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1

Oxidants in Acute and Chronic Lung Disease  

PubMed Central

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

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

2015-01-01

2

Manipulation of acute inflammatory lung disease  

Microsoft Academic Search

Inflammatory lung disease to innocuous antigens or infectious pathogens is a common occurrence and in some cases, life threatening. Often, the inflammatory infiltrate that accompanies these events contributes to pathology by deleterious effects on otherwise healthy tissue and by compromising lung function by consolidating (blocking) the airspaces. A fine balance, therefore, exists between a lung immune response and immune-mediated damage,

E L Wissinger; J Saldana; A Didierlaurent; T Hussell

2008-01-01

3

Acute Lung Failure  

PubMed Central

Lung failure is the most common organ failure seen in the intensive care unit. The pathogenesis of acute respiratory failure (ARF) can be classified as (1) neuromuscular in origin, (2) secondary to acute and chronic obstructive airway diseases, (3) alveolar processes such as cardiogenic and noncardiogenic pulmonary edema and pneumonia, and (4) vascular diseases such as acute or chronic pulmonary embolism. This article reviews the more common causes of ARF from each group, including the pathological mechanisms and the principles of critical care management, focusing on the supportive, specific, and adjunctive therapies for each condition. PMID:21989697

Mac Sweeney, Rob; McAuley, Daniel F.; Matthay, Michael A.

2013-01-01

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

Lung Disease  

MedlinePLUS

... Infections, such as influenza and pneumonia Lung cancer Sarcoidosis (sar-KOY-doh-sis) and pulmonary fibrosis Lung ... and can reduce oxygen flow into the blood. Sarcoidosis and pulmonary fibrosis. These inflammatory diseases cause stiffening ...

6

Ulcerative colitis combined with acute interstitial lung disease and airway disease: A case report and literature review  

PubMed Central

The aim of this study was to investigate the clinical features of ulcerative colitis (UC) combined with acute interstitial lung disease (ILD). One case with acute UC combined with ILD and airway disease was reported, and the pathological diagnosis of previous cases of UC combined with ILD was retrospectively analyzed according to the corresponding literature. The present case concerned a male patient with UC who presented with dry cough and progressive dyspnea. The chest computed tomography (CT) images showed as normal on the seventh day; diffuse ground-glass shadows were observed on the 11th day and diffuse reticular, patchy, nodular shadows and lung cysts were observed on the 21st day. The results of an open lung biopsy on the 23rd day indicated pleural adhesions, and the pathologies were pulmonary fibrosis and airway inflammation. Glucocorticoid therapy was ineffective in the patient, but cyclophosphamide combined with ? globulin rapidly caused the disease to remit. A total of 24 cases with UC combined with ILD and two cases of UC combined with acute ILD were retrieved through PubMed. UC combined with acute ILD was rare in clinical practice. Patients with dry cough, progressive dyspnea and diffuse ground-glass shadows in pulmonary CT images should be closely monitored. Glucocorticoid therapy should be carefully selected and precautions should be taken against opportunistic infections of the lung. Cyclophosphamide combined with ? globulin may be an effective treatment strategy. PMID:25187830

XU, LISHENG; XIAO, WEI; MA, DEDONG; ZHOU, SHENGYU; ZHANG, QINGHUI

2014-01-01

7

Biomarkers in acute lung injury.  

PubMed

Acute respiratory distress syndrome (ARDS) and its milder form acute lung injury (ALI) may result from various diseases and situations including sepsis, pneumonia, trauma, acute pancreatitis, aspiration of gastric contents, near-drowning etc. ALI/ARDS is characterized by diffuse alveolar injury, lung edema formation, neutrophil-derived inflammation, and surfactant dysfunction. Clinically, ALI/ARDS is manifested by decreased lung compliance, severe hypoxemia, and bilateral pulmonary infiltrates. Severity and further characteristics of ALI/ARDS may be detected by biomarkers in the plasma and bronchoalveolar lavage fluid (or tracheal aspirate) of patients. Changed concentrations of individual markers may suggest injury or activation of the specific types of lung cells-epithelial or endothelial cells, neutrophils, macrophages, etc.), and thereby help in diagnostics and in evaluation of the patient's clinical status and the treatment efficacy. This chapter reviews various biomarkers of acute lung injury and evaluates their usefulness in diagnostics and prognostication of ALI/ARDS. PMID:25466727

Mokra, Daniela; Kosutova, Petra

2014-10-22

8

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 ...

9

Understanding Byssinosis (Brown Lung Disease)  

MedlinePLUS

... Disparities Reports Lung Disease Finder Lung Disease List Lung HelpLine Questions about your lung health? Need help ... ENews Home > Lung Disease > Byssinosis Understanding Byssinosis (Brown Lung Disease) What is Byssinosis? Byssinosis (brown lung disease) ...

10

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

SciTech Connect

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 2?) (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 2? 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.

Lingappan, Krithika, E-mail: lingappa@bcm.edu [Department of Pediatrics, Section of Neonatology, Texas Children's Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States); Jiang, Weiwu; Wang, Lihua; Couroucli, Xanthi I. [Department of Pediatrics, Section of Neonatology, Texas Children's Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States); Barrios, Roberto [Department of Pathology and Genomic Medicine, The Methodist Hospital Physician Organization, 6565 Fannin Street, Suite M227, Houston, TX 77030 (United States); Moorthy, Bhagavatula [Department of Pediatrics, Section of Neonatology, Texas Children's Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States)

2013-10-15

11

Angiogenesis in Chronic Lung Disease  

PubMed Central

Chronic lung diseases like COPD, severe progressive pulmonary hypertension (PH), and interstitial lung diseases all have a lung vascular disease component. Cellular and molecular mechanisms of pulmonary vascular remodeling have been experimentally explored in many animal models, and it is now clear that microvessels are involved. In emphysema patients, there is a loss of lung microvessels, and in many forms of severe PH there is obliteration of precapillary arterioles by angioproliferation. Thus, COPD/emphysema and severe angioproliferative PH are on the opposite ends of a spectrum of vascular biology responses. Animal experiments have provided insight regarding some of the initiating events that shape the various forms of pulmonary vascular remodeling. In pulmonary fibrosis and in the postinjury phase of acute lung injury, the angiogenic/angiostatic balance is also affected. This review will therefore discuss angiogenesis in several chronic lung diseases and will speculate on how altered vascular homeostasis may contribute to lung disease development. PMID:17356107

Voelkel, Norbert F.; Douglas, Ivor S.; Nicolls, Mark

2015-01-01

12

Chronic Lung Disease Cerebral Palsy  

E-print Network

0 10 20 30 40 50 60 70 80 90 100 Chronic Lung Disease Diabetes Cerebral Palsy Sickle Cell Disease Hem ophilia Solid organ transplant Inflam m atory Bowel Disease Epilepsy Cystic Fibrosis Com plex Congential HeartDisease Acute Lym phoblastic Leukem ia Spina Bifida Medianencountersperyear Outpatient

Kay, Mark A.

13

Systemic disease during Streptococcus pneumoniae acute lung infection requires 12-lipoxygenase-dependent inflammation  

PubMed Central

Acute pulmonary infection by Streptococcus pneumoniae is characterized by high bacterial numbers in the lung, a robust alveolar influx of polymorphonuclear cells (PMNs) and a risk of systemic spread of the bacterium. We investigated host-mediators of S. pneumoniae-induced PMN migration and the role of inflammation in septicemia following pneumococcal lung infection. Hepoxilin A3 (HXA3) is a PMN chemoattractant and a metabolite of the 12-lipoxygenase (12-LOX) pathway. We observed that S. pneumoniae infection induced the production of 12-lipoxygenase in cultured pulmonary epithelium and in the lungs of infected mice. Inhibition of the 12- LOX pathway prevented pathogen-induced PMN transepithelial migration in vitro and dramatically reduced lung inflammation upon high-dose pulmonary challenge with S. pneumoniae in vivo, thus implicating HXA3 in pneumococcus-induced pulmonary inflammation. PMN basolateral-to-apical transmigration in vitro significantly increased apical-to-basolateral transepithelial migration of bacteria. Mice suppressed in the expression of 12-lipoxygenase exhibited little or no bacteremia and survived an otherwise lethal pulmonary challenge. Our data suggest that pneumococcal pulmonary inflammation is required for high level bacteremia and systemic infection, partly by disrupting lung epithelium through 12-LOX-dependent HXA3 production and subsequent PMN transepithelial migration. PMID:24089193

Bhowmick, Rudra; Maung, Nang; Hurley, Bryan P.; Ghanem, Elsa Bou; Gronert, Karsten

2013-01-01

14

Warning Signs of Lung Disease  

MedlinePLUS

... Lungs Warning Signs of Lung Disease Top Stories Lung HelpLine Questions about your lung health? Need help ... Warning Signs of Lung Disease Warning Signs of Lung Disease WARNING SIGNS If you have any of ...

15

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 ...

16

Alterations in nonhuman primate (M. nemestrina) lung proteoglycans during normal development and acute hyaline membrane disease.  

PubMed

Proteoglycans (PGs) and lung hyaluronan (HA) are important components of the lung matrix both during normal development and in response to injury. We combined morphologic and biochemical techniques to study changes in PG and HA in a developmental series of Macaca nemestrina lungs ranging from 62% gestation to 3 mo post-term (n = 16), in adult lungs (n = 6), and from prematurely delivered, mechanically ventilated monkeys with hyaline membrane disease (HMD) (n = 7). Three groups of cuprolinic blue-positive (CuB) precipitates, identified by size, location, and susceptibility to enzyme digestion were found in lungs from all animals. Immature alveolar interstitium is characterized by loosely woven collagen bundles and an abundance of large (100 to 200 nm) stained filaments representing chondroitin sulfate proteoglycans (CSPGs). As maturation proceeds, the interstitial matrix appears increasingly organized, with large collagen bundles associated with 20 nm CuB-stained deposits (dermatan sulfate proteoglycans, DSPGs), and fewer large CSPGs. Fetal alveolar basement membrane contains CuB-stained heparin sulfate proteoglycans (HSPGs) (10 nm) scattered throughout. Lung matrix from animals with HMD appeared to have a disruption of the collagen-DSPG relationship, in addition to an enrichment in large CSPG. Complementary biochemical analysis of lung PGs and HA was done. Minced lung parenchyma was cultured with [3H]-glucosamine and [35S]-sulfate for 24 h; PGs and HA were extracted and analyzed. While PG synthesis during development tended to be highest at 80% gestation, animals with HMD showed greatly increased synthesis, approximately 2.5-fold higher than comparable fetal animals. In the developmental series, [3H]-glucosamine incorporation into HA was maximal at term, falling abruptly thereafter. HMD animals, however, showed a 2.3-fold increase over controls in net HA synthesis. Extracted PGs were separated according to buoyant density by dissociative cesium chloride density gradient ultracentrifugation. Two peaks of 35S-labeled PGs were separated from each density gradient fraction by chromatography on Sepharose CL-4B. A large CSPG was the principal PG eluting in the voiding volume, while the second broad peak (K(av) = 0.42) contained a mixed population of CSPG, DSPG, and HSPGs, the proportions of which varied with age. Both ultrastructural and biochemical analyses indicate that production of a large, high buoyant density CSPG predominates in fetal lung tissue, and diminishes with developmental age. Synthesis of large CSPG is greatly increased in lung explants from prematurely delivered animals with HMD.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:8448019

Juul, S E; Kinsella, M G; Wight, T N; Hodson, W A

1993-03-01

17

Hyperoxic Acute Lung Injury  

PubMed Central

Prolonged breathing of very high FIO2 (FIO2 ? 0.9) uniformly causes severe hyperoxic acute lung injury (HALI) and, without a reduction of FIO2, is usually fatal. The severity of HALI is directly proportional to PO2 (particularly above 450 mm Hg, or an FIO2 of 0.6) and exposure duration. Hyperoxia produces extraordinary amounts of reactive O2 species that overwhelms natural antioxidant defenses and destroys cellular structures through several pathways. Genetic predisposition has been shown to play an important role in HALI among animals, and some genetics-based epidemiologic research suggests that this may be true for humans as well. Clinically, the risk of HALI likely occurs when FIO2exceeds 0.7, and may become problematic when FIO2 exceeds 0.8 for an extended period of time. Both high-stretch mechanical ventilation and hyperoxia potentiate lung injury and may promote pulmonary infection. During the 1960s, confusion regarding the incidence and relevance of HALI largely reflected such issues as the primitive control of FIO2, the absence of PEEP, and the fact that at the time both ALI and ventilator-induced lung injury were unknown. The advent of PEEP and precise control over FIO2, as well as lung-protective ventilation, and other adjunctive therapies for severe hypoxemia, has greatly reduced the risk of HALI for the vast majority of patients requiring mechanical ventilation in the 21st century. However, a subset of patients with very severe ARDS requiring hyperoxic therapy is at substantial risk for developing HALI, therefore justifying the use of such adjunctive therapies. PMID:23271823

Kallet, Richard H; Matthay, Michael A

2013-01-01

18

Particles causing lung disease.  

PubMed Central

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 quantify our preliminary picture of the pathogenesis of lung disease by particles, but a useful start has been made. Images FIGURE 1. PMID:6376114

Kilburn, K H

1984-01-01

19

Resolution of Acute Inflammation In The Lung  

PubMed Central

Acute inflammation in the lung is essential to health. So too is its resolution. In response to invading microbes, noxious stimuli or tissue injury, an acute inflammatory response is mounted to protect the host. To limit inflammation and prevent collateral injury of healthy, uninvolved tissue, the lung orchestrates the formation of specialized pro-resolving mediators, specifically lipoxins, resolvins, protectins and maresins. These immunoresolvents are agonists for resolution that interact with specific receptors on leukocytes and structural cells to blunt further inflammation and promote catabasis. This process appears to be defective in several common lung diseases that are characterized by excess or chronic inflammation. Here, we review the molecular and cellular effectors of resolution of acute inflammation in the lung. PMID:24313723

Levy, Bruce D.; Serhan, Charles N.

2015-01-01

20

Genetics and Lung Disease  

MedlinePLUS

... Society What should I know about genetics and lung disease? If you compare the genes of a group ... your risk of getting asthma. For a few lung diseases, genes play a much bigger role. These are ...

21

Multiple Cystic Lung Disease  

PubMed Central

A lung cyst is an air-filled lucent structure surrounded by a thin wall. The presence of multiple intrapulmonary cysts is defined as cystic lung disease. Although cystic lung disease is rare, incidental detection has increased significantly in recent years by screening using computed tomography. There are many conditions that can mimic lung cysts and cause cystic lung disease. Clinical, radiographic, and histologic findings are all necessary for a proper diagnosis, and multidisciplinary approaches are frequently required. The aim of this report is to review the causes and characteristics of cystic lung disease to better understand and improve treatment. PMID:23579924

Yoo, Chul-Gyu

2013-01-01

22

Particles causing lung disease  

SciTech Connect

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.

Kilburn, K.H.

1984-04-01

23

Effect and mechanism of acute graft versus host disease on early diffuse murine lung injury following allogeneic stem cell transplantation.  

PubMed

To explore the effect and pathogenssis of acute graft-versus-host disease (aGVHD) on early diffuse lung injury in allogeneic hematopoietic stem cell transplantation (allo-HSCT), we established an aGVHD model of C(57)BL/6-->BALB/c mice. Chest computed tomography (CT) scans, histopathology and the levels of cytokines including tumor necrosis factor alpha (TNFalpha) and Interferon (IFNgamma) in lungs were dynamically detected in recipient mice after transplantation. The incidence of aGVHD was respectively 0%, 0% and 100% in simple irradiation group (A), syngeneic transplant group(B) and allogeneic transplant group (C). Chest CT scans of recipient mice were normal in 3 groups on days +3 and +7 after transplantation. CT showed that two of ten mice had bilateral lung diffuse infiltrate on day +12 (on the brink of death) in group A and 6 of 10 mice had bilateral lung diffuse infiltrate on day +14 (3 d after aGVHD occurring) in group C, and were normal on days +12 and +14 in group B after transplantation. Histopathology of lungs in the 3 groups was similar, consisting of minor interstitial pneumonitis on day +3. Group A showed edema, hyperplasia of epithelial cells and widened alveolar interval on day +7, and epithelial cell necrosis, lymphocyte infiltration, hemorrhage, protein leakage, and local consolidation on day +12. The histopathology of group B showed slight edema of epithelial cells on +7 day, which were slighter than that on day +3, and virtually normal on day +14. The histopathology in group C was characterized by the significant expansion and congestion of capillaries, and lymphocyte infiltration on day +7, the acute pneumonitis was present involving tissue edema, lymphocyte and macrophage infiltration, protein leakage and perivascular inflammation on day +14. In group A, the levels of TNFalpha were lower on day +7 than on day +3. In group B, the levels of TNFalpha attained a peak on day +3, which decreased on days +7 and +14. In group C, the levels of TNFalpha were highest on day +7 and there was a significant difference between those on days +7 and +14 (P=0.816). In group A, the levels of IFNgamma on day +7 were higher than on day +3. In group B, the levels of IFNgamma increased progressively, but the comparison of IFNgamma levels in different times had no statistical significance (P=0.521, 0.118, 0.340). In group C, the levels of IFNgamma attained a peak by day +7 and decreased on day +14. aGVHD is the main cause of early non-infectious lung injury. T lymphocytes and TNFalpha are possibly implicated in the pathogenesis of acute GVHD-induced lung injury. The decreased levels of IFNgamma in lung tissues following transplantation might be associated with pulmonary fibrosis in late non-infectious pulmonary complications. PMID:19937199

Ning, Juan; Liu, Qi Fa; Luo, Xiao Dan; Fan, Zhi Ping; Zhang, Yu

2009-11-01

24

Lung Diseases and Conditions  

MedlinePLUS

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

25

[Granulomatous lung and systemic diseases].  

PubMed

Granuloma formation occurs in the human body if there is a particle which persists in phagocytes and which the immune system cannot eliminate. The immune reaction of granuloma formation evolved in order to combat mycobacteria with the aim of localizing mycobacteria and to avoid spreading of mycobacteria throughout the body. Granulomatous lung diseases are often accompanied by severe, systemic inflammation. However, acute phase proteins may be only slightly elevated. The spectrum of granulomatous lung diseases is broad. Sarcoidosis is the most common granulomatous lung disease. To diagnose sarcoidosis, other infectious granulomatous lung diseases such as tuberculosis, atypical mycobacterial and fungal infection have to be ruled out. Pulmonary granuloma also evolve in the context of autoimmune diseases such as rheumatoid arthritis, granulomatosis with polyangiitis (GBA, Wegener's) and eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome). Furthermore, immunodeficiencies such as common variable immunodeficiency (CVID) and immune reconstitution syndrome in HIV can be associated with systemic granulomatous inflammation. Finally, occupational lung disease, particularly hypersensitivity pneumonitis, silicosis, hard metal lung, and chronic berylliosis are associated with pulmonary granuloma formation. PMID:23463460

Prasse, A; Kayser, G; Müller-Quernheim, J

2013-04-01

26

Role of Extracellular Adenosine in Acute Lung Injury  

NSDL National Science Digital Library

Acute lung injury (ALI) is a lung disease characterized by pulmonary edema and severe hypoxia. The past decade hosted a search for endogenous mechanisms controlling lung inflammation and pulmonary edema during ALI. As such, recent evidence indicates extracellular adenosine in orchestrating the resolution of pulmonary edema and inflammation during ALI.

Tobias Eckle (University of Colorado Denver Anesthesiology, Mucosal Inflammation Program)

2009-10-01

27

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 ...

28

Interstitial lung disease - adults - discharge  

MedlinePLUS

... your breathing problems that are caused by interstitial lung disease. This disease scars your lungs, which makes it ... Raghu G. Interstitial lung disease. In: Goldman L, Schafer AI. ... ed. Philadelphia, PA: Elsevier Saunders; 2011: chap 92. Selman M, ...

29

Ubiquitination and Proteolysis in Acute Lung Injury  

PubMed Central

Ubiquitination is a posttranslational modification that regulates a variety of cellular functions depending on timing, subcellular localization, and type of tagging, as well as modulators of ubiquitin binding leading to proteasomal or lysosomal degradation or nonproteolytic modifications. Ubiquitination plays an important role in the pathogenesis of acute lung injury (ALI) and other lung diseases with pathologies secondary to inflammation, mechanical ventilation, and decreased physical mobility. Particularly, ubiquitination has been shown to affect alveolar epithelial barrier function and alveolar edema clearance by targeting the Na,K-ATPase and epithelial Na+ channels upon lung injury. Notably, the proteasomal system also exhibits distinct functions in the extracellular space, which may contribute to the pathogenesis of ALI and other pulmonary diseases. Better understanding of these mechanisms may ultimately lead to novel therapeutic modalities by targeting elements of the ubiquitination pathway. PMID:22396561

Weiss, Curtis H.; Sznajder, Jacob I.

2012-01-01

30

Flavorings-Related Lung Disease  

MedlinePLUS

... Safety & Health Topics NIOSH Share Compartir FLAVORINGS-RELATED LUNG DISEASE On this Page Background Flavorings-Related Lung ... practices that place workers at risk. Flavorings-Related Lung Disease Microwave popcorn plant and flavoring plant workers ...

31

Interstitial lung disease  

MedlinePLUS

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

32

Occupational Lung Diseases  

MedlinePLUS

... disease? Some dusts, such as asbestos, silica, and coal can cause serious scarring (fibrosis) in the lungs. ... Chlorine Gas Lun g Scarring Asbestos Silica Foundry Coal Dust Asbestos Shipyards Sandblasters Brake Manufacturers Latex Beryllium ...

33

Indium Lung Disease  

PubMed Central

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

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

34

Efferocytosis and Lung Disease  

PubMed Central

In healthy individuals, billions of cells die by apoptosis each day. Clearance of these apoptotic cells, termed “efferocytosis,” must be efficient to prevent secondary necrosis and the release of proinflammatory cell contents that disrupt tissue homeostasis and potentially foster autoimmunity. During inflammation, most apoptotic cells are cleared by macrophages; the efferocytic process actively induces a macrophage phenotype that favors tissue repair and suppression of inflammation. Several chronic lung diseases, particularly airways diseases such as chronic obstructive lung disease, asthma, and cystic fibrosis, are characterized by an increased lung burden of uningested apoptotic cells. Alveolar macrophages from individuals with these chronic airways diseases have decreased efferocytosis relative to alveolar macrophages from healthy subjects. These two findings have led to the hypothesis that impaired apoptotic cell clearance may contribute causally to sustained lung inflammation and that therapies to enhance efferocytosis might be beneficial. This review of the English-language scientific literature (2006 to mid-2012) explains how such existing therapies as corticosteroids, statins, and macrolides may act in part by augmenting apoptotic cell clearance. However, efferocytosis can also impede host defenses against lung infection. Thus, determining whether novel therapies to augment efferocytosis should be developed and in whom they should be used lies at the heart of efforts to differentiate specific phenotypes within complex chronic lung diseases to provide appropriately personalized therapies. PMID:23732585

McCubbrey, Alexandra L.

2013-01-01

35

NOD-Like Receptors in Lung Diseases  

PubMed Central

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

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

2013-01-01

36

ICAM-1 and Acute Pancreatitis Complicated by Acute Lung Injury  

Microsoft Academic Search

Summary One of the most common complications of acute pancreatitis is acute lung injury, during which intercellular adhesion molecule-1 (ICAM-1) plays an important role by participating in leukocyte adhesion and activation as well as by inducing the \\

XiPing Zhang; Dijiong Wu; Xinge Jiang

2009-01-01

37

[Granulomatous interstitial lung diseases].  

PubMed

Sarcoidosis is sometimes severe and, in this setting, some investigations like thoracic computed tomography and pulmonaruy function tests constitute an angular stone. In 25% of cases, the presentation is not typical and diagnosis may be difficult. Some lung granulomatosis may share a very similar presentation with sarcoidosis according to clinic, imaging, serum biology, broncho-alveolar lavage and pathology (berylliosis, immuno-deficiency and drug- induced lung granulomatosis). Eventually, lung Langerhans histiocytosis is a very rare disease observed in young adults with heavy smoking habits and thoracic CT is the crucial investigation to reach diagnosis in 80% of cases. PMID:25362776

Valeyre, Dominique; Musungayi, Jean-Michel

2014-09-01

38

Mitochondria in Lung Diseases  

PubMed Central

Summary Mitochondria are autonomous cellular organelles that oversee a variety of functions such as metabolism, energy production, calcium buffering, and cell fate determination. Regulation of their morphology and diverse activities beyond energy production are being recognized as playing major roles in cellular health and dysfunction. This review is aimed at summarizing what is known regarding mitochondrial contributions to pathogenesis of lung diseases. Emphasis is given to understanding the importance of structural and functional aspects of mitochondria in both normal cellular function (based on knowledge from other cell types) and in development and modulation of lung diseases such as asthma, COPD, cystic fibrosis and cancer. Emerging techniques that allow examination of mitochondria, and potential strategies to target mitochondria in the treatment of lung diseases are also discussed. PMID:23978003

Aravamudan, Bharathi; Thompson, Michael A.; Pabelick, Christina M.; Prakash, Y. S.

2014-01-01

39

HRCT score and serum ferritin level are factors associated to the 1-year mortality of acute interstitial lung disease in clinically amyopathic dermatomyositis patients.  

PubMed

The aim of this study is to evaluate the factors associated to 1-year mortality in clinically amyopathic dermatomyositis (CADM) patients with acute interstitial lung disease (ILD). A single center of 37 cases of Chinese patients with CADM was reviewed retrospectively in Renji hospital. All CADM patients were diagnosed with ILD; there were 24 cases of acute interstitial pneumonia (AIP) and 13 cases of acute exacerbation of non-acute interstitial pneumonia non-AIP. The clinical features, including blood tests, chest high-resolution computed tomography (HRCT) score, and lung function, were analyzed, respectively. Neutrophil lymphocyte ratio (NLR), serum ferritin level, serum lactate dehydrogenase (LDH) level, and HRCT score were statistically significant factors on univariate analysis. Multivariate analysis revealed that the overall HRCT score (HR 1.134, 95 % confidence interval 1.009-1.275, P?=?0.017) and serum ferritin level (HR 1.001, 95 % confidence interval 1.002-1.007, P?=?0.010) were independently significant factors of 1-year mortality. C statistic value of HRCT score (c statistic value 0.867, P?acute ILD in CADM patients. Calcineurin inhibitor might improve the outcome of CADM patients with acute ILD. PMID:25609178

Zou, Jing; Guo, Qiang; Chi, Jiachang; Wu, Huawei; Bao, Chunde

2015-04-01

40

Understanding Pneumoconiosis (Black Lung Disease)  

MedlinePLUS

... Pneumoconiosis What is Pneumoconiosis? Pneumoconiosis, also known as Black Lung Disease, is an occupational lung disease caused ... or mill, and manufacturing carbon electrodes and carbon black. Carbon electrodes are used in some large furnaces, ...

41

Preventive azithromycin treatment reduces noninfectious lung injury and acute graft-versus-host disease in a murine model of allogeneic hematopoietic cell transplantation.  

PubMed

Noninfectious lung injury and acute graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (allo-HCT) are associated with significant morbidity and mortality. Azithromycin is widely used in allogeneic HCT recipients for pulmonary chronic GVHD, although current data appear controversial. We induced GVHD and noninfectious lung injury in lethally irradiated B6D2F1 mice by transplanting bone marrow and splenic T cells from allogeneic C57BL/6 mice. Experimental groups were treated with oral azithromycin starting on day 14 until the end of week 6 or week 14 after transplantation. Azithromycin treatment resulted in improved survival and decreased lung injury; the latter characterized by improved pulmonary function, reduced peribronchial and perivascular inflammatory cell infiltrates along with diminished collagen deposition, and a decrease in lung cytokine and chemokine expression. Azithromycin also improved intestinal GVHD but did not affect liver GVHD at week 6 early after transplantation. At week 14, azithromycin decreased liver GVHD but had no effect on intestinal GVHD. In vitro, allogeneic antigen-presenting cell (APC)- dependent T cell proliferation and cytokine production were suppressed by azithromycin and inversely correlated with relative regulatory T cell (Treg) expansion, whereas no effect was seen when T cell proliferation occurred APC independently through CD3/CD28-stimulation. Further, azithromycin reduced alloreactive T cell expansion but increased Treg expansion in vivo with corresponding downregulation of MHC II on CD11c(+) dendritic cells. These results demonstrate that preventive administration of azithromycin can reduce the severity of acute GVHD and noninfectious lung injury after allo-HCT, supporting further investigation in clinical trials. PMID:25445642

Radhakrishnan, Sabarinath Venniyil; Palaniyandi, Senthilnathan; Mueller, Gunnar; Miklos, Sandra; Hager, Max; Spacenko, Elena; Karlsson, Fridrik J; Huber, Elisabeth; Kittan, Nicolai A; Hildebrandt, Gerhard C

2015-01-01

42

Clinical acute lung injury and acute respiratory distress syndrome  

Microsoft Academic Search

Opinion statement  This article provides a description of the clinical disorders associated with the development of acute noncardiogenic pulmonary\\u000a edema, better known as clinical acute lung injury (ALI) or the acute respiratory distress syndrome (ARDS). Much has been learned\\u000a about the mechanisms by which the lung is injured in patients with sepsis, pneumonia, aspiration of gastric contents, and\\u000a following major trauma.

Michael A. Matthay; Tokujiro Uchida; Xiaohui Fang

2002-01-01

43

Animal Models of Fibrotic Lung Disease  

PubMed Central

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

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

2013-01-01

44

Intravascular laser therapy in different forms of lung diseases  

NASA Astrophysics Data System (ADS)

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

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

1993-06-01

45

Ultrastructure of the lung in a murine model of malaria-associated acute lung injury/acute respiratory distress syndrome  

PubMed Central

Background The mechanisms through which infection with Plasmodium spp. result in lung disease are largely unknown. Recently a number of mouse models have been developed to research malaria-associated lung injury but no detailed ultrastructure studies of the disease in its terminal stages in a murine model have yet been published. The goal was to perform an ultrastructural analysis of the lungs of mice that died with malaria-associated acute lung injury/acute respiratory distress syndrome to better determine the relevancy of the murine models and investigate the mechanism of disease. Methods DBA/2 mice were infected with Plasmodium berghei strain ANKA. Mice had their lungs removed immediately after death, processed using standard methods and viewed by transmission electron microscopy (TEM). Results Infected red blood cell:endothelium contact, swollen endothelium with distended cytoplasmic extensions and thickening of endothelium basement membrane were observed. Septa were thick and filled with congested capillaries and leukocytes and the alveolar spaces contained blood cells, oedema and cell debris. Conclusion Results show that the lung ultrastructure of P. berghei ANKA-infected mice has similar features to what has been described in post-mortem TEM studies of lungs from individuals infected with Plasmodium falciparum. These data support the use of murine models to study malaria-associated acute lung injury. PMID:24927627

2014-01-01

46

Interstitial Lung Disease (ILD): Treatment  

MedlinePLUS

... MD Dept. of Medicine View full profile Interstitial Lung Disease (ILD): Treatment Treatment for ILD is based ... performance, improving emotional well being and reducing hospitalizations. Lung Transplant If other therapies fail to adequately treat ...

47

Common lung conditions: acute dyspnea.  

PubMed

Dyspnea is a subjective experience of breathing discomfort; patients experience qualitatively distinct sensations that vary in intensity. Acute dyspnea might be secondary to an acute problem, or it might be an exacerbation of an existing disease (eg, asthma, chronic obstructive pulmonary disease, heart failure). It also accompanies a variety of illnesses at the end of life. New information has changed differentiation between respiratory and cardiovascular etiologies of acute dyspnea, as well as rapid diagnosis of pulmonary embolism. Management of acute dyspnea from hypercapnic failure also has changed. Patients presenting with dyspnea most commonly have underlying cardiovascular and/or respiratory etiologies, and differentiating between the two can be challenging. B-type natriuretic peptide (BNP) and N-terminal proB-type natriuretic peptide (NT-proBNP) are elevated when ventricular wall tension increases (eg, during a heart failure exacerbation). BNP and NT-proBNP are most useful for identifying patients with dyspnea who do not have heart failure. A BNP level less than 50 pg/mL has a negative predictive value of 96%, effectively ruling out heart failure; a serum BNP level less than 100 pg/mL has a negative likelihood ratio of 0.11. Patients with pulmonary embolism often present with dyspnea, and this condition needs to be diagnosed and managed expeditiously. When pulmonary embolism is suspected, use a clinical decision rule (eg, the Wells rule, the Geneva rule) to establish the probability of this condition. For patients with a low probability, obtain a D-dimer test; if the D-dimer result is negative, monitor the patient. A positive D-dimer result requires further investigation. For patients with intermediate or high probability, obtain computed tomography pulmonary angiography for a definitive diagnosis. Patients who have dyspnea from a chronic obstructive pulmonary disease exacerbation can experience hypercapnic failure. As an adjunct to usual medical treatment, noninvasive positive pressure ventilation decreases the need for mechanical ventilation and is particularly useful in patients who have chosen not to be resuscitated with intubation. PMID:23767418

Delzell, John E

2013-06-01

48

Acute Leukemia Secondary to Lung Cancer  

Microsoft Academic Search

A case of acute myelomonocytic leukemia following cytotoxic therapy for an oat cell carcinoma of the lung in a 48-year-old man is reported. This case is characterized by a long phase of increasing macrocytosis during cyclophosphamide maintenance therapy. 15 other cases of secondary leukemia to lung cancer from the literature are reviewed. All patients received alkylating agents. Most patients showed

Aimery de Gramont; Ernest Rioux; Paul Fortin; Claude Shields

1985-01-01

49

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 ...

50

Risk of acute urinary retention associated with inhaled anticholinergics in patients with chronic obstructive lung disease: systematic review  

PubMed Central

Inhaled anticholinergics (ipratropium bromide and tiotropium bromide) are widely used as maintenance treatment in chronic obstructive pulmonary disease. Previous studies have reported on their cardiovascular effects but relatively little is known about their effects on the bladder. Acute urinary retention is a medical emergency which can be associated with serious complications. Our objective was to evaluate the existing literature regarding the effects of inhaled anticholinergics on urinary retention among patients with chronic obstructive pulmonary disease. We searched PubMed and the United States Food and Drug Administration (FDA) adverse events database for case reports, observational studies, randomized controlled trials (or meta-analyses of such trials) that reported on the outcome of urinary retention with inhaled anticholinergics (ipratropium or tiotropium). We checked 27 published articles and identified relevant papers including two case reports, three pooled analyses, two observational studies and one randomized controlled trial. Two of the observational studies and a pooled analysis of randomized controlled trials reported a significant increase in the risk of acute urinary retention with inhaled anticholinergics. Older patients with benign prostatic hyperplasia seem to be at the highest risk of this adverse effect which tends to occur soon after treatment initiation. Although all the links in the chain have yet to be fully elucidated, the preponderance of evidence suggests the possibility of a causal relationship between inhaled anticholinergics and urinary retention. Clinicians should carefully balance these and other adverse effects of inhaled anticholinergics against their known symptomatic benefits on exacerbations, after eliciting patient preferences for various outcomes in a shared decision-making context. PMID:25083248

Singh, Sonal

2013-01-01

51

Acute Exacerbation of Chronic Obstructive Pulmonary Disease: Cardiovascular Links  

PubMed Central

Chronic obstructive pulmonary disease (COPD) is a chronic, progressive lung disease resulting from exposure to cigarette smoke, noxious gases, particulate matter, and air pollutants. COPD is exacerbated by acute inflammatory insults such as lung infections (viral and bacterial) and air pollutants which further accelerate the steady decline in lung function. The chronic inflammatory process in the lung contributes to the extrapulmonary manifestations of COPD which are predominantly cardiovascular in nature. Here we review the significant burden of cardiovascular disease in COPD and discuss the clinical and pathological links between acute exacerbations of COPD and cardiovascular disease. PMID:24724085

Laratta, Cheryl R.; van Eeden, Stephan

2014-01-01

52

Contribution of Neutrophils to Acute Lung Injury  

PubMed Central

Treatment of acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), remain unsolved problems of intensive care medicine. ALI/ARDS are characterized by lung edema due to increased permeability of the alveolar-capillary barrier and subsequent impairment of arterial oxygenation. Lung edema, endothelial and epithelial injury are accompanied by an influx of neutrophils into the interstitium and broncheoalveolar space. Hence, activation and recruitment of neutrophils are regarded to play a key role in progression of ALI/ARDS. Neutrophils are the first cells to be recruited to the site of inflammation and have a potent antimicrobial armour that includes oxidants, proteinases and cationic peptides. Under pathological circumstances, however, unregulated release of these microbicidal compounds into the extracellular space paradoxically can damage host tissues. This review focuses on the mechanisms of neutrophil recruitment into the lung and on the contribution of neutrophils to tissue damage in ALI. PMID:21046059

Grommes, Jochen; Soehnlein, Oliver

2011-01-01

53

Sleep and Obstructive Lung Diseases  

PubMed Central

Asthma and chronic obstructive pulmonary disease (COPD) are common obstructive lung diseases affecting millions of people in the United States. As sleep disorders are also common, it is not surprising that many people with obstructive lung disease also suffer from sleep disorders. However, people with COPD and those with asthma have worse sleep quality and more sleep-related problems when compared to people with other chronic health problems. In addition, a pathologic relationship may exist between obstructive sleep apnea (OSA) and obstructive lung diseases. This review focuses on the epidemiology, pathogenesis, and clinical implications of sleep disturbances in asthma and COPD. PMID:21731527

Ezzie, Michael E.; Parsons, Jonathan P.; Mastronarde, John G.

2008-01-01

54

Claudins in lung diseases  

PubMed Central

Tight junctions are the most apically localized part of the epithelial junctional complex. They regulate the permeability and polarity of cell layers and create compartments in cell membranes. Claudins are structural molecules of tight junctions. There are 27 claudins known, and expression of different claudins is responsible for changes in the electrolyte and solute permeability in cells layers. Studies have shown that claudins and tight junctions also protect multicellular organisms from infections and that some infectious agents may use claudins as targets to invade and weaken the host's defense. In neoplastic diseases, claudin expression may be up- or downregulated. Since their expression is associated with specific tumor types or with specific locations of tumors to a certain degree, they can, in a restricted sense, also be used as tumor markers. However, the regulation of claudin expression is complex involving growth factors and integrins, protein kinases, proto-oncogens and transcription factors. In this review, the significance of claudins is discussed in lung disease and development. PMID:21619599

2011-01-01

55

[Acute lung injury and alveolar epithelial function].  

PubMed

Since its original definition forty years ago, acute lung injury/acute respiratory distress syndrome has been a challenging target for both clinicians and researchers. In this review, several progresses in the past decades in the area of research concerning the pathophysiology of alveolar epithelium in this syndrome are discussed. Understanding the mechanism of tissue injury and tissue repair are key points to develop new strategy for clinical evaluation of severity of this syndrome and possible therapeutic approaches in future. PMID:18214005

Uchida, Tokujiro; Makita, Koshi

2008-01-01

56

Stat3 activation in acute lung injury.  

PubMed

Stat3 plays diverse roles in biological processes including cell proliferation, survival, apoptosis, and inflammation. Very little is known regarding its activation and function in the lung during acute inflammation. We now show that Stat3 activation was triggered in lungs and in alveolar macrophages after intrapulmonary deposition of IgG immune complexes in rats. Low levels of constitutive Stat3 were observed in normal rat lungs as determined by the EMSA. Stat3 activity in whole lung extracts increased 2 h after initiation of IgG immune complex deposition, reaching maximal levels by 4 h, whereas Stat3 activation was found in alveolar macrophages as early as 30 min after onset of injury. Expression and activation of Stat3 mRNA, protein, and protein phosphorylation was accompanied by increased gene expression of IL-6, IL-10, and suppressor of cytokine signaling-3 in whole lung tissues. Both Tyr(705) and Ser(727) phosphorylation were involved in Stat3 activation as assessed in whole lung extracts. C5a (complement 5, fragment a) per se can induce phosphorylation of Ser(727) of Stat3. In vivo, Stat3 activation was dramatically suppressed by depletion of neutrophils or lung macrophages, resulting in reduced gene expression of IL-6 and IL-10 in whole lung tissues. Using blocking Abs to IL-6, IL-10, and C5a, Stat3 activation induced by IgG immune complexes was markedly diminished. These data suggest in the lung injury model used that activation of Stat3 in lungs is macrophage dependent and neutrophil dependent. IL-6, IL-10, and C5a contribute to Stat3 activation in inflamed rat lung. PMID:15187153

Gao, Hongwei; Guo, Ren-Feng; Speyer, Cecilia L; Reuben, Jayne; Neff, Thomas A; Hoesel, L Marco; Riedemann, Niels C; McClintock, Shannon D; Sarma, J Vidya; Van Rooijen, Nico; Zetoune, Firas S; Ward, Peter A

2004-06-15

57

Scintigraphic perfusion patterns in patients with diffuse lung disease  

SciTech Connect

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

Newman, G.E. (Duke Univ. Medical Center, Durham, NC); Sullivan, D.C.; Gottschalk, A.; Putman, C.E.

1982-04-01

58

Agricultural lung diseases.  

PubMed Central

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

Kirkhorn, S R; Garry, V F

2000-01-01

59

Acute lung injury: epidemiology, pathogenesis, and treatment.  

PubMed

Acute lung injury (ALI) remains a significant source of morbidity and mortality in the critically ill patient population. Defined by a constellation of clinical criteria (acute onset of bilateral pulmonary infiltrates with hypoxemia without evidence of hydrostatic pulmonary edema), ALI has a high incidence (200,000 per year in the US) and overall mortality remains high. Pathogenesis of ALI is explained by injury to both the vascular endothelium and alveolar epithelium. Recent advances in the understanding of pathophysiology have identified several biologic markers that are associated with worse clinical outcomes. Phase III clinical trials by the NHLBI ARDS Network have resulted in improvement in survival and a reduction in the duration of mechanical ventilation with a lung-protective ventilation strategy and fluid conservative protocol. Potential areas of future treatments include nutritional strategies, statin therapy, and mesenchymal stem cells. PMID:20073554

Johnson, Elizabeth R; Matthay, Michael A

2010-08-01

60

CXCR2 in Acute Lung Injury  

PubMed Central

In pulmonary inflammation, recruitment of circulating polymorphonuclear leukocytes is essential for host defense and initiates the following specific immune response. One pathological hallmark of acute lung injury and acute respiratory distress syndrome is the uncontrolled transmigration of neutrophils into the lung interstitium and alveolar space. Thereby, the extravasation of leukocytes from the vascular system into the tissue is induced by chemokines that are released from the site of inflammation. The most relevant chemokine receptors of neutrophils are CXC chemokine receptor (CXCR) 1 and CXCR2. CXCR2 is of particular interest since several studies implicate a pivotal role of this receptor in development and promotion of numerous inflammatory disorders. CXCR2 gets activated by ELR+ chemokines, including MIP-2, KC (rodents) and IL-8 (human). Since multiple ELR+ CXC chemokines act on both receptors—CXCR1 and CXCR2—a pharmacologic agent blocking both receptors seems to be advantageous. So far, several CXCR1/2 antagonists have been developed and have been tested successfully in experimental studies. A newly designed CXCR1 and CXCR2 antagonist can be orally administered and was for the first time found efficient in humans. This review highlights the role of CXCR2 in acute lung injury and discusses its potential as a therapeutic target. PMID:22719179

Konrad, F. M.; Reutershan, J.

2012-01-01

61

Diffuse Lung Disease in Children  

PubMed Central

Summary A multi-disciplinary scientific conference focused on diffuse and interstitial lung diseases in children was held in La Jolla, CA in June 2012. The conference brought together clinicians (including Pediatric and Adult Pulmonologists, Neonatologists, Pathologists, and Radiologists), clinical researchers, basic scientists, government agency representatives, patient advocates, as well as children affected by diffuse lung disease (DLD) and their families, to review recent scientific developments and emerging concepts in the pathophysiology of childhood DLD. Invited speakers discussed translational approaches, including genetics and proteomics, epigenetics and epigenomics, models of DLD, including animal models and induced pluripotent stem cells, and regenerative medicine approaches. The presentations of the invited speakers are summarized here. PMID:23798474

Hamvas, Aaron; Deterding, Robin; Balch, William E.; Schwartz, David A.; Albertine, Kurt H.; Whitsett, Jeffrey A.; Cardoso, Wellington V.; Kotton, Darrell N.; Kourembanas, Stella; Hagood, James S.

2014-01-01

62

Cilia dysfunction in lung disease.  

PubMed

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

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

2015-02-10

63

Role of myeloid Hif-1? in acute lung injury   

E-print Network

Acute Lung Injury, characterised clinically as the Acute Respiratory Distress Syndrome is a catastrophic response to a range of pulmonary and non-pulmonary insults. Despite much work the key mechanisms involved in generating the exaggerated immune...

MacDuff, Andrew

2011-07-05

64

Recurrent polymyositis-associated lung disease after lung transplantation.  

PubMed

The association between interstitial lung disease and polymyositis/dermatomyositis is well known. It severely affects patients' quality of life, worsens prognosis and represents a major risk factor for premature death. Current treatment is unclear and therapeutic options are based on case series. We report the case of a 15-year old female diagnosed with end-stage lung disease associated to polymyositis who received a double lung transplant after 20 days of extracorporeal membrane oxygenation. She died 9 months later and microscopic post-mortem findings revealed recurrence of interstitial lung disease. This is the first time that recurrence of polymyositis-associated lung disease following lung transplantation is described in the literature. PMID:25574033

Arboleda, Rafael; Gonzalez, Olga; Cortes, Manuel; Perez-Cerda, Francisco

2015-04-01

65

Biomarkers in Acute Lung Injury: Insights into the Pathogenesis of Acute Lung Injury  

PubMed Central

Studies of potential biomarkers in experimental models of acute lung injury (ALI) and from clinical samples from patients with ALI have provided extensive information relating to the pathophysiology of the mechanisms of lung injury and repair. The utility of biomarkers remains still solely part of the research tools to investigate lung injury and repair mechanisms and due to lack of sensitivity and specificity cannot yet be used as a clinical decision tool in patients with either acute lung injury or ARDS. We have reviewed known biomarkers in context of their major biological activity such as inflammatory mediators, coagulation/fibrinolytic mediators, growth factors and the emerging use of proteomics. The continued interest in identifying and studying biomarkers is relevant as it continues to provide important information regarding the mechanisms involved in lung injury and repair and how this may be helpful in the identification and design of future therapeutic targets and strategies as well as hopefully to identify a sensitive and specific biomarker that would be of clinical relevance. PMID:21440206

Cross, L J Mark; Matthay, Michael A

2011-01-01

66

Pathology Case Study: Lung and Liver Disease  

NSDL National Science Digital Library

The University of Pittsburgh School of Medicine's Department of Pathology has compiled a series of case studies to help both students and instructors in the health sciences field. The patient in this case is a 24 year-old man â??admitted for acute worsening of his respiratory status and liver failure.â?ť The patientâ??s history includes end-stage restrictive lung disease and end-stage liver disease. The â??Gross Descriptionâ?ť and â??Microscopic Descriptionâ?ť sections provide key information and images that contributed to the patientâ??s diagnosis. Clicking on the â??Final Diagnosisâ?ť provides a thorough explanation of the diagnosis and illness from the contributing doctors.

Johnson, Douglas R.

67

Exploring lung physiology in health and disease with lung slices  

PubMed Central

The development of therapeutic approaches to treat lung disease requires an understanding of both the normal and disease physiology of the lung. Although traditional experimental approaches only address either organ or cellular physiology, the use of lung slice preparations provides a unique approach to investigate integrated physiology that links the cellular and organ responses. Living lung slices are robust and can be prepared from a variety of species, including humans, and they retain many aspects of the cellular and structural organization of the lung. Functional portions of intrapulmonary airways, arterioles and veins are present within the alveoli parenchyma. The dynamics of macroscopic changes of contraction and relaxation associated with the airways and vessels are readily observed with conventional low-magnification microscopy. The microscopic changes associated with cellular events, that determine the macroscopic responses, can be observed with confocal or two-photon microscopy. To investigate disease processes, lung slices can either be prepared from animal models of disease or animals exposed to disease invoking conditions. Alternatively, the lung slices themselves can be experimentally manipulated. Because of the ability to observe changes in cell physiology and how these responses manifest themselves at the level of the organ, lung slices have become a standard tool for the investigation of lung disease. PMID:21600999

Sanderson, Michael J.

2011-01-01

68

Pulmonary Hypertension in Parenchymal Lung Disease  

PubMed Central

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

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

2012-01-01

69

Treatment of acute lung injury by targeting MG53-mediated cell membrane repair  

PubMed Central

Injury to lung epithelial cells has a role in multiple lung diseases. We previously identified mitsugumin 53 (MG53) as a component of the cell membrane repair machinery in striated muscle cells. Here we show that MG53 also has a physiological role in the lung and may be used as a treatment in animal models of acute lung injury. Mice lacking MG53 show increased susceptibility to ischemia-reperfusion and over-ventilation induced injury to the lung when compared with wild type mice. Extracellular application of recombinant human MG53 (rhMG53) protein protects cultured lung epithelial cells against anoxia/reoxygenation-induced injuries. Intravenous delivery or inhalation of rhMG53 reduces symptoms in rodent models of acute lung injury and emphysema. Repetitive administration of rhMG53 improves pulmonary structure associated with chronic lung injury in mice. Our data indicate a physiological function for MG53 in the lung and suggest that targeting membrane repair may be an effective means for treatment or prevention of lung diseases. PMID:25034454

Lieber, Gissela; Nishi, Miyuki; Yan, Rosalie; Wang, Zhen; Yao, Yonggang; Li, Yu; Whitson, Bryan A.; Duann, Pu; Li, Haichang; Zhou, Xinyu; Zhu, Hua; Takeshima, Hiroshi; Hunter, John C.; McLeod, Robbie L.; Weisleder, Noah; Zeng, Chunyu; Ma, Jianjie

2014-01-01

70

Circulating progenitor cells in chronic lung disease.  

