pouchitis” refers to nonspecific inflammation of the pouch and is a common complication in patients with IPAA; it occurs more often in UC patients than in FAP patients. This suggests that the pathogenetic background of UC may contribute significantly to the development of pouchitis. The symptoms of pouchitis are many, and can include increased bowel frequency, urgency, tenesmus, incontinence, nocturnal seepage, rectal bleeding, abdominal cramps, and pelvic discomfort. The diagnosis of pouchitis is based on the presence of symptoms together with endoscopic and histological evidence of inflammation of the pouch. However, “pouchitis” is a general term representing a wide spectrum of diseases and conditions, which can emerge in the pouch. Based on the etiology we can sub-divide pouchitis into 2 groups: idiopathic and secondary. In idiopathic pouchitis the etiology and pathogenesis are still unclear, while in secondary pouchitis there is an association with a specific causative or pathogenetic factor. Secondary pouchitis can occur in up to 30% of cases and can be classified as infectious, ischemic, non-steroidal anti-inflammatory drugs-induced, collagenous, autoimmune-associated, or Crohn’s disease. Sometimes, cuffitis or irritable pouch syndrome can be misdiagnosed as pouchitis. Furthermore, idiopathic pouchitis itself can be sub-classified into types based on the clinical pattern, presentation, and responsiveness to antibiotic treatment. Treatment differs among the various forms of pouchitis. Therefore, it is important to establish the correct diagnosis in order to select the appropriate treatment and further

  7. 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.

  8. 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

  9. Prediction of disease course in inflammatory bowel diseases.

    PubMed

    Lakatos, Peter Laszlo

    2010-06-07

    Clinical presentation at diagnosis and disease course of both Crohn's disease (CD) and ulcerative colitis are heterogeneous and variable over time. Since most patients have a relapsing course and most CD patients develop complications (e.g. stricture and/or perforation), much emphasis has been placed in the recent years on the determination of important predictive factors. The identification of these factors may eventually lead to a more personalized, tailored therapy. In this TOPIC HIGHLIGHT series, we provide an update on the available literature regarding important clinical, endoscopic, fecal, serological/routine laboratory and genetic factors. Our aim is to assist clinicians in the everyday practical decision-making when choosing the treatment strategy for their patients suffering from inflammatory bowel diseases.

  10. Diagnosis and treatment of cystic lung disease

    PubMed Central

    Park, Sanghoon; Lee, Eun Joo

    2017-01-01

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

  11. 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

  12. 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.

  13. Nanocarriers in therapy of infectious and inflammatory diseases

    NASA Astrophysics Data System (ADS)

    Ikoba, Ufuoma; Peng, Haisheng; Li, Haichun; Miller, Cathy; Yu, Chenxu; Wang, Qun

    2015-02-01

    Nanotechnology is a growing science that has applications in various areas of medicine. The composition of nanocarriers for drug delivery is critical to guarantee high therapeutic performance when targeting specific host sites. Applications of nanotechnology are prevalent in the diagnosis and treatment of infectious and inflammatory diseases. This review summarizes recent advancements in the application of nanotechnology to the therapy of infectious and inflammatory diseases. The major focus is on the design and fabrication of various nanomaterials, characteristics and physicochemical properties of drug-loaded nanocarriers, and the use of these nanoscale drug delivery systems in treating infectious and inflammatory diseases, such as AIDS, hepatitis, tuberculosis, melanoma, and representative inflammatory diseases. Clinical trials and future perspective of the use of nanocarriers are also discussed in detail. We hope that such a review will be valuable to researchers who are exploring nanoscale drug delivery systems for the treatment of specific infectious and inflammatory diseases.

  14. Anti-inflammatory effects of Stephania tetrandra S. Moore on interleukin-6 production and experimental inflammatory disease models

    PubMed Central

    Kang, H-S.; Kim, Y-H.; Lee, C-S.; Lee, J-J.; Pyun, K-H.

    1996-01-01

    Deregulation of interleukin-6 (IL-6) expression caused the synthesis and release of many inflammatory mediators. It is involved in chronic inflammation, autoimmune diseases, and malignancy. Stephania tetrandra S. Moore is a Chinese medicinal herb which has been used traditionary as a remedy for neuralgia and arthritis in China. To investigate the anti-inflammatory effects of S. tetrandra S. Moore in vitro and in vivo, its effects on the production of IL-6 and inflammatory mediators were analysed. When human monocytes/macrophages stimulated with silica were treated with 0.1–10 μg/ml S. tetranda S. Moore, the production of IL-6 was inhibited up to 50%. At these concentrations, it had no cytotoxicity effect on these cells. It also suppressed the production of IL-6 by alveolar macrophages stimulated with silica. In addition, it inhibited the release of superoxide anion and hydrogen peroxide from human monocytes/macrophages. To assess the anti-fibrosis effects of S. tetrandra S. Moore, its effects on in vivo experimental inflammatory models were evaluated. In the experimental silicosis model, IL-6 activities in the sera and in the culture supernatants of pulmonary fibroblasts were also inhibited by it. In vitro and in vivo treatment of S. tetrandra S. Moore reduced collagen production by rat lung fibroblasts and lung tissue. Also, S. tetrandra S. Moore reduced the levels of serum GOT and GPT in the rat cirrhosis model induced by CCL4, and it was effective in reducing hepatic fibrosis and nodular formation. Taken together, these data indicate that it has a potent anti-inflammatory and antifibrosis effect by reducing IL-6 production. PMID:18475741

  15. Exploitation of the nicotinic anti-inflammatory pathway for the treatment of epithelial inflammatory diseases.

    PubMed

    Scott, David A; Martin, Michael

    2006-12-14

    Discoveries in the first few years of the 21st century have led to an understanding of important interactions between the nervous system and the inflammatory response at the molecular level, most notably the acetylcholine (ACh)-triggered, alpha7-nicotinic acetylcholine receptor (alpha7nAChR)-dependent nicotinic anti-inflammatory pathway. Studies using the alpha7nAChR agonist, nicotine, for the treatment of mucosal inflammation have been undertaken but the efficacy of nicotine as a treatment for inflammatory bowel diseases remains debatable. Further understanding of the nicotinic anti-inflammatory pathway and other endogenous anti-inflammatory mechanisms is required in order to develop refined and specific therapeutic strategies for the treatment of a number of inflammatory diseases and conditions, including periodontitis, psoriasis, sarcoidosis, and ulcerative colitis.

  16. Probiotics in the management of lung diseases.

    PubMed

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

    2013-01-01

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

  17. [Metabolic syndrome in inflammatory rheumatic diseases].

    PubMed

    Malesci, D; Valentini, G; La Montagna, G

    2006-01-01

    Toward the end of the last century a better knowledge of cardiovascular (CV) risk factors and their associations led investigators to propose the existence of a unique pathophysiological condition called "metabolic" or "insulin resistance syndrome". Among all, insulin-resistance and compensatory hyperinsulinemia are considered its most important treatment targets. Different definitions have been provided by World Health Organization (WHO) and by The Third Report of The National Cholesterol Education Program's Adult Treatment Panel (NCEP-ATP III). In particular, abdominal obesity, hypertension, low HDL cholesterol and hyperglicemia are the most common items used for its definition. The presence of MetS is effective in predicting the future risk of diabetes and coronaropathies. The evidence of a higher CV risk rate among different rheumatic inflammatory diseases has recently been associated with high prevalence of MetS in some cases. Rheumatoid or psoriatic arthritis have the large series among arthritis, whereas systemic lupus erythematosus among connective tissue disorders. This review analyses all most important studies about the evidence of MetS in rheumatic patients and the main clinical and prognostic significance of this relation.

  18. [Management of uncomplicated pelvic inflammatory disease].

    PubMed

    Bourret, A; Fauconnier, A; Brun, J-L

    2012-12-01

    Since the 1993 French consensus conference on uncomplicated pelvic inflammatory diseases (uPID), new antibiotics appeared and bacterial resistances did evoluate. This methodic analysis of the literature updates different aspects of its treatment. Antibiotherapy must be established early (EL3). Inpatient and intravenous treatment is not superior to outpatient and oral treatment (EL1). Ofloxacine+metronidazole association can be proposed in first intention (EL1). If case of Neisseria gonorrhoeae infection, one ceftriaxone injection must be associated (EL4). All the other antibiotics associations have shown to be efficient except the metronidazole+doxycycline association, which is not indicated (EL2). Two weeks treatment seems to be a sufficient duration. Laparoscopic treatment in first intention is not justified except for diagnostic doubts or unfavorable evolution of the medical treatment (EL4). Neither non-steroidic antiinflamatorries, nor corticosteroids, have been proved to be efficient to decrease the adherence risk in uPID (EL3). Early extraction of an intra uterine device (IUD) allows symptomatologic improvement (EL2). Partners treatment with azithromycin improves the 4 months bacteriologic results (EL2). HIV positive patients do not need specific treatment (EL3).

  19. Elderly patients and inflammatory bowel disease

    PubMed Central

    Nimmons, Danielle; Limdi, Jimmy K

    2016-01-01

    The incidence and prevalence of inflammatory bowel disease (IBD) is increasing globally. Coupled with an ageing population, the number of older patients with IBD is set to increase. The clinical features and therapeutic options in young and elderly patients are comparable but there are some significant differences. The wide differential diagnosis of IBD in elderly patients may result in a delay in diagnosis. The relative dearth of data specific to elderly IBD patients often resulting from their exclusion from pivotal clinical trials and the lack of consensus guidelines have made clinical decisions somewhat challenging. In addition, age specific concerns such as co-morbidity; loco-motor and cognitive function, poly-pharmacy and its consequences need to be taken into account. In applying modern treatment paradigms to the elderly, the clinician must consider the potential for more pronounced adverse effects in this vulnerable group and set appropriate boundaries maximising benefit and minimising harm. Meanwhile, clinicians need to make personalised decisions but as evidence based as possible in the holistic, considered and optimal management of IBD in elderly patients. In this review we will cover the clinical features and therapeutic options of IBD in the elderly; as well as addressing common questions and challenges posed by its management. PMID:26855812

  20. Mouth cancer in inflammatory bowel diseases.

    PubMed

    Giagkou, E; Christodoulou, D K; Katsanos, K H

    2016-05-01

    Mouth cancer is a major health problem. Multiple risk factors for developing mouth cancer have been studied and include history of tobacco and alcohol abuse, age over 40, exposure to ultraviolet radiation, human papilloma virus infection (HPV), nutritional deficiencies, chronic irritation, and existence or oral potentially malignant lesions such as leukoplakia and lichen planus. An important risk factor for mouth cancer is chronic immunosuppression and has been extensively reported after solid organ transplantation as well as HIV-infected patients. Diagnosis of inflammatory bowel disease (IBD) is not yet considered as a risk factor for oral cancer development. However, a significant number of patients with IBD are receiving immunosuppressants and biological therapies which could represent potential oral oncogenic factors either by direct oncogenic effect or by continuous immunosuppression favoring carcinogenesis, especially in patients with HPV(+) IBD. Education on modifiable risk behaviors in patients with IBD is the cornerstone of prevention of mouth cancer. Oral screening should be performed for all patients with IBD, especially those who are about to start an immunosuppressant or a biologic.

  1. Pelvic inflammatory disease and oral contraceptive use.

    PubMed

    Feldblum, P J; Burton, N; Rosenberg, M J

    1986-10-01

    Oral contraceptive use has been shown to protect against gonococcal pelvic inflammatory disease (PID), but the effect on chlamydial PID is uncertain. Chlamydia infection is rising in incidence and has become the major cause of PID in many areas. PID may cause infertility, impairing the future reproduction of women. Previous studies on oral contraceptives and PID relied on hospitalized women, which may have biased the sample to include mainly gonococcal PID. Several studies show increased risk of endocervical chlamydia infection in users of oral contraceptives. The postulated mechanism is cervical ectopy, exposing more squamous epithelium to the organisms. Nevertheless, there is evidence indicating that despite the increased incidence of endocervical infection, oral contraceptives may inhibit the organisms from ascending, thus still offering a protective affect against both gonococcal and chlamydial PID. Future research must focus on the prevalence of chlamydia infection in Africa, and the natural history of the illness. The effect of different types of oral contraceptives on chlamydia infection must be evaluated.

  2. Role of Diet in Inflammatory Bowel Disease.

    PubMed

    Ruemmele, Frank M

    2016-01-01

    The incidence of inflammatory bowel disease (IBD) is steadily in the rise in Western as well as in developing countries paralleling the increase of westernized diets, characterized by high protein and fat as well as excessive sugar intake, with less vegetables and fiber. An interesting hypothesis is that environmental (food-) triggered changes of the intestinal microbiome might cause a proinflammatory state preceding the development of IBD. Indeed, an intact intestinal epithelial barrier assuring a normal bacterial clearance of the intestinal surface is crucial to guarantee intestinal homeostasis. Any factors affecting the epithelial barrier function directly or indirectly may impact on this homeostasis, as well as any changes of the intestinal microbial composition. It is intriguing to learn that some frequently used food components impact on the quality of the intestinal barrier, as well as on the composition of the intestinal microbiome. This highlights the close interaction between living conditions, hygiene, food habits and food quality with the bacterial composition of the intestinal microbiome and the activation status of the intestinal immune system. There is clear evidence that nutritional therapy is highly successful in the treatment of Crohn's disease (CD). Exclusive enteral nutrition is well established as induction therapy of CD. New diets, such as a CD exclusion diet or defined diets (specific carbohydrate diets, FODMAP diet, Paleolithic diet) are being discussed as treatment options for IBD. Well-designed clinical trials in IBD are urgently required to define the precise role of each of these diets in the prevention or management of IBD. Up to now, the role of diet in IBD is highly undermined by lay and anecdotal reports without sufficient scientific proof.

  3. Effects of inhaled high-molecular weight hyaluronan in inflammatory airway disease.

    PubMed

    Lamas, Adelaida; Marshburn, Jamie; Stober, Vandy P; Donaldson, Scott H; Garantziotis, Stavros

    2016-10-03

    Cystic fibrosis (CF) is a chronic inflammatory disease that is affecting thousands of patients worldwide. Adjuvant anti-inflammatory treatment is an important component of cystic fibrosis treatment, and has shown promise in preserving lung function and prolonging life expectancy. Inhaled high molecular weight hyaluronan (HMW-HA) is reported to improve tolerability of hypertonic saline and thus increase compliance, and has been approved in some European countries for use as an adjunct to hypertonic saline treatment in cystic fibrosis. However, there are theoretical concerns that HMW-HA breakdown products may be pro-inflammatory. In this clinical pilot study we show that sputum cytokines in CF patients receiving HMW-HA are not increased, and therefore HMW-HA does not appear to adversely affect inflammatory status in CF airways.

  4. 'Inflammatory breast cancer' due to metastatic adenocarcinoma of lung.

    PubMed

    Ninan, Jacob; Naik, Vinay; George, Gemy Maria

    2016-09-01

    A 67-year-old woman with a history of lung adenocarcinoma presented with 3 weeks of redness, pain, swelling and skin changes in her right breast. Her vital signs and physical examination were within physiological limits except for the right breast. She had extensive red streaks radiating from the right nipple with peau d'orange appearance of her overlying skin. Her breast was tender on examination and did not have any associated cervical or axillary lymphadenopathy. Her mammography revealed thickening of the skin, increased parenchymal markings and shrinkage the breast. Multiple skin biopsies demonstrated moderately differentiated lung adenocarcinoma with lymphovascular invasion. The patient made an informed decision to undergo radiotherapy following discussion with her oncologist and breast surgeon. She succumbed to her illness 2 months after the diagnosis of metastasis to her breast.

  5. Pemphigus vulgaris-associated interstitial lung disease.

    PubMed

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

    2016-07-01

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

  6. Ferritin, finger clubbing, and lung disease.

    PubMed Central

    Shneerson, J M; Jones, B M

    1981-01-01

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

  7. Therapeutic prospects to treat skeletal muscle wasting in COPD (chronic obstructive lung disease).

    PubMed

    Hansen, Michelle J; Gualano, Rosa C; Bozinovski, Steve; Vlahos, Ross; Anderson, Gary P

    2006-01-01

    Chronic obstructive pulmonary disease (COPD) is an incurable group of lung diseases characterised by progressive airflow limitation and loss of lung function, which lead to profound disability. It is mostly caused by cigarette smoke. Although COPD is one of the most prevalent diseases worldwide and its incidence is increasing, current therapies do little to improve the condition. Much current research focuses on strategies to halt the accelerated rate of decline in lung function that occurs in the disease. However, as most symptoms occur when the lungs are already extensively and irreversibly damaged, it is uncertain whether an agent able to slow or halt decline in lung function would actually provide relief to COPD patients. As lung function worsens, systemic comorbidities contribute markedly to disability. Loss of lean body mass (skeletal muscle) has recently been identified as a major determinant of disability in COPD and an independent predictor of mortality. In contrast to lung structure damage, skeletal muscle retains regenerative capacity in COPD. In this review, we discuss mechanisms of wasting in COPD, focusing on therapeutic strategies that might improve the health and productive life expectancy of COPD patients by improving skeletal muscle mass and function. Single or combination approaches exploiting the suppression of procatabolic inflammatory mediators, inhibition of ubiquitin ligases, repletion of anabolic hormones and growth factors, inhibition of myoblast apoptosis, remediation of systemic oxidative stress and promotion of repair, and regeneration via stimulation of satellite cell differentiation hold considerable therapeutic promise.

