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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. Inflammatory bowel diseases, chronic liver diseases and the lung.

    PubMed

    Rodriguez-Roisin, Roberto; Bartolome, Sonja D; Huchon, Gérard; Krowka, Michael J

    2016-02-01

    This review is devoted to the distinct associations of inflammatory bowel diseases (IBD) and chronic liver disorders with chronic airway diseases, namely chronic obstructive pulmonary disease and bronchial asthma, and other chronic respiratory disorders in the adult population. While there is strong evidence for the association of chronic airway diseases with IBD, the data are much weaker for the interplay between lung and liver multimorbidities. The association of IBD, encompassing Crohn's disease and ulcerative colitis, with pulmonary disorders is underlined by their heterogeneous respiratory manifestations and impact on chronic airway diseases. The potential relationship between the two most prevalent liver-induced pulmonary vascular entities, i.e. portopulmonary hypertension and hepatopulmonary syndrome, and also between liver disease and other chronic respiratory diseases is also approached. Abnormal lung function tests in liver diseases are described and the role of increased serum bilirubin levels on chronic respiratory problems are considered. Copyright ©ERS 2016.

  4. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Modulatory potential of resveratrol during lung inflammatory disease.

    PubMed

    Vargas, José Eduardo; Souto, André Arigony; Pitrez, Paulo Márcio Condessa; Stein, Renato Tetelbom; Porto, Bárbara Nery

    2016-11-01

    Neutrophils are the first cells to achieve the sites of infection or inflammation in the lungs. The massive accumulation of these cells is associated with acute and chronic lung injury. Therefore, they have been implicated in the pathogenesis of many lung diseases through the release of reactive oxygen intermediates, proteolytic enzymes and Neutrophil Extracellular Traps (NETs). The excessive and continuous release of NETs, fibers composed by decondensed chromatin coated with neutrophil proteins, are associated to the impairment of lung function in different pathological settings. Flavonoids inhibit the respiratory burst of neutrophils in mammals. However, one of these flavonoids, resveratrol has a particular chemical property. It reduce Cu(II) to Cu(I) form with concomitant formation of reactive oxygen species, which can produce DNA breakage as reported in several in vitro models. We hypothesize that direct resveratrol administration in lungs can cleave DNA in NETs, improving lung function during acute airway infections or chronic inflammatory lung diseases. If the hypothesis is correct, the control of NET formation can be used to reduce the inflammatory environment in lung after neutrophil stimuli. Additionally, the production of proinflammatory cytokines by neutrophils could be also diminished by resveratrol administration. In this sense, this flavonoid provides a multifaceted opportunity for treatment of lung diseases with strong or chronic neutrophil activation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. [Fundamentals of chronic inflammatory lung diseases (asthma, COPD, fibrosis)].

    PubMed

    Roth, Michael

    2014-05-01

    Since three decades the prevalence of chronic inflammatory lung diseases (asthma, COPD, fibrosis) are worldwide increasing. In Switzerland about 5 % of the population develops asthma, while in other countries it affects up to 20 % (Maori: New Zealand). Today, asthma is the most frequent cause from absence from school and work, and significantly reduces life quality of the patients and their families. COPD, or the smoker's lung, is the 4th most frequent cause of death worldwide and in the Western society affects mainly cigarette smokers and ex-smokers, while in developing countries it is a diseases linked to open fire cocking with most patients being middle aged women. In both diseases only the symptoms can be controlled by muscle relaxing and anti-inflammatory drugs, but there is no cure available. The third chronic inflammatory lung disease is fibrosis which is increasing with the aging population. As indicated by the terminology "chronic inflammatory lung disease" it is widely assumed that the major cause of these diseases is chronic inflammation occurring in different segments of the lung. This hypothesis is now challenged as increasing evidence from clinical and experimental studies that suggest a much different pathogenesis. There is evidence that the inflammation may come second and tissue structural changes are already pre-set during embryogenesis and may become the major driver for the development of chronic inflammatory lung diseases later in life. The mechanism of this pre-disposition is largely unknown and the difficult to perform investigations have only started in recent years. This review aims to provide an overview of key studies published in the past 2 years on clinical and experimental research.

  7. 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

  8. 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

  9. 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

  10. 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.

  11. Regulation of inflammation by PPARs: a future approach to treat lung inflammatory diseases?

    PubMed

    Becker, Julien; Delayre-Orthez, Carine; Frossard, Nelly; Pons, Françoise

    2006-10-01

    Lung inflammatory diseases, such as acute lung injury (ALI), asthma, chronic obstructive pulmonary disease (COPD) and lung fibrosis, represent a major health problem worldwide. Although glucocorticoids are the most potent anti-inflammatory drug in asthma, they exhibit major side effects and have poor activity in lung inflammatory disorders such as ALI or COPD. Therefore, there is growing need for the development of alternative or new therapies to treat inflammation in the lung. Peroxisome proliferator-activated receptors (PPARs), including the three isotypes PPARalpha, PPARbeta (or PPARdelta) and PPARgamma, are transcription factors belonging to the nuclear hormone receptor superfamily. PPARs, and in particular PPARalpha and PPARgamma, are well known for their critical role in the regulation of energy homeostasis by controlling expression of a variety of genes involved in lipid and carbohydrate metabolism. Synthetic ligands of the two receptor isotypes, the fibrates and the thiazolidinediones, are clinically used to treat dyslipidaemia and type 2 diabetes, respectively. Recently however, PPARalpha and PPARgamma have been shown to exert a potent anti-inflammatory activity, mainly through their ability to downregulate pro-inflammatory gene expression and inflammatory cell functions. The present article reviews the current knowledge of the role of PPARalpha and PPARgamma in controlling inflammation, and presents different findings suggesting that PPARalpha and PPARgamma activators may be helpful in the treatment of lung inflammatory diseases.

  12. 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.

  13. 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

  14. 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.

  15. [Autoantibodies in children with chronic inflammatory lung diseases].

    PubMed

    Markina, O A; Iastrebova, N E; Vaneeva, N P; Volkov, I K; Katosova, L K

    2001-01-01

    124 sera of children with chronic bronchitis, chronic pneumonia, bronchial asthma, exogenic allergic alveolitis, congenital developmental defects of the lungs and the syndrome of the situs inversus of organs were examined with a view to study the state of humoral immunity to tissues. The study was carried out by means of the enzyme-linked immunosorbent assay with the use of collagen, elastin, DNA (native and denaturated), membrane antigens of the lung, the liver, the small intestine and the large intestine. Among all groups of patients autoimmune disturbances, manifested by a rise in the level of autoantibodies of different specificity, were registered. The degree of manifestation of autoimmune disturbances depended on the kind of pathology. After treatment a decrease in the level of autoantibodies was registered in the examinees.

  16. Anti-proline-glycine-proline or antielastin autoantibodies are not evident in chronic inflammatory lung disease.

    PubMed

    Greene, Catherine M; Low, Teck Boon; O'Neill, Shane J; McElvaney, Noel G

    2010-01-01

    In patients with chronic inflammatory lung disease, pulmonary proteases can generate neoantigens from elastin and collagen with the potential to fuel autoreactive immune responses. Antielastin peptide antibodies have been implicated in the pathogenesis of tobacco-smoke-induced emphysema. Collagen-derived peptides may also play a role. To determine whether autoantibodies directed against elastin- and collagen-derived peptides are present in plasma from three groups of patients with chronic inflammatory lung disease compared with a nonsmoking healthy control group and to identify whether autoimmune responses to these peptides may be an important component of the disease process in these patients. A total of 124 patients or healthy control subjects were recruited for the study (Z-A1AT deficiency, n = 20; cystic fibrosis, n = 40; chronic obstructive pulmonary disease, n = 31; healthy control, n = 33). C-reactive protein, IL-32, and antinuclear antibodies were quantified. Antielastin and anti-N-acetylated-proline-glycine-proline autoantibodies were measured by reverse ELISA. All patients were deemed stable and noninfective on the basis of the absence of clinical or radiographic evidence of recent infection. There were no significant differences in the levels of autoantibodies or IL-32 in the patients groups compared with the healthy control subjects. Antielastin or anti-N-acetylated proline-glycine-proline autoantibodies are not evident in chronic inflammatory lung disease.

  17. 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

  18. 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.

  19. Potential of anti-inflammatory treatment for cystic fibrosis lung disease

    PubMed Central

    Taylor-Cousar, Jennifer L; Von Kessel, Kelsey A; Young, Robert; Nichols, David P

    2010-01-01

    Cystic fibrosis (CF) is the most common life-shortening genetic disorder in Caucasians. With improved diagnosis and treatment, survival has steadily increased. Unfortunately, the overwhelming majority of patients still die from respiratory failure caused by structural damage resulting from airway obstruction, recurrent infection, and inflammation. Here, we discuss the role of inflammation and the development of anti-inflammatory therapies to treat CF lung disease. The inflammatory host response is the least addressed component of CF airway disease at this time. Current challenges in both preclinical and clinical investigation make the identification of suitable anti-inflammatory drugs more difficult. Despite this, many researchers are making significant progress toward this goal and the CF research community has reason to believe that new therapies will emerge from these efforts. PMID:22096358

  20. Targeting PPAR receptors in the airway for the treatment of inflammatory lung disease.

    PubMed

    Belvisi, Maria G; Mitchell, Jane A

    2009-10-01

    Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that belong to the nuclear hormone receptor superfamily. PPARgamma regulates several metabolic pathways by binding to sequence-specific PPAR response elements in the promoter region of genes involved in lipid biosynthesis and glucose metabolism. However, more recently PPARgamma, PPARalpha and PPARbeta/delta agonists have been demonstrated to exhibit anti-inflammatory and immunomodulatory properties thus opening up new avenues for research. The actions of PPARgamma and PPARalpha activation are thought to be due to their ability to down regulate pro-inflammatory gene expression and inflammatory cell functions, and as such makes them an attractive target for novel drug intervention. Interestingly, PPARbeta/delta has been shown to be involved in wound healing, angiogenesis, lipid metabolism and thrombosis. In this review we will focus on the data describing the beneficial effects of these ligands in the airway and in the pulmonary vasculature and in vivo in animal models of allergic and occupational asthma, chronic obstructive pulmonary disease and pulmonary fibrosis. A clinical trial is underway to examine the effect of rosiglitazone in asthma patients and the outcome of this trial is awaited with much anticipation. In conclusion, PPARs are novel targets for lung disease and continued work with these ligands may result in a potential new treatment for chronic inflammatory lung diseases.

  1. 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

  2. Targeting PPAR receptors in the airway for the treatment of inflammatory lung disease

    PubMed Central

    Belvisi, Maria G; Mitchell, Jane A

    2009-01-01

    Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that belong to the nuclear hormone receptor superfamily. PPARγ regulates several metabolic pathways by binding to sequence-specific PPAR response elements in the promoter region of genes involved in lipid biosynthesis and glucose metabolism. However, more recently PPARγ, PPARα and PPARβ/δ agonists have been demonstrated to exhibit anti-inflammatory and immunomodulatory properties thus opening up new avenues for research. The actions of PPARγ and PPARα activation are thought to be due to their ability to down regulate pro-inflammatory gene expression and inflammatory cell functions, and as such makes them an attractive target for novel drug intervention. Interestingly, PPARβ/δ has been shown to be involved in wound healing, angiogenesis, lipid metabolism and thrombosis. In this review we will focus on the data describing the beneficial effects of these ligands in the airway and in the pulmonary vasculature and in vivo in animal models of allergic and occupational asthma, chronic obstructive pulmonary disease and pulmonary fibrosis. A clinical trial is underway to examine the effect of rosiglitazone in asthma patients and the outcome of this trial is awaited with much anticipation. In conclusion, PPARs are novel targets for lung disease and continued work with these ligands may result in a potential new treatment for chronic inflammatory lung diseases. 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:19703165

  3. 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

  4. Lung disease

    MedlinePlus

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

  5. Mesenchymal stem cell derived secretome and extracellular vesicles for acute lung injury and other inflammatory lung diseases.

    PubMed

    Monsel, Antoine; Zhu, Ying-Gang; Gudapati, Varun; Lim, Hyungsun; Lee, Jae W

    2016-07-01

    Acute respiratory distress syndrome is a major cause of respiratory failure in critically ill patients. Despite extensive research into its pathophysiology, mortality remains high. No effective pharmacotherapy exists. Based largely on numerous preclinical studies, administration of mesenchymal stem or stromal cell (MSC) as a therapeutic for acute lung injury holds great promise, and clinical trials are currently underway. However, concern for the use of stem cells, specifically the risk of iatrogenic tumor formation, remains unresolved. Accumulating evidence now suggest that novel cell-free therapies including MSC-derived conditioned medium and extracellular vesicles released from MSCs might constitute compelling alternatives. The current review summarizes the preclinical studies testing MSC conditioned medium and/or MSC extracellular vesicles as treatment for acute lung injury and other inflammatory lung diseases. While certain logistical obstacles limit the clinical applications of MSC conditioned medium such as the volume required for treatment, the therapeutic application of MSC extracellular vesicles remains promising, primarily due to ability of extracellular vesicles to maintain the functional phenotype of the parent cell. However, utilization of MSC extracellular vesicles will require large-scale production and standardization concerning identification, characterization and quantification.

  6. Perinatal antibiotic-induced shifts in gut microbiota have differential effects on inflammatory lung diseases.

    PubMed

    Russell, Shannon L; Gold, Matthew J; Reynolds, Lisa A; Willing, Benjamin P; Dimitriu, Pedro; Thorson, Lisa; Redpath, Stephen A; Perona-Wright, Georgia; Blanchet, Marie-Renée; Mohn, William W; Finlay, B Brett; McNagny, Kelly M

    2015-01-01

    Resident gut microbiota are now recognized as potent modifiers of host immune responses in various scenarios. Recently, we demonstrated that perinatal exposure to vancomycin, but not streptomycin, profoundly alters gut microbiota and enhances susceptibility to a TH2 model of allergic asthma. Here we sought to further clarify the etiology of these changes by determining whether perinatal antibiotic treatment has a similar effect on the TH1/TH17-mediated lung disease, hypersensitivity pneumonitis. Hypersensitivity pneumonitis was induced in C57BL/6 wild-type or recombination-activating gene 1-deficient mice treated perinatally with vancomycin or streptomycin by repeated intranasal administration of Saccharopolyspora rectivirgula antigen. Disease severity was assessed by measuring lung inflammation, pathology, cytokine responses, and serum antibodies. Microbial community analyses were performed on stool samples via 16S ribosomal RNA pyrosequencing and correlations between disease severity and specific bacterial taxa were identified. Surprisingly, in contrast to our findings in an allergic asthma model, we found that the severity of hypersensitivity pneumonitis was unaffected by vancomycin, but increased dramatically after streptomycin treatment. This likely reflects an effect on the adaptive, rather than innate, immune response because the effects of streptomycin were not observed during the early phases of disease and were abrogated in recombination-activating gene 1-deficient mice. Interestingly, Bacteroidetes dominated the intestinal microbiota of streptomycin-treated animals, while vancomycin promoted the expansion of the Firmicutes. Perinatal antibiotics exert highly selective effects on resident gut flora, which, in turn, lead to very specific alterations in susceptibility to TH2- or TH1/TH17-driven lung inflammatory disease. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  7. Oral non-steroidal anti-inflammatory drug therapy for lung disease in cystic fibrosis.

    PubMed

    Lands, Larry C; Stanojevic, Sanja

    2016-04-07

    Progressive lung damage causes most deaths in cystic fibrosis. Non-steroidal anti-inflammatory drugs (such as ibuprofen) may prevent progressive pulmonary deterioration and morbidity in cystic fibrosis. To assess the effectiveness of treatment with non-steroidal anti-inflammatory drugs in cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, hand searches of relevant journals and abstract books of conference proceedings. We contacted manufacturers of non-steroidal anti-inflammatory drugs.Latest search of the Group's Trials Register: 04 February 2016. Randomized controlled trials comparing oral non-steroidal anti-inflammatory drugs, at any dose for at least two months, to placebo in people with cystic fibrosis. Two authors independently assessed trials for inclusion the review and their potential risk of bias. The searches identified 10 trials; four are included (287 participants aged five to 39 years; maximum follow up of four years) and one is currently awaiting classification pending publication of the full trial report. Three trials compared ibuprofen to placebo (two from the same centre with some of the same participants); one trial assessed piroxicam versus placebo.The three ibuprofen trials were deemed to have good or adequate methodological quality, but used various outcomes and summary measures. Reviewers considered measures of lung function, nutritional status, radiological assessment of pulmonary involvement, intravenous antibiotic usage, hospital admissions, survival and adverse effects. Combined data from the two largest ibuprofen trials showed a significantly lower annual rate of decline for lung function, percent predicted forced expiratory volume in one second mean difference 1.32 (95% confidence interval 0.21 to 2.42); forced vital capacity mean difference 1.27 (95% confidence interval 0.26 to 2.28); forced expiratory

  8. 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

  9. Oral non-steroidal anti-inflammatory drug therapy for lung disease in cystic fibrosis.

    PubMed

    Lands, Larry C; Stanojevic, Sanja

    2013-06-13

    Progressive lung damage causes most deaths in cystic fibrosis (CF). Non-steroidal anti-inflammatory drugs (NSAIDs) may prevent progressive pulmonary deterioration and morbidity in CF. To assess the effectiveness of treatment with NSAIDs in CF. We searched the Cochrane CF and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, hand searches of relevant journals and abstract books of conference proceedings. We contacted manufacturers of NSAIDs.Latest search of the Group's Trials Register: 15 May 2013. Randomized controlled trials comparing oral NSAIDs, at any dose for at least two months, to placebo in people with CF. Two authors independently assessed trials for the review. The searches identified eight trials; five are included (334 participants aged five to 39 years; maximum follow up of four years). Three trials compared ibuprofen to placebo (two from the same centre with some of the same participants); one trial assessed piroxicam versus placebo, a fifth trial compared cycloxygenase-2 inhibitor nimesulide and clarithromycin. The three ibuprofen trials were deemed to have good or adequate methodological quality, but used various outcomes and summary measures. Reviewers considered measures of lung function, nutritional status, radiological assessment of pulmonary involvement, intravenous antibiotic usage, hospital admissions, survival and adverse effects. Combined data from the two largest ibuprofen trials showed a significantly lower annual rate of decline for lung function, % predicted forced expiratory volume in one second (FEV1) mean difference (MD) 1.32 (95% confidence interval (CI) 0.21 to 2.42); forced vital capacity (FVC) MD 1.27 (95% CI 0.26 to 2.28); forced expiratory flow (25-75%) MD 1.80 (95% CI 0.15 to 3.45). The post-hoc analysis of data from two trials split by age showed a statistically significant slower rate of annual decline of % predicted FEV1 and FVC in the ibuprofen group

  10. 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

  11. Lung Diseases

    MedlinePlus

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

  12. 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

  13. 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

  14. 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 ...

  15. 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

  16. 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.

  17. 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

  18. 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

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

    PubMed

    Santana, Fernanda Paula R; Pinheiro, Nathalia M; Mernak, Márcia Isabel B; Righetti, Renato F; Martins, Mílton A; Lago, João H G; Lopes, Fernanda D T Q Dos Santos; Tibério, Iolanda F L C; Prado, Carla M

    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.

  20. All the "RAGE" in lung disease: The receptor for advanced glycation endproducts (RAGE) is a major mediator of pulmonary inflammatory responses.

    PubMed

    Oczypok, Elizabeth A; Perkins, Timothy N; Oury, Tim D

    2017-06-01

    The receptor for advanced glycation endproducts (RAGE) is a pro-inflammatory pattern recognition receptor (PRR) that has been implicated in the pathogenesis of numerous inflammatory diseases. It was discovered in 1992 on endothelial cells and was named for its ability to bind advanced glycation endproducts and promote vascular inflammation in the vessels of patients with diabetes. Further studies revealed that RAGE is most highly expressed in lung tissue and spurred numerous explorations into RAGE's role in the lung. These studies have found that RAGE is an important mediator in allergic airway inflammation (AAI) and asthma, pulmonary fibrosis, lung cancer, chronic obstructive pulmonary disease (COPD), acute lung injury, pneumonia, cystic fibrosis, and bronchopulmonary dysplasia. RAGE has not yet been targeted in the lungs of paediatric or adult clinical populations, but the development of new ways to inhibit RAGE is setting the stage for the emergence of novel therapeutic agents for patients suffering from these pulmonary conditions. Copyright © 2017. Published by Elsevier Ltd.

  1. 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

  2. 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 ...

  3. Reflux and Lung Disease

    MedlinePlus

    ... Healthy Eating Reflux and Lung Disease Reflux and Lung Disease Make an Appointment Ask a Question Find a Doctor Many people with chronic lung disease also suffer from gastroesophageal reflux (GERD). In this ...

  4. Interstitial Lung Disease

    MedlinePlus

    ... Conditions Interstitial Lung Disease (ILD)/Pulmonary Fibrosis Interstitial Lung Disease (ILD)/Pulmonary Fibrosis Make an Appointment Refer ... ILD clinical trials and most effective therapies. Interstitial Lung Disease Care at National Jewish Health At National ...

  5. 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. PMID:28396872

  6. 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 ...

  7. 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

  8. 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 ...

  9. Inflammatory bowel disease and airway diseases.

    PubMed

    Vutcovici, Maria; Brassard, Paul; Bitton, Alain

    2016-09-14

    Airway diseases are the most commonly described lung manifestations of inflammatory bowel disease (IBD). However, the similarities in disease pathogenesis and the sharing of important environmental risk factors and genetic susceptibility suggest that there is a complex interplay between IBD and airway diseases. Recent evidence of IBD occurrence among patients with airway diseases and the higher than estimated prevalence of subclinical airway injuries among IBD patients support the hypothesis of a two-way association. Future research efforts should be directed toward further exploration of this association, as airway diseases are highly prevalent conditions with a substantial public health impact.

  10. Metal-Sulfide Mineral Ores, Fenton Chemistry and Disease – Particle Induced Inflammatory Stress Response in Lung Cells

    PubMed Central

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

    2014-01-01

    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 0.002 m2/mL stock) and exposure periods (beginning at 30 minutes and measured systematically for up to 24 hours). 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. PMID:25107347

  11. 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

  12. 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.

  13. 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.

  14. 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 ...

  15. 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 ...

  16. 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.

  17. [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.

  18. Inflammatory bowel disease - slideshow

    MedlinePlus

    ... presentations/100171.htm Inflammatory bowel disease - series—Normal anatomy To ... gastrointestinal tract starts at the mouth, which leads to the esophagus, stomach, small intestine, colon, and finally, the rectum and ...

  19. Pelvic Inflammatory Disease

    MedlinePlus

    ... Human Papillomavirus (HPV) Pelvic Inflammatory Disease (PID) STDs & Infertility STDs & Pregnancy Syphilis Trichomoniasis Other STDs See Also ... the upper genital tract. PID can lead to infertility and permanent damage of a woman’s reproductive organs. ...

  20. Interstitial Lung Disease

    MedlinePlus

    ... Critical Care & Sleep Medicine Interstitial Lung Disease Program Sarcoidosis Program Autoimmune Lung Center Rebecca C. Keith, MD, ... Syndromes Hypersensitivity Pneumonitis LAM Lupus Rheumatoid Arthritis (RA) Sarcoidosis Overview Scleroderma (SSC) Systemic Vasculitis Reasons to Visit ...

  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. Warning Signs of Lung Disease

    MedlinePlus

    ... Warning Signs of Lung Disease Warning Signs of Lung Disease A nagging cough or slight wheeze may ... prepare for you next office visit. Questions about Lung Health? Call our Lung HelpLine. Get free counseling ...

  3. 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

  4. Mouse ChemR23 is expressed in dendritic cell subsets and macrophages, and mediates an anti-inflammatory activity of chemerin in a lung disease model.