PubMed

Tissue regeneration and repair are fundamental both to recovery of the lung from injury and to the pathology of many chronic lung diseases. There are two potential sources for the adult progenitor cells that participate in this reparative process: resident lung progenitors and bone marrow-derived circulating cells. Bone marrow-derived cells, in particular, have been shown to give rise to airway and alveolar epithelial cells, as well as lung mesenchymal cells. Emerging data have linked specific chemokine ligand-receptor interactions to the recruitment of these cells to the lung and has implicated these cells in chronic lung disorders such as asthma and interstitial lung diseases. In this review, we summarize the current understanding of the biology of adult circulating progenitors as related to lung disease. PMID:20477275

Mehrad, Borna; Keane, Michael P; Gomperts, Brigitte N; Strieter, Robert M

2007-08-01

71

Ventilatory strategies in obstructive lung disease.  

PubMed

Chronic obstructive pulmonary disease (COPD) is characterized by expiratory flow limitation (EFL) due to progressive airflow obstruction. The various mechanisms that cause EFL are central to understanding the physiopathology of COPD. At the end of expiration, dynamic inflation may occur due to incomplete emptying the lungs. This "extra" volume increases the alveolar pressure at the end of the expiration, resulting in auto-positive end-expiratory pressure (PEEP) or PEEPi. Acute exacerbations of COPD may result in increased airway resistance and inspiratory effort, further leading to dynamic hyperinflation. COPD exacerbations may be triggered by environmental exposures, infections (viral and bacterial), or bronchial inflammation, and may result in worsening respiratory failure requiring mechanical ventilation (MV). Acute exacerbations of COPD need to be distinguished from other events such as cardiac failure or pulmonary emboli. Strategies to treat acute respiratory failure (ARF) in COPD patients include noninvasive ventilation (NIV), pressure support ventilation, and tracheal intubation with MV. In this review, we discuss invasive and noninvasive techniques to address ARF in this patient population. When invasive MV is used, settings should be adjusted in a way that minimizes hyperinflation, while providing reasonable gas exchange, respiratory muscle rest, and proper patient-ventilator interaction. Further, weaning from MV may be difficult in these patients, and factors amenable to pharmacological correction (such as increased bronchial resistance, tracheobronchial infections, and heart failure) are to be systematically searched and treated. In selected patients, early use of NIV may hasten the process of weaning from MV and improve outcomes. PMID:25111641

Parrilla, Francisco José; Morán, Indalecio; Roche-Campo, Ferran; Mancebo, Jordi

2014-08-01

72

The role of matrix metalloproteases in cystic fibrosis lung disease  

PubMed Central

Significant airway remodeling is a major component of the increased morbidity and mortality observed in cystic fibrosis (CF) patients. These airways feature ongoing leukocytic inflammation and unrelenting bacterial infection. In contrast to acute bacterial pneumonia, CF infection is not cleared efficiently and the ensuing inflammatory response causes tissue damage. This structural damage is mainly a result of free proteolytic activity released by infiltrated neutrophils and macrophages. Major proteases in this disease are serine and matrix metalloproteases (MMPs). While the role of serine proteases, such as elastase, has been characterized in detail, there is emerging evidence that MMPs could play a key role in the pathogenesis of CF lung disease. This review summarizes studies linking MMPs with CF lung disease and discusses the potential value of MMPs as future therapeutic targets in CF and other chronic lung diseases. PMID:21233269

Gaggar, Amit; Hector, Andreas; Bratcher, Preston E.; Mall, Marcus A.; Griese, Matthias; Hartl, Dominik

2014-01-01

73

Targeting maladaptive glutathione responses in lung disease  

PubMed Central

The lung is unique being exposed directly to the atmospheric environment containing xenobiotics, pathogens, and other agents which are continuously inhaled on a daily basis. Additionally, the lung is exposed to higher ambient oxygen levels which can promote the formation of a complex number of reactive oxygen and nitrogen species. Due to this constant barrage of potential damaging agents, the lung has developed a high degree of plasticity in dealing with ever changing conditions. In the present commentary, we will focus on glutathione (GSH) as a key antioxidant in the lung airways and discuss mechanisms by which the lung uses GSH to adapt to its rapidly changing environment. We will then examine the evidence on how defective and inadequate adaptive responses can lead to lung injury, inflammation and disease. Lastly, we will examine some of the recent attempts to alter lung GSH levels with therapies in a number of human lung diseases and discuss some of the limitations of such approaches. PMID:20951119

Gould, Neal S.; Day, Brian J

2010-01-01

74

Metal-induced diffuse lung disease.  

PubMed

The number of metals that are associated with the development of diffuse parenchymal lung disease continues to expand. In addition to lung fibrosis, inhalation of metal particulates can induce a wide range of lung pathology, including reactive airways disease and cancer. This article focuses on diffuse parenchymal diseases resulting from the inhalation of beryllium and cobalt. More is known regarding the immunopathogenesis of beryllium-induced disease than is known for disease induced by any other metal. Chronic beryllium disease (CBD) is a granulomatous lung disorder caused by beryllium exposure in the workplace and is characterized by the accumulation of beryllium-specific CD4 (+) T cells in the bronchoalveolar lavage. Genetic susceptibility markers associated with increased risk have been identified for both CBD and hard metal lung disease. The mechanism for the genetic susceptibility of CBD lies in the ability of certain human leukocyte antigen (HLA)-DP molecules to bind and present beryllium to pathogenic CD4 (+) T cells. Whether the same is true for hard metal lung disease is unknown. In contrast, no HLA allelic association has been identified in nickel allergic subjects. The study of metal-induced lung disease allows the investigation of the relationship between environmental exposure and genetic susceptibility. These studies will enhance our understanding of the immunopathogenesis of metal-induced disease and how exposure to these metals results in irreversible lung fibrosis. PMID:19221964

Fontenot, Andrew P; Amicosante, Massimo

2008-12-01

75

A Case of IgG4-Related Lung Disease Presenting as Interstitial Lung Disease  

PubMed Central

Intrathoracic involvement of immunoglobulin G4 (IgG4)-related disease has recently been reported. However, a subset of the disease presenting as interstitial lung disease is rare. Here, we report a case of a 35-year-old man with IgG4-related lung disease with manifestations similar to those of interstitial lung disease. Chest computed tomography showed diffuse ground glass opacities and rapidly progressive pleural and subpleural fibrosis in both upper lobes. Histological findings showed diffuse interstitial lymphoplasmacytic infiltration with an increased number of IgG4-positive plasma cells. Serum levels of IgG and IgG4 were also increased. The patient was diagnosed with IgG4-related lung disease, treated with anti-inflammatory agents, and showed improvement. Lung involvement of IgG4-related disease can present as interstitial lung disease and, therefore, should be differentiated when evaluating interstitial lung disease. PMID:25237380

Ahn, Jee Hwan; Hong, Sun In; Cho, Dong Hui; Chae, Eun Jin; Song, Joon Seon

2014-01-01

76

Non-invasive markers of inflammation in cystic fibrosis lung disease   

E-print Network

Cystic fibrosis (CF) lung disease is characterised by early airways infection and inflammation, chronic suppuration, frequent infective exacerbations and an increased influx of acute, and chronic inflammatory cells. The ...

MacGregor, Gordon

2010-01-01

77

Krypton-81m ventilation scanning: acute respiratory disease  

SciTech Connect

From experience with 700 patients undergoing ventilation and perfusion lung scanning with krypton-81m/technetium-99m technique, 34 patients suffering from nonembolic acute respiratory disease were selected for review. In 16 patients with pneumonia, all had defects of ventilation corresponding to, or larger than, the radiologic consolidation. In 13 patients there was some preservation of perfusion in the consolidated region. In two of the three patients with matched defects, the pneumonia was of long standing. In seven patients with collapse or atelectasis and in 11 patients with acute reversible bronchial obstruction and normal volume lungs, a similar pattern or ventillation and perfusion was observed.

Lavender, J.P. (Royal Postgraduate Medical School, London, England); Irving, H.; Armstrong, J.D. II

1981-02-01

78

Lung Disease Including Asthma and Adult Vaccination  

MedlinePLUS

... Share Compartir Lung Disease including Asthma and Adult Vaccination Vaccines are especially critical for people with chronic ... have immunity to this disease Learn about adult vaccination and other health conditions Asplenia Diabetes Type 1 ...

79

[Acute hepatitis in infectious diseases].  

PubMed

Hepatitis A, B, C, D, E, G are the most common causes of acute hepatitis, however, there are many infectious diseases affecting liver and with fever, early diagnostics of which is very important for the clinic of internal diseases. This review presents infections, causing fever and hepatitis, but not necessarily accompanied by jaundice. Leptospirosis, yellow fever have been considered, in which liver damage determines the clinic and the prognosis of the disease. In other cases, such as infectious mononucleosis, cytomegalovirus and herpetic hepatitis, typho-para-typhoid infections, typhoid, pneumonia, some viral diseases, malaria, Legionnaire's disease, hepatitis do not have their independent status and represent one of the important syndromes of a common disease. Modern methods of diagnostics and treatment of these diseases have been described. PMID:24294783

Podymova, S D

2013-01-01

80

Lung disease in indigenous children.  

PubMed

Children in indigenous populations have substantially higher respiratory morbidity than non-indigenous children. Indigenous children have more frequent respiratory infections that are, more severe and, associated with long-term sequelae. Post-infectious sequelae such as chronic suppurative lung disease and bronchiectasis are especially prevalent among indigenous groups and have lifelong impact on lung function. Also, although estimates of asthma prevalence among indigenous children are similar to non-indigenous groups the morbidity of asthma is higher in indigenous children. To reduce the morbidity of respiratory illness, best-practice medicine is essential in addition to improving socio-economic factors, (eg household crowding), tobacco smoke exposure, and access to health care and illness prevention programs that likely contribute to these issues. Although each indigenous group may have unique health beliefs and interfaces with modern health care, a culturally sensitive and community-based comprehensive care system of preventive and long term care can improve outcomes for all these conditions. This article focuses on common respiratory conditions encountered by indigenous children living in affluent countries where data is available. PMID:24958089

Chang, A B; Brown, N; Toombs, M; Marsh, R L; Redding, G J

2014-12-01

81

A Reconsideration of Acute Beryllium Disease  

PubMed Central

Context Although chronic beryllium disease (CBD) is clearly an immune-mediated granulomatous reaction to beryllium, acute beryllium disease (ABD) is commonly considered an irritative chemical phenomenon related to high exposures. Given reported new cases of ABD and projected increased demand for beryllium, we aimed to reevaluate the patho physiologic associations between ABD and CBD using two cases identified from a survey of beryllium production facility workers. Case Presentation Within weeks after exposure to beryllium fluoride began, two workers had systemic illness characterized by dermal and respiratory symptoms and precipitous declines in pulmonary function. Symptoms and pulmonary function abnormalities improved with cessation of exposure and, in one worker, recurred with repeat exposure. Bronchoalveolar lavage fluid analyses and blood beryllium lymphocyte proliferation tests revealed lymphocytic alveolitis and cellular immune recognition of beryllium. None of the measured air samples exceeded 100 ?g/m3, and most were < 10 ?g/m3, lower than usually described. In both cases, lung biopsy about 18 months after acute illness revealed noncaseating granulomas. Years after first exposure, the workers left employment because of CBD. Discussion Contrary to common understanding, these cases suggest that ABD and CBD represent a continuum of disease, and both involve hypersensitivity reactions to beryllium. Differences in disease presentation and progression are likely influenced by the solubility of the beryllium compound involved. Relevance to Practice ABD may occur after exposures lower than the high concentrations commonly described. Prudence dictates limitation of further beryllium exposure in both ABD and CBD. PMID:19672405

Cummings, Kristin J.; Stefaniak, Aleksandr B.; Virji, M. Abbas; Kreiss, Kathleen

2009-01-01

82

Cytokines and ventilator-induced acute lung injury  

Microsoft Academic Search

Mechanical ventilation is an indispensable therapy for patients who need respiratory support. However, im- proper ventilation can lead to acute lung injury, which contributes to the mortality and morbidity of patients with respiratory distress. Mechanical ventilator-induced production of pro-inflammatory mediators, such as cytokines and chemokines, has been suggested to play an important role in mediating acute inflammatory responses in the

Bing HAN; Mingyao LIU

2002-01-01

83

The effect of lung biopsy on lung function in diffuse lung disease.  

PubMed

The aim of this study was to investigate the effect on lung function of lung biopsy used in the diagnosis of diffuse lung disease carried out by an open procedure or by video-assisted thoracoscopy. One hundred and sixteen patients with diffuse lung disease who attended the Royal Brompton Hospital were studied retrospectively. Thirty five patients underwent open lung biopsy, and 33 video-assisted thoracoscopic biopsy and 48 had their diagnosis made without biopsy. All patients underwent lung function tests before and after surgery, or at an interval of 3-6 months in those who did not undergo biopsy. No significant differences were found in changes in lung function between those who had and had not undergone biopsy, and the proportions of patients whose lung function improved or deteriorated were similar. Lung biopsy by an open procedure or by video-assisted thoracoscopy did not differ in its effects on lung function. The results for older patients, those with severe disease and those with fibrosing alveolitis were the same as for the whole group. Open lung biopsy for the diagnosis of diffuse lung disease does not deleteriously affect lung function whether carried out by an open or a minimally invasive procedure. PMID:10933087

Daniil, Z; Gilchrist, F C; Marciniak, S J; Pantelidis, P; Goldstraw, P; Pastorino, U; du Bois, R M

2000-07-01

84

Common lung conditions: chronic obstructive pulmonary disease.  

PubMed

The etiology of chronic obstructive pulmonary disease (COPD) is chronic lung inflammation. In the United States, this inflammation most commonly is caused by smoking. COPD is diagnosed when an at-risk patient presents with respiratory symptoms and has irreversible airway obstruction indicated by a forced expiratory volume in 1 second/forced vital capacity ratio of less than 0.7. Management goals for COPD include smoking cessation, symptom reduction, exacerbation reduction, hospitalization avoidance, and improvement of quality of life. Stable patients with COPD who remain symptomatic despite using short-acting bronchodilators should start inhaled maintenance drugs to reduce symptoms and exacerbations, avoid hospitalizations, and improve quality of life. A long-acting anticholinergic or a long-acting beta2-agonist (LABA) can be used for initial therapy; these drugs have fewer adverse effects than inhaled corticosteroids (ICS). If patients remain symptomatic despite monotherapy, dual therapy with a long-acting anticholinergic and a LABA, or a LABA and an ICS, may be beneficial. Triple therapy (ie, a long-acting anticholinergic, a LABA, and an ICS) also is used, but it is unclear if triple therapy is superior to dual therapy. Roflumilast, an oral selective inhibitor of phosphodiesterase 4, is used to manage moderate to severe COPD. Continuous oxygen therapy is indicated for patients with COPD who have severe hypoxemia (ie, PaO2 less than 55 mm Hg or an oxygen saturation less than 88% on room air). Nonpharmacologic strategies also are useful to improve patient outcomes. Pulmonary rehabilitation improves dyspnea and quality of life. Pulmonary rehabilitation after an acute exacerbation reduces hospitalizations and mortality, and improves quality of life and exercise capacity. Smoking cessation is the most effective management strategy for reducing morbidity and mortality in patients with COPD. Lung volume reduction surgery, bullectomy, and lung transplantation are surgical interventions that are appropriate for some patients with COPD. PMID:23767419

Delzell, John E

2013-06-01

85

Imaging of occupational and environmental lung diseases  

SciTech Connect

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.

Akira, M. [Kinki Cuo Chest Medical Center, Osaka (Japan)

2008-03-15

86

Imaging of Childhood Interstitial Lung Disease  

PubMed Central

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

2010-01-01

87

GRANZYME A AND B-CLUSTER DEFICIENCY DELAYS ACUTE LUNG INJURY IN PNEUMOVIRUS-INFECTED MICE  

PubMed Central

Lower respiratory tract infection by the human pneumovirus respiratory syncytial virus is a frequent cause of acute lung injury in children. Severe pneumovirus disease in humans is associated with activation of the granzyme pathway by effector lymphocytes, which may promote pathology by exaggerating pro-apoptotic caspase activity and pro-inflammatory activity. The main goal of this study was to determine whether granzymes contribute to the development of acute lung injury in pneumovirus-infected mice. Granzyme-expressing mice and granzyme A, and B-cluster single and double-gene deleted mice were inoculated with the rodent pneumovirus pneumonia virus of mice strain J3666, and were studied for markers of lung inflammation and injury. Expression of granzyme A and B is detected in effector lymphocytes in mouse lungs in response to pneumovirus infection. Mice deficient for granzyme A and the granzyme B-cluster have unchanged virus titers in the lungs, but show a significantly delayed clinical response to fatal pneumovirus infection, a feature that is associated with delayed neutrophil recruitment, diminished activation of caspase-3 and reduced lung permeability. We conclude that granzyme A and B-cluster deficiency delays the acute progression of pneumovirus disease by reducing alveolar injury. PMID:20018616

Bem, Reinout A.; van Woensel, Job B.M.; Lutter, Rene; Domachowske, Joseph B.; Medema, Jan Paul; Rosenberg, Helene F.; Bos, Albert P.

2009-01-01

88

Inhaled Corticosteroids in Lung Diseases  

PubMed Central

Inhaled corticosteroids (ICSs) are used extensively in the treatment of asthma and chronic obstructive pulmonary disease (COPD) due to their broad antiinflammatory effects. They improve lung function, symptoms, and quality of life and reduce exacerbations in both conditions but do not alter the progression of disease. They decrease mortality in asthma but not COPD. The available ICSs vary in their therapeutic index and potency. Although ICSs are used in all age groups, younger and smaller children may be at a greater risk for adverse systemic effects because they can receive higher mg/kg doses of ICSs compared with older children. Most of the benefit from ICSs occurs in the low to medium dose range. Minimal additional improvement is seen with higher doses, although some patients may benefit from higher doses. Although ICSs are the preferred agents for managing persistent asthma in all ages, their benefit in COPD is more controversial. When used appropriately, ICSs have few adverse events at low to medium doses, but risk increases with high-dose ICSs. Although several new drugs are being developed and evaluated, it is unlikely that any of these new medications will replace ICSs as the preferred initial long-term controller therapy for asthma, but more effective initial controller therapy could be developed for COPD. PMID:23370915

Raissy, Hengameh H.; Kelly, H. William; Harkins, Michelle

2013-01-01

89

Pulmonary function in sickle cell disease with or without acute chest syndrome  

Microsoft Academic Search

Recurrent acute chest syndrome (ACS) has been suggested as a risk fac- tor for chronic lung dysfunction in sickle cell disease. To investigate this hypothesis, lung function tests were performed in 49 sickle cell disease outpatients whose condition was stable, including 23 patients with a history of two to four episodes of ACS (ACS+) and 26 with no history of

F. Santoli; F. Zerah; N. Vasile; D. Bachir; F. Galacteros; G. Atlan

1998-01-01

90

Glutamine Attenuates Acute Lung Injury Caused by Acid Aspiration  

PubMed Central

Inadequate ventilator settings may cause overwhelming inflammatory responses associated with ventilator-induced lung injury (VILI) in patients with acute respiratory distress syndrome (ARDS). Here, we examined potential benefits of glutamine (GLN) on a two-hit model for VILI after acid aspiration-induced lung injury in rats. Rats were intratracheally challenged with hydrochloric acid as a first hit to induce lung inflammation, then randomly received intravenous GLN or lactated Ringer’s solution (vehicle control) thirty min before different ventilator strategies. Rats were then randomized to receive mechanical ventilation as a second hit with a high tidal volume (TV) of 15 mL/kg and zero positive end-expiratory pressure (PEEP) or a low TV of 6 mL/kg with PEEP of 5 cm H2O. We evaluated lung oxygenation, inflammation, mechanics, and histology. After ventilator use for 4 h, high TV resulted in greater lung injury physiologic and biologic indices. Compared with vehicle treated rats, GLN administration attenuated lung injury, with improved oxygenation and static compliance, and decreased respiratory elastance, lung edema, extended lung destruction (lung injury scores and lung histology), neutrophil recruitment in the lung, and cytokine production. Thus, GLN administration improved the physiologic and biologic profiles of this experimental model of VILI based on the two-hit theory. PMID:25100435

Lai, Chih-Cheng; Liu, Wei-Lun; Chen, Chin-Ming

2014-01-01

91

Acute Postoperative Pain in Lung Transplant Recipients  

Microsoft Academic Search

Background. This retrospective study was designed to assess the quality of postoperative pain control and the facility of transition from epidural to oral analgesia in lung transplant recipients. Methods. After institutional review board approval, data were collected from the charts of all patients who underwent lung transplantation at our institution be- tween 1998 and 2002. The study group consisted of

Francois Girard; Pasquale Ferraro; Philippe Chouinard; Daniel Boudreault; Monique Ruel; Manon Choiniere; Charles Poirier; Dominique C. Girard

2010-01-01

92

Postoperative Acute Exacerbation of IPF after Lung Resection for Primary Lung Cancer.  

PubMed

Idiopathic pulmonary fibrosis (IPF) is characterized by slowly progressive respiratory dysfunction. Nevertheless, some IPF patients experience acute exacerbations generally characterized by suddenly worsening and fatal respiratory failure with new lung opacities and pathological lesions of diffuse alveolar damage. Acute exacerbation of idiopathic pulmonary fibrosis (AEIPF) is a fatal disorder defined by rapid deterioration of IPF. The condition sometimes occurs in patients who underwent lung resection for primary lung cancer in the acute and subacute postoperative phases. The exact etiology and pathogenesis remain unknown, but the condition is characterized by diffuse alveolar damage superimposed on a background of IPF that probably occurs as a result of a massive lung injury due to some unknown factors. This systematic review shows that the outcome, however, is poor, with postoperative mortality ranging from 33.3% to 100%. In this paper, the etiology, risk factors, pathogenesis, therapy, prognosis, and predictors of postoperative AEIPF are described. PMID:21637373

Watanabe, Atsushi; Kawaharada, Nobuyoshi; Higami, Tetsuya

2011-01-01

93

Pulmonary Hypertension Associated with Interstitial Lung Disease  

Microsoft Academic Search

\\u000a Interstitial lung diseases (ILDs) are a distinct type of chronic respiratory disorder that can result in pulmonary hypertension.\\u000a There are numerous causes of ILD but all are characterized by dyspnea and abnormal lung function, with arterial oxygen desaturation\\u000a occurring as the disease advances. Patients with idiopathic pulmonary fibrosis (IPF), a relentlessly progressive form of ILD,\\u000a are particularly likely to develop

Mary E. Strek; Julian Solway

94

Sphingolipids as cell fate regulators in lung development and disease.  

PubMed

Sphingolipids are a diverse class of signaling molecules implicated in many important aspects of cellular biology, including growth, differentiation, apoptosis, and autophagy. Autophagy and apoptosis are fundamental physiological processes essential for the maintenance of cellular and tissue homeostasis. There is great interest into the investigation of sphingolipids and their roles in regulating these key physiological processes as well as the manifestation of several disease states. With what is known to date, the entire scope of sphingolipid signaling is too broad, and a single review would hardly scratch the surface. Therefore, this review attempts to highlight the significance of sphingolipids in determining cell fate (e.g. apoptosis, autophagy, cell survival) in the context of the healthy lung, as well as various respiratory diseases including acute lung injury, acute respiratory distress syndrome, bronchopulmonary dysplasia, asthma, chronic obstructive pulmonary disease, emphysema, and cystic fibrosis. We present an overview of the latest findings related to sphingolipids and their metabolites, provide a short introduction to autophagy and apoptosis, and then briefly highlight the regulatory roles of sphingolipid metabolites in switching between cell survival and cell death. Finally, we describe functions of sphingolipids in autophagy and apoptosis in lung homeostasis, especially in the context of the aforementioned diseases. PMID:25753687

Lee, Joyce; Yeganeh, Behzad; Ermini, Leonardo; Post, Martin

2015-05-01

95

Original Contribution Acute Myocardial Infarction Mortality in Comparison with Lung and Bladder  

E-print Network

Original Contribution Acute Myocardial Infarction Mortality in Comparison with Lung and Bladder) in comparison with the unexposed region V. Increased risks were found for acute myocardial infarction (AMI; Chile; lung neoplasms; mortality; myocardial infarction; urinary bladder neoplasms; water Abbreviations

California at Berkeley, University of

96

Surfactant gene polymorphisms and interstitial lung diseases.  

PubMed

Pulmonary surfactant is a complex mixture of phospholipids and proteins, which is present in the alveolar lining fluid and is essential for normal lung function. Alterations in surfactant composition have been reported in several interstitial lung diseases (ILDs). Furthermore, a mutation in the surfactant protein C gene that results in complete absence of the protein has been shown to be associated with familial ILD. The role of surfactant in lung disease is therefore drawing increasing attention following the elucidation of the genetic basis underlying its surface expression and the proof of surfactant abnormalities in ILD. PMID:11806849

Pantelidis, Panagiotis; Veeraraghavan, Srihari; du Bois, Roland M

2002-01-01

97

Surfactant gene polymorphisms and interstitial lung diseases  

PubMed Central

Pulmonary surfactant is a complex mixture of phospholipids and proteins, which is present in the alveolar lining fluid and is essential for normal lung function. Alterations in surfactant composition have been reported in several interstitial lung diseases (ILDs). Furthermore, a mutation in the surfactant protein C gene that results in complete absence of the protein has been shown to be associated with familial ILD. The role of surfactant in lung disease is therefore drawing increasing attention following the elucidation of the genetic basis underlying its surface expression and the proof of surfactant abnormalities in ILD. PMID:11806849

Pantelidis, Panagiotis; Veeraraghavan, Srihari; du Bois, Roland M

2002-01-01

98

Immune mechanisms in beryllium lung disease  

SciTech Connect

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.

Deodhar, S.D.; Barna, B.P. (Cleveland Clinic Foundation, OH (USA))

1991-03-01

99

Regulatory effects of estrogen on acute lung inflammation in mice.  

PubMed

The role of estrogen in the regulation of the inflammatory response is not well defined. In this study, we investigated the effects of ovarian hormones on the acute inflammatory response in mouse lungs. Acute lung injury was induced by intratracheal instillation of bacterial lipopolysaccharide (LPS) in male, female, and ovariectomized (OVX) mice. End points of injury were polymorphonuclear neutrophil (PMN) content in bronchoalveolar lavage (BAL) fluids, myeloperoxidase activity in whole lung, and leak of albumin into the lung. After intratracheal instillation of LPS, all end points of injury were substantially increased in male and OVX mice compared with the female mice with intact ovaries. BAL fluids of all mice showed similar levels of chemokines (macrophage inflammatory protein MIP-2, KC, and monocyte chemoattractant proteins MCP-1 and MCP-3) and TNF-alpha, but enhanced levels of IL-1beta were found in OVX and male mice. Serum levels of IL-6 and ICAM-1 levels in lung homogenates from OVX and male mice, compared with those in female mice with intact ovaries, were also enhanced after instillation of LPS. Albumin and PMN content in LPS-injured lungs were reduced to levels found in female mice after administration of estradiol in OVX mice and corresponded to reduced IL-1beta, IL-6, and ICAM-1 levels. These data suggest that estrogen suppresses lung inflammatory responses in mice through an effect on vascular cell adhesion molecules and proinflammatory mediators. PMID:15761213

Speyer, Cecilia L; Rancilio, Nicholas J; McClintock, Shannon D; Crawford, Jeffrey D; Gao, Hongwei; Sarma, J Vidya; Ward, Peter A

2005-04-01

100

Acute lung injury: functional genomics and genetic susceptibility.  

PubMed

Initiated by numerous factors, acute lung injury is marked by epithelial and endothelial cell perturbation and inflammatory cell influx that leads to surfactant disruption, pulmonary edema, and atelectasis. This syndrome has been associated with a myriad of mediators including cytokines, oxidants, and growth factors. To better understand gene-environmental interactions controlling this complex process, the sensitivity of inbred mouse strains was investigated following acute lung injury that was induced by fine nickel sulfate aerosol. Measuring survival time, protein and neutrophil concentrations in BAL fluid, lung wet-to-dry weight ratio, and histology, we found that these responses varied between inbred mouse strains and that susceptibility is heritable. To assess the progression of acute lung injury, the temporal expression of genes and expressed sequence tags was assessed by complementary DNA microarray analysis. Enhanced expression was noted in genes that were associated with oxidative stress, antiprotease function, and extracellular matrix repair. In contrast, expression levels of surfactant proteins (SPs) and Clara cell secretory protein (ie, transcripts that are constitutively expressed in the lung) decreased markedly. Genome-wide analysis was performed with offspring derived from a sensitive and resistant strain (C57BL/6xA F(1) backcrossed with susceptible A strain). Significant linkage was identified for a locus on chromosome 6 (proposed as Aliq4), a region that we had identified previously following ozone-induced acute lung injury. Two suggestive linkages were identified on chromosomes 1 and 12. Using haplotype analysis to estimate the combined effect of these regions (along with putative modifying loci on chromosomes 9 and 16), we found that five loci interact to account for the differences in survival time of the parental strains. Candidate genes contained in Aliq4 include SP-B, aquaporin 1, and transforming growth factor-alpha. Thus, the functional genomic approaches of large gene set expression (complementary DNA microarray) and genome-wide analyses continue to provide novel insights into the genetic susceptibility of lung injury. PMID:11893692

Leikauf, George D; McDowell, Susan A; Wesselkamper, Scott C; Hardie, William D; Leikauf, John E; Korfhagen, Thomas R; Prows, Daniel R

2002-03-01

101

DNaseI Protects against Paraquat-Induced Acute Lung Injury and Pulmonary Fibrosis Mediated by Mitochondrial DNA  

PubMed Central

Background. Paraquat (PQ) poisoning is a lethal toxicological challenge that served as a disease model of acute lung injury and pulmonary fibrosis, but the mechanism is undetermined and no effective treatment has been discovered. Methods and Findings. We demonstrated that PQ injures mitochondria and leads to mtDNA release. The mtDNA mediated PBMC recruitment and stimulated the alveolar epithelial cell production of TGF-?1 in vitro. The levels of mtDNA in circulation and bronchial alveolar lavage fluid (BALF) were elevated in a mouse of PQ-induced lung injury. DNaseI could protect PQ-induced lung injury and significantly improved survival. Acute lung injury markers, such as TNF?, IL-1?, and IL-6, and marker of fibrosis, collagen I, were downregulated in parallel with the elimination of mtDNA by DNaseI. These data indicate a possible mechanism for PQ-induced, mtDNA-mediated lung injury, which may be shared by other causes of lung injury, as suggested by the same protective effect of DNaseI in bleomycin-induced lung injury model. Interestingly, increased mtDNA in the BALF of patients with amyopathic dermatomyositis-interstitial lung disease can be appreciated. Conclusions. DNaseI targeting mtDNA may be a promising approach for the treatment of PQ-induced acute lung injury and pulmonary fibrosis that merits fast tracking through clinical trials.

Li, Guo; Yuzhen, Li; Yi, Chen; Xiaoxiang, Chen; Wei, Zhou; Changqing, Zhu; Shuang, Ye

2015-01-01

102

Mechanisms of beta-receptor stimulation-induced improvement of acute lung injury and pulmonary edema  

Microsoft Academic Search

Acute lung injury (ALI) and the acute respiratory distress syndrome are complex syndromes because both inflammatory and coagulation cascades cause lung injury. Transport of salt and water, repair and remodeling of the lung, apoptosis, and necrosis are additional important mechanisms of injury. Alveolar edema is cleared by active transport of salt and water from the alveoli into the lung interstitium

Horacio E Groshaus; Sanjay Manocha; Keith R Walley; James A Russell

2004-01-01

103

Noninvasive assessment for acute allograft rejection in a rat lung transplantation model  

PubMed Central

Abstract After lung transplantation, early detection of acute allograft rejection is important not only for timely and optimal treatment, but also for the prediction of chronic rejection which is a major cause of late death. Many biological and immunological approaches have been developed to detect acute rejection; however, it is not well known whether lung mechanics correlate with disease severity, especially with pathological rejection grade. In this study, we examined the relationship between lung mechanics and rejection grade development in a rat acute rejection model using the forced oscillation technique, which provides noninvasive assessment of lung function. To this end, we assessed lung resistance and elastance (RL and EL) from implanted left lung of these animals. The perivascular/interstitial component of rejection severity grade (A?grade) was also quantified from histological images using tissue fraction (TF; tissue + cell infiltration area/total area). We found that TF, RL, and EL increased according to A?grade. There was a strong positive correlation between EL at the lowest frequency (Elow; EL at 0.5 Hz) and TF (r2 = 0.930). Furthermore, the absolute difference between maximum value of EL (Emax) and Elow (Ehet; Emax ? Elow) showed the strong relationship with standard deviation of TF (r2 = 0.709), and A?grade (Spearman's correlation coefficients; rs = 0.964, P < 0.0001). Our results suggest that the dynamic elastance as well as its frequency dependence have the ability to predict A?grade. These indexes should prove useful for noninvasive detection and monitoring the progression of disease in acute rejection. PMID:25524280

Takahashi, Ayuko; Hamakawa, Hiroshi; Sakai, Hiroaki; Zhao, Xiangdong; Chen, Fengshi; Fujinaga, Takuji; Shoji, Tsuyoshi; Bando, Toru; Wada, Hiromi; Date, Hiroshi

2014-01-01

104

Alveolar Fluid Clearance Is Impaired in the Majority of Patients with Acute Lung Injury and the Acute Respiratory Distress Syndrome  

Microsoft Academic Search

Because experimental studies have shown that intact alveolar epi- thelial fluid transport function is critical for resolution of pulmo- nary edema and acute lung injury, we measured net alveolar fluid clearance in 79 patients with acute lung injury or the acute respi- ratory distress syndrome. Pulmonary edema fluid and plasma were sampled serially in the first 4 hours after intubation.

LORRAINE B. WARE; MICHAEL A. MATTHAY

2001-01-01

105

Electronic Nose for Identification of Lung Diseases  

NASA Astrophysics Data System (ADS)

In the paper, the authors analyze the preliminary results of testing a classical gas sensing instrument - the electronic nose (a metal oxide transistor sensor of chemical substances) in a hospital where patients with different lung diseases are treated. To reveal the correlation between the amplitudes of the sensor's responses and the patients' diagnoses, different statistical analysis methods have been used. It is shown that the lung cancer can easily be discriminated from other lung diseases if short breath sampling and analysis time (less than 1 min) is used in the test. Volatiles obtained from a breath sample of a patient with lung cancer give the major contribution to the responses of different e-nose sensors, so in these cases highly precise identification could be achieved.

Ogorodnik, V.; Kleperis, J.; Taivans, I.; Jurka, N.; Bukovskis, M.

2008-01-01

106

Hydatid lung disease (echinococcosis/hydatidosis).  

PubMed

Two Echinococcus species may exhibit medical relevance as causative agents of pulmonary forms of echinococcosis. Most importantly, infections with Echinococcus granulosus result in "cystic hydatid disease" or "cystic echinococcosis," which affects the lungs in a considerable ratio of cases. Echinococcus multilocularis, which causes "alveolar echinococcosis," affects the lungs relatively rarely and then usually upon metastasizing from primary hepatic lesions. Cystic echinococcus and alveolar echinococcus differ pathologically and clinically so greatly that they are considered separately in this article, although alveolar echinococcus is covered minimally because of its minor importance regarding lung infections. PMID:12092034

Gottstein, Bruno; Reichen, Jürg

2002-06-01

107

Early lung disease in cystic fibrosis.  

PubMed

Lung disease in patients with cystic fibrosis is characterised by inflammation and recurrent and chronic infections leading to progressive loss in pulmonary function and respiratory failure. Early management of disease results in substantially improved pulmonary function at first testing (at roughly 6 years of age), but the annual decline in pulmonary function tests in older patients has remained unchanged showing how important the early years are in the disease process. Treatment regimens for patients with cystic fibrosis have changed from predominantly symptomatic treatment to preventive or causal (ie, treatments that address the underlying mechanisms of disease) therapeutic interventions. The infant and preschool age (2-5 years) could represent a unique period of opportunity to postpone or even prevent the onset of cystic fibrosis lung disease. We summarise the current knowledge and the methods used to characterise and quantify early lung disease. We discuss treatment strategies including new drugs that are being developed and their potential role in the treatment of early lung disease in patients with cystic fibrosis. PMID:24429095

Grasemann, Hartmut; Ratjen, Felix

2013-04-01

108

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 ...

109

Connective Tissue Disease-Associated Interstitial Lung Disease: A Focused Review.  

PubMed

The connective tissue diseases (CTDs) are a group of systemic disorders characterized by autoimmunity and autoimmune-mediated organ damage. The lung is a frequent target and all components of the respiratory system are at risk. Interstitial lung disease (ILD) represents a broad group of diffuse parenchymal lung injury patterns characterized by varying degrees of inflammation and fibrosis, is a common manifestation of CTD particularly common in systemic sclerosis, polymyositis/dermatomyositis, and rheumatoid arthritis, and is a leading cause of significant morbidity and mortality. The lung injury patterns of CTD-associated ILD (CTD-ILD) mirror those of idiopathic interstitial pneumonia and may arise at any time during the course of the CTD or may be the first manifestation of CTD. Patients with CTD that present with respiratory failure often present significant diagnostic dilemmas. Thorough and comprehensive assessments to exclude respiratory *infection, acute interstitial pneumonia, medication toxicity, pulmonary embolism, cardiac dysfunction, and diffuse alveolar hemorrhage are the fundamental components for the evaluation of such patients. Furthermore, patients with CTD are also at risk of acute exacerbations of underlying ILD. Acute exacerbations are manifested by subacute respiratory deterioration with worsening hypoxemia in the setting of new radiographic abnormalities. The prognosis of patients with CTD having respiratory failure is often quite poor, highlighting the need for prompt and thorough clinical assessments to determine the underlying etiology and implementation of appropriate therapeutic strategies. PMID:24371251

Solomon, Joshua J; Fischer, Aryeh

2013-12-25

110

Focus on acute diarrhoeal disease  

PubMed Central

Diarrhoea is an alteration of normal bowel movement characterized by an increase in the water content, volume, or frequency of stools. Diarrhoea needs to be classified according to the trends over time (acute or chronic) and to the characteristics of the stools (watery, fatty, inflammatory). Secretory diarrhoeas, mostly acute and of viral aetiology in more than 70% of cases, are by far the most important subtype of diarrhoeas in terms of frequency, incidence and mortality (over 2.5 million deaths/year in developing countries). Natural and synthetic opiates such as morphine, codeine, and loperamide which react with endogenous opiates (enkephalins, beta-endorphins, dynorphins) mainly act on intestinal motility and slow down transit. An antidiarrhoeal drug developed in recent years, racecadotril, acts as an enkephalinase inhibitor. Clinical studies have shown that it is just as effective as loperamide in resolving acute diarrhoea but with greater reduction in pain and abdominal distension. Some studies have explored the prevalence of diarrhoea in old age. An epidemiological study carried out in Italy by 133 General Practitioners on 5515 elderly outpatients reported a prevalence of diarrhoea, defined according to the Rome criteria, of 9.1%. Infectious diseases (19%) and drug use (16%) were the most common causes of diarrhoea in old age. Regardless of the cause, the treatment of elderly patients with diarrhoea must include rehydration and nutritional support. Every year, more than 50 million tourists travel from industrialized countries to places where hygiene levels are poor. At least 75% of those travelling for short periods mention health problems, and in particular traveller’s diarrhoea. PMID:19610134

Baldi, Fabio; Bianco, Maria Antonia; Nardone, Gerardo; Pilotto, Alberto; Zamparo, Emanuela

2009-01-01

111

Effects of acute hypercapnia with and without acidosis on lung inflammation and apoptosis in experimental acute lung injury.  

PubMed

We investigated the effects of acute hypercapnic acidosis and buffered hypercapnia on lung inflammation and apoptosis in experimental acute lung injury (ALI). Twenty-four hours after paraquat injection, 28 Wistar rats were randomized into four groups (n=7/group): (1) normocapnia (NC, PaCO2=35-45 mmHg), ventilated with 0.03%CO2+21%O2+balancedN2; (2) hypercapnic acidosis (HC, PaCO2=60-70 mmHg), ventilated with 5%CO2+21%O2+balancedN2; and (3) buffered hypercapnic acidosis (BHC), ventilated with 5%CO2+21%O2+balancedN2 and treated with sodium bicarbonate (8.4%). The remaining seven animals were not mechanically ventilated (NV). The mRNA expression of interleukin (IL)-6 (p=0.003), IL-1? (p<0.001), and type III procollagen (PCIII) (p=0.001) in lung tissue was more reduced in the HC group in comparison with NC, with no significant differences between HC and BHC. Lung and kidney cell apoptosis was reduced in HC and BHC in comparison with NC and NV. In conclusion, in this experimental ALI model, hypercapnia, regardless of acidosis, reduced lung inflammation and lung and kidney cell apoptosis. PMID:25246186

Nardelli, L M; Rzezinski, A; Silva, J D; Maron-Gutierrez, T; Ornellas, D S; Henriques, I; Capelozzi, V L; Teodoro, W; Morales, M M; Silva, P L; Pelosi, P; Garcia, C S N B; Rocco, P R M

2015-01-01

112

Metallothionein-induced zinc partitioning exacerbates hyperoxic acute lung injury  

PubMed Central

Hypozincemia, with hepatic zinc accumulation at the expense of other organs, occurs in infection, inflammation, and aseptic lung injury. Mechanisms underlying zinc partitioning or its impact on extrahepatic organs are unclear. Here we show that the major zinc-binding protein, metallothionein (MT), is critical for zinc transmigration from lung to liver during hyperoxia and preservation of intrapulmonary zinc during hyperoxia is associated with an injury-resistant phenotype in MT-null mice. Particularly, lung-to-liver zinc ratios decreased in wild-type (WT) and increased significantly in MT-null mice breathing 95% oxygen for 72 h. Compared with female adult WT mice, MT-null mice were significantly protected against hyperoxic lung injury indicated by reduced inflammation and interstitial edema, fewer necrotic changes to distal airway epithelium, and sustained lung function at 72 h hyperoxia. Lungs of MT-null mice showed decreased levels of immunoreactive LC3, an autophagy marker, compared with WT mice. Analysis of superoxide dismutase (SOD) activity in the lungs revealed similar levels of manganese-SOD activity between strains under normoxia and hyperoxia. Lung extracellular SOD activity decreased significantly in both strains at 72 h of hyperoxia, although there was no difference between strains. Copper-zinc-SOD activity was ?4× higher under normoxic conditions in MT-null compared with WT mice but was not affected in either group by hyperoxia. Collectively the data suggest that genetic deletion of MT-I/II in mice is associated with compensatory increase in copper-zinc-SOD activity, prevention of hyperoxia-induced zinc transmigration from lung to liver, and hyperoxia-resistant phenotype strongly associated with differences in zinc homeostasis during hyperoxic acute lung injury. PMID:23275622

Lee, Sang-Min; McLaughlin, Joseph N.; Frederick, Daniel R.; Zhu, Lin; Thambiayya, Kalidasan; Wasserloos, Karla J.; Kaminski, Iris; Pearce, Linda L.; Peterson, Jim; Li, Jin; Latoche, Joseph D.; Peck Palmer, Octavia M.; Stolz, Donna Beer; Fattman, Cheryl L.; Alcorn, John F.; Oury, Tim D.; Angus, Derek C.; Pitt, Bruce R.

2013-01-01

113

Epigenetic contributions to the developmental origins of adult lung disease.  

PubMed

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

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

2015-04-01

114

Hypoxia and chronic lung disease  

Microsoft Academic Search

The lung is both the conduit for oxygen uptake and is also affected by hypoxia and hypoxia signaling. Decreased ventilatory\\u000a drive, airway obstructive processes, intra-alveolar exudates, septal thickening by edema, inflammation, fibrosis, or damage\\u000a to alveolar capillaries will all interpose a significant and potentially life-threatening barrier to proper oxygenation, therefore\\u000a enhancing the alveolar\\/arterial pO2 gradient. These processes result in decreased

Rubin M. Tuder; Jeong H. Yun; Anil Bhunia; Iwona Fijalkowska

2007-01-01

115

Xuan Bai Cheng Qi formula as an adjuvant treatment of acute exacerbation of chronic obstructive pulmonary disease of the syndrome type phlegm-heat obstructing the lungs: a multicenter, randomized, double-blind, placebo-controlled clinical trial  

PubMed Central

Background Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common cause of morbidity and mortality. Traditional Chinese medicine (TCM) is used to treat AECOPD as adjunctive therapy. This study aimed to evaluate the efficacy and safety of the TCM formula Xuan Bai Cheng Qi as an adjuvant therapy for AECOPD patients with the syndrome type of phlegm-heat obstructing the lungs. Methods A multicenter, randomized, double-blind, placebo-controlled clinical trial was conducted. A total of 244 patients were divided into the intervention group (n?=?122, treated with conventional medicine and Xuan Bai Cheng Qi) and the control group (n?=?122, treated with conventional medicine and placebo). Total symptom scores (cough, phlegm, wheezing, chest congestion) before treatment and at 3, 5, 7, 10 days post-treatment were recorded. Lung function, arterial blood gas, serum inflammatory cytokines, oxidation/anti-oxidation index were observed before treatment and at the end of the 10-day treatment. Results A total of 242 patients completed the study. The full analysis set (FAS) population was 244 and the per-protocol analysis set (PPS) population was 229. After the 10-day treatment, symptom scores of the Xuan Bai Cheng Qi group were significantly lower over time compared with the control group (FAS: mean difference -1.84, 95% CI -2.66 to -1.03, P?lungs syndrome type. PMID:25014996

2014-01-01

116

Diabetes, insulin, and development of acute lung injury  

PubMed Central

Objectives Recently, many studies have investigated the immunomodulatory effects of insulin and glucose control in critical illness. This review examines evidence regarding the relationship between diabetes and the development of acute lung injury/acute respiratory distress syndrome (ALI/ARDS), reviews studies of lung injury related to glycemic and nonglycemic metabolic features of diabetes, and examines the effect of diabetic therapies. Data Sources and Study Selection A MEDLINE/PubMed search from inception to August 1, 2008, was conducted using the search terms acute lung injury, acute respiratory distress syndrome, hyperglycemia, diabetes mellitus, insulin, hydroxymethylglutaryl-CoA reductase inhibitors (statins), angiotensin-converting enzyme inhibitor, and peroxisome proliferator-activated receptors, including combinations of these terms. Bibliographies of retrieved articles were manually reviewed. Data Extraction and Synthesis Available studies were critically reviewed, and data were extracted with special attention to the human and animal studies that explored a) diabetes and ALI; b) hyperglycemia and ALI; c) metabolic nonhyperglycemic features of diabetes and ALI; and d) diabetic therapies and ALI. Conclusions Clinical and experimental data indicate that diabetes is protective against the development of ALI/ARDS. The pathways involved are complex and likely include effects of hyperglycemia on the inflammatory response, metabolic abnormalities in diabetes, and the interactions of therapeutic agents given to diabetic patients. Multidisciplinary, multifaceted studies, involving both animal models and clinical and molecular epidemiology techniques, are essential. PMID:19531947

Honiden, Shyoko; Gong, Michelle N.

2009-01-01

117

Autophagy in lung disease pathogenesis and therapeutics.  

PubMed

Autophagy, a cellular pathway for the degradation of damaged organelles and proteins, has gained increasing importance in human pulmonary diseases, both as a modulator of pathogenesis and as a potential therapeutic target. In this pathway, cytosolic cargos are sequestered into autophagosomes, which are delivered to the lysosomes where they are enzymatically degraded and then recycled as metabolic precursors. Autophagy exerts an important effector function in the regulation of inflammation, and immune system functions. Selective pathways for autophagic degradation of cargoes may have variable significance in disease pathogenesis. Among these, the autophagic clearance of bacteria (xenophagy) may represent a crucial host defense mechanism in the pathogenesis of sepsis and inflammatory diseases. Our recent studies indicate that the autophagic clearance of mitochondria, a potentially protective program, may aggravate the pathogenesis of chronic obstructive pulmonary disease by activating cell death programs. We report similar findings with respect to the autophagic clearance of cilia components, which can contribute to airways dysfunction in chronic lung disease. In certain diseases such as pulmonary hypertension, autophagy may confer protection by modulating proliferation and cell death. In other disorders, such as idiopathic pulmonary fibrosis and cystic fibrosis, impaired autophagy may contribute to pathogenesis. In lung cancer, autophagy has multiple consequences by limiting carcinogenesis, modulating therapeutic effectiveness, and promoting tumor cell survival. In this review we highlight the multiple functions of autophagy and its selective autophagy subtypes that may be of significance to the pathogenesis of human disease, with an emphasis on lung disease and therapeutics. PMID:25617802

Ryter, Stefan W; Choi, Augustine M K

2015-01-01

118

Quantitative stratification of diffuse parenchymal lung diseases.  