  8. Clinical application of expectorant therapy in chronic inflammatory airway diseases (Review)

    PubMed Central

    ZHANG, TING; ZHOU, XIANGDONG

    2014-01-01

    Airway mucus hypersecretion is a significant clinical and pathological feature of chronic inflammatory airway diseases. Its clinical presentations include recurrent coughing and phlegm. Airway mucus is closely associated with the occurrence, development and prognosis of chronic inflammatory airway diseases and critically affects the lung function, quality of life, hospitalization rate and mortality of patients with chronic inflammatory airway diseases. Therefore, expectorant therapies targeting the potential mechanisms of mucus hypersecretion have been the focus of numerous studies. Conventional expectorants are mainly mucoactive medicines, including nausea-stimulating expectorants, mucolytics, mucokinetics, and proteases and nucleases. In addition, certain traditional Chinese herbal medicines and non-mucoactive agents, including muscarinic acetylcholine receptor antagonists, corticosteroids, leukotriene receptor antagonists and macrolide antibiotics, have also shown expectorant effects. Several novel medicines for expectorant therapy have emerged, including cholesterol-lowering statins, epidermal growth factor receptor tyrosine kinase inhibitors, phosphodiesterase-4 inhibitors, stanozolol, surfactants, flavonoids, tachykinin receptor antagonists, protease inhibitors, cytokine antagonists and purinergic agonists. With the increasing number of multidisciplinary studies, the effectiveness of expectorant therapy for the treatment of chronic inflammatory airway diseases has been confirmed. Therefore, the development of novel expectorants and the standardization of expectorant therapy are the direction and focus of future studies, thus benefiting patients who have a chronic inflammatory airway disease. PMID:24660026

  9. Matrix metalloproteinases in destructive lung disease.

    PubMed

    Houghton, A McGarry

    2015-01-01

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

  10. Tracheal lipoma mimicking obstructive lung disease.

    PubMed

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

    2010-01-01

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

  11. Irritable bowel syndrome and inflammatory bowel disease: interrelated diseases?

    PubMed

    Quigley, Eamonn M M

    2005-01-01

    In the past inflammatory bowel disease (IBD), celiac disease and irritable bowel syndrome (IBS) were regarded as completely separate disorders. Now, with the description of inflammation, albeit low-grade, in IBS, and of symptom overlap between IBS and celiac disease, this contention has come under question. Is there true overlap between these disorders? Despite the limitations of available data one cannot but be struck by some areas of apparent convergence: IBD and celiac disease in remission, lymphocytic colitis and microscopic inflammation in IBS, in general, and, especially, in the post-infectious IBS category. The convergence between latent celiac disease and sub-clinical IBD, on the one hand, and IBS, on the other, appears, based on available evidence, to be somewhat spurious and may largely relate to misdiagnosis, a phenomenon which may also explain the apparent evolution of IBS into IBD in some studies. Similarities between IBS and lymphocytic colitis are more striking and less readily dismissed; as for IBS, well documented instances of progression of lymphocytic colitis to full-blown IBD are infrequent, suggesting a true separation between this disorder and classical IBD. Do IBS and lymphocytic colitis represent different responses to similar triggers? Will some of the 'inflamed' IBS subgroup be reclassified as part of the spectrum of lymphocytic colitis in the future? Will inflammation emerge as a common underlying factor in the pathogenesis of IBS? The answer to these and many questions must await further study of this fascinating area.

  12. Macrophage Targeted Theranostics as Personalized Nanomedicine Strategies for Inflammatory Diseases

    PubMed Central

    Patel, Sravan Kumar; Janjic, Jelena M.

    2015-01-01

    Inflammatory disease management poses challenges due to the complexity of inflammation and inherent patient variability, thereby necessitating patient-specific therapeutic interventions. Theranostics, which integrate therapeutic and imaging functionalities, can be used for simultaneous imaging and treatment of inflammatory diseases. Theranostics could facilitate assessment of safety, toxicity and real-time therapeutic efficacy leading to personalized treatment strategies. Macrophages are an important cellular component of inflammatory diseases, participating in varied roles of disease exacerbation and resolution. The inherent phagocytic nature, abundance and disease homing properties of macrophages can be targeted for imaging and therapeutic purposes. This review discusses the utility of theranostics in macrophage ablation, phenotype modulation and inhibition of their inflammatory activity leading to resolution of inflammation in several diseases. PMID:25553105

  13. Gene expression profiling of the effects of organic dust in lung epithelial and THP-1 cells reveals inductive effects on inflammatory and immune response genes.

    PubMed

    Boggaram, Vijay; Loose, David S; Gottipati, Koteswara R; Natarajan, Kartiga; Mitchell, Courtney T

    2016-04-01

    The intensification and concentration of animal production operations expose workers to high levels of organic dusts in the work environment. Exposure to organic dusts is a risk factor for the development of acute and chronic respiratory symptoms and diseases. Lung epithelium plays important roles in the control of immune and inflammatory responses to environmental agents to maintain lung health. To better understand the effects of organic dust on lung inflammatory responses, we characterized the gene expression profiles of A549 alveolar and Beas2B bronchial epithelial and THP-1 monocytic cells influenced by exposure to poultry dust extract by DNA microarray analysis using Illumina Human HT-12 v4 Expression BeadChip. We found that A549 alveolar and Beas2B bronchial epithelial and THP-1 cells responded with unique changes in the gene expression profiles with regulation of genes encoding inflammatory cytokines, chemokines, and other inflammatory proteins being common to all the three cells. Significantly induced genes included IL-8, IL-6, IL-1β, ICAM-1, CCL2, CCL5, TLR4, and PTGS2. Validation by real-time qRT-PCR, ELISA, Western immunoblotting, and immunohistochemical staining of lung sections from mice exposed to dust extract validated DNA microarray results. Pathway analysis indicated that dust extract induced changes in gene expression influenced functions related to cellular growth and proliferation, cell death and survival, and cellular development. These data show that a broad range of inflammatory mediators produced in response to poultry dust exposure can modulate lung immune and inflammatory responses. This is the first report on organic dust induced changes in expression profiles in lung epithelial and THP-1 monocytic cells.

  14. Predicting Outcomes to Optimize Disease Management in Inflammatory Bowel Diseases

    PubMed Central

    Torres, Joana; Caprioli, Flavio; Katsanos, Konstantinos H.; Lobatón, Triana; Micic, Dejan; Zerôncio, Marco; Van Assche, Gert; Lee, James C.; Lindsay, James O.; Rubin, David T.; Panaccione, Remo

    2016-01-01

    Background and Aims: Efforts to slow or prevent the progressive course of inflammatory bowel diseases [IBD] include early and intensive monitoring and treatment of patients at higher risk for complications. It is therefore essential to identify high-risk patients – both at diagnosis and throughout disease course. Methods: As a part of an IBD Ahead initiative, we conducted a comprehensive literature review to identify predictors of long-term IBD prognosis and generate draft expert summary statements. Statements were refined at national meetings of IBD experts in 32 countries and were finalized at an international meeting in November 2014. Results: Patients with Crohn’s disease presenting at a young age or with extensive anatomical involvement, deep ulcerations, ileal/ileocolonic involvement, perianal and/or severe rectal disease or penetrating/stenosing behaviour should be regarded as high risk for complications. Patients with ulcerative colitis presenting at young age, with extensive colitis and frequent flare-ups needing steroids or hospitalization present increased risk for colectomy or future hospitalization. Smoking status, concurrent primary sclerosing cholangitis and concurrent infections may impact the course of disease. Current genetic and serological markers lack accuracy for clinical use. Conclusions: Simple demographic and clinical features can guide the clinician in identifying patients at higher risk for disease complications at diagnosis and throughout disease course. However, many of these risk factors have been identified retrospectively and lack validation. Appropriately powered prospective studies are required to inform algorithms that can truly predict the risk for disease progression in the individual patient. PMID:27282402

  15. 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.

  16. Nicotinamide Phosphoribosyltransferase Inhibitor Is a Novel Therapeutic Candidate in Murine Models of Inflammatory Lung Injury

    PubMed Central

    Moreno-Vinasco, Liliana; Quijada, Hector; Sammani, Saad; Siegler, Jessica; Letsiou, Eleftheria; Deaton, Ryan; Saadat, Laleh; Zaidi, Rafe S.; Messana, Joe; Gann, Peter H.; Machado, Roberto F.; Camp, Sara M.; Wang, Ting

    2014-01-01

    We previously identified the intracellular nicotinamide phosphoribosyltransferase (iNAMPT, aka pre–B-cell colony enhancing factor) as a candidate gene promoting acute respiratory distress syndrome (ARDS) and ventilator-induced lung injury (VILI) with circulating nicotinamide phosphoribosyltransferase potently inducing NF-κB signaling in lung endothelium. iNAMPT also synthesizes intracellular nicotinamide adenine dinucleotide (iNAD) in response to extracellular oxidative stress, contributing to the inhibition of apoptosis via ill-defined mechanisms. We now further define the role of iNAMPT activity in the pathogenesis of ARDS/VILI using the selective iNAMPT inhibitor FK-866. C57/B6 mice were exposed to VILI (40 ml/kg, 4 h) or LPS (1.5 mg/kg, 18 h) after osmotic pump delivery of FK-866 (100 mg/kg/d, intraperitoneally). Assessment of total bronchoalveolar lavage (BAL) protein, polymorphonuclear neutrophil (PMN) levels, cytokine levels (TNF-α, IL-6, IL-1α), lung iNAD levels, and injury scores revealed that FK-866–mediated iNAMPT inhibition successfully reduced lung tissue iNAD levels, BAL injury indices, inflammatory cell infiltration, and lung injury scores in LPS- and VILI-exposed mice. FK-866 further increased lung PMN apoptosis, as reflected by caspase-3 activation in BAL PMNs. These findings support iNAMPT inhibition via FK-866 as a novel therapeutic agent for ARDS via enhanced apoptosis in inflammatory PMNs. PMID:24588101

  17. Contribution of Lung Macrophages to the Inflammatory Responses Induced by Exposure to Air Pollutants

    PubMed Central

    van Eeden, Stephan F.

    2013-01-01

    Large population cohort studies have indicated an association between exposure to particulate matter and cardiopulmonary morbidity and mortality. The inhalation of toxic environmental particles and gases impacts the innate and adaptive defense systems of the lung. Lung macrophages play a critically important role in the recognition and processing of any inhaled foreign material such as pathogens or particulate matter. Alveolar macrophages and lung epithelial cells are the predominant cells that process and remove inhaled particulate matter from the lung. Cooperatively, they produce proinflammatory mediators when exposed to atmospheric particles. These mediators produce integrated local (lung, controlled predominantly by epithelial cells) and systemic (bone marrow and vascular system, controlled predominantly by macrophages) inflammatory responses. The systemic response results in an increase in the release of leukocytes from the bone marrow and an increased production of acute phase proteins from the liver, with both factors impacting blood vessels and leading to destabilization of existing atherosclerotic plaques. This review focuses on lung macrophages and their role in orchestrating the inflammatory responses induced by exposure to air pollutants. PMID:24058272

  18. Rapid progressive interstitial lung disease as initial manifestation of primary Sjögren’s syndrome: a case report

    PubMed Central

    Lin, Yihua; Yi, Qun; Cheng, Deyun

    2014-01-01

    Primary Sjögren’s syndrome is a chronic inflammatory disorder with many extraglandular organ systems involved, including the lungs. Diffuse interstitial lung disease is the most serious form of lung involvement. Parenchymal lung involvement in primary Sjögren’s syndrome is usually manifested by cough and/or slowly progressive dyspnea and most of the cases present as chronic course. We describe here a case of primary Sjögren’s syndrome who presented as rapid progressive interstitial lung disease. Improvement was obtained with treatment of corticosteroids and ventilatory support at early time. To the best of our knowledge, this is the first report documenting primary Sjögren’s syndrome initially presenting as rapid progressive interstitial lung disease and it enriches our understanding of the clinical manifestations of primary Sjögren’s syndrome. PMID:25664130

  19. Baicalin from Scutellaria baicalensis blocks respiratory syncytial virus (RSV) infection and reduces inflammatory cell infiltration and lung injury in mice

    PubMed Central

    Shi, Hengfei; Ren, Ke; Lv, Baojie; Zhang, Wei; Zhao, Ying; Tan, Ren Xiang; Li, Erguang

    2016-01-01

    The roots of Scutellaria baicalensis has been used as a remedy for inflammatory and infective diseases for thousands of years. We evaluated the antiviral activity against respiratory syncytial virus (RSV) infection, the leading cause of childhood infection and hospitalization. By fractionation and chromatographic analysis, we determined that baicalin was responsible for the antiviral activity of S. baicalensis against RSV infection. The concentration for 50% inhibition (IC50) of RSV infection was determined at 19.9 ± 1.8 μM, while the 50% cytotoxic concentration (CC50) was measured at 370 ± 10 μM. We then used a mouse model of RSV infection to further demonstrate baicalin antiviral effect. RSV infection caused significant lung injury and proinflammatory response, including CD4 and CD8 T lymphocyte infiltration. Baicalin treatment resulted in reduction of T lymphocyte infiltration and gene expression of proinflammatory factors, while the treatment moderately reduced RSV titers recovered from the lung tissues. T lymphocyte infiltration and cytotoxic T lymphocyte modulated tissue damage has been identified critical factors of RSV disease. The study therefore demonstrates that baicalin subjugates RSV disease through antiviral and anti-inflammatory effect. PMID:27767097

  20. Casticin, an active compound isolated from Vitex Fructus, ameliorates the cigarette smoke-induced acute lung inflammatory response in a murine model.

    PubMed

    Lee, Hyeonhoon; Jung, Kyung-Hwa; Lee, Hangyul; Park, Soojin; Choi, Woosung; Bae, Hyunsu

    2015-10-01

    The aim of this study was to determine of the effect of casticin, as an anti-inflammatory agent, on an acute lung inflammation in vivo model established through exposure to cigarette smoke (CS). Casticin is a phytochemical from Vitex species such as Vitex rotundifolia and Vitex agnus-castus that was recently shown to exert an anti-inflammatory effect in vivo. To demonstrate the effects of casticin, C57BL/6 mice were whole-body exposed to mainstream CS or fresh air for two weeks and treated with 1, 2, and 10mg/kg casticin via an i.p. injection. Immune cell infiltrations and cytokine productions were assessed from bronchoalveolar lavage Fluid (BALF), and lung histological analysis was performed. Treatment with casticin was observed to significantly inhibit the numbers of total cells, neutrophils, macrophages, and lymphocytes and reduce the levels of proinflammatory cytokines and chemokines in the BALF. In addition, casticin significantly decreased the infiltration of peribronchial and perivascular inflammatory cells and the epithelium thickness. The results of this study indicate that casticin has significant effects on the lung inflammation induced by CS in a mouse model. According to these outcomes, casticin may have therapeutic potential in inflammatory lung diseases, such as chronic obstructive pulmonary disease (COPD).

  1. 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

  2. Noninvasive Markers of Disease Activity in Inflammatory Bowel Disease

    PubMed Central

    Kane, Sunanda

    2014-01-01

    It is often difficult to assess disease activity in inflammatory bowel disease (IBD). Noninvasive biomarkers are a means of quantifying often nebulous symptoms without subjecting patients to endoscopy or radiation. This paper highlights markers present in feces, serum, or urine that have all been compared with the gold standard, histologic analysis of endoscopically collected specimens. Two categories of markers are featured: well-researched markers of mucosal inflammation with high sensitivity and specificity (calprotectin, lactoferrin, and S100A12) and novel promising markers, some of which are already clinically employed for reasons unrelated to IBD (interleukin [IL]-17, IL-33/ST2, adenosine deaminase, polymorphonuclear elastase, matrix metalloproteinase-9, neopterin, serum M30, and fecal immunohistochemistry). The data pertaining to the more-established markers are intended to highlight recent clinical applications for these markers (ie, assessing disease outside of the colon or in the pediatric population as well as being a cost-saving alternative to colonoscopy to screen for IBD). As there is no evidence to date that a specific marker will accurately be able to represent the entire IBD patient population, it is likely that a combination of the existing markers will be most clinically relevant to the practicing gastroenterologist attempting to evaluate disease severity in a specific patient. Familiarity with the most promising emerging markers will allow a better understanding of new studies and their impact on patient care. PMID:27551251

  3. Medicinal plants used in treatment of inflammatory skin diseases

    PubMed Central

    2013-01-01

    Skin is an organ providing contact with the environment and protecting the human body from unfavourable external factors. Skin inflammation, reflected adversely in its functioning and appearance, also unfavourably affects the psyche, the condition of which is important during treatment of chronic skin diseases. The use of plants in treatment of inflammatory skin diseases results from their influence on different stages of inflammation. The paper presents results of the study regarding the anti-inflammatory activity of the plant raw material related to its influence on skin. The mechanism of action, therapeutic indications and side effects of medicinal plants used for treatment of inflammatory diseases of the skin are described. PMID:24278070

  4. [Update on the use of PET radiopharmaceuticals in inflammatory disease].