    PubMed

    Luangsay, Souphalone; Wittamer, Valérie; Bondue, Benjamin; De Henau, Olivier; Rouger, Laurie; Brait, Maryse; Franssen, Jean-Denis; de Nadai, Patricia; Huaux, François; Parmentier, Marc

    2009-11-15

    Chemerin is the ligand of the ChemR23 receptor and a chemoattractant factor for human immature dendritic cells (DCs), macrophages, and NK cells. In this study, we characterized the mouse chemerin/ChemR23 system in terms of pharmacology, structure-function, distribution, and in vivo biological properties. Mouse chemerin is synthesized as an inactive precursor (prochemerin) requiring, as in human, the precise processing of its C terminus for generating an agonist of ChemR23. Mouse ChemR23 is highly expressed in immature plasmacytoid DCs and at lower levels in myeloid DCs, macrophages, and NK cells. Mouse prochemerin is expressed in most epithelial cells acting as barriers for pathogens but not in leukocytes. Chemerin promotes calcium mobilization and chemotaxis on DCs and macrophages and these functional responses were abrogated in ChemR23 knockout mice. In a mouse model of acute lung inflammation induced by LPS, chemerin displayed potent anti-inflammatory properties, reducing neutrophil infiltration and inflammatory cytokine release in a ChemR23-dependent manner. ChemR23 knockout mice were unresponsive to chemerin and displayed an increased neutrophil infiltrate following LPS challenge. Altogether, the mouse chemerin/ChemR23 system is structurally and functionally conserved between human and mouse, and mouse can therefore be considered as a good model for studying the anti-inflammatory role of this system in the regulation of immune responses and inflammatory diseases.

  5. 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

  6. [Pelvic inflammatory disease].

    PubMed

    Hoof, Kathrin

    2007-07-01

    Pelvic inflammatory disease and upper genital tract infection describe inflammatory changes in the upper female genital tract of any combination: endometritis, salpingitis, tubo-ovarian abscess and peritonitis in the small pelvis. In most cases the infection is ascending, Chlamydia trachomatis and Neisseria gonorrhoeae are common with increasing incidence. The spectrum ranges from subclinical, asymptomatic infection to severe, life-threatening illness. Antibiotic treatment should be initiated promptly and must cover a broad spectrum of germs. Surgical treatment is necessary in cases of failure of antibiotic treatment and in cases with persisting symptoms after antibiotic treatment. Pelvic inflammatory diseases are one of the main causes of tubal sterility, ectopic pregnancies and chronic abdominal pain.

  7. Lung disease - resources

    MedlinePlus

    ... gov/health/dci/Diseases/Asthma/Asthma_WhatIs.html Emphysema/COPD (Chronic Obstructive Pulmonary Disease): COPD Foundation -- www.copdfoundation.org National Emphysema Foundation -- www.emphysemafoundation.org National Heart, Lung, and ...

  8. 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

  9. Pelvic inflammatory disease.

    PubMed

    Ross, Jonathan D C

    2013-12-11

    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. 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). 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. 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).

  10. Indium lung disease.

    PubMed

    Cummings, Kristin J; 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

    2012-06-01

    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. 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. 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. 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.

  11. 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. ...

  12. Nonantibiotic macrolides restore airway macrophage phagocytic function with potential anti-inflammatory effects in chronic lung diseases.

    PubMed

    Hodge, Sandra; Tran, Hai B; Hamon, Rhys; Roscioli, Eugene; Hodge, Greg; Jersmann, Hubertus; Ween, Miranda; Reynolds, Paul N; Yeung, Arthur; Treiberg, Jennifer; Wilbert, Sibylle

    2017-05-01

    We reported defective efferocytosis associated with cigarette smoking and/or airway inflammation in chronic lung diseases, including chronic obstructive pulmonary disease, severe asthma, and childhood bronchiectasis. We also showed defects in phagocytosis of nontypeable Haemophilus influenzae (NTHi), a common colonizer of the lower airway in these diseases. These defects could be substantially overcome with low-dose azithromycin; however, chronic use may induce bacterial resistance. The aim of the present study was therefore to investigate two novel macrolides-2'-desoxy-9-(S)-erythromycylamine (GS-459755) and azithromycin-based 2'-desoxy molecule (GS-560660)-with significantly diminished antibiotic activity against Staphylococcus aureus, Streptococcus pneumonia, Moraxella catarrhalis, and H. influenzae We tested their effects on efferocytosis, phagocytosis of NTHi, cell viability, receptors involved in recognition of apoptotic cells and/or NTHi (flow cytometry), secreted and cleaved intracellular IL-1β (cytometric bead array, immunofluorescence/confocal microscopy), and nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) using primary alveolar macrophages and THP-1 macrophages ± 10% cigarette smoke extract. Dose-response experiments showed optimal prophagocytic effects of GS-459755 and GS-560660 at concentrations of 0.5-1 µg/ml compared with our findings with azithromycin. Both macrolides significantly improved phagocytosis of apoptotic cells and NTHi (e.g., increases in efferocytosis and phagocytosis of NTHi: GS-459755, 23 and 22.5%, P = 0.043; GS-560660, 23.5 and 22%, P = 0.043, respectively). Macrophage viability remained >85% following 24 h exposure to either macrolide at concentrations up to 20 µg/ml. Secreted and intracellular-cleaved IL-1β was decreased with both macrolides with no significant changes in recognition molecules c-mer proto-oncogene tyrosine kinase; scavenger receptor class A, member 1; Toll

  13. Pelvic inflammatory disease.

    PubMed

    Gradison, Margaret

    2012-04-15

    Pelvic inflammatory disease is a polymicrobial infection of the upper genital tract. It primarily affects young, sexually active women. The diagnosis is made clinically; no single test or study is sensitive or specific enough for a definitive diagnosis. Pelvic inflammatory disease should be suspected in at-risk patients who present with pelvic or lower abdominal pain with no identified etiology, and who have cervical motion, uterine, or adnexal tenderness. Chlamydia trachomatis and Neisseria gonorrhoeae are the most commonly implicated microorganisms; however, other microorganisms may be involved. The spectrum of disease ranges from asymptomatic to life-threatening tubo-ovarian abscess. Patients should be treated empirically, even if they present with few symptoms. Most women can be treated successfully as outpatients with a single dose of a parenteral cephalosporin plus oral doxycycline, with or without oral metronidazole. Delay in treatment may lead to major sequelae, including chronic pelvic pain, ectopic pregnancy, and infertility. Hospitalization and parenteral treatment are recommended if the patient is pregnant, has human immunodeficiency virus infection, does not respond to oral medication, or is severely ill. Strategies for preventing pelvic inflammatory disease include routine screening for chlamydia and patient education.

  14. 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 ...

  15. 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

  16. Diffuse Cystic Lung Disease. Part I

    PubMed Central

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

    2015-01-01

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

  17. Diffuse Cystic Lung Disease. Part I.

    PubMed

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

    2015-06-15

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

  18. Interstitial lung disease

    MedlinePlus

    ... screened for lung disease. These jobs include coal mining, sand blasting, and working on a ship. Treatment ... Traveling with breathing problems Using oxygen at home Images Clubbing Coal workers pneumoconiosis - stage II Coal workers ...

  19. 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

  20. 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

  1. Interstitial lung disease in children.

    PubMed

    Cazzato, Salvatore; di Palmo, Emanuela; Ragazzo, Vincenzo; Ghione, Silvia

    2013-10-01

    Children's interstitial lung disease (ILD) includes a wide range of rare respiratory disorders associated with high morbidity and mortality. Genetic factors, systemic disease processes, nonspecific inflammatory or fibrotic patterns of repair seen in a number of clinical settings are involved in the ILD pathogenesis. Specific disorders more prevalent in young children include diffuse developmental disorders, alveolar growth abnormalities, genetic surfactant disorders, pulmonary interstitial glycogenosis and neuroendocrine cell hyperplasia of infancy. It may be difficult to recognize these entities and this can lead to delayed treatment. The diagnostic approach is based on a combination of history/physical examinations, imaging studies, pulmonary function testing, genetic testing, bronchoalveolar lavage (BAL) and in most cases an open lung biopsy. Although some disease types overlap with those seen in adults, in this review emphasis is placed on entities unique to the pediatric population focusing on clinical characteristics, histologic definitions, radiologic-pathologic correlation and therapeutic strategies. © 2013.

  2. 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

  3. 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

  4. 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

  5. Pelvic inflammatory disease.

    PubMed

    Soper, David E

    2010-08-01

    Pelvic inflammatory disease (PID) is an infection-caused inflammatory continuum from the cervix to the peritoneal cavity. Most importantly, it is associated with fallopian tube inflammation, which can lead to infertility, ectopic pregnancy, and chronic pelvic pain. The microbial etiology is linked to sexually transmitted microorganisms, including Chlamydia trachomatis, Neisseria gonorrheae, Mycoplasma genitalium, and bacterial vaginosis-associated microorganisms, predominantly anaerobes. Pelvic pain and fever are commonly absent in women with confirmed PID. Clinicians should consider milder symptoms such as abnormal vaginal discharge, metrorrhagia, postcoital bleeding, and urinary frequency as potential symptoms associated with the disease, particularly in women at risk of sexually transmitted infection. The diagnosis of PID is based on the findings of lower genital tract inflammation associated with pelvic organ tenderness. The outpatient treatment of mild-to-moderate PID should include tolerated antibiotic regimens with activity against the commonly isolated microorganisms associated with PID and usually consists of an extended spectrum cephalosporin in conjunction with either doxycycline or azithromycin. Clinically severe PID should prompt hospitalization and imaging to rule out a tuboovarian abscess. Parenteral broad-spectrum antibiotic therapy with activity against a polymicrobial flora, particularly gram-negative aerobes and anaerobes, should be implemented. Screening for and treatment of Chlamydia infection can prevent PID.

  6. 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

  7. Immunogenetics of ocular inflammatory disease.

    PubMed

    Levinson, R D

    2007-02-01

    Ocular inflammatory disease comprises of a diverse group of clinical entities that may result from autoimmune processes, infections, or both. While many individual ocular inflammatory diseases are quite rare, ocular inflammation is one of the more common causes of visual disability, including blindness, in the developed world. Better understanding of ocular inflammatory disease is an important step in designing more sophisticated therapies that may help prevent loss of visual function for these patients.

  8. 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

  9. 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

  10. Osteoporosis in Inflammatory Bowel Disease

    PubMed Central

    Ali, Tauseef; Lam, David; Bronze, Michael S.; Humphrey, Mary Beth

    2010-01-01

    Osteoporosis commonly afflicts patients with inflammatory bowel disease, and many factors link the 2 states together. A literature review was conducted about the pathophysiology of osteoporosis in relation to inflammatory bowel disease. Screening guidelines for osteoporosis in general as well as those directed at patients with inflammatory bowel disease are reviewed, as are currently available treatment options. The purpose of this article is to increase physician awareness about osteopenia and osteoporosis occurring in patients with inflammatory bowel disease and to provide basic, clinically relevant information about the pathophysiology and guidelines to help them treat these patients in a cost-effective manner. PMID:19559158

  11. Extracellular Vesicles in Lung Disease.

    PubMed

    Kubo, Hiroshi

    2017-07-03

    Accumulating evidence suggests that extracellular vesicles (EVs) play a role in the pathogenesis of lung diseases. These vesicles include exosomes, ectosomes (ie, microparticles, extracellular vesicles, microvesicles, and shedding vesicles), and apoptotic bodies. Exosomes are generated by inward budding of the membrane (endocytosis), subsequent forming of multivesicular bodies, and release by exocytosis. Ectosomes are formed by outward blebbing from the plasma membrane and are then released by proteolytic cleavage from the cell surface. Apoptotic bodies are generated on apoptotic cell shrinkage and death. Extracellular vesicles are released when the cells are activated or undergo apoptosis under inflammatory conditions. The number and types of released EVs are different according to the pathophysiological status of the disease. Therefore, EVs can be novel biomarkers for various lung diseases. EVs contain several molecules, including proteins, mRNA, microRNA, and DNA; they transfer these molecules to distant recipient cells. Circulating EVs modify the targeted cells and influence the microenvironment of the lungs. For this unique capability, EVs are expected to be a new drug delivery system and a novel therapeutic target. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  12. 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.

  13. 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

  14. [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.

  15. CD11b immunophenotyping identifies inflammatory profiles in the mouse and human lungs.

    PubMed

    Duan, M; Steinfort, D P; Smallwood, D; Hew, M; Chen, W; Ernst, M; Irving, L B; Anderson, G P; Hibbs, M L

    2016-03-01

    The development of easily accessible tools for human immunophenotyping to classify patients into discrete disease endotypes is advancing personalized therapy. However, no systematic approach has been developed for the study of inflammatory lung diseases with often complex and highly heterogeneous disease etiologies. We have devised an internally standardized flow cytometry approach that can identify parallel inflammatory alveolar macrophage phenotypes in both the mouse and human lungs. In mice, lung innate immune cell alterations during endotoxin challenge, influenza virus infection, and in two genetic models of chronic obstructive lung disease could be segregated based on the presence or absence of CD11b alveolar macrophage upregulation and lung eosinophilia. Additionally, heightened alveolar macrophage CD11b expression was a novel feature of acute lung exacerbations in the SHIP-1(-/-) model of chronic obstructive lung disease, and anti-CD11b antibody administration selectively blocked inflammatory CD11b(pos) but not homeostatic CD11b(neg) alveolar macrophages in vivo. The identification of analogous profiles in respiratory disease patients highlights this approach as a translational avenue for lung disease endotyping and suggests that heterogeneous innate immune cell phenotypes are an underappreciated component of the human lung disease microenvironment.

  16. 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.

  17. Cefotaxime Treatment of Pelvic Inflammatory Disease

    PubMed Central

    Monson, Thomas P.; Miller, Timothy T.; Nolan, Charles M.

    1981-01-01

    We studied cefotaxime in the treatment of gonococcal and nongonococcal pelvic inflammatory disease. Cefotaxime was uniformly effective against gonococcal pelvic inflammatory disease. However, 4 of 11 patients with nongonococcal pelvic inflammatory disease had a suboptimal response. PMID:6275789

  18. 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.

  19. Respiratory Viral Infections in Chronic Lung Diseases.

    PubMed

    Britto, Clemente J; Brady, Virginia; Lee, Seiwon; Dela Cruz, Charles S

    2017-03-01

    Chronic lung diseases, such as chronic obstructive pulmonary disease (COPD), asthma, cystic fibrosis (CF) and interstitial lung diseases (ILD), affect many individuals worldwide. Patients with these chronic lung diseases are susceptible to respiratory lung infections and some of these viral infections can contribute to disease pathogenesis. This review highlights the associations of lung infections and the respective chronic lung diseases and how infection in the different lung diseases affects disease exacerbation and progression. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. 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

  1. 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

  2. Lung dendritic cells and the inflammatory response.

    PubMed

    Grayson, Mitchell H

    2006-05-01

    To discuss the role of conventional and plasmacytoid dendritic cells in inducing and modulating immune responses in the lung. The primary literature and selected review articles studying the role of dendritic cells in both rodent and human lungs as identified via a PubMed/MEDLINE search using the keywords dendritic cell, antigen-presenting cell, viral airway disease, asthma, allergy, and atopy. The author's knowledge of the field was used to identify studies that were relevant to the stated objective. Dendritic cells are well positioned in the respiratory tract and other mucosal surfaces to respond to any foreign protein. These cells are crucial to the initiation of the adaptive immune response through induction of antigen specific T-cell responses. These cells also play an important role in the regulation of developing and ongoing immune responses, an area that is currently under intense investigation. This review discusses the various subsets of human and rodent dendritic cells and the pathways involved in antigen processing and subsequent immune regulation by dendritic cells in the lung using both viral and nonviral allergenic protein exposure as examples. Conventional and plasmacytoid dendritic cells are uniquely situated in the immune cascade to not only initiate but also modulate immune responses. Therapeutic interventions in allergic and asthmatic diseases will likely be developed to take advantage of this exclusive position of the dendritic cell.

  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. Inflammatory cytokines in animal health and disease.

    PubMed

    Murtaugh, M P; Baarsch, M J; Zhou, Y; Scamurra, R W; Lin, G

    1996-11-01

    Inflammatory cytokines, including tumor necrosis factor (TNF), interleukin-1 (IL-1), IL-6 and IL-8, are rapidly induced early in a disease or injury process. They mediate and modulate myriad healing processes but, if overexpressed, may exacerbate the severity of a disease condition. In order to test this concept and to establish a foundation for the role of inflammatory cytokines in the pathogenesis of gram-negative bacterial infections in the respiratory tract of animals, the patterns of inflammatory cytokine expression were determined in experimental porcine pleuropneumonia. We observed that IL-1 and IL-6, but not TNF, were rapidly and dramatically elevated in the lavage fluid of the lung within 24 h of infection. The increased levels of IL-1 might contribute to increased severity of disease, but elevated IL-6 levels were consistent with a protective acute phase response. Additional studies were performed to examine the hypothesis that IL-4 expression later in infection might be involved in turning off the inflammatory response and promoting an antigen-specific humoral immune response. Interleukin-4 efficiently suppressed inflammatory cytokine production in alveolar macrophages. Its expression was induced in peripheral blood mononuclear cells by TNF, IL-4, and by reexposure to a specific antigen. To obtain the maximum amount of information on the role of inflammatory cytokines in animals of veterinary significance it will be useful to perform studies in species such that evolutionary relatedness will allow widespread application of the findings. Furthermore, the variety of molecules involved in inflammatory cytokine regulation will require much more extensive investigations of the relevant enzymes, inhibitors and receptors in veterinary species. Finally, the complexity and redundancy of immune defenses in animals mean that attempts to modulate health status through manipulation of inflammatory cytokines must be performed with caution and that a multiplicity of

  5. 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.

  6. Marijuana and lung diseases.

    PubMed

    Joshi, Manish; Joshi, Anita; Bartter, Thaddeus

    2014-03-01

    Cannabis sativa (marijuana) is used throughout the world, and its use is increasing. In much of the world, marijuana is illicit. While inhalation of smoke generated by igniting dried components of the plant is the most common way marijuana is used, there is concern over potential adverse lung effects. The purpose of this review is to highlight recent studies that explore the impact upon the respiratory system of inhaling marijuana smoke. Smoking marijuana is associated with chronic bronchitis symptoms and large airway inflammation. Occasional use of marijuana with low cumulative use is not a risk factor for the development of chronic obstructive pulmonary disease. The heavy use of marijuana alone may lead to airflow obstruction. The immuno-histopathologic and epidemiologic evidence in marijuana users suggests biological plausibility of marijuana smoking as a risk for the development of lung cancer; at present, it has been difficult to conclusively link marijuana smoking and cancer development. There is unequivocal evidence that habitual or regular marijuana smoking is not harmless. A caution against regular heavy marijuana usage is prudent. The medicinal use of marijuana is likely not harmful to lungs in low cumulative doses, but the dose limit needs to be defined. Recreational use is not the same as medicinal use and should be discouraged.

  7. 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.

  8. 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

  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. 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 ...

  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. 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.

  13. 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.

  14. Somatostatin in inflammatory bowel disease

    PubMed Central

    Wilson, J. H. P.

    1997-01-01

    Intestinal inflammation is controlled by various immunomodulating cells, interacting by molecular mediators. Neuropeptides, released by enteric nerve cells and neuroendocrine mucosa cells, are able to affect several aspects of the general and intestinal immune system, with both pro- as well as anti-inflammatory activities. In inflammatory bowel disease (IBD) there is both morphological as well as experimental evidence for involvement of neuropeptides in the pathogenesis. Somatostatin is the main inhibitory peptide in inflammatory processes, and its possible role in IBD is discussed. PMID:18472863

  15. 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 ...

  16. [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. Copyright © 2015 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  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. 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.

  19. 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.

  20. Connexins as therapeutic targets in lung disease.

    PubMed

    Losa, Davide; Chanson, Marc; Crespin, Sophie

    2011-08-01

    The lung is a mechanically active system exposed to the external environment and is particularly sensitive to injury and inflammation. Studies have identified intercellular communication pathways that promote proper lung function in response to injury and disease. These pathways involve connexins (Cxs) and gap junctional intercellular communication (GJIC). The functional expression of Cxs in airway epithelium and vasculature, under normal and pathological conditions, is reviewed. Inhibition of GJIC and/or silencing of Cxs have been shown to modulate the course of disease development. Cx-based channels: i) coordinate ciliary beating and fluid transport to promote clearance of particulates, ii) regulate secretion of pulmonary surfactant, in response to deep inhalation by interconnecting type I and type II alveolar epithelial cells, and iii) are key mediators of pro- and anti-inflammatory signalling by the pulmonary endothelium, in order to modulate leukocyte recruitment from the circulation. Cx-based channels play several central roles in promoting a regulated inflammatory response and facilitating lung repair, thus enabling the pulmonary epithelium and vasculature to behave as integrated systems. Several pathologies can disrupt the normal communication pathways required for proper lung function, including acute lung injury, asthma, cystic fibrosis, pulmonary fibrosis and cancer.

  1. Occupational and environmental lung disease.

    PubMed

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

    2015-06-01

    Occupational and environmental lung disease remains a major cause of respiratory impairment worldwide. Despite regulations, increasing rates of coal worker's pneumoconiosis and progressive massive fibrosis are being reported in the United States. Dust exposures are occurring in new industries, for instance, silica in hydraulic fracking. Nonoccupational environmental lung disease contributes to major respiratory disease, asthma, and COPD. Knowledge of the imaging patterns of occupational and environmental lung disease is critical in diagnosing patients with occult exposures and managing patients with suspected or known exposures. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. 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 ...

  3. Rheumatoid arthritis-associated interstitial lung disease

    PubMed Central

    Solomon, Joshua J; Brown, Kevin K

    2012-01-01

    Rheumatoid arthritis (RA) is a systemic inflammatory disorder affecting 1% of the US population. Patients can have extra-articular manifestations of their disease and the lungs are commonly involved. RA can affect any compartment of the respiratory system and high resolution computed tomography (HRCT) of the lung is abnormal in over half of these patients. Interstitial lung disease is a dreaded complication of RA. It is more prevalent in smokers, males, and those with high antibody titers. The pathogenesis is unknown but data suggest an environmental insult in the setting of a genetic predisposition. Smoking may play a role in the pathogenesis of disease through citrullination of protein in the lung leading to the development of autoimmunity. Patients usually present in middle age with cough and dyspnea. Pulmonary function testing most commonly shows reduced diffusion capacity for carbon monoxide and HRCT reveals a combination of reticulation and ground glass abnormalities. The most common pattern on HRCT and histopathology is usual interstitial pneumonia (UIP), with nonspecific interstitial pneumonia seen less frequently. There are no large-scale well-controlled treatment trials. In severe or progressive cases, treatment usually consists of corticosteroids with or without a cytotoxic agent for 6 months or longer. RA interstitial lung disease is progressive; over half of patients show radiographic progression within 2 years. Patients with a UIP pattern on biopsy have a survival similar to idiopathic pulmonary fibrosis. PMID:27790009

  4. 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

  5. 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.

  6. Chronic Inflammatory Disease, Lifestyle and Treatment Response

    ClinicalTrials.gov

    2017-05-30

    Autoimmune Diseases; Inflammatory Bowel Diseases; Crohn Disease (CD); Colitis, Ulcerative (UC); Arthritis, Rheumatoid (RA); Spondylarthropathies; Arthritis, Psoriatic (PsA); Psoriasis; Hidradenitis Suppurativa (HS); Uveitis

  7. 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.

  8. 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.

  9. 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

  10. Immunopathogenesis of inflammatory bowel disease

    PubMed Central

    Shih, David Q; Targan, Stephan R

    2008-01-01

    Crohn’s disease and ulcerative colitis are chronic relapsing immune mediated disorders that results from an aberrant response to gut luminal antigen in genetically susceptible host. The adaptive immune response that is then triggered was widely considered to be a T-helper-1 mediated condition in Crohn’s disease and T-helper-2 mediated condition in ulcerative colitis. Recent studies in animal models, genome wide association, and basic science has provided important insights in in the immunopathogenesis of inflammatory bowel disease, one of which was the characterization of the interleukin-23/Th-17 axis. PMID:18200661

  11. 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.

  12. 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. Copyright ©ERS 2015.