PubMed

Diffuse parenchymal lung diseases (DPLDs) are characterized by widespread pathological changes within the pulmonary tissue that impair the elasticity and gas exchange properties of the lungs. Clinical-radiological diagnosis of these diseases remains challenging and their clinical course is characterized by variable disease progression. These challenges have hindered the introduction of robust objective biomarkers for patient-specific prediction based on specific phenotypes in clinical practice for patients with DPLD. Therefore, strategies facilitating individualized clinical management, staging and identification of specific phenotypes linked to clinical disease outcomes or therapeutic responses are urgently needed. A classification schema consistently reflecting the radiological, clinical (lung function and clinical outcomes) and pathological features of a disease represents a critical need in modern pulmonary medicine. Herein, we report a quantitative stratification paradigm to identify subsets of DPLD patients with characteristic radiologic patterns in an unsupervised manner and demonstrate significant correlation of these self-organized disease groups with clinically accepted surrogate endpoints. The proposed consistent and reproducible technique could potentially transform diagnostic staging, clinical management and prognostication of DPLD patients as well as facilitate patient selection for clinical trials beyond the ability of current radiological tools. In addition, the sequential quantitative stratification of the type and extent of parenchymal process may allow standardized and objective monitoring of disease, early assessment of treatment response and mortality prediction for DPLD patients. PMID:24676019

Raghunath, Sushravya; Rajagopalan, Srinivasan; Karwoski, Ronald A; Maldonado, Fabien; Peikert, Tobias; Moua, Teng; Ryu, Jay H; Bartholmai, Brian J; Robb, Richard A

2014-01-01

119

Quantitative Stratification of Diffuse Parenchymal Lung Diseases  

PubMed Central

Diffuse parenchymal lung diseases (DPLDs) are characterized by widespread pathological changes within the pulmonary tissue that impair the elasticity and gas exchange properties of the lungs. Clinical-radiological diagnosis of these diseases remains challenging and their clinical course is characterized by variable disease progression. These challenges have hindered the introduction of robust objective biomarkers for patient-specific prediction based on specific phenotypes in clinical practice for patients with DPLD. Therefore, strategies facilitating individualized clinical management, staging and identification of specific phenotypes linked to clinical disease outcomes or therapeutic responses are urgently needed. A classification schema consistently reflecting the radiological, clinical (lung function and clinical outcomes) and pathological features of a disease represents a critical need in modern pulmonary medicine. Herein, we report a quantitative stratification paradigm to identify subsets of DPLD patients with characteristic radiologic patterns in an unsupervised manner and demonstrate significant correlation of these self-organized disease groups with clinically accepted surrogate endpoints. The proposed consistent and reproducible technique could potentially transform diagnostic staging, clinical management and prognostication of DPLD patients as well as facilitate patient selection for clinical trials beyond the ability of current radiological tools. In addition, the sequential quantitative stratification of the type and extent of parenchymal process may allow standardized and objective monitoring of disease, early assessment of treatment response and mortality prediction for DPLD patients. PMID:24676019

Raghunath, Sushravya; Rajagopalan, Srinivasan; Karwoski, Ronald A.; Maldonado, Fabien; Peikert, Tobias; Moua, Teng; Ryu, Jay H.; Bartholmai, Brian J.; Robb, Richard A.

2014-01-01

120

Characterization of Lung's Emphysema Distribution: Numerical Assessment of Disease Development  

E-print Network

Characterization of Lung's Emphysema Distribution: Numerical Assessment of Disease Development M that block airflow and make it increasingly difficult for you to breathe. Emphysema and chronic bronchitis bronchitis. Pulmonary emphysema is defined as a lung disease characterized by "abnormal enlargement

Paris-Sud XI, Université de

121

[Interstitial lung disease due to domestic moulds].  

PubMed

Identifying the role of fungi present in the domestic environment in the development of interstitial pneumonia can be a difficult clinical problem. We report a case of interstitial lung disease case occurring in a 53-year-old patient. He presented with profound hypoxemia (PaO(2) 54mmHg). Chest CT showed diffuse ground glass opacities. Initial blood tests for allergy and autoimmune disease were negative. Faced with a worsening of his clinical status after returning home he was hospitalized several times. At fibreoptic bronchoscopy, multiple white deposits were observed. Bronchoalveolar lavage with differential cell count was performed, revealing a 23% lymphocytosis. Serology for specific household molds showed moderate reaction to various molds found in homes, especially Stachybotrys chartarum. Pulmonary function tests revealed a moderate restrictive pattern with impaired diffusion of carbon monoxide and a bronchiolocentric interstitial pneumonia was found at lung biopsy. After a permanent move to a new residence, clinical parameters, radiological, biological and functional normalized. The final diagnosis was interstitial lung disease related to mycotoxins of S. Chartarum. The diagnosis of hypersensitivity pneumonitis to domestic mold or interstitial lung disease secondary to mycotoxins should be considered in patients presenting with interstitial pneumonia and requires specific investigations to ensure that an environmental cause with an allergic or toxic role is not missed. PMID:21943538

Blanc, A-L; Delhaes, L; Copin, M-C; Stach, B; Faivre, J-B; Wallaert, B

2011-09-01

122

[Sodium dichloroisocyanurate-induced acute lung injury in a child].  

PubMed

Intoxication, by cyanurate and its chlorated derivatives in children, is increasingly reported in the literature due to accidental ingestion compared to accidental inhalation. We report a case in a 5-year-old child who presented with acute lung injury due to accidental inhalation of gas formed after a reaction of sodium dichloroisocyanurate tablets with water. Prevention remains the best way to reduce the risk of children being intoxicated by inhalation of the gas formed after contact of tablets with water. PMID:23433843

Wiel, E; Sicot, J; Leteurtre, S; Binoche, A; Nisse, P; Assez, N

2013-04-01

123

Life-threatening acute lung injury after gamma butyrolactone ingestion.  

PubMed

We describe a case of a 44-year-old woman with a borderline personality disorder and chronic gamma- butyrolactone (GBL) use who presented with progressive dyspnoea and an altered mental status. A high anion gap metabolic acidosis and acute lung injury was diagnosed. We hypothesise this was caused by GBL. In this case report we describe the diagnostic process and possible pathophysiological mechanisms that may have led to this life-threatening condition. PMID:25852114

van Gerwen, M; Scheper, H; Touw, D J; van Nieuwkoop, C

2015-03-01

124

Ceftiofur attenuates lipopolysaccharide-induced acute lung injury  

Microsoft Academic Search

Ceftiofur is a new broad-spectrum, third-generation cephalosporin antibiotic for veterinary use. Our laboratory has previously been reported that ceftiofur can modulate early cytokine responses and increase mouse survival in endotoxemia. In the present study, we investigated the effect of ceftiofur on acute lung injury (ALI) induced by lipopolysaccharide (LPS) in vivo. Mice were pretreated with ceftiofur 1h before challenge with

Xiao Chu; Keji Song; Kan Xu; Xiaozhe Zhang; Xuemei Zhang; Yu Song; Dacheng Wang; Songcai Liu; Xuming Deng

2010-01-01

125

Transfusion-related acute lung injury; clinical perspectives  

PubMed Central

Transfusion-related acute lung injury (TRALI) was introduced in 1983 to describe a clinical syndrome seen within 6 h of a plasma-containing blood products transfusion. TRALI is a rare transfusion complication; however, the FDA has suggested that TRALI is the leading cause of transfusion-related mortality. Understanding the pathogenesis of TRALI will facilitate adopting preventive strategies, such as deferring high plasma volume female product donors. This review outlines the clinical features, pathogenesis, treatment, and prevention of TRALI.

Kim, Jeongmin

2015-01-01

126

Reversing disability of irreversible lung disease.  

PubMed Central

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

Tiep, B. L.

1991-01-01

127

Extracellular matrix mechanics in lung parenchymal diseases  

PubMed Central

In this review, we examine how the extracellular matrix (ECM) of the lung contributes to the overall mechanical properties of the parenchyma, and how these properties change in disease. The connective tissues of the lung are composed of cells and ECM, which includes a variety of biological macromolecules and water. The macromolecules that are most important in determining the mechanical properties of the ECM are collagen, elastin, and proteoglycans. We first discuss the various components of the ECM and how their architectural organization gives rise to the mechanical properties of the parenchyma. Next, we examine how mechanical forces can affect the physiological functioning of the lung parenchyma. Collagen plays an especially important role in determining the homeostasis and cellular responses to injury because it is the most important load-bearing component of the parenchyma. We then demonstrate how the concept of percolation can be used to link microscopic pathologic alterations in the parenchyma to clinically measurable lung function during the progression of emphysema and fibrosis. Finally, we speculate about the possibility of using targeted tissue engineering to optimize treatment of these two major lung diseases. PMID:18485836

Suki, Béla; Bates, Jason H.T.

2008-01-01

128

Antioxidant vitamins and prevention of lung disease  

SciTech Connect

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.

Menzel, D.B. (Univ. of California, Irvine (United States))

1992-09-30

129

RNAi Therapeutic Platforms for Lung Diseases  

PubMed Central

RNA interference (RNAi) is rapidly becoming an important method for analyzing gene functions in many eukaryotes and holds promise for the development of therapeutic gene silencing. The induction of RNAi relies on small silencing RNAs, which affect specific messenger RNA (mRNA) degradation. Two types of small RNA molecules, i.e. small interfering RNAs (siRNAs) and microRNAs (miRNAs), are central to RNAi. Drug discovery studies and novel treatments of siRNAs are currently targeting a wide range of diseases, including various viral infections and cancers. Lung diseases in general are attractive targets for siRNA therapeutics because of their lethality and prevalence. In addition, the lung is anatomically accessible to therapeutic agents via the intrapulmonary route. Recently, increasing evidence indicates that miRNAs play an important role in lung abnormalities, such as inflammation and oncogenesis. Therefore, miRNAs are being targeted for therapeutic purposes. In this review, we present strategies for RNAi delivery and discuss the current state-of-the-art RNAi-based therapeutics for various lung diseases. PMID:24275949

Fujita, Yu; Takeshita, Fumitaka; Kuwano, Kazuyoshi; Ochiya, Takahiro

2013-01-01

130

Risk factors for post-pneumonectomy acute lung injury/acute respiratory distress syndrome in primary lung cancer patients.  

PubMed

Acute lung injury/acute respiratory distress syndrome (ALI / ARDS) is the most serious pulmonary complication after lung resection. This study investigated the incidence and outcome of patients with ALI / ARDS who required mechanical ventilation within one week of undergoing pneumonectomy for primary lung cancer and analysed the risk factors. We retrospectively reviewed the medical records of 146 patients who underwent pneumonectomy for primary lung cancer between May 2001 and April 2006. Preoperative, perioperative and postoperative clinical data were analysed. Post-pneumonectomy ALI / ARDS developed within the first postoperative week in 18 (12%) patients. Patients who developed ALI / ARDS had a longer hospital duration of stay (median [interquartile range], 26 [18 to 75] vs. 8 [7 to 11] days; P < 0.001) and higher in-hospital mortality (12 [67%] vs. 0 [0%]; P < 0.001). In an univariate analysis, post-pneumonectomy ALI / ARDS was associated with larger tidal volume (V(T)) and higher airway pressure (P(aw)) during one-lung ventilation (V(T) 8.2 [7.5 to 9.0] vs. 7.7 [6.9 to 8.2] ml/kg predicted body weight, P = 0.016; P(aw), 28.9 [27.6 to 30.0] vs. 27.2 [25.6 to 28.5] cmH2O, P = 0.001). V(T) during two-lung ventilation was also greater in patients who developed ALI / ARDS (P = 0.014) than in those who did not, but P(aw) during two-lung ventilation did not differ (P = 0.950). In a multiple logistic regression analysis, post-pneumonectomy ALI / ARDS was independently associated with a larger V(T) (OR 3.37 per 1 ml/kg predicted body weight increase; 95% confidence interval 1.65 to 6.86) and higher P(aw) (OR 2.32 per 1 cmH2O increase; 95% confidence interval 1.46 to 3.67) during the period of one-lung ventilation. In conclusion, a large V(T) and high P(aw) during one-lung ventilation were associated with an increased risk of post-pneumonectomy ALI / ARDS in primary lung cancer patients. PMID:19157340

Jeon, K; Yoon, J W; Suh, G Y; Kim, J; Kim, K; Yang, M; Kim, H; Kwon, O J; Shim, Y M

2009-01-01

131

Translational models of lung disease.  

PubMed

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. PMID:25328010

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

2015-02-01

132

Acute Chest Syndrome of Sickle Cell Disease  

E-print Network

The acute chest syndrome (ACS) is an acute pulmonary illness that occurs in patients with sickle cell disease. ACS is currently defined as a new infiltrate on chest radiograph in conjunction with 1 other new symptom or sign: chest pain, cough, wheezing, tachypnea, and/or fever (> 38.5°C). 1 The

Aaron W. Bernard; Zahida Yasin Md; Arvind Venkat Md

133

Thaliporphine Derivative Improves Acute Lung Injury after Traumatic Brain Injury  

PubMed Central

Acute lung injury (ALI) occurs frequently in patients with severe traumatic brain injury (TBI) and is associated with a poor clinical outcome. Aquaporins (AQPs), particularly AQP1 and AQP4, maintain water balances between the epithelial and microvascular domains of the lung. Since pulmonary edema (PE) usually occurs in the TBI-induced ALI patients, we investigated the effects of a thaliporphine derivative, TM-1, on the expression of AQPs and histological outcomes in the lung following TBI in rats. TM-1 administered (10?mg/kg, intraperitoneal injection) at 3 or 4?h after TBI significantly reduced the elevated mRNA expression and protein levels of AQP1 and AQP4 and diminished the wet/dry weight ratio, which reflects PE, in the lung at 8 and 24?h after TBI. Postinjury TM-1 administration also improved histopathological changes at 8 and 24?h after TBI. PE was accompanied with tissue pathological changes because a positive correlation between the lung injury score and the wet/dry weight ratio in the same animal was observed. Postinjury administration of TM-1 improved ALI and reduced PE at 8 and 24?h following TBI. The pulmonary-protective effect of TM-1 may be attributed to, at least in part, downregulation of AQP1 and AQP4 expression after TBI. PMID:25705683

Chen, Gunng-Shinng; Huang, Kuo-Feng; Huang, Chien-Chu; Wang, Jia-Yi

2015-01-01

134

Classification algorithm of lung lobe for lung disease cases based on multislice CT images  

NASA Astrophysics Data System (ADS)

With the development of multi-slice CT technology, to obtain an accurate 3D image of lung field in a short time is possible. To support that, a lot of image processing methods need to be developed. In clinical setting for diagnosis of lung cancer, it is important to study and analyse lung structure. Therefore, classification of lung lobe provides useful information for lung cancer analysis. In this report, we describe algorithm which classify lungs into lung lobes for lung disease cases from multi-slice CT images. The classification algorithm of lung lobes is efficiently carried out using information of lung blood vessel, bronchus, and interlobar fissure. Applying the classification algorithms to multi-slice CT images of 20 normal cases and 5 lung disease cases, we demonstrate the usefulness of the proposed algorithms.

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

2011-03-01

135

Lung parenchyma-derived IL-6 promotes IL-17A-dependent acute lung injury after allogeneic stem cell transplantation.  

PubMed

Idiopathic pneumonia syndrome (IPS) is a relatively common, frequently fatal clinical entity, characterized by noninfectious acute lung inflammation following allogeneic stem cell transplantation (SCT), the mechanisms of which are unclear. In this study, we demonstrate that immune suppression with cyclosporin after SCT limits T-helper cell (Th) 1 differentiation and interferon-? secretion by donor T cells, which is critical for inhibiting interleukin (IL)-6 generation from lung parenchyma during an alloimmune response. Thereafter, local IL-6 secretion induces donor alloantigen-specific Th17 cells to preferentially expand within the lung, and blockade of IL-17A or transplantation of grafts lacking the IL-17 receptor prevents disease. Studies using IL-6(-/-) recipients or IL-6 blockade demonstrate that IL-6 is the critical driver of donor Th17 differentiation within the lung. Importantly, IL-6 is also dysregulated in patients undergoing clinical SCT and is present at very high levels in the plasma of patients with IPS compared with SCT recipients without complications. Furthermore, at the time of diagnosis, plasma IL-6 levels were higher in a subset of IPS patients who were nonresponsive to steroids and anti-tumor necrosis factor therapy. In sum, pulmonary-derived IL-6 promotes IPS via the induction of Th17 differentiation, and strategies that target these cytokines represent logical therapeutic approaches for IPS. PMID:25673640

Varelias, Antiopi; Gartlan, Kate H; Kreijveld, Ellen; Olver, Stuart D; Lor, Mary; Kuns, Rachel D; Lineburg, Katie E; Teal, Bianca E; Raffelt, Neil C; Cheong, Melody; Alexander, Kylie A; Koyama, Motoko; Markey, Kate A; Sturgeon, Elise; Leach, Justine; Reddy, Pavan; Kennedy, Glen A; Yanik, Gregory A; Blazar, Bruce R; Tey, Siok-Keen; Clouston, Andrew D; MacDonald, Kelli P A; Cooke, Kenneth R; Hill, Geoffrey R

2015-04-01

136

Protective effects of Isofraxidin against lipopolysaccharide-induced acute lung injury in mice.  

PubMed

Acute lung injury (ALI) is a life-threatening disease characterized by serious lung inflammation and increased capillary permeability, which presents a high mortality worldwide. Isofraxidin (IF), a Coumarin compound isolated from the natural medicinal plants such as Sarcandra glabra and Acanthopanax senticosus, has been reported to have definite anti-bacterial, anti-oxidant, and anti-inflammatory activities. However, the effects of IF against lipopolysaccharide-induced ALI have not been clarified. The aim of the present study is to explore the protective effects and potential mechanism of IF against LPS-induced ALI in mice. In this study, We found that pretreatment with IF significantly lowered LPS-induced mortality and lung wet-to-dry weight (W/D) ratio and reduced the levels of tumor necrosis factor-? (TNF-?), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) in serum and bronchoalveolar lavage fluid (BALF). We also found that total cells, neutrophils and macrophages in BALF, MPO activity in lung tissues were markedly decreased. Besides, IF obviously inhibited lung histopathological changes and cyclooxygenase-2 (COX-2) protein expression. These results suggest that IF has a protective effect against LPS-induced ALI, and the protective effect of IF seems to result from the inhibition of COX-2 protein expression in the lung, which regulates the production of PGE2. PMID:25596039

Niu, Xiaofeng; Wang, Yu; Li, Weifeng; Mu, Qingli; Li, Huani; Yao, Huan; Zhang, Hailin

2015-02-01

137

Trauma-associated lung injury differs clinically and biologically from acute lung injury due to other clinical disorders*  

PubMed Central

Objective Patients with trauma-associated acute lung injury have better outcomes than patients with other clinical risks for lung injury, but the mechanisms behind these improved outcomes are unclear. We sought to compare the clinical and biological features of patients with trauma-associated lung injury with those of patients with other risks for lung injury and to determine whether the improved outcomes of trauma patients reflect their baseline health status or less severe lung injury, or both. Design, Setting, and Patients Analysis of clinical and biological data from 1,451 patients enrolled in two large randomized, controlled trials of ventilator management in acute lung injury. Measurements and Main Results Compared with patients with other clinical risks for lung injury, trauma patients were younger and generally less acutely and chronically ill. Even after adjusting for these baseline differences, trauma patients had significantly lower plasma levels of intercellular adhesion molecule-1, von Willebrand factor antigen, surfactant protein-D, and soluble tumor necrosis factor receptor-1, which are biomarkers of lung epithelial and endothelial injury previously found to be prognostic in acute lung injury. In contrast, markers of acute inflammation, except for interleukin-6, and disordered coagulation were similar in trauma and nontrauma patients. Trauma-associated lung injury patients had a significantly lower odds of death at 90 days, even after adjusting for baseline clinical factors including age, gender, ethnicity, comorbidities, and severity of illness (odds ratio, 0.44; 95% confidence interval, 0.24 – 0.82; p = .01). Conclusions Patients with trauma-associated lung injury are less acutely and chronically ill than other lung injury patients; however, these baseline clinical differences do not adequately explain their improved outcomes. Instead, the better outcomes of the trauma population may be explained, in part, by less severe lung epithelial and endothelial injury. PMID:17944012

Calfee, Carolyn S.; Eisner, Mark D.; Ware, Lorraine B.; Thompson, B. Taylor; Parsons, Polly E.; Wheeler, Arthur P.; Korpak, Anna; Matthay, Michael A.

2009-01-01

138

Quantitative CT Imaging of Interstitial Lung Diseases  

PubMed Central

Purpose High-Resolution chest CT (HRCT) is essential in the characterization of interstitial lung disease (ILD). The HRCT features of some diseases can be diagnostic. Longitudinal monitoring with HRCT can assess progression of ILD; however, subtle changes in the volume and character of abnormalities can be difficult to assess. Accuracy of diagnosis can be dependent on expertise and experience of the radiologist, pathologist or clinician. Quantitative analysis of thoracic HRCT has the potential to determine the extent of disease reproducibly, classify the types of abnormalities and automate the diagnostic process. Materials and Methods Novel software that utilizes histogram signatures to characterize pulmonary parenchyma was used to interrogate chest HRCT data, including retrospective processing of clinical CT scans and research data from the Lung Tissue Research Consortium (LTRC). Additional information including physiologic, pathologic and semi-quantitative radiologist assessment was available to allowcomparison of quantitative results with visual estimates of disease, physiologic parameters and measures of disease outcome. Results Quantitative analysis results were provided in regional volumetric quantities for statistical analysis as well as a graphical representation. Analysis suggests that quantitative HRCT analysis can serve as a biomarker with physiologic, pathologic and prognostic significance. Conclusion It is likely that quantitative analysis of HRCT can be used in clinical practice as a means to aid in identifying probable diagnosis, stratifying prognosis in early disease, and consistently determining progression of disease or response to therapy. Further optimization of quantitative techniques and longitudinal analysis of well-characterized subjects would be helpful to validate these methods. PMID:23966094

Bartholmai, Brian J; Raghunath, Sushravya; Karwoski, Ronald A; Moua, Teng; Rajagopalan, Srinivasan; Maldonado, Fabien; Decker, Paul A; Robb, Richard A

2013-01-01

139

Posttransplant lymphoproliferative disease after lung transplantation.  

PubMed

Posttransplant lymphoproliferative disease (PTLD) after lung transplantation occurs due to immunosuppressant therapy which limits antiviral host immunity and permits Epstein-Barr viral (EBV) replication and transformation of B cells. Mechanistically, EBV survives due to latency, escape from cytotoxic T cell responses, and downregulation of host immunity to EBV. Clinical presentation of EBV may occur within the lung allograft early posttransplantation or later onset which is more likely to be disseminated. Improvements in monitoring through EBV viral load have provided a means of earlier detection; yet, sensitivity and specificity of EBV load monitoring after lung transplantation may require further optimization. Once PTLD develops, staging and tissue diagnosis are essential to appropriate histopathological classification, prognosis, and guidance for therapy. The overall paradigm to treat PTLD has evolved over the past several years and depends upon assessment of risk such as EBV-naďve status, clinical presentation, and stage and sites of disease. In general, clinical practice involves reduction in immunosuppression, anti-CD20 biologic therapy, and/or use of plasma cell inhibition, followed by chemotherapy for refractory PTLD. This paper focuses upon the immunobiology of EBV and PTLD, as well as the clinical presentation, diagnosis, prognosis, and emerging treatments for PTLD after lung transplantation. PMID:23533455

Neuringer, Isabel P

2013-01-01

140

A therapeutic role for mesenchymal stem cells in acute lung injury independent of hypoxia-induced mitogenic factor  

PubMed Central

Abstract Bone marrow mesenchymal stem cells (BM-MSCs) have therapeutic potential in acute lung injury (ALI). Hypoxia-induced mitogenic factor (HIMF) is a lung-specific growth factor that participates in a variety of lung diseases. In this study, we evaluated the therapeutic role of BM-MSC transplantation in lipopolysaccharide (LPS)- induced ALI and assessed the importance of HIMF in MSC transplantation. MSCs were isolated and identified, and untransduced MSCs, MSCs transduced with null vector or MSCs transduced with a vector encoding HIMF were transplanted into mice with LPS-induced ALI. Histopathological changes, cytokine expression and indices of lung inflammation and lung injury were assessed in the various experimental groups. Lentiviral transduction did not influence the biological features of MSCs. In addition, transplantation of BM-MSCs alone had significant therapeutic effects on LPS-induced ALI, although BM-MSCs expressing HIMF failed to improve the histopathological changes observed with lung injury. Unexpectedly, tumour necrosis factor ? levels in lung tissues, lung oedema and leucocyte infiltration into lungs were even higher after the transplantation of MSCs expressing HIMF, followed by a significant increase in lung hydroxyproline content and ?-smooth muscle actin expression on day 14, as compared to treatment with untransduced MSCs. BM-MSC transplantation improved LPS-induced lung injury independent of HIMF. PMID:21477220

Song, Lin; Xu, Jinfu; Qu, Jieming; Sai, Yin; Chen, Chunmei; Yu, Long; Li, Dechun; Guo, Xuejun

2012-01-01

141

Serial lung magnetic resonance imaging to monitor disease progression in a child with a diffuse alveolar hemorrhage syndrome.  

PubMed

Serial lung magnetic resonance imaging (MRI) was performed in a child with diffuse alveolar hemorrhage (DAH). To minimize radiation exposure with conventional serial chest computerized tomography (CT), serial MRIs of the lungs were used. This effectively monitored her disease process as well as detected acute hemorrhage after 5 years remission. PMID:25699125

Kaleel, Mohammed; Schramm, Craig; Pascal, Melanie; O'Louglin, Michael; Collins, Melanie Sue

2015-04-01

142

Serial Lung Magnetic Resonance Imaging to Monitor Disease Progression in a Child With a Diffuse Alveolar Hemorrhage Syndrome  

PubMed Central

Serial lung magnetic resonance imaging (MRI) was performed in a child with diffuse alveolar hemorrhage (DAH). To minimize radiation exposure with conventional serial chest computerized tomography (CT), serial MRIs of the lungs were used. This effectively monitored her disease process as well as detected acute hemorrhage after 5 years remission. PMID:25699125

Kaleel, Mohammed; Schramm, Craig; Pascal, Melanie; O’Louglin, Michael; Collins, Melanie Sue

2015-01-01

143

Identification and examination of a novel 9-bp insert/deletion polymorphism on porcine SFTPA1 exon 2 associated with acute lung injury using an oleic acid-acute lung injury model.  

PubMed

The pulmonary surfactant-associated protein (SFTPA1, SP-A) gene has been studied as a candidate gene for lung disease resistance in humans and livestock. The objective of the present study was to identify polymorphisms of the porcine SFTPA1 gene coding region and its association with acute lung injury (ALI). Through DNA sequencing and the PCR-single-strand conformation polymorphism method, a novel 9-bp nucleotide insertion (+) or deletion (-) was detected on exon 2 of SFTPA1, which causes a change in three amino acids, namely, alanine (Ala), glycine (Gly) and proline (Pro). Individuals of three genotypes (-/-, +/- and +/+) were divided into equal groups from 60 Rongchang pigs that were genotyped. These pigs were selected for participation in the oleic acid (OA)-ALI model by 1-h and 3-h injections of OA, and there were equal numbers of pigs in the control and injection groups. The lung water content, a marker for acute lung injury, was measured in this study; there is a significant correlation between high lung water content and the presence of the 9-bp indel polymorphism (P?lung water content of the OA injection group was markedly higher than that of the control group and lung water content for the +/+ genotype was significantly higher than that of the others in the 1-h group (P?lung water content than the +/+ genotype pigs, which suggests that polymorphism could be a potential marker for lung disease-resistant pig breeding and that pig can be a potential animal model for human lung disease resistance in future studies. PMID:25442010

Zhang, Yuebo; Zhang, Longchao; Wang, Ligang; Qiao, Lijuan; Liang, Jing; Yan, Hua; Zhao, Kebin; Liu, Xin; Wang, Lixian

2014-11-30

144

Angiotensin-converting enzyme 2 (ACE2) mediates influenza H7N9 virus-induced acute lung injury  

PubMed Central

Since March 2013, the emergence of an avian-origin influenza A (H7N9) virus has raised concern in China. Although most infections resulted in respiratory illness, some severe cases resulted in acute respiratory distress syndrome (ARDS), which is a severe form of acute lung injury (ALI) that further contributes to morbidity. To date, no effective drugs that improve the clinical outcome of influenza A (H7N9) virus-infected patients have been identified. Angiotensin-converting enzyme (ACE) and ACE2 are involved in several pathologies such as cardiovascular functions, renal disease, and acute lung injury. In the current study, we report that ACE2 could mediate the severe acute lung injury induced by influenza A (H7N9) virus infection in an experimental mouse model. Moreover, ACE2 deficiency worsened the disease pathogenesis markedly, mainly by targeting the angiotensin II type 1 receptor (AT1). The current findings demonstrate that ACE2 plays a critical role in influenza A (H7N9) virus-induced acute lung injury, and suggest that might be a useful potential therapeutic target for future influenza A (H7N9) outbreaks. PMID:25391767

Yang, Penghui; Gu, Hongjing; Zhao, Zhongpeng; Wang, Wei; Cao, Bin; Lai, Chengcai; Yang, Xiaolan; Zhang, LiangYan; Duan, Yueqiang; Zhang, Shaogeng; Chen, Weiwen; Zhen, Wenbo; Cai, Maosheng; Penninger, Josef M.; Jiang, Chengyu; Wang, Xiliang

2014-01-01

145

Instilled air promotes lipopolysaccharide-induced acute lung injury  

PubMed Central

Optimization of intratracheal instillation is necessary to establish an ideal animal model of acute lung injury (ALI) in order to further reveal the cellular and molecular pathogenesis of ALI. It is possible that instilling air from a prefilled syringe may promote the delivery of reagents into the alveolar spaces, resulting in different pulmonary responses. In the present study, the influence of instilling air by trans-tracheal intratracheal instillation in a lipopolysaccharide (LPS)-induced mouse model of ALI was investigated. The bronchoalveolar lavage (BAL) fluid biochemical index, BAL fluid differential cell counts, lung wet/dry weight ratio, lung histology and BAL fluid interleukin-8 (IL-8) levels were assessed 24 h subsequent to intratracheal instillation. Instilled air promoted LPS-induced ALI, as indicated by the severity of acute pulmonary inflammation and increased IL-8 release. In conclusion, this study indicates that instilled air may be used to improve the intratracheal instillation procedure and to establish a more reliable animal model of ALI. PMID:24660029

ZOU, YINGGANG; DONG, CHUNLING; YUAN, MINGZHEN; GAO, GUANGYUAN; WANG, SIYI; LIU, XIAODING; HAN, HUIQIAO; LI, BO

2014-01-01

146

Does detoxification reverse the acute lung injury of crack smokers?  

PubMed

The effect on chronic crack users of a 3 month detoxification programme on lung clearance of inhaled 99Tcm-diethylenetriamine pentaacetate (99Tcm-DTPA) aerosol, spirometry and gas exchange was determined in a controlled in-patient clinical treatment setting. Imaging studies were carried out in eight chronic crack users (four crack-only and four crack plus tobacco) before and after the successful completion of the detoxification programme to measure the clearance of inhaled 99Tcm-DTPA from the lungs, an index of lung epithelial permeability. 99Tcm-DTPA lung clearance, expressed in terms of the biological half-time, T1/2, was determined from the slopes of the least-squares fit regression lines of the respective time-activity plots. The mean (+/- S.D.) global T1/2 values of the crack-only (75 +/- 39 min) and crack plus tobacco users (22 +/- 10 min) were significantly shorter (P < 0.02 and P < 0.001, respectively) than from the lungs of the non-smoking controls (124 +/- 29 min). This was consistent with increased lung epithelial permeability secondary to crack-related lung injury. The mean global T1/2 value of the crack plus tobacco users was significantly shorter (P < 0.05) than that of the crack-only users. After detoxification, the abnormally rapid lung clearance became normal in two of the four crack-only users studied, improved in a third and remained unchanged in the fourth, a subject whose T1/2 value was already normal initially. However, lung clearance improved in only one of the four crack plus tobacco users studied. Faster 99Tcm-DTPA clearance was the only impairment found in seven of the eight crack users, the eighth having restrictive lung disease. Crack-related lung injury, reflected by abnormally rapid 99Tcm-DTPA lung clearance, may be at least partially reversible after a 3 month period of abstinence from crack. PMID:8971868

Susskind, H; Weber, D A; Atkins, H L; Franceschi, D; Volkow, N D

1996-11-01

147

Asbestos-induced lung diseases: an update  

PubMed Central

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

KAMP, DAVID W.

2009-01-01

148

The Epithelial Cell and Lung Cancer: The Link between Chronic Obstructive Pulmonary Disease and Lung Cancer  

Microsoft Academic Search

Chronic obstructive pulmonary disease (COPD) and lung cancer currently form the basis for an enormous disease burden in the developed world. As a result of changing smoking trends and tobacco use, regrettably, a similar picture is arising rapidly within the developing world. COPD is a recognised risk factor for lung cancer, and a significant proportion of patients diagnosed with lung

Claire Rooney; Tariq Sethi

2011-01-01

149

Electroacupuncture Ameliorates Acute Lung Injury through Promoting Gastrointestinal Motility in Rats with Acute Pancreatitis  

PubMed Central

Objective. Gastrointestinal disfunction and acute lung injury (ALI) were common in acute pancreatitis (AP). The effect of electro-acupuncture (EA) on gastrointestinal motility and ALI in rats with AP was investigated to verify the theory of “lung and large intestine are interior exteriorly related” in traditional Chinese medicine. Methods. Male Sprague-Dawley rats were randomly divided into the normal group, model group, and EA group. AP model was established by three injections of 20% L-arginine at 1?h intervals. EA were applied to bilateral ST-25 and ST-36 for 30 minutes twice a day after modeling for 3 days. Arterial blood, pancreas, lung, and intestinal tissues were collected for detecting the inflammatory factors and histopathology. Intestinal propulsion rate (IPR) was also measured at 72?h. Results. EA treatment improved IPR and increased CCK-8 level compared with model group (P < 0.05). It lowered the serum levels of TNF-? and IL-6 and increased the level of IL-4 with no effect on IL-10. EA treatment reduced serum vasoactive intestinal peptide (VIP) and myeloperoxidase (MPO) level in the lung and the pathologic scores of pancreas, lung and intestine were decreased (P < 0.05). Conclusion. EA treatment could promote gastrointestinal motility through inhibiting VIP, and promoting CCK expression and regulate pro- and anti-inflammatory mediators to ameliorate ALI in AP. PMID:24876883

Guo, Hui; Zhu, Shi-Feng; Zhang, Rong-Rong; Zhao, Xian-Lin; Wan, Mei-Hua; Tang, Wen-Fu

2014-01-01

150

Cystathionine-gamma-lyase inhibitor attenuates acute lung injury induced by acute pancreatitis in rats  

PubMed Central

Introduction Acute pancreatitis (AP) is known to induce injuries to extrapancreatic organs. Because respiratory dysfunction is the main cause of death in patients with severe AP, acute pancreatitis-associated lung injury (APALI) is a great challenge for clinicians. This study aimed to investigate the potential role of hydrogen sulfide (H2S) in the pathogenesis of APALI. Material and methods Fifty-four SD rats were randomly divided into three groups: the AP group of rats that received injection of sodium deoxycholate into the common bile duct, the control group that underwent a sham operation, and the treatment group made by intraperitoneal injection of propargylglycine (PAG), an inhibitor of cystathionine-?-lyase (CSE), into rats with AP. Histopathology of the lung was examined and the expression of CSE and TNF-? mRNA in lung tissue was detected by real-time polymerase chain reaction. The H2S level in the serum was detected spectrophotometrically. Results The serum concentration of H2S and CSE and TNF-? expression in the lung were increased in AP rats modeled after 3 h and 6 h than in control rats (p < 0.05). Intraperitoneal injection of PAG could reduce the serum concentration of H2S, reduce CSE and TNF-? expression, and alleviate the lung pathology (p < 0.05). Conclusions Taken together, our findings suggest that the H2S/CSE system is crucially involved in the pathological process of APALI and represents a novel target for the therapy of APALI. PMID:25276170

Qu, Zhen; Wu, Bao-Qiang; Duan, Yun-Fei; Sun, Zhen-Di; Luo, Guang-Hua

2014-01-01

151

[Pulmonary hypertension in chronic lung diseases].  

PubMed

Chronic obstructive lung disease (COPD) and diffuse parenchymal lung diseases (DPLD), including idiopathic pulmonary fibrosis (IPF) and sarcoidosis, are associated with a high incidence of pulmonary hypertension (PH), which is linked with exercise limitation and a worse prognosis. Patients with combined pulmonary fibrosis and emphysema (CPFE) are particularly prone to the development of PH. Echocardiography and right heart catheterization are the principal modalities for the diagnosis of COPD and DPLD. For discrimination between group 1 PH patients with concomitant respiratory abnormalities and group 3 PH patients (PH caused by lung disease), patients should be transferred to a center with expertise in both PH and lung diseases for comprehensive evaluation. The task force encompassing the .authors of this article provided criteria for this discrimination and suggested using the following definitions for group 3 patients, as exemplified for COPD, IPF, and CPFE: COPD/IPF/CPFE without PH (mean pulmonary artery pressure [mPAP]<25mmHg); COPD/IPF/CPFE with PH (mPAP25mmHg); PH-COPD, PH-IPF, and PH-CPFE); COPD/IPF/CPFE with severe PH (mPAP 35 mmHg or mPAP 25 mmHg with low cardiac index [CI <2.0.l/min/m2]; severe PH-COPD, severe PH-IPF, and severe PH-CPFE). The "severe PH group" includes only a minority of chronic lung disease patients who are suspected of having strong general vascular abnormalities (remodeling) accompanying the parenchymal disease and with evidence of an exhausted circulatory reserve rather than an exhausted ventilatory reserve underlying the limitation of exercise capacity. Exertional dyspnea disproportionate to pulmonary function tests, low carbon monoxide diffusion capacity, and rapid decline of arterial oxygenation upon exercise are typical clinical features of this subgroup with poor prognosis. Studies evaluating the effect of pulmonary arterial hypertension drugs currently not approved for group 3 PH patients should focus on this severe PH group, and for the time being, these patients should be transferred to expert centers for individualized patient care. (J Am Coll Cardiol 2013;62:D109-16) ©2013 by the American College of Cardiology Foundation. PMID:25697041

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

2014-10-01

152

Pulmonary hypertension in chronic lung diseases.  

PubMed

Chronic obstructive lung disease (COPD) and diffuse parenchymal lung diseases (DPLD), including idiopathic pulmonary fibrosis (IPF) and sarcoidosis, are associated with a high incidence of pulmonary hypertension (PH), which is linked with exercise limitation and a worse prognosis. Patients with combined pulmonary fibrosis and emphysema (CPFE) are particularly prone to the development of PH. Echocardiography and right heart catheterization are the principal modalities for the diagnosis of COPD and DPLD. For discrimination between group 1 PH patients with concomitant respiratory abnormalities and group 3 PH patients (PH caused by lung disease), patients should be transferred to a center with expertise in both PH and lung diseases for comprehensive evaluation. The task force encompassing the authors of this article provided criteria for this discrimination and suggested using the following definitions for group 3 patients, as exemplified for COPD, IPF, and CPFE: COPD/IPF/CPFE without PH (mean pulmonary artery pressure [mPAP] <25 mm Hg); COPD/IPF/CPFE with PH (mPAP ?25 mm Hg); PH-COPD, PH-IPF, and PH-CPFE); COPD/IPF/CPFE with severe PH (mPAP ?35 mm Hg or mPAP ?25 mm Hg with low cardiac index [CI <2.0 l/min/m(2)]; severe PH-COPD, severe PH-IPF, and severe PH-CPFE). The "severe PH group" includes only a minority of chronic lung disease patients who are suspected of having strong general vascular abnormalities (remodeling) accompanying the parenchymal disease and with evidence of an exhausted circulatory reserve rather than an exhausted ventilatory reserve underlying the limitation of exercise capacity. Exertional dyspnea disproportionate to pulmonary function tests, low carbon monoxide diffusion capacity, and rapid decline of arterial oxygenation upon exercise are typical clinical features of this subgroup with poor prognosis. Studies evaluating the effect of pulmonary arterial hypertension drugs currently not approved for group 3 PH patients should focus on this severe PH group, and for the time being, these patients should be transferred to expert centers for individualized patient care. PMID:24355635

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

2013-12-24

153

Original article Lentivirus-induced interstitial lung disease  

E-print Network

Original article Lentivirus-induced interstitial lung disease: pulmonary pathology in sheep a chronic disease in sheep affecting, among other organs, the lungs. Interstitial pneumonitis is similar the pathological features of lungs of sheep naturally infected with visna-maedi virus with the results obtained

Boyer, Edmond

154

Nilotinib ameliorates lipopolysaccharide-induced acute lung injury in rats  

SciTech Connect

The present study aimed to investigate the effect of the new tyrosine kinase inhibitor, nilotinib on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats and explore its possible mechanisms. Male Sprague-Dawley rats were given nilotinib (10 mg/kg) by oral gavage twice daily for 1 week prior to exposure to aerosolized LPS. At 24 h after LPS exposure, bronchoalveolar lavage fluid (BALF) samples and lung tissue were collected. The lung wet/dry weight (W/D) ratio, protein level and the number of inflammatory cells in the BALF were determined. Optical microscopy was performed to examine the pathological changes in lungs. Malondialdehyde (MDA) content, superoxidase dismutase (SOD) and reduced glutathione (GSH) activities as well as nitrite/nitrate (NO{sub 2}{sup -}/NO{sub 3}{sup -}) levels were measured in lung tissues. The expression of inflammatory cytokines, tumor necrosis factor-{alpha} (TNF-{alpha}), transforming growth factor-{beta}{sub 1} (TGF-{beta}{sub 1}) and inducible nitric oxide synthase (iNOS) were determined in lung tissues. Treatment with nilotinib prior to LPS exposure significantly attenuated the LPS-induced pulmonary edema, as it significantly decreased lung W/D ratio, protein concentration and the accumulation of the inflammatory cells in the BALF. This was supported by the histopathological examination which revealed marked attenuation of LPS-induced ALI in nilotinib treated rats. In addition, nilotinib significantly increased SOD and GSH activities with significant decrease in MDA content in the lung. Nilotinib also reduced LPS mediated overproduction of pulmonary NO{sub 2}{sup -}/NO{sub 3}{sup -} levels. Importantly, nilotinib caused down-regulation of the inflammatory cytokines TNF-{alpha}, TGF-{beta}{sub 1} and iNOS levels in the lung. Taken together, these results demonstrate the protective effects of nilotinib against the LPS-induced ALI. This effect can be attributed to nilotinib ability to counteract the inflammatory cells infiltration and hence ROS generation and regulate cytokine effects. - Research highlights: > The protective effects of nilotinib against LPS-induced ALI in rats were studied. > Nilotinib showed potent anti-inflammatory activity as it attenuated PMN infiltration and hence ROS generation. > In addition, nilotinib caused down-regulation of proinflammatory cytokine production.

El-Agamy, Dina S., E-mail: dinaagamy1@yahoo.com

2011-06-01

155

The Heat Shock Response and Acute Lung Injury  

PubMed Central

All cells respond to stress through the activation of primitive, evolutionarily conserved genetic programs that maintain homeostasis and assure cell survival. Stress adaptation, which is known in the literature by a myriad of terms, including tolerance, desensitization, conditioning, and reprogramming, is a common paradigm found throughout nature, in which a primary exposure of a cell or organism to a stressful stimulus (e.g., heat) results in an adaptive response by which a second exposure to the same stimulus produces a minimal response. More interesting is the phenomenon of cross-tolerance, by which a primary exposure to a stressful stimulus results in an adaptive response whereby the cell or organism is resistant to a subsequent stress that is different from the initial stress (i.e. exposure to heat stress leading to resistance to oxidant stress). The heat shock response is one of the more commonly described examples of stress adaptation and is characterized by the rapid expression of a unique group of proteins collectively known as heat shock proteins (also commonly referred to as stress proteins). The expression of heat shock proteins is well described in both whole lungs and in specific lung cells from a variety of species and in response to a variety of stressors. More importantly, in vitro data, as well as data from various animal models of acute lung injury, demonstrate that heat shock proteins, especially Hsp27, Hsp32, Hsp60, and Hsp70 have an important cytoprotective role during lung inflammation and injury. PMID:17157189

Wheeler, Derek S.; Wong, Hector R.

2006-01-01

156

Polydatin attenuates ipopolysaccharide-induced acute lung injury in rats  

PubMed Central

Anti-inflammatory and anti-apoptotic effects of polydatin (PD) have been demonstrated in our previous studies. Recently, we have found that PD treatment can ameliorate burn-induced acute lung injury (ALI). In the present study, we hypothesized that PD may provide protective effect against LPS-induced ALI through reducing inflammation and apoptosis. Rats were respectively pretreated with PD at doses of 15, 30 and 45 mg/kg weight, followed by intratracheal administration of lipopolysaccharide (LPS). LPS-challenged rats exhibited significant lung injury characterized by the deterioration of histopathology, pulmonary microvascular hyperpermeability, wet-to-dry weight ratio, and oxygenation index, which was attenuated by PD (30 and 45 mg/kg) treatment. Moreover, PD (30 and 45 mg/kg) treatment inhibited LPS-induced inflammatory response, as evidenced by the downregulation of lung myeloperoxidase activity, total cells and PMNs in bronchoalveolar lavage fluid, and the systemic levels of the pro-inflammatory cytokines. Furthermore, PD (30 and 45 mg/kg) treatment remarkably improved LPS-induced increase in TUNEL (deoxynucleotidyl transferase dUTP nick end labeling) staining-positive cells, caspase 3 activity, Bax over-expression and Bcl-2 down-expression. In conclusion, these results demonstrate that PD (30 and 45 mg/kg) treatment attenuates LPS-induced ALI through reducing lung inflammation and apoptosis. PMID:25674204

Li, Tao; Liu, Youtan; Li, Guicheng; Wang, Xiang; Zeng, Zhenhua; Cai, Shumin; Li, Fengyun; Chen, Zhongqing

2014-01-01

157

Fibrocytes and the pathogenesis of diffuse parenchymal lung disease  

PubMed Central

Fibrosis is fundamental to the pathogenesis of many chronic lung diseases, including some lung infections, airway diseases such as bronchiectasis and asthma, and most of the diffuse parenchymal lung diseases. Idiopathic pulmonary fibrosis, the prototypical fibrotic lung disease, is amongst the most common diffuse parenchymal lung diseases and is characterized by progressive decline in lung function and premature death from respiratory failure. The clinical management of patients with this illness is hampered by our current inability to predict clinical deterioration and lack of an effective therapy. Fibrocytes are a population of bone marrow-derived circulating progenitor cells that home to injured tissues and differentiate into fibroblasts and myofibroblasts, thus contributing to scar formation. We summarize the evidence supporting the role of these cells in the pathogenesis of fibrotic lung diseases. PMID:23259468

2012-01-01

158

Fibrocytes and the pathogenesis of diffuse parenchymal lung disease.  

PubMed

Fibrosis is fundamental to the pathogenesis of many chronic lung diseases, including some lung infections, airway diseases such as bronchiectasis and asthma, and most of the diffuse parenchymal lung diseases. Idiopathic pulmonary fibrosis, the prototypical fibrotic lung disease, is amongst the most common diffuse parenchymal lung diseases and is characterized by progressive decline in lung function and premature death from respiratory failure. The clinical management of patients with this illness is hampered by our current inability to predict clinical deterioration and lack of an effective therapy. Fibrocytes are a population of bone marrow-derived circulating progenitor cells that home to injured tissues and differentiate into fibroblasts and myofibroblasts, thus contributing to scar formation. We summarize the evidence supporting the role of these cells in the pathogenesis of fibrotic lung diseases. PMID:23259468

Mehrad, Borna; Strieter, Robert M

2012-01-01

159

Agmatine Protects against Zymosan-Induced Acute Lung Injury in Mice by Inhibiting NF-?B-Mediated Inflammatory Response  

PubMed Central

Acute lung injury (ALI) is characterized by overwhelming lung inflammation and anti-inflammation treatment is proposed to be a therapeutic strategy for ALI. Agmatine, a cationic polyamine formed by decarboxylation of L-arginine, is an endogenous neuromodulator that plays protective roles in diverse central nervous system (CNS) disorders. Consistent with its neuromodulatory and neuroprotective properties, agmatine has been reported to have beneficial effects on depression, anxiety, hypoxic ischemia, Parkinson's disease, and gastric disorder. In this study, we tested the effect of agmatine on the lung inflammation induced by Zymosan (ZYM) challenge in mice. We found that agmatine treatment relieved ZYM-induced acute lung injury, as evidenced by the reduced histological scores, wet/dry weight ratio, and myeloperoxidase activity in the lung tissue. This was accompanied by reduced levels of TNF-?, IL-1?, and IL-6 in lung and bronchoalveolar lavage fluid and decreased iNOS expression in lung. Furthermore, agmatine inhibited the phosphorylation and degradation of I?B and subsequently blocked the activation of nuclear factor (NF)-?B induced by Zymosan. Taken together, our results showed that agmatine treatment inhibited NF-?B signaling in lungs and protected mice against ALI induced by Zymosan, suggesting agmatine may be a potential safe and effective approach for the treatment of ALI. PMID:25243152

Liu, Zheng; Jin, He; Fan, Xia; Yang, Xue; Tang, Wanqi; Liang, Huaping

2014-01-01

160

Bilateral versus single lung transplantation for chronic obstructive pulmonary disease  

Microsoft Academic Search

Objective: Traditionally, despite ventilation\\/perfusion mismatch, single lung transplantation has been the mainstay for end-stage chronic obstructive pulmonary disease. We tested the hypothesis that bilateral sequential lung transplantation has better short- and intermediate-term results than single lung transplantation for chronic obstructive pulmonary disease.Methods: One hundred twenty-six consecutive lung transplants have been performed from November 1991 to March 1996. Seventy-six have been

Joseph E. Bavaria; Robert Kotloff; Harold Palevsky; Bruce Rosengard; John R. Roberts; Peter M. Wahl; Nancy Blumenthal; Christine Archer; Larry R. Kaiser

1997-01-01

161

Effect of acute lung injury on metabolism of adenine nucleotides in rat perfused lung.  