    PubMed

    Martínez-Rodríguez, I; Carril, J M

    2013-01-01

    The use of molecular imaging with PET/CT technology using different radiotracers, especially the (18)F-FDG is currently spreading beyond the area of oncology, the most interest being placed on inflammatory and infectious diseases. This article presents a review of its contribution in different inflammatory conditions in the context of structural and conventional nuclear medicine imaging. Special emphasis is placed on the more significant diseases such as large-vessel vasculitis, sarcoidosis, rheumatoid arthritis and inflammatory bowel disease and the study of the atheroma plaque.

  5. 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

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

    PubMed

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

    2013-01-01

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

  7. Sleep disorders and inflammatory disease activity: chicken or the egg?

    PubMed

    Parekh, Parth J; Oldfield Iv, Edward C; Challapallisri, Vaishnavi; Ware, J Catsby; Johnson, David A

    2015-04-01

    Sleep dysfunction is a highly prevalent condition that has long been implicated in accelerating disease states characterized by having an inflammatory component such as systemic lupus erythematosus, HIV, and multiple sclerosis. Inflammatory bowel disease (IBD) is a chronic, debilitating disease that is characterized by waxing and waning symptoms, which are a direct result of increased circulating inflammatory cytokines. Recent studies have demonstrated sleep dysfunction and the disruption of the circadian rhythm to result in an upregulation of inflammatory cytokines. Not only does this pose a potential trigger for disease flares but also an increased risk of malignancy in this subset of patients. This begs to question whether or not there is a therapeutic role of sleep cycle and circadian rhythm optimization in the prevention of IBD flares. Further research is needed to clarify the role of sleep dysfunction and alterations of the circadian rhythm in modifying disease activity and also in reducing the risk of malignancy in patients suffering from IBD.

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

    PubMed

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

    2003-05-01

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

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

    PubMed

    Adnot, Serge

    2014-01-01

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

  10. The role of methionine metabolism in inflammatory bowel disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Methionine (Met) cycle activity is critical for normal cell functions. Met metabolites S-adenosylmethionine (SAM) and methylthioadenosine (MTA) are anti-inflammatory, yet their role in inflammatory bowel disease (IBD) is poorly understood. We hypothesize that active IBD leads to changes in Met metab...

  11. Effects of presurgical exercise training on systemic inflammatory markers among patients with malignant lung lesions.

    PubMed

    Jones, Lee W; Eves, Neil D; Peddle, Carolyn J; Courneya, Kerry S; Haykowsky, Mark; Kumar, Vikaash; Winton, Timothy W; Reiman, Tony

    2009-04-01

    Systemic inflammation plays an important role in the initiation, promotion, and progression of lung carcinogenesis. The effects of interventions to lower inflammation have not been explored. Accordingly, we conducted a pilot study to explore the effects of exercise training on changes in biomarkers of systemic inflammation among patients with malignant lung lesions. Using a single-group design, 12 patients with suspected operable lung cancer were provided with structured exercise training until surgical resection. Participants underwent cardiopulmonary exercise testing, 6 min walk testing, pulmonary function testing, and blood collection at baseline and immediately prior to surgical resection. Systemic inflammatory markers included intracellular adhesion molecule (ICAM)-1, macrophage inflammatory protein-1alpha, interleukin (IL)-6, IL-8, monocyte chemotactic protein-1, C-reactive protein, and tumor necrosis factor-alpha. The overall exercise adherence rate was 78%, with patients completing a mean of 30 +/- 25 sessions. Mean peak oxygen consumption increased 2.9 mL.kg-1.min-1 from baseline to presurgery (p = 0.016). Results indicate that exercise training resulted in a significant reduction in ICAM-1 (p = 0.041). Changes in other inflammatory markers did not reach statistical significance. Change in cardiorespiratory fitness was not associated with change in systemic inflammatory markers. This exploratory study provides an initial step for future studies to elucidate the potential role of exercise, as well as identify the underlying mechanisms of action, as a means of modulating the relationship between inflammation and cancer pathogenesis.

  12. Evaluation of the anti-inflammatory effects of β-adrenoceptor agonists on human lung macrophages.

    PubMed

    Gill, Sharonjit K; Marriott, Helen M; Suvarna, S Kim; Peachell, Peter T

    2016-12-15

    The principal mechanism by which bronchodilator β-adrenoceptor agonists act is to relax airways smooth muscle although they may also be anti-inflammatory. However, the extent of anti-inflammatory activity and the cell types affected by these agonists are uncertain. The purpose of this study was to evaluate whether β-adrenoceptor agonists prevent pro-inflammatory cytokine generation from activated human lung macrophages. Macrophages were isolated and purified from human lung. The cells were pre-treated with both short-acting (isoprenaline, salbutamol, terbutaline) and long-acting (formoterol, salmeterol, indacaterol) β-agonists before activation with lipopolysaccharide (LPS) to induce cytokine (TNFα, IL-6, IL-8 and IL-10) generation. The experiments showed that short-acting β-agonists were poor inhibitors of cytokine generation. Of the long-acting β-agonists studied, formoterol was also a weak inhibitor of cytokine generation whereas only indacaterol and salmeterol showed moderate inhibitory activity. Further experiments using the β2-adrenoceptor antagonist ICI-118,551 suggested that the effects of indacaterol were likely to be mediated by β2-adrenoceptors whereas those of salmeterol were not. These findings were corroborated by functional desensitization studies in which the inhibitory effects of indacaterol appeared to be receptor-mediated whereas those of salmeterol were not. Taken together, the data indicate that the anti-inflammatory effects of β-adrenoceptor agonists on human lung macrophages are modest.

  13. In vivo effect of surfactant on inflammatory cytokines during endotoxin-induced lung injury in rodents.

    PubMed

    Mittal, Neha; Sanyal, Sankar Nath

    2011-01-01

    Lipopolysaccharide (LPS) is a known inducer of acute respiratory distress syndrome (ARDS) in humans and animals. In this study, ARDS was developed in rats by intratracheal instillation of LPS and the effect of two types of surfactant (natural vs. synthetic) was examined to determine their potential corrective roles in general, as well as to compare the two surfactants against one another in particular, in endotoxin-induced lung injury. Sprague-Dawley male rats were divided into four groups, i.e., rats given: buffer controls; 055:B5 E. coli LPS only; LPS and then porcine surfactant (P-SF); or, LPS and then synthetic surfactant (S-SF). In vivo administration of LPS led to an increase in expression of the cytokines tumor necrosis factor-α, interleukin (IL)-1β, IL-2, IL-4, interferon-γ, monocyte chemotactic protein-1, and macrophage inflammatory protein-1β in the lungs of rats. These effects were confirmed by immunofluorescence in lung tissue sections and/or by protein (Western immunoblot) and mRNA expression (reverse transcription polymerase chain reaction) analyses of tissue samples. Apart from IL-4, concentrations of each of these cytokines in bronchoalveolar lavage fluid recovered from the animals were significantly increased in the LPS-treated hosts. Instillation of either surfactant (70 h after the LPS) into the airways diminished the expression of each of the inducible-cytokines, with the porcine (natural) form seeming having the greater inhibitory effect. These data suggest that surfactant can play an important role in the treatment of endotoxin-induced lung injury and might possess robust anti-inflammatory effects. Further, it seems that both the natural and synthetic surfactants prevent inflammatory outcomes in the lungs by controlling cytokine(s) production by various inflammatory cells. Last, the studies here clearly indicated that in this aspect, natural surfactant appears to be more beneficial compared to synthetic surfactant.

  14. Nutritional impact of inflammatory bowel diseases on children and adolescents☆

    PubMed Central

    dos Santos, Gilton Marques; Silva, Luciana Rodrigues; Santana, Genoile Oliveira

    2014-01-01

    OBJECTIVE: To perform a sistematiy review of the literature about the nutritional impact of inflammatory bowel diseases in children and adolescents. DATA SOURCES: A systematic review was performed using PubMed/MEDLINE, LILACS and SciELO databases, with inclusion of articles in Portuguese and in English with original data, that analyzed nutritional aspects of inflammatory bowel diseases in children and adolescents. The initial search used the terms "inflammatory bowel diseases" and "children" or "adolescents" and "nutritional evaluation" or "nutrition deficiency". The selection of studies was initially performed by reading the titles and abstracts. Review studies and those withouth data for pediatric patients were excluded. Subsequently, the full reading of the articles considered relevant was performed. RESULTS: 237 studies were identified, and 12 of them were selected according to the inclusion criteria. None of them was performed in South America. During the analysis of the studies, it was observed that nutritional characteristics of patients with inflammatory bowel disease may be altered; the main reports were related to malnutrition, growth stunting, delayed puberty and vitamin D deficiency. CONCLUSION: There are nutritional consequences of inflammatory bowel diseases in children and adolescents, mainly growth stunting, slower pubertal development, underweight and vitamin deficiencies. Nutritional impairments were more significant in patients with Crohn's disease; overweight and obesity were more common in patients with ulcerative rectocolitis. A detailed nutritional assessment should be performed periodically in children and adolescents with inflammatory bowel disease. PMID:25511006

  15. 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.

  16. Challenges and Current Efforts in the Development of Biomarkers for Chronic Inflammatory and Remodeling Conditions of the Lungs

    PubMed Central

    Grunig, Gabriele; Baghdassarian, Aram; Park, Sung-Hyun; Pylawka, Serhiy; Bleck, Bertram; Reibman, Joan; Berman-Rosenzweig, Erika; Durmus, Nedim

    2015-01-01

    This review discusses biomarkers that are being researched for their usefulness to phenotype chronic inflammatory lung diseases that cause remodeling of the lung’s architecture. The review focuses on asthma, chronic obstructive pulmonary disease (COPD), and pulmonary hypertension. Bio-markers of environmental exposure and specific classes of biomarkers (noncoding RNA, metabolism, vitamin, coagulation, and microbiome related) are also discussed. Examples of biomarkers that are in clinical use, biomarkers that are under development, and biomarkers that are still in the research phase are discussed. We chose to present examples of the research in biomarker development by diseases, because asthma, COPD, and pulmonary hypertension are distinct entities, although they clearly share processes of inflammation and remodeling. PMID:26917944

  17. IL-1 family cytokines trigger sterile inflammatory disease

    PubMed Central

    Lukens, John R.; Gross, Jordan M.; Kanneganti, Thirumala-Devi

    2012-01-01

    Inflammation plays vital roles in protective responses against pathogens and tissue repair, however, improper resolution of inflammatory networks is centrally involved in the pathogenesis of many acute and chronic diseases. Extensive advances have been made in recent years to define the inflammatory processes that are required for pathogen clearance, however, in comparison, less is known about the regulation of inflammation in sterile settings. Over the past decade non-communicable chronic diseases that are potentiated by sterile inflammation have replaced infectious diseases as the major threat to global human health. Thus, improved understanding of the sterile inflammatory process has emerged as one of the most important areas of biomedical investigation during our time. In this review we highlight the central role that interleukin-1 family cytokines play in sterile inflammatory diseases. PMID:23087690

  18. [Non steroidal anti-inflammatory drugs and rheumatic diseases].

    PubMed

    Cossermelli, W; Pastor, E H

    1995-01-01

    Nonsteroidal anti-inflammatory drugs (NSAID) comprise an important class of medicaments that reduced the symptoms of inflamation in rheumatic disease. This article emphasizes similarities and class characteristics of the NSAID, mechanisms of action, and drug-interactions.

  19. Common lung conditions: chronic obstructive pulmonary disease.

    PubMed

    Delzell, John E

    2013-06-01

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

  20. Clinical application of exhaled nitric oxide measurement in pediatric lung diseases

    PubMed Central

    2012-01-01

    Summary Fractional exhaled nitric oxide (FeNO) is a non invasive method for assessing the inflammatory status of children with airway disease. Different ways to measure FeNO levels are currently available. The possibility of measuring FeNO levels in an office setting even in young children, and the commercial availability of portable devices, support the routine use of FeNO determination in the daily pediatric practice. Although many confounding factors may affect its measurement, FeNO is now widely used in the management of children with asthma, and seems to provide significantly higher diagnostic accuracy than lung function or bronchial challenge tests. The role of FeNO in airway infection (e.g. viral bronchiolitis and common acquired pneumonia), in bronchiectasis, or in cases with diffuse lung disease is less clear. This review focuses on the most recent advances and the current clinical applications of FeNO measurement in pediatric lung disease. PMID:23273317

  1. Folate Receptor-Targeted Diagnostics and Therapeutics for Inflammatory Diseases

    PubMed Central

    2016-01-01

    Inflammation, an innate immune response mediated by macrophages, forms the first line of defence to protect our body from the invasion of various pathogens. Although inflammation is a defensive response, chronic inflammation has been regarded as the major cause of many types of human diseases such as inflammatory/autoimmune diseases, cancers, neurological diseases, and cardiovascular diseases. Folate receptor (FR) is a cell surface glycosylphosphatidylinositol (GPI)-anchored glycoprotein, and its three isoforms, FR-α, FR-β, and FR-γ, are found in humans. Interestingly, FRs are highly expressed on a variety of cells, including cancer cells and activated macrophages, whereas their expression on normal cells is undetectable, indicating that FR-targeting could be a good selective strategy for the diagnosis and therapeutic treatment of cancers and activated macrophage-mediated inflammatory diseases. Previous studies successfully showed FR-targeted imaging of many types of cancers in animal models as well as human patients. Recently, a number of emerging studies have found that activated macrophages, which are critical players for a variety of inflammatory diseases, highly express FRs, and selective targeting of these FR-positive activated macrophages is a good approach to diagnose and treat inflammatory diseases. In this review, we describe the characteristics and structure of FRs, and further discuss FR-targeted diagnostics and therapeutics of human diseases, in particular, activated macrophage-mediated inflammatory diseases. PMID:28035209

  2. Parkinson’s disease and enhanced inflammatory response

    PubMed Central

    Stojkovska, Iva; Wagner, Brandon M

    2015-01-01

    Parkinson’s disease (PD) is the first and second most prevalent motor and neurodegenerative disease, respectively. The clinical symptoms of PD result from a loss of midbrain dopaminergic (DA) neurons. However, the molecular cause of DA neuron loss remains elusive. Mounting evidence implicates enhanced inflammatory response in the development and progression of PD pathology. This review examines current research connecting PD and inflammatory response. PMID:25769314

  3. Curcumin protects against cytotoxic and inflammatory effects of quartz particles but causes oxidative DNA damage in a rat lung epithelial cell line

    SciTech Connect

    Li Hui; Berlo, Damien van; Shi Tingming; Speit, Guenter; Knaapen, Ad M.; Borm, Paul J.A.; Albrecht, Catrin; Schins, Roel P.F.

    2008-02-15

    Chronic inhalation of high concentrations of respirable quartz particles has been implicated in various lung diseases including lung fibrosis and cancer. Generation of reactive oxygen species (ROS) and oxidative stress is considered a major mechanism of quartz toxicity. Curcumin, a yellow pigment from Curcuma longa, has been considered as nutraceutical because of its strong anti-inflammatory, antitumour and antioxidant properties. The aim of our present study was to investigate whether curcumin can protect lung epithelial cells from the cytotoxic, genotoxic and inflammatory effects associated with quartz (DQ12) exposure. Electron paramagnetic resonance (EPR) measurements using the spin-trap DMPO demonstrated that curcumin reduces hydrogen peroxide-dependent hydroxyl-radical formation by quartz. Curcumin was also found to reduce quartz-induced cytotoxicity and cyclooxygenase 2 (COX-2) mRNA expression in RLE-6TN rat lung epithelial cells (RLE). Curcumin also inhibited the release of macrophage inflammatory protein-2 (MIP-2) from RLE cells as observed upon treatment with interleukin-1 beta (IL-1{beta}) and tumour necrosis factor-alpha (TNF{alpha}). However, curcumin failed to protect the RLE cells from oxidative DNA damage induced by quartz, as shown by formamidopyrimidine glycosylase (FPG)-modified comet assay and by immunocytochemistry for 8-hydroxydeoxyguanosine. In contrast, curcumin was found to be a strong inducer of oxidative DNA damage itself at non-cytotoxic and anti-inflammatory concentrations. In line with this, curcumin also enhanced the mRNA expression of the oxidative stress response gene heme oxygenase-1 (ho-1). Curcumin also caused oxidative DNA damage in NR8383 rat alveolar macrophages and A549 human lung epithelial cells. Taken together, these observations indicate that one should be cautious in considering the potential use of curcumin in the prevention or treatment of lung diseases associated with quartz exposure.