  13. Autophagy in lung disease pathogenesis and therapeutics.

    PubMed

    Ryter, Stefan W; Choi, Augustine M K

    2015-01-01

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

  14. 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

  15. Nutrigenomics and inflammatory bowel diseases.

    PubMed

    Ferguson, Lynnette R

    2010-07-01

    The field of nutrigenomics recognizes gene-diet interactions, with regard to both the impact of genetic variation on nutrient requirements, and conversely nutrient regulation of the expression of genes. Crohn's disease and ulcerative colitis are inflammatory bowel diseases for which twin studies reveal genetic susceptibility that is impacted by diet and environment. Apparently contradictory data on the role of diet in inflammatory bowel disease would be entirely explainable if genetic variability determined dietary requirements and intolerances. Considering Crohn's disease, we recognize three major classes of genes. The first of these involves bacterial recognition through pattern recognition receptors and autophagy genes, while the second act through secondary immune response, and the third concern epithelial barrier integrity. Despite genetic overlap with CD, the first two groups of genes appear to be less important in ulcerative colitis, while other genes, particularly those involved in barrier function, gain prominence. Case-control studies suggest that these different genetic groups reflect distinct dietary requirements. Such studies suggest nutrigenomic approaches to maintaining disease remission at present, and preventing disease development in the future.

  16. 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.

  17. Lung Transplantation for Scleroderma-related Lung Disease

    PubMed Central

    Richardson, Claire B.; Singer, Jonathan P

    2014-01-01

    Lung transplantation for scleroderma-related lung disease is controversial due to extra-pulmonary organ involvement that may threaten allograft and patient survival after transplant surgery. Despite concerns, several lung transplant programs do offer lung transplantation to patients with scleroderma-related lung disease. In this review, we evaluate the scleroderma-related extra-pulmonary organ involvement that may result in poorer outcomes after lung transplantation as well as the existing evidence on survival, freedom from bronchiolitis obliterans syndrome (BOS), and other important clinical outcomes after lung transplantation. Among the nine studies reviewed, comprising 226 subjects, survival and freedom from BOS appears to be similar for subjects undergoing lung transplantation for scleroderma compared to non-scleroderma lung diseases. Although scleroderma is a systemic disease with several unique potential threats to allograft and patient survival, lung transplantation appears to be a reasonable intervention for this patient population. PMID:27833787

  18. Autophagy: Friend or Foe in Lung Disease?

    PubMed Central

    Mizumura, Kenji; Cloonan, Suzanne; Hashimoto, Shu; Nakahira, Kiichi; Ryter, Stefan W.; Choi, Augustine M. K.

    2016-01-01

    Autophagy is a highly conserved process by which cells can recycle organelles and proteins by degrading them in the lysosomes. Although autophagy is considered a dynamic system responsible for cellular renovation and homeostasis under physiological conditions, it is increasingly clear that autophagy is directly relevant to clinical disease. During disease progression, autophagy not only serves as a cellular protective mechanism but also can represent a harmful event under certain conditions. In addition, although autophagy can act as a nonselective bulk degradation process, recent research shows that autophagy can selectively degrade specific proteins, organelles, and invading bacteria, in processes termed “selective autophagy.” Selective autophagy has drawn the attention of researchers because of its potential importance in clinical diseases. In this article, we outline the most recent studies implicating autophagy and selective autophagy in human lung diseases, including chronic obstructive pulmonary disease, pulmonary hypertension, idiopathic pulmonary fibrosis, and sepsis. We also discuss the relationship between autophagy and other molecular mechanisms related to disease progression, including programmed necrosis (necroptosis) and the inflammasome, an inflammatory signaling platform that regulates the secretion of IL-1β and IL-18. Finally, we examine the dual nature of autophagy and selective autophagy in the lung, which have both protective and injurious effects for human lung disease. PMID:27027951

  19. 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

  20. 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

  1. [Helminths and inflammatory bowel diseases].

    PubMed

    Laclotte, C; Oussalah, A; Rey, P; Bensenane, M; Pluvinage, N; Chevaux, J-B; Trouilloud, I; Serre, A-A; Boucekkine, T; Bigard, M-A; Peyrin-Biroulet, L

    2008-12-01

    The current etiologic model of inflammatory bowel diseases proposes a genetically predisposed host responding to a variety of environmental triggers by exhibiting an abnormal immune response to normal luminal flora. Crohn's disease is common in highly industrialized western countries where helminths are rare and uncommon in less developed areas of the world where most people carry worms. From this observation grew the hygiene hypothesis, which states that our failure to be exposed to previously common infectious agents alters the immune repertoire established in childhood. Helminths diminish immune responsiveness in naturally colonised humans and reduce inflammation in experimental colitis. Crohn's disease involves over reactive T-helper (Th1) pathways, and helminths blunt Th1 responses, inducing production of Th2 cytokines. Helminths also induce regulatory T cells to maintain host mucosal homeostasis. Thus, there is an immunological basis to expect that exposure to helminths such as Trichuris suis will prove beneficial in Crohn's disease. Exposure to helminths may be effective in treating inflammatory bowel diseases and was well tolerated, according to the results of few studies. Its long-term safety remains unknown.

  2. Drug Induced Interstitial Lung Disease

    PubMed Central

    Schwaiblmair, Martin; Behr, Werner; Haeckel, Thomas; Märkl, Bruno; Foerg, Wolfgang; Berghaus, Thomas

    2012-01-01

    With an increasing number of therapeutic drugs, the list of drugs that is responsible for severe pulmonary disease also grows. Many drugs have been associated with pulmonary complications of various types, including interstitial inflammation and fibrosis, bronchospasm, pulmonary edema, and pleural effusions. Drug-induced interstitial lung disease (DILD) can be caused by chemotherapeutic agents, antibiotics, antiarrhythmic drugs, and immunosuppressive agents. There are no distinct physiologic, radiographic or pathologic patterns of DILD, and the diagnosis is usually made when a patient with interstitial lung disease (ILD) is exposed to a medication known to result in lung disease. Other causes of ILD must be excluded. Treatment is avoidance of further exposure and systemic corticosteroids in patients with progressive or disabling disease. PMID:22896776

  3. Probiotics and inflammatory bowel diseases.

    PubMed

    Bai, A-P; Ouyang, Q

    2006-06-01

    Enteric microflora profiles vary considerably between active inflammatory bowel diseases (IBD) and healthy conditions. Intestinal microflora may partake in the pathogenesis of IBD by one or some ways: specific pathogenic infection induces abnormal intestinal mucosal inflammation; aberrant microflora components trigger the onset of IBD; abnormal host immune response loses normal immune tolerance to luminal components; luminal antigens permeate through the defective mucosal barrier into mucosal lamina propria and induce abnormal inflammatory response. Preliminary studies suggest that administration of probiotics may be benefit for experimental colitis and clinical trials for IBD. Researches have been studying the function of probiotics. Introduction of probiotics can balance the aberrant enteric microflora in IBD patients, and reinforce the various lines of intestinal defence by inhibiting microbial pathogens growth, increasing intestinal epithelial tight junction and permeability, modulating immune response of intestinal epithelia and mucosal immune cells, secreting antimicrobial products, decomposing luminal pathogenic antigens.

  4. Types of Childhood Interstitial Lung Disease

    MedlinePlus

    ... from the NHLBI on Twitter. Types of Childhood Interstitial Lung Disease The broad term "childhood interstitial lung disease" (chILD) ... therapeutic intervention Lung and bone marrow transplant-associated lung diseases Diffuse alveolar damage of unknown cause The various types ...

  5. 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

  6. 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.

  7. Molecular diagnosis in lung diseases.

    PubMed

    Calabrese, Fiorella; Lunardi, Francesca; Popper, Helmut

    2015-01-01

    The development of different molecular biology techniques in the past decade has led to an explosion of new research in molecular pathology with consequent important applications to diagnosis, prognosis, and therapeutics, as well as a clearer concept of the disease pathogenesis. Many methods used in molecular pathology are now validated and used in several areas of pathological diagnosis, particularly on infectious and neoplastic diseases. The spectrum of infectious diseases, especially lung infective diseases, is now broadening and modifying, thus the pathologist is increasingly involved in the diagnosis of these pathologies. The precise tissue characterization of lung infections has an important impact on specific therapeutic treatment. Increased knowledge of significant alterations in lung cancer has led today to a better understanding of the pathogenic substrate underlying the development, progression and metastasis of neoplastic processes. Molecular tests are now routinely performed in different lung tumors allowing a more precise patient stratification in terms of prognosis and therapy. This review focuses on molecular pathology of the principal infective lung diseases and tumors.

  8. 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.

  9. 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. Published by Elsevier Inc.

  10. Mechanical ventilation increases the inflammatory response induced by lung contusion.

    PubMed

    van Wessem, Karlijn J P; Hennus, Marije P; van Wagenberg, Linda; Koenderman, Leo; Leenen, Luke P H

    2013-07-01

    Posttraumatic lung contusion is common after blunt chest trauma, and patients often need ventilatory support. Lung contusion induces an inflammatory response signified by primed polymorph neutrophil granulocytes (PMNs) in blood and tissue. Mechanical ventilation (MV) can also cause an inflammatory response. The aim of this study was to develop an animal model to investigate the effect of high-volume ventilation on the inflammatory response in blunt chest trauma. We assigned 23 male Sprague-Dawley rats to either MV or bilateral lung contusion followed by MV. We used three extra rats as controls. Lung contusion was induced by a blast generator, a device releasing a single pressure blast wave centered on the chest. We determined tissue and systemic inflammation by absolute PMN numbers in blood and bronchoalveolar lavage fluid (BALF), myeloperoxidase, interleukin (IL)-6, IL 1β, growth-related oncogene-KC, and IL-10 in both plasma and BALF. Survival after blunt chest trauma was correlated to the distance to the blast generator. Compared with controls, both MV and blast plus MV rats showed increased systemic and pulmonary inflammation, expressed by higher PMNs, myeloperoxidase levels, and cytokine levels in both blood and BALF. Blast plus MV rats showed a higher systemic and pulmonary inflammatory response than MV rats. The blast generator generated reproducible blunt chest trauma in rats. Mechanical ventilation after lung contusion induced a larger overall inflammatory response than MV alone, which indicates that local damage contributes not only to local inflammation, but also to systemic inflammation. This emphasizes the importance of lung protective ventilation strategies after pulmonary contusion. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Proteases and oxidant stress control organic dust induction of inflammatory gene expression in lung epithelial cells.

    PubMed

    Natarajan, Kartiga; Gottipati, Koteswara R; Berhane, Kiflu; Samten, Buka; Pendurthi, Usha; Boggaram, Vijay

    2016-10-22

    Persistant inflammatory responses to infectious agents and other components in organic dust underlie lung injury and development of respiratory diseases. Organic dust components responsible for eliciting inflammation and the mechanisms by which they cause lung inflammation are not fully understood. We studied the mechanisms by which protease activities in poultry dust extracts and intracellular oxidant stress induce inflammatory gene expression in A549 and Beas2B lung epithelial cells. The effects of dust extracts on inflammatory gene expression were analyzed by quantitative polymerase chain reaction (qPCR), enzyme linked immunosorbent (ELISA) and western blot assays. Oxidant stress was probed by dihydroethidium (DHE) labeling, and immunostaining for 4-hydroxynonenal (4-HNE). Effects on interleukin-8 (IL-8) promoter regulation were determined by transient transfection assay. Dust extracts contained trypsin and elastase activities, and activated protease activated receptor (PAR)-1 and -2. Serine protease inhibitors and PAR-1 or PAR-2 knockdown suppressed inflammatory gene induction. Dust extract induction of IL-8 gene expression was associated with increased DHE-fluorescence and 4-HNE staining, and antioxidants suppressed inflammatory gene induction. Protease inhibitors and antioxidants suppressed protein kinase C and NF-κB activation and induction of IL-8 promoter activity in cells exposed to dust extract. Our studies demonstrate that proteases and intracellular oxidants control organic dust induction of inflammatory gene expression in lung epithelial cells. Targeting proteases and oxidant stress may serve as novel approaches for the treatment of organic dust induced lung diseases. This is the first report on the involvement of oxidant stress in the induction of inflammatory gene expression by organic dust.

  12. 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.

  13. Infections in inflammatory bowel disease.

    PubMed

    Rodríguez de Santiago, Enrique; Albillos Martínez, Agustín; López-Sanromán, Antonio

    2017-05-10

    Patients with inflammatory bowel disease constitute a population with a special predisposition to develop bacterial, viral and fungal infections. Iatrogenic immunosuppression, frequent contact with healthcare facilities and surgical interventions are some of the risk factors that explain why these infections are one of the main causes of morbi-mortality in this disease. Some of these infections follow a subtle and paucisymptomatic evolution; their diagnosis and management may become a real challenge for the attending physician if their screening is not systematized or they are not considered in the differential diagnosis. The objective of this review is to provide an update from a practical and concise perspective on the knowledge regarding the epidemiology, prevention, diagnosis and treatment of the most common infections. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  14. 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

  15. 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.

  16. Comparison of inflammatory responses in mouse lungs exposed to atranones A and C from Stachybotrys chartarum.

    PubMed

    Rand, Thomas G; Flemming, J; David Miller, J; Womiloju, Taiwo O

    2006-07-01

    Stachybotrys chartarum isolates can be separated into two distinct chemotypes based on the toxins they produce. One chemotype produces macrocyclic trichothecenes; the other produces atranones (and sometimes simple trichothecenes, e.g., trichodermol and trichodermin). Studies using in vivo models of lung disease revealed that exposure to spores of the atranone producing S. chartarum isolates led to a variety of immunotoxic, inflammatory, and other pathological changes. However, it is unclear from these studies what role the pure atranone toxins sequestered in spores of these isolates exert on lung disease onset. This study examined dose-response (0.2, 1.0, 2.0, 5.0, or 20 microg atranone/animal) and time-course (3, 6, 24, and 48 h postinstillation [PI]) relationships associated with inflammatory cell and proinflammatory chemokine/cytokine responses in mouse lungs intratracheally instilled with two pure atranones (either A or C) isolated from S. chartarum. High doses (2.0 to 20 microg toxin/animal) of atranone A and C induced significant inflammatory responses manifested as differentially elevated macrophage, neutrophil, macrophage inflammatory protein (MIP)-2, tumor necrosis factor (TNF) and interleukin (IL)-6 concentrations in the bronchioalveolar lavage fluid (BALF) of intratracheally exposed mice. Compared to controls, BALF macrophage and neutrophil numbers were increased to significant levels from 6 to 48 h (PI). Except for macrophage numbers in atranone A treatment animals, cells exhibited significant dose dependent-like responses. The chemokine/cytokine marker responses were significantly and dose-dependently increased from 3 to 24 h PI and declined to nonsignificant levels at 48 h PI. The results suggest not only that atranones are inflammatory but also that they exhibit different inflammatory potency with different toxicokinetics. Data also suggest that exposure to these toxins in spores of S. chartarum in contaminated building environments could contribute

  17. Inflammation and angiogenesis in fibrotic lung disease.

    PubMed

    Keane, Michael P; Strieter, Robert M; Lynch, Joseph P; Belperio, John A

    2006-12-01

    The pathogenesis of pulmonary fibrosis is poorly understood. Although inflammation has been presumed to have an important role in the development of fibrosis this has been questioned recently, particularly with regard to idiopathic pulmonary fibrosis (IPF). It is, however, increasingly recognized that the polarization of the inflammatory response toward a type 2 phenotype supports fibroproliferation. Increased attention has been on the role of noninflammatory structural cells such as the fibroblast, myofibroblast, epithelial cell, and endothelial cells. Furthermore, the origin of these cells appears to be multifactorial and includes resident cells, bone marrow-derived cells, and epithelial to mesenchymal transition. Increasing evidence supports the presence of vascular remodeling in fibrotic lung disease, although the precise role in the pathogenesis of fibrosis remains to be determined. Therefore, the pathogenesis of pulmonary fibrosis is complex and involves the interaction of multiple cell types and compartments within the lung.

  18. 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

  19. 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

  20. 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.

  1. Nutrition in inflammatory bowel disease

    PubMed

    Martínez Gómez, María Josefa; Melián Fernández, Cristóbal; Romeo Donlo, María

    2016-07-12

    Inflammatory bowel disease (IBD) is a chronic pathology that has an outbreaks course that in recent years have seen an increase in incidence, especially at younger ages. Malnutrition is frequently associated with this condition, therefore, it is very important to ensure a right nutritional intervention, especially in pediatric patients, to ensure an optimal growth and also an improvement in the clinic. Our goal will be updated the role of nutrition in this disease and in its treatment based on the published evidence. Malnutrition in these patients is frequent and is influenced by various factors such as, decreased food intake, increased nutrient requirements, increased protein loss and malabsorption of nutrients. Therefore there should be a nutritional monitoring of all of them, in which anthropometric measurements, laboratory tests and densitometry were made to establish the needs and sufficient caloric intake tailored to each patient. The use of enteral nutrition as a treatment in Crohn’s disease with mild to moderate outbreak in child population, is amply demonstrated, has even shown to be superior to the use of corticosteroids. Therefore we can conclude by stressing that nutritional intervention is a mainstay in the management of patients with IBD, which aims to prevent and / or control disease-related malnutrition to decrease morbidity and mortality and improve quality of life.

  2. 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

  3. 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.

  4. 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.

  5. 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. Copyright © 2015 the American Physiological Society.

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

    PubMed Central

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

    2015-01-01

    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. PMID:26342085

  7. 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

  8. 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.

  9. Angiogenesis in Inflammatory Bowel Disease

    PubMed Central

    Alkim, Canan; Alkim, Huseyin; Koksal, Ali Riza; Boga, Salih; Sen, Ilker

    2015-01-01

    Angiogenesis is an important component of pathogenesis of inflammatory bowel disease (IBD). Chronic inflammation and angiogenesis are two closely related processes. Chronic intestinal inflammation is dependent on angiogenesis and this angiogenesis is modulated by immune system in IBD. Angiogenesis is a very complex process which includes multiple cell types, growth factors, cytokines, adhesion molecules, and signal transduction. Lymphangiogenesis is a new research area in the pathogenesis of IBD. While angiogenesis supports inflammation via leukocyte migration, carrying oxygen and nutrients, on the other hand, it has a major role in wound healing. Angiogenic molecules look like perfect targets for the treatment of IBD, but they have risk for serious side effects because of their nature. PMID:26839731

  10. 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

  11. Quick-Relief Medications for Lung Diseases

    MedlinePlus

    ... relief medications are used to treat asthma, other lung disease symptoms or an acute episode (such as an ... about the following quick-relief asthma and other lung disease medications: Anticholinergics Anticholinergics are quick-relief asthma and ...

  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. Rare Lung Diseases: Interstitial Lung Diseases and Lung Manifestations of Rheumatological Diseases.

    PubMed

    Ramamurthy, Mahesh Babu; Goh, Daniel Y T; Lim, Michael Teik Chung

    2015-10-01

    The concept of Childhood Interstitial Lung Disease (ChILD) is relatively young. There has been tremendous progress in this field in the last decade. The key advance has been the recognition of interstitial lung diseases that are often distinct and occur mainly in infants. Diagnosis is challenging because the incidence is low and no single center in the world has enough cases to promote experience and clinical skills. This has led to formation of international groups of people interested in the field and the "Children's interstitial and diffuse lung disease research network" (ChILDRN) is one such group which contributed to the progress of this field. Clinically, these disorders overlap with those of other common respiratory disorders. Hence, clinical practice guidelines emphasize the additional role of chest imaging, genetic testing and lung biopsy in the diagnostic evaluation. Genetic testing, in particular, has shown tremendous progress in this field. Being noninvasive, it has the potential to help early recognition in a vast majority. Despite progress, definitive therapeutic modalities are still lacking and supportive care is still the backbone of management in the majority. Early recognition of the definitive diagnosis helps in the management, even if, in a significant number, it helps in avoiding unnecessary therapy. Also discussed in this article, is the pulmonary manifestation of rheumatic diseases in children. The incidence and spectrum of pulmonary involvement in rheumatic conditions vary and can be result of the primary disease or its management or due to an concurrent infection.

  14. Nutrition in inflammatory bowel disease.

    PubMed

    Alastair, Forbes; Emma, Goldesgeyme; Emma, Paulon

    2011-09-01

    The diet of industrialized nations may contribute to the pathogenesis of both ulcerative colitis (UC) and Crohn disease (CD). Malnutrition is relatively unusual in UC, but in CD, which often affects the small intestine, it is frequent and may be severe. Nutrition support is therefore frequently indicated. First principles of artificial nutrition can be applied effectively using the gut whenever possible. Parenteral nutrition is generally required only in those with short bowel syndrome. An increasing literature (especially in pediatrics) favors the use of defined exclusive enteral nutrition (EN) in the primary treatment of active CD. Controlled trials are, however, lacking, and recommendations are accordingly not of the highest rank. It appears that in this context, simple polymeric regimens are usually sufficient, and there is currently insufficient evidence to make a strong recommendation for disease-specific feeds. In the maintenance of remission in CD, controlled data demonstrate that defined EN reduces the risk of relapse requiring steroid treatment. There are no data in support of primary nutrition therapy in UC either in management of the acute flare or in maintenance. In conclusion, nutrition therapy in adults with inflammatory bowel disease is probably both undervalued and underused, but the evidence base needs to be strengthened to confirm its efficacy, determine better those patients most likely to benefit, and optimize the regimens to be employed.

  15. Immune and Inflammatory Cell Composition of Human Lung Cancer Stroma

    PubMed Central

    Banat, G-Andre; Tretyn, Aleksandra; Pullamsetti, Soni Savai; Wilhelm, Jochen; Weigert, Andreas; Olesch, Catherine; Ebel, Katharina; Stiewe, Thorsten; Grimminger, Friedrich; Seeger, Werner; Fink, Ludger; Savai, Rajkumar

    2015-01-01

    Recent studies indicate that the abnormal microenvironment of tumors may play a critical role in carcinogenesis, including lung cancer. We comprehensively assessed the number of stromal cells, especially immune/inflammatory cells, in lung cancer and evaluated their infiltration in cancers of different stages, types and metastatic characteristics potential. Immunohistochemical analysis of lung cancer tissue arrays containing normal and lung cancer sections was performed. This analysis was combined with cyto-/histomorphological assessment and quantification of cells to classify/subclassify tumors accurately and to perform a high throughput analysis of stromal cell composition in different types of lung cancer. In human lung cancer sections we observed a significant elevation/infiltration of total-T lymphocytes (CD3+), cytotoxic-T cells (CD8+), T-helper cells (CD4+), B cells (CD20+), macrophages (CD68+), mast cells (CD117+), mononuclear cells (CD11c+), plasma cells, activated-T cells (MUM1+), B cells, myeloid cells (PD1+) and neutrophilic granulocytes (myeloperoxidase+) compared with healthy donor specimens. We observed all of these immune cell markers in different types of lung cancers including squamous cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma, small cell carcinoma, papillary adenocarcinoma, metastatic adenocarcinoma, and bronchioloalveolar carcinoma. The numbers of all tumor-associated immune cells (except MUM1+ cells) in stage III cancer specimens was significantly greater than those in stage I samples. We observed substantial stage-dependent immune cell infiltration in human lung tumors suggesting that the tumor microenvironment plays a critical role during lung carcinogenesis. Strategies for therapeutic interference with lung cancer microenvironment should consider the complexity of its immune cell composition. PMID:26413839

  16. Adenosine signaling and the regulation of chronic lung disease

    PubMed Central

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

    2009-01-01

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

  17. 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

  18. 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

  19. 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

  20. 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

  1. Imaging of Occupational Lung Disease.

    PubMed

    Champlin, Jay; Edwards, Rachael; Pipavath, Sudhakar

    2016-11-01

    Occupational lung diseases span a variety of pulmonary disorders caused by inhalation of dusts or chemical antigens in a vocational setting. Included in these are the classic mineral pneumoconioses of silicosis, coal worker's pneumoconiosis, and asbestos-related diseases as well as many immune-mediated and airway-centric diseases, and new and emerging disorders. Although some of these have characteristic imaging appearances, a multidisciplinary approach with focus on occupational exposure history is essential to proper diagnosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. 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.