PubMed Central

1. The hydrolysis of adenosine di- and monophosphate (ADP, AMP) was studied in perfused lungs isolated from rats treated with alpha-naphthylthiourea (ANTU) to induce acute lung injury. This injury is associated with damage to the endothelium, the locus of the ADP and AMP hydrolysing enzymes. 2. Treatment with ANTU did not change the proportion of [3H]-ADP surviving a single passage through the pulmonary circulation, at any time up to 50 h after ANTU. Less than 8% and 2% respectively of 1 or 0.1 mumol ADP, given as a bolus, appeared in lung effluent. 3. The metabolites of ADP, AMP and adenosine in lung effluent were increased fro 2 h after ANTU. 4. Metabolism of [3H]-AMP as substrate was always low but, following ANTU treatment, the adenosine content of lung effluent increased four fold. 5. It appears that, in spite of considerable endothelial cell damage, as demonstrated by pulmonary oedema, the ectoenzymes catalysing ADP and AMP hydrolysis were relatively little affected by ANTU. PMID:3145086

Grantham, C. J.; Bakhle, Y. S.

1988-01-01

162

Neuraminidase reprograms lung tissue and potentiates LPS-induced acute lung injury in mice  

PubMed Central

We previously reported that removal of sialyl residues primed PBMCs to respond to bacterial LPS stimulation in vitro. Therefore, we speculated that prior desialylation can sensitize the host to generate an enhanced inflammatory response upon exposure to a TLR ligand, such as LPS, in a murine model of acute lung injury. Intratracheal instillation of neuraminidase (NA) 30 min prior to intratracheal administration of LPS increased PMNs in the bronchoalveolar lavage fluid (BALF) and the wet-to-dry lung weight ratio, a measure of pulmonary edema, compared to mice that received LPS alone. Administration of NA alone resulted in desialylation of bronchiolar and alveolar surfaces and induction of TNF-?, IL-1?, and chemokines in lung homogenates and BALF; however, PMN recruitment in mice treated with NA alone did not differ from those of PBS-administered controls. NA pretreatment alone induced apoptosis and markedly enhanced LPS-induced endothelial apoptosis. Administration of recombinant Bcl-2, an anti-apoptotic molecule, abolished the effect of NA treatment on LPS-induced PMN recruitment and pulmonary edema formation. We conclude that NA pretreatment potentiates LPS-induced lung injury through enhanced PMN recruitment, pulmonary edema formation, and endothelial and myeloid cell apoptosis. A similar “reprogramming” of immune responses with desialylation may occur during respiratory infection with NA-expressing microbes and contribute to severe lung injury. PMID:24068662

Feng, Chiguang; Zhang, Lei; Nguyen, Chinh; Vogel, Stefanie N.; Goldblum, Simeon E.; Blackwelder, William C.; Cross, Alan S.

2013-01-01

163

Inflammation and angiogenesis in fibrotic lung disease.  

PubMed

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. PMID:17195136

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

2006-12-01

164

Family history of cancer and non-malignant lung diseases as risk factors for lung cancer  

PubMed Central

Family history (FH) of lung cancer is an established risk factor for lung cancer, but the modifying effect of smoking in relatives has been rarely examined. Also, the role of FH of non-malignant lung diseases on lung cancer risk is not well known. We examined the role of FH of cancer and FH of non-malignant lung diseases in lung cancer risk, overall, and by personal smoking, FH of smoking, and histology in 1,946 cases and 2,116 population-based controls within the Environment And Genetics in Lung cancer Etiology (EAGLE) study. Odds ratios (ORs) and 95% CI from logistic regression were calculated adjusting for age, gender, residence, education, and cigarette smoking. FH of lung cancer in any family member was associated with increased lung cancer risk (OR = 1.57, 95% CI = 1.25–1.98). The odds associated with fathers’, mothers’ and siblings’ history of lung cancer were 1.41, 2.14, and 1.53, respectively. The associations were generally stronger in never smokers, younger subjects, and for the adenocarcinoma and squamous cell carcinoma subtypes. FH of chronic bronchitis and pneumonia were associated with increased (OR =1.49, 95% CI = 1.23–1.80) and decreased (OR = 0.73, 95% CI = 0.61–0.87) lung cancer risk, respectively. FH of lung cancer and FH of non-malignant lung diseases affected lung cancer risk independently, and did not appear to be modified by FH of smoking. PMID:19350630

Gao, Ying; Goldstein, Alisa M.; Consonni, Dario; Pesatori, Angela C.; Wacholder, Sholom; Tucker, Margaret A.; Caporaso, Neil E.; Goldin, Lynn; Landi, Maria Teresa

2010-01-01

165

Circulating peripheral blood fibrocytes in human fibrotic interstitial lung disease.  

PubMed

Fibrotic interstitial lung diseases are illnesses of unknown cause characterized by progressive decline in lung function. Fibrocytes are bone marrow-derived, circulating progenitor cells capable of differentiating into diverse mesenchymal cell types. Prior work has shown fibrocytes to traffic to the lung via the CXCL12-CXCR4 chemokine axis in an animal model of pulmonary fibrosis. We therefore assessed the relevance of fibrocytes in patients with fibrotic interstitial lung disease. We found enhanced expression of CXCL12 in both the lungs and plasma of patients with lung fibrosis. CXCL12 levels were associated with an order of magnitude higher number of circulating fibrocytes in the peripheral blood of these patients. Most of the circulating fibrocytes in patients with interstitial lung diseases were negative for the myofibroblast marker alpha-smooth muscle actin, suggesting a relatively undifferentiated phenotype. Taken together, these data suggest that fibrocytes are involved in the pathogenesis of human lung fibrosis. PMID:17174272

Mehrad, Borna; Burdick, Marie D; Zisman, David A; Keane, Michael P; Belperio, John A; Strieter, Robert M

2007-02-01

166

Ethanol Ingestion Increases Activation of Matrix Metalloproteinases in Rat Lungs during Acute Endotoxemia  

Microsoft Academic Search

Previously we reported that alcohol abuse increases the incidence of the acute respiratory distress syndrome (ARDS) in septic patients, and that chronic ethanol ingestion in rats depletes alveolar epi- thelial glutathione and increases endotoxin-mediated lung edema. In this study we examined a po- tential mechanism by which ethanol-induced glutathione depletion could predispose to acute lung injury. We hypothesized that glutathione

MANUEL LOIS; LOU ANN S. BROWN; I. MARC; JESSE ROMAN; DAVID M. GUIDOT

167

Aerosolised surfactant generated by a novel noninvasive apparatus reduced acute lung injury in rats  

Microsoft Academic Search

INTRODUCTION: Exogenous surfactant has been explored as a potential therapy for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In the present study, a nebuliser driven by oxygen lines found in the hospital was developed to deliver aerosolised porcine pulmonary surfactant (PPS). We hypothesised that aerosolised surfactant inhaled through spontaneous breathing may effectively reduce severe lung injury. METHODS:

Yu Sun; Rui Yang; Ji-gen Zhong; Feng Fang; Jin-jin Jiang; Ming-yao Liu; Jian Lu

2009-01-01

168

Peroxisome Proliferator-Activated Receptors and Acute Lung Injury  

PubMed Central

Peroxisome proliferator-activated receptors are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. PPARs regulate several metabolic pathways by binding to sequence-specific PPAR response elements in the promoter region of target genes, including lipid biosynthesis and glucose metabolism. Recently, PPARs and their respective ligands have been implicated as regulators of cellular inflammatory and immune responses. These molecules are thought to exert anti-inflammatory effects by negatively regulating the expression of proinflammatory genes. Several studies have demonstrated that PPAR ligands possess anti-inflammatory properties and that these properties may prove helpful in the treatment of inflammatory diseases of the lung. This review will outline the anti-inflammatory effects of PPARs and PPAR ligands and discuss their potential therapeutic effects in animal models of inflammatory lung disease. PMID:17710233

Paola, Rosanna Di; Cuzzocrea, Salvatore

2007-01-01

169

Prognostic Factors for Myositis-Associated Interstitial Lung Disease  

PubMed Central

Background Interstitial lung disease (ILD) is a common manifestation of polymyositis (PM), dermatomyositis (DM), and clinically amyopathic dermatomyositis (CADM); however, little is known about the factors influencing the prognosis for PM/DM/CADM-associated ILD. (PM/DM/CADM-ILD). The aim of the present study is to assess prognostic factors for PM/DM/CADM-ILD. Methods The clinical features and survival of 114 consecutive patients diagnosed with PM/DM/CADM-ILD (39 men and 75 women; median age, 56 years) were analyzed retrospectively. Results The study group included 30 PM-associated ILD, 41 DM-associated ILD, and 43 CADM-associated ILD cases. The clinical presentation of ILD was acute/subacute form in 59 patients (51.8%) and chronic form in 55 patients (48.2%). The major pulmonary symptoms were dyspnea, cough, and fever. High-resolution computed tomography frequently revealed ground-glass opacities, traction bronchiectasis, and consolidation. Most of the patients were treated with corticosteroids or corticosteroids in combination with immunosuppressive agents. The all-cause mortality was 27.2%. Acute/subacute form, % forced vital capacity (FVC), age, % of neutrophils in bronchoalveolar lavage (BAL) fluid, and a diagnosis of CADM (vs. PM) were significantly associated with poor outcome in univariate Cox proportional hazards models. Multivariate Cox proportional hazards analysis validated acute/subacute ILD, %FVC, age, and diagnosis of CADM (vs. PM) as significant predictors of overall mortality. Patients with acute/subacute ILD had a much lower survival rate than those with the chronic form (p<0.001). Patients with CADM-ILD had a lower survival rate than those with PM-ILD (p?=?0.034). Conclusions Acute/subacute form, older age, lower level of FVC and diagnosis of CADM predict poor outcome in PM/DM/CADM-ILD. PMID:24905449

Fujisawa, Tomoyuki; Hozumi, Hironao; Kono, Masato; Enomoto, Noriyuki; Hashimoto, Dai; Nakamura, Yutaro; Inui, Naoki; Yokomura, Koshi; Koshimizu, Naoki; Toyoshima, Mikio; Shirai, Toshihiro; Yasuda, Kazumasa; Hayakawa, Hiroshi; Suda, Takafumi

2014-01-01

170

Regulation of Na,K-ATPase during acute lung injury.  

PubMed

A hallmark of acute lung injury is the accumulation of a protein rich edema which impairs gas exchange and leads to hypoxemia. The resolution of lung edema is effected by active sodium transport, mostly contributed by apical Na(+) channels and the basolateral located Na,K-ATPase. It has been reported that the decrease of Na,K-ATPase function seen during lung injury is due to its endocytosis from the cell plasma membrane into intracellular pools. In alveolar epithelial cells exposed to severe hypoxia, we have reported that increased production of mitochondrial reactive oxygen species leads to Na,K-ATPase endocytosis and degradation. We found that this regulated process follows what is referred as the Phosphorylation-Ubiquitination-Recognition-Endocytosis-Degradation (PURED) pathway. Cells exposed to hypoxia generate reactive oxygen species which activate PKC zeta which in turn phosphorylates the Na,K-ATPase at the Ser18 residue in the N-terminus of the alpha1-subunit leading the ubiquitination of any of the four lysines (K16, K17, K19, K20) adjacent to the Ser18 residue. This process promotes the alpha1-subunit recognition by the mu2 subunit of the adaptor protein-2 and its endocytosis trough a clathrin dependent mechanism. Finally, the ubiquitinated Na,K-ATPase undergoes degradation via a lysosome/proteasome dependent mechanism. PMID:17972021

Lecuona, Emilia; Trejo, Humberto E; Sznajder, Jacob I

2007-12-01

171

Arctigenin attenuates lipopolysaccharide-induced acute lung injury in rats.  

PubMed

Arctigenin (ATG) has been reported to possess anti-inflammatory properties. However, the effects of ATG on lipopolysaccharide (LPS)-induced acute lung injury (ALI) remains not well understood. In the present study, our investigation was designed to reveal the effect of ATG on LPS-induced ALI in rats. We found that ATG pretreatment attenuated the LPS-induced ALI, as evidenced by the reduced histological scores, myeloperoxidase activity, and wet-to-dry weight ratio in the lung tissues. This was accompanied by the decreased levels of tumor necrosis factor alpha (TNF-?), interleukin-1? (IL-1?), and interleukin-1 (IL-6) in the bronchoalveolar lavage fluid. Furthermore, ATG downregulated the expression of nuclear factor kappa B (NF-?B) p65, promoted the phosphorylation of inhibitor of nuclear factor-?B-? (I?B?) and activated the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK?) in the lung tissues. Our results suggested that ATG attenuates the LPS-induced ALI via activation of AMPK and suppression of NF-?B signaling pathway. PMID:25008149

Shi, Xianbao; Sun, Hongzhi; Zhou, Dun; Xi, Huanjiu; Shan, Lina

2015-04-01

172

Fatal interstitial lung disease associated with icotinib  

PubMed Central

The most serious, and maybe fatal, yet rare, adverse reaction of gefitinib and erlotinib is drug-associated interstitial lung disease (ILD), which has been often described. However, it has been less well described for icotinib, a similar orally small-molecule tyrosine kinase inhibitor (TKI). The case of a 25-year-old female patient with stage IV lung adenocarcinoma who developed fatal ILD is reported here. She denied chemotherapy, and received palliative treatment with icotinib (125 mg po, three times daily) on March 1, 2013. One month after treatment initiation, the patient complained of continuous dry cough and rapid progressive dyspnea. Forty one days after icotinib treatment, icotinib associated ILD was suspected when the patient became increasingly dyspnoeic despite of treatment of pericardial effusion, left pleural effusion and lower respiratory tract infection, and X-ray computed tomography (CT) of chest revealed multiple effusion shadows and ground-glass opacities in bilateral lungs. Then, icotinib was discontinued and intravenous corticosteroid was started (methylprednisolone 40 mg once daily, about 1 mg per kilogram) respectively. Forty three days after icotinib treatment, the patient died of hypoxic respiratory failure. ILD should be considered as a rare, but often fatal side effect associated with icotinib treatment. PMID:25590006

Zhang, Jiexia; Zhan, Yangqing; Ouyang, Ming; Qin, Yinyin; Zhou, Chengzhi

2014-01-01

173

Nicotine Exerts an Anti-inflammatory Effect in a Murine Model of Acute Lung Injury  

PubMed Central

Activation of the cholinergic anti-inflammatory pathway through direct activation of nicotinic acetylcholine receptors on immune cells can inhibit pro-inflammatory chemokine and cytokine release and thereby protect in a variety of inflammatory diseases. The aim of this study was to investigate whether nicotine treatment protected against acute lung inflammation. Mice challenged with intratracheal lipopolysaccharide (LPS, 50 ?g) were treated with nicotine (0.2 or 0.4 mg/kg, sc). After 24 h, bronchoalveolar lavage fluid (BALF) was obtained to measure leukocyte infiltration, lung edema, and pro-inflammatory chemokine (MIP-1?, MIP-2, and eotaxin) and cytokine (IL-1, IL-6, and TNF-?) levels. Nicotine treatment reduced the LPS-mediated infiltration of leukocytes and edema as evidenced by decreased BALF inflammatory cells, myeloperoxidase, and protein. Nicotine also downregulated lung production of pro-inflammatory chemokines and cytokines. These data support the proposal that activation of the cholinergic anti-inflammatory pathway may represent a useful addition to the therapy of acute respiratory distress syndrome. PMID:20625922

Mabley, Jon; Gordon, Sevelanne; Pacher, Pal

2010-01-01

174

Image based diagnostic aid system for interstitial lung diseases  

Microsoft Academic Search

Automatic classification of lung tissue patterns in high-resolution computed tomography (HRCT) images of patients affected with interstitial lung diseases (ILD) is an important stage in the construction of a computer-aided diagnosis system. In this study, we propose a new image based system for classification of lung tissue patterns. The proposed system comprises three stages. In the first stage, the parenchyma

Azar Tolouee; Hamid Abrishami Moghaddam; Mohamad Forouzanfar; Masoumeh Gity; Rahil Garnavi

2011-01-01

175

Reflux esophagitis in war-related sulfur mustard lung disease  

PubMed Central

Background Sulfur mustard (SM) has acute and chronic effects on skin and mucosal surfaces. The aim of the study was to evaluate the frequency of esophagitis in a historical cohort of veterans who had been exposed to SM in Iran-Iraq war nearly 25 years ago. Methods: One hundred two veterans with dyspepsia and/or heartburn underwent esophago-gastroduodenoscopy. Of them, 52 cases had been exposed to SM and had chronic mustard lung disease. Controls included 50 veterans without SM exposure. Esophagitis was defined according to standard criteria. Results: 81.6% of cases and 70.6% of controls had heart burn and/or regurgitation (p= 0.224). Esophagitis was seen in 40% of cases and 26.5% of controls (p= 0.155). Conclusion: Based on our findings, SM exposure seems not to be associated with increased esophagitis. PMID:25250271

Roushan, Nader; Zali, Fateme; Abtahi, Hamidreza; Asadi, Mehrnaz; Taslimi, Reza; Aletaha, Najme

2014-01-01

176

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

PubMed Central

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

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

2013-01-01

177

Pathogenetic and prognostic significance of altered coagulation and fibrinolysis in acute lung injury/acute respiratory distress syndrome*  

PubMed Central

Objective The coagulation and inflammatory cascades may be linked in the pathogenesis of acute lung injury and acute respiratory distress syndrome. However, direct evidence for the contribution of abnormalities in coagulation and fibrinolysis proteins to outcomes in patients with acute lung injury/acute respiratory distress syndrome is lacking. Design Retrospective measurement of plasma levels of protein C and plasminogen activator inhibitor-1 in plasma samples that were collected prospectively as part of a large multicenter clinical trial. The primary outcome was hospital mortality. To evaluate the potential additive value of abnormalities of these biomarkers, the excess relative risk of death was calculated for each combination of quartiles of protein-C and plasminogen activator inhibitor-1 levels. Setting Ten university medical centers. Patients The study included 779 patients from a multicenter clinical trial of a protective ventilatory strategy in acute lung injury/acute respiratory distress syndrome and 99 patients with acute cardiogenic pulmonary edema, as well as ten normal controls. Measurements and Main Results Compared with plasma from controls and patients with acute cardiogenic pulmonary edema, baseline protein-C levels were low and baseline plasminogen activator inhibitor-1 levels were elevated in acute lung injury/acute respiratory distress syndrome. By multivariate analysis, lower protein C and higher plasminogen activator inhibitor-1 were strong independent predictors of mortality, and ventilator-free and organ-failure-free days. Plasminogen activator inhibitor-1 and protein C had a synergistic interaction for the risk of death. Conclusions Early acute lung injury/acute respiratory distress syndrome is characterized by decreased plasma levels of protein C and increased plasma levels of plasminogen activator inhibitor-1 that are independent risk factors for mortality and adverse clinical outcomes. Measurement of plasminogen activator inhibitor-1 and protein-C levels may be useful to identify those at highest risk of adverse clinical outcomes for the development of new therapies. PMID:17667242

Ware, Lorraine B.; Matthay, Michael A.; Parsons, Polly E.; Thompson, B. Taylor; Januzzi, James L.; Eisner, Mark D.

2009-01-01

178

Higher urine desmosine levels are associated with mortality in patients with acute lung injury  

PubMed Central

Desmosine is a stable breakdown product of elastin that can be reliably measured in urine samples. We tested the hypothesis that higher baseline urine desmosine would be associated with higher mortality in 579 of 861 patients included in the recent Acute Respiratory Distress Syndrome Network trial of lower tidal volume ventilation (1). We also correlated urine desmosine levels with indexes of disease severity. Finally, we assessed whether urine desmosine was lower in patients who received lower tidal volumes. Desmosine was measured by radioimmunoassay in urine samples from days 0, 1, and 3 of the study. The data were expressed as a ratio of urine desmosine to urine creatinine to control for renal dilution. The results show that higher baseline (day 0) urine desmosine-to-creatinine concentration was associated with a higher risk of death on adjusted analysis (odds ratio 1.36, 95% confidence interval 1.02-1.82, P = 0.03). Urine desmosine increased in both ventilator groups from day 0 to day 3, but the average rise was higher in the 12-ml/kg predicted body weight group compared with the 6-ml/kg predicted body weight group (P = 0.053, repeated-measures model). In conclusion, patients with acute lung injury ventilated with lower tidal volumes have lower urine desmosine levels, a finding that may reflect reduced extracellular matrix breakdown. These results illustrate the value of evaluating urinary biological markers that may have prognostic and pathogenetic significance in acute lung injury. PMID:16698854

McClintock, Dana E.; Starcher, Barry; Eisner, Mark D.; Thompson, B. Taylor; Hayden, Doug L.; Church, Gwynne D.; Matthay, Michael A.

2009-01-01

179

Traditional Chinese medicine, Qing Ying Tang, ameliorates the severity of acute lung injury induced by severe acute pancreatitis in rats via the upregulation of aquaporin-1  

PubMed Central

Aquaporin-1 (AQP-1) is expressed in lung endothelial cells and regulates water transport; thus, AQP-1 plays an important role in a number of edema-associated lung diseases. Qing Yin Tang (QYT), a traditional Chinese medicine, has been shown to effectively reduce the mortality rate of acute lung injury (ALI) induced by severe acute pancreatitis (SAP). The current study aimed to investigate the detailed mechanisms underlying the effects of QYT on ALI induced by SAP, particularly the effects on the expression levels of AQP-1 in the lung tissue. ALI was established in Wister rats who were subsequently divided into four groups: SHAM, ALI, dexamethasone (DEX) and QYT groups (n=8 per group). In the QYT group, 20 ml/kg QYT was administered by gavage immediately following the induction of SAP. Blood and lung tissues were collected 8 h following the induction of pancreatitis. The lung wet/dry ratio, as well as the levels of blood gases, serum amylase and tumor necrosis factor-? (TNF-?), were measured at 4, 8 and 12 h following SAP-associated ALI induction surgery. The expression levels of AQP-1 in the lung tissue were detected by quantitative polymerase chain reaction, immunohistochemistry and western blot analysis. No statistically significant differences were observed with regard to the levels of serum amylase, wet/dry ratio, partial pressure of oxygen, serum TNF-? and pathological changes in the pulmonary tissue between the QYT and DEX groups; however, a statistically significant difference was observed when compared with the ALI group. The expression levels of AQP-1 significantly increased (P<0.05) and lung edema was alleviated in the QYT and DEX groups, when compared with ALI group. Therefore, the expression level of AQP-1 is associated with pulmonary edema. QYT protects the lungs from injury induced by SAP via the upregulation of AQP-1, which suppresses TNF-? expression. PMID:25371738

GAO, ZHENMING; XU, JUNFENG; SUN, DEGUANG; ZHANG, RIXIN; LIANG, RUI; WANG, LIMING; FAN, RONG

2014-01-01

180

Acute Heart Failure and Systemic Diseases  

Microsoft Academic Search

Acute heart failure in systemic lupus erythematosus (SLE) may result from myocarditis, endocarditis, systemic hypertension,\\u000a coronary artery disease, and left ventricular dysfunction secondary to drug toxicity. Pericarditis is an early and common\\u000a cardiac manifestation of active lupus. Moderate to severe pericardial disease is infrequent (1), and constrictive pericarditis is rare. Pericardial fluid is usually exudative (1), and may contain anti-DNA

Iris Cohen; Nadia Benyounes-Iglesias; Nadia Belmatoug; Ariel A. Cohen

181

Endothelial Semaphorin 7A Promotes Inflammation in Seawater Aspiration-Induced Acute Lung Injury  

PubMed Central

Inflammation is involved in the pathogenesis of seawater aspiration-induced acute lung injury (ALI). Although several studies have shown that Semaphorin 7A (SEMA7A) promotes inflammation, there are limited reports regarding immunological function of SEMA7A in seawater aspiration-induced ALI. Therefore, we investigated the role of SEMA7A during seawater aspiration-induced ALI. Male Sprague–Dawley rats were underwent seawater instillation. Then, lung samples were collected at an indicated time for analysis. In addition, rat pulmonary microvascular endothelial cells (RPMVECs) were cultured and then stimulated with 25% seawater for indicated time point. After these treatments, cells samples were collected for analysis. In vivo, seawater instillation induced lung histopathologic changes, pro-inflammation cytokines release and increased expression of SEMA7A. In vitro, seawater stimulation led to pro-inflammation cytokine release, cytoskeleton remodeling and increased monolayer permeability in pulmonary microvascular endothelial cells. In addition, knockdown of hypoxia-inducible factor (HIF)-1? inhibited the seawater induced increase expression of SEMA7A. Meanwhile, knockdown of SEMA7A by specific siRNA inhibited the seawater induced aberrant inflammation, endothelial cytoskeleton remodeling and endothelial permeability. These results suggest that SEMA7A is critical in the development of lung inflammation and pulmonary edema in seawater aspiration-induced ALI, and may be a therapeutic target for this disease. PMID:25353180

Zhang, Minlong; Wang, Li; Dong, Mingqing; Li, Zhichao; Jin, Faguang

2014-01-01

182

Anti-Inflammatory Effects of Ellagic Acid on Acute Lung Injury Induced by Acid in Mice  

PubMed Central

Acute lung injury (ALI) is characterized by alveolar edema and uncontrolled neutrophil migration to the lung, and no specific therapy is still available. Ellagic acid, a compound present in several fruits and medicinal plants, has shown anti-inflammatory activity in several experimental disease models. We used the nonlethal acid aspiration model of ALI in mice to determine whether preventive or therapeutic administration of ellagic acid (10?mg/kg; oral route) could interfere with the development or establishment of ALI inflammation. Dexamethasone (1?mg/kg; subcutaneous route) was used as a positive control. In both preventive and therapeutic treatments, ellagic acid reduced the vascular permeability changes and neutrophil recruitment to the bronchoalveolar lavage fluid (BALF) and to lung compared to the vehicle. In addition, the ellagic acid accelerated the resolution for lung neutrophilia. Moreover, ellagic acid reduced the COX-2-induced exacerbation of inflammation. These results were similar to the dexamethasone. However, while the anti-inflammatory effects of dexamethasone treatment were due to the reduced activation of NF-?B and AP-1, the ellagic acid treatment led to reduced BALF levels of IL-6 and increased levels of IL-10. In addition, dexamethasone treatment reduced IL-1?. Together, these findings identify ellagic acid as a potential therapeutic agent for ALI-associated inflammation. PMID:23533300

Cornélio Favarin, Daniely; Martins Teixeira, Maxelle; Lemos de Andrade, Ednéia; de Freitas Alves, Claudiney; Lazo Chica, Javier Emilio; Artério Sorgi, Carlos; Paula Rogerio, Alexandre

2013-01-01

183

Acute effects of volcanic ash from Mount Saint Helens on lung function in children.  

PubMed

To evaluate the acute effects of volcanic ash from Mt. St. Helens on the lung function of children, we studied 101 children 8 to 13 yr of age who were attending a 2-wk summer camp for children with diabetes mellitus in an area where about 1.2 cm of ash had fallen after the June 12, 1980, eruption. The outcome variables used were forced vital capacity, forced expiratory volume in one second, their ratio and mean transit time. Total and respirable dust levels were measured using personal sampling pumps. The children were tested on arrival and twice (early morning [A.M.] and late afternoon [P.M.]) every second or third day during the session. A within-day effect was measured by the P.M./A.M. ratio for the lung function variables; a between-day effect was measured by the change in the P.M. measurements over the 2 wk of camp. We found no strong evidence of either a within-day or a between-day effect on lung function, even in a subgroup of children who had preexisting lung disease or symptoms, despite daytime dust/ash levels that usually exceeded the Environmental Protection Agency's significant harm level for particulate matter. PMID:6859654

Buist, A S; Johnson, L R; Vollmer, W M; Sexton, G J; Kanarek, P H

1983-06-01

184

Pulmonary hypertension complicating interstitial lung disease and COPD.  

PubMed

Pulmonary hypertension (PH) may complicate parenchymal lung disease, specifically interstitial lung diseases and chronic obstructive pulmonary disease, and uniformly increases the mortality risk. The epidemiology and degree of PH is variable and unique to the underlying lung disease. The clinician should exercise a high index of suspicion for PH complicating parenchymal lung disease especially given the nonspecific symptomatology and the limitations of echocardiography in this patient population. In general, PH-specific therapies in this setting have been poorly studied, with concern for increased shunting and/or ventilation/perfusion (V/Q) mismatch and resultant hypoxemia. A better understanding of the mechanisms underlying PH related to parenchymal lung disease may lead to novel pharmacological targets to prevent or treat this serious complication. PMID:24037628

Shino, Michael Y; Lynch, Joseph P; Saggar, Rajeev; Abtin, Fereidoun; Belperio, John A; Saggar, Rajan

2013-10-01

185

Malfolded Protein Structure and Proteostasis in Lung Diseases  

PubMed Central

Recent discoveries indicate that disorders of protein folding and degradation play a particularly important role in the development of lung diseases and their associated complications. The overarching purpose of the National Heart, Lung, and Blood Institute workshop on “Malformed Protein Structure and Proteostasis in Lung Diseases” was to identify mechanistic and clinical research opportunities indicated by these recent discoveries in proteostasis science that will advance our molecular understanding of lung pathobiology and facilitate the development of new diagnostic and therapeutic strategies for the prevention and treatment of lung disease. The workshop's discussion focused on identifying gaps in scientific knowledge with respect to proteostasis and lung disease, discussing new research advances and opportunities in protein folding science, and highlighting novel technologies with potential therapeutic applications for diagnosis and treatment. PMID:24033344

Balch, William E.; Sznajder, Jacob I.; Budinger, Scott; Finley, Daniel; Laposky, Aaron D.; Cuervo, Ana Maria; Benjamin, Ivor J.; Barreiro, Esther; Morimoto, Richard I.; Postow, Lisa; Weissman, Allan M.; Gail, Dorothy; Banks-Schlegel, Susan; Croxton, Thomas

2014-01-01

186

Biomarkers in Acute Lung Injury – Marking Forward Progress  

PubMed Central

In this article we review the ‘state of the art’ with regards to biomarkers for prediction, diagnosis and prognosis in acute lung injury (ALI). We begin by defining biomarkers and the goals of biomarker research in ALI including their ability to define more homogenous populations for recruitment into trials of novel therapies as well as to identify important biological pathways in the pathogenesis of ALI. Progress along four general routes is then examined. First the results of wide-ranging existing protein biomarkers are reported. Secondly, we describe newer biomarkers awaiting or with strong potential for validation. Thirdly, we report progress in the fields of genomics and proteomics. Finally given the complexity and number of potential biomarkers, we examine the results of combining clinical predictors with protein and other biomarkers to produce better prognostic and diagnostic indices. PMID:21742222

Barnett, Nicolas; Ware, Lorraine B.

2011-01-01

187

Role of Macrophage Migration Inhibitory Factor in Acute Lung Injury in Mice with Acute Pancreatitis Complicated by Endotoxemia  

Microsoft Academic Search

Acute pancreatitis accompanied by a subsequent infectious attack can often lead to multisystem organ dysfunction, including acute lung injury (ALI), but the molecular mechanisms are poorly defined. In this study, we explored the roleof the priming insult by induction of cerulein pancreatitis, which was followed by the second attack due to endotoxemia, in the development of ALI in mice. Experi-

Naoyuki Matsuda; Jun Nishihira; Yoshika Takahashi; Osamu Kemmotsu; Yuichi Hattori

188

Minimal acute rejection in pediatric lung transplantation does it matter?  

PubMed Central

In adult lung transplantation, a single minimal acute rejection (AR) episode is a significant predictor of bronchiolitis obliterans syndrome (BOS) independent of other factors. However, the significance of single minimal AR episodes in children is unknown. A retrospective, multi-center analysis was performed to determine if isolated single AR episodes are associated with an increased BOS risk in children. Risk factors for BOS, death or re-transplantation, and a combined outcome of BOS, death or re-transplantation were assessed. Original data included 577 patients (<21 yr of age). 383 subjects were eligible for the study. 15% of patients developed BOS, 13% either died or underwent re-transplant within one year post-transplant. In the multivariable survival model for time to BOS, there was no significant risk to developing BOS after a single minimal AR (A1) episode (HR 1.7, 95% CI 0.64–4.8; p=0.28). Even after a second minimal AR episode, no significant risk for BOS was appreciated. However, a single episode of mild AR (A2) was associated with twice the risk of BOS within one year post-transplant. In this select cohort, a single minimal AR episode was not associated with an increased risk for BOS within one year following lung transplantation, in contrast to previous reports in adults. PMID:20059725

Benden, Christian; Faro, Albert; Worley, Sarah; Arrigain, Susana; Aurora, Paul; Ballmann, Manfred; Boyer, Debra; Conrad, Carol; Eichler, Irmgard; Elidemir, Okan; Goldfarb, Samuel; Mallory, George B; Mogayzel, Peter J; Parakininkas, Daiva; Solomon, Melinda; Visner, Gary; Sweet, Stuart C; Danziger-Isakov, Lara A

2009-01-01

189

Blue journal conference. Aging and susceptibility to lung disease.  

PubMed

The aging of the population in the United States and throughout the developed world has increased morbidity and mortality attributable to lung disease, while the morbidity and mortality from other prevalent diseases has declined or remained stable. Recognizing the importance of aging in the development of lung disease, the American Thoracic Society (ATS) highlighted this topic as a core theme for the 2014 annual meeting. The relationship between aging and lung disease was discussed in several oral symposiums and poster sessions at the annual ATS meeting. In this article, we used the input gathered at the conference to develop a broad framework and perspective to stimulate basic, clinical, and translational research to understand how the aging process contributes to the onset and/or progression of lung diseases. A consistent theme that emerged from the conference was the need to apply novel, systems-based approaches to integrate a growing body of genomic, epigenomic, transcriptomic, and proteomic data and elucidate the relationship between biologic hallmarks of aging, altered lung function, and increased susceptibility to lung diseases in the older population. The challenge remains to causally link the molecular and cellular changes of aging with age-related changes in lung physiology and disease susceptibility. The purpose of this review is to stimulate further research to identify new strategies to prevent or treat age-related lung disease. PMID:25590812

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

2015-02-01

190

CHRONIC EXPOSURE TO OZONE CAUSES RESTRICTIVE LUNG DISEASE  

EPA Science Inventory

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

191

Current view of epidemiologic study designs for occupational and environmental lung diseases.  

PubMed Central

Epidemiologic studies long have played a role in the understanding of the effects of the general environment and various occupational exposures on the occurrence of acute and chronic diseases of the lung. This article is an overview of epidemiologic study designs that have particular relevance to studies of environmental and occupational lung disease. The application of times-series designs in the context of epidemiologic studies is discussed, as such designs have become widely used in studies of health effects ambient air pollution. The article emphasizes recent developments in the application of case-control study designs, many of which have had particular applications in epidemiologic studies related to environmental and occupational lung disease. These case-control designs offer efficient and valid alternatives for studies that in the past might have been conducted as more costly and time-consuming cohort studies. PMID:10931780

Tager, I B

2000-01-01

192

Stem Cells and Cell Therapy Approaches in Lung Biology and Diseases  

PubMed Central

Cell-based therapies with embryonic or adult stem cells, including induced pluripotent stem cells, have emerged as potential novel approaches for several devastating and otherwise incurable lung diseases including emphysema, pulmonary fibrosis, pulmonary hypertension, and the acute respiratory distress syndrome. Although initial studies suggested engraftment of exogenously administered stem cells in lung, this is now generally felt to be a rare occurrence of uncertain physiologic significance. However, more recent studies have demonstrated paracrine effects of administered cells, including stimulation of angiogenesis and modulation of local inflammatory and immune responses in mouse lung disease models. Based on these studies and on safety and initial efficacy data from trials of adult stem cells in other diseases, groundbreaking clinical trials of cell-based therapy have been initiated for pulmonary hypertension and for chronic obstructive pulmonary disease. In parallel, the identity and role of endogenous lung progenitor cells in development and in repair from injury and potential contribution as lung cancer stem cells continue to be elucidated. Most recently, novel bioengineering approaches have been applied to develop functional lung tissue ex vivo. Advances in each of these areas will be described in this review with particular reference to animal models. PMID:20801416

Sueblinvong, Viranuj; Weiss, Daniel J.

2013-01-01

193

Ultrahigh resolution optical coherence tomography imaging of diseased rat lung using Gaussian shaped super continuum sources  

NASA Astrophysics Data System (ADS)

We have been investigating ultrahigh resolution optical coherence tomography (UHR-OCT) imaging of lung tissues using fiber super continuum sources. The high power, low-noise, Gaussian shaped supercontinuum generated with ultrashort pulses and optical fibers at several wavelengths were used as the broadband light sources for UHR-OCT. For the 800 nm wavelength region, the axial resolution was 3.0 um in air and 2.0 um in tissue. Since the lung consists of tiny alveoli which are separated by thin wall, the UHR-OCT is supposed to be effective for lung imaging. The clear images of alveoli of rat were observed with and without index matching effects by saline. In this work, we investigated the UHR-OCT imaging of lung disease model. The lipopolysaccharide (LPS) induced acute lung injury / acute respiratory distress syndrome (ALI/ARDS) model of rat was prepared as the sample with disease and the UHR-OCT imaging of the disease part was demonstrated. The increment of signal intensity by pleural thickening was observed. The accumulation of exudative fluid in alveoli was also observed for two samples. By the comparison with normal lung images, we can obviously show the difference in the ALI/ARDS models. Since the lung consists of alveolar surrounded by capillary vessels, the effect of red-blood cells (RBC) is considered to be important. In this work, ex-vivo UHR-OCT imaging of RBC was demonstrated. Each RBC was able to be observed individually using UHR-OCT. The effect of RBC was estimated with the rat lung perfused with PBS.

Nishizawa, N.; Ishida, S.; Kitatsuji, M.; Ohshima, H.; Hasegawa, Y.; Matsushima, M.; Kawabe, T.

2012-02-01

194

Complex care: Ventilation management when brain injury and acute lung injury coexist.  

PubMed

The purpose of this article is to explore the management of coexisting brain insult and acute lung injury to help guide clinicians in balancing what may appear to be competing goals. First, contemporary management of mechanically ventilated patients with either brain or lung injury diagnoses is reviewed, followed by a review of intracranial pressure and acute lung injury/acute respiratory distress syndrome. The article ends with a discussion of a literature review regarding possible treatment balance when the two conditions coexist. PMID:24556654

Modock, Jacqueline

2014-04-01

195

Aerosol Therapy for Obstructive Lung Diseases  

PubMed Central

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

2011-01-01

196

The serpentine path to a novel mechanism-based inhibitor of acute inflammatory lung injury.  

PubMed

The Comroe lecture on which this review is based described my research path during the past 45 years, beginning with studies of oxidant stress (hyperoxia) and eventuating in the discovery of a synthetic inhibitor of phospholipase A2 activity (called MJ33) that prevents acute lung injury in mice exposed to lipopolysaccharide. In between were studies of lung ischemia, lung surfactant metabolism, the protein peroxiredoxin 6 and its phospholipase A2 activity, and mechanisms for NADPH oxidase activation. These seemingly unrelated research activities provided the nexus for identification of a novel target and a potentially novel therapeutic agent for prevention or treatment of acute lung injury. PMID:24744383

Fisher, Aron B

2014-06-15

197

Lung disease with chronic obstruction in opium smokers in Singapore  

PubMed Central

Fifty-four opium smokers with chronic obstructive lung disease were studied for two-and-a-half years. Forty-eight patients had a cough for at least two years before the onset of inappropriate exertional dyspnoea. Fine, bubbling adventitious sounds suggesting small airway disease were heard on auscultation over the middle and lower lobes in 38 patients. The prevalence of inflammatory lung disease and chronic respiratory failure in this series is suggested as the main cause for the frequent finding of right ventricular hypertrophy and congestive heart failure. Physiological studies revealed moderate to severe airways obstruction with gross over-inflation and, in 32 patients, an additional restrictive defect probably due to peribronchiolar fibrosis. Radiological evidence of chronic bronchitis and bronchiolitis was observed in 45 patients, `pure' chronic bronchiolitis in six patients, and `widespread' emphysema in 25 patients respectively. Necropsy examinations in nine patients, however, showed destructive emphysema of variable severity in all. Chronic bronchiolitis often associated with striking bronchiolectasis was present in six cases. More severe bronchiolar rather than bronchial inflammation was noted. The heavy opium smokers had characteristic nodular shadows on chest radiography, sometimes associated with a striking reticular pattern not seen in `pure' cigarette smokers. This was due to gross pigmented dust (presumably carbon) deposition in relation to blood vessels, lymphatics, and bronchioles, and also within the alveoli. It is speculated that the initial lesion is an acquired bronchiolitis. Opium smoking induces an irritative bronchopathy favouring repeated attacks of acute bronchiolitis and eventually resulting in obliterative bronchiolitis, peribronchiolar fibrosis, chronic bronchitis, and destructive emphysema. Images PMID:5134057

Da Costa, J. L.; Tock, E. P. C.; Boey, H. K.

1971-01-01

198

Bone Marrow Mesenchymal Stem Cells Ameliorates Seawater-Exposure-Induced Acute Lung Injury by Inhibiting Autophagy in Lung Tissue  

PubMed Central

Seawater drowning can lead to acute lung injury (ALI). Several studies have shown that bone marrow mesenchymal stem cells (BMSC) treatment could attenuate ALI. However, the mechanisms underlying this phenomenon still remain elusive. Therefore, this study aimed to investigate whether BMSC treatment can ameliorate seawater-induced ALI and its underlying mechanisms in a rat model. In this study, arterial blood gas, lung weight coefficient, and TNF-?, and IL-8 in bronchoalveolar lavage fluid (BALF), as well as histopathology examination, were used to detect the lung injury of seawater exposure. Moreover, western blot and RT-PCR were used to explore autophagy in lung tissues. The results demonstrated that seawater exposure induced ALI including impaired arterial blood gas, pulmonary edema, histopathologic changes, and inflammatory response in lung tissues. What is more, these changes were partly ameliorated by BMSC treatment through inhibition of autophagy in lung tissues. The application of BMSC may be a potential effective treatment for seawater-induced ALI. PMID:25215261

Liu, Qiu-ping; Zhou, Dang-xia; Sun, Li; Ling, Luo; Wu, Chang-gui; Lin, Pu; Han, Shui-ping

2014-01-01

199

Development of a Multicomponent Prediction Model for Acute Esophagitis in Lung Cancer Patients Receiving Chemoradiotherapy  

SciTech Connect

Purpose: To construct a model for the prediction of acute esophagitis in lung cancer patients receiving chemoradiotherapy by combining clinical data, treatment parameters, and genotyping profile. Patients and Methods: Data were available for 273 lung cancer patients treated with curative chemoradiotherapy. Clinical data included gender, age, World Health Organization performance score, nicotine use, diabetes, chronic disease, tumor type, tumor stage, lymph node stage, tumor location, and medical center. Treatment parameters included chemotherapy, surgery, radiotherapy technique, tumor dose, mean fractionation size, mean and maximal esophageal dose, and overall treatment time. A total of 332 genetic polymorphisms were considered in 112 candidate genes. The predicting model was achieved by lasso logistic regression for predictor selection, followed by classic logistic regression for unbiased estimation of the coefficients. Performance of the model was expressed as the area under the curve of the receiver operating characteristic and as the false-negative rate in the optimal point on the receiver operating characteristic curve. Results: A total of 110 patients (40%) developed acute esophagitis Grade {>=}2 (Common Terminology Criteria for Adverse Events v3.0). The final model contained chemotherapy treatment, lymph node stage, mean esophageal dose, gender, overall treatment time, radiotherapy technique, rs2302535 (EGFR), rs16930129 (ENG), rs1131877 (TRAF3), and rs2230528 (ITGB2). The area under the curve was 0.87, and the false-negative rate was 16%. Conclusion: Prediction of acute esophagitis can be improved by combining clinical, treatment, and genetic factors. A multicomponent prediction model for acute esophagitis with a sensitivity of 84% was constructed with two clinical parameters, four treatment parameters, and four genetic polymorphisms.

De Ruyck, Kim, E-mail: kim.deruyck@UGent.be [Department of Basic Medical Sciences, Ghent University, Ghent (Belgium); Sabbe, Nick [Department of Applied Mathematics, Biometrics and Process Control, Ghent University, Ghent (Belgium); Oberije, Cary [Department of Radiation Oncology (MAASTRO Clinic), Research Institute of Growth and Development, Maastricht University Medical Center, Maastricht (Netherlands); Vandecasteele, Katrien [Department of Radiation Oncology, Ghent University Hospital, Ghent (Belgium); Thas, Olivier [Department of Applied Mathematics, Biometrics and Process Control, Ghent University, Ghent (Belgium); De Ruysscher, Dirk; Lambin, Phillipe [Department of Radiation Oncology (MAASTRO Clinic), Research Institute of Growth and Development, Maastricht University Medical Center, Maastricht (Netherlands); Van Meerbeeck, Jan [Department of Respiratory Medicine, Ghent University Hospital, Ghent (Belgium); De Neve, Wilfried [Department of Radiation Oncology, Ghent University Hospital, Ghent (Belgium); Thierens, Hubert [Department of Basic Medical Sciences, Ghent University, Ghent (Belgium)

2011-10-01

200

Role of MicroRNAs in lung disease.  

PubMed

MicroRNAs (miRNAs) are small non-coding RNA molecules that negatively regulate gene expression. They actively participate in the modulation of important cell physiological processes and are involved in the pathogenesis of lung diseases such as lung cancer, pulmonary fibrosis, asthma and chronic obstructive pulmonary disease. A better understanding of the role that miRNAs play in these diseases could lead to the development of new diagnostic and therapeutic tools. In this review, we discuss the role of some miRNAs in different lung diseases as well as the possible future of these discoveries in clinical applications. PMID:22607962

Angulo, Martín; Lecuona, Emilia; Sznajder, Jacob Iasha

2012-09-01

201

Role of MicroRNAs in Lung Disease?  

PubMed Central

MicroRNAs (miRNAs) are small non-coding RNA molecules that negatively regulate gene expression. They actively participate in the modulation of important cell physiological processes and are involved in the pathogenesis of lung diseases such as lung cancer, pulmonary fibrosis, asthma and chronic obstructive pulmonary disease. A better understanding of the role that miRNAs play in these diseases could lead to the development of new diagnostic and therapeutic tools. In this review, we discuss the role of some miRNAs in different lung diseases as well as the possible future of these discoveries in clinical applications. PMID:22607962

Angulo, Martín; Lecuona, Emilia; Sznajder, Jacob Iasha

2013-01-01

202

Loss of Extracellular Superoxide Dismutase Leads to Acute Lung Damage in the Presence of Ambient Air  

PubMed Central

The extracellular superoxide dismutase 3 (SOD3) is highly expressed in both blood vessels and lungs. In different models of pulmonary injury, SOD3 is reduced; however, it is unclear whether this contributes to lung injury. To study the role of acute SOD3 reduction in lung injury, the SOD3 gene was deleted in adult mice by using the Cre-Lox technology. Acute reduction of SOD3 led to a fivefold increase in lung superoxide, marked inflammatory cell infiltration, a threefold increase in the arterial-alveolar gradient, respiratory acidosis, histological changes similar to those observed in adult respiratory distress syndrome, and 85% mortality. Treatment with the SOD mimetic MnTBAP and intranasal administration of SOD-containing polyketal microparticles reduced mortality, prevented the histological alterations, and reduced lung superoxide levels. To understand how mice with the SOD3 embryonic deletion survived without lung injury, gene array analysis was performed. These data demonstrated the up-regulation of 37 genes and down-regulation of nine genes, including those involved in cell signaling, inflammation, and gene transcription in SOD3?/? mice compared with either mice with acute SOD3 reduction or wild-type controls. These studies show that SOD3 is essential for survival in the presence of ambient oxygen and that acute loss of this enzyme can lead to severe lung damage. Strategies either to prevent SOD3 inactivation or to augment its levels might prove useful in the treatment of acute lung injury. PMID:18787098

Gongora, Maria Carolina; Lob, Heinrich E.; Landmesser, Ulf; Guzik, Tomasz J.; Martin, W. David; Ozumi, Kiyoski; Wall, Susan M.; Wilson, David Scott; Murthy, Niren; Gravanis, Michael; Fukai, Tohru; Harrison, David G.