  4. Curcumin protects against cytotoxic and inflammatory effects of quartz particles but causes oxidative DNA damage in a rat lung epithelial cell line.

    PubMed

    Li, Hui; van Berlo, Damien; Shi, Tingming; Speit, Günter; Knaapen, Ad M; Borm, Paul J A; Albrecht, Catrin; Schins, Roel P F

    2008-02-15

    Chronic inhalation of high concentrations of respirable quartz particles has been implicated in various lung diseases including lung fibrosis and cancer. Generation of reactive oxygen species (ROS) and oxidative stress is considered a major mechanism of quartz toxicity. Curcumin, a yellow pigment from Curcuma longa, has been considered as nutraceutical because of its strong anti-inflammatory, antitumour and antioxidant properties. The aim of our present study was to investigate whether curcumin can protect lung epithelial cells from the cytotoxic, genotoxic and inflammatory effects associated with quartz (DQ12) exposure. Electron paramagnetic resonance (EPR) measurements using the spin-trap DMPO demonstrated that curcumin reduces hydrogen peroxide-dependent hydroxyl-radical formation by quartz. Curcumin was also found to reduce quartz-induced cytotoxicity and cyclooxygenase 2 (COX-2) mRNA expression in RLE-6TN rat lung epithelial cells (RLE). Curcumin also inhibited the release of macrophage inflammatory protein-2 (MIP-2) from RLE cells as observed upon treatment with interleukin-1 beta (IL-1beta) and tumour necrosis factor-alpha (TNFalpha). However, curcumin failed to protect the RLE cells from oxidative DNA damage induced by quartz, as shown by formamidopyrimidine glycosylase (FPG)-modified comet assay and by immunocytochemistry for 8-hydroxydeoxyguanosine. In contrast, curcumin was found to be a strong inducer of oxidative DNA damage itself at non-cytotoxic and anti-inflammatory concentrations. In line with this, curcumin also enhanced the mRNA expression of the oxidative stress response gene heme oxygenase-1 (ho-1). Curcumin also caused oxidative DNA damage in NR8383 rat alveolar macrophages and A549 human lung epithelial cells. Taken together, these observations indicate that one should be cautious in considering the potential use of curcumin in the prevention or treatment of lung diseases associated with quartz exposure.

  5. Bacterial Intestinal Superinfections in Inflammatory Bowel Diseases Beyond Clostridum difficile.

    PubMed

    Lobatón, Triana; Domènech, Eugeni

    2016-07-01

    Besides genetics and environmental factors, intestinal microbiota seem to play a major role in the pathogenesis of inflammatory bowel diseases. For many decades, it has been said that some enteropathogens may even trigger both inflammatory bowel disease development and disease flares. For this reason, stool testing had been performed in inflammatory bowel disease flares but current guidelines only recommend to rule out Clostridium difficile infection and there is no clear advice for other enteropathogens given that the scarce available evidence points at a low prevalence of this sort of intestinal superinfections with no clear impact on disease course. The present article reviews the current knowledge about the role of bacterial enteropathogens on disease pathogenesis and flares beyond C. difficile.

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

    PubMed

    Aparicio, Irene Jarana; Lee, Joyce S

    2016-06-01

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

  7. Idiopathic inflammatory myopathies: definition and management of refractory disease.

    PubMed

    Brandão, Mariana; Marinho, António

    2011-09-01

    Adult idiopathic inflammatory myopathies, commonly referred to as myositis, are a heterogeneous group of diseases with an autoimmune etiology. In this review, the authors are going to focus on myositis excluding inclusion body myositis. They will review the prognostic factors (for mortality and response to steroids), define refractory disease, introduce a new concept (presumed refractory disease), analyze definitions of active disease, damage and improvement criteria, and summarize therapeutic alternatives for refractory patients, based on different disease phenotypes.

  8. Anti-inflammatory treatment in dysfunction of pulmonary surfactant in meconium-induced acute lung injury.

    PubMed

    Mokra, D; Drgova, A; Kopincova, J; Pullmann, R; Calkovska, A

    2013-01-01

    Inflammation, oxidation, lung edema, and other factors participate in surfactant dysfunction in meconium aspiration syndrome (MAS). Therefore, we hypothesized that anti-inflammatory treatment may reverse surfactant dysfunction in the MAS model. Oxygen-ventilated rabbits were given meconium intratracheally (25 mg/ml, 4 ml/kg; Mec) or saline (Sal). Thirty minutes later, meconium-instilled animals were treated by glucocorticoids budesonide (0.25 mg/kg, i.t.) and dexamethasone (0.5 mg/kg, i.v.), or phosphodiesterase inhibitors aminophylline (2 mg/kg, i.v.) and olprinone (0.2 mg/kg, i.v.), or the antioxidant N-acetylcysteine (10 mg/kg, i.v.). Healthy, non-ventilated animals served as controls (Con). At the end of experiments, left lung was lavaged and a differential leukocyte count in sediment was estimated. The supernatant of lavage fluid was adjusted to a concentration of 0.5 mg phospholipids/ml. Surfactant quality was evaluated by capillary surfactometer and expressed by initial pressure and the time of capillary patency. The right lung was used to determine lung edema by wet/dry (W/D) weight ratio. Total antioxidant status (TAS) in blood plasma was evaluated. W/D ratio increased and capillary patency time shortened significantly, whereas the initial pressure increased and TAS decreased insignificantly in Sal vs. Con groups. Meconium instillation potentiated edema formation and neutrophil influx into the lungs, reduced capillary patency and TAS, and decreased the surfactant quality compared with both Sal and Con groups (p > 0.05). Each of the anti-inflammatory agents reduced lung edema and neutrophil influx into the lung and partly reversed surfactant dysfunction in the MAS model, with a superior effect observed after glucocorticoids and the antioxidant N-acetylcysteine.

  9. Eicosapentaenoic acid attenuates cigarette smoke-induced lung inflammation by inhibiting ROS-sensitive inflammatory signaling

    PubMed Central

    Liu, Meng-Han; Lin, An-Hsuan; Lu, Shing-Hwa; Peng, Ruo-Yun; Lee, Tzong-Shyuan; Kou, Yu Ru

    2014-01-01

    Cigarette smoking causes chronic lung inflammation that is mainly regulated by redox-sensitive pathways. Our previous studies have demonstrated that cigarette smoke (CS) activates reactive oxygen species (ROS)-sensitive mitogen-activated protein kinases (MAPKs)/nuclear factor-κB (NF-κB) signaling resulting in induction of lung inflammation. Eicosapentaenoic acid (EPA), a major type of omega-3 polyunsaturated fatty acid, is present in significant amounts in marine-based fish and fish oil. EPA has been shown to possess antioxidant and anti-inflammatory properties in vitro and in vivo. However, whether EPA has similar beneficial effects against CS-induced lung inflammation remains unclear. Using a murine model, we show that subchronic CS exposure for 4 weeks caused pulmonary inflammatory infiltration (total cell count in bronchoalveolar lavage fluid (BALF), 11.0-fold increase), increased lung vascular permeability (protein level in BALF, 3.1-fold increase), elevated levels of chemokines (11.4–38.2-fold increase) and malondialdehyde (an oxidative stress biomarker; 2.0-fold increase) in the lungs, as well as lung inflammation; all of these CS-induced events were suppressed by daily supplementation with EPA. Using human bronchial epithelial cells, we further show that CS extract (CSE) sequentially activated NADPH oxidase (NADPH oxidase activity, 1.9-fold increase), increased intracellular levels of ROS (3.0-fold increase), activated both MAPKs and NF-κB, and induced interleukin-8 (IL-8; 8.2-fold increase); all these CSE-induced events were inhibited by pretreatment with EPA. Our findings suggest a novel role for EPA in alleviating the oxidative stress and lung inflammation induced by subchronic CS exposure in vivo and in suppressing the CSE-induced IL-8 in vitro via its antioxidant function and by inhibiting MAPKs/NF-κB signaling. PMID:25452730

  10. Discovery of a New Inhibitor of Myeloid Differentiation 2 from Cinnamamide Derivatives with Anti-Inflammatory Activity in Sepsis and Acute Lung Injury.

    PubMed

    Chen, Gaozhi; Zhang, Yali; Liu, Xing; Fang, Qilu; Wang, Zhe; Fu, Lili; Liu, Zhiguo; Wang, Yi; Zhao, Yunjie; Li, Xiaokun; Liang, Guang

    2016-03-24

    Acute inflammatory diseases, including acute lung injury and sepsis, remain the most common life-threatening illness in intensive care units worldwide. Cinnamamide has been incorporated in several synthetic compounds with therapeutic potentials including anti-inflammatory properties. However, the possible mechanism and direct molecular target of cinnamamides for their anti-inflammatory effects were rarely investigated. In this study, we synthesized a series of cinnamamides and evaluated their anti-inflammatory activities. The most active compound, 2i, was found to block LPS-induced MD2/TLR4 pro-inflammatory signaling activation in vitro and to attenuate LPS-caused sepsis and acute lung injury in vivo. Mechanistically, we demonstrated that 2i exerts its anti-inflammatory effects by directly targeting and binding MD2 in Arg90 and Tyr102 residues and inhibiting MD2/TLR4 complex formation. Taken together, this work presents a novel MD2 inhibitor, 2i, which has the potential to be developed as a candidate for the treatment of sepsis, and provides a new lead structure for the development of anti-inflammatory agents targeting MD2.

  11. Inflammatory cytokines, goblet cell hyperplasia and altered lung mechanics in Lgl1+/- mice

    PubMed Central

    2009-01-01

    Background Neonatal lung injury, a leading cause of morbidity in prematurely born infants, has been associated with arrested alveolar development and is often accompanied by goblet cell hyperplasia. Genes that regulate alveolarization and inflammation are likely to contribute to susceptibility to neonatal lung injury. We previously cloned Lgl1, a developmentally regulated secreted glycoprotein in the lung. In rat, O2 toxicity caused reduced levels of Lgl1, which normalized during recovery. We report here on the generation of an Lgl1 knockout mouse in order to determine whether deficiency of Lgl1 is associated with arrested alveolarization and contributes to neonatal lung injury. Methods An Lgl1 knockout mouse was generated by introduction of a neomycin cassette in exon 2 of the Lgl1 gene. To evaluate the pulmonary phenotype of Lgl1+/- mice, we assessed lung morphology, Lgl1 RNA and protein, elastin fibers and lung function. We also analyzed tracheal goblet cells, and expression of mucin, interleukin (IL)-4 and IL-13 as markers of inflammation. Results Absence of Lgl1 was lethal prior to lung formation. Postnatal Lgl1+/- lungs displayed delayed histological maturation, goblet cell hyperplasia, fragmented elastin fibers, and elevated expression of TH2 cytokines (IL-4 and IL-13). At one month of age, reduced expression of Lgl1 was associated with elevated tropoelastin expression and altered pulmonary mechanics. Conclusion Our findings confirm that Lgl1 is essential for viability and is required for developmental processes that precede lung formation. Lgl1+/- mice display a complex phenotype characterized by delayed histological maturation, features of inflammation in the post-natal period and altered lung mechanics at maturity. Lgl1 haploinsufficiency may contribute to lung disease in prematurity and to increased risk for late-onset respiratory disease. PMID:19772569

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

    PubMed

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

    2015-02-01

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

  13. Progressive lung disease in a malt-worker.

    PubMed Central

    Ellis, M E; Friend, J A

    1981-01-01

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

  14. Chronic suppurative lung disease in adults

    PubMed Central

    Mangardich, Antranik

    2016-01-01

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

  15. 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.

  16. Nontypeable Haemophilus influenzae in chronic obstructive pulmonary disease and lung cancer.

    PubMed

    Moghaddam, Seyed Javad; Ochoa, Cesar E; Sethi, Sanjay; Dickey, Burton F

    2011-01-01

    Chronic obstructive pulmonary disease (COPD) is predicted to become the third leading cause of death in the world by 2020. It is characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lungs to noxious particles and gases, most commonly cigarette smoke. Among smokers with COPD, even following withdrawal of cigarette smoke, inflammation persists and lung function continues to deteriorate. One possible explanation is that bacterial colonization of smoke-damaged airways, most commonly with nontypeable Haemophilus influenzae (NTHi), perpetuates airway injury and inflammation. Furthermore, COPD has also been identified as an independent risk factor for lung cancer irrespective of concomitant cigarette smoke exposure. In this article, we review the role of NTHi in airway inflammation that may lead to COPD progression and lung cancer promotion.

  17. 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

  18. Biopharmaceuticals: reference products and biosimilars to treat inflammatory diseases.

    PubMed

    Gils, Ann; Bertolotto, Antonio; Mulleman, Denis; Bejan-Angoulvant, Theodora; Declerck, Paul J

    2017-02-20

    Biopharmaceuticals are primarily therapeutic proteins developed to perform specific functions by acting on the disease pathophysiology. Compared to low molecular chemically synthesized drugs, production of biopharmaceuticals is much more complex and routes of administration and pharmacokinetics differ. Biopharmaceuticals are blockbusters in the treatment of inflammatory diseases such as psoriasis, multiple sclerosis, rheumatic diseases, and inflammatory bowel diseases, and the introduction of these drugs has revolutionized treatment. Disadvantages include their high costs and the fact that they can evoke antidrug antibodies leading to decreased efficacy. Treatment can be optimized through the development of dosing algorithms and cost can be reduced by biosimilars, after a comparable biological activity, safety, and efficacy have been demonstrated.

  19. Serological markers in inflammatory bowel disease: the pros and cons.

    PubMed

    Lerner, Aaron; Shoenfeld, Yehuda

    2002-02-01

    Accurate serological assays are desirable for the diagnosis of inflammatory bowel disease. Among several serological markers anti-Saccharomyces cerevisiae mannan antibodies and perinuclear antineutrophil cytoplasmic autoantibodies are highly disease specific for Crohn's disease and ulcerative colitis, respectively. Combining the two improves their specificity. Sensitivity, however, is still low. Due to lack of standardization and vast interobserver variability, they cannot be used as the only diagnostic criteria but can assist clinicians in diagnosing and categorizing patients with inflammatory bowel disease as well as in helping them to take therapeutic decisions.

  20. Study of inflammatory responses to crocidolite and basalt wool in the rat lung.

    PubMed

    Adamis, Z; Kerényi, T; Honma, K; Jäckel, M; Tátrai, E; Ungváry, G

    2001-03-09

    The subacute effects of crocidolite and basalt wool dusts were studied by nmeans of biochemical, morphological. and histological methods 1 and .3 mo after intrabronchial instillation. The cell count, protein and phospholipid contents, and lactate dehydrogenase (LDH) activity were determined in the bronchoalveolar lavage (BAL). Both types of fibers induced a prolonged inflammatory reaction in the lung. All the parameters studied in the experimental groups were more markedly elevated after 3 mo. Relative to the control, the protein and LDH values were increased three- to fivefold, the phospholipid content twofold, and the number of free cells in the BAL exceeded the control level up to ninefold. The inflammatory responses to crocidolite and basalt wool in the lung did not differ significantly. In spite of this, basalt wool is recoinmended as an asbestos substitute, as the use of this man-nade fiber may result in a significantly lower release of dust than that from crocidolite.

  1. Therapeutic antibodies that target inflammatory cytokines in autoimmune diseases.

    PubMed

    Lai, Yuping; Dong, Chen

    2016-04-01

    Inflammatory cytokines are key regulators of immune responses. Persistent and excessive production of inflammatory cytokines underscores the development of autoimmune diseases. Therefore, neutralizing inflammatory cytokines or antagonizing their receptor function is considered as a useful therapeutic strategy to treat autoimmune diseases. To achieve the success of such a strategy, understanding of the complex actions of these cytokines and cytokine networks is required. In this review we focus on four inflammatory cytokines--tumor necrosis factor α (TNFα), interleukin-6 (IL-6), IL-23 and IL-17--and dissect how the dysregulation of these cytokines regulates autoimmune diseases. On the basis of pre-clinical and clinical data, we specifically discuss the therapeutic rationale for targeting these cytokines and describe the potential adverse effects.