  3. Caring for Women with Inflammatory Bowel Disease.

    PubMed

    Feagins, Linda A; Kane, Sunanda V

    2016-06-01

    Ulcerative colitis and Crohn disease are chronic inflammatory diseases with typical onset in early adulthood. These diseases, therefore, can affect a woman throughout the many stages of her life, including menstruation, sexuality, pregnancy, and menopause. Unique health issues face women during these stages and can affect the course of their inflammatory bowel disease as well as treatment strategies and health maintenance. This article covers the non-pregnancy-related issues that are important in caring for women with inflammatory bowel disease. The topics of pregnancy and fertility are covered in a separate review. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. 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

  5. Parenteral nutrition in inflammatory bowel disease.

    PubMed Central

    Matuchansky, C

    1986-01-01

    Nutritional support, administered via the enteral or parenteral routes, has been widely introduced in the treatment of inflammatory bowel disease over the past decade. The precise place of total parenteral nutrition, however, as a sole or adjunct treatment of inflammatory bowel disease, has yet to be defined. PMID:3098647

  6. [The temporomandibular joint and inflammatory rheumatic diseases].

    PubMed

    Marotte, H

    2016-09-01

    Some inflammatory rheumatic diseases can involve the temporomandibular joint, such as rheumatoid arthritis and spondylarthritis. The aim of our work was to evaluate the current prevalence of these inflammatory TMJ diseases, to indicate the new therapeutics and to describe the collaboration between rheumatologist and maxillofacial surgeon in these pathologies. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  7. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Diffuse lung diseases in cigarette smokers.

    PubMed

    Vassallo, Robert

    2012-10-01

    Cigarette smoking is a recognized causative agent or precipitant of specific diffuse lung diseases characterized by bronchiolar and interstitial lung inflammation. Respiratory bronchiolitis-associated interstitial lung disease and pulmonary Langerhans cell histiocytosis are now considered smoking-induced diffuse lung diseases. Desquamative interstitial pneumonia is also recognized as a smoking-induced interstitial pneumonia in most cases. These disorders affect relatively young adult smokers and may be progressive. Although distinguishable by histopathological and radiographic features, significant overlap occurs in many cases with chest radiography and lung histology showing overlapping features of smoking-related bronchiolar and interstitial lung injury. Cigarette smoking is also recognized as an important precipitant of many acute eosinophilic pneumonia cases. Smokers are at higher risk of developing fibrotic interstitial lung diseases such as idiopathic pulmonary fibrosis and rheumatoid arthritis-associated interstitial lung disease. Certain smokers also develop combined emphysema and lung fibrosis. The avoidance of primary and second-hand cigarette smoke is a critical component of management for patients afflicted with these smoking-induced diffuse lung diseases. The role of corticosteroids and other immunosuppressive treatments in the management of smoking-related interstitial lung diseases remains poorly defined and should be reserved for individuals with progressive disease despite smoking cessation. Understanding mechanisms by which tobacco induces diffuse lung pathology is critical in the pursuit of novel therapeutic approaches for these diseases. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  9. [Drug-induced lung diseases].

    PubMed

    Camus, Philippe

    2007-12-31

    Drug-induced interstitial pneumonias are systematically considered in the differential diagnosis of the interstitial pneumonias. The presentation may be acute, sub-acute or chronic, with the same drug possibly leading to either acute or subacute/chronic interstitial lung disease (e.g. amiodarone). There is no definite diagnostic criterion, the final diagnosis relying on the clinical and imaging features, the chronology of pulmonary manifestations, and the prevalence of reported cases with the suspected drug.

  10. Diffuse cystic lung diseases: differential diagnosis.

    PubMed

    Baldi, Bruno Guedes; Carvalho, Carlos Roberto Ribeiro; Dias, Olívia Meira; Marchiori, Edson; Hochhegger, Bruno

    2017-01-01

    Diffuse cystic lung diseases are characterized by cysts in more than one lung lobe, the cysts originating from various mechanisms, including the expansion of the distal airspaces due to airway obstruction, necrosis of the airway walls, and parenchymal destruction. The progression of these diseases is variable. One essential tool in the evaluation of these diseases is HRCT, because it improves the characterization of pulmonary cysts (including their distribution, size, and length) and the evaluation of the regularity of the cyst wall, as well as the identification of associated pulmonary and extrapulmonary lesions. When combined with clinical and laboratory findings, HRCT is often sufficient for the etiological definition of diffuse lung cysts, avoiding the need for lung biopsy. The differential diagnoses of diffuse cystic lung diseases are myriad, including neoplastic, inflammatory, and infectious etiologies. Pulmonary Langerhans cell histiocytosis, lymphangioleiomyomatosis, lymphocytic interstitial pneumonia, and follicular bronchiolitis are the most common diseases that produce this CT pattern. However, new diseases have been included as potential determinants of this pattern. RESUMO As doenças pulmonares císticas difusas se caracterizam pela presença de cistos envolvendo mais de um lobo pulmonar, que se originam por diversos mecanismos, incluindo dilatação dos espaços aéreos distais por obstrução, necrose das paredes das vias aéreas e destruição do parênquima. Essas doenças apresentam evolução variável. A TCAR é fundamental na avaliação dessas doenças uma vez que permite uma melhor caracterização dos cistos pulmonares, incluindo sua distribuição, tamanho, extensão e regularidade das paredes, assim como a determinação de outras lesões pulmonares e extrapulmonares associadas. Frequentemente a TCAR é suficiente para a definição etiológica dos cistos pulmonares difusos, associada a achados clínicos e laboratoriais, sem a necessidade

  11. 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

  12. 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

  13. 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.

  14. Farmer's Lung Disease. A Review.

    PubMed

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

    2016-06-01

    Farmer's lung disease (FLD) is a form of hypersensitivity pneumonitis (HP) caused by inhaling microorganisms from hay or grain stored in conditions of high humidity in the agricultural workplace. It is probably underdiagnosed, especially in northern Spain, where climatic conditions favor the development of this disease. According to previous studies, the most common antigens are usually thermophilic actinomycetes and fungi. The epidemiology of the disease is not well known, and is based on studies conducted by Central European and Asian groups. The clinical presentation may vary, differentiating the chronic (exposure to lower concentrations of the antigen over a longer period time) and the acute forms (after exposure to high concentrations of the antigen). In patients with respiratory symptoms and agricultural occupational exposure, radiological, lung function and/or anatomical pathology findings must be compatible with FLD, bronchoalveolar lavage must show lymphocytosis, and tests must find sensitivity to the antigen. The main treatment is avoidance of the antigen, so it is essential to educate patients on preventive measures. To date, no controlled studies have assessed the role of immunosuppressive therapy in this disease. Corticosteroid treatment has only been shown to accelerate resolution of the acute forms, but there is no evidence that it is effective in preventing disease progression in the long-term or reducing mortality. Copyright © 2016 SEPAR. Published by Elsevier Espana. All rights reserved.

  15. 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.

  16. 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

  17. 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.

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

    PubMed Central

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

    2013-01-01

    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. PMID:20883710

  19. 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

  20. Genetics of Inflammatory Bowel Diseases

    PubMed Central

    McGovern, Dermot; Kugathasan, Subra; Cho, Judy H.

    2015-01-01

    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 non-coding genetic variation. In the small minority of loci where major association signals correspond to non-synonymous variation, we summarize studies defining their functional effects and implications for therapeutic targeting. Importantly, the large majority of GWAS-associated loci involve non-coding variation, many of which modulate levels of gene expression. Recent expression quantitative trait loci (eQTL) studies have established that expression of the large majority of human genes is regulated by non-coding genetic variation. 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 (i.e. odds ratios markedly deviating from one) is increasingly being identified through sequencing efforts. These sequencing studies have been particularly productive in very-early onset, more severe cases. A major challenge in IBD genetics will be harnessing the vast array of genetic discovery for clinical utility, through emerging precision medicine initiatives. We discuss the rapidly evolving area of direct to consumer genetic testing, as well as 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 of partitioning patient responses to anti-TNF and thiopurine therapies. Highly collaborative studies across research

  1. 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.

  2. [Coexistence of coeliac disease and inflammatory bowel disease in children].

    PubMed

    Krawiec, Paulina; Pawłowska-Kamieniak, Agnieszka; Pac-Kożuchowska, Elżbieta; Mroczkowska-Juchkiewcz, Agnieszka; Kominek, Katarzyna

    2016-01-01

    Coeliac disease and inflammatory bowel disease are chronic inflammatory conditions of gastrointestinal tract with complex aetiology with genetic, environmental and immunological factors contributing to its pathogenesis. It was noted that immune-mediated disorders often coexist. There is well-known association between coeliac disease and type 1 diabetes and ulcerative colitis and primary sclerosing cholangitis. However, growing body of literature suggests the association between coeliac disease and inflammatory bowel disease, particularly ulcerative colitis. This is an extremely rare problem in paediatric gastroenterology. To date there have been reported several cases of children with coexisting coeliac disease and inflammatory bowel disease. Herewith we present review of current literature on coexistence of coeliac disease and inflammatory bowel disease in children. © 2016 MEDPRESS.

  3. [Recent advances in the study of AMPK and inflammatory pulmonary disease].

    PubMed

    Xuan, Ling-Ling; Hou, Qi

    2014-08-01

    AMP-activated protein kinase (AMPK) is an important regulator of cellular energy homeostasis. Recent studies demonstrated that AMPK is a novel signaling molecule modulating inflammatory responses and oxidative stress which are involved in inflammatory pulmonary diseases, such as asthma, chronic obstructive pulmonary disease (COPD), pulmonary infectious diseases and pulmonary fibrosis. AMPK attenuates inflammatory lung injury by phosphorylating its downstream targets, such as sirtuin1 (SIRT1), peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha), p53 and forkhead box O3a (FoxO3a). This review summarized the relationship between AMPK and the development of inflammatory pulmonary diseases.

  4. 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.

  5. Pulmonary Hypertension in Parenchymal Lung Disease

    PubMed Central

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

    2012-01-01

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

  6. 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.

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

    PubMed Central

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

    2012-01-01

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

  8. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Cyclosporine for Ocular Inflammatory Diseases

    PubMed Central

    Kaçmaz, R. Oktay; Kempen, John H.; Newcomb, Craig; Daniel, Ebenezer; Gangaputra, Sapna; Nussenblatt, Robert B.; Rosenbaum, James T.; Suhler, Eric B.; Thorne, Jennifer E.; Jabs, Douglas A.; Levy-Clarke, Grace A.; Foster, C. Stephen

    2009-01-01

    Purpose To evaluate the clinical outcomes of cyclosporine treatment for non-infectious ocular inflammation Design Retrospective cohort study Participants Three hundred seventy-three patients with non-infectious ocular inflammation managed at four tertiary ocular inflammation clinics in the United States observed to use cyclosporine as a single non-corticosteroid immunosuppressive agent to their treatment regimen, between 1979-2007 inclusive. Methods Participants were identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Demographic and clinical characteristics, including dosage of cyclosporine and main outcome measures were obtained for every eye of every patient at every visit via medical record review by trained expert reviewers. Main Outcome Measures: Control of inflammation, sustained control after reducing corticosteroid dosages, and discontinuation of therapy because of toxicity. Results Of the 373 patients (681 eyes) initiating cyclosporine monotherapy, 33.4% by six months and 51.9% by one year gained sustained, complete control of inflammation over at least two visits spanning at least 28 days. Approximately 25% more improved to a level of slight inflammatory activity by each of these time points. Corticosteroid-sparing success (completely controlled inflammation for at least 28 days with prednisone 10 mg/day or less) was achieved by 22.1% by six months and 36.1% within one year. Toxicity led to discontinuation of therapy within one year by 10.7% of the population. Patients over 55 years of age were over 3-fold more likely to discontinue therapy because of toxicity than patients ages 18-39 years. Doses of 151-250 mg/day tended to be more successful than lower doses, and were not associated with a higher discontinuation for toxicity rate; higher doses did not appear to offer a therapeutic advantage. Conclusion Cyclosporine, with corticosteroid therapy as indicated, was modestly effective for controlling ocular inflammation

  10. Genotoxic and inflammatory effects of nanofibrillated cellulose in murine lungs.

    PubMed

    Catalán, Julia; Rydman, Elina; Aimonen, Kukka; Hannukainen, Kati-Susanna; Suhonen, Satu; Vanhala, Esa; Moreno, Carlos; Meyer, Valérie; Perez, Denilson da Silva; Sneck, Asko; Forsström, Ulla; Højgaard, Casper; Willemoes, Martin; Winther, Jacob R; Vogel, Ulla; Wolff, Henrik; Alenius, Harri; Savolainen, Kai M; Norppa, Hannu

    2017-01-01

    Nanofibrillated cellulose (NFC) is a sustainable and renewable nanomaterial, with diverse potential applications in the paper and medical industries. As NFC consists of long fibres of high aspect ratio, we examined here whether TEMPO-(2,2,6,6-tetramethyl-piperidin-1-oxyl) oxidised NFC (length 300-1000nm, thickness 10-25nm), administrated by a single pharyngeal aspiration, could be genotoxic to mice, locally in the lungs or systemically in the bone marrow. Female C57Bl/6 mice were treated with four different doses of NFC (10, 40, 80 and 200 µg/mouse), and samples were collected 24h later. DNA damage was assessed by the comet assay in bronchoalveolar lavage (BAL) and lung cells, and chromosome damage by the bone marrow erythrocyte micronucleus assay. Inflammation was evaluated by BAL cell counts and analysis of cytokines and histopathological alterations in the lungs. A significant induction of DNA damage was observed at the two lower doses of NFC in lung cells, whereas no increase was seen in BAL cells. No effect was detected in the bone marrow micronucleus assay, either. NFC increased the recruitment of inflammatory cells to the lungs, together with a dose-dependent increase in mRNA expression of tumour necrosis factor α, interleukins 1β and 6, and chemokine (C-X-C motif) ligand 5, although there was no effect on the levels of the respective proteins. The histological analysis showed a dose-related accumulation of NFC in the bronchi, the alveoli and some in the cytoplasm of macrophages. In addition, neutrophilic accumulation in the alveolar lung space was observed with increasing dose. Our findings showed that NFC administered by pharyngeal aspiration caused an acute inflammatory response and DNA damage in the lungs, but no systemic genotoxic effect in the bone marrow. The present experimental design did not, however, allow us to determine whether the responses were transient or could persist for a longer time. © The Author 2016. Published by Oxford University

  11. 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.

  12. 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.

  13. 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.

  14. 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 ...

  15. 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.

  16. 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.

  17. Lung Disease at High Altitude

    PubMed Central

    Stream, JO; Luks, AM; Grissom, CK

    2016-01-01

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

  18. Nutrigenetics, nutrigenomics and inflammatory bowel diseases.

    PubMed

    Ferguson, Lynnette R

    2013-08-01

    Inflammatory bowel disease includes ulcerative colitis and Crohn's disease, which are both inflammatory disorders of the gastrointestinal tract. Both types of inflammatory bowel disease have a complex etiology, resulting from a genetically determined susceptibility interacting with environmental factors, including the diet and gut microbiota. Genome Wide Association Studies have implicated more than 160 single-nucleotide polymorphisms in disease susceptibility. Consideration of the different pathways suggested to be involved implies that specific dietary interventions are likely to be appropriate, dependent upon the nature of the genes involved. Epigenetics and the gut microbiota are also responsive to dietary interventions. Nutrigenetics may lead to personalized nutrition for disease prevention and treatment, while nutrigenomics may help to understand the nature of the disease and individual response to nutrients.

  19. Seasonal trend of acute pelvic inflammatory disease.

    PubMed

    Xholli, Anjeza; Cannoletta, Marianna; Cagnacci, Angelo

    2014-05-01

    Many infections follow a seasonal trend. Aim of our study was to check whether acute pelvic inflammatory disease (PID) follows a seasonal progress. In a retrospective study on 12,152 hospital records, 158 cases of acute pelvic inflammatory disease were identified. Periodogram analysis was applied to the date of pelvic inflammatory disease admission and to related environmental factors, such as temperature and photoperiod. Pelvic inflammatory disease follows a seasonal rhythm with mean to peak variation of 23 % and maximal values in September (±37.2 days). The rhythm, more evident in married women, is related to the rhythm of temperature advanced by 2 months and of photoperiod advanced by 3 months. Cases of pelvic inflammatory disease are more frequent than expected in unmarried (36 vs. 17.3/34,626, p = 0.015), particularly divorced women 30-40 years of age. Our study evidences a seasonal trend and confirms unmarried, particularly divorced status, as important risk factor for acute pelvic inflammatory disease.

  20. 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.

  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. 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...

  3. INFLAMMATORY BOWEL DISEASE: OUTPATIENT TREATMENT PROFILE.

    PubMed

    Santos, Rachael Miranda Dos; Carvalho, Ana Teresa Pugas; Silva, Kelly Dos Santos; Sá, Selma Petra Chaves; Santos, Aparecida Helena Dos; Sandinha, Millene Ramos

    2017-01-01

    Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease. The incidence and prevalence of both conditions have increased and are progressively increasing. These diseases are frequently recurrent and clinically highly severe. In Brazil, the lack of epidemiological data related to such diseases has left these patients in a vulnerable state and contributed to increased morbidity. To describe the profiles of patients with inflammatory bowel disease treated in an outpatient service in Brazil. This descriptive, exploratory, and retrospective documentary study with a quantitative approach was performed in an outpatient treatment service for inflammatory bowel disease, at a university polyclinic located in Rio de Janeiro, Brazil, from May to July 2016. The study included 556 patients and was approved by the research ethics committee of the institution (CAAE no. 55179316.6.0000.5259/2016). The data showed a high prevalence of inflammatory bowel disease in white female patients. Crohn's disease was diagnosed in more patients than was ulcerative colitis; the ileocolon was the most commonly affected location in patients with Crohn's disease. The stenotic phenotype was prevalent in patients with Crohn's disease. The prevalence of the stenotic phenotype in Crohn's disease in relation to others demonstrates the need for further investigations in this field of study in Brazil. In conclusion, the data showed that the epidemiologic profile of the study population is similar to that published in the national and international literature.

  4. 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.

  5. Sex steroid signaling: implications for lung diseases.

    PubMed

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

    2015-06-01

    There is increasing recognition that 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. 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

  7. 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.

  8. Smoking-related interstitial lung diseases.

    PubMed

    Caminati, A; Graziano, P; Sverzellati, N; Harari, S

    2010-12-01

    In pulmonary pathology, a wide spectrum of morphological changes is related to the consequences of smoking, and recognizing them on surgical specimens and on small transbronchial biopsies represents a challenge for the pathologist. Respiratory bronchiolitis, also referred to as smoker's bronchiolitis, is a common histologic feature found in the lung tissue of cigarette smokers. When identified as the sole histopathologic finding in the clinical setting of symptomatic interstitial lung disease, a diagnosis of respiratory bronchiolitis-interstitial lung disease is made. Since smoking is recognized to cause a variety of histologic patterns encompassing respiratory bronchiolitis, respiratory bronchiolitis-interstitial lung disease, desquamative interstitial pneumonia and pulmonary Langerhans cell hystiocytosis, smoking-related interstitial lung disease may be a useful concept to keep in mind for the pathologists. The relationship of smoking with each of these entities has been largely established on the basis of epidemiologic evidence. Although they have been retained as distinct and separate conditions in various classifications of interstitial lung diseases, these entities share a number of clinical, radiologic, and pathologic features suggesting that they represent a spectrum of patterns of interstitial lung disease occurring in predisposed individuals who smoke. Evaluation of histologic features, particularly in surgical lung biopsy samples, is important in making the distinction between these disorders. However, even after tissue biopsy, it may sometimes be difficult to clearly separate these entities. Recently, respiratory bronchiolitis-interstitial lung disease with fibrosis has been described and postulated that this is a smoking-related condition distinct from fibrotic non-specific interstitial pneumonia.

  9. 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. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

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

    PubMed

    Inamdar, Ajinkya C; Inamdar, Arati A

    2013-10-01

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

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. 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

  18. 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.

  19. 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, ...

  20. 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.

  1. 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.

  2. 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

  3. [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.

  4. Inflammatory Bowel Disease (For Children)

    MedlinePlus

    ... IBD. Doctors don't think that IBD is caused by emotional stress or specific foods. You can't catch it from someone, like a cold, but the disease may be genetic or hereditary, meaning it is passed down in families. About 20% of people with the disease also ...

  5. 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

  6. The role of female hormones on lung function in chronic lung diseases

    PubMed Central

    2011-01-01

    Background The prevalence, morbidity, and mortality of inflammatory lung diseases such as asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) are increasing in women. There is a dearth of data on the biological mechanisms to explain such observations. However, some large epidemiologic studies suggest that lung function fluctuates during the menstrual cycle in female patients with airways disease but not in women without disease, suggesting that circulating estradiol and progesterone may be involved in this process. Discussion In asthma, estradiol shuttles adaptive immunity towards the TH2 phenotype while in smokers estrogens may be involved in the generation of toxic intermediate metabolites in the airways of female smokers, which may be relevant in COPD pathogenesis. In CF, estradiol has been demonstrated to up-regulate MUC5B gene in human airway epithelial cells and inhibit chloride secretion in the airways. Progesterone may augment airway inflammation. Summary Taken together, clinical and in-vivo data have demonstrated a sex-related difference in that females may be more susceptible to the pathogenesis of lung diseases. In this paper, we review the effect of female sex hormones in the context of these inflammatory airway diseases. PMID:21639909

  7. 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.

  8. 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

  9. 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

  10. 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 ...

  11. 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

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

    PubMed

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

    2014-03-27

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

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

    PubMed Central

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

    2014-01-01

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

  14. Smoking-related interstitial lung diseases.

    PubMed

    Vassallo, Robert; Ryu, Jay H

    2012-03-01

    Cigarette smoke, a toxic collection of thousands of chemicals generated from combustion of tobacco, is recognized as the primary causative agent of certain diffuse interstitial and bronchiolar lung diseases. Most patients afflicted with these disorders are cigarette smokers, and smoking cessation has been shown to be capable of inducing disease remission and should occupy a pivotal role in the management of all smokers with these diffuse lung diseases. The role of pharmacotherapy with corticosteroids or other immunomodulating agents is not well established but may be considered in patients with progressive forms of smoking-related interstitial lung diseases. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Imaging of occupational and environmental lung diseases

    SciTech Connect

    Akira, M.

    2008-03-15

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

  16. 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

  17. 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

  18. Update on Diffuse Lung Disease in Children.

    PubMed

    Vece, Timothy J; Young, Lisa R

    2016-03-01

    Diffuse lung diseases in children, also called children's interstitial lung disease, are a diverse group of rare disorders that cause disturbances of gas exchange in the lungs. Although individually rare, there are many different forms of diffuse lung disease in children, and collectively these disorders are associated with significant morbidity and mortality, as well as health-care resource utilization. Over the past several years, there have been many significant advances in the field, including genetic discoveries and the development of clinical practice guidelines. This review summarizes recent advances in the understanding, diagnosis, and treatment of diffuse lung diseases in children. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  19. Diffuse Cystic Lung Disease. Part II

    PubMed Central

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

    2015-01-01

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

  20. Imaging of Childhood Interstitial Lung Disease

    PubMed Central

    2010-01-01

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

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. Lung Contusion: Inflammatory Mechanisms and Interaction with Other Injuries

    PubMed Central

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

    2009-01-01

    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 like 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. PMID:19174738

  6. Diffuse interstitial lung disease: overlaps and uncertainties.

    PubMed

    Walsh, Simon L F; Hansell, David M

    2010-08-01

    Histopathological analysis of lung biopsy material allows the diagnosis of idiopathic interstitial pneumonias; however, the strength of this diagnosis is sometimes subverted by interobserver variation and sampling. The American Thoracic Society and European Respiratory Society recommendations of 2002 provide a framework for the diagnosis of interstitial lung disease (ILD) and proposed an integrated clinical, radiological and histopathological approach. These recommendations represent a break with tradition by replacing the 'gold standard' of histopathology with the combined 'silver standards' of clinical, imaging and histopathological information. One of the pitfalls of a rigid classification system for the diagnosis of interstitial lung disease is its failure to accommodate the phenomenon of overlapping disease patterns. This article reviews the various ways that interstitial lung disease may be classified and discusses their applicability. In addition the issue of overlap disease patterns is considered in the context of histopathological interobserver variation and sampling error and how a pigeonhole approach to disease classification may overlook these hybrid entities.

  7. 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.