2008-01-01

203

Wnt signalling in lung development and diseases  

Microsoft Academic Search

There are several signalling pathways involved in lung organogenesis including Notch, TGF? \\/BMP, Sonic hedgehog (Shh), FGF, EGF, and Wnt. Despite the widely acknowledged significance of Wnt signalling in embryonic lung development, the role of different Wnt pathways in lung pathologies has been slow to emerge. In this review, we will present a synopsis of current Wnt research with particular

Judit E Pongracz; Robert A Stockley

2006-01-01

204

Sirtinol Inhibits Neutrophil Elastase Activity and Attenuates Lipopolysaccharide-Mediated Acute Lung Injury in Mice  

PubMed Central

Enhanced activity of neutrophil elastase leads to a protease–antiprotease imbalance, and plays an essential pathogenic role in acute lung injury (ALI) and acute respiratory distress syndrome. We assayed the pharmacological effects and mechanisms of the action of sirtinol in human neutrophils, and in neutrophil elastase (HNE)-induced paw edema and lipopolysaccharide (LPS)-mediated ALI in mice. Sirtinol significantly inhibited the activity of HNE from human neutrophils in response to various stimulators. The inhibitory effects on HNE activity were not mediated through protein kinase A, calcium, extracellular-regulated kinase, c-Jun N-terminal kinase, p38 mitogen-activated protein kinase, Akt, or Src family kinases. Analysis of enzymatic activities showed that sirtinol inhibited HNE activity in a concentration-dependent manner. These results demonstrate that sirtinol does not affect neutrophil function and is an HNE inhibitor. In addition, administration of sirtinol significantly inhibited HNE-induced paw edema, and attenuated the myeloperoxidase activity and reduced pulmonary wet/dry weight ratio in the LPS-induced ALI mouse model. Our study indicates that sirtinol has anti-inflammatory effects through direct inhibition of HNE activity and attenuates HNE-induced and LPS-mediated tissue or organ injury in vivo. Sirtinol is a novel HNE inhibitor and may have the potential for clinical application in the treatment of inflammatory lung diseases. PMID:25666548

Tsai, Yung-Fong; Yu, Huang-Ping; Chang, Wen-Yi; Liu, Fu-Chao; Huang, Zhen-Cheng; Hwang, Tsong-Long

2015-01-01

205

Sirtinol inhibits neutrophil elastase activity and attenuates lipopolysaccharide-mediated acute lung injury in mice.  

PubMed

Enhanced activity of neutrophil elastase leads to a protease-antiprotease imbalance, and plays an essential pathogenic role in acute lung injury (ALI) and acute respiratory distress syndrome. We assayed the pharmacological effects and mechanisms of the action of sirtinol in human neutrophils, and in neutrophil elastase (HNE)-induced paw edema and lipopolysaccharide (LPS)-mediated ALI in mice. Sirtinol significantly inhibited the activity of HNE from human neutrophils in response to various stimulators. The inhibitory effects on HNE activity were not mediated through protein kinase A, calcium, extracellular-regulated kinase, c-Jun N-terminal kinase, p38 mitogen-activated protein kinase, Akt, or Src family kinases. Analysis of enzymatic activities showed that sirtinol inhibited HNE activity in a concentration-dependent manner. These results demonstrate that sirtinol does not affect neutrophil function and is an HNE inhibitor. In addition, administration of sirtinol significantly inhibited HNE-induced paw edema, and attenuated the myeloperoxidase activity and reduced pulmonary wet/dry weight ratio in the LPS-induced ALI mouse model. Our study indicates that sirtinol has anti-inflammatory effects through direct inhibition of HNE activity and attenuates HNE-induced and LPS-mediated tissue or organ injury in vivo. Sirtinol is a novel HNE inhibitor and may have the potential for clinical application in the treatment of inflammatory lung diseases. PMID:25666548

Tsai, Yung-Fong; Yu, Huang-Ping; Chang, Wen-Yi; Liu, Fu-Chao; Huang, Zhen-Cheng; Hwang, Tsong-Long

2015-01-01

206

The Role of Fibrocytes in Sickle Cell Lung Disease  

PubMed Central

Background Interstitial lung disease is a frequent complication in sickle cell disease and is characterized by vascular remodeling and interstitial fibrosis. Bone marrow-derived fibrocytes have been shown to contribute to the pathogenesis of other interstitial lung diseases. The goal of this study was to define the contribution of fibrocytes to the pathogenesis of sickle cell lung disease. Methodology/Principal Findings Fibrocytes were quantified and characterized in subjects with sickle cell disease or healthy controls, and in a model of sickle cell disease, the NY1DD mouse. The role of the chemokine ligand CXCL12 in trafficking of fibrocytes and phenotype of lung disease was examined in the animal model. We found elevated concentration of activated fibrocytes in the peripheral blood of subjects with sickle cell disease, which increased further during vaso-occlusive crises. There was a similar elevations in the numbers and activation phenotype of fibrocytes in the bone marrow, blood, and lungs of the NY1DD mouse, both at baseline and under conditions of hypoxia/re-oxygenation. In both subjects with sickle cell disease and the mouse model, fibrocytes expressed a hierarchy of chemokine receptors, with CXCR4 expressed on most fibrocytes, and CCR2 and CCR7 expressed on a smaller subset of cells. Depletion of the CXCR4 ligand, CXCL12, in the mouse model resulted in a marked reduction of fibrocyte trafficking into the lungs, reduced lung collagen content and improved lung compliance and histology. Conclusions These data support the notion that activated fibrocytes play a significant role in the pathogenesis of sickle cell lung disease. PMID:22442712

Field, Joshua J.; Burdick, Marie D.; DeBaun, Michael R.; Strieter, Brett A.; Liu, Ling; Mehrad, Borna; Rose, C. Edward; Linden, Joel; Strieter, Robert M.

2012-01-01

207

Inflammatory Lung Disease in Rett Syndrome  

PubMed Central

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

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

208

Inflammatory lung disease in Rett syndrome.  

PubMed

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

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

209

Effect of high-dose pentoxifylline on acute radiation-induced lung toxicity in a rat lung perfusion model  

Microsoft Academic Search

Purpose: The purpose of this study was to study the effect of high-dose oral pentoxifylline on radiation-induced acute lung injury as assessed with a rat lung perfusion model.Methods and Materials: Adult male Sprague-Dawley rats were used throughout this study. A preliminary experiment determined that treatment with 2 g\\/liter pentoxifylline in drinking water resulted in an average consumption of 1.38 g\\/m2\\/day,

Keith J. Stelzer; Wui-Jin Koh; Lanell M. Peterson; Thomas W. Griffin

1996-01-01

210

Colonic metastases from small cell carcinoma of the lung presenting with an acute abdomen: A case report  

PubMed Central

Introduction Colonic metastases are rare, and usually secondary from malignant tumours of the stomach, breast, ovarian, cervix, kidney, lung, prostate, or skin. Around one third are asymptomatic or found only at autopsy. Case Report A middle-aged male smoker, who had a small cell carcinoma of the lung diagnosed two years previously and treated with radiotherapy and chemotherapy, was admitted to the emergency room with intense abdominal pain and constipation. With the suspicion of an acute appendicitis he was submitted to surgery. At laparotomy he was found to have a normal appendix but two hard colonic lesions: a mobile one in the right colon and the other fixing the sigmoid colon to the sacrum. A right hemicolectomy and a sigmoid loop colostomy were performed. Pathology showed those lesions to be colonic metastases from small cell carcinoma of the lung. Discussion Colonic secondaries are most frequently diagnosed in patients who have had a known primary tumour, and may present with bowel obstruction, lower gastrointestinal haemorrhage, gastrointestinal fistula, or intestinal perforation. Presentation with acute abdomen is rare, and survival is usually limited. Conclusion Colonic metastatic disease should be considered in any patient presenting with an acute abdomen and past history of lung malignancy. PMID:25732616

Costa Almeida, Carlos Eduardo; dos Reis, Luís Simőes; Costa Almeida, Carlos Manuel

2015-01-01

211

Relationship of acute lung inflammatory injury to Fas/FasL system.  

PubMed

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

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

2005-03-01

212

Relationship of Acute Lung Inflammatory Injury to Fas/FasL System  

PubMed Central

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

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

2005-01-01

213

Kinetics of the angiogenic response in lung endothelium following acute inflammatory injury with bleomycin  

PubMed Central

Purpose/Aim Angiogenesis is a central component of normal wound healing but it has not been fully characterized in lung repair following acute inflammatory injury. The current literature lacks vital information pertaining to the extent, timing, and location of this process. This information is necessary for examining mechanisms that drive normal lung repair in resolving acute inflammatory injury. The goal of our study was to formally characterize lung angiogenesis over a time course of bleomycin induced lung injury. Materials and Methods Female C57BL/6 mice age 8-12 weeks were treated with a single dose of intratracheal bleomycin. Total lung endothelial cells were quantified with flow cytometry 0, 7, 14, 21, and 28 days following bleomycin administration, and endothelial cell replication was assessed using bromodeoxyuridine (BrdU) incorporation. Results Endothelial cell replication was maximal 14 days after bleomycin administration, while total lung endothelial cells peaked at day 21. Tissue analysis with stereology was performed to measure total lung vascular surface area in bleomycin at day 21 relative to controls and demonstrated a trend toward increased vasculature in the bleomycin group. Conclusions Angiogenesis begins shortly after injury in the bleomycin model and leads to an expansion in the lung endothelial cell population that peaks at day 21. This study offers the first longitudinal examination of angiogenesis following acute inflammatory lung injury induced by bleomycin. Information provided in this study will be vital for further investigating mechanisms of angiogenesis in both normal and abnormal lung repair. PMID:25153689

Yunt, Zulma X; Mohning, Michael P; Barthel, Lea; Kearns, Mark T; Tuder, Rubin M; Hyde, Dallas M; Henson, Peter M; Janssen, William J

2014-01-01

214

Sphingosine-1–Phosphate Receptor–3 Is a Novel Biomarker in Acute Lung Injury  

PubMed Central

The inflamed lung exhibits oxidative and nitrative modifications of multiple target proteins, potentially reflecting disease severity and progression. We identified sphingosine-1–phosphate receptor–3 (S1PR3), a critical signaling molecule mediating cell proliferation and vascular permeability, as a nitrated plasma protein in mice with acute lung injury (ALI). We explored S1PR3 as a potential biomarker in murine and human ALI. In vivo nitrated and total S1PR3 concentrations were determined by immunoprecipitation and microarray studies in mice, and by ELISA in human plasma. In vitro nitrated S1PR3 concentrations were evaluated in human lung vascular endothelial cells (ECs) or within microparticles shed from ECs after exposure to barrier-disrupting agonists (LPS, low-molecular-weight hyaluronan, and thrombin). The effects of S1PR3-containing microparticles on EC barrier function were assessed by transendothelial electrical resistance (TER). Nitrated S1PR3 was identified in the plasma of murine ALI and in humans with severe sepsis-induced ALI. Elevated total S1PR3 plasma concentrations (> 251 pg/ml) were linked to sepsis and ALI mortality. In vitro EC exposure to barrier-disrupting agents induced S1PR3 nitration and the shedding of S1PR3-containing microparticles, which significantly reduced TER, consistent with increased permeability. These changes were attenuated by reduced S1PR3 expression (small interfering RNAs). These results suggest that microparticles containing nitrated S1PR3 shed into the circulation during inflammatory lung states, and represent a novel ALI biomarker linked to disease severity and outcome. PMID:22771388

Sun, Xiaoguang; Singleton, Patrick A.; Letsiou, Eleftheria; Zhao, Jing; Belvitch, Patrick; Sammani, Saad; Chiang, Eddie T.; Moreno-Vinasco, Liliana; Wade, Michael S.; Zhou, Tong; Liu, Bin; Parastatidis, Ioannis; Thomson, Leonor; Ischiropoulos, Harry; Natarajan, Viswanathan; Jacobson, Jeffrey R.; Machado, Roberto F.; Dudek, Steven M.

2012-01-01

215

The epidemiology of interstitial lung diseases.  

PubMed

Little epidemiologic data are available on the occurrence of interstitial lung diseases (ILDs) in the general population. To describe the prevalence and incidence of ILDs a population-based registry of patients with ILDs was established in Bernalillo County, New Mexico in October 1988. All patients 18 yr of age and older who had a clinical diagnosis of an ILD were identified during the period 10/1/88 through 9/30/90 from physician referrals, hospital discharge diagnoses, histopathology reports, and death certificates. In addition, the prevalence of preclinical or undiagnosed cases was identified by screening lung specimens from 510 autopsy cases. A total of 2,936 referrals were screened; 8.8% were prevalent cases and 6.9% were incident cases. Overall, the prevalence of ILDs was 20% higher in males (80.9 per 100,000) than in females (67.2 per 100,000). Similarly the overall incidence of ILDs was slightly more common in males (31.5 per 100,000/year) than females (26.1 per 100,000/year). The estimated prevalence of preclinical or undiagnosed ILDs among all deaths was 1.8%. The most common incident diagnosed among both sexes were pulmonary fibrosis and idiopathic pulmonary fibrosis, together accounting for 46.2% of all ILD diagnoses in males and 44.2% in females. We conclude that the occurrence of ILDs in the general population may be more common than previous estimates based on selected populations, and these disorders may frequently be unrecognized. PMID:7921471

Coultas, D B; Zumwalt, R E; Black, W C; Sobonya, R E

1994-10-01

216

Dexamethasone in patients with acute lung injury from acute monocytic leukaemia.  

PubMed

The use of steroids is not required in myeloid malignancies and remains controversial in patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). We sought to evaluate dexamethasone in patients with ALI/ARDS caused by acute monocytic leukaemia (AML FAB-M5) via either leukostasis or leukaemic infiltration. Dexamethasone (10 mg every 6 h until neutropenia) was added to chemotherapy and intensive care unit (ICU) management in 20 consecutive patients between 2005 and 2008, whose data were compared with those from 20 historical controls (1994-2002). ICU mortality was the primary criterion. We also compared respiratory deterioration rates, need for ventilation and nosocomial infections. 17 (85%) patients had hyperleukocytosis, 19 (95%) had leukaemic masses, and all 20 had severe pancytopenia. All patients presented with respiratory symptoms and pulmonary infiltrates prior to AML FAB-M5 diagnosis. Compared with historical controls, dexamethasone-treated patients had a significantly lower ICU mortality rate (20% versus 50%; p = 0.04) and a trend for less respiratory deterioration (50% versus 80%; p = 0.07). There were no significant increases in the rates of infections with dexamethasone. In conclusion, in patients with ALI/ARDS related to AML FAB-M5, adding dexamethasone to conventional chemotherapy seemed effective and safe. These results warrant a controlled trial of dexamethasone versus placebo in AML FAB-M5 patients with noninfectious pulmonary infiltrates. PMID:21828031

Azoulay, É; Canet, E; Raffoux, E; Lengliné, E; Lemiale, V; Vincent, F; de Labarthe, A; Seguin, A; Boissel, N; Dombret, H; Schlemmer, B

2012-03-01

217

Circulating peripheral blood fibrocytes in human fibrotic interstitial lung disease  

Microsoft Academic Search

Fibrotic interstitial lung diseases are illnesses of unknown cause characterized by progressive decline in lung function. Fibrocytes are bone marrow-derived, circulating progenitor cells capable of differentiating into diverse mesenchymal cell types. Prior work has shown fibrocytes to traffic to the lung via the CXCL12–CXCR4 chemokine axis in an animal model of pulmonary fibrosis. We therefore assessed the relevance of fibrocytes

Borna Mehrad; Marie D. Burdick; David A. Zisman; Michael P. Keane; John A. Belperio; Robert M. Strieter

2007-01-01

218

Ventilation-perfusion scan in the acutely ill patient with unilateral hyperlucent lung  

SciTech Connect

A patient with a unilateral hyperlucent lung with acute respiratory complaints is presented. A ventilation-perfusion scan was performed to rule out pulmonary embolism. The perfusion scan ( (/sup 99m/TC)MAA) showed peripheral perfusion defects in the hyperlucent lung. The ventilation study (/sup 133/Xe) demonstrated peripheral ventilatory defects on the single breath image in the hyperlucent lung, the filling in of these on the equilibrium view, and diffusely delayed washout in the affected lung. These findings were suggestive of the Swyer-James syndrome and critical in excluding the numerous other causes of unilateral hyperlucent lung, which are discussed. The importance of the ventilation-perfusion study (and particularly the ventilation scan) in the patient with unilateral hyperlucent lung and acute respiratory symptoms is stressed. In addition, a discussion of the Swyer-James syndrome is included.

Miller, M.B.; Caride, V.J.

1988-01-01

219

Oxygen therapy in acute exacerbations of chronic obstructive pulmonary disease  

PubMed Central

Acute exacerbations of chronic obstructive pulmonary disease (COPD) are important events in the history of this debilitating lung condition. Associated health care utilization and morbidity are high, and many patients require supplemental oxygen or ventilatory support. The last 2 decades have seen a substantial increase in our understanding of the best way to manage the respiratory failure suffered by many patients during this high-risk period. This review article examines the evidence underlying supplemental oxygen therapy during exacerbations of COPD. We first discuss the epidemiology and pathophysiology of respiratory failure in COPD during exacerbations. The rationale and evidence underlying oxygen therapy, including the risks when administered inappropriately, are then discussed, along with further strategies for ventilatory support. We also review current recommendations for best practice, including methods for improving oxygen provision in the future. PMID:25404854

Brill, Simon E; Wedzicha, Jadwiga A

2014-01-01

220

Neurofibromatosis-associated diffuse lung disease: case report.  

PubMed

Since the initial report in 1963 several small case series described an association between neurofibromatosis (NF) and interstitial lung disease. To date, more than 60 cases of interstitial lung disease associated with NF have been reported, but relatively few reports included high-resolution computed tomographic (HRCT) scans. Typical findings on HRCT include upper lobe predominant cystic and bullous disease, ground-glass opacification, and basilar reticular abnormalities. We present the case of a 34-year-old male smoker with NF and HRCT findings of diffuse lung disease including bullous emphysema, thin-walled cysts, and diffuse ground glass. Although NF-associated diffuse lung disease (NF-DLD) is disputed as a clinical entity by some, the case presented here adds to the accumulating evidence that NF-DLD is a distinct manifestation of neurofibromatosis. PMID:23001809

Shino, Michael Y; Rabbani, Shehrzad; Belperio, John A; Lynch, Joseph P; Weigt, S Samuel

2012-10-01

221

Genetic variant associations of human SP-A and SP-D with acute and chronic lung injury  

PubMed Central

Pulmonary surfactant, a lipoprotein complex, maintains alveolar integrity and plays an important role in lung host defense, and control of inflammation. Altered inflammatory processes and surfactant dysfunction are well described events that occur in patients with acute or chronic lung disease that can develop secondary to a variety of insults. Genetic variants of surfactant proteins, including single nucleotide polymorphisms, haplotypes, and other genetic variations have been associated with acute and chronic lung disease throughout life in several populations and study groups. The hydrophilic surfactant proteins SP-A and SP-D, also known as collectins, in addition to their surfactant-related functions, are important innate immunity molecules as these, among others, exhibit the ability to bind and enhance clearance of a wide range of pathogens and allergens. This review focuses on published association studies of human surfactant proteins A and D genetic polymorphisms with respiratory, and non-respiratory diseases in adults, children, and newborns. The potential role of genetic variations in pulmonary disease or pathogenesis is discussed following an evaluation, and comparison of the available literature. PMID:22201752

Silveyra, Patricia; Floros, Joanna

2013-01-01

222

New Insights into Mechanisms Controlling the NLRP3 Inflammasome and Its Role in Lung Disease  

PubMed Central

Inflammasomes are large macromolecular signaling complexes that control the proteolytic activation of two highly proinflammatory IL-1 family cytokines, IL-1? and IL-18. The NLRP3 inflammasome is of special interest because it can assemble in response to a diverse array of stimuli and because the inflammation it triggers has been implicated in a wide variety of disease pathologies. To avoid aberrant activation, the NLRP3 inflammasome is modulated on multiple levels, ranging from transcriptional control to post-translational protein modifications. Emerging genetic and pharmacological evidence suggests that NLRP3 inflammasome activation may also be involved in acute lung inflammation after viral infection and during progression of several chronic pulmonary diseases, including idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, and asthma. Here, we review the most recent contributions to our understanding of the regulatory mechanisms controlling activation of the NLRP3 inflammasome and discuss the contribution of the NLRP3 inflammasome to the pathology of lung diseases. PMID:24183846

De Nardo, Dominic; De Nardo, Christine M.; Latz, Eicke

2015-01-01

223

Acute and Short-term Effects of Secondhand Smoke on Lung Function and Cytokine Production  

Microsoft Academic Search

Rationale: The acute effect of secondhand smoke (SHS) on lung function and the duration of system disruption remain unknown. Objectives: To assess the SHS effects and their duration on lung function and inflammatory markers. Methods: In a randomized single-blind crossover experiment data were obtained from 16 (8 women) nonsmoking adults at baseline and at 0, 1, and 3 hours after

Andreas D. Flouris; Giorgos S. Metsios; Andres E. Carrillo; Athanasios Z. Jamurtas; Konstantinos Gourgoulianis; Theodoros Kiropoulos; Manolis N. Tzatzarakis; Aristidis M. Tsatsakis; Yiannis Koutedakis

2009-01-01

224

Detection of porcine oleic acid-induced acute lung injury using pulmonary acoustics  

Microsoft Academic Search

Abstract To evaluate the utility of monitoring the sound filtering characteristics of the respiratory system in the assessment of acute lung injury, we injected a multi- frequency broadband sound signal into the airway of five anesthetized, intubated pigs, while recording transmitted sound over the trachea and on the chest wall. Oleic acid injections effected a severe lung injury predominately,in the

Jukka Räsänen; Noam Gavriely

2002-01-01

225

[Management of unilateral or asymmetrical lung disease (author's transl)].  

PubMed

To determine the indications of body position, continuous positive airway pressure and independent lung ventilation in unilateral lung disease, we turned 10 patients with overwhelming unilateral lung disease from supine to lateral position. All patients were breathing spontaneously with a mask, then associated with continuous airway pressure (10 cm H2O PEEP) in five cases. During these spontaneous ventilation methods, hemodynamic parameters did not change, but arterial blood oxygen tension increased and intra-pulmonary shunting decreased significantly. Final recovery was obtained in 7 cases. In the 3 others, mechanical ventilation was needed because spontaneous breathing methods were ineffective in improving blood gases. Lateral position and conventional ventilation with positive airway pressure were also ineffective. Only independent ventilation enhanced arterial blood oxygen tension. But only one patient survived. We conclude that spontaneous breathing methods are able to provide successful treatment in most of patients with unilateral lung disease. In other patients, only independent lung ventilation is effective. PMID:7036794

Bons, J; Dhainaut, J F; Lesgourgues, B; Schlemmer, B; Carli, A; Monsallier, J F

1981-01-01

226

Effects of the Prone Position on Respiratory Mechanics and Gas Exchange during Acute Lung Injury  

Microsoft Academic Search

We studied 16 patients with acute lung injury receiving volume-controlled ventilation to assess the relationships between gas exchange and respiratory mechanics before, during, and after 2 h in the prone position. We measured the end-expiratory lung volume (EELV, helium dilution), the total respi- ratory system (Cst,rs), the lung (Cst,L) and the thoracoabdominal cage (Cst,w) compliances (end- inspiratory occlusion technique and

PAOLO PELOSI; DANIELA TUBIOLO; DANIELE MASCHERONI; PIERLUIGI VICARDI; STEFANIA CROTTI; FRANCO VALENZA; LUCIANO GATTINONI

1998-01-01

227

Redistribution of pulmonary blood flow impacts thermodilution-based extravascular lung water measurements in a model of acute lung injury  

PubMed Central

Background Studies using transthoracic thermodilution have demonstrated increased extravascular lung water (EVLW) measurements attributed to progression of edema and flooding during sepsis and acute lung injury. We hypothesize that redistribution of pulmonary blood flow can cause increased apparent EVLW secondary to increased perfusion of thermally silent tissue, not increased lung edema. Methods Anesthetized, mechanically ventilated canines were instrumented with PiCCO® (Pulsion Medical, Munich, Germany) catheters and underwent lung injury by repetitive saline lavage. Hemodynamic and respiratory physiologic data were recorded. After stabilized lung injury, endotoxin was administered to inactivate hypoxic pulmonary vasoconstriction. Computerized tomographic imaging was performed to quantify in vivo lung volume, total tissue (fluid) and air content, and regional distribution of blood flow. Results Lavage injury caused an increase in airway pressures and decreased arterial oxygen content with minimal hemodynamic effects. EVLW and shunt fraction increased after injury and then markedly following endotoxin administration. Computerized tomographic measurements quantified an endotoxin-induced increase in pulmonary blood flow to poorly aerated regions with no change in total lung tissue volume. Conclusions The abrupt increase in EVLW and shunt fraction after endotoxin administration is consistent with inactivation of hypoxic pulmonary vasoconstriction and increased perfusion to already flooded lung regions that were previously thermally silent. Computerized tomographic studies further demonstrate in vivo alterations in regional blood flow (but not lung water) and account for these alterations in shunt fraction and EVLW. PMID:19809280

Easley, R. Blaine; Mulreany, Daniel G.; Lancaster, Christopher T.; Custer, Jason W.; Fernandez-Bustamante, Ana; Colantuoni, Elizabeth; Simon, Brett A.

2009-01-01

228

Bronchoalveolar immunologic profile of acute human lung transplant allograft rejection.  

PubMed

Bronchoalveolar lavage fluid (BALF) offers a potential means to diagnose acute rejection and could provide insight into the immune mechanisms responsible for lung allograft rejection. Transbronchial biopsies from 29 bronchoscopic procedures were assessed for rejection. Concurrent BALF lymphocyte subsets were examined by flow cytometry, including CD4 and CD8 T cells and their activation status by CD38 expression, natural killer (NK), NK-like T (NT), B, regulatory T, and invariant receptor NK-T cells. Percentages of CD4 were reduced, and CD8 and activation of CD4 T cells correlated with rejection. There were trends for increased NT, reduced NK, and increased B cell percentages with rejection, suggesting potential roles of these cells. Among regulatory cells, the percentages of regulatory T cells decreased and CD4/CD8 invariant NK-T cells increased during rejection, suggesting a proinflammatory profile. A unique BALF lymphocyte profile was associated with rejection and may provide insight into the pathogenesis of allograft rejection. PMID:18408589

Gregson, Aric L; Hoji, Aki; Saggar, Rajan; Ross, David J; Kubak, Bernard M; Jamieson, Beth D; Weigt, S Samuel; Lynch, Joseph P; Ardehali, Abbas; Belperio, John A; Yang, Otto O

2008-04-15

229

Bronchoalveolar Immunologic Profile of Acute Human Lung Transplant Allograft Rejection  

PubMed Central

Bronchoalveolar lavage fluid (BALF) offers a potential means to diagnose acute rejection and could provide insight into the immune mechanisms responsible for lung allograft rejection. Transbronchial biopsies from 29 bronchoscopic procedures were assessed for rejection. Concurrent BALF lymphocyte subsets were examined by flow cytometry, including CD4+ and CD8+ T cells and their activation status via CD38 expression, NK, NK-like T (NT), B, T regulatory (Treg) and invariant receptor NK-T cells (iNKT). Percentages of CD4+ were reduced, CD8+ and activation of CD4+ T cells correlated with rejection. There were trends for increased NT, reduced NK and increased B cell percentages with rejection, suggesting potential roles of these cells. Among regulatory cells, the percentages of Treg decreased and CD4?/CD8? iNKT increased during rejection, suggesting a pro-inflammatory profile. A unique BALF lymphocyte profile was associated with rejection and may provide insight into the pathogenesis of allograft rejection. PMID:18408589

Gregson, Aric L.; Hoji, Aki; Saggar, Rajan; Ross, David J.; Kubak, Bernard M.; Jamieson, Beth D.; Weigt, S. Samuel; Lynch, Joseph P.; Ardehali, Abbas; Belperio, John A.; Yang, Otto O.

2009-01-01

230

Pathogenesis and risk factors for nontuberculous mycobacterial lung disease.  

PubMed

Nontuberculous mycobacteria (NTM) infections are broadly classified as skin and soft tissue infections, isolated lung disease, and visceral or disseminated disease. The degree of underlying immune abnormalities varies between each classification. Skin and soft tissue infections are usually the result of iatrogenic or accidental inoculation of NTM in otherwise normal hosts. Visceral and disseminated NTM disease invariably occurs in individuals with more severe immunosuppression. Although the focus of this article is to discuss the pathogenesis of NTM lung disease, the risk factors of visceral/disseminated NTM disease are also summarized, as they provide insights into host-defense mechanisms against these organisms. PMID:25676515

Honda, Jennifer R; Knight, Vijaya; Chan, Edward D

2015-03-01

231

Pulmonary endothelium in acute lung injury: from basic science to the critically ill  

Microsoft Academic Search

BackgroundPulmonary endothelium is an active organ possessing numerous physiological, immunological, and metabolic functions. These functions may be altered early in acute lung injury (ALI) and further contribute to the development of acute respiratory distress syndrome (ARDS). Pulmonary endothelium is strategically located to filter the entire blood before it enters the systemic circulation; consequently its integrity is essential for the maintenance

S. E. Orfanos; I. Mavrommati; I. Korovesi; C. Roussos

2004-01-01

232

Combined effects of sivelestat and resveratrol on severe acute pancreatitis-associated lung injury in rats.  

PubMed

Despite extensive research and clinical efforts made in the management of acute pancre-atitis during the past few decades, to date no effective cure is available and the mortality from severe acute pancre-atitis remains high. Given that lung is the primary cause of early death in acute pancreatitis patients, novel therapeutic approaches aiming to prevent lung injury have become a subject of intensive investigation. In a previous study, we demonstrated that sivelestat, a specific inhibitor of neutrophil elastase, is effective in protecting against lung failure in rats with taurocholate-induced acute pancreatitis. As part of the analyses extended from that study, the present study aimed to evaluate the role of sivelestat and/or resveratrol in the protection against acute pancreatitis-associated lung injury. The extended analyses demonstrated the following: (1) sodium taurocholate induced apparent lung injury and dysfunction manifested by histological anomalies, including vacuolization and apoptosis of the cells in the lung, as well as biochemical aberrations in the blood (an increase in amylase concentration and a decrease in partial arterial oxygen pressure) and increases in activities of reactive oxygen species, interleukin 6, myeloperoxidase, neutrophil elastase, lung edema, bronchotracho alveolar lavage protein concentration, and bronchotracho alveolar lavage cell infiltration in the lung; and (2) in lung tissues, either sivelestat or resveratrol treatment effectively attenuated the taurocholate-induced abnormalities in all parameters analyzed except for serum amylase concentration. In addition, combined treatment with both sivelestat and resveratrol demonstrated additive protective effects on pancreatitis-associated lung injury compared with single treatment. PMID:24785170

Wang, Houhong; Wang, Shuai; Tang, Amao; Gong, Huihui; Ma, Panpan; Chen, Li

2014-08-01

233

Circulating IL-6 mediates lung injury via CXCL1 production after acute kidney injury in mice  

PubMed Central

Serum IL-6 is increased in patients with acute kidney injury (AKI) and is associated with prolonged mechanical ventilation and increased mortality. Inhibition of IL-6 in mice with AKI reduces lung injury associated with a reduction in the chemokine CXCL1 and lung neutrophils. Whether circulating IL-6 or locally produced lung IL-6 mediates lung injury after AKI is unknown. We hypothesized that circulating IL-6 mediates lung injury after AKI by increasing lung endothelial CXCL1 production and subsequent neutrophil infiltration. To test the role of circulating IL-6 in AKI-mediated lung injury, recombinant murine IL-6 was administered to IL-6-deficient mice. To test the role of CXCL1 in AKI-mediated lung injury, CXCL1 was inhibited by use of CXCR2-deficient mice and anti-CXCL1 antibodies in mice with ischemic AKI or bilateral nephrectomy. Injection of recombinant IL-6 to IL-6-deficient mice with AKI increased lung CXCL1 and lung neutrophils. Lung endothelial CXCL1 was increased after AKI. CXCR2-deficient and CXCL1 antibody-treated mice with ischemic AKI or bilateral nephrectomy had reduced lung neutrophil content. In summary, we demonstrate for the first time that circulating IL-6 is a mediator of lung inflammation and injury after AKI. Since serum IL-6 is increased in patients with either AKI or acute lung injury and predicts prolonged mechanical ventilation and increased mortality in both conditions, our data suggest that serum IL-6 is not simply a biomarker of poor outcomes but a pathogenic mediator of lung injury. PMID:22791336

Ahuja, Nilesh; Andres-Hernando, Ana; Altmann, Christopher; Bhargava, Rhea; Bacalja, Jasna; Webb, Ryan G.; He, Zhibin; Edelstein, Charles L.

2012-01-01

234

Usefulness of texture features for segmentation of lungs with severe diffuse interstitial lung disease  

NASA Astrophysics Data System (ADS)

We developed an automated method for the segmentation of lungs with severe diffuse interstitial lung disease (DILD) in multi-detector CT. In this study, we would like to compare the performance levels of this method and a thresholdingbased segmentation method for normal lungs, moderately abnormal lungs, severely abnormal lungs, and all lungs in our database. Our database includes 31 normal cases and 45 abnormal cases with severe DILD. The outlines of lungs were manually delineated by a medical physicist and confirmed by an experienced chest radiologist. These outlines were used as reference standards for the evaluation of the segmentation results. We first employed a thresholding technique for CT value to obtain initial lungs, which contain normal and mildly abnormal lung parenchyma. We then used texture-feature images derived from co-occurrence matrix to further segment lung regions with severe DILD. The segmented lung regions with severe DILD were combined with the initial lungs to generate the final segmentation results. We also identified and removed the airways to improve the accuracy of the segmentation results. We used three metrics, i.e., overlap, volume agreement, and mean absolute distance (MAD) between automatically segmented lung and reference lung to evaluate the performance of our segmentation method and the thresholding-based segmentation method. Our segmentation method achieved a mean overlap of 96.1%, a mean volume agreement of 98.1%, and a mean MAD of 0.96 mm for the 45 abnormal cases. On the other hand the thresholding-based segmentation method achieved a mean overlap of 94.2%, a mean volume agreement of 95.8%, and a mean MAD of 1.51 mm for the 45 abnormal cases. Our new method obtained higher performance level than the thresholding-based segmentation method.

Wang, Jiahui; Li, Feng; Li, Qiang

2010-03-01

235

Interstitial lung disease in children – genetic background and associated phenotypes  

PubMed Central

Interstitial lung disease in children represents a group of rare chronic respiratory disorders. There is growing evidence that mutations in the surfactant protein C gene play a role in the pathogenesis of certain forms of pediatric interstitial lung disease. Recently, mutations in the ABCA3 transporter were found as an underlying cause of fatal respiratory failure in neonates without surfactant protein B deficiency. Especially in familiar cases or in children of consanguineous parents, genetic diagnosis provides an useful tool to identify the underlying etiology of interstitial lung disease. The aim of this review is to summarize and to describe in detail the clinical features of hereditary interstitial lung disease in children. The knowledge of gene variants and associated phenotypes is crucial to identify relevant patients in clinical practice. PMID:15819986

Hartl, Dominik; Griese, Matthias

2005-01-01

236

Spirometry: Simulations of Obstructive and Restrictive Lung Diseases  

NSDL National Science Digital Library

Description of spirometry exercises that enhance studentsÂ? understanding of pulmonary physiology and pathophysiology, as well as allowing them to experience the difficulty, discomfort, and apprehension associated with lung disease

Mr. David W. Rodenbaugh (Wayne State University Department of Physiology)

2002-09-01

237

Assessment of Lung Volume Collapsibility in Chronic Obstructive Lung Disease Patients Using CT  

PubMed Central

Objective To investigate the collapsibility of the lung and individual lobes in patients with COPD during inspiration/expiration and assess the association of whole lung and lobar volume changes with pulmonary function tests (PFTs) and disease severity. Methods PFT measures used were RV/TLC%, FEV1% predicted, FVC, FEV1/FVC%, DLco% predicted and GOLD category. A total of 360 paired inspiratory and expiratory CT examinations acquired in 180 subjects were analysed. Automated computerised algorithms were used to compute individual lobe and total lung volumes. Lung volume collapsibility was assessed quantitatively using the simple difference between CT computed inspiration (I) and expiration (E) volumes (I-E), and a relative measure of volume changes, (I-E)/I. Results Mean absolute collapsibility (I-E) decreased in all lung lobes with increasing disease severity defined by GOLD classification. Relative collapsibility (I-E)/I showed a similar trend. Upper lobes had lower volume collapsibility across all GOLD categories and lower lobes collectively had the largest volume collapsibility. Whole lung and left lower lobe collapsibility measures tended to have the highest correlations with PFT measures. Collapsibility of lung lobes and whole lung were also negatively correlated with the degree of air trapping between expiration and inspiration, as measured by mean lung density. All measured associations were statistically significant (P < 0.01). Conclusion Severity of COPD appears associated with increased collapsibility in the upper lobes, but change (decline) in collapsibility is faster in the lower lobes. PMID:23494492

Kundu, Shinjini; Gu, Suicheng; Leader, Joseph K.; Tedrow, John R.; Sciurba, Frank C.; Gur, David; Kaminski, Naftali; Pu, Jiantao

2013-01-01

238

Role of the pulmonary epithelium and inflammatory signals in acute lung injury  

PubMed Central

Acute lung injury (ALI) is a clinical disease marked by respiratory failure due to disruption of the epithelial and endothelial barrier, flooding of the alveolar compartment with protein-rich fluid and recruitment of neutrophils into the alveolar space. ALI affects approximately 200,000 patients annually in the USA and results in approximately 75,000 deaths. It is associated with prolonged mechanical ventilation, intensive medical care, high morbidity and mortality, and rising healthcare costs. Owing to its impact on public health, great strides have been made towards understanding the pathobiology of ALI to affect outcome. This review will focus on the role of the epithelial cell in the pathogenesis and resolution of ALI and the role of various inflammatory mediators in ALI. PMID:19885383

Manicone, Anne M

2009-01-01

239

Lung Cancer and Rosai-Dorfman's Disease  

Microsoft Academic Search

Case Report: A 60-year-old female patient underwent craniotomy for a cerebral lesion in the frontoparietal lobe. Histologically, it turned out to be a metastasis from an adenocarcinoma. The primary tumor was found in the upper lobe of the left lung. The patient had whole brain radiation therapy only, the lung tumor was not treated. 4 years later, she presented with

Johannes Lutterbach; Karl Henne; Axel Pagenstecher; Joachim Böhm

2003-01-01

240

Asbestos-Related Lung Disease: A Pictorial Review.  

PubMed

Asbestos exposure can lead to a variety of adverse effects in the thorax. Although currently in the western world, levels of exposure are kept in check by strict regulations, history of previous asbestos exposure continues to have an effect on many, owing to the latent nature of the pathophysiological response of the body to the inhaled fibers. The adverse effects of asbestos generally fall under 3 categories: pleural disease, lung parenchymal disease, and neoplastic disease. Effects on the pleura include pleural effusions, plaques, and diffuse pleural thickening. In the parenchyma, rounded atelectasis, fibrotic bands, and asbestosis are observed. Differentiating asbestosis from other forms of interstitial lung diseases, such as idiopathic pulmonary fibrosis, usual interstitial pneumonia, smoking-related lung disease, and mixed interstitial lung diseases, is important because the prognosis, course of disease, and management of the patient should be tailored based on the specific etiology of the disease. In this review, imaging findings specific to asbestosis are discussed. Finally, exposure to asbestos can lead to neoplastic disease such as pleural mesothelioma, peritoneal mesothelioma, and bronchogenic carcinoma. The purpose of this article is to review the effects of asbestos exposure in the thorax, pathophysiology of these responses, and disease course. Particular emphasis is placed on the radiographic appearance of the disease, discussion of various imaging modalities and their utility, and the role of imaging in the management of patients with previous asbestos exposure and asbestos-related pulmonary disease. PMID:25444537

Norbet, Christopher; Joseph, Amanda; Rossi, Santiago S; Bhalla, Sanjeev; Gutierrez, Fernando R

2014-10-30

241

Asbestos lung burden and disease patterns in man  

SciTech Connect

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

Churg, A. [Univ. of British Columbia, Vancouver (Canada)

1993-12-31

242

Increased T cell glucose uptake reflects acute rejection in lung grafts  

PubMed Central

Although T cells are required for acute lung rejection, other graft-infiltrating cells such as neutrophils accumulate in allografts and are also high glucose utilizers. Positron emission tomography (PET) with the glucose probe [18F]fluorodeoxyglucose ([18F]FDG) has been employed to image solid organ acute rejection, but the sources of glucose utilization remain undefined. Using a mouse model of orthotopic lung transplantation, we analyzed glucose probe uptake in the grafts of syngeneic and allogeneic recipients with or without immunosuppression treatment. Pulmonary microPET scans demonstrated significantly higher [18F]FDG uptake in rejecting allografts when compared to transplanted lungs of either immunosuppressed or syngeneic recipients. [18F]FDG uptake was also markedly attenuated following T cell depletion therapy in lung recipients with ongoing acute rejection. Flow-cytometric analysis using the fluorescent deoxyglucose analog 2-NBDG revealed that T cells, and in particular CD8+ T cells, were the largest glucose utilizers in acutely rejecting lung grafts followed by neutrophils and antigen presenting cells. These data indicate that imaging modalities tailored toward assessing T cell metabolism may be useful in identifying acute rejection in lung recipients PMID:23927673

Chen, Delphine L.; Wang, Xingan; Yamamoto, Sumiharu; Carpenter, Danielle; Engle, Jacquelyn T.; Li, Wenjun; Lin, Xue; Kreisel, Daniel; Krupnick, Alexander S.; Huang, Howard J.; Gelman, Andrew E.

2013-01-01

243

Collagenolytic matrix metalloproteinases in chronic obstructive lung disease and cancer.  

PubMed

Chronic obstructive pulmonary disease (COPD) and lung cancer result in significant morbidity and mortality worldwide. In addition to the role of environmental smoke exposure in the development of both diseases, recent epidemiological studies suggests a connection between the development of COPD and lung cancer. Furthermore, individuals with concomitant COPD and cancer have a poor prognosis when compared with individuals with lung cancer alone. The modulation of molecular pathways activated during emphysema likely lead to an increased susceptibility to lung tumor growth and metastasis. This review summarizes what is known in the literature examining the molecular pathways affecting matrix metalloproteinases (MMPs) in this process as well as external factors such as smoke exposure that have an impact on tumor growth and metastasis. Increased expression of MMPs provides a unifying link between lung cancer and COPD. PMID:25664615

Woode, Denzel; Shiomi, Takayuki; D'Armiento, Jeanine

2015-01-01

244

Effects of acute and chronic administration of methylprednisolone on oxidative stress in rat lungs* **  

PubMed Central

Objective: To determine the effects of acute and chronic administration of methylprednisolone on oxidative stress, as quantified by measuring lipid peroxidation (LPO) and total reactive antioxidant potential (TRAP), in rat lungs. Methods: Forty Wistar rats were divided into four groups: acute treatment, comprising rats receiving a single injection of methylprednisolone (50 mg/kg i.p.); acute control, comprising rats i.p. injected with saline; chronic treatment, comprising rats receiving methylprednisolone in drinking water (6 mg/kg per day for 30 days); and chronic control, comprising rats receiving normal drinking water. Results: The levels of TRAP were significantly higher in the acute treatment group rats than in the acute control rats, suggesting an improvement in the pulmonary defenses of the former. The levels of lung LPO were significantly higher in the chronic treatment group rats than in the chronic control rats, indicating oxidative damage in the lung tissue of the former. Conclusions: Our results suggest that the acute use of corticosteroids is beneficial to lung tissue, whereas their chronic use is not. The chronic use of methylprednisolone appears to increase lung LPO levels. PMID:25029646

Torres, Ronaldo Lopes; Torres, Iraci Lucena da Silva; Laste, Gabriela; Ferreira, Maria Beatriz Cardoso; Cardoso, Paulo Francisco Guerreiro; Belló-Klein, Adriane

2014-01-01

245

Extracellular ATP mediates the late phase of neutrophil recruitment to the lung in murine models of acute lung injury  

PubMed Central

Acute lung injury (ALI) is a severe inflammatory condition whose pathogenesis is irrevocably linked to neutrophil emigration to the lung. Activation and recruitment of neutrophils to the lung is mostly attributable to local production of the chemokines. However, much of our understanding of neutrophil recruitment to the lung is based on studies focusing on early time points after initiation of injury. In this study, we sought to evaluate the extended temporal relationship between neutrophil chemotactic factor expression and influx of neutrophils into the lung after intratracheal administration of either LPS or bleomycin. In both models, results demonstrated two phases of neutrophil chemotactic factor expression; first, an early phase characterized by high levels of CXCL1/keratinocyte-derived chemokine, CXCL2/monocyte-inhibitory protein-2, and CXCL5/LPS-induced chemokine expression, and second, a late phase distinguished by increases in extracellular ATP. Furthermore, we show that strategies aimed at either enhancing ATP catabolism (ip ecto-5?-nucleotidase administration) or inhibiting glycolytic ATP production (ip 2-deoxy-d-glucose treatment) reduce extracellular ATP accumulation, limit vascular leakage, and effectively block the late, but not the early, stages of neutrophil recruitment to the lung after LPS instillation. In conclusion, this study illustrates that neutrophil recruitment to the lung is mediated by the time-dependent expression of chemotactic factors and suggests that novel strategies, which reduce extracellular ATP accumulation, may attenuate late neutrophil recruitment and limit lung injury during ALI. PMID:24285266

Shah, Dilip; Romero, Freddy; Stafstrom, William; Duong, Michelle

2013-01-01

246

Changes in the Bacterial Microbiota in Gut, Blood, and Lungs following Acute LPS Instillation into Mice Lungs  

PubMed Central

Introduction Previous reports have shown that the gastrointestinal (GI) bacterial microbiota can have profound effects on the lungs, which has been described as the “gut-lung axis”. However, whether a “lung-gut” axis exists wherein acute lung inflammation perturbs the gut and blood microbiota is unknown. Methods Adult C57/Bl6 mice were exposed to one dose of LPS or PBS instillation (n?=?3 for each group) directly into lungs. Bacterial microbiota of the bronchoalveolar lavage fluid, blood, and cecum were determined using 454 pyrotag sequencing and quantitative polymerase chain reaction (qPCR) at 4 through 168 hours post-instillation. We then investigated the effects of oral neomycin and streptomycin (n?=?8) on the microbiota at 4 and 24 hours post LPS instillation versus control treatment (n?=?5 at baseline and 4 hours, n?=?7 at 24 hours). Results At 24 hours post LPS instillation, the total bacterial count was significantly increased in the cecum (P<0.05); whereas the total bacterial count in blood was increased at 4, 48, and 72 hours (P<0.05). Antibiotic treatment reduced the total bacteria in blood but not in the cecum. The increase in total bacteria in the blood correlated with Phyllobacteriaceae OTU 40 and was significantly reduced in the blood for both antibiotic groups (P<0.05). Conclusion LPS instillation in lungs leads to acute changes in the bacterial microbiota in the blood and cecum, which can be modulated with antibiotics. PMID:25333938

Sze, Marc A.; Tsuruta, Masashi; Yang, Shun-Wei Julia; Oh, Yeni; Man, S. F. Paul; Hogg, James C.; Sin, Don D.

2014-01-01

247

The Rabbit as a Model for Studying Lung Disease and Stem Cell Therapy  

PubMed Central

No single animal model can reproduce all of the human features of both acute and chronic lung diseases. However, the rabbit is a reliable model and clinically relevant facsimile of human disease. The similarities between rabbits and humans in terms of airway anatomy and responses to inflammatory mediators highlight the value of this species in the investigation of lung disease pathophysiology and in the development of therapeutic agents. The inflammatory responses shown by the rabbit model, especially in the case of asthma, are comparable with those that occur in humans. The allergic rabbit model has been used extensively in drug screening tests, and this model and humans appear to be sensitive to similar drugs. In addition, recent studies have shown that the rabbit serves as a good platform for cell delivery for the purpose of stem-cell-based therapy. PMID:23653896

Kamaruzaman, Nurfatin Asyikhin; Kamaldin, Nurulain ‘Atikah; Latahir, Ahmad Zaeri; Yahaya, Badrul Hisham

2013-01-01

248

Use of risk reclassification with multiple biomarkers improves mortality prediction in acute lung injury  

PubMed Central

Objective Multiple single biomarkers have been associated with poor outcomes in acute lung injury; however, no single biomarker has sufficient discriminating power to clearly indicate prognosis. Using both derivation and replication cohorts, we tested novel risk reclassification methods to determine whether measurement of multiple plasma biomarkers at the time of acute lung injury diagnosis would improve mortality prediction in acute lung injury. Design Analysis of plasma biomarker levels and prospectively collected clinical data from patients enrolled in two randomized controlled trials of ventilator therapy for acute lung injury. Setting Intensive care units of university hospitals participating in the National Institutes of Health Acute Respiratory Distress Syndrome Network. Patients Subjects enrolled in a trial of lower tidal volume ventilation (derivation cohort) and subjects enrolled in a trial of higher vs. lower positive end-expiratory pressure (replication cohort). Interventions None. Measurements and Main Results The plasma biomarkers were intercellular adhesion molecule-1, von Willebrand factor, interleukin-8, soluble tumor necrosis factor receptor-1, and surfactant protein-D. In the derivation cohort (n = 547), adding data on these biomarkers to clinical predictors (Acute Physiology and Chronic Health Evaluation III score) at the time of study enrollment improved the accuracy of risk prediction, as reflected by a net reclassification improvement of 22% (95% confidence interval 13% to 32%; p < .001). In the replication cohort (n = 500), the net reclassification improvement was 17% (95% confidence interval 7% to 26%; p < .001). A reduced set of three biomarkers (interleukin-8, soluble tumor necrosis factor receptor-1, and surfactant protein-D) had nearly equivalent prognostic value in both cohorts. Conclusions When combined with clinical data, plasma biomarkers measured at the onset of acute lung injury can improve the accuracy of risk prediction. Combining three or more biomarkers may be useful for selecting a high-risk acute lung injury population for enrollment in clinical trials of novel therapies. PMID:21283009

Calfee, Carolyn S.; Ware, Lorraine B.; Glidden, David V.; Eisner, Mark D.; Parsons, Polly E.; Thompson, B. Taylor; Matthay, Michael A.