  2. Discovery of new MD2 inhibitor from chalcone derivatives with anti-inflammatory effects in LPS-induced acute lung injury

    PubMed Central

    Zhang, Yali; Wu, Jianzhang; Ying, Shilong; Chen, Gaozhi; Wu, Beibei; Xu, Tingting; Liu, Zhiguo; Liu, Xing; Huang, Lehao; Shan, Xiaoou; Dai, Yuanrong; Liang, Guang

    2016-01-01

    Acute lung injury (ALI) is a life-threatening acute inflammatory disease with limited options available for therapy. Myeloid differentiation protein 2, a co-receptor of TLR4, is absolutely required for TLR4 sense LPS, and represents an attractive target for treating severe inflammatory diseases. In this study, we designed and synthesized 31 chalcone derivatives that contain the moiety of (E)-4-phenylbut-3-en-2-one, which we consider the core structure of current MD2 inhibitors. We first evaluated the anti-inflammatory activities of these compounds in MPMs. For the most active compound 20, we confirmed that it is a specific MD2 inhibitor through a series of biochemical experiments and elucidated that it binds to the hydrophobic pocket of MD2 via hydrogen bonds with Arg90 and Tyr102 residues. Compound 20 also blocked the LPS-induced activation of TLR4/MD2 -downstream pro-inflammatory MAPKs/NF-κB signaling pathways. In a rat model with ALI induced by intracheal LPS instillation, administration with compound 20 exhibited significant protective effect against ALI, accompanied by the inhibition of TLR4/MD2 complex formation in lung tissues. Taken together, the results of this study suggest the specific MD2 inhibitor from chalcone derivatives we identified is a potential candidate for treating acute inflammatory diseases. PMID:27118147

  3. In vitro effects of oxpentifylline on inflammatory cytokine release in patients with inflammatory bowel disease.

    PubMed Central

    Reimund, J M; Dumont, S; Muller, C D; Kenney, J S; Kedinger, M; Baumann, R; Poindron, P; Duclos, B

    1997-01-01

    BACKGROUND: Inflammatory cytokines, including tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1 beta, have been implicated as primary mediators of intestinal inflammation in inflammatory bowel disease. AIM: To investigate the in vitro effects of oxpentifylline (pentoxifylline; PTX; a phosphodiesterase inhibitor) on inflammatory cytokine production (1) by peripheral mononuclear cells (PBMCs) and (2) by inflamed intestinal mucosa cultures from patients with Crohn's disease and patients with ulcerative colitis. METHODS: PBMCs and mucosal biopsy specimens were cultured for 24 hours in the absence or presence of PTX (up to 100 micrograms/ml), and the secretion of TNF-alpha, IL-1 beta, IL-6, and IL-8 determined by enzyme linked immunosorbent assays (ELISAs). RESULTS: PTX inhibited the release of TNF-alpha by PBMCs from patients with inflammatory bowel disease and the secretion of TNF-alpha and IL-1 beta by organ cultures of inflamed mucosa from the same patients. Secretion of TNF-alpha by PBMCs was inhibited by about 50% at a PTX concentration of 25 micrograms/ml (IC50). PTX was equally potent in cultures from controls, patients with Crohn's disease, and those with ulcerative colitis. The concentrations of IL-6 and IL-8 were not significantly modified in PBMCs, but IL-6 increased slightly in organ culture supernatants. CONCLUSIONS: PTX or more potent related compounds may represent a new family of cytokine inhibitors, potentially interesting for treatment of inflammatory bowel disease. PMID:9176074

  4. [Chorioamnionitis and inflammatory disease in the premature newborn infant].

    PubMed

    Vedovato, S; Zanardo, V

    2010-06-01

    Preterm births occurs in 6-12% of all pregnancies, accounts for 75% of neonatal death and causes significant neonatal morbidity. A large number of preterm birth is associated with infection (30%), because of the release of many cytokines. In fact acute chorioamnionitis represents the inflammatory response to extracellular microorganisms that gain access to the gestational sac. Clinical signs of infection compare in the 12% of cases, while the prevalence of positive amniotic fluid cultures is approximately 50% in patients with preterm PROM. Despite the recent studies about the dosage of inflammatory biomarkers in the amniotic fluid or in fetal and maternal blood, placenta histology remains the gold standard for the diagnosis of chorioamnionitis. Histological chorioamnionitis describes the progression of the inflammatory process. Organisms first colonise the chorioamnionic surface. Then, the neutrophils migrates to the chorion (chorionitis) and to the amnion (chorioamnionitis) and, in the last stage, amnionic epithelial cells undergo necrosis (necrotising chorioamnionitis). It represents the mother inflammatory response and it differs from the fetal inflammatory response (funisitis). Funisitis first appears in vessels of the chorionic plate (chorionic vasculitis) or in the umbilical vein (umbilical phlebitis), then in the umbilical artery (umbilical arteritis), and in the Wharton's jelly (umbilical perivasculitis). The fetal inflammatory response has been associated with inflammatory diseases of preterm infants, increasing the risk of neonatal sepsis and meningitis, bronchopulmonary dysplasia and cerebral palsy. We present our experience on the relationship between histological chorioamnionitis, preterm birth and inflammatory diseases of VLBW infants.

  5. Diabetic Retinopathy: Vascular and Inflammatory Disease

    PubMed Central

    Semeraro, F.; Cancarini, A.; dell'Omo, R.; Rezzola, S.; Romano, M. R.; Costagliola, C.

    2015-01-01

    Diabetic retinopathy (DR) is the leading cause of visual impairment in the working-age population of the Western world. The pathogenesis of DR is complex and several vascular, inflammatory, and neuronal mechanisms are involved. Inflammation mediates structural and molecular alterations associated with DR. However, the molecular mechanisms underlying the inflammatory pathways associated with DR are not completely characterized. Previous studies indicate that tissue hypoxia and dysregulation of immune responses associated with diabetes mellitus can induce increased expression of numerous vitreous mediators responsible for DR development. Thus, analysis of vitreous humor obtained from diabetic patients has made it possible to identify some of the mediators (cytokines, chemokines, and other factors) responsible for DR pathogenesis. Further studies are needed to better understand the relationship between inflammation and DR. Herein the main vitreous-related factors triggering the occurrence of retinal complication in diabetes are highlighted. PMID:26137497

  6. Skin gangrene as an extraintestinal manifestation of inflammatory bowel disease*

    PubMed Central

    Komatsu, Yumi Cristina; Capareli, Gabriela Cunha; Boin, Maria Fernanda Feitosa de Camargo; Lellis, Rute; de Freitas, Thaís Helena Proença; Simone, Karine

    2014-01-01

    Inflammatory bowel diseases can commonly present many cutaneous lesions which can contribute to the diagnosis of the disease or its activity. The most frequent cutaneous or mucocutaneous manifestations suggesting ulcerative rectocolitis activity are erythema nodosum (3-10%), pyoderma gangrenosum (5-12%) and aphthous stomatitis (4%). Other reactive skin manifestations related to immunological mechanisms associated with the inflammatory bowel disease are: Sweet's syndrome, arthritis-dermatitis syndrome associated with inflammatory bowel disease and leukocytoclastic vasculitis. We describe the case of a young man with diagnosis of ulcerative rectocolitis, which presented an extensive cutaneous gangrene secondary to microvascular thrombosis. The case represents a dermatologic rarity and should be recognized as a cutaneous manifestation related to the hypercoagulability state observed in the disease's activity. PMID:25387503

  7. Skin gangrene as an extraintestinal manifestation of inflammatory bowel disease.

    PubMed

    Komatsu, Yumi Cristina; Capareli, Gabriela Cunha; Boin, Maria Fernanda Feitosa de Camargo; Lellis, Rute; Freitas, Thaís Helena Proença de; Simone, Karine

    2014-01-01

    Inflammatory bowel diseases can commonly present many cutaneous lesions which can contribute to the diagnosis of the disease or its activity. The most frequent cutaneous or mucocutaneous manifestations suggesting ulcerative rectocolitis activity are erythema nodosum (3-10%), pyoderma gangrenosum (5-12%) and aphthous stomatitis (4%). Other reactive skin manifestations related to immunological mechanisms associated with the inflammatory bowel disease are: Sweet's syndrome, arthritis-dermatitis syndrome associated with inflammatory bowel disease and leukocytoclastic vasculitis. We describe the case of a young man with diagnosis of ulcerative rectocolitis, which presented an extensive cutaneous gangrene secondary to microvascular thrombosis. The case represents a dermatologic rarity and should be recognized as a cutaneous manifestation related to the hypercoagulability state observed in the disease's activity.

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

    PubMed

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

    2011-06-01

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

  9. Anti-Inflammatory Effects of Adrenomedullin on Acute Lung Injury Induced by Carrageenan in Mice

    PubMed Central

    Elena, Talero; Rosanna, Di Paola; Emanuela, Mazzon; Esposito, Emanuela; Virginia, Motilva; Salvatore, Cuzzocrea

    2012-01-01

    Adrenomedullin (AM) is a 52 amino acid peptide that has shown predominant anti-inflammatory activities. In the present study, we evaluated the possible therapeutic effect of this peptide in an experimental model of acute inflammation, the carrageenan- (CAR-) induced pleurisy. Pleurisy was induced by injection of CAR into the pleural cavity of mice. AM (200 ng/kg) was administered by intraperitoneal route 1 h after CAR, and the animals were sacrificed 4 h after that. AM treatment attenuated the recruitment of leucocytes in the lung tissue and the generation and/or the expression of the proinflammatory cytokines as well as the expression of the intercellular cell adhesion molecules. Moreover, AM inhibited the induction of inducible nitric oxide synthase (iNOS), thereby abating the generation of nitric oxide (NO) and prevented the oxidative and nitroxidative lung tissue injury, as shown by the reduction of nitrotyrosine, malondialdehyde (MDA), and poly (ADP-ribose) polymerase (PARP) levels. Finally, we demonstrated that these anti-inflammatory effects of AM were associated with the inhibition of nuclear factor-κB (NF-κB) activation. All these parameters were markedly increased by intrapleural CAR in the absence of any treatment. We report that treatment with AM significantly reduces the development of acute lung injury by downregulating a broad spectrum of inflammatory factors. PMID:22685374

  10. AGER -429T/C Is Associated with an Increased Lung Disease Severity in Cystic Fibrosis

    PubMed Central

    Beucher, Julie; Boëlle, Pierre-Yves; Busson, Pierre-François; Muselet-Charlier, Céline; Clement, Annick; Corvol, Harriet; Abely, M.; Belleguic, C.; Bellon, G.; Bessaci, K.; Bonnel, A.S.; Brémont, F.; Brouard, J.; Bui, S.; Chiron, R.; Chumbi-Flores, R.; Clement, A.; Corvol, H.; Dalphin, J.C.; Dalphin, M.L.; David, V.; de Miranda, S.; Derelle, J.; Domblides, P.; Dominique, S.; Dubus, J.C.; Durieu, I.; Dury, S.; Ellaffi, M.; Epaud, R.; Fanton, A.; Fayon, M.; Fleurence, E.; Foucaud, P.; Ginies, J.L.; Godbert, B.; Grenet, D.; Guillot, M.; Héraud, M. C.; Housset, B.; Hubert, D.; Huet, F.; Kessler, R.; Labbé, A.; Laurans, M.; le Bourgeois, M.; le Roux, P.; Llerena, C.; Loeuille, G.A.; Marguet, C.; Mely, L.; Moisan-Petit, V.; Munck, A.; Murris-Espin, M.; Nove Josserand, R.; Pautard, J.C.; Pin, I.; Pramil, S.; Prevotat, A.; Rault, G.; Reix, P.; Remus, N.; Renouil, M.; Reynaud-Gaubert, M.; Richaud Thiriez, B.; Roussey, M.; Sermet-Gaudelus, I.; Stremler, N.; Uffredi, M.L.; Urban, T.; Vigneron, P.; Wallaert, B.; Weiss, L.

    2012-01-01

    The clinical course of cystic fibrosis (CF) varies between patients bearing identical CFTR mutations, suggesting the involvement of modifier genes. We assessed the association of lung disease severity with the variant AGER -429 T/C, coding for RAGE, a pro-inflammatory protein, in CF patients from the French CF Gene Modifier Study. We analyzed the lung function of 967 CF patients p.Phe508del homozygous. FEV1 was analyzed as CF-specific percentile adjusted on age, height and mortality. AGER -429T/C polymorphism was genotyped and its function was evaluated in vitro by measurement of the luciferase activity. AGER -429 minor allele (C) was associated with poorer lung function (p = 0.03). In vitro, the promoter activity was higher in cells transfected with AGER -429C compared to cells transfected with the AGER -429T allele (p = 0.016 in BEAS-2B cells). AGER seems to be a modifier gene of lung disease severity in CF, and could be an interesting biomarker of CF airway inflammation. The functional promoter AGER -429C variant is associated with an increased RAGE expression that can lead to an increased lung inflammation and a more severe lung disease. PMID:22860029

  11. AGER -429T/C is associated with an increased lung disease severity in cystic fibrosis.

    PubMed

    Beucher, Julie; Boëlle, Pierre-Yves; Busson, Pierre-François; Muselet-Charlier, Céline; Clement, Annick; Corvol, Harriet

    2012-01-01

    The clinical course of cystic fibrosis (CF) varies between patients bearing identical CFTR mutations, suggesting the involvement of modifier genes. We assessed the association of lung disease severity with the variant AGER -429 T/C, coding for RAGE, a pro-inflammatory protein, in CF patients from the French CF Gene Modifier Study. We analyzed the lung function of 967 CF patients p.Phe508del homozygous. FEV(1) was analyzed as CF-specific percentile adjusted on age, height and mortality. AGER -429T/C polymorphism was genotyped and its function was evaluated in vitro by measurement of the luciferase activity. AGER -429 minor allele (C) was associated with poorer lung function (p = 0.03). In vitro, the promoter activity was higher in cells transfected with AGER -429C compared to cells transfected with the AGER -429T allele (p = 0.016 in BEAS-2B cells). AGER seems to be a modifier gene of lung disease severity in CF, and could be an interesting biomarker of CF airway inflammation. The functional promoter AGER -429C variant is associated with an increased RAGE expression that can lead to an increased lung inflammation and a more severe lung disease.

  12. Adipokine CTRP-5 as a Potential Novel Inflammatory Biomarker in Chronic Obstructive Pulmonary Disease

    PubMed Central

    Li, Diandian; Wu, Yanqiu; Tian, Panwen; Zhang, Xue; Wang, Hao; Wang, Tao; Ying, Binwu; Wang, Lanlan; Shen, Yongchun; Wen, Fuqiang

    2015-01-01

    Abstract Local and systemic inflammation often present in chronic obstructive pulmonary disease (COPD). Adipokines are secretory protein mediators by adipose tissue, which have been found to involve in inflammatory responses in many chronic inflammatory diseases. Therefore, we performed this preliminary clinical study to investigate the possible association between 2 adipokines, C1q/tumor necrosis factor-related protein-3 and -5 (CTRP-3 and CTRP-5), with lung function and other markers of inflammation in COPD. Serum CTRP-3 and CTRP-5 levels were measured in 73 COPD patients and 54 health controls, together with lung function and levels of adiponectin, CRP, TNF-α, and MPO in both groups. Pearson's partial correlation was used to analyze the correlations between CTRPs and other serum markers or lung function. Serum CTRP-5 was significantly elevated in COPD patients (0.41 ± 0.35 versus 0.29 ± 0.28 μg/ml, P = 0.01) and correlated inversely with FEV1/FVC ratio in all patients (r = −0.31, P = 0.001). In COPD patients, CTRP-5 was also correlated negatively with FEV1% predicted (r = −0.464, P < 0.001) and had a positive association with CRP levels (r = 0.262, P = 0.04). However, serum CTRP-3 levels were not correlated with measures of lung function or systemic inflammation. In conclusion, circulating CTRP-5 was associated with the severity of airflow obstruction and systemic inflammation in patients with COPD, which suggests that it may be used as a potential novel inflammatory biomarker in COPD. Further studies should be performed to clarify the exact role of CTRP-5 on the pathogenesis and outcomes of COPD. PMID:26356719

  13. Update on Janus Kinase Antagonists in Inflammatory Bowel Disease

    PubMed Central

    Boland, Brigid S.; Sandborn, William J.; Chang, John T.