  8. 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

  9. Respiratory bronchiolitis-interstitial lung disease.

    PubMed

    Sieminska, Alicja; Kuziemski, Krzysztof

    2014-07-11

    Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) is a rare, mild inflammatory pulmonary disorder that occurs almost exclusively in current or former heavy smokers, usually between the third and sixth decades, most likely with no gender predilection. The onset is usually insidious with exertional dyspnea and persistent cough, which may be non-productive, developing over a course of weeks or months. RB-ILD may also be diagnosed in asymptomatic patients with functional impairment and chest radiograph or high-resolution computed tomography (HRCT) abnormalities. Histologically, RB-ILD is characterized by the accumulation of yellow-brown pigmented macrophages within the lumens of respiratory bronchioles and alveolar ducts, associated with a patchy submucosal and peribronchiolar chronic inflammation. Common findings also include mild bronchiolar and peribronchiolar alveolar fibrosis that expands contiguous alveolar septa and leads to architectural distortion as well as centrilobular emphysema. Chest radiographs in patients with RB-ILD typically show fine reticulonodular interstitial opacities, while on HRCT central and peripheral bronchial wall thickening, centrilobular nodules, and ground-glass opacities associated with upper lobe centrilobular emphysema are most frequently reported. Pulmonary function testing may be normal but usually demonstrates mixed, predominantly obstructive abnormalities, often combined with hyperinflation and usually associated with a mild to moderate reduction in carbon monoxide diffusion capacity (DLco). The course of RB-ILD is heterogeneous. Some patients respond favorably to corticosteroids and/or smoking cessation, but often there is no functional improvement and the disease progresses despite smoking cessation and treatment.

  10. Respiratory bronchiolitis-interstitial lung disease

    PubMed Central

    2014-01-01

    Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) is a rare, mild inflammatory pulmonary disorder that occurs almost exclusively in current or former heavy smokers, usually between the third and sixth decades, most likely with no gender predilection. The onset is usually insidious with exertional dyspnea and persistent cough, which may be non-productive, developing over a course of weeks or months. RB-ILD may also be diagnosed in asymptomatic patients with functional impairment and chest radiograph or high-resolution computed tomography (HRCT) abnormalities. Histologically, RB-ILD is characterized by the accumulation of yellow-brown pigmented macrophages within the lumens of respiratory bronchioles and alveolar ducts, associated with a patchy submucosal and peribronchiolar chronic inflammation. Common findings also include mild bronchiolar and peribronchiolar alveolar fibrosis that expands contiguous alveolar septa and leads to architectural distortion as well as centrilobular emphysema. Chest radiographs in patients with RB-ILD typically show fine reticulonodular interstitial opacities, while on HRCT central and peripheral bronchial wall thickening, centrilobular nodules, and ground-glass opacities associated with upper lobe centrilobular emphysema are most frequently reported. Pulmonary function testing may be normal but usually demonstrates mixed, predominantly obstructive abnormalities, often combined with hyperinflation and usually associated with a mild to moderate reduction in carbon monoxide diffusion capacity (DLco). The course of RB-ILD is heterogeneous. Some patients respond favorably to corticosteroids and/or smoking cessation, but often there is no functional improvement and the disease progresses despite smoking cessation and treatment. PMID:25011486

  11. Cryptogenic Organizing Pneumonia With Lung Nodules Secondary to Pulmonary Manifestation of Crohn Disease

    PubMed Central

    Zaman, Taufiq; Watson, Joseph; Zaman, Mohammad

    2017-01-01

    Crohn disease is an immune-mediated inflammatory condition with gastrointestinal and extraintestinal manifestations in patients. Pulmonary involvement of Crohn disease is one manifestation. There have been case reports which have shown Crohn disease and lung nodules which were noted to be histopathological as cryptogenic organizing pneumonia (COP). In our case, a 22-year-old woman with Crohn disease was seen with complaints of chest pain and cough. Computed tomographic scan of chest showed multiple bilateral lung nodules, for which biopsy was done, which showed COP. The case study is followed by a deeper discussion of COP and the extraintestinal manifestation seen in inflammatory bowel disease. PMID:28579861

  12. Cryptogenic Organizing Pneumonia With Lung Nodules Secondary to Pulmonary Manifestation of Crohn Disease.

    PubMed

    Zaman, Taufiq; Watson, Joseph; Zaman, Mohammad

    2017-01-01

    Crohn disease is an immune-mediated inflammatory condition with gastrointestinal and extraintestinal manifestations in patients. Pulmonary involvement of Crohn disease is one manifestation. There have been case reports which have shown Crohn disease and lung nodules which were noted to be histopathological as cryptogenic organizing pneumonia (COP). In our case, a 22-year-old woman with Crohn disease was seen with complaints of chest pain and cough. Computed tomographic scan of chest showed multiple bilateral lung nodules, for which biopsy was done, which showed COP. The case study is followed by a deeper discussion of COP and the extraintestinal manifestation seen in inflammatory bowel disease.

  13. 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

  14. [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.

  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. Innovative therapeutics for inflammatory bowel disease.

    PubMed

    Yamamoto-Furusho, Jesus-K

    2007-04-07

    Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal tract, which clinically present as one of two disorders, Crohn's disease or ulcerative colitis. Mainstays of drug treatments for IBD include aminosalicylates, corticosteroids and immunosuppressants such as azathioprine, methotrexate and cyclosporin. Advances in basic research of the pathophysiological process in IBD have been applied to generate a variety of new therapeutics targeting at different levels of the inflammatory processes. New therapies are classified as: (1) Anti-TNFalpha antibodies; (2) Recombinant cytokines; (3) Selective adhesion blockade; (4) Growth factors; (5) Innate immunostimulation; (6) Nucleic acid based therapies; (7) Gene therapy; (8) Autologous bone-marrow transplantation; (9) Helminths and (10) Extracorporeal immunomodulation. All treatments have the potential to provide more effective and safe treatment for IBD.

  18. Innovative therapeutics for inflammatory bowel disease

    PubMed Central

    Yamamoto-Furusho, Jesus K

    2007-01-01

    Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal tract, which clinically present as one of two disorders, Crohn’s disease or ulcerative colitis. Mainstays of drug treatments for IBD include aminosalicylates, corticosteroids and immunosuppressants such as azathioprine, methotrexate and cyclosporin. Advances in basic research of the pathophysiological process in IBD have been applied to generate a variety of new therapeutics targeting at different levels of the inflammatory processes. New therapies are classified as: (1) Anti-TNFα antibodies; (2) Recombinant cytokines; (3) Selective adhesion blockade; (4) Growth factors; (5) Innate immunostimulation; (6) Nucleic acid based therapies; (7) Gene therapy; (8) Autologous bone-marrow transplantation; (9) Helminths and (10) Extracorporeal immunomodulation. All treatments have the potential to provide more effective and safe treatment for IBD. PMID:17461487

  19. 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.

  20. 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

    USDA-ARS?s Scientific Manuscript database

    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...

  1. Symptom management in inflammatory bowel disease.

    PubMed

    Abraham, Bincy P

    2015-07-01

    Patients with inflammatory bowel disease can present with a wide variety of symptoms. Most are related to disease activity and should be managed with appropriate medical therapy for inflammatory bowel disease. However, some patients may develop symptoms due to the side effects of the medications, or due to immunosuppression. In these cases, the offending medications should be discontinued until resolution of the symptoms and a few may be able to restart therapy. Symptoms can also occur as an extraintestinal manifestation of the disease or due to concomitant autoimmune-mediated disorders. Regardless of the etiology, symptoms should be addressed promptly with immediate evaluation and appropriate therapy, as a delay may lead to permanent sequela.

  2. [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.

  3. Inflammatory Bowel Disease: School Nurse Management

    ERIC Educational Resources Information Center

    Kitto, Lisa

    2010-01-01

    Initial symptoms and diagnosis of inflammatory bowel disease (IBD) usually occur between 10 and 20 years of age, although younger cases are reported. The complicated nature of IBD diagnosis and treatment can interfere with physical and emotional development that normally occurs in school-age children and adolescents. The school nurse should be…

  4. Microbiota and Pelvic Inflammatory Disease

    PubMed Central

    Sharma, Harsha; Tal, Reshef; Clark, Natalie A.; Segars, James H.

    2014-01-01

    Female genital tract microbiota play a crucial role in maintaining health. Disequilibrium of the microbiota has been associated with increased risk of pelvic infections. In recent years, culture-independent molecular techniques have expanded understanding of the composition of genital microbiota and the dynamic nature of the microbiota. There is evidence that upper genital tract may not be sterile and may harbor microflora in the physiologic state. The isolation of bacterial vaginosis-associated organisms in women with genital infections establishes a link between pelvic infections and abnormal vaginal flora. With the understanding of the composition of the microbiota in healthy and diseased states, the next logical step is to identify the function of the newly identified microbes. This knowledge will further expand our understanding of the causation of pelvic infections, which may lead to more effective prevention and treatment strategies. PMID:24390920

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

    PubMed

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

    2016-03-21

    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.

  6. 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

  7. 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

  8. Managing pregnancy in inflammatory rheumatological diseases

    PubMed Central

    2011-01-01

    Historically, pregnancy in women with many inflammatory rheumatic diseases was not considered safe and was discouraged. Combined care allows these pregnancies to be managed optimally, with the majority of outcomes being favorable. Disease activity at the time of conception and anti-phospholipid antibodies are responsible for most complications. Disease flares, pre-eclampsia, and thrombosis are the main maternal complications, whereas fetal loss and intrauterine growth restriction are the main fetal complications. Antirheumatic drugs used during pregnancy and lactation to control disease activity are corticosteroids, hydroxychloroquine, sulphasalzine, and azathioprine. Vaginal delivery is possible in most circumstances, with cesarean section being reserved for complications. PMID:21371350

  9. 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.

  10. 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.

  11. 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

  12. Current laparoscopic management of inflammatory bowel disease.

    PubMed

    Zoccali, M; Fichera, A

    2011-12-01

    Since the introduction of laparoscopic surgery in the management of colorectal disease in the early '90s, minimally invasive techniques have gained popularity. While good quality studies have been published in the literature on laparoscopy for colorectal cancer, evidence supporting the use of minimally invasive surgery for inflammatory bowel disease is lacking. This patient population represents a challenge to the colorectal surgeon even in conventional open surgery and this has limited the widespread application of minimally invasive techniques especially in Crohn's disease. Laparoscopic ileocecal resection for Crohn's disease is the most performed minimally invasive procedure in the field of inflammatory bowel disease, with promising short-term outcomes but with still some concerns related to prolonged operative times and overall costs. For ulcerative colitis the magnitude of restorative procedures has also restricted the use of minimally invasive approaches to highly specialized tertiary referral centers. The benefits of performing restorative procedures laparoscopically for ulcerative colitis are less obvious based on the limited reports available in the literature with adequate follow-up for assessing long-term outcomes, and controversies still remains about the need for a staged approach in the era of biologic therapy. Nevertheless, surgeons are actively working in an effort to obviate to the current technical limitations of laparoscopy, and to further minimize surgical trauma. In this manuscript we will present the current evidence supporting the use of laparoscopy and minimally invasive techniques in inflammatory bowel disease and present the future direction of development and research.

  13. Long-Term Control Medications for Lung Diseases

    MedlinePlus

    ... medications are taken daily to control and prevent lung disease symptoms. These medicines should be taken every day ... long-acting beta-agonist. They improve symptoms of lung disease and increase lung function. Inhaled Steroids Inhaled steroids ...

  14. 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.

  15. 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.

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

    PubMed

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

    2015-04-01

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

  17. 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.

  18. Dry Eye: an Inflammatory Ocular Disease

    PubMed Central

    Hessen, Michelle; Akpek, Esen Karamursel

    2014-01-01

    Keratoconjunctivitis sicca, or dry eye, is a common ocular disease prompting millions of individuals to seek ophthalmological care. Regardless of the underlying etiology, dry eye has been shown to be associated with abnormalities in the pre-corneal tear film and subsequent inflammatory changes in the entire ocular surface including the adnexa, conjunctiva and cornea. Since the recognition of the role of inflammation in dry eye, a number of novel treatments have been investigated designed to inhibit various inflammatory pathways. Current medications that are used, including cyclosporine A, corticosteroids, tacrolimus, tetracycline derivatives and autologous serum, have been effective for management of dry eye and lead to measurable clinical improvement. PMID:25279127

  19. Inflammatory links between obesity and metabolic disease

    PubMed Central

    Lumeng, Carey N.; Saltiel, Alan R.

    2011-01-01

    The obesity epidemic has forced us to evaluate the role of inflammation in the health complications of obesity. This has led to a convergence of the fields of immunology and nutrient physiology and the understanding that they are inextricably linked. The reframing of obesity as an inflammatory condition has had a wide impact on our conceptualization of obesity-associated diseases. In this Review, we highlight the cellular and molecular mechanisms at play in the generation of obesity-induced inflammation. We also emphasize how defining the immune regulation in metabolic tissues has broadened the understanding of the diversity of inflammatory responses. PMID:21633179

  20. [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.

  1. 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.

  2. Reflectance confocal microscopy for inflammatory skin diseases.

    PubMed

    Ardigò, M; Prow, T; Agozzino, M; Soyer, P; Berardesca, E

    2015-10-01

    Reflectance confocal microscopy evaluation of inflammatory skin diseases represents a relatively new indication that, during the last 5 years, has shown an increasing interest with consequent progressive increment of publications in literature. The success of RCM in this filed of dermatology is directly related to the high needing of non-invasive techniques able to reduce the number of skin biopsies and support the clinical diagnosis and patient's management. RCM demonstrated to visualize microscopic descriptors of inflammatory and pigmentary skin conditions with good reproducibility between observer and high grade of correspondence with optical histology. Moreover, RCM has shown to provide sufficient data to support clinical diagnosis and differential diagnosis of inflammatory and pigmentary skin diseases. Recently, several works published in literature have opened the prospective to use RCM also for therapeutic follow-up in order to monitor the improvement of the microscopic parameters and help to prevent treatment side effects. In this review article we present some examples of RCM application in inflammatory and pigmentary diseases.

  3. [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.

  4. Cytomegalovirus infection associated with inflammatory bowel disease.

    PubMed

    Siegmund, Britta

    2017-05-01

    Refractory colitis in patients with inflammatory bowel disease is a complicated clinical disorder that might, in some patients, even necessitate surgery. Hence the diagnosis of additional complications is of utmost importance. Colitis mediated by cytomegalovirus is one such complication. The high seroprevalence and latent nature of cytomegalovirus, with the possibility of viral replication without mediating disease, poses a real challenge for the diagnosis of cytomegalovirus-mediated colitis. The challenge in daily clinical practice is to distinguish cytomegalovirus replication from cytomegalovirus-mediated colitis in patients with inflammatory bowel disease who have refractory colitis. This Review discusses the scientific literature and provides a diagnostic and therapeutic algorithm for clinical practice. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Dysplasia and cancer in inflammatory bowel disease.

    PubMed

    Basseri, Robert J; Basseri, Benjamin; Papadakis, Konstantinos A

    2011-02-01

    Inflammatory bowel disease (IBD) is a chronic gastrointestinal disease associated with an increased risk of colorectal cancer (CRC). Although CRC occurs in a minority of IBD patients (1%), it carries a high mortality and accounts for 20% of IBD-related mortality. Established risk factors for the development of CRC in IBD include disease duration of 8 years or more, family history of CRC, extensive colitis and primary sclerosing cholangitis. Meticulous colonoscopy and anti-inflammatory medications can reduce the risk of developing CRC. The future of IBD surveillance involves the use of novel endoscopic techniques (chromoendoscopy, narrow-band imaging, confocal laser endomicroscopy and autofluorescence) to enhance colonoscopic accuracy, in concert with chemopreventative medications to help reduce the risk of CRC in IBD.

  6. Diabetes mellitus and inflammatory periodontal diseases.

    PubMed

    Mealey, Brian L; Rose, Louis F

    2008-09-01

    THE PURPOSE OF REVIEW: Periodontal diseases are inflammatory conditions that were once thought to have manifestations localized to the oral cavity alone, and were therefore considered the concern of only dentists and other oral health professionals. Emerging evidence has changed this view and now suggests that periodontal diseases may play a role in numerous conditions that impact systemic well-being, including diabetes mellitus. This review examines the relationships that exist between periodontal diseases and diabetes mellitus, with a focus on potential common pathophysiologic pathways including those associated with inflammation, altered host responses, and insulin resistance. Periodontal inflammation is associated with an elevated systemic inflammatory state and an increased risk of major cardiovascular events such as myocardial infarction and stroke, adverse pregnancy outcomes such as preeclampsia, low birth weight, and preterm birth, and altered glycemic control in people with diabetes. Intervention trials suggest that periodontal therapy, which decreases the intraoral bacterial bioburden and reduces periodontal inflammation, can have a significant impact on systemic inflammatory status. Evidence suggests that periodontal therapy is associated with improved glycemic control in many patients with both diabetes and periodontal diseases. Recognition of the bilateral relationships between oral and systemic health will challenge physicians and dentists to work together closely in the future when managing patients with diabetes and periodontal disease.

  7. Challenges in pulmonary fibrosis. 3: Cystic lung disease.

    PubMed

    Cosgrove, Gregory P; Frankel, Stephen K; Brown, Kevin K

    2007-09-01

    Cystic lung disease is a frequently encountered problem caused by a diverse group of diseases. Distinguishing true cystic lung disease from other entities, such as cavitary lung disease and emphysema, is important given the differing prognostic implications. In this paper the features of the cystic lung diseases are reviewed and contrasted with their mimics, and the clinical and radiographic features of both diffuse (pulmonary Langerhans' cell histiocytosis and lymphangioleiomyomatosis) and focal or multifocal cystic lung disease are discussed.

  8. Challenges in pulmonary fibrosis · 3: Cystic lung disease

    PubMed Central

    Cosgrove, Gregory P; Frankel, Stephen K; Brown, Kevin K

    2007-01-01

    Cystic lung disease is a frequently encountered problem caused by a diverse group of diseases. Distinguishing true cystic lung disease from other entities, such as cavitary lung disease and emphysema, is important given the differing prognostic implications. In this paper the features of the cystic lung diseases are reviewed and contrasted with their mimics, and the clinical and radiographic features of both diffuse (pulmonary Langerhans' cell histiocytosis and lymphangioleiomyomatosis) and focal or multifocal cystic lung disease are discussed. PMID:17726170

  9. 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.

  10. Peroxiredoxin 6 differentially regulates acute and chronic cigarette smoke–mediated lung inflammatory response and injury

    PubMed Central

    Sundar, Isaac K.; Chung, Sangwoon; Hwang, Jae-Woong; Arunachalam, Gnanapragasam; Cook, Suzanne; Yao, Hongwei; Mazur, Witold; Kinnula, Vuokko L.; Fisher, Aron B.; Rahman, Irfan

    2011-01-01

    Peroxiredoxin 6 (Prdx6) exerts its protective role through peroxidase activity against H2O2 and phospholipid hydroperoxides. We hypothesized that targeted disruption of Prdx6 would lead to enhanced susceptibility to cigarette smoke (CS)-mediated lung inflammation and/or emphysema in mouse lung. Prdx6 null (Prdx6−/−) mice exposed to acute CS showed no significant increase of inflammatory cell influx or any alterations in lung levels of pro inflammatory cytokines compared to wild-type (WT) mice. Lung levels of antioxidant enzymes were significantly increased in acute CS-exposed Prdx6−/− compared to WT mice. Overexpressing (Prdx6+/+) mice exposed to acute CS showed significant decrease in lung antioxidant enzymes associated with increased inflammatory response compared to CS-exposed WT mice or air-exposed Prdx6−/− mice. However, chronic 6 months of CS exposure resulted in increased lung inflammatory response, mean linear intercept (Lm), and alteration in lung mechanical properties in Prdx6−/− when compared to WT mice exposed to CS. These data show that targeted disruption of Prdx6 does not lead to increased lung inflammatory response but is associated with increased antioxidants, suggesting a critical role of lung Prdx6 and several compensatory mechanisms during acute CS-induced adaptive response, whereas this protection is lost in chronic CS exposure leading to emphysema. PMID:20939758

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. (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.

  18. 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

  19. 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.

  20. Inflammatory diseases of the parathyroid gland.

    PubMed

    Talat, Nadia; Diaz-Cano, Salvador; Schulte, Klaus-Martin

    2011-11-01

    Inflammatory disorders of the parathyroid gland are very rare as compared with those of other endocrine organs. The aim of this study was to provide the first systematic review of this condition. A 42-year-old patient underwent surgery for recurrent secondary hyperparathyroidism. Histology showed hyperplastic parathyroiditis defined by a mixed inflammatory infiltrate with active germinal centres. Molecular markers revealed significant upregulation of CD68 in an ischaemic background (hypoxia-inducible factor 1 upregulation) with mitochondrial reaction (malate dehydrogenase 2 upregulation) and hyperparathyroidism (carbonic anhydrase 4 upregulation). Our case demonstrates true intraparathyroid inflammation with terminal B-cell differentiation. We searched PubMed, ISI Thompson and Google Scholar up to January 2011, using the terms 'parathyroiditis', 'inflammation of parathyroid gland', 'lymphocytic infiltrate', 'tuberculosis of the parathyroid', 'sarcoidosis', and 'graulomatous inflammation'. Three autopsy series, 27 articles and 96 case reports with inflammatory parathyroid disorders were identified. Autopsy series showed lymphocytic infiltrates in up to 16% of all cases. The entire material reported lymphocytic infiltrates (n=69), parathyroiditis with germinal centres (n=15), sarcoidosis (n=6), tuberculosis (n=4), and other granulomatous diseases (n=2). Distinct inflammatory and granulomatous processes in the parathyroid gland are rare. Scanty lymphocytic infiltrates are common, and occur in generalized inflammatory conditions or venous congestion. We note the surprising absence of an association between histological proof of parathyroiditis and hypoparathyroidism. © 2011 Blackwell Publishing Limited.

  1. Changes in ion transport in inflammatory disease

    PubMed Central

    Eisenhut, Michael

    2006-01-01

    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 abnormalites 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. PMID:16571116

  2. 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

  3. Lung Ischemia Reperfusion (IR) is a Sterile Inflammatory Process influenced by Commensal Microbiota in Mice

    PubMed Central

    Prakash, Arun; Sundar, Shirin V.; Zhu, Ying-gang; Tran, Alphonso; Lee, Jae-Woo; Lowell, Clifford; Hellman, Judith

    2015-01-01

    Background Lung ischemia reperfusion (IR) complicates numerous clinical processes, such as cardiac arrest, transplantation, and major trauma. These conditions generate sterile inflammation, which can cause or augment acute lung injury. We previously reported that lung and systemic inflammation in a mouse model of ventilated lung IR depends on Toll-like receptor (TLR) 4 signaling and the presence of alveolar macrophages. Here, we tested the hypothesis that the intestinal microbiome has a role in influencing the inflammatory response to lung IR. Methods Lung IR was created in intubated mechanically ventilated mice via reversible left pulmonary artery occlusion followed by reperfusion. Inflammatory markers and histology were tracked over varying periods of reperfusion (from 1h to 24h). Separate groups of mice were given intestinally-localized antibiotics for 8-10 weeks, and then were subjected to left lung IR and analysis of lungs and plasma for markers of inflammation. Alveolar macrophages from antibiotic-treated or control mice were tested ex vivo for inflammatory responses to bacterial TLR agonists, namely LPS and Pam3Cys. Results Inflammation generated by left lung IR was rapid in onset and dissipated within 12-24h. Treatment of mice with intestinally localized antibiotics was associated with a marked attenuation of circulating and lung inflammatory markers, and histologic evidence of infiltrating cells and edema in the lung following IR. Alveolar macrophages from antibiotic-treated mice produced less cytokines ex vivo when stimulated with TLR agonists as compared to those from control mice. Conclusions Our data indicate that the inflammatory response induced by lung IR is transient and is strongly influenced by intestinal microbiota. These data suggest that the intestinal microbiome could potentially be manipulated to attenuate the post-IR pulmonary inflammatory response. PMID:26196836

  4. Unfulfilled inflammatory resolution leads to chronic inflammatory diseases.

    PubMed

    Musk, Philip

    2004-06-01

    Extract: Inflammatory conditions, particularly those that involve chronic inflammation, represent an area of great interest to the pharmaceutical industry. Regulated as they are by a diverse array of ligand-receptor interactions, inflammatory responses are amenable to small molecule pharmaceutical intervention and a wide variety of anti-histamines and anti-inflammatory treatments. Both steroidal and non-steroidal treatments have been developed to treat pro-inflammatory conditions. In their review, Gilroy et al. (2004) present the case for developing novel anti-inflammatory drugs not by finding more effective inhibitors of the inflammatory response, but by developing small molecule drugs that positively regulate the processes and mechanisms by which inflammatory responses are attenuated (i.e., the little known process of inflammatory resolution).