2012-01-01

249

Granulocyte colony-stimulating factor-producing lung cancer and acute respiratory distress syndrome.  

PubMed

Granulocyte colony-stimulating factor (G-CSF)-producing lung cancers are known to cause extreme leukocytosis. However, acute respiratory distress syndrome (ARDS) caused by G-CSF-producing lung cancer is extremely rare. We present a case of G-CSF-producing lung cancer with marked leukocytosis, which rapidly led to severe ARDS after the patient developed pneumonia. The present case suggests that extreme leukocytosis may easily lead to ARDS, triggered by infection. Thus, G-CSF-producing lung cancer with marked leukocytosis should be carefully monitored before surgery and during treatment. PMID:24460739

Inokuchi, Ryota; Manabe, Haruki; Ohta, Fumihito; Nakamura, Kensuke; Nakajima, Susumu; Yahagi, Naoki

2014-01-24

250

Diagnosis and management of chronic lung disease in deployed military personnel.  

PubMed

Military personnel are a unique group of individuals referred to the pulmonary physician for evaluation. Despite accession standards that limit entrance into the military for individuals with various pre-existing lung diseases, the most common disorders found in the general population such as asthma and chronic obstructive pulmonary disease remain frequently diagnosed. Military personnel generally tend to be a more physically fit population who are required to exercise on a regular basis and as such may have earlier presentations of disease than their civilian counterparts. Exertional dyspnea is a common complaint; establishing a diagnosis may be challenging given the subtle nature of symptoms and lack of specificity with pulmonary function testing. The conflicts over the past 10 years in Iraq and Afghanistan have also given rise to new challenges for deployed military. Various respiratory hazards in the deployed environment include suspended geologic dusts, burn pits, vehicle exhaust emissions, industrial air pollution, and isolated exposure incidents and may give rise to both acute respiratory symptoms and chronic lung disease. In the evaluation of deployed military personnel, establishing the presence of actual pulmonary disease and the relationship of existing disease to deployment is an ongoing issue to both military and civilian physicians. This paper reviews the current evidence for chronic lung disease in the deployed military population and addresses any differences in diagnosis and management. PMID:23470637

Morris, Michael J; Lucero, Pedro F; Zanders, Thomas B; Zacher, Lisa L

2013-08-01

251

Depressive Symptoms and Impaired Physical Function after Acute Lung Injury  

PubMed Central

Rationale: Survivors of acute lung injury (ALI) frequently have substantial depressive symptoms and physical impairment, but the longitudinal epidemiology of these conditions remains unclear. Objectives: To evaluate the 2-year incidence and duration of depressive symptoms and physical impairment after ALI, as well as risk factors for these conditions. Methods: This prospective, longitudinal cohort study recruited patients from 13 intensive care units (ICUs) in four hospitals, with follow-up 3, 6, 12, and 24 months after ALI. The outcomes were Hospital Anxiety and Depression Scale depression score greater than or equal to 8 (“depressive symptoms”) in patients without a history of depression before ALI, and two or more dependencies in instrumental activities of daily living (“impaired physical function”) in patients without baseline impairment. Measurements and Main Results: During 2-year follow-up of 186 ALI survivors, the cumulative incidences of depressive symptoms and impaired physical function were 40 and 66%, respectively, with greatest incidence by 3-month follow-up; modal durations were greater than 21 months for each outcome. Risk factors for incident depressive symptoms were education 12 years or less, baseline disability or unemployment, higher baseline medical comorbidity, and lower blood glucose in the ICU. Risk factors for incident impaired physical function were longer ICU stay and prior depressive symptoms. Conclusions: Incident depressive symptoms and impaired physical function are common and long-lasting during the first 2 years after ALI. Interventions targeting potentially modifiable risk factors (e.g., substantial depressive symptoms in early recovery) should be evaluated to improve ALI survivors’ long-term outcomes. PMID:22161158

Colantuoni, Elizabeth; Mendez-Tellez, Pedro A.; Dinglas, Victor D.; Shanholtz, Carl; Husain, Nadia; Dennison, Cheryl R.; Herridge, Margaret S.; Pronovost, Peter J.; Needham, Dale M.

2012-01-01

252

General anxiety symptoms after acute lung injury: Predictors and correlates  

PubMed Central

Objective Acute lung injury (ALI) is common in the intensive care unit (ICU), typically requiring life support ventilation. Survivors often experience anxiety after hospital discharge. We evaluated general anxiety symptoms 3 months after ALI for: (1) associations with patient characteristics and ICU variables, and (2) cross-sectional associations with physical function and quality of life (QOL). Methods General anxiety was assessed as part of a prospective cohort study recruiting patients from 13 ICUs at four hospitals in Baltimore, MD using the Hospital Anxiety and Depression Scale — Anxiety Subscale (HAD-A), with associations evaluated using multivariable linear and logistic regression models. Results Of 152 patients, 38% had a positive screening test for general anxiety (HAD-A ? 8). Pre-ICU body mass index and psychiatric comorbidity were associated with general anxiety (OR, 95% confidence interval (CI): 1.06 (1.00, 1.13) and 3.59 (1.25, 10.30), respectively). No ICU-related variables were associated with general anxiety. General anxiety was associated with the number of instrumental ADL dependencies (Spearman's rho = 0.22; p = 0.004) and worse overall QOL as measured by EQ-5D visual analog scale (VAS) (rho = ?0.34; p < 0.001) and utility score (rho = ?0.30; p < 0.001), and by the SF-36 mental health domain (rho = ?0.70; p < 0.001) and Mental Component Summary score (rho = ?0.73; p < 0.001). Conclusion Many patients have substantial general anxiety symptoms 3 months after ALI. General anxiety was associated with patient characteristics and impaired physical function and quality of life. Early identification and treatment of general anxiety may enhance physical and emotional function in patients surviving critical illnesses. PMID:23972420

Stevenson, Jennifer E.; Colantuoni, Elizabeth; Bienvenu, O. Joseph; Sricharoenchai, Thiti; Wozniak, Amy; Shanholtz, Carl; Mendez-Tellez, Pedro A.; Needham, Dale M.

2014-01-01

253

[Acute lung injury as a consequence of fresh frozen plasma administration in a patient with factor XII deficiency].  

PubMed

Along with the complete blood count, the coagulation tests are those most demanded before a surgical procedure. The activated partial thromboplastin time (APPT) quantifies the intrinsic and common coagulation pathways, including factors XII, XI, IX, VIII, X, V and II. Factor XII deficiency is associated with a prolonged APPT and an increase in thromboembolic phenomena, without increasing the intraoperative bleeding risk. A 20 year old man with factor XII deficiency was receiving two units of fresh frozen plasma because of an APPT of 100 seconds, with the intention of normalizing it before an urgent surgery procedure, and the fear of intraoperative bleeding. An hour after starting the transfusion the patient developed an acute lung injury (ALI) compatible with the diagnosis of a transfusion related acute lung injury (TRALI). The surgery continued without complications, and the patient was admitted to the resuscitation unit for 72 h, needing respiratory support. If the APTT is prolonged in the absence of bleeding, the presence of a non-specific circulating anticoagulant, a deficiency of factor XI, XII and VIII (associated to Von Willebrand disease) must be ruled out. Therefore, in the case presented here, the administration of hemoderivatives was unnecessary and can have consequences as serious as the one that the patient presented, a transfusion related acute lung injury. PMID:24252352

San Juan-Álvarez, M; Sánchez-Zamora, P; de la Flor-Robledo, M

2014-10-01

254

Assessing Pseudomonas aeruginosa virulence and the host response using murine models of acute and chronic lung infection.  

PubMed

Murine models of acute and chronic lung infection have been used in studying Pseudomonas aeruginosa for assessing in vivo behavior and for monitoring of the host response. These models provide an important resource for studies of the initiation and maintenance of bacterial infection, identify bacterial genes essential for in vivo maintenance and for the development and testing of new therapies. The rat has been used extensively as a model of chronic lung infection, whereas the mouse has been a model of acute and chronic infection. Intratracheal administration of planktonic bacterial cells in the mouse provides a model of acute pneumonia. Bacteria enmeshed in agar beads can be used in the rat and mouse to reproduce the lung pathology of cystic fibrosis patients with advanced chronic pulmonary disease. Here, we describe the methods to assess virulence of P. aeruginosa using prototype and clinical strains in the Sprague-Dawley rat and the C57BL/6NCrlBR mouse by monitoring several measurable read-outs including weight loss, mortality, in vivo growth curves, the competitive index of infectivity, and the inflammatory response. PMID:24818948

Kukavica-Ibrulj, Irena; Facchini, Marcella; Cigana, Cristina; Levesque, Roger C; Bragonzi, Alessandra

2014-01-01

255

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

PubMed

Interstitial lung diseases comprise a heterogeneous group of pulmonary conditions that cause restrictive lung disease of poor prognosis, especially if growth failure, pulmonary hypertension and fibrosis appears. We report on the case of a girl of 11 years of age who suffered from severe nonallergic asthma in early childhood and who developed severe interstitial pulmonary disease caused by gastro-oesophageal reflux at the age of 8 years. This diagnosis was established by lung biopsy, bronchoalveolar lavage and a high amount of lipid-laden alveolar macrophages, 2-level pH measurement and oesophageal biopsy. Because therapy with oral and inhaled steroids failed and Omeprazol showed benificial effects, hemifundoplication according to THAL was performed. At present the lung function is clearly normal and there is no need of any medicaments. Following the history, we can assume the pathological gastro-oesophageal reflux to be the cause of the disease. It is important to state that there were no typical symptoms at any time pointing to gastro-oesophageal reflux disease. The development of pulmonary disease by pathological reflux is very often caused by "silent aspiration". Very typically there are no symptoms such as vomiting, heartburn and pain but only signs of chronic lung disease. PMID:10444954

Ahrens, P; Weimer, B; Hofmann, D

1999-07-01

256

Heritability of Lung Disease Severity in Cystic Fibrosis  

PubMed Central

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

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

2007-01-01

257

Animal models of beryllium-induced lung disease  

SciTech Connect

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

Finch, G.L.; Hoover, M.D.; Hahn, F.F. [Inhalation Toxicology Research Institute, Albuquerque, NM (United States)] [and others

1996-10-01

258

Acute respiratory distress syndrome caused by leukemic infiltration of the lung.  

PubMed

Respiratory distress syndrome resulting from leukemic pulmonary infiltrates is seldom diagnosed antemortem. Two 60- and 80-year-old women presented with general malaise, progressive shortness of breath, and hyperleukocytosis, which progressed to acute respiratory distress syndrome (ARDS) after admission. Acute leukemia with pulmonary infection was initially diagnosed, but subsequent examinations including open lung biopsy revealed leukemic pulmonary infiltrates without infection. In one case, the clinical condition and chest radiography improved initially after combination therapy with chemotherapy for leukemia and aggressive pulmonary support. However, new pulmonary infiltration on chest radiography and hypoxemia recurred, which was consistent with acute lysis pneumopathy. Despite aggressive treatment, both patients died due to rapidly deteriorating condition. Leukemic pulmonary involvement should be considered in acute leukemia patients with non-infectious diffusive lung infiltration, especially in acute leukemia with a high blast count. PMID:18492627

Wu, Yao-Kuang; Huang, Yi-Chih; Huang, Shiu-Feng; Huang, Chung-Chi; Tsai, Ying-Huang

2008-05-01

259

Asialoerythropoietin ameliorates bleomycin-induced acute lung injury in rabbits by reducing inflammation  

PubMed Central

Acute lung injury, a critical illness characterized by acute respiratory failure with bilateral pulmonary infiltrates, remains unresponsive to current treatments. The condition involves injury to the alveolar capillary barrier, neutrophil accumulation and the induction of proinflammatory cytokines followed by lung fibrosis. In the present study, a rabbit model of bleomycin-induced acute lung injury was established to examine the effects of asialoerythropoietin (AEP), an agent with tissue-protective activities, on pulmonary inflammation. Six Japanese white rabbits were randomly divided into two equal groups. Acute lung injury was induced in all rabbits by intratracheally injecting bleomycin. The control group was injected with bleomycin only; the experimental (AEP) group was injected intravenously with AEP (80 ?g/kg) prior to the bleomycin injection. Computed tomography (CT) studies were performed seven days later. The CT inflammatory scores of areas exhibiting abnormal density and the pathological inflammatory scores were recorded as a ratio on a 7×7 mm grid. The CT and pathological inflammatory scores were significantly different between the control and AEP groups [122±10 and 16.3±1.5 (controls) vs. 71±8.5 and 9.7±1.4 (AEP), respectively; P<0.01]. Thus, the present study revealed that AEP prevents bleomycin-induced acute lung injury in rabbits. PMID:25289037

SONODA, AKINAGA; NITTA, NORIHISA; TSUCHIYA, KEIKO; OTANI, HIDEJI; WATANABE, SHOBU; MUKAISHO, KENICHI; TOMOZAWA, YUKI; NAGATANI, YUKIHIRO; OHTA, SHINICHI; TAKAHASHI, MASASHI; MURATA, KIYOSHI

2014-01-01

260

Angiopoietin-1 variant, COMP-Ang1 attenuates hydrogen peroxide-induced acute lung injury.  

PubMed

Reactive oxygen species (ROS) play a crucial role in acute lung injury. Tissue inflammation, the increased vascular permeability, and plasma exudation are cardinal features of acute lung injury. Angiopoietin-1 (Ang1) has potential therapeutic applications in preventing vascular leakage and also has beneficial effects in several inflammatory disorders. Recently developed COMP-Ang1 is more potent than native Ang1 in phosphorylating tyrosine kinase with immunoglobulin and EGF homology domain 2 receptor in endothelial cells. However, there are no data on effects and related molecular mechanisms of COMP- Ang1 on ROS-induced acute lung injury. We used hydrogen peroxide (H2O2)-inhaled mice to evaluate the effect of COMP-Ang1 on pulmonary inflammation, bronchial hyper-responsiveness, and vascular leakage in acute lung injury. The results have revealed that VEGF expression, the levels of IL-4, TNF-alpha, IL-1beta, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in lungs, the levels of hypoxia-inducible factor-1alpha (HIF-1alpha) and NF-kappaB in nuclear protein extracts, phosphorylation of Akt, and vascular permeability were increased after inhalation of H2O2 and that the administration of COMP-Ang1 markedly reduced airway hyper-responsiveness, pulmonary inflammation, plasma extravasation, and the increases of cytokines, adhesion molecules, and VEGF in lungs treated with H2O2. We have also found that the activation of HIF-1a and NF-kB and the increase of phosphoinositide 3-kinase activity in lung tissues after H2O2 inhalation were decreased by the administration of COMP-Ang1. These results suggest that COMP-Ang1 ameliorates ROS-induced acute lung injury through attenuating vascular leakage and modulating inflammatory mediators. PMID:18587270

Kim, So Ri; Lee, Kyung Sun; Park, Seoung Ju; Min, Kyung Hoon; Lee, Ka Young; Choe, Yeong Hun; Hong, Sang Hyun; Koh, Gou Young; Lee, Yong Chul

2008-06-30

261

The Role of the Bacterial Microbiome in Lung Disease  

PubMed Central

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

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

2014-01-01

262

[Diffuse parenchymal lung diseases: clinical-radiological correlation].  

PubMed

Diffuse parenchymal lung diseases can have various clinical and radiological presentations. The high-resolution CT scan has a central role in the diagnostic process of an interstitial disease. As a first step in the analysis of such an exam, one has to look for the major radiological sign and then to describe it to build a differential diagnosis in order to guide the management. The goal of this article is to illustrate this approach with examples of diffuse parenchymal lung diseases. PMID:20052866

Pralong, Jacques-André; Martins-Favre, Martina; Howarth, Nigel; Montet, Xavier; Rochat, Thierry

2009-11-18

263

Diagnosis and management of diffuse lung disease in children.  

PubMed

Diffuse lung disease [DLD] in children comprises a group of heterogeneous, rare disorders. Despite the rarity of these diseases there has been a considerable increase in our knowledge of DLD in children including their diagnosis and management. Diagnosis of these diseases requires a detailed history and physical examination, diagnostic imaging, pulmonary function testing, selected and directed laboratory testing, bronchoalveolar lavage and in most cases an open lung biopsy. Once a diagnosis is made, treatment is centred on supportive care including nutritional and supplemental oxygen therapy when needed. Medications including corticosteroids and other immunomodulatory medications are often used. Lung transplantation has been used for final treatment in some cases of DLD. Formation of research collaborations will continue to further our understanding of these diseases. PMID:22018037

Vece, Timothy J; Fan, Leland L

2011-12-01

264

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

PubMed Central

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

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

265

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

Microsoft Academic Search

Interstitial lung disease (ILD) is a challenging clinical entity associated with multiple connective tissue diseases, and is a significant cause of morbidity and mortality. Effective therapies for connective tissue disease-associated interstitial lung disease (CTD-ILD) are still lacking. Multidisciplinary clinics dedicated to the early diagnosis and improved management of patients with CTD-ILD are now being established. There is rapid progress in

Flavia V Castelino; John Varga

2010-01-01

266

WORK-RELATED LUNG DISEASES (WORLD) SURVEILLANCE REPORT  

EPA Science Inventory

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

267

Dual Oxidase 2 in Lung Epithelia Is Essential for Hyperoxia-Induced Acute Lung Injury in Mice  

PubMed Central

Abstract Aims: Acute lung injury (ALI) induced by excessive hyperoxia has been employed as a model of oxidative stress imitating acute respiratory distress syndrome. Under hyperoxic conditions, overloading quantities of reactive oxygen species (ROS) are generated in both lung epithelial and endothelial cells, leading to ALI. Some NADPH oxidase (NOX) family enzymes are responsible for hyperoxia-induced ROS generation in lung epithelial and endothelial cells. However, the molecular mechanisms of ROS production in type II alveolar epithelial cells (AECs) and ALI induced by hyperoxia are poorly understood. Results: In this study, we show that dual oxidase 2 (DUOX2) is a key NOX enzyme that affects hyperoxia-induced ROS production, particularly in type II AECs, leading to lung injury. In DUOX2 mutant mice (DUOX2thyd/thyd) or mice in which DUOX2 expression is knocked down in the lungs, hyperoxia-induced ALI was significantly lower than in wild-type (WT) mice. DUOX2 was mainly expressed in type II AECs, but not endothelial cells, and hyperoxia-induced ROS production was markedly reduced in primary type II AECs isolated from DUOX2thyd/thyd mice. Furthermore, DUOX2-generated ROS are responsible for caspase-mediated cell death, inducing ERK and JNK phophorylation in type II AECs. Innovation: To date, no role for DUOX2 has been defined in hyperoxia-mediated ALI despite it being a NOX homologue and major ROS source in lung epithelium. Conclusion: Here, we present the novel finding that DUOX2-generated ROS induce AEC death, leading to hyperoxia-induced lung injury. Antioxid. Redox Signal. 21, 1803–1818. PMID:24766345

Kim, Min-Ji; Ryu, Jae-Chan; Kwon, Younghee; Lee, Suhee; Bae, Yun Soo; Yoon, Joo-Heon

2014-01-01

268

Association of Soluble HLA-G with Acute Rejection Episodes and Early Development of Bronchiolitis Obliterans in Lung Transplantation  

PubMed Central

Lung transplantation has evolved into a life-saving therapy for select patients with end-stage lung diseases. However, long-term survival remains limited because of bronchiolitis obliterans syndrome (BOS). Soluble HLA-G, a mediator of adaptive immunity that modulates regulatory T cells and certain classes of effector T cells, may be a useful marker of survival free of BOS. We conducted a retrospective, single-center, pilot review of 38 lung transplant recipients who underwent collection of serum and bronchoalveolar lavage fluid 3, 6 and 12 months after transplantation, and compared soluble HLA-G concentrations in each to the presence of type A rejection and lymphocytic bronchiolitis in the first 12 months and to the presence of BOS at 24 months after transplantation. Lung soluble HLA-G concentrations were directly related to the presence of type A rejection but not to lymphocytic bronchiolitis. Our data demonstrate that soluble HLA-G concentrations in bronchoalveolar lavage but not in serum correlates with the number of acute rejection episodes in the first 12 months after lung transplantation, and thus may be a reactive marker of rejection. PMID:25068264

White, Steven R.; Floreth, Timothy; Liao, Chuanhong; Bhorade, Sangeeta M.

2014-01-01

269

ARDS (Acute Respiratory Distress Syndrome)  

MedlinePLUS

... NHLBI on Twitter. What Is ARDS? ARDS, or acute respiratory distress syndrome, is a lung condition that leads to low ... obstructive pulmonary disease (COPD) or lower mortality from acute respiratory distress syndrome (ARDS), report two studies that rigorously tested the ...

270

Toll-like receptor 4 implicated in acute lung injury induced by paraquat poisoning in mice  

PubMed Central

Objective: To investigate the possible relationship and mechanism of Toll-like receptor 4 (TLR4) and acute lung injury induced by paraquat (PQ) poisoning. Methods: Male wild type mice and male TLR4-knockout mice were used in this study. After paraquat treatment for 24 hours, mice were euthanized and pathology, TLR4 expression and pro-inflammatory cytokines were evaluated. Results: Wild type mice showed deteriorated lung injury, pathological damages and increased TLR4 expression and pulmonary TNF-?, IL-1? and NF-?B p65 levels after PQ treatment. TLR4-deficient mice were significantly resistant to paraquat-induced lung injury. Conclusion: TLR4 may be required as a mediator and may play an important role in acute lung injury induced by paraquat. PMID:25419373

Liu, Wei; Shan, Li-Ping; Dong, Xue-Song; Liu, Zhi

2014-01-01

271

Drugs in the acute porphyrias--toxicogenetic diseases.  

PubMed

The acute Porphyrias are examples of toxico-genetic diseases and diseases genetically acquired, which show an idiosyncratic reaction to certain chemicals and drugs. Porphyrics are at risk of developing an acute attack if exposed to various precipitating factors of which drugs are the most common factor. This paper presents lists of drugs complied into those hazardous for patients with acute porphyria and those thought to be safe. PMID:9074793

Moore, M R; Hift, R J

1997-02-01

272

Occupational Disease in Connecticut, 2011  

E-print Network

...........................................................................................................18 Acute Respiratory Conditions, and Poisonings...........................................................................................23 E. Occupational Disease Surveillance System (Physicians' Reports................................................................................................................28 Lung/Respiratory Diseases and Poisonings

Oliver, Douglas L.

273

Partial liquid ventilation with perfluorocarbon in acute lung injury: light and transmission electron microscopy studies.  

PubMed

Liquid ventilation using perfluorocarbon has been shown to improve gas exchange in animal models of acute lung injury as well as in children with acute respiratory distress syndrome. This study was designed to define structural features of lung injury following partial liquid ventilation (PLV) using light and transmission electron microscopy in a rabbit model of acute respiratory distress. Animals were treated with either conventional mechanical ventilation (CMV-gas) (n = 6) or PLV (n = 5) for 4 h after the induction of acute lung injury with saline lavage. Control animals were killed after the lung injury. PLV significantly improved alveolar-arterial oxygen tension and the oxygen index compared with CMV (P < 0.05). Morphometric studies using light microscopy show less alveolar hemorrhage, less edema, and fewer hyaline membranes in the PLV group (P < 0.05). Polymorphonuclear leukocyte sequestration in lung capillaries (11.4 +/- 1.5 versus 19.2 +/- 3 x 10(8)/ml, P < 0.05, PLV versus CMV) and migration into airspaces (3.1 +/- 1.2 versus 4.5 +/- 1.1 x 10(8)/ml, P < 0.05, PLV versus CMV) were lower in the gravity-dependent lung regions. There were fewer alveolar macrophages in the PLV group compared with other groups (P < 0.05). Fluorescence microscopy analysis shows fewer type II alveolar epithelial cells in the CMV group and brighter type II cells in the PLV group. Transmission electron microscopy studies show more alveolar wall damage in the CMV group, with type II cells detached from their basement membrane with fewer surfactant-containing lamellar bodies. We conclude that quantitative histologic analysis shows less lung damage and inflammation when perfluorocarbon is combined with CMV in the management of acute respiratory distress syndrome. PMID:10745025

van Eeden, S F; Klut, M E; Leal, M A; Alexander, J; Zonis, Z; Skippen, P

2000-04-01

274

CT of chronic infiltrative lung disease: Prevalence of mediastinal lymphadenopathy  

SciTech Connect

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

Niimi, Hiroshi; Kang, Eun-Young; Kwong, S. [Univ. of British Columbia and Vancouver Hospital and Health Sciences Centre (Canada)] [and others] [Univ. of British Columbia and Vancouver Hospital and Health Sciences Centre (Canada); and others

1996-03-01

275

PARP inhibitor, olaparib ameliorates acute lung and kidney injury upon intratracheal administration of LPS in mice.  

PubMed

We have previously shown that PARP-1 inhibition provides protection against lung inflammation in the context of asthma and acute lung injury. Olaparib is a potent new generation PARP inhibitor that has been approved for human testing. The present work was designed to evaluate its beneficial potential against LPS-induced acute lung injury and acute kidney injury upon intratracheal administration of the endotoxin in mice. Administration of olaparib at different doses, 30 min after LPS treatment showed that single intraperitoneal injection of the drug at 5 mg/kg b.wt. reduced the total number of inflammatory cells particularly neutrophils in the lungs. This was associated with reduced pulmonary edema as the total protein content in the bronchoalveolar fluid was found to be decreased substantially. Olaparib provided strong protection against LPS-mediated secondary kidney injury as reflected by restoration of serum levels of urea, creatinine, and uric acid toward normal. The drug restored the LPS-mediated redox imbalance toward normal in lung and kidney tissues as assessed by measuring malondialdehyde and GSH levels. Finally, RT-PCR data revealed that olaparib downregulates the LPS-induced expression of NF-?B-dependent genes namely TNF-?, IL-1?, and VCAM-1 in the lungs without altering the expression of total p65NF-?B. Overall, the data suggest that olaparib has a strong potential to protect against LPS-induced lung injury and associated dysfunctioning of kidney in mice. Given the fact that olaparib is approved by FDA for human testing, our findings can pave the way for testing of the drug on humans inflicted with acute lung injury. PMID:25404465

Kapoor, Kunal; Singla, Esha; Sahu, Bijayani; Naura, Amarjit S

2015-02-01

276

Granulomatous lymphocytic interstitial lung disease in infancy  

PubMed Central

The authors report a case involving a child with chronic respiratory symptoms, who did not respond to conventional treatment. Low serum immunoglobin levels and pathological findings on lung biopsy revealed an unusual diagnosis for his age group. A specific treatment led to clinical improvement. PMID:24288696

Adeleye, Adetayo; Kelly, Margaret M; Wright, Nicola AM; Yu, Weiming; Anselmo, Mark A

2014-01-01

277

Treatment for sulfur mustard lung injuries; new therapeutic approaches from acute to chronic phase  

PubMed Central

Objective Sulfur mustard (SM) is one of the major potent chemical warfare and attractive weapons for terrorists. It has caused deaths to hundreds of thousands of victims in World War I and more recently during the Iran-Iraq war (1980–1988). It has ability to develop severe acute and chronic damage to the respiratory tract, eyes and skin. Understanding the acute and chronic biologic consequences of SM exposure may be quite essential for developing efficient prophylactic/therapeutic measures. One of the systems majorly affected by SM is the respiratory tract that numerous clinical studies have detailed processes of injury, diagnosis and treatments of lung. The low mortality rate has been contributed to high prevalence of victims and high lifetime morbidity burden. However, there are no curative modalities available in such patients. In this review, we collected and discussed the related articles on the preventive and therapeutic approaches to SM-induced respiratory injury and summarized what is currently known about the management and therapeutic strategies of acute and long-term consequences of SM lung injuries. Method This review was done by reviewing all papers found by searching following key words sulfur mustard; lung; chronic; acute; COPD; treatment. Results Mustard lung has an ongoing pathological process and is active disorder even years after exposure to SM. Different drug classes have been studied, nevertheless there are no curative modalities for mustard lung. Conclusion Complementary studies on one hand regarding pharmacokinetic of drugs and molecular investigations are mandatory to obtain more effective treatments. PMID:23351279

2012-01-01

278

Genetic susceptibility to irritant-induced acute lung injury in mice.  

PubMed

Recent studies suggest that genetic variability can influence irritant-induced lung injury and inflammation. To begin identifying genes controlling susceptibility to inhaled irritants, seven inbred mouse strains were continuously exposed to nickel sulfate (NiSO(4)), polytetrafluoroethylene, or ozone (O(3)), and survival time was recorded. The A/J (A) mouse strain was sensitive, the C3H/He (C3) strain was intermediate, and the C57BL/6 (B6) strain was resistant to NiSO(4)-induced acute lung injury. The B6AF(1) offspring were also resistant. The strain sensitivity pattern for NiSO(4) exposure was similar to that of polytetrafluoroethylene or ozone (O(3)). Pulmonary pathology was comparable for A and B6 mice. In the A strain, 15 microg/m(3) of NiSO(4) produced 20% mortality. The strain sensitivity patterns for lavage fluid proteins (B6 > C3 > A) and neutrophils (A >/= B6 > C3) differed from those for acute lung injury. This phenotype discordance suggests that these traits are not causally linked (i.e., controlled by independent arrays of genes). As in acute lung injury, B6C3F(1) offspring exhibited phenotypes (lavage fluid proteins and neutrophils) resembling those of the resistant parental strain. Agreement of acute lung injury strain sensitivity patterns among irritants suggested a common mechanism, possibly oxidative stress, and offspring resistance suggested that sensitivity is inherited as a recessive trait. PMID:10956633

Wesselkamper, S C; Prows, D R; Biswas, P; Willeke, K; Bingham, E; Leikauf, G D

2000-09-01

279

Supplementation of parenteral nutrition with fish oil attenuates acute lung injury in a rat model  

PubMed Central

Fish oil rich in n-3 polyunsaturated fatty acids has diverse immunomodulatory properties and attenuates acute lung injury when administered in enternal nutrition. However, enteral nutrition is not always feasible. Therefore, we investigated the ability of parenteral nutrition supplemented with fish oil to ameliorate acute lung injury. Rats were infused with parenteral nutrition solutions (without lipids, with soybean oil, or with soybean oil and fish oil) for three days. Lipopolysaccharide (15 mg/kg) was then administered intratracheally to induce acute lung injury, characterized by impaired lung function, polymorphonuclear leukocyte recruitment, parenchymal tissue damage, and upregulation of mRNAs for inflammatory mediators. Administration of parenteral nutrition supplemented with fish oil prior to lung insult improved gas exchange and inhibited neutrophil recruitment and upregulation of mRNAs for inflammatory mediators. Parenteral nutrition supplemented with fish oil also prolonged survival. To investigate the underlying mechanisms, leukotriene B4 and leukotriene B5 secretion was measured in neutrophils from the peritoneal cavity. The neutrophils from rats treated with fish oil-rich parenteral nutrition released significantly more leukotriene B5, an anti-inflammatory eicosanoid, than neutrophils isolated from rats given standard parenteral nutrition. Parenteral nutrition with fish oil significantly reduced lipopolysaccharide-induced lung injury in rats in part by promoting the synthesis of anti-inflammatory eicosanoids. PMID:24688221

Kohama, Keisuke; Nakao, Atsunori; Terashima, Mariko; Aoyama-Ishikawa, Michiko; Shimizu, Takayuki; Harada, Daisuke; Nakayama, Mitsuo; Yamashita, Hayato; Fujiwara, Mayu; Kotani, Joji

2014-01-01

280

NOX enzymes: potential target for the treatment of acute lung injury.  

PubMed

Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS), is characterized by acute inflammation, disruption of the alveolar-capillary barrier, and in the organizing stage by alveolar pneumocytes hyperplasia and extensive lung fibrosis. The cellular and molecular mechanisms leading to the development of ALI/ARDS are not completely understood, but there is evidence that reactive oxygen species (ROS) generated by inflammatory cells as well as epithelial and endothelial cells are responsible for inflammatory response, lung damage, and abnormal repair. Among all ROS-producing enzymes, the members of NADPH oxidases (NOXs), which are widely expressed in different lung cell types, have been shown to participate in cellular processes involved in the maintenance of lung integrity. It is not surprising that change in NOXs' expression and function is involved in the development of ALI/ARDS. In this context, the use of NOX inhibitors could be a possible therapeutic perspective in the management of this syndrome. In this article, we summarize the current knowledge concerning some cellular aspects of NOXs localization and function in the lungs, consider their contribution in the development of ALI/ARDS and discuss the place of NOX inhibitors as potential therapeutical target. PMID:22581364

Carnesecchi, Stéphanie; Pache, Jean-Claude; Barazzone-Argiroffo, Constance

2012-07-01

281

Therapeutic effect of intravenous infusion of perfluorocarbon emulsion on LPS-induced acute lung injury in rats.  

PubMed

Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS) are the leading causes of death in critical care. Despite extensive efforts in research and clinical medicine, mortality remains high in these diseases. Perfluorocarbon (PFC), a chemical compound known as liquid ventilation medium, is capable of dissolving large amounts of physiologically important gases (mainly oxygen and carbon dioxide). In this study we aimed to investigate the effect of intravenous infusion of PFC emulsion on lipopolysaccharide (LPS) induced ALI in rats and elucidate its mechanism of action. Forty two Wistar rats were randomly divided into three groups: 6 rats were treated with saline solution by intratracheal instillation (control group), 18 rats were treated with LPS by intratracheal instillation (LPS group) and the other 18 rats received PFC through femoral vein prior to LPS instillation (LPS+PFC group). The rats in the control group were sacrificed 6 hours later after saline instillation. At 2, 4 and 6 hours of exposure to LPS, 6 rats in the LPS group and 6 rats in LPS+PFC group were sacrificed at each time point. By analyzing pulmonary pathology, partial pressure of oxygen in the blood (PaO2) and lung wet-dry weight ratio (W/D) of each rat, we found that intravenous infusion of PFC significantly alleviated acute lung injury induced by LPS. Moreover, we showed that the expression of pulmonary myeloperoxidase (MPO), intercellular adhesion molecule-1 (ICAM-1) of endothelial cells and CD11b of polymorphonuclear neutrophils (PMN) induced by LPS were significantly decreased by PFC treatment in vivo. Our results indicate that intravenous infusion of PFC inhibits the infiltration of PMNs into lung tissue, which has been shown as the core pathogenesis of ALI/ARDS. Thus, our study provides a theoretical foundation for using intravenous infusion of PFC to prevent and treat ALI/ARDS in clinical practice. PMID:24489970

Hou, Shike; Ding, Hui; Lv, Qi; Yin, Xiaofeng; Song, Jianqi; Landén, Ning Xu; Fan, Haojun

2014-01-01

282

Lung disease due to the more common nontuberculous mycobacteria.  

PubMed

As the prevalence of tuberculosis (TB) declines in the developed world, the proportion of mycobacterial lung disease due to nontuberculous mycobacteria (NTM) is increasing. It is not clear whether there is a real increase in prevalence or whether NTM disease is being recognized more often because of the introduction of more sensitive laboratory techniques, and that more specimens are being submitted for mycobacterial staining and culture as the result of a greater understanding of the role of NTM in conditions such as cystic fibrosis, posttransplantation and other forms of iatrogenic immunosuppression, immune reconstitution inflammatory syndrome, fibronodular bronchiectasis, and hypersensitivity pneumonitis. The introduction of BACTEC liquid culture systems (BD; Franklin Lakes, NJ) and the development of nucleic acid amplification and DNA probes allow more rapid diagnosis of mycobacterial disease and the quicker differentiation of NTM from TB isolates. High-performance liquid chromatography, polymerase chain reaction, and restriction fragment length polymorphism analysis have helped to identify new NTM species. Although treatment regimens that include the newer macrolides are more effective than the earlier regimens, failure rates are still too high and relapse may occur after apparently successful therapy. Moreover, treatment regimens are difficult to adhere to because of their long duration, adverse effects, and interactions with the other medications that these patients require. The purpose of this article is to review the common presentations of NTM lung disease, the conditions associated with NTM lung disease, and the clinical features and treatment of the NTM that most commonly cause lung disease. PMID:16778288

Field, Stephen K; Cowie, Robert L

2006-06-01

283

Pulmonary endothelium in acute lung injury: from basic science to the critically ill  

Microsoft Academic Search

\\u000a Background: Pulmonary endothelium is an active organ possessing numerous physiological, immunological, and metabolic functions. These\\u000a functions may be altered early in acute lung injury (ALI) and further contribute to the development of acute respiratory distress\\u000a syndrome (ARDS). Pulmonary endothelium is strategically located to filter the entire blood before it enters the systemic circulation;\\u000a consequently its integrity is essential for the

S. E. Orfanos; I. Mavrommati; I. Korovesi; C. Roussos

284

Pulmonary endothelium in acute lung injury: from basic science to the critically ill  

Microsoft Academic Search

\\u000a \\u000a Background  Pulmonary endothelium is an active organ possessing numerous physiological, immunological, and metabolic functions. These\\u000a functions may be altered early in acute lung injury (ALI) and further contribute to the development of acute respiratory distress\\u000a syndrome (ARDS). Pulmonary endothelium is strategically located to filter the entire blood before it enters the systemic circulation;\\u000a consequently its integrity is essential for the maintenance

S. E. Orfanos; I. Mavrommati; I. Korovesi; C. Roussos

285

Effects of prone position on alveolar recruitment and oxygenation in acute lung injury  

Microsoft Academic Search

Objective: To investigate the effects of prone position (PP) on alveolar recruitment and oxygenation in acute respiratory failure.¶Design: Prospective physiologic study.¶Setting: Medical ICU two in a university hospital.¶Patients: Twelve adult patients intubated and mechanically ventilated with medical primary acute lung injury\\/adult respiratory distress\\u000a syndrome (ALI\\/ARDS) in whom PP was indicated.¶Measurements and results: We constructed the static inflation volume-pressure curves (V-P)

C. Guerin; M. Badet; S. Rosselli; L. Heyer; J.-M. Sab; B. Langevin; F. Philit; G. Fournier; D. Robert

1999-01-01

286

Inhibition of NADPH oxidase prevents acute lung injury in obese rats following severe trauma.  

PubMed

Lung capillary filtration coefficient (Kf) and impacts of oxidative stress have not been determined in the setting of severe trauma, especially in obese patients who exhibit increased lung injury. We hypothesized that severe trauma leads to a greater increase in lung Kf in obesity due to exacerbated production of and/or vulnerability to oxidative stress. Severe trauma was induced in lean and obese Zucker rats by muscle injury, fibula fracture, and bone component injection to both hindlimbs, with or without 24-h treatments of apocynin, a NADPH oxidase (NOX) inhibitor. Lung wet/dry weight ratios, lung vascular Kf, lung neutrophil counts, lung NOX and myeloperoxidase (MPO) activity, and plasma IL-6 levels were measured 24 h after trauma. In an additional study, lungs were isolated from nontrauma lean and obese rats to determine the acute effect of phenazime methosulfate, a superoxide donor, on pulmonary vascular Kf. After trauma, compared with lean rats, obese rats exhibited greater increases in lung capillary Kf, neutrophil accumulation, NOX and MPO activity, and plasma IL-6. The lung wet/dry weight ratio was increased in obese rats but not in lean rats. Apocynin treatment decreased lung Kf, neutrophil counts, NOX and MPO activities, wet/dry weight ratio, and plasma IL-6 in obese rats. Phenazime methosulfate treatment resulted in a greater increase in lung Kf in nontrauma obese rats compared with nontrauma lean rats. These results suggest that obese rats are susceptible to lung injury following severe trauma due to increased production of and responsiveness to pulmonary oxidative stress. PMID:24414071

Xiang, Lusha; Lu, Silu; Mittwede, Peter N; Clemmer, John S; Hester, Robert L

2014-03-01

287

Inhibition of NADPH oxidase prevents acute lung injury in obese rats following severe trauma  

PubMed Central

Lung capillary filtration coefficient (Kf) and impacts of oxidative stress have not been determined in the setting of severe trauma, especially in obese patients who exhibit increased lung injury. We hypothesized that severe trauma leads to a greater increase in lung Kf in obesity due to exacerbated production of and/or vulnerability to oxidative stress. Severe trauma was induced in lean and obese Zucker rats by muscle injury, fibula fracture, and bone component injection to both hindlimbs, with or without 24-h treatments of apocynin, a NADPH oxidase (NOX) inhibitor. Lung wet/dry weight ratios, lung vascular Kf, lung neutrophil counts, lung NOX and myeloperoxidase (MPO) activity, and plasma IL-6 levels were measured 24 h after trauma. In an additional study, lungs were isolated from nontrauma lean and obese rats to determine the acute effect of phenazime methosulfate, a superoxide donor, on pulmonary vascular Kf. After trauma, compared with lean rats, obese rats exhibited greater increases in lung capillary Kf, neutrophil accumulation, NOX and MPO activity, and plasma IL-6. The lung wet/dry weight ratio was increased in obese rats but not in lean rats. Apocynin treatment decreased lung Kf, neutrophil counts, NOX and MPO activities, wet/dry weight ratio, and plasma IL-6 in obese rats. Phenazime methosulfate treatment resulted in a greater increase in lung Kf in nontrauma obese rats compared with nontrauma lean rats. These results suggest that obese rats are susceptible to lung injury following severe trauma due to increased production of and responsiveness to pulmonary oxidative stress. PMID:24414071

Lu, Silu; Mittwede, Peter N.; Clemmer, John S.; Hester, Robert L.

2014-01-01

288

Akt2 deficiency as therapeutic strategy protects against acute lung injury  

PubMed Central

Acute respiratory distress syndrome (ARDS) currently has limited effective treatments, however, recent evidence suggest that modulation of alveolar macrophage responses may be an effective method for protection or repair of lung injury. Vergadi et al. are the first to demonstrate that depletion of Akt2 kinase and microRNA-146a induction in mice resulted in polarization of alveolar macrophages towards an M2 activation phenotype and resulted in less severe injury following acid-induced lung injury. However, this M2 polarization also resulted in increased lung bacterial load following infection with Pseudomonas aeruginosa. PMID:24815778

Gauna, Adrienne E; Cha, Seunghee

2015-01-01

289

Chronic kidney disease in acute coronary syndromes  

PubMed Central

Chronic kidney disease (CKD) is associated with a high burden of coronary artery disease. In patients with acute coronary syndromes (ACS), CKD is highly prevalent and associated with poor short- and long-term outcomes. Management of patients with CKD presenting with ACS is more complex than in the general population because of the lack of well-designed randomized trials assessing therapeutic strategies in such patients. The almost uniform exclusion of patients with CKD from randomized studies evaluating new targeted therapies for ACS, coupled with concerns about further deterioration of renal function and therapy-related toxic effects, may explain the less frequent use of proven medical therapies in this subgroup of high-risk patients. However, these patients potentially have much to gain from conventional revascularization strategies used in the general population. The objective of this review is to summarize the current evidence regarding the epidemiology and the clinical and prognostic relevance of CKD in ACS patients, in particular with respect to unresolved issues and uncertainties regarding recommended medical therapies and coronary revascularization strategies. PMID:24175251

Marenzi, Giancarlo; Cabiati, Angelo; Assanelli, Emilio

2012-01-01

290

Endogenous lung stem cells and contribution to disease  

PubMed Central

Epithelial branching during the process of lung development results in the establishment of distinct functional zones, each of which is characterized by a unique cellular composition and repertoire of local progenitor cells. Significant new insights into cellular and molecular mechanisms of epithelial maintenance that provide insights into the pathophysiology of lung disease have been made in recent years. This review focuses on the complex structure–function relationship in the airway epithelium, how this epithelium is maintained in the normal state and repaired following injury, and how deregulation may contribute to airway disease and cancer. PMID:19039828

Snyder, JC; Teisanu, RM; Stripp, BR

2009-01-01

291

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

PubMed Central

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

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

2014-01-01

292

Pulmonary Macrophage Subpopulations in the Induction and Resolution of Acute Lung Injury  

PubMed Central

Macrophages are key orchestrators of the inflammatory and repair responses in the lung, and the diversity of their function is indicated by their polarized states and distinct subpopulations and localization in the lung. Here, we characterized the pulmonary macrophage populations in the interstitial and alveolar compartments during the induction and resolution of acute lung injury induced by Pseudomonas aeruginosa infection. We identified macrophage subpopulations and polarity according to FACS analysis of cell surface protein markers, combined with cell sorting for gene expression using real-time PCR. With these techniques, we validated a novel, alternatively activated (M2) marker (transferrin receptor), and we described three interstitial and alveolar macrophage subpopulations in the lung whose distribution and functional state evolved from the induction to resolution phases of lung injury. Together, these findings indicate the presence and evolution of distinct macrophage subsets in the lung that serve specific niches in regulating the inflammatory response and its resolution. Alterations in the balance and function of these subpopulations could lead to nonresolving acute lung injury. PMID:22721830

Johnston, Laura K.; Rims, Cliff R.; Gill, Sean E.; McGuire, John K.

2012-01-01

293

Particle-induced pulmonary acute phase response may be the causal link between particle inhalation and cardiovascular disease  

PubMed Central

Inhalation of ambient and workplace particulate air pollution is associated with increased risk of cardiovascular disease. One proposed mechanism for this association is that pulmonary inflammation induces a hepatic acute phase response, which increases risk of cardiovascular disease. Induction of the acute phase response is intimately linked to risk of cardiovascular disease as shown in both epidemiological and animal studies. Indeed, blood levels of acute phase proteins, such as C-reactive protein and serum amyloid A, are independent predictors of risk of cardiovascular disease in prospective epidemiological studies. In this review, we present and review emerging evidence that inhalation of particles (e.g., air diesel exhaust particles and nanoparticles) induces a pulmonary acute phase response, and propose that this induction constitutes the causal link between particle inhalation and risk of cardiovascular disease. Increased levels of acute phase mRNA and proteins in lung tissues, bronchoalveolar lavage fluid and plasma clearly indicate pulmonary acute phase response following pulmonary deposition of different kinds of particles including diesel exhaust particles, nanoparticles, and carbon nanotubes. The pulmonary acute phase response is dose-dependent and long lasting. Conversely, the hepatic acute phase response is reduced relative to lung or entirely absent. We also provide evidence that pulmonary inflammation, as measured by neutrophil influx, is a predictor of the acute phase response and that the total surface area of deposited particles correlates with the pulmonary acute phase response. We discuss the implications of these findings in relation to occupational exposure to nanoparticles. How to cite this article: WIREs Nanomed Nanobiotechnol 2014, 6:517–531. doi: 10.1002/wnan.1279 PMID:24920450

Saber, Anne T; Jacobsen, Nicklas R; Jackson, Petra; Poulsen, Sarah Sřs; Kyjovska, Zdenka O; Halappanavar, Sabina; Yauk, Carole L; Wallin, Hĺkan; Vogel, Ulla

2014-01-01

294

CMVIG decreases the risk of cytomegalovirus infection but not disease after pediatric lung transplantation  

PubMed Central

A retrospective review of pediatric lung transplant recipients at fourteen sites in North America and Europe was conducted to evaluate the impact of adding cytomegalovirus immunoglobulin (CMVIG) prophylaxis to at least three weeks of intravenous ganciclovir in pediatric lung transplant recipients. Data were recorded for the first year after transplantation. Associations between time to CMV and risk factors, including CMVIG use, were assessed by multivariable Cox proportional hazards models. Of 599 subjects whose charts were reviewed, 329 received at least three weeks of ganciclovir with 62 (19%) receiving CMVIG. CMVIG was administered more frequently with CMV donor-positive/recipient-negative (D+/R?) serostatus (p<0.05). In multivariable models, subjects who did not receive CMVIG as part of their prophylaxis were three times more likely to develop CMV infection (HR 3.4; 95% CI 1.2, 9.5) independent of CMV serostatus. However, CMVIG administration was not associated with decreased risk of episodes of CMV disease. Receipt of CMVIG was not associated with decreased risks of post-transplant morbidities (acute rejection, respiratory viral infection or early bronchiolitis obliterans) or morbidity within the first year after pediatric lung transplantation. The use of CMVIG in addition to antiviral prophylaxis in pediatric lung transplantation requires further evaluation in pediatric lung transplant recipients. PMID:19782286

Ranganathan, K; Worley, S; Michaels, MG; Arrigain, S; Aurora, P; Ballmann, M; Boyer, D; Conrad, C; Eichler, I; Elidemir, O; Goldfarb, S; Mallory, GB; Mogayzel, PJ; Parakininkas, D; Solomon, M; Visner, G; Sweet, S; Faro, A; Danziger-Isakov, LA

2009-01-01

295

LPS-Induced Lung Inflammation in Marmoset Monkeys – An Acute Model for Anti-Inflammatory Drug Testing  

PubMed Central

Increasing incidence and substantial morbidity and mortality of respiratory diseases requires the development of new human-specific anti-inflammatory and disease-modifying therapeutics. Therefore, new predictive animal models that closely reflect human lung pathology are needed. In the current study, a tiered acute lipopolysaccharide (LPS)-induced inflammation model was established in marmoset monkeys (Callithrix jacchus) to reflect crucial features of inflammatory lung diseases. Firstly, in an ex vivo approach marmoset and, for the purposes of comparison, human precision-cut lung slices (PCLS) were stimulated with LPS in the presence or absence of the phosphodiesterase-4 (PDE4) inhibitor roflumilast. Pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-?) and macrophage inflammatory protein-1 beta (MIP-1?) were measured. The corticosteroid dexamethasone was used as treatment control. Secondly, in an in vivo approach marmosets were pre-treated with roflumilast or dexamethasone and unilaterally challenged with LPS. Ipsilateral bronchoalveolar lavage (BAL) was conducted 18 hours after LPS challenge. BAL fluid was processed and analyzed for neutrophils, TNF-?, and MIP-1?. TNF-? release in marmoset PCLS correlated significantly with human PCLS. Roflumilast treatment significantly reduced TNF-? secretion ex vivo in both species, with comparable half maximal inhibitory concentration (IC50). LPS instillation into marmoset lungs caused a profound inflammation as shown by neutrophilic influx and increased TNF-? and MIP-1? levels in BAL fluid. This inflammatory response was significantly suppressed by roflumilast and dexamethasone. The close similarity of marmoset and human lungs regarding LPS-induced inflammation and the significant anti-inflammatory effect of approved pharmaceuticals assess the suitability of marmoset monkeys to serve as a promising model for studying anti-inflammatory drugs. PMID:22952743

Seehase, Sophie; Lauenstein, Hans-Dieter; Schlumbohm, Christina; Switalla, Simone; Neuhaus, Vanessa; Förster, Christine; Fieguth, Hans-Gerd; Pfennig, Olaf; Fuchs, Eberhard; Kaup, Franz-Josef; Bleyer, Martina; Hohlfeld, Jens M.; Braun, Armin

2012-01-01

296

Perinatal factors in neonatal and pediatric lung diseases.  