    2014-01-01

    Janus kinase (JAK) inhibitors have emerged as a novel orally administered small molecule therapy for the treatment of ulcerative colitis and possibly Crohn’s disease. These molecules are designed to selectively target the activity of specific JAKs and offer a targeted mechanism of action without risk of immunogenicity. Based on data from clinical trials in rheumatoid arthritis and phase 2 studies in inflammatory bowel disease, tofacitinib and other JAK inhibitors are likely to become a new form of medical therapy for the treatment of inflammatory bowel disease. PMID:25110261

  14. Inflammatory bowel disease related innate immunity and adaptive immunity.

    PubMed

    Huang, Yuan; Chen, Zhonge

    2016-01-01

    Inflammatory bowel disease (IBD) is a chronic nonspecific intestinal inflammatory disease, including ulcerative colitis (UC) and Crohn's disease (CD). Its pathogenesis remains not yet clear. Current researchers believe that after environmental factors act on individuals with genetic susceptibility, an abnormal intestinal immune response is launched under stimulation of intestinal flora. However, previous studies only focused on adaptive immunity in the pathogenesis of IBD. Currently, roles of innate immune response in the pathogenesis of intestinal inflammation have also drawn much attention. In this study, IBD related innate immunity and adaptive immunity were explained, especially the immune mechanisms in the pathogenesis of IBD.

  15. Vaccines and recommendations for their use in inflammatory bowel disease

    PubMed Central

    Sánchez-Tembleque, María Dolores; Corella, Carmen; Pérez-Calle, Jose L

    2013-01-01

    The patient with inflammatory bowel disease will be predisposed to numerous infections due their immune status. It is therefore important to understand the immune and serologic status at diagnosis and to put the patient into an adapted vaccination program. This program would be applied differently according to two patient groups: the immunocompromised and the non-immunocom-promised. In general, the first group would avoid the use of live-virus vaccines, and in all cases, inflammatory bowel disease treatment would take precedence over vaccine risk. It is important to individualize vaccination schedules according to the type of patient, the treatment used and the disease pattern.In addition, patient with inflammatory bowel disease should be considered for the following vaccines: varicella vaccine, human papilloma virus, influenza, pneumococcal polysaccharide vaccine and hepatitis B vaccine. PMID:23538680

  16. Control of inflammatory heart disease by CD4+ T cells.

    PubMed

    Barin, Jobert G; Čiháková, Daniela

    2013-05-01

    This review focuses on autoimmune myocarditis and its sequela, inflammatory dilated cardiomyopathy (DCMI), and the inflammatory and immune mechanisms underlying the pathogenesis of these diseases. Several mouse models of myocarditis and DCMI have improved our knowledge of the pathogenesis of these diseases, informing more general problems of cardiac remodeling and heart failure. CD4(+) T cells are critical in driving the pathogenesis of myocarditis. We discuss in detail the role of T helper cell subtypes in the pathogenesis of myocarditis, the biology of T cell-derived effector cytokines, and the participation of other leukocytic effectors in mediating disease pathophysiology. We discuss interactions between these subsets in both suppressive and collaborative fashions. These findings indicate that cardiac inflammatory disease, and autoimmunity in general, may be more diverse in divergent effector mechanisms than has previously been appreciated.

  17. Extraintestinal manifestations and complications in inflammatory bowel diseases

    PubMed Central

    Rothfuss, Katja S; Stange, Eduard F; Herrlinger, Klaus R

    2006-01-01

    Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases (IBD) that often involve organs other than those of the gastrointestinal tract. These nonintestinal affections are termed extraintestinal symptoms. Differentiating the true extraintestinal manifestations of inflammatory bowel diseases from secondary extraintestinal complications, caused by malnutrition, chronic inflammation or side effects of therapy, may be difficult. This review concentrates on frequency, clinical presentation and therapeutic implications of extraintestinal symptoms in inflammatory bowel diseases. If possible, extraintestinal manifestations are differentiated from extraintestinal complications. Special attention is given to the more recently described sites of involvement; i.e. thromboembolic events, osteoporosis, pulmonary involvement and affection of the central nervous system. PMID:16937463

  18. Endoscopic Diagnosis and Differentiation of Inflammatory Bowel Disease

    PubMed Central

    Lee, Ji Min; Lee, Kang-Moon

    2016-01-01

    Patients with inflammatory bowel disease have significantly increased in recent decades in Korea. Intestinal tuberculosis (ITB) and intestinal Behcet’s disease (BD), which should be differentiated from Crohn’s disease (CD), are more frequent in Korea than in the West. Thus, the accurate diagnosis of these inflammatory diseases is problematic in Korea and clinicians should fully understand their clinical and endoscopic characteristics. Ulcerative colitis mostly presents with rectal inflammation and continuous lesions, while CD presents with discontinuous inflammatory lesions and frequently involves the ileocecal area. Involvement of fewer than four segments, a patulous ileocecal valve, transverse ulcers, and scars or pseudopolyps are more frequently seen in ITB than in CD. A few ulcers with discrete margins are a typical endoscopic finding of intestinal BD. However, the differential diagnosis is difficult in many clinical situations because typical endoscopic findings are not always observed. Therefore, clinicians should also consider symptoms and laboratory, pathological, and radiological findings, in addition to endoscopic findings. PMID:27484813

  19. [Inflammatory spinal diseases: axial spondyloarthritis : Central importance of imaging].

    PubMed

    Baraliakos, X; Fruth, M; Kiltz, U; Braun, J

    2017-03-01

    The diagnosis of axial spondyloarthritis (axSpA) includes classical ankylosing spondylitis (AS) as well as earlier stages and abortive courses of the disease, in which structural alterations have not yet occurred. These are classified as non-radiographic axSpA (nr-axSpa). Inflammatory changes in the entire axial skeleton are characteristic for axSpA and can be visualized by magnetic resonance imaging (MRI), while in most patients structural alterations, such as new bone formation with syndesmophytes and ankylosis develop in the later course of the disease. These bony alterations can best be visualized by conventional radiography and by computed tomography. Certain MRI sequences are nowadays considered as the standard method for depiction of inflammatory changes in axSpA. The introduction of MRI has led to a paradigm shift for this disease because the inflammatory lesions characteristic for the disease can be visualized at an early stage using appropriate MRI sequences.

  20. Primary Histoplasma capsulatum Enterocolitis Mimicking Peptic and Inflammatory Bowel Disease

    PubMed Central

    Nakshabendi, Rahman; Torres-Miranda, Daisy; LaBarbera, Francis Daniel; Nakshabandi, Ahmad; Nakshabendi, Imad

    2016-01-01

    In immunocompromised patients, histoplasmosis may present as disseminated disease. We present a 52-year-old Caucasian male with symptoms of dyspepsia, postprandial epigastric pain, nausea, and nonbloody diarrhea. Upper and lower gastrointestinal endoscopies were suspicious for inflammatory bowel disease (IBD); however, biopsies were consistent with histoplasmosis, specifically in the duodenum. PMID:27812393

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

    SciTech Connect

    Akino, T.; Ohno, K.

    1981-01-01

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

  2. Management of Musculoskeletal Manifestations in Inflammatory Bowel Disease

    PubMed Central

    Sheth, Tejas; Pitchumoni, C. S.; Das, Kiron M.

    2015-01-01

    Musculoskeletal manifestations are the most common extraintestinal manifestations in inflammatory bowel diseases. Some appendicular manifestations are independent of gut inflammation and are treated with standard anti-inflammatory strategies. On the other hand, axial involvement is linked to gut inflammatory activity; hence, there is a considerable amount of treatment overlap. Biological therapies have revolutionized management of inflammatory bowel diseases as well as of associated articular manifestations. Newer mechanisms driving gut associated arthropathy have surfaced in the past decade and have enhanced our interests in novel treatment targets. Introduction of biosimilar molecules is expected in the US market in the near future and will provide an opportunity for considerable cost savings on healthcare. A multidisciplinary approach involving a gastroenterologist, rheumatologist, and physical therapist is ideal for these patients. PMID:26170832

  3. Lucinactant attenuates pulmonary inflammatory response, preserves lung structure, and improves physiologic outcomes in a preterm lamb model of RDS

    PubMed Central

    Wolfson, Marla R.; Wu, Jichuan; Hubert, Terrence L.; Gregory, Timothy J.; Mazela, Jan; Shaffer, Thomas H.

    2013-01-01

    Background Acute inflammatory responses to supplemental oxygen and mechanical ventilation have been implicated in the pathophysiological sequelae of respiratory distress syndrome (RDS). Although surfactant replacement therapy (SRT) has contributed to lung stability, the effect on lung inflammation is inconclusive. Lucinactant contains sinapultide (KL4), a novel synthetic peptide that functionally mimics surfactant protein B, a protein with anti-inflammatory properties. We tested the hypothesis that lucinactant may modulate lung inflammatory response to mechanical ventilation in the management of RDS and may confer greater protection than animal-derived surfactants. Methods Preterm lambs (126.8 ± 0.2 SD d gestation) were randomized to receive lucinactant, poractant alfa, beractant, or no surfactant and studied for 4 h. Gas exchange and pulmonary function were assessed serially. Lung inflammation biomarkers and lung histology were assessed at termination. Results SRT improved lung compliance relative to no SRT without significant difference between SRT groups. Lucinactant attenuated lung and systemic inflammatory response, supported oxygenation at lower ventilatory requirements, and preserved lung structural integrity to a greater degree than either no SRT or SRT with poractant alfa or beractant. Conclusion These data suggest that early intervention with lucinactant may more effectively mitigate pulmonary pathophysiological sequelae of RDS than the animal-derived surfactants poractant alfa or beractant. PMID:22821059

  4. 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.

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

    PubMed Central

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

    1998-01-01

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

 PMID:9797766

  6. 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

  7. Interleukin-1 in the pathogenesis and treatment of inflammatory diseases

    PubMed Central

    2011-01-01

    More than any other cytokine family, the IL-1 family of ligands and receptors is primarily associated with acute and chronic inflammation. The cytosolic segment of each IL-1 receptor family member contains the Toll-IL-1-receptor domain. This domain is also present in each Toll-like receptor, the receptors that respond to microbial products and viruses. Since Toll-IL-1-receptor domains are functional for both receptor families, responses to the IL-1 family are fundamental to innate immunity. Of the 11 members of the IL-1 family, IL-1β has emerged as a therapeutic target for an expanding number of systemic and local inflammatory conditions called autoinflammatory diseases. For these, neutralization of IL-1β results in a rapid and sustained reduction in disease severity. Treatment for autoimmune diseases often includes immunosuppressive drugs whereas neutralization of IL-1β is mostly anti-inflammatory. Although some autoinflammatory diseases are due to gain-of-function mutations for caspase-1 activity, common diseases such as gout, type 2 diabetes, heart failure, recurrent pericarditis, rheumatoid arthritis, and smoldering myeloma also are responsive to IL-1β neutralization. This review summarizes acute and chronic inflammatory diseases that are treated by reducing IL-1β activity and proposes that disease severity is affected by the anti-inflammatory members of the IL-1 family of ligands and receptors. PMID:21304099

  8. SWCNT suppress inflammatory mediator responses in human lung epithelium in vitro

    SciTech Connect

    Herzog, Eva Byrne, Hugh J.; Casey, Alan; Davoren, Maria; Lenz, Anke-Gabriele; Maier, Konrad L.; Duschl, Albert; Oostingh, Gertie Janneke

    2009-02-01

    Single-walled carbon nanotubes have gained enormous popularity due to a variety of potential applications which will ultimately lead to increased human and environmental exposure to these nanoparticles. This study was carried out in order to evaluate the inflammatory response of immortalised and primary human lung epithelial cells (A549 and NHBE) to single-walled carbon nanotube samples (SWCNT). Special focus was placed on the mediating role of lung surfactant on particle toxicity. The toxicity of SWCNT dispersed in cell culture medium was compared to that of nanotubes dispersed in dipalmitoylphosphatidylcholine (DPPC, the main component of lung lining fluid). Exposure was carried out for 6 to 48 h with the latter time-point showing the most significant responses. Moreover, exposure was performed in the presence of the pro-inflammatory stimulus tumour necrosis factor-{alpha} (TNF-{alpha}) in order to mimic exposure of stimulated cells, as would occur during infection. Endpoints evaluated included cell viability, proliferation and the analysis of inflammatory mediators such as interleukin (IL)-8, IL-6, TNF-{alpha} and macrophage chemoattractant protein-1 (MCP-1). Crocidolite asbestos was included as a well characterised, toxic fibre control. The results of this study showed that HiPco SWCNT samples suppress inflammatory responses of A549 and NHBE cells. This was also true for TNF-{alpha} stimulated cells. The use of DPPC improved the degree of SWCNT dispersion in A549 medium and in turn, leads to increased particle toxicity, however, it was not shown to modify NHBE cell responses.

  9. 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.

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

    PubMed

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

    2016-12-01

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

  11. 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.

  12. Ultrasonographic imaging of inflammatory bowel disease in pediatric patients

    PubMed Central

    Chiorean, Liliana; Schreiber-Dietrich, Dagmar; Braden, Barbara; Cui, Xin-Wu; Buchhorn, Reiner; Chang, Jian-Min; Dietrich, Christoph F

    2015-01-01

    Inflammatory bowel disease (IBD) is one of the most common chronic gastrointestinal diseases in pediatric patients. Choosing the optimal imaging modality for the assessment of gastrointestinal disease in pediatric patients can be challenging. The invasiveness and patient acceptance, the radiation exposure and the quality performance of the diagnostic test need to be considered. By reviewing the literature regarding imaging in inflammatory bowel disease the value of ultrasound in the clinical management of pediatric patients is highlighted. Transabdominal ultrasound is a useful, noninvasive method for the initial diagnosis of IBD in children; it also provides guidance for therapeutic decisions and helps to characterize and predict the course of the disease in individual patients. Ultrasound techniques including color Doppler imaging and contrast-enhanced ultrasound are promising imaging tools to determine disease activity and complications. Comparative studies between different imaging methods are needed. PMID:25954096

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

    PubMed Central

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

    2012-01-01

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

  14. Marine bioactives: pharmacological properties and potential applications against inflammatory diseases.

    PubMed

    D'Orazio, Nicolantonio; Gammone, Maria Alessandra; Gemello, Eugenio; De Girolamo, Massimo; Cusenza, Salvatore; Riccioni, Graziano

    2012-04-01

    Inflammation is a hot topic in medical research, because it plays a key role in inflammatory diseases: rheumatoid arthritis (RA) and other forms of arthritis, diabetes, heart diseases, irritable bowel syndrome, Alzheimer's disease, Parkinson's disease, allergies, asthma, even cancer and many others. Over the past few decades, it was realized that the process of inflammation is virtually the same in different disorders, and a better understanding of inflammation may lead to better treatments for numerous diseases. Inflammation is the activation of the immune system in response to infection, irritation, or injury, with an influx of white blood cells, redness, heat, swelling, pain, and dysfunction of the organs involved. Although the pathophysiological basis of these conditions is not yet fully understood, reactive oxygen species (ROS) have often been implicated in their pathogenesis. In fact, in inflammatory diseases the antioxidant defense system is compromised, as evidenced by increased markers of oxidative stress, and decreased levels of protective antioxidant enzymes in patients with rheumatoid arthritis (RA). An enriched diet containing antioxidants, such as vitamin E, vitamin C, β-carotene and phenolic substances, has been suggested to improve symptoms by reducing disease-related oxidative stress. In this respect, the marine world represents a largely untapped reserve of bioactive ingredients, and considerable potential exists for exploitation of these bioactives as functional food ingredients. Substances such as n-3 oils, carotenoids, vitamins, minerals and peptides provide a myriad of health benefits, including reduction of cardiovascular diseases, anticarcinogenic and anti-inflammatory activities. New marine bioactives are recently gaining attention, since they could be helpful in combating chronic inflammatory degenerative conditions. The aim of this review is to examine the published studies concerning the potential pharmacological properties and

  15. Marine Bioactives: Pharmacological Properties and Potential Applications against Inflammatory Diseases

    PubMed Central

    D’Orazio, Nicolantonio; Gammone, Maria Alessandra; Gemello, Eugenio; De Girolamo, Massimo; Cusenza, Salvatore; Riccioni, Graziano

    2012-01-01

    Inflammation is a hot topic in medical research, because it plays a key role in inflammatory diseases: rheumatoid arthritis (RA) and other forms of arthritis, diabetes, heart diseases, irritable bowel syndrome, Alzheimer’s disease, Parkinson’s disease, allergies, asthma, even cancer and many others. Over the past few decades, it was realized that the process of inflammation is virtually the same in different disorders, and a better understanding of inflammation may lead to better treatments for numerous diseases. Inflammation is the activation of the immune system in response to infection, irritation, or injury, with an influx of white blood cells, redness, heat, swelling, pain, and dysfunction of the organs involved. Although the pathophysiological basis of these conditions is not yet fully understood, reactive oxygen species (ROS) have often been implicated in their pathogenesis. In fact, in inflammatory diseases the antioxidant defense system is compromised, as evidenced by increased markers of oxidative stress, and decreased levels of protective antioxidant enzymes in patients with rheumatoid arthritis (RA). An enriched diet containing antioxidants, such as vitamin E, vitamin C, β-carotene and phenolic substances, has been suggested to improve symptoms by reducing disease-related oxidative stress. In this respect, the marine world represents a largely untapped reserve of bioactive ingredients, and considerable potential exists for exploitation of these bioactives as functional food ingredients. Substances such as n-3 oils, carotenoids, vitamins, minerals and peptides provide a myriad of health benefits, including reduction of cardiovascular diseases, anticarcinogenic and anti-inflammatory activities. New marine bioactives are recently gaining attention, since they could be helpful in combating chronic inflammatory degenerative conditions. The aim of this review is to examine the published studies concerning the potential pharmacological properties and

  16. Angiotensin-converting enzyme 2 in lung diseases.

    PubMed

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

    2006-06-01

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

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

    PubMed

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

    2008-04-01

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

  18. Inflammatory bowel disease as a model for translating the microbiome

    PubMed Central

    Huttenhower, Curtis; Kostic, Aleksandar D.; Xavier, Ramnik J.