  5. Modifiable Environmental Factors in Inflammatory Bowel Disease.

    PubMed

    Burke, Kristin E; Boumitri, Christine; Ananthakrishnan, Ashwin N

    2017-05-01

    Environmental factors may influence predisposition to develop inflammatory bowel diseases (Crohn's disease, ulcerative colitis) or alter its natural history by modification of both the host immune response and intestinal microbial composition. The purpose of this review is to translate such evidence into clinical practice by a focus on interventional studies that have modified such environmental influences to improve disease outcomes. Several environmental influences have been identified in the recent literature including tobacco use, diet, antibiotics, vitamin D deficiency, stress, appendectomy, and oral contraceptive use. Some risk factors have similar influences on both Crohn's disease and ulcerative colitis while others are disease-specific or have divergent effects. Emerging epidemiologic evidence has confirmed the association of many of these factors with incident disease using prospective data. In addition, laboratory data has supported their mechanistic plausibility and relevance to intestinal inflammation.

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. [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.

  11. 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. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email

  12. Nematode modulation of inflammatory bowel disease.

    PubMed

    Whelan, Rose A K; Hartmann, Susanne; Rausch, Sebastian

    2012-10-01

    Inflammatory bowel disease (IBD) is a chronic disease arising due to a culmination of genetic, environmental, and lifestyle-associated factors and resulting in an excessive pro-inflammatory response to bacterial populations in the gastrointestinal tract. The prevalence of IBD in developing nations is relatively low, and it has been proposed that this is directly correlated with a high incidence of helminth infections in these areas. Gastrointestinal nematodes are the most prevalent parasitic worms, and they efficiently modulate the immune system of their hosts in order to establish chronic infections. Thus, they may be capable of suppressing unrelated inflammation in disorders such as IBD. This review describes how nematodes, or their products, suppress innate and adaptive pro-inflammatory immune responses and how the mechanisms involved in the induction of anti-nematode responses regulate colitis in experimental models and clinical trials with IBD patients. We also discuss how refinement of nematode-derived therapies should ultimately result in the development of potent new therapeutics of clinical inflammatory disorders.

  13. 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.

  14. 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.

  15. 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.

  16. Histopathologic approach to the surgical lung biopsy in interstitial lung disease.

    PubMed

    Jones, Kirk D; Urisman, Anatoly

    2012-03-01

    Interpretation of lung biopsy specimens is an integral part in the diagnosis of interstitial lung disease (ILD). The process of evaluating a surgical lung biopsy for disease involves answering several questions. Unlike much of surgical pathology of neoplastic lung disease, arriving at the correct diagnosis in nonneoplastic lung disease often requires correlation with clinical and radiologic findings. The topic of ILD or diffuse infiltrative lung disease covers several hundred entities. This article is meant to be a launching point in the clinician's approach to the histologic evaluation of lung disease. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Surgical Lung Biopsy for Interstitial Lung Diseases.

    PubMed

    Raj, Rishi; Raparia, Kirtee; Lynch, David A; Brown, Kevin K

    2017-05-01

    This review addresses common questions regarding the role of surgical lung biopsy (SLB) in the diagnosis and treatment of interstitial lung disease (ILD). We specifically address when a SLB can be diagnostic as well as when it may be avoided; for example, when the combination of the clinical context and the imaging pattern seen on high-resolution CT (HRCT) chest scans can provide a confident diagnosis. Existing studies on the diagnostic utility as well as the complications associated with SLB are reviewed; also reviewed are the performance characteristics and reliability of HRCT scans of the chest in predicting the underlying histopathologic findings of the lung. The review is formatted in the form of answers to questions that clinicians regularly ask when considering an SLB in a patient with ILD. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  18. 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

  19. Environment and the inflammatory bowel diseases

    PubMed Central

    Frolkis, Alexandra; Dieleman, Levinus A; Barkema, Herman W; Panaccione, Remo; Ghosh, Subrata; Fedorak, Richard N; Madsen, Karen; Kaplan, Gilaad G

    2013-01-01

    Inflammatory bowel diseases (IBD), which consists of Crohn disease and ulcerative colitis, are chronic inflammatory conditions of the gas-trointestinal tract. In genetically susceptible individuals, the interaction between environmental factors and normal intestinal commensal flora is believed to lead to an inappropriate immune response that results in chronic inflammation. The incidence of IBD have increased in the past century in developed and developing countries. The purpose of the present review is to summarize the current knowledge of the association between environmental risk factors and IBD. A number of environmental risk factors were investigated including smoking, hygiene, microorganisms, oral contraceptives, antibiotics, diet, breast-feeding, geographical factors, pollution and stress. Inconsistent findings among the studies highlight the complex pathogenesis of IBD. Additional studies are necessary to identify and elucidate the role of environmental factors in IBD etiology. PMID:23516681

  20. 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

  1. 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

  2. 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

  3. 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.

  4. The Role of Transient Receptor Potential Vanilloid 4 in Pulmonary Inflammatory Diseases

    PubMed Central

    Scheraga, Rachel G.; Southern, Brian D.; Grove, Lisa M.; Olman, Mitchell A.

    2017-01-01

    Ion channels/pumps are essential regulators of organ homeostasis and disease. In the present review, we discuss the role of the mechanosensitive cation channel, transient receptor potential vanilloid 4 (TRPV4), in cytokine secretion and pulmonary inflammatory diseases such as asthma, cystic fibrosis (CF), and acute lung injury/acute respiratory distress syndrome (ARDS). TRPV4 has been shown to play a role in lung diseases associated with lung parenchymal stretch or stiffness. TRPV4 indirectly mediates hypotonicity-induced smooth muscle contraction and airway remodeling in asthma. Further, the literature suggests that in CF TRPV4 may improve ciliary beat frequency enhancing mucociliary clearance, while at the same time increasing pro-inflammatory cytokine secretion/lung tissue injury. Currently it is understood that the role of TRPV4 in immune cell function and associated lung tissue injury/ARDS may depend on the injury stimulus. Uncovering the downstream mechanisms of TRPV4 action in pulmonary inflammatory diseases is likely important to understanding disease pathogenesis and may lead to novel therapeutics. PMID:28523001

  5. [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.

  6. 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.

  7. The bone scan in inflammatory osseous disease.

    PubMed

    Handmaker, H; Leonards, R

    1976-01-01

    The 99mTc-phosphate bone scan has become a sensitive, reliable, and safe method for evaluating the patient with suspected inflammatory disease of bone. The scan may become positive as early as the first 24 hr after the symptoms and 10-14 days before roentgenographic changes occur. It can be used to differentiate successfully a variety of diseases from osteomyelitis, and in conjunction with 67Ga-citrate scan has become a mainstay in the work-up of the patient with infectious disease. Applications of the bone scan to infectious diseases in pediatric practice are especially helpful, since these diseases are common problems in this age group. Increased experience with the 99mTc-phosphate bone scan has already defined several areas of "limitations" in evaluating inflammatory disease. "Cold" defects, negative scans in early stages of osteomyelitis, and "extended uptake" may all pose problems in interpretation, but careful correlation of the bone scan results with clinical history and physical findings, blood cultures, and roentgenography will significantly reduce these problems.

  8. Hepatobiliary Manifestations of Inflammatory Bowel Disease

    PubMed Central

    Memon, Mohammed Iqbal; Memon, Breda

    2000-01-01

    Hepatobiliary manifestations occur quite frequently in patients suffering from chronic ulcerative colitis and Crohn's disease and carry with them considerable morbidity and mortality. Although the true incidence is difficult to determine, clinically, significant hepatobiliary disease occurs in 5%–10% of patients. At the present moment, the aetiology and pathogenesis of inflammatory bowel disease and its systemic manifestations remains speculative. For those hepatobiliary manifestations that respond to therapy of the underlying bowel disease, medical and/or surgical therapy must be aggressively pursued. More urgent research is required towards understanding the underlying cause(s) of the primary bowel disease and its systemic manifestations in order to improve the overall management of this condition. PMID:10977114

  9. Exhaled breath condensate: a new method for lung disease diagnosis.

    PubMed

    Cepelak, Ivana; Dodig, Slavica

    2007-01-01

    Analysis of exhaled breath composition in lung disease patients can indirectly point to biochemical changes that occur in the fluid lining airway surfaces. The parameters of redox and acid-base changes, and of inflammatory changes relevant in the pathogenesis of most pulmonary diseases are currently most widely determined in exhaled breath condensate. The collection of exhaled breath condensate is a safe, non-invasive, easy and simple diagnostic procedure that is suitable for longitudinal studies and applicable in patients of all age groups, irrespective of the disease severity. In spite of many scientific studies involving lung disease patients, methodology for exhaled breath condensate collection and analysis has not yet been realized for daily utilization. Additional studies of the exact origin of condensate constituents and standardization of the overall analytical process, including collection, storage, analysis and result interpretation, are needed. Irrespective of these limitations, further investigation of this sample type is fully justified by the fact that classical specimens used in the management of pulmonary disease are either obtained by invasive procedures (e.g., induced sputum, biopsy, bronchoalveolar lavage) or cannot provide appropriate information (e.g., urine, serum). Analysis of exhaled breath condensate in the future might contribute significantly to our understanding of the physiological and pathophysiological processes in lungs, to early detection, diagnosis and follow up of disease progression, and to evaluation of therapeutic response.

  10. 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

  11. 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.

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

    PubMed

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

    2015-01-01

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

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. Uncommon causes of occupational interstitial lung diseases.

    PubMed

    Gong, H

    1996-09-01

    Uncommon causes of occupational interstitial lung disease, or pneumoconiosis, are being increasingly recognized and diagnosed. The fibrogenic potential of numerous types of respirable inorganic particles remains poorly understood but is significantly determined by lung deposition and clearance, the agent's size and solubility, host susceptibility, and other factors. Microanalytic techniques have improved the identification of uncommon or unusual biopersistent particles or elements in fibrotic lung tissue. Recent findings in workers exposed to manmade vitreous fibers, silicon carbide, talc, titanium, cerium, and polyvinyl chloride provide new clinical insights into not only their specific fibrogenic capabilities but also in the broader appreciation that many cases of unexplained interstitial lung disease may be caused by occupational exposures to one or more uncommon airborne substances.

  18. 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.

  19. 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

  20. Trichuris suis ova in inflammatory bowel disease.

    PubMed

    Schölmerich, Jürgen

    2013-01-01

    Some but not all epidemiological studies suggest that helminth infection in childhood protects against development of inflammatory bowel disease (IBD) in later years. In animal models of IBD, helminths have shown protective effects and changed bacterial flora in the gut. Based on these concepts, small trials and series have been published showing some positive effects of Trichuris suis ova in ulcerative colitis and Crohn's disease. Currently, large randomized placebo-controlled trials are under way. Results remain to be awaited in order to clarify a possible role of T. suis ova in the treatment of IBD.

  1. 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

  2. Effect of lornoxicam in lung inflammatory response syndrome after operations for cardiac surgery with cardiopulmonary bypass.

    PubMed

    Tsakiridis, Kosmas; Zarogoulidis, Paul; Vretzkakis, Giorgos; Mikroulis, Dimitris; Mpakas, Andreas; Kesisis, Georgios; Arikas, Stamatis; Kolettas, Alexandros; Moschos, Giorgios; Katsikogiannis, Nikolaos; Machairiotis, Nikolaos; Tsiouda, Theodora; Siminelakis, Stavros; Beleveslis, Thomas; Zarogoulidis, Konstantinos

    2014-03-01

    The establishment of Extracorporeal Circulation (EC) significantly contributed to improvement of cardiac surgery, but this is accompanied by harmful side-effects. The most important of them is systemic inflammatory response syndrome. Many efforts have been undertaken to minimize this problem but unfortunately without satisfied solution to date. Lornoxicam is a non steroid anti-inflammatory drug which temporally inhibits the cycloxygenase. In this clinical trial we study the effect of lornoxicam in lung inflammatory response after operations for cardiac surgery with cardiopulmonary bypass. In our study we conclude 14 volunteers patients with ischemic coronary disease undergoing coronary artery bypass grafting with EC. In seven of them 16 mg lornoxicam was administered iv before the anesthesia induction and before the connection in heart-lung machine. In control group (7 patients) we administered the same amount of normal saline. Both groups are equal regarding pro-operative and intra-operative parameters. The inflammatory markers were calculated by Elisa method. We measured the levels of cytokines (IL-6, IL-8, TNF-a), adhesion molecules (ICAM-1, e-Selectin, p-Selectin) and matrix metaloproteinase-3 (MMP-3) just after anesthesia induction, before and after cardiopulmonary bypass, just after the patients administration in ICU and after 8 and 24 hrs. In all patients we estimated the lung's inflammatory reaction with lung biopsy taken at the begging and at the end of the operation. We calculated hemodynamics parameters: Cardiac Index (CI), Systemic Vascular Resistance Index (SVRI), Pulmonary Vascular Resistance Index (PVRI), Left Ventricular Stroke Work Index (LVSWI), Right Ventricular Stroke Work Index (RVSWI), and the Pulmonary arterial pressure, and respiratory parameters too: alveolo-arterial oxygen difference D (A-a), intrapulmonary shunt (Qs/Qt) and pulmonary Compliance. IL-6 levels of lornoxicam group were statistical significant lower at 1st postoperative day

  3. 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

  4. [Drug-induced interstitial lung diseases].

    PubMed

    Bonniaud, Philippe; Georges, Marjolaine; Favrolt, Nicolas; Camus, Philippe

    2014-09-01

    Drug-induced infiltrative lung disease may manifest as variable clinical radiological patterns, including subacute or chronic interstitial pneumonia, pulmonary fibrosis, eosinophilic pneumonia, organising pneumonia, pulmonary edema, or sarcoidosis. A large amount of drugs have been incriminated, including those used in cardiovascular diseases (amiodarone, statins and angiotensin converting enzyme inhibitors), antibiotics (minocycline, nitrofurantoin), most of anticancer drugs (and especially chemotherapy and chest radiation), treatment of rheumatoid arthritis, as well as more recent drugs. A high index of suspicion is therefore required in any patient with infiltrative lung disease and the web-based tool www.pneumotox.com will help to list possible causative drugs. The following steps are necessary: history and timing of drug exposure, clinical and imaging pattern, exclusion of other causes of infiltrative lung disease, improvement following drug discontinuation. Rechallenge, dangerous, is not recommended.

  5. 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.

  6. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. 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

  8. 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.

  9. [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.

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. Diffuse and interstitial lung disease and childhood rheumatologic disorders.

    PubMed

    Dell, Sharon; Cernelc-Kohan, Matejka; Hagood, James S

    2012-09-01

    Advances in genetics and clinical diagnostics, along with recently described clinical entities and refined classification schemes, have improved our understanding of diffuse and interstitial lung diseases in children. This review presents recent updates in these disorders in the context of systemic inflammatory conditions. Classification of childhood diffuse lung disease (DLD) using adult paradigms is not useful. Distinct clinical-pathologic entities exist in children. Infants are more likely to present with genetic and developmental disorders, and older children with inflammatory and immune-mediated conditions. A combination of clinical evaluation, high-resolution computed tomography scanning, pulmonary function testing and serology, with bronchoscopy and surgical lung biopsy in selected cases, is most useful in the evaluation of DLD in the context of rheumatologic conditions. Common causes of DLD, such as infection, especially in the setting of immunodeficiency, must be ruled out. Optimal therapy for specific disorders will require careful analysis of data from national registries. Emerging use of biomarkers and high-throughput molecular analysis will yield novel insight into these disorders. In the setting of known or suspected rheumatologic disorders, diagnosis and management of DLD are challenging, and require close collaboration among rheumatologists, pulmonologists, and other specialists.

  15. 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

  16. Hypoxic-ischemic brain damage induces distant inflammatory lung injury in newborn piglets.

    PubMed

    Arruza, Luis; Pazos, M Ruth; Mohammed, Nagat; Escribano, Natalia; Lafuente, Hector; Santos, Martín; Alvarez-Díaz, Francisco J; Martínez-Orgado, Jose

    2016-03-01

    We aimed to investigate whether neonatal hypoxic-ischemic (HI) brain injury induces inflammatory lung damage. Thus, hypoxic (HYP, FiO2 10% for 30 min), ischemic (ISC, bilateral carotid flow interruption for 30 min), or HI event was performed in 1-2-d-old piglets. Dynamic compliance (Cdyn), oxygenation index (OI), and extravascular lung water (EVLW) were monitored for 6 h. Then, histologic damage was assessed in brain and lung (lung injury severity score). Total protein content (TPC) was determined in broncoalveolar lavage fluid (BALF), and IL-1β concentration was measured in lung and brain tissues and blood. Piglets without hypoxia or ischemia served as controls (SHM). HI-induced brain damage was associated with decreased Cdyn, increased OI and EVLW, and histologic lung damage (interstitial leukocyte infiltration, congestive hyperemia, and interstitial edema). BALF TPC was increased, suggesting inflammatory damage. In agreement, tissue IL-1β concentration increased in the brain and lung, in correspondence with increased IL-1β serum concentration. Neither HYP nor ISC alone led to brain or lung damage. HI brain damage in newborn piglets led to inflammatory lung damage, suggesting an additional mechanism accounting for the development of lung dysfunction after neonatal HI encephalopathy.

  17. 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.

  18. 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

  19. 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.

  20. 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 ...

  1. 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 ...

  2. Lung epithelial CCAAT/enhancer-binding protein-β is necessary for the integrity of inflammatory responses to cigarette smoke.

    PubMed

    Didon, Lukas; Barton, Jenny L; Roos, Abraham B; Gaschler, Gordon J; Bauer, Carla M T; Berg, Tove; Stämpfli, Martin R; Nord, Magnus

    2011-07-15

    Cigarette smoke is the major cause of chronic obstructive pulmonary disease and lung cancer. The mechanisms by which smoking induces pulmonary dysfunction are complex, involving stress from toxic components and inflammatory responses. Although CCCAAT/enhancer-binding protein (C/EBP)-β is known as a key intracellular regulator of inflammatory signaling, its role in pulmonary inflammation has not been established. To characterize the role of C/EBPβ in the airway epithelial response to cigarette smoke. mRNA expression in the airway epithelium of current, former, and never-smokers, and in in vitro cigarette smoke extract-treated primary human airway epithelial cells, was analyzed by microarray and quantitative real-time polymerase chain reaction, respectively. Mice with lung epithelial-specific inactivation of C/EBPβ were generated and exposed to cigarette smoke for 4 or 11 days. Lung histology, bronchoalveolar lavage cell differentials, and expression of inflammatory and innate immune mediators in the lungs were assessed. C/EBPβ was significantly down-regulated in the airway epithelium of both current and former smokers compared with never-smokers, and in cigarette smoke-treated primary human airway epithelial cells in vitro. Cigarette smoke-exposed mice with a lung epithelial-specific inactivation of C/EBPβ displayed blunted respiratory neutrophil influx and compromised induction of neutrophil chemoattractants growth-regulated oncogene-α, macrophage inflammatory protein-1γ, granulocyte colony-stimulating factor, and serum amyloid A 3 and proinflammatory cytokines tumor necrosis factor-α and interleukin-1β, compared with smoke-exposed controls. Inhibition of C/EBPβ in human airway cells in vitro caused a similarly compromised response to smoke. Our data suggest a previously unknown role for C/EBPβ and the airway epithelium in mediating inflammatory and innate immune responses to cigarette smoke.

  3. 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

  4. 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

  5. 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.

  6. Is the disease course predictable in inflammatory bowel diseases?

    PubMed Central

    Lakatos, Peter Laszlo; Kiss, Lajos S

    2010-01-01

    During the course of the disease, most patients with Crohn’s disease (CD) may eventually develop a stricturing or a perforating complication, and a significant number of patients with both CD and ulcerative colitis will undergo surgery. In recent years, research has focused on the determination of factors important in the prediction of disease course in inflammatory bowel diseases to improve stratification of patients, identify individual patient profiles, including clinical, laboratory and molecular markers, which hopefully will allow physicians to choose the most appropriate management in terms of therapy and intensity of follow-up. This review summarizes the available evidence on clinical, endoscopic variables and biomarkers in the prediction of short and long-term outcome in patients with inflammatory bowel diseases. PMID:20518079

  7. 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.

  8. [Lung transplantation in pulmonary fibrosis and other interstitial lung diseases].

    PubMed

    Berastegui, Cristina; Monforte, Victor; Bravo, Carlos; Sole, Joan; Gavalda, Joan; Tenório, Luis; Villar, Ana; Rochera, M Isabel; Canela, Mercè; Morell, Ferran; Roman, Antonio

    2014-09-15

    Interstitial lung disease (ILD) is the second indication for lung transplantation (LT) after emphysema. The aim of this study is to review the results of LT for ILD in Hospital Vall d'Hebron (Barcelona, Spain). We retrospectively studied 150 patients, 87 (58%) men, mean age 48 (r: 20-67) years between August 1990 and January 2010. One hundred and four (69%) were single lung transplants (SLT) and 46 (31%) bilateral-lung transplants (BLT). The postoperative diagnoses were: 94 (63%) usual interstitial pneumonia, 23 (15%) nonspecific interstitial pneumonia, 11 (7%) unclassifiable interstitial pneumonia and 15% miscellaneous. We describe the functional results, complications and survival. The actuarial survival was 87, 70 and 53% at one, 3 and 5 years respectively. The most frequent causes of death included early graft dysfunction and development of chronic rejection in the form of bronchiolitis obliterans (BOS). The mean postoperative increase in forced vital capacity and forced expiratory volume in the first second (FEV1) was similar in SLT and BLT. The best FEV1 was reached after 10 (r: 1-36) months. Sixteen percent of patients returned to work. At some point during the evolution, proven acute rejection was diagnosed histologically in 53 (35%) patients. The prevalence of BOS among survivors was 20% per year, 45% at 3 years and 63% at 5 years. LT is the best treatment option currently available for ILD, in which medical treatment has failed. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  9. Host-microorganism interactions in lung diseases.

    PubMed

    Marsland, Benjamin J; Gollwitzer, Eva S

    2014-12-01

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

  10. 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.

  11. 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

  12. 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

  13. 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

  14. Novel therapeutic options in the inflammatory bowel disease world.

    PubMed

    Noble, A; Baldassano, R; Mamula, P

    2008-01-01

    Advances in the understanding of the pathogenesis of inflammatory bowel disease have encouraged the development of many new therapies targeted at specific and non-specific mediators of the inflammatory bowel disease inflammatory pathway. The role of these therapies, including novel anti-tumour necrosis factor-alpha agents, anti-adhesion molecules, recombinant cytokines, myeloid growth factors, helminths, and probiotics, in the management of paediatric onset inflammatory bowel disease is promising and warrants further investigation.