PubMed

Wheezing and asthma are significant clinical problems for infants and young children, particularly following premature birth. Recurrent wheezing in infants can progress to persistent asthma. As in adults, altered airway structure (remodeling) and function (increased bronchoconstriction) are also important in neonatal and pediatric airway diseases. Accumulating evidence suggests that airway disease in children is influenced by perinatal factors including perturbations in normal fetal lung development, postnatal interventions in the intensive care unit (ICU) and environmental and other insults in the neonatal period. Here, in addition to genetics, maternal health, environmental processes, innate immunity and impaired lung development/function can all influence pathogenesis of airway disease in children. We summarize current understanding of how prenatal and postnatal factors can contribute to development of airway diseases in neonates and children. Understanding these mechanisms will help identify and develop novel therapies for childhood airway diseases. PMID:24090092

Britt, Rodney D; Faksh, Arij; Vogel, Elizabeth; Martin, Richard J; Pabelick, Christina M; Prakash, Y S

2013-10-01

297

Successful extracorporeal membranous oxygenation for a patient with life-threatening transfusion-related acute lung injury.  

PubMed

A case of transfusion-related acute lung injury (TRALI) that was successfully treated with extracorporeal membranous oxygenation (ECMO) is reported. A 58-year-old male patient underwent hepatectomy, and pulmonary edema occurred after the administration of fresh-frozen plasma and packed red cells. In the postoperative period, the impaired oxygenation progressively worsened, resulting in life-threatening hypoxemia, despite vigorous treatments. ECMO was therefore applied to the patient as a method of safe emergency support. Aggressive treatments under ECMO led to the successful improvement of the impaired oxygenation. TRALI is recognized as part of acute respiratory distress syndrome (ARDS). As a treatment for ARDS, ECMO does not cure the underlying disease of the lungs, however, with ECMO, TRALI, usually improves within 96 h with respiratory support. ECMO for TRALI-induced lethal hypoxemia is useful for providing time to allow the injured lung to recover. It is suggested that ECMO might be a useful option for the treatment of TRALI-induced, potentially lethal hypoxemia. PMID:19685127

Kuroda, Hiromitsu; Masuda, Yoshiki; Imaizumi, Hitoshi; Kozuka, Yuji; Asai, Yasufumi; Namiki, Akiyoshi

2009-01-01

298

Emodin Ameliorates LPS-Induced Acute Lung Injury, Involving the Inactivation of NF-?B in Mice  

PubMed Central

Acute lung injury (ALI) and its severe manifestation of acute respiratory distress syndrome (ARDS) are well-known illnesses. Uncontrolled and self-amplified pulmonary inflammation lies at the center of the pathology of this disease. Emodin, the bio-active coxund of herb Radix rhizoma Rhei, shows potent anti-inflammatory properties through inactivation of nuclear factor-?B (NF-?B). The aim of this study was to evaluate the effect of emodin on lipopolysaccharide (LPS)-induced ALI in mice, and its potential bio-mechanism. In our study, BALB/c mice were stimulated with LPS to induce ALI. After 72 h of LPS stimulation, pulmonary pathological changes, lung injury scores, pulmonary edema, myeloperoxidase (MPO) activity, total cells, neutrophils, macrophages, TNF-?, IL-6 and IL-1? in bronchoalveolar lavage fluid (BALF), and MCP-1 and E-selectin expression were notably attenuated by emodin in mice. Meanwhile, our data also revealed that emodin significantly inhibited the LPS-enhanced the phosphorylation of NF-?B p65 and NF-?B p65 DNA binding activity in lung. Our data indicates that emodin potently inhibits LPS-induced pulmonary inflammation, pulmonary edema and MCP-1 and E-selectin expression, and that these effects were very likely mediated by inactivation of NF-?B in mice. These results suggest a therapeutic potential of emodin as an anti-inflammatory agent for ALI/ARDS treatment. PMID:25347274

Xiao, Min; Zhu, Tao; Zhang, Wei; Wang, Tao; Shen, Yong-Chun; Wan, Qiong-Fang; Wen, Fu-Qiang

2014-01-01

299

Flow cytometric identification of fibrocytes in scleroderma lung disease.  

PubMed

Scleroderma is an autoimmune disease characterized by the progressive and dysregulated accumulation of collagen in the skin and internal organs. Pulmonary complications including interstitial lung disease have emerged as the greatest cause of mortality in this disease. Because treatments are limited, new areas of investigation are sorely needed. An emerging area of interest in this field is a potential role for fibrocytes as biomarkers or mediators of disease. Fibrocytes are monocyte-derived mesenchymal progenitor cells that exhibit features of extracellular matrix production and wound contraction in addition to immunologic functions such as cytokine and chemokine production, antigen presentation, leukocyte trafficking, and modulation of angiogenesis. Fibrocytes could participate in the pathogenesis of scleroderma lung disease through any or all of these functions and may be useful biomarkers of disease activity. This chapter presents protocols that have been developed for the study of fibrocytes obtained from human circulation and tissues. Protocols for the quantification of fibrocytes in murine models also are described, along with discussion of common technical challenges. It is hoped that this information will allow further investigation of the role that fibrocytes might play in Scleroderma-related lung disease and perhaps lead to new areas of study in this difficult-to-treat and deadly disease. PMID:22933077

Russell, Thomas M; Herzog, Erica L; Bucala, Richard

2012-01-01

300

Therapeutic Potential of Heme Oxygenase-1/Carbon Monoxide in Lung Disease  

PubMed Central

Heme oxygenase (HO), a catabolic enzyme, provides the rate-limiting step in the oxidative breakdown of heme, to generate carbon monoxide (CO), iron, and biliverdin-IX?. Induction of the inducible form, HO-1, in tissues is generally regarded as a protective mechanism. Over the last decade, considerable progress has been made in defining the therapeutic potential of HO-1 in a number of preclinical models of lung tissue injury and disease. Likewise, tissue-protective effects of CO, when applied at low concentration, have been observed in many of these models. Recent studies have expanded this concept to include chemical CO-releasing molecules (CORMs). Collectively, salutary effects of the HO-1/CO system have been demonstrated in lung inflammation/acute lung injury, lung and vascular transplantation, sepsis, and pulmonary hypertension models. The beneficial effects of HO-1/CO are conveyed in part through the inhibition or modulation of inflammatory, apoptotic, and proliferative processes. Recent advances, however, suggest that the regulation of autophagy and the preservation of mitochondrial homeostasis may serve as additional candidate mechanisms. Further preclinical and clinical trials are needed to ascertain the therapeutic potential of HO-1/CO in human clinical disease. PMID:22518295

Constantin, Myrna; Choi, Alexander J. S.; Cloonan, Suzanne M.; Ryter, Stefan W.

2012-01-01

301

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

PubMed

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

Young, Iven H; Bye, Peter T P

2011-04-01

302

Lung injury in mice and rats acutely exposed to beryllium  

SciTech Connect

The effect of lung injury, in rats and mice, exposed to an aerosol of beryllium sulfate (BE) for one hour, through nose-only inhalation, was evaluated by the methods of bronchoalveolar lavage (BAL) and lung cell kinetics. The BAL in rats, sacrificed over a 21 day period following exposure, showed lactate dehydrogenase (LDH) and alkaline phosphatase (Alk Pase) activities as the most sensitive indicators of lung damage. LDH activity peaked at day 8 while Alk Pase activity peaked at day 5, both being 30 times greater than comparable control values. Acid phosphatase activity and albumin levels were also increased, but not to the same extent as LDH and Alk Pase. The BAL of mice showed LDH activity as the most sensitive indicator of lung damage, with a maximum response 3 times greater than controls at day 5. In another series of experiments, animals were treated with three agents capable of inducing fibrosis: beryllium sulfate, bleomycin, and butylated hydroxytoluene (BHT). Cy A completely inhibited the fibrogenic effects of BHT in mice, as measured through total lung hydroxyproline content. Bleomycin-induced fibrosis was significantly reduced by Cy A treatment in rats, but showed no effect in mice. Additionally, the effect of iron salt administration to rats decreased the intravenous LD/sub 50/ dose, and significantly reduced the inhalation toxicity, of beryllium sulfate. The protective mechanism of iron salt administration, through the induction of ferritin synthesis, is postulated.

Sendelbach, L.E. Jr.

1985-01-01

303

Modulation of LPS-stimulated pulmonary inflammation by Borneol in murine acute lung injury model.  

PubMed

The object of our study is to investigate the protective effects of Borneol on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. To determine the effects of Borneol on the histopathological changes in mice with ALI, inflammatory cell count in bronchoalveolar lavage fluid (BALF) and lung wet/dry weight ratio were measured in LPS-challenged mice, and lung histopathologic changes observed via paraffin section were assessed. Next, cytokine production induced by LPS in BALF and RAW 264.7 cells was measured by enzyme-linked imunosorbent assay (ELISA). To further study the mechanism of Borneol-protective effects on ALI, nuclear factor-kappaB (NF-?B) and mitogen-activated protein kinases (MAPKs) pathways were investigated. In the present study, Borneol obviously alleviated pulmonary inflammation by reducing inflammatory infiltration, histopathological changes, descended cytokine production, and pulmonary edema initiated by LPS. Furthermore, Borneol significantly suppressed phosphorylation of NF-?B/P65, I?Ba, p38, JNK, and ERK. Taken together, our results suggest that Borneol suppressed inflammatory responses in LPS-induced acute lung injury through inhibition of the NF-?B and MAPKs signaling pathways. Borneol may be a promising potential preventive agent for acute lung injury treatment. PMID:24566873

Zhong, Weiting; Cui, Yiwen; Yu, Qinlei; Xie, Xianxing; Liu, Yan; Wei, Miaomiao; Ci, Xinxin; Peng, Liping

2014-08-01

304

A case of metastasis-induced acute pancreatitis in a patient with small cell lung cancer  

PubMed Central

Key Clinical Message We report a rare case of metastasis-induced acute pancreatitis (MIAP) from small cell lung cancer (SCLC) diagnosed on autopsy, indicating a diagnosis of MIAP with SCLC. Our case suggests that MIAP can arise as a complication of SCLC and has an extremely poor prognosis.

Yamanashi, Keiji; Marumo, Satoshi; Saitoh, Motoh; Kato, Motokazu

2015-01-01

305

Overexpression of extracellular superoxide dismutase reduces acute radiation induced lung toxicity  

Microsoft Academic Search

BACKGROUND: Acute RT-induced damage to the lung is characterized by inflammatory changes, which proceed to the development of fibrotic lesions in the late phase of injury. Ultimately, complete structural ablation will ensue, if the source of inflammatory \\/ fibrogenic mediators and oxidative stress is not removed or attenuated. Therefore, the purpose of this study is to determine whether overexpression of

Zahid N Rabbani; Mitchell S Anscher; Rodney J Folz; Emerald Archer; Hong Huang; Liguang Chen; Maria L Golson; Thaddeus S Samulski; Mark W Dewhirst; Zeljko Vujaskovic

2005-01-01

306

Gap Junction Channel Modulates Pulmonary Vascular Permeability through Calcium in Acute Lung Injury: An Experimental Study  

Microsoft Academic Search

Background: Increased pulmonary vascular permeability is a hallmark of acute lung injury (ALI). Gap junction channels (GJCs) connect adjacent cells and facilitate ion exchange. It remained unclear whether GJCs modulate pulmonary permeability in ALI through intracellular calcium. Objectives: This study aimed to verify if GJCs in pulmonary microvessel endothelial cells (PMVECs) modulate pulmonary vascular permeability in ALI via intracellular calcium.

Jinzhou Zhang; Wen Wang; Jing Sun; Qiang Li; Jincheng Liu; Hailong Zhu; Tao Chen; Hongbing Wang; Shiqiang Yu; Guocheng Sun; Wensheng Chen; Dinghua Yi

2010-01-01

307

A phase 1 trial of nebulised heparin in acute lung injury  

Microsoft Academic Search

INTRODUCTION: Animal studies of acute lung injury (ALI) suggest nebulised heparin may limit damage from fibrin deposition in the alveolar space and microcirculation. No human studies have been undertaken to date. We assessed the feasibility, safety and potential anticoagulant effects of administration of nebulised heparin to patients with ALI. METHODS: An open label phase 1 trial of four escalating doses

Barry Dixon; John D Santamaria; Duncan J Campbell

2008-01-01

308

ROLE OF CELL SIGNALING IN PROTECTION FROM DIESEL AND LPS INDUCED ACUTE LUNG INJURY  

EPA Science Inventory

We have previously demonstrated in CD-1 mice that pre-administration of N-acetyl cysteine (NAC) or the p38 MAP kinase inhibitor (SB203580) reduces acute lung injury and inflammation following pulmonary exposures to diesel exhaust particles (DEP) or lipopolysaccharide (LPS). Here ...

309

MATRILYSIN PARTICIPATES IN THE ACUTE LUNG INJURY INDUCED BY OIL COMBUSTION PRODUCTS  

EPA Science Inventory

ROLE OF MATRILYSIN IN THE ACUTE LUNG INJURY INDUCED BY OIL COMBUSTION PARTICLES. K L Dreher1, WY Su2 and C L Wilson3. 1US Environmental Protection Agency, Research Triangle Park, NC; 2Duke University, Durham, NC;3Washington University, St. Louis, MO. Mechanisms by ...

310

Polymer-Surfactant Treatment of Meconium-induced Acute Lung Injury  

Microsoft Academic Search

Substances (for example, serum proteins or meconium) that inter- fere with the activity of pulmonary surfactant in vitro may also be important in the pathogenesis or progression of acute lung injury. Addition of polymers such as dextran or polyethylene glycol (PEG) to surfactants prevents and reverses surfactant inactivation. The purpose of this study was to find out whether surfactant\\/polymer mixtures

KAREN W. LU; H. WILLIAM TAEUSCH; BENGT ROBERTSON; JON GOERKE; JOHN A. CLEMENTS

2000-01-01

311

The effects of Gamijinhae-tang on elastase/lipopolysaccharide-induced lung inflammation in an animal model of acute lung injury  

PubMed Central

Background Gamijinhae-tang (GJHT) has long been used in Korea to treat respiratory diseases. The therapeutic effect of GJHT is likely associated with its anti-inflammatory activity. However, the precise mechanisms underlying its effects are unknown. This study was conducted to evaluate the protective effects of GJHT in a porcine pancreatic elastase (PPE) and lipopolysaccharide(LPS) induced animal model of acute lung injury (ALI). Methods In this study, mice were intranasally exposed to PPE and LPS for 4 weeks to induce chronic obstructive pulmonary disease (COPD)-like lung inflammation. Two hours prior to PPE and LPS administration, the treatment group was administered GJHT extracts via an oral injection. The numbers of neutrophils, lymphocytes, macrophages and total cells in the bronchoalveolar lavage (BAL) fluid were counted, and pro-inflammatory cytokines were also measured. For histologic analysis, hematoxylin and eosin (H&E) stains and periodic acid-Schiff (PAS) stains were evaluated. Results After inducing ALI by treating mice with PPE and LPS for 4 weeks, the numbers of neutrophils, lymphocytes and total cells were significantly lower in the GJHT group than in the ALI group. In addition, the IL-1? and IL-6 levels were significantly decreased in the GJHT group. The histological results also demonstrated the attenuation effect of GJHT on PPE- and LPS-induced lung inflammation. Conclusions The results of this study indicate that GJHT has significantly reduces PPE- and LPS-induced lung inflammation. The remarkable protective effects of GJHT suggest its therapeutic potential in COPD treatment. PMID:23866260

2013-01-01

312

Spred-2 Deficiency Exacerbates Lipopolysaccharide-Induced Acute Lung Inflammation in Mice  

PubMed Central

Background Acute respiratory distress syndrome (ARDS) is a severe and life-threatening acute lung injury (ALI) that is caused by noxious stimuli and pathogens. ALI is characterized by marked acute inflammation with elevated alveolar cytokine levels. Mitogen-activated protein kinase (MAPK) pathways are involved in cytokine production, but the mechanisms that regulate these pathways remain poorly characterized. Here, we focused on the role of Sprouty-related EVH1-domain-containing protein (Spred)-2, a negative regulator of the Ras-Raf-extracellular signal-regulated kinase (ERK)-MAPK pathway, in lipopolysaccharide (LPS)-induced acute lung inflammation. Methods Wild-type (WT) mice and Spred-2?/? mice were exposed to intratracheal LPS (50 µg in 50 µL PBS) to induce pulmonary inflammation. After LPS-injection, the lungs were harvested to assess leukocyte infiltration, cytokine and chemokine production, ERK-MAPK activation and immunopathology. For ex vivo experiments, alveolar macrophages were harvested from untreated WT and Spred-2?/? mice and stimulated with LPS. In in vitro experiments, specific knock down of Spred-2 by siRNA or overexpression of Spred-2 by transfection with a plasmid encoding the Spred-2 sense sequence was introduced into murine RAW264.7 macrophage cells or MLE-12 lung epithelial cells. Results LPS-induced acute lung inflammation was significantly exacerbated in Spred-2?/? mice compared with WT mice, as indicated by the numbers of infiltrating leukocytes, levels of alveolar TNF-?, CXCL2 and CCL2 in a later phase, and lung pathology. U0126, a selective MEK/ERK inhibitor, reduced the augmented LPS-induced inflammation in Spred-2?/? mice. Specific knock down of Spred-2 augmented LPS-induced cytokine and chemokine responses in RAW264.7 cells and MLE-12 cells, whereas Spred-2 overexpression decreased this response in RAW264.7 cells. Conclusions The ERK-MAPK pathway is involved in LPS-induced acute lung inflammation. Spred-2 controls the development of LPS-induced lung inflammation by negatively regulating the ERK-MAPK pathway. Thus, Spred-2 may represent a therapeutic target for the treatment of ALI. PMID:25275324

Xu, Yang; Ito, Toshihiro; Fushimi, Soichiro; Takahashi, Sakuma; Itakura, Junya; Kimura, Ryojiro; Sato, Miwa; Mino, Megumi; Yoshimura, Akihiko; Matsukawa, Akihiro

2014-01-01

313

in vivo tomographic velocimetry of the lung for the detailed study of lung disease and its treatments  

NASA Astrophysics Data System (ADS)

All lung disease dramatically alters the local motion of the lung during breathing. It stands to reason, therefore, that detailed measurement of lung motion could provide dramatic improvements in assessment of lung function. Using synchrotron-based phase contrast imaging, we have developed and applied tools for lung motion and function measurement. We demonstrate a low-dose alternative to traditional 4D-CT methods, capable of measuring instantaneous 3D tissue motion using only 6 projection images. Additionally, our technique provides estimation of the airflow distribution throughout the bronchial tree during the breathing cycle. The ability to measure lung function at a regional level will provide invaluable information for studies into normal and pathological lung dynamics, and may provide new pathways for diagnosis of regional lung diseases. Although proof-of-concept data were acquired on a synchrotron, the low-dose methodology developed lends itself to clinical scanning and offers translational opportunities.

Dubsky, Stephen; Hooper, Stuart B.; Siu, Karen K. W.; Fouras, Andreas

2012-10-01

314

Occupational lung diseases and the mining industry in Mongolia.  

PubMed

Mining production has accounted for around 50% of the gross industrial product in Mongolia since 1998. Dust-induced chronic bronchitis and pneumoconiosis currently account for the largest relative share (67.8%) of occupational diseases in Mongolia, and cases are increasing annually. In 1967-2004, medically diagnosed cases of occupational diseases in Mongolia numbered 7,600. Of these, 5,154 were confirmed cases of dust-induced chronic bronchitis and pneumoconiosis. Lung diseases and other mining-sector health risks pose major challenges for Mongolia. Gold and coal mines, both formal and informal, contribute significantly to economic growth, but the prevalence of occupational lung diseases is high and access to health care is limited. Rapid implementation of an effective national program of silicosis elimination and pneumoconiosis reduction is critical to ensure the health and safety of workers in this important sector of the Mongolian economy. PMID:17718177

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

2007-01-01

315

About 1 in 7 Older Adults Has Some Form of Lung Disease: CDC  

MedlinePLUS

... in 7 Older Adults Has Some Form of Lung Disease: CDC COPD, asthma affect many aging Americans (* ... January 6, 2015 Related MedlinePlus Pages Asthma COPD Lung Diseases TUESDAY, Jan. 6, 2015 (HealthDay News) -- Nearly ...

316

1 in 5 Preemies with Lung Disease Exposed to Secondhand Smoke  

MedlinePLUS

... please enable JavaScript. 1 in 5 Preemies With Lung Disease Exposed to Secondhand Smoke 22 percent were from ... hair of many children with premature birth-related lung disease whose parents claimed not to smoke, a new ...

317

Treatment with antileukinate, a CXCR2 chemokine receptor antagonist, protects mice against acute pancreatitis and associated lung injury  

Microsoft Academic Search

Acute pancreatitis is a common, and as yet incurable, clinical condition, the incidence of which has been increasing over recent years. Chemokines are believed to play a key role in the pathogenesis of acute pancreatitis. We have earlier shown that treatment with a neutralizing antibody against CINC, a CXC chemokine, protects rats against acute pancreatitis-associated lung injury. The hexapeptide antileukinate

Madhav Bhatia; Akhil Hegde

2007-01-01

318

Dimethylthiourea decreases acute lung edema in phorbol myristate acetate-treated rabbits  

SciTech Connect

Treatment with dimethylthiourea (DMTU), a potent O/sub 2/ metabolite scavenger, prevented neutrophil-mediated acute edema in lungs of rabbits given phorbol myristate acetate (PMA) and in isolated rabbit lungs perfused with neutrophils and PMA. DMTU-treated rabbits given PMA did not increase their lung weight-to-total body weight ratios (5.0 +/- 0.3) or lung lavage albumin concentrations (14 +/- 4.6 mg/dl) in comparison to untreated rabbits given PMA (6.6 +/- 0.5 and 60 +/- 10 mg/dl, respectively). Similarly, DMTU-treated isolated rabbit lungs perfused with neutrophils and PMA did not gain weight (0 g) or increase their lavage albumin concentrations (82 +/- 17 mg/dl) in comparison to untreated lungs perfused with neutrophils and PMA (71 +/- 3.1 g and 1299 +/- 47 mg/dl, respectively). DMTU did not appear to decrease edema by preventing increases in pulmonary arterial pressures (PAP). First, treatment with DMTU did not decrease initial PAP increases in rabbits given PMA. Second, even though addition of DMTU attenuated PAP increased in isolated lungs perfused with neutrophils and PMA, DMTU-treated isolated lungs did not develop acute edema when subjected to mechanical increases in venous outflow pressures. The mechanism by which DMTU decreases lung edema is unclear by may involve scavenging of toxic O/sub 2/ metabolites, since DMTU also decrease hydrogen peroxide (H/sub 2/O/sub 2/) and hydroxyl radical (OH) concentrations in in vitro mixtures containing neutrophils and PMA.

Jackson, J.H.; White, C.W.; McMurtry, I.F.; Berger, E.M.; Repine, J.E.

1986-07-01

319

DOES CHRONIC OZONE EXPOSURE LEAD TO LUNG DISEASE?  

EPA Science Inventory

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

320

Miners’ Lung: A History of Coal Dust Disease in Britain  

Microsoft Academic Search

Arthur McIvor and Ronald Johnston explore the experience of coal miners' lung diseases and the attempts at voluntary and legal control of dusty conditions in British mining from the late nineteenth century to the present. In this way, the book addresses the important issues of occupational health and safety within the mining industry; issues that have been severely neglected in

Arthur McIvor; Ronald Johnston

2007-01-01

321

Respiratory Symptoms of Obstructive Lung Disease in European Crop Farmers  

Microsoft Academic Search

Crop farming as a risk factor for respiratory symptoms of obstruc- tive lung disease was assessed. Random samples of crop farmers from four European countries were studied following a cross-sec- tional design. A questionnaire on respiratory symptoms and occu- pation was administered to determine prevalences, and the roles of the various crops as risk factors for respiratory symptoms were assessed

EDUARD MONSÓ; RAMÓN MAGAROLAS; KATJA RADON; BRIGITTA DANUSER; MARTIN IVERSEN; CHRISTOPH WEBER; ULRIKE OPRAVIL; KELLEY J. DONHAM; DENNIS NOWAK

2000-01-01

322

Rare Infiltrative Lung Diseases: A Challenge for Clinicians  

Microsoft Academic Search

Rare diffuse infiltrative lung diseases are a challenge for clinicians, radiologists, and pathologists for at least three reasons: (a) their low incidence and prevalence hamper the acquisition of expertise and frequently the diagnosis is delayed; (b) therapeutic actions are mainly empirical and based on steroid use, and (c) pathogenetic events are difficult to explain and only recently new therapeutic measures

Venerino Poletti; Ulrich Costabel; Gian Luca Casoni; Caterina Bigliazzi; Marjolein Drent; Dario Olivieri

2004-01-01

323

Epigenetic targets for novel therapies of lung diseases.  

PubMed

In spite of substantial advances in defining the immunobiology and function of structural cells in lung diseases there is still insufficient knowledge to develop fundamentally new classes of drugs to treat many lung diseases. For example, there is a compelling need for new therapeutic approaches to address severe persistent asthma that is insensitive to inhaled corticosteroids. Although the prevalence of steroid-resistant asthma is 5-10%, severe asthmatics require a disproportionate level of health care spending and constitute a majority of fatal asthma episodes. None of the established drug therapies including long-acting beta agonists or inhaled corticosteroids reverse established airway remodeling. Obstructive airways remodeling in patients with chronic obstructive pulmonary disease (COPD), restrictive remodeling in idiopathic pulmonary fibrosis (IPF) and occlusive vascular remodeling in pulmonary hypertension are similarly unresponsive to current drug therapy. Therefore, drugs are needed to achieve long-acting suppression and reversal of pathological airway and vascular remodeling. Novel drug classes are emerging from advances in epigenetics. Novel mechanisms are emerging by which cells adapt to environmental cues, which include changes in DNA methylation, histone modifications and regulation of transcription and translation by noncoding RNAs. In this review we will summarize current epigenetic approaches being applied to preclinical drug development addressing important therapeutic challenges in lung diseases. These challenges are being addressed by advances in lung delivery of oligonucleotides and small molecules that modify the histone code, DNA methylation patterns and miRNA function. PMID:25448041

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

2015-03-01

324

Identification of Early Interstitial Lung Disease in Smokers from the  

E-print Network

: Early interstitial lung disease; CT scan; smoker. ÂŞAUR, 2010 I diopathic pulmonary fibrosis (IPF most patients have advanced pulmonary fibrosis that does not respond to therapeutic intervention. Some for the identification of early ILD in a population of smokers (both with and without chronic obstructive pulmonary

325

Mycophenolate Mofetil Improves Lung Function in Connective Tissue Disease-associated Interstitial Lung Disease  

PubMed Central

Objective Small series suggest mycophenolate mofetil (MMF) is well tolerated and may be an effective therapy for connective tissue disease-associated interstitial lung disease (CTD-ILD). We examined the tolerability and longitudinal changes in pulmonary physiology in a large and diverse cohort of patients with CTD-ILD treated with MMF. Methods We identified consecutive patients evaluated at our center between January 2008 and January 2011 and prescribed MMF for CTD-ILD. We assessed safety and tolerability of MMF and used longitudinal data analyses to examine changes in pulmonary physiology over time, before and after initiation of MMF. Results We identified 125 subjects treated with MMF for a median 897 days. MMF was discontinued in 13 subjects. MMF was associated with significant improvements in estimated percentage of predicted forced vital capacity (FVC%) from MMF initiation to 52, 104, and 156 weeks (4.9% ± 1.9%, p = 0.01; 6.1% ± 1.8%, p = 0.0008; and 7.3% ± 2.6%, p = 0.004, respectively); and in estimated percentage predicted diffusing capacity (DLCO%) from MMF initiation to 52 and 104 weeks (6.3% ± 2.8%, p = 0.02; 7.1% ± 2.8%, p = 0.01). In the subgroup without usual interstitial pneumonia (UIP)-pattern injury, MMF significantly improved FVC% and DLCO%, and in the subgroup with UIP-pattern injury, MMF was associated with stability in FVC% and DLCO%. Conclusion In a large diverse cohort of CTD-ILD, MMF was well tolerated and had a low rate of discontinuation. Treatment with MMF was associated with either stable or improved pulmonary physiology over a median 2.5 years of followup. MMF appears to be a promising therapy for the spectrum of CTD-ILD. PMID:23457378

Fischer, Aryeh; Brown, Kevin K.; Du Bois, Roland M.; Frankel, Stephen K.; Cosgrove, Gregory P.; Fernandez-Perez, Evans R.; Huie, Tristan J.; Krishnamoorthy, Mahalakshmi; Meehan, Richard T.; Olson, Amy L.; Solomon, Joshua J.; Swigris, Jeffrey J.

2013-01-01

326

Protective effects of intranasal curcumin on paraquot induced acute lung injury (ALI) in mice.  

PubMed

Paraquot (PQ) is widely and commonly used as herbicide and has been reported to be hazardous as it causes lung injury. However, molecular mechanism underlying lung toxicity caused by PQ has not been elucidated. Curcumin, a known anti-inflammatory molecule derived from rhizomes of Curcuma longa has variety of pharmacological activities including free-radical scavenging properties but the protective effects of curcumin on PQ-induced acute lung injury (ALI) have not been studied. In this study, we aimed to study the effects of curcumin on ALI caused by PQ in male parke's strain mice which were challenged acutely by PQ (50mg/kg, i.p.) with or without curcumin an hour before (5mg/kg, i.n.) PQ intoxication. Lung specimens and the bronchoalveolar lavage fluid (BALF) were isolated for pathological and biochemical analysis after 48h of PQ exposure. Curcumin administration has significantly enhanced superoxide dismutase (SOD) and catalase activities. Lung wet/dry weight ratio, malondialdehyde (MDA) and lactate dehydrogenase (LDH) content, total cell number and myeloperoxidase (MPO) levels in BALF as well as neutrophil infiltration were attenuated by curcumin. Pathological studies also revealed that intranasal curcumin alleviate PQ-induced pulmonary damage and pro-inflammatory cytokine levels like tumor necrosis factor-? (TNF-?) and nitric oxide (NO). These results suggest that intranasal curcumin may directly target lungs and curcumin inhalers may prove to be effective in PQ-induced ALI treatment in near future. PMID:25461551

Tyagi, Namitosh; Kumari, Asha; Dash, D; Singh, Rashmi

2014-11-01

327

Grading acute graft-versus-host disease: Time to reconsider.  

PubMed

Acute graft-versus-host disease (GVHD) is a common and serious complication of allogeneic blood and marrow transplantation. Acute GVHD is commonly graded according to modified Glucksberg criteria. There is considerable within-grade heterogeneity with different patterns of skin, liver, or gut involvement. In this commentary, we provide an analytical review of ambiguities in acute GVHD severity scoring and offer specific proposals meant to generate discussion in the BMT community for adoption, refinement, and where appropriate, validation studies. PMID:25599820

Goyal, Rakesh K; Goyal, Manu; Sankaranarayan, Kumar

2015-05-01

328

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

PubMed Central

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

2011-01-01

329

Genetic disruption of Fra-1 decreases susceptibility to endotoxin-induced acute lung injury and mortality in mice.  

PubMed

The activator protein-1 (AP-1) transcription factor, comprising Jun and Fos family proteins, distinctly regulates various cellular processes, including those involved in inflammation. FOS like antigen 1 (Fra-1), a member of the Fos family, dimerizes with members of the Jun family and regulates gene expression in a context-dependent manner. Although respiratory toxicants are known to stimulate the expression of Fra-1 in the lung, whether Fra-1 promotes or decreases susceptibility to the development and progression of toxicant-induced lung disease in vivo is not well established. To determine the role of Fra-1 in LPS-induced acute lung injury and mortality, we administered LPS either intraperitoneally or intratracheally to Fra-1-sufficient (Fra-11(+/+)) and Fra-1-deficient (Fra-1(?/?)) mice. LPS-induced mortality, lung injury, inflammation, cytokine measurements, and AP-1 and NF-?B activities were then assessed in these mice. Fra-1(?/?) mice showed a greater resistance to LPS-induced mortality than did their Fra-1(+/+) counterparts. Consistent with this result, LPS-induced lung injury and inflammatory responses were markedly lower in Fra-1(?/?) mice than in Fra-1(+/+) mice. Compared with Fra-1(+/+) mice, Fra-1(?/?) mice showed a reduced influx of neutrophils into the lungs, accompanied by a decreased expression of proinflammatory cytokines in response to treatment with LPS. The decreased inflammatory responses in Fra-1(?/?) mice coincided with diminished and increased levels of NF-?B and c-Jun/AP-1 binding, respectively. These results demonstrate that Fra-1/AP-1 plays a key role in promoting LPS-induced injury and mortality in mice, and they suggest that targeting (i.e., inhibiting) this transcription factor may be a useful approach to dampening the adverse effects of exposure to endotoxins. PMID:21816965

Vaz, Michelle; Reddy, Narsa M; Rajasekaran, Subbiah; Reddy, Sekhar P

2012-01-01

330

Work of breathing in children with diffuse parenchymal lung disease.  

PubMed

Respiratory mechanics have been poorly studied in children with chronic diffuse parenchymal lung disease (DPLD). The aim of the study was to assess the usefulness of respiratory mechanics to monitor lung function alteration in children with DPLD. Respiratory mechanics, total (WOBt), elastic (WOBe) and resistive (WOBr) work of breathing, gas exchange, lung function and respiratory muscle strength were measured in 10 children, aged 1.8-18.4 years old, who were followed in our national reference centre. Mean tidal volume (Vt) was normal (11±4mL/kg) but respiratory rate (fr, 32±19breaths/min), fr/Vt (118±75breaths/min/L) and total lung resistance (10.2±4.8cmH2OL(-1)s) were increased. Mean WOBt was increased mainly due to WOBe. Dynamic lung compliance (Cldyn) was severely reduced (26±24mL/cmH2O). Cldyn and the oesophageal pressure-time product strongly correlated with vital capacity and functional residual capacity. Respiratory muscle strength was within the normal range. In conclusion, lung mechanics may be considered as useful complementary or alternative markers of functional abnormalities in children with DPLD. PMID:25445729

Khirani, Sonia; Nathan, Nadia; Ramirez, Adriana; Aloui, Sabrina; Delacourt, Christophe; Clément, Annick; Fauroux, Brigitte

2015-01-15

331

Computational modeling of the obstructive lung diseases asthma and COPD.  

PubMed

Asthma and chronic obstructive pulmonary disease (COPD) are characterized by airway obstruction and airflow imitation and pose a huge burden to society. These obstructive lung diseases impact the lung physiology across multiple biological scales. Environmental stimuli are introduced via inhalation at the organ scale, and consequently impact upon the tissue, cellular and sub-cellular scale by triggering signaling pathways. These changes are propagated upwards to the organ level again and vice versa. In order to understand the pathophysiology behind these diseases we need to integrate and understand changes occurring across these scales and this is the driving force for multiscale computational modeling. There is an urgent need for improved diagnosis and assessment of obstructive lung diseases. Standard clinical measures are based on global function tests which ignore the highly heterogeneous regional changes that are characteristic of obstructive lung disease pathophysiology. Advances in scanning technology such as hyperpolarized gas MRI has led to new regional measurements of ventilation, perfusion and gas diffusion in the lungs, while new image processing techniques allow these measures to be combined with information from structural imaging such as Computed Tomography (CT). However, it is not yet known how to derive clinical measures for obstructive diseases from this wealth of new data. Computational modeling offers a powerful approach for investigating this relationship between imaging measurements and disease severity, and understanding the effects of different disease subtypes, which is key to developing improved diagnostic methods. Gaining an understanding of a system as complex as the respiratory system is difficult if not impossible via experimental methods alone. Computational models offer a complementary method to unravel the structure-function relationships occurring within a multiscale, multiphysics system such as this. Here we review the currentstate-of-the-art in techniques developed for pulmonary image analysis, development of structural models of therespiratory system and predictions of function within these models. We discuss application of modeling techniques to obstructive lung diseases, namely asthma and emphysema and the use of models to predict response to therapy. Finally we introduce a large European project, AirPROM that is developing multiscale models toinvestigate structure-function relationships in asthma and COPD. PMID:25471125

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

2014-11-28

332

Computational modeling of the obstructive lung diseases asthma and COPD  

PubMed Central

Asthma and chronic obstructive pulmonary disease (COPD) are characterized by airway obstruction and airflow limitation and pose a huge burden to society. These obstructive lung diseases impact the lung physiology across multiple biological scales. Environmental stimuli are introduced via inhalation at the organ scale, and consequently impact upon the tissue, cellular and sub-cellular scale by triggering signaling pathways. These changes are propagated upwards to the organ level again and vice versa. In order to understand the pathophysiology behind these diseases we need to integrate and understand changes occurring across these scales and this is the driving force for multiscale computational modeling. There is an urgent need for improved diagnosis and assessment of obstructive lung diseases. Standard clinical measures are based on global function tests which ignore the highly heterogeneous regional changes that are characteristic of obstructive lung disease pathophysiology. Advances in scanning technology such as hyperpolarized gas MRI has led to new regional measurements of ventilation, perfusion and gas diffusion in the lungs, while new image processing techniques allow these measures to be combined with information from structural imaging such as Computed Tomography (CT). However, it is not yet known how to derive clinical measures for obstructive diseases from this wealth of new data. Computational modeling offers a powerful approach for investigating this relationship between imaging measurements and disease severity, and understanding the effects of different disease subtypes, which is key to developing improved diagnostic methods. Gaining an understanding of a system as complex as the respiratory system is difficult if not impossible via experimental methods alone. Computational models offer a complementary method to unravel the structure-function relationships occurring within a multiscale, multiphysics system such as this. Here we review the current state-of-the-art in techniques developed for pulmonary image analysis, development of structural models of the respiratory system and predictions of function within these models. We discuss application of modeling techniques to obstructive lung diseases, namely asthma and emphysema and the use of models to predict response to therapy. Finally we introduce a large European project, AirPROM that is developing multiscale models to investigate structure-function relationships in asthma and COPD. PMID:25471125

2014-01-01

333

The ultrastructure of rat lung following acute primary blast injury.  

PubMed Central

While a number of workers have described the effects of blast waves upon the lung at both the macroscopic and light microscopic level, studies involving the use of the electron microscope have not been reported. In the experiments reported here the ultrastructural changes seen in lungs from rats exposed to a blast wave impacting on the right side of the chest are described. Considerable damage to the right lower lobe was observed which took the form of tearing of the inter-alveolar septa with capillary rupture and intra-alveolar haemorrhage. Changes to the alveolar epithelium and type II pneumocytes were also noted. Lesions were also identified in the left lung; these included intra-alveolar oedema with a minimal amount of interstitial oedema together with increased pinocytosis and isolated rupture of the alveolar epithelium. 'Ballooning' of the endothelium into the lumen of the capillary was also observed. There was an indication that lesions noted in the left lung at the electron microscopic level may be progressive in the first 24 hours following injury. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 PMID:8499315

Brown, R. F.; Cooper, G. J.; Maynard, R. L.

1993-01-01

334

Regulatory effects of iNOS on acute lung inflammatory responses in mice.  

PubMed

The role of endogenous NO in the regulation of acute lung injury is not well defined. We investigated the effects of inducible nitric oxide synthase (iNOS) and endothelial NOS (eNOS) on the acute inflammatory response in mouse lungs. Acute lung injury was induced by intratracheal instillation of bacterial lipopolysaccharide (LPS) into wild-type (WT) mice and mice deficient in iNOS (iNOS(-/-)) or eNOS (eNOS(-/-)). Endpoints of inflammatory injury were myeloperoxidase (MPO) content and leak of albumin into lung. Inflammatory injury was similar in WT and eNOS(-/-) mice but was substantially increased in iNOS(-/-) mice. Bronchoalveolar lavage (BAL) fluids of iNOS(-/-) and WT mice showed similar levels of CXC chemokines (MIP-2, KC) but enhanced levels of CC chemokines (MCP-1, MCP-3). Increased lung content of MPO in iNOS(-/-) mice was reduced by anti-MCP-1 to values found in WT mice. In vitro stimulation of microvascular endothelial cells with LPS and IFN gamma revealed elevated production of CXC and CC chemokines in cells from iNOS(-/-) mice when compared to endothelial cells from iNOS(+/+) mice. Peritoneal macrophages from iNOS(-/-) donors also revealed increased production of CC chemokines after stimulation with LPS and interferon (IFN gamma). These data indicate that absence of iNOS causes enhanced lung inflammatory responses in mice which may be related to enhanced production of MCP-1 by endothelial cells and macrophages. It appears that iNOS affects the lung inflammatory response by regulating chemokine production. PMID:14633605

Speyer, Cecilia L; Neff, Thomas A; Warner, Roscoe L; Guo, Ren-Feng; Sarma, J Vidya; Riedemann, Niels C; Murphy, Megan E; Murphy, Hedwig S; Ward, Peter A

2003-12-01

335

Regulatory Effects of iNOS on Acute Lung Inflammatory Responses in Mice  

PubMed Central

The role of endogenous NO in the regulation of acute lung injury is not well defined. We investigated the effects of inducible nitric oxide synthase (iNOS) and endothelial NOS (eNOS) on the acute inflammatory response in mouse lungs. Acute lung injury was induced by intratracheal instillation of bacterial lipopolysaccharide (LPS) into wild-type (WT) mice and mice deficient in iNOS (iNOS?/?) or eNOS (eNOS?/?). Endpoints of inflammatory injury were myeloperoxidase (MPO) content and leak of albumin into lung. Inflammatory injury was similar in WT and eNOS?/? mice but was substantially increased in iNOS?/? mice. Bronchoalveolar lavage (BAL) fluids of iNOS?/? and WT mice showed similar levels of CXC chemokines (MIP-2, KC) but enhanced levels of CC chemokines (MCP-1, MCP-3). Increased lung content of MPO in iNOS?/? mice was reduced by anti-MCP-1 to values found in WT mice. In vitro stimulation of microvascular endothelial cells with LPS and IFN? revealed elevated production of CXC and CC chemokines in cells from iNOS?/? mice when compared to endothelial cells from iNOS+/+ mice. Peritoneal macrophages from iNOS?/? donors also revealed increased production of CC chemokines after stimulation with LPS and interferon (IFN?). These data indicate that absence of iNOS causes enhanced lung inflammatory responses in mice which may be related to enhanced production of MCP-1 by endothelial cells and macrophages. It appears that iNOS affects the lung inflammatory response by regulating chemokine production. PMID:14633605

Speyer, Cecilia L.; Neff, Thomas A.; Warner, Roscoe L.; Guo, Ren-Feng; Sarma, J. Vidya; Riedemann, Niels C.; Murphy, Megan E.; Murphy, Hedwig S.; Ward, Peter A.

2003-01-01

336

Prevention of Acute Rheumatic Fever and Rheumatic Heart Disease  

MedlinePLUS

Prevention of Acute Rheumatic Fever and Rheumatic Heart Disease Mariana Mirabel , MD ; Kumar Narayanan , MD ; Xavier Jouven , MD, PhD ; Eloi Marijon , MD, PhD From the ... at}yahoo.fr Next Section Introduction Acute rheumatic fever (ARF) is primarily the result of a bacterial ...

337

Captopril Ameliorates Myocarditis in Acute Experimental Chagas Disease  

E-print Network

Captopril Ameliorates Myocarditis in Acute Experimental Chagas Disease Juan S. Leon, BA; Kegiang, is commonly prescribed to patients with Chagas heart disease (CHD). There are few human studies and no animal collagen myosin Chagas heart disease (CHD), caused by the protozoan Trypanosoma cruzi, is a significant

Engman, David M.

338

Types of Childhood Interstitial Lung Disease  

MedlinePLUS

... age groups. Diseases more common in infancy include: Surfactant (sur-FAK-tant) dysfunction mutations Developmental disorders, such ... as the bronchioles, neuroendocrine cells, alveoli, capillary network, surfactant, and interstitial space. Rate This Content: Next >> March ...

339

[Serrapeptase-induced lung injury manifesting as acute eosiniphilic pneumonia].  

PubMed

An 84-year-old man was referred to our hospital because of fever, cough, and hemoptysis. The patient had acute respiratory failure (PaO2 < 40 mmHg) on admission, with diffuse interstitial infiltration and bilateral pleural effusion. The bronchoalveolar lavage fluid was bloody, and contained a high percentage of eosinophils (32%). A diagnosis of acute eosinophilic pneumonia was established, and the patient made a rapid recovery after corticosteroids were administered. When the DLST (drug lymphocyte stimulation test) was performed after the corticosteroid therapy was stopped, it was positive for serrapeptase, which had been prescribed for chronic cystitis for 3 months before the onset of the pneumonia. This was a case of drug (serrapeptase)-induced pneumonitis manifesting as acute eosinophilic pneumonia. PMID:11019569

Sasaki, S; Kawanami, R; Motizuki, Y; Nakahara, Y; Kawamura, T; Tanaka, A; Watanabe, S

2000-07-01

340

Baclofen, a GABABR Agonist, Ameliorates Immune-Complex Mediated Acute Lung Injury by Modulating Pro-Inflammatory Mediators  

PubMed Central

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 ? (TNF-? 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 I?B 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 I?B degradation. Additionally, baclofen significantly inhibited pro-inflammatory TNF-? and IL-1?AcP release and promoted BAL neutrophil apoptosis. Protective effects of baclofen treatment on ALI were possibly mediated by inhibition of TNF-?- and IL-1?-mediated inflammatory signaling. Interestingly, GABABR2 expression was regulated in the type II pneumocytes in lung tissue sections from lung injured patients, further suggesting a physiological role for GABABR2 in the repair process of lung damage. GABABR2 agonists may play a potential therapeutic role in ALI. PMID:25848767

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

341

Non-coding RNA as lung disease biomarkers.  

PubMed

Biomarkers are quantifiable indicators of disease. These surrogates should be specific, sensitive, predictive, robust and easily accessible. A major class of RNA described as non-coding RNA fulfils many of these criteria, and recent studies have demonstrated that the two major subclasses of non-coding RNA, long non-coding RNA and, in particular, microRNA are promising potential biomarkers. The ability to detect non-coding RNAs in biofluids has highlighted their usefulness as non-invasive markers of lung disease. Because expression of specific non-coding RNAs is altered in many lung diseases and their levels in the circulation often reflect the changes in expression of their lung-specific counterparts, exploiting these biomolecules as diagnostic tools seems an obvious goal. New technology is driving developments in this area and there has been significant recent progress with respect to lung cancer diagnostics. The non-coding RNA biomarker field represents a clear example of modern-day bench-to-bedside research. PMID:25550385

Vencken, Sebastian F; Greene, Catherine M; McKiernan, Paul J

2015-05-01

342

Pituitary and adrenal disease in acute medicine  

Microsoft Academic Search

The foundation doctor may need to deal with pituitary or adrenal pathology in the acute setting as part of a medical emergency or because an incidental lesion within the gland has been found on imaging. Pituitary apoplexy refers to a vascular event within a pituitary tumour, and the clinical features include acute onset headache, reduced consciousness, visual disturbance and diplopia.