    2014-01-01

    The inflammatory bowel diseases (IBD) are among the most closely studied chronic inflammatory disorders that involve environmental, host genetic, and commensal microbial factors. This combination of features has made IBD both an appropriate and a high-priority platform for translatable research in host-microbiome interactions. Decades of epidemiology have identified environmental risk factors, although most mechanisms of action remain unexplained. The genetic architecture of IBD has been carefully dissected in multiple large populations, identifying several responsible host epithelial and immune pathways but without yet a complete systems-level explanation. Most recently, the commensal gut microbiota have been found to be both ecologically and functionally perturbed during the disease, but with as-yet-unexplained heterogeneity among IBD subtypes and individual patients. IBD thus represents perhaps the most comprehensive current model for understanding the human microbiome’s role in complex inflammatory disease. Here, we review the influences of the microbiota on IBD and its potential for translational medicine. PMID:24950204

  19. [Fecal calprotectin in the diagnosis of inflammatory bowel diseases].

    PubMed

    Rodríguez-Moranta, Francisco; Lobatón, Triana; Rodríguez-Alonso, Lorena; Guardiola, Jordi

    2013-01-01

    The diagnosis of inflammatory bowel diseases has classically been based on assessment of digestive symptoms. The development of these symptoms usually results in colonoscopy, which has a low diagnostic yield. Likewise, there is an increasing tendency to base treatment of inflammatory bowel disease on objective data, since the disappearance of signs of activity on colonoscopy (called « mucosal cure ») has been associated with sustained clinical remission and reduced rates of hospitalization and surgery. Consequently, there is a need for biomarkers that would aid the selection of those patients who would derive most benefit from an endoscopic examination. One substance that has been proposed as a biomarker of bowel inflammation is fecal calprotectin. This substance allows inflammatory bowel disease to be distinguished from irritable bowel syndrome and shows a better correlation with the degree of inflammation than clinical indicators and serological markers. In addition, it could also be useful to predict mucosal cure and the risk of recurrence.

  20. [The mediterranean diet model in inflammatory rheumatic diseases].

    PubMed

    Sales, C; Oliviero, F; Spinella, P

    2009-01-01

    The Mediterranean diet is based on a pattern of eating closely tied to the Mediterranean region, which includes Greece and southern Italy. Essentially, the traditional diet emphasizes foods from plant sources, limited meat consumption, small amounts of wine and olive oil as the main fat source. The beneficial effects of the Mediterranean diet has been proven not only to cardiovascular diseases but also for diabetes, obesity, arthritis and cancer. Its anti-inflammatory and protective properties are linked to the large presence of omega-3 polyunsaturated fatty acids, vitamins, but especially to the constituents of extra virgin olive oil: oleic acid, phenolic compounds olecanthal, a new recently discovered molecule, with natural anti-inflammatory properties. It has been shown that the Mediterranean diet can reduce disease activity, pain and stiffness in patients with inflammatory arthritis and may thus constitute a valuable support for patients suffering from these diseases.

  1. Interleukin-23: as a drug target for autoimmune inflammatory diseases

    PubMed Central

    Tang, Chunlei; Chen, Shu; Qian, Hai; Huang, Wenlong

    2012-01-01

    Interleukin-23 (IL-23) is a member of the IL-12 family of cytokines with pro-inflammatory properties. Its ability to potently enhance the expansion of T helper type 17 (Th17) cells indicates the responsibility for many of the inflammatory autoimmune responses. Emerging data demonstrate that IL-23 is a key participant in central regulation of the cellular mechanisms involved in inflammation. Both IL-23 and IL-17 form a new axis through Th17 cells, which has evolved in response to human diseases associated with immunoactivation and immunopathogeny, including bacterial or viral infections and chronic inflammation. Targeting of IL-23 or the IL-23 receptor or IL-23 axis is a potential therapeutic approach for autoimmune diseases including psoriasis, inflammatory bowel disease, rheumatoid arthritis and multiple sclerosis. The current review focuses on the immunobiology of IL-23 and summarizes the most recent findings on the role of IL-23 in the pre-clinical and ongoing clinical studies. PMID:22044352

  2. The NF-kappaB signaling in cystic fibrosis lung disease: pathophysiology and therapeutic potential.

    PubMed

    Bodas, Manish; Vij, Neeraj

    2010-04-01

    Lung disease is the major cause of morbidity and mortality of cystic fibrosis (CF), an autosomal recessive disease caused by mutations in CF transmembrane-conductance regulator (CFTR) gene. In CF, elevated levels of interleukin-8 (IL-8) signaling mediated by the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) result in chronic infection, neutrophilic inflammation, and progressive airway destruction. The most frequent mutation in the CFTR gene is the deletion of phenylalanine 508 (DeltaF508), which results in its endoplasmic reticulum associated degradation (ERAD) by the ubiquitin-proteasome system. The inability of DeltaF508-CFTR to reach cell surface leads to inherently high levels of NF-kappaB. Severity of CF lung disease depends on the levels of functional CFTR on cell surface that control its chloride transport and NF-kappaB mediated innate immune response functions. NF-kappaB mediated chronic inflammation is a prominent feature of CF lung disease and the mechanism(s) by which CFTR regulates these inflammatory signaling pathways is becoming apparent. Recent data suggest that CFTR localization to lipid-rafts is critical for regulating NF-kappaB mediated innate immune response and chronic CF lung disease. We anticipate that targeting the pathways, which facilitates CFTR's rescue to the cell surface and lipid-rafts, will not only restore CFTR channel function but also control NF-kappaB mediated chronic inflammation, although the level of correction may be a critical factor for therapeutic efficacy. We discuss here the mechanisms of NF-kappaB induction in CF, pathogenesis of CF lung disease, and novel therapeutic strategies that may help in reversing the chronic CF lung disease.

  3. The NFκB Signaling in Cystic Fibrosis Lung Disease: Pathophysiology and Therapeutic Potential

    PubMed Central

    Bodas, Manish; Vij, Neeraj

    2010-01-01

    Lung disease is the major cause of morbidity and mortality of cystic fibrosis (CF), an autosomal recessive disease caused by mutations in CF transmembrane-conductance regulator (CFTR) gene. In CF, elevated levels of interleukin-8 (IL-8) signaling mediated by the nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) result in chronic infection, neutrophilic inflammation, and progressive airway destruction. The most frequent mutation in the CFTR gene is the deletion of phenylalanine 508 (ΔF508), which results in its endoplasmic reticulum associated degradation (ERAD) by the ubiquitin-proteasome system. The inability of ΔF508-CFTR to reach cell surface leads to inherently high levels of NFκB. Severity of CF lung disease depends on the levels of functional CFTR on cell surface that control its chloride transport and NFκB mediated innate immune response functions. NFκB mediated chronic inflammation is a prominent feature of CF lung disease and the mechanism(s) by which CFTR regulates these inflammatory signaling pathways is becoming apparent. Recent data suggest that CFTR localization to lipid-rafts is critical for regulating NFκB mediated innate immune response and chronic CF lung disease. We anticipate that targeting the pathways, which facilitates CFTR’s rescue to the cell surface and lipid-rafts, will not only restore CFTR channel function but also control NFκB mediated chronic inflammation, although the level of correction may be a critical factor for therapeutic efficacy. We discuss here the mechanisms of NFκB induction in CF, pathogenesis of CF lung disease, and novel therapeutic strategies that may help in reversing the chronic CF lung disease. PMID:20423679

  4. Microscopic features for initial diagnosis and disease activity evaluation in inflammatory bowel disease.

    PubMed

    Bressenot, Aude; Geboes, Karel; Vignaud, Jean-Michel; Guéant, Jean-Louis; Peyrin-Biroulet, Laurent

    2013-07-01

    Inflammatory bowel disease is characterized by 2 major entities: Crohn's disease (CD) and ulcerative colitis (UC). In clinical practice, separation of UC and CD has been based on a variety of clinical features, symptoms, endoscopic and radiological, gross and microscopic characteristics. The microscopic diagnosis of inflammatory bowel disease is based on a combination of 2 types of lesions: architectural abnormalities and inflammatory features. However, microscopic distinction between these 2 entities can be difficult and often results in an interim diagnosis of "indeterminate colitis." Recommendations are made to encourage pathologists to give an indication of the activity of the disease: in UC, biopsies are used to discriminate between quiescent disease, inactive disease, and different grades of activity; in CD, evaluation of disease activity is limited and inactivity in the biopsy may not reflect inactivity in the patient. The aim of this review was to summarize microscopic features of inflammatory bowel disease for initial diagnosis and evaluation of disease activity in both CD and UC.

  5. Intestinal microbiota, probiotics and prebiotics in inflammatory bowel disease.

    PubMed

    Orel, Rok; Kamhi Trop, Tina

    2014-09-07

    It has been presumed that aberrant immune response to intestinal microorganisms in genetically predisposed individuals may play a major role in the pathogenesis of the inflammatory bowel disease, and there is a good deal of evidence supporting this hypothesis. Commensal enteric bacteria probably play a central role in pathogenesis, providing continuous antigenic stimulation that causes chronic intestinal injury. A strong biologic rationale supports the use of probiotics and prebiotics for inflammatory bowel disease therapy. Many probiotic strains exhibit anti-inflammatory properties through their effects on different immune cells, pro-inflammatory cytokine secretion depression, and the induction of anti-inflammatory cytokines. There is very strong evidence supporting the use of multispecies probiotic VSL#3 for the prevention or recurrence of postoperative pouchitis in patients. For treatment of active ulcerative colitis, as well as for maintenance therapy, the clinical evidence of efficacy is strongest for VSL#3 and Escherichia coli Nissle 1917. Moreover, some prebiotics, such as germinated barley foodstuff, Psyllium or oligofructose-enriched inulin, might provide some benefit in patients with active ulcerative colitis or ulcerative colitis in remission. The results of clinical trials in the treatment of active Crohn's disease or the maintenance of its remission with probiotics and prebiotics are disappointing and do not support their use in this disease. The only exception is weak evidence of advantageous use of Saccharomyces boulardii concomitantly with medical therapy in maintenance treatment.

  6. Intestinal microbiota, probiotics and prebiotics in inflammatory bowel disease

    PubMed Central

    Orel, Rok; Kamhi Trop, Tina

    2014-01-01

    It has been presumed that aberrant immune response to intestinal microorganisms in genetically predisposed individuals may play a major role in the pathogenesis of the inflammatory bowel disease, and there is a good deal of evidence supporting this hypothesis. Commensal enteric bacteria probably play a central role in pathogenesis, providing continuous antigenic stimulation that causes chronic intestinal injury. A strong biologic rationale supports the use of probiotics and prebiotics for inflammatory bowel disease therapy. Many probiotic strains exhibit anti-inflammatory properties through their effects on different immune cells, pro-inflammatory cytokine secretion depression, and the induction of anti-inflammatory cytokines. There is very strong evidence supporting the use of multispecies probiotic VSL#3 for the prevention or recurrence of postoperative pouchitis in patients. For treatment of active ulcerative colitis, as well as for maintenance therapy, the clinical evidence of efficacy is strongest for VSL#3 and Escherichia coli Nissle 1917. Moreover, some prebiotics, such as germinated barley foodstuff, Psyllium or oligofructose-enriched inulin, might provide some benefit in patients with active ulcerative colitis or ulcerative colitis in remission. The results of clinical trials in the treatment of active Crohn’s disease or the maintenance of its remission with probiotics and prebiotics are disappointing and do not support their use in this disease. The only exception is weak evidence of advantageous use of Saccharomyces boulardii concomitantly with medical therapy in maintenance treatment. PMID:25206258

  7. Experimental chronic kidney disease attenuates ischemia-reperfusion injury in an ex vivo rat lung model

    PubMed Central

    Huang, Kun-Lun; Lan, Chou-Chin; Hsu, Yu-Juei; Wu, Geng-Chin; Peng, Chia-Hui

    2017-01-01

    Lung ischemia reperfusion injury (LIRI) is one of important complications following lung transplant and cardiopulmonary bypass. Although patients on hemodialysis are still excluded as lung transplant donors because of the possible effects of renal failure on the lungs, increased organ demand has led us to evaluate the influence of chronic kidney disease (CKD) on LIRI. A CKD model was induced by feeding Sprague-Dawley rats an adenine-rich (0.75%) diet for 2, 4 and 6 weeks, and an isolated rat lung in situ model was used to evaluate ischemia reperfusion (IR)-induced acute lung injury. The clinicopathological parameters of LIRI, including pulmonary edema, lipid peroxidation, histopathological changes, immunohistochemistry changes, chemokine CXCL1, inducible nitric oxide synthase (iNOS), proinflammatory and anti-inflammatory cytokines, heat shock protein expression, and nuclear factor-κB (NF-κB) activation were determined. Our results indicated that adenine-fed rats developed CKD as characterized by increased blood urea nitrogen and creatinine levels and the deposition of crystals in the renal tubules and interstitium. IR induced a significant increase in the pulmonary arterial pressure, lung edema, lung injury scores, the expression of CXCL1 mRNA, iNOS level, and protein concentration of the bronchial alveolar lavage fluid (BALF). The tumor necrosis factor-α levels in the BALF and perfusate; the interleukin-10 level in the perfusate; and the malondialdehyde levels in the lung tissue and perfusate were also significantly increased by LIRI. Counterintuitively, adenine-induced CKD significantly attenuated the severity of lung injury induced by IR. CKD rats exhibited increased heat shock protein 70 expression and decreased activation of NF-κB signaling. In conclusion, adenine-induced CKD attenuated LIRI by inhibiting the NF-κB pathway. PMID:28291795

  8. High-density Lipoproteins and Apolipoprotein A-I: Potential New Players in the Prevention and Treatment of Lung Disease

    PubMed Central

    Gordon, Elizabeth M.; Figueroa, Debbie M.; Barochia, Amisha V.; Yao, Xianglan; Levine, Stewart J.

    2016-01-01

    Apolipoprotein A-I (apoA-I) and high-density lipoproteins (HDL) mediate reverse cholesterol transport out of cells. Furthermore, HDL has additional protective functions, which include anti-oxidative, anti-inflammatory, anti-apoptotic, and vasoprotective effects. In contrast, HDL can become dysfunctional with a reduction in both cholesterol efflux and anti-inflammatory properties in the setting of disease or the acute phase response. These paradigms are increasingly being recognized to be active in the pulmonary system, where apoA-I and HDL have protective effects in normal lung health, as well as in a variety of disease states, including acute lung injury (ALI), asthma, chronic obstructive pulmonary disease, lung cancer, pulmonary arterial hypertension, pulmonary fibrosis, and viral pneumonia. Similar to observations in cardiovascular disease, however, HDL may become dysfunctional and contribute to disease pathogenesis in respiratory disorders. Furthermore, synthetic apoA-I mimetic peptides have been shown to have protective effects in animal models of ALI, asthma, pulmonary hypertension, and influenza pneumonia. These findings provide evidence to support the concept that apoA-I mimetic peptides might be developed into a new treatment that can either prevent or attenuate the manifestations of lung diseases, such as asthma. Thus, the lung is positioned to take a page from the cardiovascular disease playbook and utilize the protective properties of HDL and apoA-I as a novel therapeutic approach. PMID:27708582

  9. [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.