  15. Biologic therapy for inflammatory bowel disease.

    PubMed

    Ardizzone, Sandro; Bianchi Porro, Gabriele

    2005-01-01

    Despite all of the advances in our understanding of the pathophysiology of inflammatory bowel disease (IBD), we still do not know its cause. Some of the most recently available data are discussed in this review; however, this field is changing rapidly and it is increasingly becoming accepted that immunogenetics play an important role in the predisposition, modulation and perpetuation of IBD. The role of intestinal milieu, and enteric flora in particular, appears to be of greater significance than previously thought. This complex interplay of genetic, microbial and environmental factors culminates in a sustained activation of the mucosal immune and non-immune response, probably facilitated by defects in the intestinal epithelial barrier and mucosal immune system, resulting in active inflammation and tissue destruction. Under normal situations, the intestinal mucosa is in a state of 'controlled' inflammation regulated by a delicate balance of proinflammatory (tumour necrosis factor [TNF]-alpha, interferon [IFN]-gamma, interleukin [IL]-1, IL-6, IL-12) and anti-inflammatory cytokines (IL-4, IL-10, IL-11). The mucosal immune system is the central effector of intestinal inflammation and injury, with cytokines playing a central role in modulating inflammation. Cytokines may, therefore, be a logical target for IBD therapy using specific cytokine inhibitors. Biotechnology agents targeted against TNF, leukocyte adhesion, T-helper cell (T(h))-1 polarisation, T-cell activation or nuclear factor (NF)-kappaB, and other miscellaneous therapies are being evaluated as potential therapies for IBD. In this context, infliximab is currently the only biologic agent approved for the treatment of inflammatory and fistulising Crohn's disease. Other anti-TNF biologic agents have emerged, including CDP 571, certolizumab pegol (CDP 870), etanercept, onercept and adalimumab. However, ongoing research continues to generate new biologic agents targeted at specific pathogenic mechanisms involved

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

    PubMed Central

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

    2014-01-01

    Sex-specific differences in pulmonary morbidity in humans are well documented. Hyperoxia contributes to lung injury in experimental animals and humans. The mechanisms responsible for sex differences in the susceptibility towards hyperoxic lung injury remain largely unknown. In this investigation, we tested the hypothesis that mice will display sex-specific differences in hyperoxic lung injury. Eight week-old male and female mice (C57BL/6J) were exposed to 72 h of hyperoxia (FiO2>0.95). After exposure to hyperoxia, lung injury, levels of 8-iso-prostaglandin F2 alpha (8-iso-PGF 2α) (LC-MS/MS), apoptosis (TUNEL) and inflammatory markers (suspension bead array) were determined. CytochromeP450 (CYP)1A expression in the lung was assessed using immunohistochemistry and western blotting. After exposure to hyperoxia, males showed greater lung injury, neutrophil infiltration and apoptosis, compared to air-breathing controls than females. Pulmonary 8-iso-PGF 2α levels were higher in males than females after hyperoxia exposure. Sexually dimorphic increases in levels of IL-6 (F>M) and VEGF (M>F) in the lungs were also observed. CYP1A1 expression in the lung was higher in female mice compared to males under hyperoxic conditions. Overall, our results support the hypothesis that male mice are more susceptible than females to hyperoxic lung injury and that differences in inflammatory and oxidative stress markers contribute to these sex-specific dimorphic effects. In conclusion, this paper describes the establishment of an animal model that shows sex differences in hyperoxic lung injury in a temporal manner and thus has important implications for lung diseases mediated by hyperoxia in humans. PMID:23792423

  17. 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

  18. 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.

  19. 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

  20. 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

  1. 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

  2. Managing end stage lung disease in children.

    PubMed

    Ringholz, Fiona; Devins, Mary; McNally, Paul

    2014-03-01

    Over the course of a career most physicians will manage only a handful of children through End Stage Lung Disease. Nonetheless, the approach of the physician to this challenge will have a profound impact on the children and families they encounter. Managing the end of life well can bring personal growth and professional satisfaction. In this review we highlight aspects of the Palliative Care approach and its integration with restorative and life-prolonging care. We review the role of active treatment, respiratory support, symptom management and psychosocial aspects of the management of End Stage Lung Disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. 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.

  4. 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.

  5. Interstitial lung disease associated with amrubicin chemotherapy in patients with lung cancer: a single institutional study.

    PubMed

    Miura, Yukiko; Saito, Yoshinobu; Atsumi, Kenichiro; Takeuchi, Susumu; Miyanaga, Akihiko; Mizutani, Hideaki; Minegishi, Yuji; Noro, Rintaro; Seike, Masahiro; Shinobu, Kunugi; Kubota, Kaoru; Gemma, Akihiko

    2016-07-01

    Amrubicin, which is used as a chemotherapeutic agent for lung cancer, can induce interstitial lung disease. There is insufficient evidence on the incidence of amrubicin-associated interstitial lung disease under practical use settings. We therefore investigated the occurrence of interstitial lung disease in the patients with lung cancer who received amrubicin in our institution. We reviewed the data of all patients with lung cancer who received amrubicin at the Nippon Medical School Hospital from March 2002 to April 2015. Interstitial lung disease was diagnosed based on clinical symptoms, radiographic findings and the exclusion of other diseases. We reviewed 92 consecutive patients with lung cancer. Amrubicin-associated interstitial lung disease occurred in 3 of the 92 patients (3.3%): 2 were definite interstitial lung disease and 1 was possible interstitial lung disease. The severity of interstitial lung disease was mild to moderate, and interstitial lung disease improved with or without corticosteroid therapy in all cases. The findings in a computed tomography image analysis showed preexisting pulmonary fibrosis (n = 13), including interstitial pneumonitis (n = 10) and radiation fibrosis (n = 3). No patients showed the presence of honeycomb lung. Among the 13 patients, 1 (7.7%) developed interstitial lung disease after amrubicin chemotherapy. Interstitial lung disease occurred in 3.3% of the patients in our study; this appeared to be less frequent than the rates in previous reports. Preexisting pulmonary fibrosis may be a risk factor for interstitial lung disease; however, no fatal cases were found among the patients with asymptomatic pulmonary fibrosis without honeycomb lung. It is thus considered to be necessary to carefully assess the possibility of preexisting pulmonary fibrosis and clarify the presence or absence of honeycomb lung before starting amrubicin chemotherapy. © The Author 2016. Published by Oxford University Press. All rights reserved

  6. Targeted therapies in inflammatory bowel disease.

    PubMed

    Siegmund, Britta

    2009-01-01

    The pathogenesis of inflammatory bowel disease (IBD) is still not completely understood, however the ongoing research of the last decade is allowing the hypothesis that in genetically predisposed individuals distinct environmental factors result in a dysregulation of the mucosal immune system and thus IBD. Until today the majority of patients are being treated with rather unspecific medications exerting suppressive effects on the mucosal immune system. Nevertheless, theses substances including azathioprine and steroids have proven excellent efficacy for defined subgroups of patients. However, the better understanding of the underlying pathogenesis resulted in the clinical development of novel therapeutic strategies with specific targets. The most prominent example being antibodies targeting tumor necrosis factor-alpha which are routinely administered in patients suffering from either Crohn's disease (CD) or ulcerative colitis. A second strategy is targeting the protein subunit p40 which heterodimerizes either with p35 resulting in the pro-inflammatory cytokine IL-12 or with p19 thus forming the pro-inflammatory IL-23. Experimental data suggest a crucial role for both cytokines in experimental colitis. Various antibodies against p40 are currently in clinical trials for patients with CD. In areas of inflammation, the blood vessel endothelial cells upregulate adhesion molecules resulting in the infiltration of leukocytes into the respective area. Natalizumab blocks these adhesion molecules. Treatment with natalizumab was associated with clinical improvement in patients with CD and has been approved in the USA. In summary, several therapeutic targets have already entered our clinical routine and have for some patients resulted in significant changes of the disease course.

  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. 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

  10. 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.

  11. 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

  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. Inflammatory myofibroblastic tumor of the lung: a rare cause of atelectasis in children.

    PubMed

    Dhouib, Amira; Barrazzone, Constance; Reverdin, Alexandra; Anooshiravani, Mehrak; Hanquinet, Sylviane

    2013-03-01

    Although rare, inflammatory myofibroblastic tumor is the most common primary lung mass in children. We report the case of an 11-year-old boy investigated for persistent cough and dyspnea with complete left lung atelectasis mimicking pneumonia. CT and MRI showed an endobronchial mass of the left main bronchus. The boy underwent endoscopic resection of the tumor and histology was in favor of an inflammatory myofibroblastic tumor of the lung. This diagnosis should be suspected in children with recurrent pneumonia. The prognosis is good after complete resection.

  14. Interstitial lung diseases in the hospitalized patient.

    PubMed

    Disayabutr, Supparerk; Calfee, Carolyn S; Collard, Harold R; Wolters, Paul J

    2015-09-25

    Interstitial lung diseases (ILDs) are disorders of the lung parenchyma. The pathogenesis, clinical manifestations, and prognosis of ILDs vary depending on the underlying disease. The onset of most ILDs is insidious, but they may also present subacutely or require hospitalization for management. ILDs that may present subacutely include acute interstitial pneumonia, connective tissue disease-associated ILDs, cryptogenic organizing pneumonia, acute eosinophilic pneumonia, drug-induced ILDs, and acute exacerbation of idiopathic pulmonary fibrosis. Prognosis and response to therapy depend on the type of underlying ILD being managed. This opinion piece discusses approaches to differentiating ILDs in the hospitalized patient, emphasizing the role of bronchoscopy and surgical lung biopsy. We then consider pharmacologic treatments and the use of mechanical ventilation in hospitalized patients with ILD. Finally, lung transplantation and palliative care as treatment modalities are considered. The diagnosis of ILD in hospitalized patients requires input from multiple disciplines. The prognosis of ILDs presenting acutely vary depending on the underlying ILD. Patients with advanced ILD or acute exacerbation of idiopathic pulmonary fibrosis have poor outcomes. The mainstay treatment in these patients is supportive care, and mechanical ventilation should only be used in these patients as a bridge to lung transplantation.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. Lung microbiome for clinicians. New discoveries about bugs in healthy and diseased lungs.

    PubMed

    Segal, Leopoldo N; 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.

  1. 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

  2. Structure-activity association of flavonoids in lung diseases.

    PubMed

    Lago, João Henrique G; Toledo-Arruda, Alessandra C; Mernak, Márcia; Barrosa, Kaidu H; Martins, Milton A; Tibério, Iolanda F L C; Prado, Carla M

    2014-03-24

    Flavonoids are polyphenolic compounds classified into flavonols, flavones, flavanones, isoflavones, catechins, anthocyanidins, and chalcones according to their chemical structures. They are abundantly found in Nature and over 8,000 flavonoids have from different sources, mainly plant materials, have been described. Recently reports have shown the valuable effects of flavonoids as antiviral, anti-allergic, antiplatelet, antitumor, antioxidant, and anti-inflammatory agents and interest in these compounds has been increasing since they can be helpful to human health. Several mechanisms of action are involved in the biological properties of flavonoids such as free radical scavenging, transition metal ion chelation, activation of survival genes and signaling pathways, regulation of mitochondrial function and modulation of inflammatory responses. The anti-inflammatory effects of flavonoids have been described in a number of studies in the literature, but not frequently associated to respiratory disease. Thus, this review aims to discuss the effects of different flavonoids in the control of lung inflammation in some disorders such as asthma, lung emphysema and acute respiratory distress syndrome and the possible mechanisms of action, as well as establish some structure-activity relationships between this biological potential and chemical profile of these compounds.

  3. The sickle cell mouse lung: pro-inflammatory and primed for allergic inflammation

    PubMed Central

    Andemariam, Biree; Adami, Alexander J.; McNamara, Jeffrey T.; Secor, Eric R.; Guernsey, Linda A.; Thrall, Roger S.

    2015-01-01

    Co-morbid asthma in sickle cell disease (SCD) confers higher rates of vaso-occlusive pain and mortality, yet the physiological link between these two distinct diseases remains puzzling. We utilized a mouse model of SCD to study pulmonary immunology and physiology before and after the induction of allergic airway disease (AAD). SCD mice were sensitized with ovalbumin (OVA) and aluminum hydroxide by the intraperitoneal (IP) route followed by daily, nose-only OVA-aerosol challenge to induce AAD. The lungs of naive SCD mice showed signs of inflammatory and immune processes: (1) histologic and cytochemical evidence of airway inflammation as compared to naïve wildtype mice; (2) bronchoalveolar lavage fluid (BAL) contained increased total lymphocytes, %CD8+ T cells, G-CSF, IL-5, IL-7, and CXCL1, and (3) lung tissue and hilar lymph node (HLN) had increased CD4+, CD8+, and regulatory T cells (Tregs). Further, SCD mice at AAD demonstrated significant changes compared to the naïve state: (1) BAL with increased %CD4+ T cells and Tregs, lower %CD8+ T cells, and decreased IFNγ, CXCL10, CCL2, and IL-17, (2) serum with increased OVA-specific IgE, IL-6, and IL-13, and decreased IL-1α and CXCL10, (3) no increase in Tregs in the lung tissue or HLN, and (4) hypo-responsiveness to methacholine challenge. In conclusion, SCD mice have an altered immunologic pulmonary milieu and physiologic responsiveness. These findings suggest that the clinical phenotype of AAD in SCD mice differs from that of wildtype mice and suggests that individuals with SCD may also have a unique, divergent phenotype perhaps amenable to a different therapeutic approach. PMID:25843670

  4. 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.

  5. 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

  6. [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.

  7. Inflammatory bowel disease pathogenesis: where are we?

    PubMed

    Fiocchi, Claudio

    2015-03-01

    Inflammatory bowel disease (IBD) is presently one of the most investigated human disorders. Expansion of knowledge of its pathophysiology has helped in developing novel medications to combat gut inflammation with a considerably degree of success. Despite this progress, much more remains to be done in regard to gaining a more profound understanding of IBD pathogenesis, detecting inflammation before it clinically manifests, implementing lifestyle modifications, and developing agents that can modify the natural course of the disease. One of the limitations to achieve these goals is the lack of integration of the major components of IBD pathogenesis, that is the exposome, the genome, the gut microbiome, and the immunome. An "IBD integrome" approach that takes advantage of all functional information derived from the detailed investigation of each single pathogenic component through the use of systems biology may offer the solution to understand IBD and cure it. © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  8. 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

  9. Biomarkers in canine inflammatory bowel disease diagnostics.

    PubMed

    Wdowiak, M; Rychlik, A; Kołodziejska-Sawerska, A

    2013-01-01

    Canine inflammatory bowel disease (IBD) is a heterogeneous group of chronic gastrointestinal disorders. The etiology, similar to human IBD, remains unknown. Canine IBD is diagnosed by exclusion, which is a long, time and money-consuming process due to the need of elimination of other diseases presenting with similar symptoms. Therefore, a search for a specific and sensitive marker is needed to overcome these difficulties. The article is divided into 3 sections presenting up-to-date information about laboratory markers, immunohistochemical markers and changes in the neurochemical coding of the enteric nervous system, concentrating on their usefulness and future applications. Data concerning laboratory and immunohistochemical markers is based mainly on canine IBD, while the neuroimmunohistochemistry section presents knowledge from human IBD due to the lack of such studies in veterinary medicine.

  10. Inflammatory mechanisms linking obesity and metabolic disease.

    PubMed

    Saltiel, Alan R; Olefsky, Jerrold M

    2017-01-03

    There are currently over 1.9 billion people who are obese or overweight, leading to a rise in related health complications, including insulin resistance, type 2 diabetes, cardiovascular disease, liver disease, cancer, and neurodegeneration. The finding that obesity and metabolic disorder are accompanied by chronic low-grade inflammation has fundamentally changed our view of the underlying causes and progression of obesity and metabolic syndrome. We now know that an inflammatory program is activated early in adipose expansion and during chronic obesity, permanently skewing the immune system to a proinflammatory phenotype, and we are beginning to delineate the reciprocal influence of obesity and inflammation. Reviews in this series examine the activation of the innate and adaptive immune system in obesity; inflammation within diabetic islets, brain, liver, gut, and muscle; the role of inflammation in fibrosis and angiogenesis; the factors that contribute to the initiation of inflammation; and therapeutic approaches to modulate inflammation in the context of obesity and metabolic syndrome.

  11. 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

  12. Environmental Risk Factors for Inflammatory Bowel Disease

    PubMed Central

    Molodecky, Natalie A.

    2010-01-01

    Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract and is associated with significant morbidity. The etiology of IBD has been extensively studied during the last several decades; however, causative factors in disease pathology are not yet fully understood. IBD is thought to result from the interaction between genetic and environmental factors that influence the normal intestinal commensal flora to trigger an inappropriate mucosal immune response. Although many IBD susceptibility genes have been discovered, similar advances in defining environmental risk factors have lagged. A number of environmental risk factors have been explored, including smoking, appendectomy, oral contraceptives, diet, breastfeeding, infections/ vaccinations, antibiotics, and childhood hygiene. However, most of these factors have demonstrated inconsistent findings, thus making additional studies necessary to better understand the etiology of IBD. PMID:20567592

  13. 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.

  14. [Risk factors associated with pelvic inflammatory disease].

    PubMed

    Pelayo Vera, Salvador; Hernández Landa, Tomás; Rodríguez Guzmán, Leoncio Miguel; Hernández Cruz, Leticia

    2002-08-01

    To determine the socio-demographic and gynecological risk factors in pelvic inflammatory disease (EPI). A study of the cases and controls divided by the age and the medical attention unit was performed. Women with an active sex life, who chose to participate in the study, were included. The definition of a case were the women who presented at least four of the clinical manifestations identified as critical as the principal criteria for EPI. For both groups a questionnaire was applied which contained the socio-demographical, gynecological and obstetric variables. 50 cases and 50 controls were evaluated. The risk factors associated with EPI were: scholastic level below high school, RMp 2.22 (IC95% 1.03-5.13); low scholastic level of the couple, RMp 2.33 (0.91-6.6); working women, RMp 3.17 (IC95% 1.3-8.7); women with a low socioeconomic level, RMp 2.86 (IC95% 1.24-7.26); a history of infectious vaginitis in the previous three months, RMp 41 (IC95% 7.94-838). The history of a use of intrauterine devices (DIU) did not present any association (RMp 0.06). The presence of EPI was found to be associated to socio-demographic and previous infectious vaginitis variables. The use of oral hormones and IUD did not show any relation. A greater amount of sexual education is needed for women with an active sex life in order to avoid the pelvic inflammatory disease.

  15. 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

  16. 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.

  17. 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.

  18. Living with Childhood Interstitial Lung Disease

    MedlinePlus

    ... doctors, nurses, dietitians, social workers, physical therapists, and home health aides. Each of these specialists may have services that can help you and your child cope with his or her lung disease. You also ... you manage care at home and inform various doctors about your child's medical ...

  19. 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.

  20. 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.

  1. 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.

  2. Transplant size mismatch in restrictive lung disease.

    PubMed

    Ganapathi, Asvin M; Mulvihill, Michael S; Englum, Brian R; Speicher, Paul J; Gulack, Brian C; Osho, Asishana A; Yerokun, Babatunde A; Snyder, Laurie R; Davis, Duane; Hartwig, Matthew G

    2017-04-01

    To maximize the benefit of lung transplantation, the effect of size mismatch on survival in lung transplant recipients with restrictive lung disease (RLD) was examined. All single and bilateral RLD lung transplants from 1987 to 2011 in the United Network for Organ Sharing (UNOS) Database were identified. Donor predicted total lung capacity (pTLC):Recipient pTLC ratio (pTLCr) quantified mismatch. pTLCr was segregated into five strata. A Cox proportional hazards model evaluated the association of pTLCr with mortality hazard. To identify a critical pTLCr, a Cox model using a restricted cubic spline for pTLCr was used. A total of 6656 transplants for RLD were identified. Median pTLCr for single orthotopic lung transplant (SOLT) and bilateral orthotopic lung transplant (BOLT) was 1.0 (0.69-1.47) and 0.98 (0.66-1.45). Examination of pTLCr as a categorical variable revealed that undersizing (pTLCr <0.8) for SOLT and moderate oversizing (pTLCr = 1.1-1.2) for SOLT and BOLT had a harmful survival effect [for SOLT pTLC <0.8: HR 1.711 (95% CI 1.146-2.557), P = 0.01 and for BOLT pTLC 1.1-1.2: HR 1.717 (95% CI 1.112-2.651), P = 0.02]. Spline analysis revealed significant changes in SOLT mortality by variation of pTLCr between 0.8-0.9 and 1.1-1.2. RLD patients undergoing SOLT are susceptible to detriments of an undersized lung. RLD patients undergoing BOLT have higher risk of mortality when pTLCr falls between 1.1 and 1.2. © 2017 Steunstichting ESOT.

  3. 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.

  4. 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

  5. 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

  6. Colonoscopic Perforation in Inflammatory Bowel Disease

    PubMed Central

    Makkar, Rohit

    2013-01-01

    Colonoscopy has become the diagnostic and therapeutic modality of choice in patients with inflammatory bowel disease (IBD) by allowing for the assessment of disease extent and activity; the distinction between ulcerative colitis, Crohn’s disease, and other differential diagnoses; the surveillance of dysplasia; and the delivery of treatment (eg, stricture dilation). Colonoscopy-associated perforation is a dreaded complication associated with significant mortality and morbidity. Understanding and mitigating the risks of perforation in patients with IBD has become an important issue with the increasing use of immunomodulators and biologic agents. Studies have shown that patients with IBD are at a higher risk for perforation from diagnostic or therapeutic endos-copy than individuals in the general population. Reported risk factors associated with colonoscopic perforation include female sex, advanced age, severe colitis, use of corticosteroids, presence of multiple comorbidities, and stricture dilation. Disease-, tech-nique-, and endoscopist-associated risk factors for perforation can be stratified and modified. This review, based on current available literature and the authors’ expertise, should shed some light on the proper management of this challenging disease phenotype. PMID:24729766

  7. 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.

  8. Toxic Inhalational Injury-Associated Interstitial Lung Disease in Children

    PubMed Central

    Lee, Eun; Seo, Ju-Hee; Kim, Hyung Young; Yu, Jinho; Jhang, Won-Kyoung; Park, Seong-Jong; Kwon, Ji-Won; Kim, Byoung-Ju; Do, Kyung-Hyun; Cho, Young Ah; Kim, Sun-A; Jang, Se Jin

    2013-01-01

    Interstitial lung disease in children (chILD) is a group of disorders characterized by lung inflammation and interstitial fibrosis. In the past recent years, we noted an outbreak of child in Korea, which is possibly associated with inhalation toxicity. Here, we report a series of cases involving toxic inhalational injury-associated chILD with bronchiolitis obliterans pattern in Korean children. This study included 16 pediatric patients confirmed by lung biopsy and chest computed tomography, between February 2006 and May 2011 at Asan Medical Center Children's Hospital. The most common presenting symptoms were cough and dyspnea. The median age at presentation was 26 months (range: 12-47 months), with high mortality (44%). Histopathological analysis showed bronchiolar destruction and centrilobular distribution of alveolar destruction by inflammatory and fibroproliferative process with subpleural sparing. Chest computed tomography showed ground-glass opacities and consolidation in the early phase and diffuse centrilobular nodular opacity in the late phase. Air leak with severe respiratory difficulty was associated with poor prognosis. Although respiratory chemicals such as humidifier disinfectants were strongly considered as a cause of this disease, further studies are needed to understand the etiology and pathophysiology of the disease to improve the prognosis and allow early diagnosis and treatment. PMID:23772158

  9. 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.

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

    PubMed Central

    Leslie, K O

    2009-01-01

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

  11. 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.

  12. The association between combined non-cystic fibrosis bronchiectasis and lung cancer in patients with chronic obstructive lung disease

    PubMed Central

    Kim, Yeon Wook; Jin, Kwang-Nam; Heo, Eun Young; Park, Sung Soo; Chung, Hee Soon; Kim, Deog Kyeom

    2015-01-01

    Background Whereas the epidemiological association between lung cancer and chronic obstructive pulmonary disease (COPD), a chronic inflammatory respiratory disease, is well known, limited studies have examined the association between lung cancer and non-cystic fibrosis bronchiectasis, a representative chronic airway inflammatory disease. This study evaluated the association between bronchiectasis and lung cancer in patients with COPD. Methods A matched case–control study was conducted in a referral hospital in South Korea. Among COPD patients with moderate to very severe airflow limitation (forced expiratory volume in one second/forced vital capacity <0.7 and forced expiratory volume in one second ≤70% [% predicted]) who underwent chest computed tomography (CT) between January 1, 2010 and May 30, 2013, patients with lung cancer and controls matched for age, sex, and smoking history were selected. The risk of lung cancer was assessed according to the presence of underlying bronchiectasis confirmed by chest CT. Results The study enrolled 99 cases and 198 controls. Combined bronchiectasis on chest CT was inversely associated with the risk of lung cancer compared with controls (odds ratio [OR] 0.25, 95% confidence interval [CI] 0.12–0.52, P<0.001). Significant associations were found in patients with squamous cell carcinoma (OR 0.11, 95% CI 0.03–0.49, P=0.001) and history of smoking (OR 0.27, 95% CI 0.12–0.57, P<0.001). However, the severity and location of bronchiectasis were not associated with the risk of lung cancer. Conclusion Interestingly, the concomitant presence of bronchiectasis in COPD patients was associated with a lower risk of lung cancer. PMID:26005340

  13. The association between combined non-cystic fibrosis bronchiectasis and lung cancer in patients with chronic obstructive lung disease.

    PubMed

    Kim, Yeon Wook; Jin, Kwang-Nam; Heo, Eun Young; Park, Sung Soo; Chung, Hee Soon; Kim, Deog Kyeom

    2015-01-01

    Whereas the epidemiological association between lung cancer and chronic obstructive pulmonary disease (COPD), a chronic inflammatory respiratory disease, is well known, limited studies have examined the association between lung cancer and non-cystic fibrosis bronchiectasis, a representative chronic airway inflammatory disease. This study evaluated the association between bronchiectasis and lung cancer in patients with COPD. A matched case-control study was conducted in a referral hospital in South Korea. Among COPD patients with moderate to very severe airflow limitation (forced expiratory volume in one second/forced vital capacity <0.7 and forced expiratory volume in one second ≤70% [% predicted]) who underwent chest computed tomography (CT) between January 1, 2010 and May 30, 2013, patients with lung cancer and controls matched for age, sex, and smoking history were selected. The risk of lung cancer was assessed according to the presence of underlying bronchiectasis confirmed by chest CT. The study enrolled 99 cases and 198 controls. Combined bronchiectasis on chest CT was inversely associated with the risk of lung cancer compared with controls (odds ratio [OR] 0.25, 95% confidence interval [CI] 0.12-0.52, P<0.001). Significant associations were found in patients with squamous cell carcinoma (OR 0.11, 95% CI 0.03-0.49, P=0.001) and history of smoking (OR 0.27, 95% CI 0.12-0.57, P<0.001). However, the severity and location of bronchiectasis were not associated with the risk of lung cancer. Interestingly, the concomitant presence of bronchiectasis in COPD patients was associated with a lower risk of lung cancer.

  14. The anti-inflammatory effects of PGE2 on human lung macrophages are mediated by the EP4 receptor.

    PubMed

    Gill, Sharonjit K; Yao, Yiwen; Kay, Linda J; Bewley, Martin A; Marriott, Helen M; Peachell, Peter T

    2016-11-01

    PGE2 inhibits cytokine generation from human lung macrophages. However, the EP receptor that mediates this beneficial anti-inflammatory effect of PGE2 has not been defined. The aim of this study was to identify the EP receptor by which PGE2 inhibits cytokine generation from human lung macrophages. This was determined by using recently developed EP receptor ligands. The effects of PGE2 and EP-selective agonists on LPS-induced generation of TNF-α and IL-6 from macrophages were evaluated. The effects of EP2 -selective (PF-04852946, PF-04418948) and EP4 -selective (L-161,982, CJ-042794) receptor antagonists on PGE2 responses were studied. The expression of EP receptor subtypes by human lung macrophages was determined by RT-PCR. PGE2 inhibited LPS-induced and Streptococcus pneumoniae-induced cytokine generation from human lung macrophages. Analysis of mRNA levels indicated that macrophages expressed EP2 and EP4 receptors. L-902,688 (EP4 receptor-selective agonist) was considerably more potent than butaprost (EP2 receptor-selective agonist) as an inhibitor of TNF-α generation from macrophages. EP2 receptor-selective antagonists had marginal effects on the PGE2 inhibition of TNF-α generation, whereas EP4 receptor-selective antagonists caused rightward shifts in the PGE2 concentration-response curves. These studies demonstrate that the EP4 receptor is the principal receptor that mediates the anti-inflammatory effects of PGE2 on human lung macrophages. This suggests that EP4 receptor agonists could be effective anti-inflammatory agents in human lung disease. © 2016 The British Pharmacological Society.

  15. 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.

  16. Biomass smoke exposure and chronic lung disease.

    PubMed

    Assad, Nour A; Kapoor, Vidit; Sood, Akshay

    2016-03-01

    Approximately 3 billion people worldwide rely on coal and biomass fuel for cooking and heating. Biomass smoke exposure is associated with several chronic lung diseases, including chronic obstructive pulmonary disease (COPD), asthma-COPD overlap syndrome, usual interstitial pneumonitis, hut lung, and bronchial anthracofibrosis. Household air pollution primarily from biomass smoke is the biggest risk factor for COPD worldwide. Despite the significant burden of biomass smoke-related respiratory disease, the exposure is still underappreciated worldwide, especially in high-income countries. Recent literature highlights the immunoinflammatory differences between biomass smoke-related COPD and tobacco smoke-related COPD that may lead to better understanding of the differences in the clinical phenotypes between the two entities, suggests an association with the recently recognized asthma-COPD overlap syndrome, and elucidates the burden of disease in high-income countries. The current review focuses on the association between biomass smoke and common chronic respiratory diseases, discuss differences between biomass smoke-related COPD and tobacco smoke-related COPD, highlights chronic respiratory diseases that are specific for biomass smoke exposure such as hut lung and bronchial anthracofibrosis, and discusses the known impact of beneficial interventions.

  17. Seasonality and pediatric inflammatory bowel disease.

    PubMed

    Lee, Grace J; Dotson, Jennifer L; Kappelman, Michael D; King, Eileen; Pratt, Jesse M; Colletti, Richard B; Bistrick, Sarah; Burkam, Jennifer L; Crandall, Wallace V

    2014-07-01

    Seasonal and geographic variations of inflammatory bowel disease (IBD) exacerbations have been described in adults, with inconsistent findings. We sought to determine whether disease activity in pediatric-onset IBD is associated with a seasonal pattern. We examined children with Crohn disease (CD) and ulcerative colitis (UC) using data from the ImproveCareNow Collaborative between December 2008 and November 2010. We compared the proportion of patients in continuous remission for all recorded visits in each season. We also compared the distribution of all recorded visits with a physician global assessment (PGA) of remission or active disease across seasons. A total of 1325 patients with CD (6102 visits) and 587 patients with UC (2394 visits) were included. The proportion of patients with UC in continuous remission during each season was highest in the summer (67%) and lowest in the winter (55%) (P=0.01). A similar pattern was found for CD but was not significant. Similarly, the proportion of visits in remission was highest in the summer and lowest in the winter for both UC (29%, 21%; P<0.001) and CD (28%, 23%; P<0.001); however, the distribution of visits with active disease was not significantly different across seasons. The higher proportion of patients with UC in continuous remission in the summer may be related to the higher proportion of remission visits in the summer, because the proportion of visits with active disease was similar across seasons. These findings do not support any strong associations between season of the year and disease activity in pediatric IBD.

  18. Monocyte and macrophage differentiation: circulation inflammatory monocyte as biomarker for inflammatory diseases.

    PubMed

    Yang, Jiyeon; Zhang, Lixiao; Yu, Caijia; Yang, Xiao-Feng; Wang, Hong

    2014-01-07

    Monocytes express various receptors, which monitor and sense environmental changes. Monocytes are highly plastic and heterogeneous, and change their functional phenotype in response to environmental stimulation. Evidence from murine and human studies has suggested that monocytosis can be an indicator of various inflammatory diseases. Monocytes can differentiate into inflammatory or anti-inflammatory subsets. Upon tissue damage or infection, monocytes are rapidly recruited to the tissue, where they can differentiate into tissue macrophages or dendritic cells. Given the rapid progress in monocyte research from broad spectrum of inflammatory diseases, there is a need to summarize our knowledge in monocyte heterogeneity and its impact in human disease. In this review, we describe the current understanding of heterogeneity of human and murine monocytes, the function of distinct subsets of monocytes, and a potential mechanism for monocyte differentiation. We emphasize that inflammatory monocyte subsets are valuable biomarkers for inflammatory diseases, including cardiovascular diseases.

  19. 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

  20. Pelvic Inflammatory Disease: Diagnosis And Treatment In The Emergency Department.

    PubMed

    Bugg, Charles Walter; Taira, Taku

    2016-12-01

    Pelvic inflammatory disease is a common disease that is associated with significant complications including infertility, chronic pelvic pain, ruptured tubo-ovarian abscess, and ectopic pregnancy. The diagnosis may be delayed when the presentation has nonspecific signs and symptoms. Even when it is properly identified, pelvic inflammatory disease is often treated suboptimally. This review provides evidence-based recommendations for the diagnosis, treatment, disposition, and follow-up of patients with pelvic inflammatory disease. Arranging follow-up of patients within 48 to 72 hours and providing clear patient education are fundamental to ensuring good patient outcomes. Emerging issues, including new pathogens and evolving resistance patterns among pelvic inflammatory disease pathogens are reviewed.

  1. 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

  2. Smell and taste in inflammatory bowel disease.

    PubMed

    Steinbach, Silke; Reindl, Wolfgang; Dempfle, Astrid; Schuster, Anna; Wolf, Petra; Hundt, Walter; Huber, Wolfgang

    2013-01-01

    To investigate the olfactory/gustatory functions of patients with inflammatory bowel disease (IBD) by smell/taste tests, and to determine if disease activity or medication might influence the olfactory/gustatory functions of patients. In total, 59 IBD patients (37 Crohn's disease (CD) and 22 ulcerative colitis (UC) patients) were studied using "Sniffin' sticks" and "taste strips" for olfactory and gustatory tests, respectively, and compared to healthy controls and published normative data. Among IBD (CD and UC) patients, the values for odor threshold, but not for odor identification or discrimination, were significantly lower than that of the normative data. Further, these patients showed lower values than the normative taste values and the control group for all tastes, except sour; 57.6% of the IBD patients were hyposmic, while 30.5% were hypogeusic. Subjective self-assessments showed that the patients were not aware of their reduced olfactory/gustatory functions. There were no relevant differences in taste and smell abilities between the CD and UC patients. Disease activity and treatment did not influence the olfactory/gustatory functions. IBD (CD and UC) patients exhibited significant reductions in the olfactory and gustatory functions. Therefore, patients should be tested by smell/taste tests, in order to be adequately informed of their olfactory/gustatory functions and provided an understanding of how to overcome their limitations, and thus improve their quality of life.

  3. Smell and Taste in Inflammatory Bowel Disease

    PubMed Central

    Dempfle, Astrid; Schuster, Anna; Wolf, Petra; Hundt, Walter; Huber, Wolfgang

    2013-01-01

    Objective To investigate the olfactory/gustatory functions of patients with inflammatory bowel disease (IBD) by smell/taste tests, and to determine if disease activity or medication might influence the olfactory/gustatory functions of patients. Patients and Methods In total, 59 IBD patients (37 Crohn's disease (CD) and 22 ulcerative colitis (UC) patients) were studied using “Sniffin' sticks” and “taste strips” for olfactory and gustatory tests, respectively, and compared to healthy controls and published normative data. Results Among IBD (CD and UC) patients, the values for odor threshold, but not for odor identification or discrimination, were significantly lower than that of the normative data. Further, these patients showed lower values than the normative taste values and the control group for all tastes, except sour; 57.6% of the IBD patients were hyposmic, while 30.5% were hypogeusic. Subjective self-assessments showed that the patients were not aware of their reduced olfactory/gustatory functions. There were no relevant differences in taste and smell abilities between the CD and UC patients. Disease activity and treatment did not influence the olfactory/gustatory functions. Conclusion IBD (CD and UC) patients exhibited significant reductions in the olfactory and gustatory functions. Therefore, patients should be tested by smell/taste tests, in order to be adequately informed of their olfactory/gustatory functions and provided an understanding of how to overcome their limitations, and thus improve their quality of life. PMID:24086282

  4. 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

  5. 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.

  6. Bile acid malabsorption in inflammatory bowel disease.

    PubMed

    Vítek, Libor

    2015-02-01

    Bile acid malabsorption (BAM) is a common but an underestimated and often neglected sign of inflammatory bowel diseases (IBDs), especially those affecting the distal ileum. Clinically relevant BAM is most often present in patients with Crohn's ileitis and particularly in ileal-resected Crohn's disease patients. However, deterioration of bile acid (BA) metabolism occurs also in patients with IBD without ileal disease or in those in clinical remission, and the role of BAM in these patients is not well appreciated by clinicians. In a majority of cases, BAM in IBD is caused by impaired conjugated BA reabsorption, mediated by apical sodium/BA cotransporting polypeptide, localized at the luminal surface of the ileal enterocytes. As a consequence, numerous pathological sequelae may occur, including the malfunction of lipid digestion with clinical steatorrhea, impaired intestinal motility, and/or significant changes in the intestinal microflora environment. In this review, a detailed description of the pathophysiological mechanisms of BAM-related diarrhea is presented. Although BAM is present in a significant number of patients with Crohn's disease, its laboratory assessment is not routinely included in diagnostic workups, partially because of costs, logistical reasons, or the unavailability of the more sophisticated laboratory equipment needed. Simultaneously, novel findings related to the effects of the BA signaling pathways on immune functions (mediated through TGR5, cell membrane G protein-coupled BA receptor 1, nuclear farnesoid X receptor, nuclear pregnane X receptor, or nuclear vitamin D receptor) are discussed along with intestinal metabolism in its relationship to the pathogenesis of IBD.

  7. Ocular manifestations of inflammatory bowel disease.

    PubMed

    Thomas, Akshay S; Lin, Phoebe

    2016-11-01

    Extraintestinal manifestations (EIMs) of inflammatory bowel disease (IBD) are numerous and can often involve the eye. This review highlights the ocular complications associated with IBD including the critical role the ophthalmologist can play in the diagnosis of IBD, the pathogenesis of IBD, its ocular complications, and the treatment of ocular inflammation associated with IBD. Polygenic and environmental influences, as well as gut microbial dysbiosis, have been implicated in the pathogenesis of IBD. IBD and its EIMs appear to respond well to TNFα-targeted biologics. IBD is thought to be caused by polygenic and environmental influences, including a dysbiotic gut microbiota. It is a systemic immune-mediated disease with varying types of ocular manifestations that can precede, occur simultaneously, or follow intestinal involvement. The diagnosis of IBD can be confused with other seronegative spondyloarthropathies as well as Behçet's disease. Treatment of IBD-associated ocular inflammation can range from corticosteroids to steroid-sparing immunosuppression such as azathioprine or methotrexate. Refractory disease can respond well to TNFα inhibitors.

  8. 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.

  9. Interstitial lung disease in scleroderma. Analysis by bronchoalveolar lavage.

    PubMed

    Silver, R M; Metcalf, J F; Stanley, J H; LeRoy, E C

    1984-11-01

    Interstitial pulmonary fibrosis is a common feature of scleroderma (systemic sclerosis) which may result in impairment of pulmonary function and may be a major determinant of morbidity and mortality. Clinicopathologic observations suggest that interstitial and alveolar inflammation may appear prior to fibrosis. Using the bronchoalveolar lavage (BAL) technique, we have characterized the nature of the inflammatory process in the lower respiratory tracts of 19 non-smoking scleroderma patients. Eleven of 19 patients (58%) had increased percentages of neutrophils and/or eosinophils in BAL fluid. Five of 10 patients (50%) had elevations of IgG in BAL fluid. The presence of neutrophils was associated with a decreased lung diffusing capacity for carbon monoxide (P less than 0.05) and with more advanced radiographic features of interstitial fibrosis in patients with disease of more than 1 year's duration. This study suggests that scleroderma lung involvement may be characterized by an inflammatory alveolitis and that the presence of such inflammation may relate to the severity of the pulmonary disease.

  10. Common inflammatory mechanisms in Lewy body disease and Alzheimer disease.

    PubMed

    Mrak, Robert E; Griffin, W Sue T

    2007-08-01

    Cortical Lewy body disease as a cause of dementia has been recognized for more than 40 years. Only in the past 15 to 20 years, however, has the true frequency of this entity come to be appreciated, primarily because of the advent of sensitive and specific immunohistochemical diagnostic techniques. We now know that there is frequent and extensive overlap, both clinically and pathologically, between Lewy body and Alzheimer diseases. Although some of this overlap may be attributable to common genetic and environmental risk factors, it is also now apparent that the 2 diseases share common neuroinflammatory mechanisms involving activation of microglia, overexpression of interleukin-1 and other inflammatory mediators, and inflammatory toxicity to neurons. Activated microglia are found in association with alpha-synuclein-containing neurons and glia in Parkinson disease, in dementia with Lewy bodies, and in multiple system atrophy, and these associations are reminiscent of microglial associations with neurofibrillary tangle-containing neurons in Alzheimer disease. In vitro and in vivo experimental work has shown reciprocal induction between alpha-synuclein and injured neurons on one hand and activated microglia and cytokine overexpression on the other. These neuroinflammatory processes may be a common link driving progression in both diseases and explaining the frequent overlap between the 2 diseases.

  11. 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.

  12. Translational models of lung disease.

    PubMed

    Mercer, Paul F; Abbott-Banner, Katharine; Adcock, Ian M; Knowles, Richard G

    2015-02-01

    The 2nd Cross Company Respiratory Symposium (CCRS), held in Horsham, U.K. in 2012, brought together representatives from across the pharmaceutical industry with expert academics, in the common interest of improving the design and translational predictiveness of in vivo models of respiratory disease. Organized by the respiratory representatives of the European Federation of Pharmaceutical Industries and Federations (EFPIA) group of companies involved in the EU-funded project (U-BIOPRED), the aim of the symposium was to identify state-of-the-art improvements in the utility and design of models of respiratory disease, with a view to improving their translational potential and reducing wasteful animal usage. The respiratory research and development community is responding to the challenge of improving translation in several ways: greater collaboration and open sharing of data, careful selection of the species, complexity and chronicity of the models, improved practices in preclinical research, continued refinement in models of respiratory diseases and their sub-types, greater understanding of the biology underlying human respiratory diseases and their sub-types, and finally greater use of human (and especially disease-relevant) cells, tissues and explants. The present review highlights these initiatives, combining lessons from the symposium and papers published in Clinical Science arising from the symposium, with critiques of the models currently used in the settings of asthma, idiopathic pulmonary fibrosis and COPD. The ultimate hope is that this will contribute to a more rational, efficient and sustainable development of a range of new treatments for respiratory diseases that continue to cause substantial morbidity and mortality across the world.

  13. 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.

  14. Nutrigenomics and nutrigenetics in inflammatory bowel diseases.

    PubMed

    Gruber, Lisa; Lichti, Pia; Rath, Eva; Haller, Dirk

    2012-10-01

    Inflammatory bowel diseases (IBD) including ulcerative colitis and Crohn's disease are chronically relapsing, immune-mediated disorders of the gastrointestinal tract. A major challenge in the treatment of IBD is the heterogenous nature of these pathologies. Both, ulcerative colitis and Crohn's disease are of multifactorial etiology and feature a complex interaction of host genetic susceptibility and environmental factors such as diet and gut microbiota. Genome-wide association studies identified disease-relevant single-nucleotide polymorphisms in approximately 100 genes, but at the same time twin studies also clearly indicated a strong environmental impact in disease development. However, attempts to link dietary factors to the risk of developing IBD, based on epidemiological observations showed controversial outcomes. Yet, emerging high-throughput technologies implying complete biological systems might allow taking nutrient-gene interactions into account for a better classification of patient subsets in the future. In this context, 2 new scientific fields, "nutrigenetics" and "nutrigenomics" have been established. "Nutrigenetics," studying the effect of genetic variations on nutrient-gene interactions and "Nutrigenomics," describing the impact of nutrition on physiology and health status on the level of gene transcription, protein expression, and metabolism. It is hoped that the integration of both research areas will promote the understanding of the complex gene-environment interaction in IBD etiology and in the long-term will lead to personalized nutrition for disease prevention and treatment. This review briefly summarizes data on the impact of nutrients on intestinal inflammation, highlights nutrient-gene interactions, and addresses the potential of applying "omic" technologies in the context of IBD.

  15. 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

  16. 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.

  17. 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

  18. [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.

  19. 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

  20. Management of arthropathy in inflammatory bowel diseases

    PubMed Central

    Manguso, Francesco; Vitiello, Maria; Iervolino, Salvatore; Di Minno, Matteo Nicola Dario

    2015-01-01

    The most common extra-intestinal manifestation in patients with inflammatory bowel disease (IBD) is articular involvement, with a prevalence ranging between 17% and 39%. It is frequently characterized by an involvement of the axial joints but may also be associated with peripheral arthritis. The target of therapy in the management of arthritis associated with IBD is to reduce the inflammation and prevent any disability and/or deformity. This requires active cooperation between gastroenterologist and rheumatologist. The treatment of axial involvement has focused on the combination of exercise with nonsteroidal anti-inflammatory drugs. Immunomodulators have been efficacious in patients with peripheral arthritis and other extra-intestinal manifestations, but they are not effective for the treatment of axial symptoms of spondylitis. Tumor necrosis factor (TNF) α inhibitors have been proven to be highly effective in the treatment of IBD patients which are steroid-dependent or refractory to conventional therapy and in patients with associated articular manifestations. The treatment of peripheral involvement and/or enthesitis and/or dactylitis is based on local steroid injections, while sulfasalazine and/or low doses of systemic steroids may be useful in case of inadequate response to intra-articular steroids. Sulfasalazine induces only a little improvement in peripheral arthritis. Immunomodulators such as methotrexate, azathioprine, cyclosporine and leflunomide show their efficacy in some patients with peripheral arthritis and other extra-intestinal components. TNF-α inhibitors should be considered the first-line therapeutic approach when moderate-to-severe luminal Crohn’s disease or ulcerative colitis is associated with polyarthritis. The aim of this review is to provide a fair summary of current treatment options for the arthritis associated with IBD. PMID:25729557

  1. Future directions in inflammatory bowel disease management.

    PubMed

    D'Haens, Geert R; Sartor, R Balfour; Silverberg, Mark S; Petersson, Joel; Rutgeerts, Paul

    2014-08-01

    Clinical management of inflammatory bowel diseases (IBD), new treatment modalities and the potential impact of personalised medicine remain topics of intense interest as our understanding of the pathophysiology of IBD expands. Potential future strategies for IBD management are discussed, based on recent preclinical and clinical research. A top-down approach to medical therapy is increasingly being adopted for patients with risk factors for severe inflammation or an unfavourable disease course in an attempt to halt the inflammatory process as early as possible, prevent complications and induce mucosal healing. In the future, biological therapies for IBD are likely to be used more selectively based on personalised benefit/risk assessment, determined through reliable biomarkers and tissue signatures, and will probably be optimised throughout the course of treatment. Biologics with different mechanisms of action will be available; when one drug fails, patients will be able to switch to another and even combination biologics may become a reality. The role of biotherapeutic products that are similar to currently licensed biologics in terms of quality, safety and efficacy - i.e. biosimilars - is at an early stage and requires further experience. Other therapeutic strategies may involve manipulation of the microbiome using antibiotics, probiotics, prebiotics, diet and combinations of all these approaches. Faecal microbiota transplantation is also a potential option in IBD although controlled data are lacking. The future of classifying, prognosticating and managing IBD involves an outcomes-based approach to identify biomarkers reflecting various biological processes that can be matched with clinically important endpoints. Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

  2. 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.

  3. [Lung Cancer as an Occupational Disease].

    PubMed

    Baur, X; Woitowitz, H-J

    2016-08-01

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

  4. 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

  5. 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.

  6. OXIDANTS AND THE PATHOGENESIS OF LUNG DISEASES

    PubMed Central

    Ciencewicki, Jonathan; Trivedi, Shweta; Kleeberger, Steven R.

    2009-01-01

    The increasing number of population-based and epidemiological associations between oxidant pollutant exposures and cardiopulmonary disease exacerbation, decrements in pulmonary function, and mortality underscores the important detrimental effects of oxidants on public health. Because inhaled oxidants initiate a number of pathologic processes, including inflammation of the airways which may contribute to the pathogenesis and/or exacerbation of airways disease, it is critical to understand the mechanisms through which exogenous and endogenous oxidants interact with molecules in the cells, tissues, and epithelial lining fluid (ELF) of the lung. Furthermore, it is clear that inter-individual variation in response to a given exposure also exists across an individual lifetime. Because of the potential impact that oxidant exposures may have on reproductive outcomes and infant, child, and adult health, identification of the intrinsic and extrinsic factors that may influence susceptibility to oxidants remains an important issue. In this review, we discuss mechanisms of oxidant stress in the lung, the role of oxidants in lung disease pathogenesis and exacerbation (e.g. asthma, COPD, and ARDS), and the potential risk factors (e.g. age, genetics) for enhanced susceptibility to oxidant-induced disease. PMID:18774381

  7. 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

  8. [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.

  9. 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.

  10. Inflammatory bowel disease and celiac