  10. Neuroendocrine host factors and inflammatory disease susceptibility.

    PubMed Central

    Ligier, S; Sternberg, E M

    1999-01-01

    The etiology of autoimmune diseases is multifactorial, resulting from a combination of genetically predetermined host characteristics and environmental exposures. As the term autoimmune implies, immune dysfunction and dysregulated self-tolerance are key elements in the pathophysiology of all these diseases. The neuroendocrine and sympathetic nervous systems are increasingly recognized as modulators of the immune response at the levels of both early inflammation and specific immunity. As such, alterations in their response represent a potential mechanism by which pathologic autoimmunity may develop. Animal models of autoimmune diseases show pre-existing changes in neuroendocrine responses to a variety of stimuli, and both animal and human studies have shown altered stress responses in the setting of active immune activation. The potential role of the neuroendocrine system in linking environmental exposures and autoimmune diseases is 2-fold. First, it may represent a direct target for toxic compounds. Second, its inadequate function may result in the inappropriate response of the immune system to an environmental agent with immunogenic properties. This article reviews the relationship between autoimmune diseases and the neuroendocrine system and discusses the difficulties and pitfalls of investigating a physiologic response that is sensitive to such a multiplicity of environmental exposures. PMID:10502534

  11. Associations between periodontitis and systemic inflammatory diseases: response to treatment.

    PubMed

    El-Shinnawi, Una; Soory, Mena

    2013-09-01

    There is a significant prevalence of subjects with periodontitis presenting with other inflammatory conditions such as coronary heart disease, insulin resistance and arthritis. This pattern of disease presentation underscores the importance of inflammatory loading from chronic diseases, in driving their pathogeneses in a multidirectional manner. Pro-inflammatory cytokines and other agents play an important role in this process; for example, a single nucleotide polymorphism of the TNF-α gene is associated with significant periodontal attachment loss in patients with coronary heart disease. Changes in gene expression associated with inflammation and lipid metabolism in response to oral infection with the periodontal pathogen Porphyromonas gingivalis (Pg) have been demonstrated in mouse models, independent of the demonstration of atherosclerotic lesions. Insulin resistance is considered to be a chronic low-grade inflammatory condition, associated with altered glucose tolerance, hypertriglyceridemia, central obesity and coronary heart disease. It is accompanied by elevated levels of IL-1, IL-6 and TNF-α also relevant to the progression of periodontitis. There is evidence that uncontrolled periodontal disease contributes to maintenance of systemic diseases, including rheumatoid arthritis (RA), with increased risk of periodontitis in subjects with RA. The periodontal pathogen Pg is significant in contributing to citrullination of proteins resulting in immune dysregulation and autoimmune responses, seen in RA. However, they are both multifactorial chronic diseases with complex etiopathogeneses that affect their presentation. Consistent but weak associations are seen for surrogate markers of periodontitis such as tooth loss, with multiple systemic conditions. Effective treatment of periodontitis would be important in reducing systemic inflammatory loading from chronic local inflammation and in achieving systemic health. Lack of a consistent cause and effect relationship

  12. Imaging of inflammatory bowel disease: CT and MR.

    PubMed

    Zalis, Michael; Singh, Ajay K

    2004-01-01

    Cross-sectional imaging has come to play a central role in the imaging of the abdomen. Concurrent to this, the role of CT and MRI in the imaging of inflammatory bowel disease has also increased in importance. These modalities offer numerous advantages over more traditional methods of radiologic diagnosis, and provide essential information not only for initial diagnosis, but for management, follow-up and detection of potential complications. On the horizon are several derivative techniques involving CT and MRI, potentially in combination with PET imaging; these may further improve the specificity and sensitivity of imaging modalities for diagnosis of inflammatory bowel disease.

  13. Current stage in inflammatory bowel disease: What is next?

    PubMed Central

    Gómez-Gómez, Gonzalo Jesús; Masedo, Ángeles; Yela, Carmen; Martínez-Montiel, Maria del Pilar; Casís, Begoña

    2015-01-01

    In recent years, the incidence of inflammatory bowel disease (IBD) has been on the rise, extending to countries where it was infrequent in the past. As a result, the gap between high and low incidence countries is decreasing. The disease, therefore, has an important economic impact on the healthcare system. Advances in recent years in pharmacogenetics and clinical pharmacology have allowed for the development of treatment strategies adjusted to the patient profile. Concurrently, new drugs aimed at inflammatory targets have been developed that may expand future treatment options. This review examines advances in the optimization of existing drug treatments and the development of novel treatment options for IBD. PMID:26525013

  14. Lymphocyte homing antagonists in the treatment of inflammatory bowel diseases.

    PubMed

    Saruta, Masayuki; Papadakis, Konstantinos A

    2014-09-01

    Lymphocyte homing antagonists represent promising therapeutic agents for the treatment of idiopathic inflammatory bowel disease (IBD). Several critical molecules involved in the recruitment of inflammatory cells in the intestine, including integrins and chemokine receptors, have been successfully targeted for the treatment of IBD. These agents have shown great promise for the induction and maintenance of remission for both Crohn disease and ulcerative colitis. This article discusses currently approved prototypic agents for the treatment of IBD (natalizumab, anti-α4 integrin; vedolizumab, anti-α4β7 integrin), and several other agents in the same class currently under development.

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

    PubMed

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

    2015-01-01

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

  16. 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.

  17. Phenomics in Autoimmune and Inflammatory Diseases

    ClinicalTrials.gov

    2016-12-12

    Healthy Volunteer; Rheumatoid Arthritis; Ankylosing Spondylitis; Systemic Lupus Erythematosus/Antiphospholipid Syndrome; FMF; Cryopyrin-Associated Periodic Syndromes /TNF-receptor Associated Periodic Syndrome; Vasculitis; Uveitis; Myositis; Crohn's Disease; Ulcerative Rectocolitis; Type 1 Diabetes; Unclassified IAD Knee and/or Hip Arthritis, Muscular Dystrophy

  18. 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.

  19. Radiation-induced heart disease in lung cancer radiotherapy

    PubMed Central

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

    2016-01-01

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

  20. 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.

  1. Magnetic resonance imaging in inflammatory rheumatoid diseases.

    PubMed

    Sudoł-Szopińska, Iwona; Mróz, Joanna; Ostrowska, Monika; Kwiatkowska, Brygida

    2016-01-01

    Magnetic resonance (MR) is used more and more frequently to diagnose changes in the musculoskeletal system in the course of rheumatic diseases, at their initial assessment, for treatment monitoring and for identification of complications. The article presents the history of magnetic resonance imaging, the basic principles underlying its operation as well as types of magnets, coils and MRI protocols used in the diagnostic process of rheumatic diseases. It enumerates advantages and disadvantages of individual MRI scanners. The principles of MRI coil operation are explained, and the sequences used for MR image analysis are described, particularly in terms of their application in rheumatology, including T1-, T2-, PD-weighted, STIR/TIRM and contrast-enhanced T1-weighted images. Furthermore, views on the need to use contrast agents to optimise diagnosis, particularly in synovitis-like changes, are presented. Finally, methods for the assessment of MR images are listed, including the semi-quantitative method by RAMRIS and quantitative dynamic examination.

  2. The TNF Family Molecules LIGHT and Lymphotoxin αβ Induce a Distinct Steroid-Resistant Inflammatory Phenotype in Human Lung Epithelial Cells

    PubMed Central

    Antunes, Ricardo da Silva; Madge, Lisa; Soroosh, Pejman; Tocker, Joel; Croft, Michael

    2015-01-01

    Lung epithelial cells are considered important sources of inflammatory molecules and extracellular matrix proteins that contribute to diseases such as asthma. Understanding the factors that stimulate epithelial cells may lead to new insights into controlling lung inflammation. This study sought to investigate the responsiveness of human lung epithelial cells to the TNF family molecules LIGHT and lymphotoxin αβ (LTαβ). Bronchial and alveolar epithelial cell lines, and primary human bronchial epithelial cells, were stimulated with LIGHT and LTαβ, and expression of inflammatory cytokines and chemokines, and markers of epithelial-mesenchymal transition and fibrosis/remodeling, were measured. LTβR, the receptor shared by LIGHT and LTαβ, was constitutively expressed on all epithelial cells. Correspondingly, LIGHT and LTαβ strongly induced a limited but highly distinct set of inflammatory genes in all epithelial cells tested, namely the adhesion molecules ICAM-1 and VCAM-1; the chemokines CCL5, CCL20, CXCL1, CXCL3, CXCL5 and CXCL11; the cytokines IL-6, activin A, and GM-CSF; and metalloproteinases MMP-9 and ADAM-8. Importantly, induction of the majority of these inflammatory molecules was insensitive to the suppressive effects of the corticosteroid budesonide. LIGHT and LTαβ also moderately downregulated E-cadherin, a protein associated with maintaining epithelial integrity, but did not significantly drive production of extracellular matrix proteins or alpha-smooth muscle actin. Thus, LIGHT and LTαβ induce a distinct steroid-resistant inflammatory signature in airway epithelial cells via constitutively expressed LTβR. These findings support our prior murine studies that suggested the receptors for LIGHT and LTαβ contribute to development of lung inflammation characteristic of asthma and idiopathic pulmonary fibrosis. PMID:26209626

  3. [Relationship between grade I and II inflammatory foci and certain inflammatory ophthalmic diseases].

    PubMed

    Ilewicz, L; Ciechocińska, J; Chruściel, H

    1990-09-01

    The purpose of the study was demonstration of relations between grade I and II inflammatory foci in the oral cavity and certain inflammatory diseases of the eyes. Forty-three patients of either sex were studied. They were aged 19 to 78 years and were referred with the diagnosis of optic neuritis (intraocular and retrobulbar), iritis, retinitis and keratitis. Apart from routine clinical and radiological investigations the electrocutaneous test, the test for pulp viability with faradic current, and Schüller's iodine test were done. In 31 patients the electrocutaneous test was positive.

  4. [Biological treatment of rare inflammatory rheumatic diseases].

    PubMed

    Baslund, Bo

    2008-06-09

    The current status of the use of biological medicine in the treatment of adult onset morbus still, Wegeners granulomatosis and systemic lupus erythematosus (SLE) is reviewed. The need for controlled trials is emphasized. Anti-CD20 treatment for SLE patients with kidney involvement and patients with Wegeners granulomatosis seems promising. Anti-TNF and IL1 receptor antagonist can control disease activity in most patients with adult morbus still.

  5. Inflammatory lipid mediator generation elicited by viable hemolysin- forming Escherichia coli in lung vasculature

    PubMed Central

    1990-01-01

    Escherichia coli hemolysin, a transmembrane pore-forming exotoxin, is considered an important virulence factor for E. coli-related extraintestinal infections and sepsis. The possible significance of hemolysin liberation for induction of inflammatory lipid mediators was investigated in isolated rabbit lungs infused with viable bacteria (concentration range, 10(4)-10(7)/ml). Hemolysin-secreting E. coli (E. coli-Hly+), but not an E. coli strain that releases an inactive form of the exotoxin, induced marked lung leukotriene (LT) generation with predominance of cysteinyl LTs. Eicosanoid synthesis was not inhibited in the presence of plasma with toxin-neutralizing capacity. Pre- application of 2 x 10(8) human granulocytes, which sequestered in the lung microvasculature, caused a severalfold increase in leukotriene generation in response to E. coli-Hly+ challenge both in the absence and presence of plasma. Data are presented indicating neutrophil- endothelial cell cooperation in arachidonic acid lipoxygenase metabolism as an underlying mechanism. We conclude that liberation of hemolysin from viable E. coli induces marked lipid mediator generation in lung vasculature, which is potentiated in the presence of neutrophil sequestration and may contribute to microcirculatory disturbances during the course of severe infections. PMID:2120384

  6. Inflammatory synovial fluid microenvironment drives primary human chondrocytes to actively take part in inflammatory joint diseases.

    PubMed

    Röhner, Eric; Matziolis, Georg; Perka, Carsten; Füchtmeier, Bernd; Gaber, Timo; Burmester, Gerd-Rüdiger; Buttgereit, Frank; Hoff, Paula

    2012-06-01

    The role of human chondrocytes in the pathogenesis of cartilage degradation in rheumatic joint diseases has presently gained increasing interest. An active chondrocyte participation in local inflammation may play a role in the initiation and progression of inflammatory joint diseases and in a disruption of cartilage repair mechanisms resulting in cartilage degradation. In the present study, we hypothesized that inflammatory synovial fluid triggers human chondrocytes to actively take part in inflammatory processes in rheumatic joint diseases. Primary human chondrocytes were incubated in synovial fluids gained from patients with rheumatoid arthritis, psoriasis arthritis and reactive arthritis. The detection of vital cell numbers was determined by using Casy Cell Counter System. Apoptosis was measured by Annexin-V and 7AAD staining. Cytokine and chemokine secretion was determined by a multiplex suspension array. Detection of vital cells showed a highly significant decrease in chondrocyte numbers. Flow cytometry demonstrated a significant increase in apoptotic chondrocytes after the incubation. An active secretion of cytokines such as MCP-1 and MIF by chondrocytes was observed. The inflammatory synovial fluid microenvironment mediates apoptosis and cell death of chondrocytes. Moreover, in terms of cytokine secretion, it also induces an active participation of chondrocytes in ongoing inflammation.

  7. 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

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

    PubMed

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

    2013-10-03

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

  9. Matrix Metalloproteinases in Inflammatory Bowel Disease: An Update

    PubMed Central

    O'Sullivan, Shane; Gilmer, John F.

    2015-01-01

    Matrix metalloproteinases (MMPs) are known to be upregulated in inflammatory bowel disease (IBD) and other inflammatory conditions, but while their involvement is clear, their role in many settings has yet to be determined. Studies of the involvement of MMPs in IBD since 2006 have revealed an array of immune and stromal cells which release the proteases in response to inflammatory cytokines and growth factors. Through digestion of the extracellular matrix and cleavage of bioactive proteins, a huge diversity of roles have been revealed for the MMPs in IBD, where they have been shown to regulate epithelial barrier function, immune response, angiogenesis, fibrosis, and wound healing. For this reason, MMPs have been recognised as potential biomarkers for disease activity in IBD and inhibition remains a huge area of interest. This review describes new roles of MMPs in the pathophysiology of IBD and suggests future directions for the development of treatment strategies in this condition. PMID:25948887

  10. [Chronic inflammatory bowel disease--pathogenic concepts and therapeutic perspectives].

    PubMed

    Madsen, J R

    2000-03-06

    Chronic inflammatory bowel disease (IBD) is considered to be a consequence of inappropriate upregulation of immune reactions evoked by the colonic microflora. Abnormalities observed in IBD may be explained, at least in part, by an unfavourable balance between pro- and anti-inflammatory cytokines. Conventional drug treatment of IBD may soon be replaced by more selective inhibitors that act centrally in the inflammatory process. Immunoneutralisation with chimeric anti-tumour necrosis factor-alpha (TNF alpha) antibodies reduces treatment refractory IBD, including fistular Chrons' disease, but recombinant human TNF alpha-receptor fusion proteins may be equally effective with potentially fewer side effects. This view also applies to chimeric antibodies directed against cytokines or adhesion molecules. Potentially more promising are antisense oligonucleotides and matrix-metalloproteinase inhibitors. Whether sustained remission can be achieved probably depends on successful unravelling of the aetiology of IBD.

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

    PubMed Central

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

    2009-01-01

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

  12. A novel imidazopyridine derivative, X22, attenuates sepsis-induced lung and liver injury by inhibiting the inflammatory response in vitro and in vivo

    PubMed Central

    Ge, Xiangting; Feng, Zhiguo; Xu, Tingting; Wu, Beibei; Chen, Hongjin; Xu, Fengli; Fu, Lili; Shan, Xiaoou; Dai, Yuanrong; Zhang, Yali; Liang, Guang

    2016-01-01

    Sepsis remains a leading cause of death worldwide. Despite years of extensive research, effective drugs to treat sepsis in the clinic are lacking. In this study, we found a novel imidazopyridine derivative, X22, which has powerful anti-inflammatory activity. X22 dose-dependently inhibited lipopolysaccharide (LPS)-induced proinflammatory cytokine production in mouse primary peritoneal macrophages and RAW 264.7 macrophages. X22 also downregulated the LPS-induced proinflammatory gene expression in vitro. In vivo, X22 exhibited a significant protection against LPS-induced death. Pretreatment or treatment with X22 attenuated the sepsis-induced lung and liver injury by inhibiting the inflammatory response. In addition, X22 showed protection against LPS-induced acute lung injury. We additionally found that pretreatment with X22 reduced the inflammatory pain in the acetic acid and formalin models and reduced the dimethylbenzene-induced ear swelling and acetic acid-increased vascular permeability. Together, these data confirmed that X22 has multiple anti-inflammatory effects and may be a potential therapeutic option in the treatment of inflammatory diseases. PMID:27390516

  13. CLA reduces inflammatory mediators from A427 human lung cancer cells and A427 conditioned medium promotes differentiation of C2C12 murine muscle cells.

    PubMed

    Oraldi, Manuela; Maggiora, Marina; Paiuzzi, Elena; Canuto, Rosa A; Muzio, Giuliana

    2013-01-01

    Conjugated linoleic acid (CLA) is thought to h