Miles Levy

2008-01-01

343

Eliminating or blocking 12/15-lipoxygenase reduces neutrophil recruitment in mouse models of acute lung injury  

PubMed Central

Introduction Acute lung injury (ALI) is a common disease in critically ill patients with a high morbidity and mortality. 12/15-lipoxygenase (12/15-LO) is an enzyme generating 12-hydroxy-eicosatetraenoic acid (12-HETE) and 15-HETE from arachidonic acid. It has been shown that 12/15-LO is involved in the regulation of vascular permeability during ALI. Methods To test whether 12/15-LO participates in leukocyte recruitment into the lung, we investigated the role of 12/15-LO in mouse models of lipopolysaccharide (LPS)-induced pulmonary inflammation and acid-induced ALI, a clinically relevant model of acute lung injury. Results The increase in neutrophil recruitment following LPS inhalation was reduced in 12/15-LO-deficient (Alox15-/-) mice and in wild-type (WT) mice after the blocking of 12/15-LO with a pharmacological inhibitor. Bone marrow chimeras revealed that 12/15-LO in hematopoietic cells regulates neutrophil accumulation in the interstitial and alveolar compartments, whereas the accumulation of neutrophils in the intravascular compartment is regulated by 12/15-LO in non-hematopoietic and hematopoietic cells. Mechanistically, the increased plasma levels of the chemokine CXCL1 in Alox15-/- mice led to a reduced response of the neutrophil chemokine receptor CXCR2 to stimulation with CXCL1, which in turn abrogated neutrophil recruitment. Alox15-/- mice also showed decreased edema formation, reduced neutrophil recruitment and improved gas exchange in an acid-induced ALI model. Conclusions Our findings suggest that 12/15-LO modulates neutrophil recruitment into the lung by regulating chemokine/chemokine receptor homeostasis. PMID:22973824

2012-01-01

344

Autophagy: a potential therapeutic target in lung diseases  

PubMed Central

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

Nakahira, Kiichi

2013-01-01

345

Acute Demyelinating Disease after Oral Therapy with Herbal Extracts  

PubMed Central

Central nervous system demyelinating processes such as multiple sclerosis and acute disseminated encephalomyelitis constitute a group of diseases not completely understood in their physiopathology. Environmental and toxic insults are thought to play a role in priming autoimmunity. The aim of the present report is to describe a case of acute demyelinating disease with fatal outcome occurring 15 days after oral exposure to herbal extracts. PMID:21738505

Kostianovsky, Alex; Maskin, Patricio; Noriega, María M.; Soler, Cristina; Bonelli, Ignacio; Riley, Claire S.; O'Connor, Kevin C.; Saubidet, Cristi´n López; Alvarez, Paulino A.

2011-01-01

346

Nose and lungs: one way, one disease  

PubMed Central

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

2012-01-01

347

Probiotics in the Management of Lung Diseases  

PubMed Central

The physiology and pathology of the respiratory and gastrointestinal tracts are closely related. This similarity between the two organs may underlie why dysfunction in one organ may induce illness in the other. For example, smoking is a major risk factor for COPD and IBD and increases the risk of developing Crohn's disease. Probiotics have been defined as “live microorganisms which, when administered in adequate amounts, confer health benefits on the host.” In model systems probiotics regulate innate and inflammatory immune responses. Commonly used probiotics include lactic acid bacteria, particularly Lactobacillus, Bifidobacterium, and Saccharomyces, and these are often used as dietary supplements to provide a health benefit in gastrointestinal diseases including infections, inflammatory bowel disease, and colon cancer. In this respect, probiotics probably act as immunomodulatory agents and activators of host defence pathways which suggest that they could influence disease severity and incidence at sites distal to the gut. There is increasing evidence that orally delivered probiotics are able to regulate immune responses in the respiratory system. This review provides an overview of the possible role of probiotics and their mechanisms of action in the prevention and treatment of respiratory diseases. PMID:23737654

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

2013-01-01

348

Bifunctional Lipocalin Ameliorates Murine Immune Complex-induced Acute Lung Injury  

PubMed Central

Molecules that simultaneously inhibit independent or co-dependent proinflammatory pathways may have advantages over conventional monotherapeutics. OmCI is a bifunctional protein derived from blood-feeding ticks that specifically prevents complement (C)-mediated C5 activation and also sequesters leukotriene B4 (LTB4) within an internal binding pocket. Here, we examined the effect of LTB4 binding on OmCI structure and function and investigated the relative importance of C-mediated C5 activation and LTB4 in a mouse model of immune complex-induced acute lung injury (IC-ALI). We describe two crystal structures of bacterially expressed OmCI: one binding a C16 fatty acid and the other binding LTB4 (C20). We show that the C5 and LTB4 binding activities of the molecule are independent of each other and that OmCI is a potent inhibitor of experimental IC-ALI, equally dependent on both C5 inhibition and LTB4 binding for full activity. The data highlight the importance of LTB4 in IC-ALI and activation of C5 by the complement pathway C5 convertase rather than by non-C proteases. The findings suggest that dual inhibition of C5 and LTB4 may be useful for treatment of human immune complex-dependent diseases. PMID:23625922

Roversi, Pietro; Ryffel, Bernhard; Togbe, Dieudonnée; Maillet, Isabelle; Teixeira, Mauro; Ahmat, Nurfilza; Paesen, Guido C.; Lissina, Olga; Boland, Wilhelm; Ploss, Kerstin; Caesar, Joseph J. E.; Leonhartsberger, Susanne; Lea, Susan M.; Nunn, Miles A.

2013-01-01

349

Using a non-invasive assessment of lung injury in a murine model of acute lung injury  

PubMed Central

Arterial oxygen saturation has not been assessed sequentially in conscious mice as a direct consequence of an in vivo murine model of acute lung injury. Here, we report daily changes in arterial oxygen saturation and other cardiopulmonary parameters by using infrared pulse oximetry following intratracheal lipopolysaccharide (IT-LPS) for up to 9?days, and following IT-phosphate buffered saline up to 72?h as a control. We show that arterial oxygen saturation decreases, with maximal decline at 96?h post IT-LPS. Blood oxygen levels negatively correlate with 7 of 10 quantitative markers of murine lung injury, including neutrophilia and interleukin-6 expression. This identifies infrared pulse oximetry as a method to non-invasively monitor arterial oxygen saturation following direct LPS instillations. PMID:25478170

Lax, Siân; Wilson, Michael R; Takata, Masao; Thickett, David R

2014-01-01

350

[Diffuse infiltrative lung disease in scleroderma. Analysis of radio-clinical and functional semiology].  

PubMed

Scleroderma (SD) is a systemic disease that predominantly affects the skin. Diffuse infiltrative lung disease (DILD) is rare and occurs most often in the course of the disease. We analyzed seven cases of DILO of SD recorded between 2003 and 2010 among 196 PID (3.6%). Functional signs were limited to respiratory dyspnea, it was associated to dysphagia in six cases, dry syndrome in five cases and Raynaud's phenomenon in four cases. Clinical examination found crackles in the bases of the thorax in all cases and specific cutaneous signs in six cases. The chest radiograph showed that interstitial disease predominates at the lung bases in all cases with a large aspect of the pulmonary arteries in two cases. The chest CT scan confirmed the predominance of basal and peripheral damage with signs of fibrosis in six cases. The pulmonary function objectified a severe restrictive ventilatory defect in all cases. Bronchoscopy showed a normal macroscopic appearance in all cases, the broncho-alveolar lavage was predominated by neutrophilic formula in four cases. SCL 70 antibodies were positive in four cases. All patients were treated by steroids with improvement of dyspnea and stabilization of radiographs. A patient had died in an array of acute respiratory failure and one patient was lost to follow-up. DILD in scleroderma is rare and seldom reveals the disease, it affects the patient's prognosis especially when associated with arterial pulmonary hypertension. PMID:23587414

El Khattabi, W; Afif, H; Moussali, N; Aichane, A; Abdelouafi, A; Bouayad, Z

2013-06-01

351

ROLE OF TACHYKININS IN OZONE-INDUCED ACUTE LUNG INJURY  

EPA Science Inventory

To examine the hypothesis that the acute, reversible changes caused by O3 exposure are mediated by techykinin release, guinea pigs were depleted of tachykinins using repeated capsaicin (CAP) injections prior to O3 exposure, in an attempt to prevent O3-induced functional changes. ...

352

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

NASA Astrophysics Data System (ADS)

The goal of Lung Tissue Resource Consortium (LTRC) is to improve the management of diffuse lung diseases through a better understanding of the biology of Chronic Obstructive Pulmonary Disease (COPD) and fibrotic interstitial lung disease (ILD) including Idiopathic Pulmonary Fibrosis (IPF). Participants are subjected to a battery of tests including tissue biopsies, physiologic testing, clinical history reporting, and CT scanning of the chest. The LTRC is a repository from which investigators can request tissue specimens and test results as well as semi-quantitative radiology reports, pathology reports, and automated quantitative image analysis results from the CT scan data performed by the LTRC core laboratories. The LTRC Radiology Core Laboratory (RCL), in conjunction with the Biomedical Imaging Resource (BIR), has developed novel processing methods for comprehensive characterization of pulmonary processes on volumetric high-resolution CT scans to quantify how these diseases manifest in radiographic images. Specifically, the RCL has implemented a semi-automated method for segmenting the anatomical regions of the lungs and airways. In these anatomic regions, automated quantification of pathologic features of disease including emphysema volumes and tissue classification are performed using both threshold techniques and advanced texture measures to determine the extent and location of emphysema, ground glass opacities, "honeycombing" (HC) and "irregular linear" or "reticular" pulmonary infiltrates and normal lung. Wall thickness measurements of the trachea, and its branches to the 3 rd and limited 4 th order are also computed. The methods for processing, segmentation and quantification are described. The results are reviewed and verified by an expert radiologist following processing and stored in the public LTRC database for use by pulmonary researchers. To date, over 1200 CT scans have been processed by the RCL and the LTRC project is on target for recruitment of the 2200 patients with 1800 CT scans in the repository for the 5-year effort. Ongoing analysis of the results in the LTRC database by the LTRC participating institutions and outside investigators are underway to look at the clinical and physiological significance of the imaging features of these diseases and correlate these findings with quality of life and other important prognostic indicators of severity. In the future, the quantitative measures of disease may have greater utility by showing correlation with prognosis, disease severity and other physiological parameters. These imaging features may provide non-invasive alternative endpoints or surrogate markers to alleviate the need for tissue biopsy or provide an accurate means to monitor rate of disease progression or response to therapy.

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

2008-03-01

353

Natural Antioxidant Betanin Protects Rats from Paraquat-Induced Acute Lung Injury Interstitial Pneumonia  

PubMed Central

The effect of betanin on a rat paraquat-induced acute lung injury (ALI) model was investigated. Paraquat was injected intraperitoneally at a single dose of 20?mg/kg body weight, and betanin (25 and 100?mg/kg/d) was orally administered 3 days before and 2 days after paraquat administration. Rats were sacrificed 24 hours after the last betanin dosage, and lung tissue and bronchoalveolar lavage fluid (BALF) were collected. In rats treated only with paraquat, extensive lung injury characteristic of ALI was observed, including histological changes, elevation of lung?:?body weight ratio, increased lung permeability, increased lung neutrophilia infiltration, increased malondialdehyde (MDA) and myeloperoxidase (MPO) activity, reduced superoxide dismutase (SOD) activity, reduced claudin-4 and zonula occluden-1 protein levels, increased BALF interleukin (IL-1) and tumor necrosis factor (TNF)-? levels, reduced BALF IL-10 levels, and increased lung nuclear factor kappa (NF-?B) activity. In rats treated with betanin, paraquat-induced ALI was attenuated in a dose-dependent manner. In conclusion, our results indicate that betanin attenuates paraquat-induced ALI possibly via antioxidant and anti-inflammatory mechanisms. Thus, the potential for using betanin as an auxilliary therapy for ALI should be explored further.

Ma, Deshun; Zhang, Miao; Yang, Xuelian; Tan, Dehong

2015-01-01

354

Activation of PPAR? by Wy-14643 ameliorates systemic lipopolysaccharide-induced acute lung injury  

SciTech Connect

Highlights: •Activation of PPAR? attenuated LPS-mediated acute lung injury. •Pretreatment with Wy-14643 decreased the levels of IFN-? and IL-6 in ALI. •Nitrosative stress and lipid peroxidation were downregulated by PPAR? activation. •PPAR? agonists may be potential therapeutic targets for acute lung injury. -- Abstract: Acute lung injury (ALI) is a major cause of mortality and morbidity worldwide. The activation of peroxisome proliferator-activated receptor-? (PPAR?) by its ligands, which include Wy-14643, has been implicated as a potential anti-inflammatory therapy. To address the beneficial efficacy of Wy-14643 for ALI along with systemic inflammation, the in vivo role of PPAR? activation was investigated in a mouse model of lipopolysaccharide (LPS)-induced ALI. Using age-matched Ppara-null and wild-type mice, we demonstrate that the activation of PPAR? by Wy-14643 attenuated LPS-mediated ALI. This was evidenced histologically by the significant alleviation of inflammatory manifestations and apoptosis observed in the lung tissues of wild-type mice, but not in the corresponding Ppara-null mice. This protective effect probably resulted from the inhibition of LPS-induced increases in pro-inflammatory cytokines and nitroxidative stress levels. These results suggest that the pharmacological activation of PPAR? might have a therapeutic effect on LPS-induced ALI.

Yoo, Seong Ho, E-mail: yoosh@snu.ac.kr [Seoul National University Hospital, Biomedical Research Institute and Institute of Forensic Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Abdelmegeed, Mohamed A. [Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD (United States)] [Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD (United States); Song, Byoung-Joon, E-mail: bj.song@nih.gov [Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD (United States)] [Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD (United States)

2013-07-05

355

Immunopathogenesis of Severe Acute Respiratory Disease in Zaire ebolavirus-Infected Pigs  

PubMed Central

Ebola viruses (EBOV) are filamentous single-stranded RNA viruses of the family Filoviridae. Zaire ebolavirus (ZEBOV) causes severe haemorrhagic fever in humans, great apes and non-human primates (NHPs) with high fatality rates. In contrast, Reston ebolavirus (REBOV), the only species found outside Africa, is lethal to some NHPs but has never been linked to clinical disease in humans despite documented exposure. REBOV was isolated from pigs in the Philippines and subsequent experiments confirmed the susceptibility of pigs to both REBOV and ZEBOV with predilection for the lungs. However, only ZEBOV caused severe lung pathology in 5–6 weeks old pigs leading to respiratory distress. To further elucidate the mechanisms for lung pathology, microarray analysis of changes in gene expression was performed on lung tissue from ZEBOV-infected pigs. Furthermore, systemic effects were monitored by looking at changes in peripheral blood leukocyte subsets and systemic cytokine responses. Following oro-nasal challenge, ZEBOV replicated mainly in the respiratory tract, causing severe inflammation of the lungs and consequently rapid and difficult breathing. Neutrophils and macrophages infiltrated the lungs but only the latter were positive for ZEBOV antigen. Genes for proinflammatory cytokines, chemokines and acute phase proteins, known to attract immune cells to sites of infection, were upregulated in the lungs, causing the heavy influx of cells into this site. Systemic effects included a decline in the proportion of monocyte/dendritic and B cells and a mild proinflammatory cytokine response. Serum IgM was detected on day 5 and 6 post infection. In conclusion, a dysregulation/over-activation of the pulmonary proinflammatory response may play a crucial role in the pathogenesis of ZEBOV infection in 5–6 weeks old pigs by attracting inflammatory cells to the lungs. PMID:23626748

Nfon, Charles K.; Leung, Anders; Smith, Greg; Embury-Hyatt, Carissa; Kobinger, Gary; Weingartl, Hana M.

2013-01-01

356

Immunoglobulin G4-related lung disease: a disease with many different faces.  

PubMed

Immunoglobulin (Ig) G4-related lung disease is a fibroinflammatory entity that presents in protean ways. Diagnostically, IgG4-related lung disease requires a high clinical index of suspicion complemented by elevated serum IgG4 levels and?or biopsy that shows the characteristic pathological features. The disease is almost always responsive to systemic corticosteroids. However, relapse is common following their discontinuation. The authors present three cases to highlight the diverse clinical features, and to illustrate the diagnostic and therapeutic approaches to this disease. PMID:24093112

Hui, Phillip; Mattman, Andre; Wilcox, Pearce G; Wright, Joanne L; Sin, Don D

2013-01-01

357

Early acute lung injury: Criteria for identifying lung Injury prior to the need for positive pressure ventilation  

PubMed Central

Objective Mortality associated with acute lung injury (ALI) remains high. Early identification of ALI prior to onset of respiratory failure may provide a therapeutic window to target in future clinical trials. The recently validated Lung Injury Prediction Score (LIPS) identifies patients at risk for ALI but may be limited for routine clinical use. We sought to empirically derive clinical criteria for a pragmatic definition of Early Acute Lung Injury (EALI) to identify patients with lung injury prior to the need for positive pressure ventilation. Design Prospective observational cohort study. Setting Stanford University Hospital. Patients We prospectively evaluated 256 patients admitted to Stanford University Hospital with bilateral opacities on chest radiograph without isolated left atrial hypertension. Interventions None. Measurements and Main Results Of the 256 patients enrolled, 62 (25%) progressed to ALI requiring positive pressure ventilation. Clinical variables (through first 72 hours or up to 6 hours prior to ALI) associated with progression to ALI were analyzed by backward regression. Oxygen requirement, maximal respiratory rate, and baseline immune suppression were independent predictors of progression to ALI. A simple 3 component EALI score (1 point for oxygen requirement > 2 to 6 liters/min or 2 points for > 6 liters/min; and 1 point each for a respiratory rate ? 30 and immune suppression) accurately identified patients who progressed to ALI requiring positive pressure ventilation (AUC 0.86) and performed similarly to the LIPS. An EALI score ? 2 identified patients who progressed to ALI with 89% sensitivity and 75% specificity. Median time of progression from EALI criteria to ALI requiring positive pressure ventilation was 20 hours. Conclusions This pragmatic definition of EALI accurately identified patients who progressed to ALI prior to requiring positive pressure ventilation. Pending further validation, these criteria could be useful for future clinical trials targeting early treatment of ALI. PMID:23782966

Levitt, Joseph E.; Calfee, Carolyn S.; Goldstein, Benjamin A; Vojnik, Rosemary; Matthay, Michael A.

2013-01-01

358

Building a reference multimedia database for interstitial lung diseases.  

PubMed

This paper describes the methodology used to create a multimedia collection of cases with interstitial lung diseases (ILDs) at the University Hospitals of Geneva. The dataset contains high-resolution computed tomography (HRCT) image series with three-dimensional annotated regions of pathological lung tissue along with clinical parameters from patients with pathologically proven diagnoses of ILDs. The motivations for this work is to palliate the lack of publicly available collections of ILD cases to serve as a basis for the development and evaluation of image-based computerized diagnostic aid. After 38 months of data collection, the library contains 128 patients affected with one of the 13 histological diagnoses of ILDs, 108 image series with more than 41l of annotated lung tissue patterns as well as a comprehensive set of 99 clinical parameters related to ILDs. The database is available for research on request and after signature of a license agreement. PMID:21803548

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

2012-04-01

359

Aerosolised surfactant generated by a novel noninvasive apparatus reduced acute lung injury in rats  

PubMed Central

Introduction Exogenous surfactant has been explored as a potential therapy for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In the present study, a nebuliser driven by oxygen lines found in the hospital was developed to deliver aerosolised porcine pulmonary surfactant (PPS). We hypothesised that aerosolised surfactant inhaled through spontaneous breathing may effectively reduce severe lung injury. Methods Rats were intravenously injected with oleic acid (OA) to induce ALI and 30 minutes later they were divided into five groups: model (injury only), PPS aerosol (PPS-aer), saline aerosol (saline-aer), PPS instillation (PPS-inst), and saline instillation (Saline-Inst). Blood gases, lung histology, and protein and TNF-? concentrations in the bronchoalveolar lavage fluid (BALF) were examined. Results The PPS aerosol particles were less than 2.0 ?m in size as determined by a laser aerosol particle counter. Treatment of animals with a PPS aerosol significantly increased the phospholipid content in the BALF, improved lung function, reduced pulmonary oedema, decreased total protein and TNF-? concentrations in BALF, ameliorated lung injury and improved animal survival. These therapeutic effects are similar to those seen in the PPS-inst group. Conclusions This new method of PPS aerosolisation combines the therapeutic effects of a surfactant with partial oxygen inhalation under spontaneous breathing. It is an effective, simple and safe method of administering an exogenous surfactant. PMID:19257907

Sun, Yu; Yang, Rui; Zhong, Ji-gen; Fang, Feng; Jiang, Jin-jin; Liu, Ming-yao; Lu, Jian

2009-01-01

360

Acquired Cell-Mediated Immunodepression in Acute Chagas' Disease  

PubMed Central

In this study two groups of patients with acute Chagas' disease were identified. Group one consisted of five patients with apparent acute Chagas' disease. These patients showed symptoms and signals of an acute illness, such as high fever and enlarged spleen. One of these patients developed severe myocarditis and heart failure. Group two consisted of seven patients with inapparent acute Chagas' disease. This was a nonclinical entity, not perceived by the patient who did not seek medical care. The diagnosis was made by the shift of a serologic test which indicates the presence of immunoglobulin M antibodies to Trypanosoma cruzi. The patients with apparent acute Chagas' disease showed positive delayed-type skin response to T. cruzi antigen. Also, their leukocytes showed significant inhibition of migration in the presence of this antigen. By contrast, the patients with the inapparent acute Chagas' disease did not show positive delayed-type skin response to T. cruzi antigen and no significant inhibition was observed when their cells migrated in the presence of this antigen. Of interest, none of these patients was capable of developing contact sensitivity to 2,4-dinitrochlorobenzene. However, three out of five patients with the apparent acute disease and all the normal control subjects showed positive contact reaction after sensitization to this drug. The results of these experiments would suggest that the thymus-derived (T)-lymphocyte function is depressed in patients with the clinically inapparent acute Chagas' disease. This immunodepression seems to be acquired in the course of the T. cruzi infection because all patients showed positive delayed-type skin response to at least one ubiquitous microbial extract, thus indicating previously normal T-cell function. We hypothesize that T. cruzi antigens may directly stimulate T cells with the concomitant release of factors that might become supressive for T-cell responses. Furthermore, the suppressive effect might interfere with the T-cell response to other antigens, such as to 2,4-dinitrochlorobenzene. Images PMID:107195

Teixeira, Antonio R. L.; Teixeira, Glória; Macędo, Vanize; Prata, Aluizio

1978-01-01

361

Translational toxicological research: investigating and preventing acute lung injury in organophosphorus insecticide poisoning.  

PubMed

Poisoning through ingestion of organophosphorus (OP) insecticide is a leading cause of suicide globally. Severe poisoning with OP compounds creates an unconscious, paralysed patient with respiratory failure. These symptoms make pulmonary aspiration of stomach contents highly likely, potentially causing an acute lung injury. To explore this hypothesis, we created a Gottingen minipig pulmonary aspiration model (n=26) to investigate the mechanism and severity of lung injury created through pulmonary instillation of 0.5?mL/kg mixtures of porcine gastric juice (GJ), OP and/or its solvent. Early results show that aspiration of OP and GJ causes pulmonary neutrophil sequestration, alveolar haemorrhage and interstitial oedema, with disruption of the alveolar-capillary membrane. Further measurements will include quantitative CT imaging, histopathology scoring, acute lung injury biomarkers and respiratory function. In order to test the validity of the minipig model, a pilot study in Sri Lanka has been devised to observe signs of lung injury in human patients who have ingested OP insecticide with or without clinical evidence of pulmonary aspiration. Lung injury will be assessed with PaO2/FIO2 ratios and physiological dead space measurement. Blood, bronchoalveolar lavage and urine will be taken at 24 and 48?h after poisoning and at 3-4?h in surgical control patients to measure acute lung injury biomarkers. An unpublished toxicology study from Sri Lanka, 2011-2012, showed that over 40% of unconscious poisoned patients with a GCS <9 were not intubated for ambulance transfer between rural and district hospitals. Delay in intubation leads to aspiration pneumonitis and pneumonia in 38%-45% of unconscious poisoned patients. We hypothesise that non-drug assisted placement of supraglottic airways may be a good tool for use in unconscious poisoned patients requiring transfer from small rural hospitals in Asia. They could confer better airway protection than no airway intervention and reduce both morbidity and mortality. PMID:24351316

Hulse, Elspeth J; Clutton, R E; Drummond, G; Eddleston, M

2014-06-01

362

Efficacy and safety of mesenchymal stromal cells in preclinical models of acute lung injury: a systematic review protocol  

PubMed Central

Background Acute respiratory distress syndrome (ARDS) in humans is caused by an unchecked proinflammatory response that results in diffuse and severe lung injury, and it is associated with a mortality rate of 35 to 45%. Mesenchymal stromal cells (MSCs; ‘adult stem cells’) could represent a promising new therapy for this syndrome, since preclinical evidence suggests that MSCs may ameliorate lung injury. Prior to a human clinical trial, our aim is to conduct a systematic review to compare the efficacy and safety of MSC therapy versus controls in preclinical models of acute lung injury that mimic some aspects of the human ARDS. Methods/Design We will include comparative preclinical studies (randomized and non-randomized) of acute lung injury in which MSCs were administered and outcomes compared to animals given a vehicle control. The primary outcome will be death. Secondary outcomes will include the four key features of preclinical acute lung injury as defined by the American Thoracic Society consensus conference (histologic evidence of lung injury, altered alveolar capillary barrier, lung inflammatory response, and physiological dysfunction) and pathogen clearance for acute lung injury models that are caused by infection. Electronic searches of MEDLINE, Embase, BIOSIS Previews, and Web of Science will be constructed and reviewed by the Peer Review of Electronic Search Strategies (PRESS) process. Search results will be screened independently and in duplicate. Data from eligible studies will be extracted, pooled, and analyzed using random effects models. Risk of bias will be assessed using the Cochrane risk of bias tool, and individual study reporting will be assessed according to the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines. Discussion The results of this systematic review will comprehensively summarize the safety and efficacy of MSC therapy in preclinical models of acute lung injury. Our results will help translational scientists and clinical trialists to determine whether sufficient evidence exists to perform a human clinical trial. These results may also guide future acute lung injury preclinical and clinical research. PMID:24887266

2014-01-01

363

Mechanisms of Indirect Acute Lung Injury: A Novel Role for the Co-Inhibitory Receptor, Programmed Death-1 (PD-1)  

PubMed Central

Objective To determine the contribution of PD-1 in the morbidity and mortality associated with the development of indirect-acute lung injury Summary Background Data The immune cell interaction(s) leading to indirect-acute lung injury are not completely understood. In this respect, while we have recently shown that the murine cell surface co-inhibitory receptor, Programmed Cell death receptor (PD)-1, has a role in septic morbidity/mortality that is mediated in part through the effects on the innate immune arm. However, it is not know if PD-1 has a role in the development of indirect-acute lung injury and how this may be mediated at a cellular level. Methods PD-1 ?/? mice were used in a murine model of indirect-acute lung injury (hemorrhagic shock followed 24 h after with cecal ligation & puncture-septic challenge) and compared to wild type controls. Groups were initially compared for survival and subsequently for markers of pulmonary inflammation, influx of lymphocytes and neutrophils, and expression of PD-1 and its ligand, PD-L1. In addition, peripheral blood leukocytes of patients with indirect-acute lung injury were examined to assess changes in cellular PD-1 expression relative to mortality. Results PD-1 ?/? mice showed improved survival compared to wild type controls. In the mouse lung, CD4+, CD11c+ and Gr-1+ cells showed increased PD-1 expression in response to indirect-acute lung injury. However, while the rise in BAL fluid protein concentrations, lung IL-6, and lung MCP-1 were similar between PD-1 ?/? and wild type animals subjected to indirect acute lung injury, the PD-1 ?/? animals that were subjected to shock/septic challenge had reduced CD4:CD8 ratios, TNF-? levels, MPO activity, and caspase 3 levels in the lung. Comparatively, we observed that humans, who survived their acute lung injury, had significantly lower expression of PD-1 on T cells. Conclusions PD-1 expression contributes to mortality following the induction of indirect-acute lung injury and this appears to be associated with modifications in the cellular and cytokine profiles in the lung. PMID:21997806

Monaghan, Sean F.; Thakkar, Rajan K.; Heffernan, Daithi S.; Huang, Xin; Chung, Chun-Shiang; Lomas-Neira, Joanne; Cioffi, William G.; Ayala, Alfred

2011-01-01

364

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

PubMed Central

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

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

365

Pathogenesis and therapeutics of interstitial lung disease in systemic sclerosis.  

PubMed

Interstitial lung disease is a common manifestation in systemic sclerosis and is considered as one of the two main causes of death among these patients. Although the pathogenesis of interstitial lung disease related to systemic sclerosis (SSc-ILD) is very complex and not yet fully understood, diverse mechanisms such as vascular injury, altered immunological response and inflammatory activation have been proposed. Vascular injury is considered as the earliest event in the pathogenesis of this disease and has been associated with an excessive formation of alveolar capillaries, circulating endothelial cells, and increased expression of endothelin-1. Different cells like myofibroblasts, fibroblasts, endothelial cells and T lymphocytes are involved in the inflammatory activation. Meanwhile, lymphocyte activation, release of several cytokines and autoantibody production play an important role in the immunological response. To date, the treatment of SSc-ILD is not totally defined, as studies have shown mixed results. Given the high progression of the disease, it is difficult to enroll patients for clinical trials. Therefore, there is lack of evidence to guide therapeutic approaches. Throughout this paper, we present evidence supporting that the combination of glucocorticoids and cyclophosphamide is considered the best regimen for patients with SSc-ILD. In addition, we present data regarding the use of azathioprine, mycophenolate, anti-fibrosing agents, bosentan, rituximab, and imatinib mesylate as alternative therapies. Finally, for patients who are unresponsive to pharmacologic interventions, we present data regarding the efficacy of highdose immunosuppression with autologous transplantation of hematopoietic stem cells, and lung transplantation. PMID:25409668

Castillo-Tandazo, Wilson; González, José; Flores-Fortty, Adolfo

2013-01-01

366

Comparison of the Spo2/Fio2 Ratio and the Pao2/Fio2 Ratio in Patients With Acute Lung Injury or Acute Respiratory Distress Syndrome  

PubMed Central

Introduction: Diagnostic criteria for acute lung injury (ALI) and Acute Respiratory Distress syndrome (ARDS) includes acute onset of disease, chest radiograph demonstrating bilateral pulmonary infiltrates, lack of significant left ventricular dysfunction and Pao2/Fio2 (PF) ratio ?300 for ALI or ?200 for ARDS. Recent criteria require invasive arterial sampling. The pulse oximetric saturation Spo2/Fio2 (SF) ratio may be a reliable non-invasive alternative to the PF ratio. Methods: In this cross-sectional study, we enrolled 70 patients with ALI or ARDS who were admitted in Tabriz children’s hospital pediatrics intensive care unit (PICU). Spo2, Fio2, Pao2, charted within 5 minutes of each other and calculated SF and PF were recorded to determine the relationship between SF and PF ratio. SF values were examined as a substitute of PF ratio for diagnosis ARDS and ALI. Results: The relationship between SF and PF ratio was described by the following regression equation: SF=57+0.61 PF (P<0.001). SF ratios of 181 and 235 corresponded of PF ratio 300 and 200. The SF cutoff of 235 had 57% sensitivity and 100% specificity for diagnosis of ALI. The SF cutoff of 181 had 71% sensitivity and 82% specificity for diagnosis of ARDS. Conclusion: SF ratio is a reliable noninvasive surrogate for PF ratio to identify children with ALI or ARDS with the advantage of replacing invasive arterial blood sampling by non-invasive pulse oximetry.

Bilan, Nemat; Dastranji, Azar; Ghalehgolab Behbahani, Afshin

2015-01-01

367

Effect of volume reduction on lung transplant timing and selection for chronic obstructive pulmonary disease  

Microsoft Academic Search

Background: End-stage chronic obstructive pulmonary disease has traditionally been treated with lung transplantation. For 2 years, our lung transplantation program has placed patients with appropriate criteria for lung transplantation and volume reduction into a prospective management algorithm. These patients are offered the lung volume reduction option as a “bridge” to “extend” the eventual time to transplantation. We examine the results

Joseph E. Bavaria; Alberto Pochettino; Robert M. Kotloff; Bruce R. Rosengard; Peter M. Wahl; J. Roberts; Harold I. Palevsky; Larry R. Kaiser

1998-01-01

368

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

PubMed

Vitamin D deficiency is a global public health problem and has been associated with an increased incidence and severity of many diseases including diseases of the respiratory system. These associations have largely been demonstrated epidemiologically and have formed the basis of the justification for a large number of clinical supplementation trials with a view to improving disease outcomes. However, the trials that have been completed to date and the ongoing experimental studies that have attempted to demonstrate a mechanistic link between vitamin D deficiency and lung disease have been disappointing. This observation raises many questions regarding whether vitamin D deficiency is truly associated with disease pathogenesis, is only important in the exacerbation of disease or is simply an indirect biomarker of other disease mechanisms? In this review, we will briefly summarize our current understanding of the role of vitamin D in these processes with a focus on lung disease. PMID:23896653

Foong, Rachel E; Zosky, Graeme R

2013-08-01

369

Corticosteroids found ineffective for phosgene-induced acute lung injury in rats.  

PubMed

Various therapeutic regimes have been proposed with limited success for treatment of phosgene-induced acute lung injury (P-ALI). Corticoids were shown to be efficacious against chlorine-induced lung injury but there is still controversy whether this applies also to P-ALI. This study investigates whether different regimen of curatively administered budesonide (BUD, 10 mg/kg bw, i.p. bid; 100 mg/m(3)×30 min, nose-only inhalation), mometasone (MOM, 3 mg/kg bw, i.p. bid) and dexamethasone (DEX, 10, 30 mg/kg bw, i.p. bid), show efficacy to alleviate P-ALI. Efficacy of drugs was judged by nitric oxide (eNO) and carbon dioxide (eCO2) in exhaled air and whether these non-invasive biomarkers are suitable to assess the degree of airway injury (chlorine) relative to alveolar injury (phosgene). P-ALI related analyses included lung function (enhanced pause, Penh), morbidity, increased lung weights, and protein in bronchial alveolar lavage fluid (BALF) one day postexposure. One of the pathophysiological hallmarks of P-ALI was indicated by increased Penh lasting for approximately 20 h postexposure. Following the administration of BUD, this increase could be suppressed; however, without significant improvement in survival and lung edema (increased lung weights and BALF-protein). Collectively, protocols shown to be efficacious for chlorine (Chen et al., 2013) were ineffective and even increased adversity in the P-ALI model. This outcome warrants further study to seek for early biomarkers suitable to differentiate chlorine- and phosgene-induced acute lung injury at yet asymptomatic stage. The patterns of eNO and eCO2 observed following exposure to chlorine and phosgene may be suitable to guide the specialized clinical interventions required for each type of ALI. PMID:24910984

Luo, Sa; Pauluhn, Jürgen; Trübel, Hubert; Wang, Chen

2014-08-17

370

Ulinastatin reduces pathogenesis of phosgene-induced acute lung injury in rats.  

PubMed

Phosgene (CG) is an industrial chemical used to make plastics, rubbers, dyestuff, and pesticides. Although the inhalation of CG is relatively uncommon, its accidental exposure can lead to acute lung injury (ALI). Ulinastatin, a urinary trypsin inhibitor, has been emerged to use for the treatment of acute inflammatory state of a number of organs including the lung. In this study, we examined the pathogenic changes in the lungs after the inhalation of CG gas and also examined the effect of ulinastatin treatment in reversing these changes in rats. We found that the rats exposed to CG gas at a dose of 5.0 g/m(3) for 5 min led to ALI after 6 h. The signs of lung injury include pulmonary edema, hemorrhage, and cellular infiltration in pulmonary alveoli. In addition, interleukin-15 (IL-15) and intercellular adhesion molecule-1 (ICAM-1) were significantly increased in CG-inhaled animals. Ulinastatin administration at 1 h postexposure significantly reduced the intensity of all the pathological changes in the lungs of these CG-exposed animals. Ulinastatin at a dose of 400 U/g was shown to decrease the total number of cells in bronchoalveolar lavage fluid and the levels of IL-15 and ICAM-1 in the serum. We also found that the structure of the lung was protected by ulinastatin treatment. Thus, our data suggest that ulinastatin can be used as an effective drug for the treatment of CG-induced ALI. The serum levels of IL-15 and ICAM-1 can be used as the markers of lung injury after exposure to CG and may also serve as useful therapeutic targets at an early stage. The effects of long-term treatment of ulinastatin and the mechanisms by which ulinastatin decreases the infiltration of blood cells and reduces cytokines need further investigation. PMID:23075575

Shen, Jie; Gan, Zhengyi; Zhao, Jie; Zhang, Liming; Xu, Guoxiong

2014-10-01

371

Staphylococcal Enterotoxin B-Induced MicroRNA-155 Targets SOCS1 To Promote Acute Inflammatory Lung Injury  

PubMed Central

Staphylococcal enterotoxin B (SEB) causes food poisoning in humans. It is considered a biological weapon, and inhalation can trigger lung injury and sometimes respiratory failure. Being a superantigen, SEB initiates an exaggerated inflammatory response. While the role of microRNAs (miRNAs) in immune cell activation is getting increasing recognition, their role in the regulation of inflammatory disease induced by SEB has not been studied. In this investigation, we demonstrate that exposure to SEB by inhalation results in acute inflammatory lung injury accompanied by an altered miRNA expression profile in lung-infiltrating cells. Among the miRNAs that were significantly elevated, miR-155 was the most overexpressed. Interestingly, miR-155?/? mice were protected from SEB-mediated inflammation and lung injury. Further studies revealed a functional link between SEB-induced miR-155 and proinflammatory cytokine gamma interferon (IFN-?). Through the use of bioinformatics tools, suppressor of cytokine signaling 1 (SOCS1), a negative regulator of IFN-?, was identified as a potential target of miR-155. While miR-155?/? mice displayed increased expression of Socs1, the overexpression of miR-155 led to its suppression, thereby enhancing IFN-? levels. Additionally, the inhibition of miR-155 resulted in restored Socs1expression. Together, our data demonstrate an important role for miR-155 in promoting SEB-mediated inflammation in the lungs through Socs1 suppression and suggest that miR-155 may be an important target in preventing SEB-mediated inflammation and tissue injury. PMID:24778118

Rao, Roshni; Nagarkatti, Prakash

2014-01-01

372

Preventing cleavage of Mer promotes efferocytosis and suppresses acute lung injury in bleomycin treated mice  

SciTech Connect

Mer receptor tyrosine kinase (Mer) regulates macrophage activation and promotes apoptotic cell clearance. Mer activation is regulated through proteolytic cleavage of the extracellular domain. To determine if membrane-bound Mer is cleaved during bleomycin-induced lung injury, and, if so, how preventing the cleavage of Mer enhances apoptotic cell uptake and down-regulates pulmonary immune responses. During bleomycin-induced acute lung injury in mice, membrane-bound Mer expression decreased, but production of soluble Mer and activity as well as expression of disintegrin and metalloproteinase 17 (ADAM17) were enhanced . Treatment with the ADAM inhibitor TAPI-0 restored Mer expression and diminished soluble Mer production. Furthermore, TAPI-0 increased Mer activation in alveolar macrophages and lung tissue resulting in enhanced apoptotic cell clearance in vivo and ex vivo by alveolar macrophages. Suppression of bleomycin-induced pro-inflammatory mediators, but enhancement of hepatocyte growth factor induction were seen after TAPI-0 treatment. Additional bleomycin-induced inflammatory responses reduced by TAPI-0 treatment included inflammatory cell recruitment into the lungs, levels of total protein and lactate dehydrogenase activity in bronchoalveolar lavage fluid, as well as caspase-3 and caspase-9 activity and alveolar epithelial cell apoptosis in lung tissue. Importantly, the effects of TAPI-0 on bleomycin-induced inflammation and apoptosis were reversed by coadministration of specific Mer-neutralizing antibodies. These findings suggest that restored membrane-bound Mer expression by TAPI-0 treatment may help resolve lung inflammation and apoptosis after bleomycin treatment. -- Highlights: ?Mer expression is restored by TAPI-0 treatment in bleomycin-stimulated lung. ?Mer signaling is enhanced by TAPI-0 treatment in bleomycin-stimulated lung. ?TAPI-0 enhances efferocytosis and promotes resolution of lung injury.

Lee, Ye-Ji [Department of Physiology, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of) [Department of Physiology, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of); Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of); Lee, Seung-Hae [Department of Physiology, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of)] [Department of Physiology, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of); Youn, Young-So; Choi, Ji-Yeon [Department of Physiology, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of) [Department of Physiology, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of); Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of); Song, Keung-Sub [Department of Physiology, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of)] [Department of Physiology, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of); Cho, Min-Sun [Department of Pathology, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of)] [Department of Pathology, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of); Kang, Jihee Lee, E-mail: jihee@ewha.ac.kr [Department of Physiology, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of); Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, Seoul (Korea, Republic of)

2012-08-15

373

Platelet Vascular Endothelial Growth Factor is a Potential Mediator of Transfusion-Related Acute Lung Injury  

PubMed Central

Objective The occurrence of non-hemolytic transfusion reactions is highest with platelet and plasma administration. Some of these reactions are characterized by endothelial leak, especially transfusion related acute lung injury (TRALI). Elevated concentrations of inflammatory mediators secreted by contaminating leukocytes during blood product storage may contribute to such reactions, but platelet-secreted mediators may also contribute. We hypothesized that platelet storage leads to accumulation of the endothelial permeability mediator vascular endothelial growth factor (VEGF), and that intravascular administration of exogenous VEGF leads to extensive binding to its lung receptors. Methods Single donor, leukocyte-reduced apheresis platelet units were sampled over 5 days of storage. VEGF protein content of the centrifuged supernatant was determined by ELISA, and the potential contribution of VEGF from contaminating leukocytes was quantified. Isolated-perfused rat lungs were used to study the uptake of radiolabeled VEGF administered intravascularly, and the effect of unlabeled VEGF on lung leak. Results There was a time-dependent release of VEGF into the plasma fraction of the platelet concentrates (62 ± 9 pg/ml on day one, 149 ± 23 pg/ml on day 5; mean ± SEM, p<0.01, n=8) and a contribution by contaminating leukocytes was excluded. Exogenous 125I-VEGF bound avidly and specifically to the lung vasculature, and unlabeled VEGF in the lung perfusate caused vascular leak. Conclusion Rising concentrations of VEGF occur during storage of single donor platelet concentrates due to platelet secretion or disintegration, but not due to leukocyte contamination. Exogenous VEGF at these concentrations rapidly binds to its receptors in the lung vessels. At higher VEGF concentrations, VEGF causes vascular leak in uninjured lungs. These data provide further evidence that VEGF may contribute to the increased lung permeability seen in TRALI associated with platelet products. PMID:25705568

Maloney, James P; Ambruso, Daniel R; Voelkel, Norbert F; Silliman, Christopher C

2015-01-01

374

Developing novel therapeutic strategies for acute lung injury and infection-peripheral blood monocyte depletion and prophylactic antimicrobial therapy   

E-print Network

BACKGROUND Acute lung injury (ALI) and nosocomial pneumonia are major causes of morbidity and mortality. There are 200,000 cases per year of ALI in the US with a mortality of 40%. On the intensive care unit (ICU), ALI ...

Dhaliwal, Kanwaldeep

2013-07-06

375

Endothelial dysfunction and lung capillary injury in cardiovascular diseases.  

PubMed

Cardiac dysfunction of both systolic and diastolic origins leads to increased left atrial pressure, lung capillary injury and increased resistance to gas transfer. Acutely, pressure-induced trauma disrupts the endothelial and alveolar anatomical configuration and definitively causes an impairment of cellular pathways involved in fluid-flux regulation and gas exchange efficiency, a process well identified as stress failure of the alveolar-capillary membrane. In chronic heart failure (HF), additional stimuli other than pressure may trigger the true remodeling process of capillaries and small arteries characterized by endothelial dysfunction, proliferation of myofibroblasts, fibrosis and extracellular matrix deposition. In parallel there is a loss of alveolar gas diffusion properties due to the increased path from air to blood (thickening of extracellular matrix) and loss of fine molecular mechanism involved in fluid reabsorption and clearance. Deleterious changes in gas transfer not only reflect the underlying lung tissue damage but also portend independent prognostic information and may play a role in the pathogenesis of exercise limitation and ventilatory abnormalities observed in these patients. Few currently approved treatments for chronic HF have the potential to positively affect structural remodeling of the lung capillary network; angiotensin-converting enzyme inhibitors are one of the few currently established options. Recently, more attention has been paid to novel therapies specifically targeting the nitric oxide pathway as a suitable target to improve endothelial function and permeability as well as alveolar gas exchange properties. PMID:25446556

Guazzi, Marco; Phillips, Shane A; Arena, Ross; Lavie, Carl J

2015-01-01

376

Method Of Treating Silicosis And Other Occupational Lung Diseases  

Cancer.gov

The inhalation of dust containing crystalline silica particles causes silicosis, an incurable lung disease that progresses even after dust exposure ceases. Over a million US workers are exposed to silica dust annually, and thousands worldwide die each year from silicosis. The pulmonary inflammation caused by silica inhalation is characterized by a cellular infiltrate and the accumulation of chemokines, cytokines, and Reactive Oxygen Species (ROS) in bronchoalveolar lavage fluid.

377

Neonatal Chronic Lung Disease in Extremely Immature Baboons  

Microsoft Academic Search

A borderline viability model of bronchopulmonary dysplasia (BPD)\\/chronic lung disease of infancy (CLD) with pathophysiologic parameters consistent with those in extremely immature humans with BPD\\/CLD is described. After prenatal steroid treatment of pregnant dams, 12 premature baboons were delivered by cesarean-section at 125 d (term gestation, 185 d), treated with exogenous surfac- tant, and maintained on appropriate oxygen and positive

JACQUELINE J. COALSON; VICKI T. WINTER; THERESA SILER-KHODR; BRADLEY A. YODER

1999-01-01

378

Interstitial lung disease in systemic sclerosis: optimizing evaluation and management  

Microsoft Academic Search

Since angiotensin-converting-enzyme (ACE) inhibitors are saving the lives of the majority of systemic sclerosis (SSc) patients affect- ed by scleroderma renal crisis (SRC), most SSc deaths are now the result of end-stage lung disease (both interstitial and pulmonary vascular). Although ~90% of SSc patients have been found to have pulmonary interstitial fibrotic changes at postmortem exam- ination or on high-resolution

Richard M. Silver; Philip J. Clements

2003-01-01

379

Interstitial Lung Disease in Coppersmiths in High Serum Copper Levels  

Microsoft Academic Search

Coppersmith is a worker who uses copper most commonly for the production of kitchen appliances in Turkey. This is an ancient\\u000a occupation practiced for centuries in Turkey. Our objective was to investigate the prevalence of parenchymal lung diseases\\u000a among coppersmiths in Kahramanmaras city in Turkey. Thirty coppersmiths were included to the study, and they all signed an\\u000a informed consent. Demographics,

Canan Eren Dagli; Abdullah Cetin Tanrikulu; Nurhan Koksal; Abdurrahman Abakay; Mehmet Emin Gelen; Gulen Demirpolat; Murvet Yuksel; Nurhan Atilla; Fatma Inanc Tolun

2010-01-01

380

Interstitial Lung Disease Induced by Drugs and Radiation  

Microsoft Academic Search

An ever-increasing number of drugs can reproduce variegated patterns of naturally occurring interstitial lung disease (ILD), including most forms of interstitial pneumonias, alveolar involvement and, rarely, vasculitis. Drugs in one therapeutic class may collectively produce the same pattern of involvement. A few drugs can produce more than one pattern of ILD. The diagnosis of drug-induced ILD (DI-ILD) essentially rests on

Philippe Camus; Annlyse Fanton; Philippe Bonniaud; Clio Camus; Pascal Foucher

2004-01-01

381

Cerebrospinal Fluid Proteome of Patients with Acute Lyme Disease  

SciTech Connect

Acute Lyme disease results from transmission of and infection by the bacterium Borrelia burgdorferi following a tick bite. During acute infection, bacteria can disseminate to the central nervous system (CNS) leading to the development of Lyme meningitis. Here we have analyzed pooled cerebrospinal fluid (CSF) allowing for a deep view into the proteome for a cohort of patients with early-disseminated Lyme disease and CSF inflammation leading to the identification of proteins that reflect host responses, which are distinct for subjects with acute Lyme disease. Additionally, we analyzed individual patient samples and quantified changes in protein abundance employing label-free quantitative mass spectrometry based methods. The measured changes in protein abundances reflect the impact of acute Lyme disease on the CNS as presented in CSF. We have identified 89 proteins that differ significantly in abundance in patients with acute Lyme disease. A number of the differentially abundant proteins have been found to be localized to brain synapse and thus constitute important leads for better understanding of the neurological consequence of disseminated Lyme disease.

Angel, Thomas E.; Jacobs, Jon M.; Smith, Robert P.; Pasternack, Mark S.; Elias, Susan; Gritsenko, Marina A.; Shukla, Anil K.; Gilmore, Edward C.; McCarthy, Carol; Camp, David G.; Smith, Richard D.

2012-10-05

382

Identification of Transforming Growth Factor b1Driven Genetic Programs of Acute Lung Fibrosis  

Microsoft Academic Search

Lung fibrosis is characterized by excessive accumulation of extracel- lular matrix components leading to progressive airflow limitation. Distinct profibrotic pathways converge on the activation of trans- forming growth factor-b (TGF-b), a central growth factor impli- cated in most fibroproliferative diseases. Recently, enforced expression of bioactive human TGF-b1 (hTGF-b1) in lungs of trans- genic mice was shownto recapitulateseveral key pathophysiologies observed

Anne-Marie Pulichino; I-Ming Wang; Alexandre Caron; James Mortimer; Anick Auger; Yves Boie; Jack A. Elias; Aileen Kartono; Lijing Xu; Joseph Menetski; Camil E. Sayegh

2008-01-01

383

Inhalation of glycopyrronium inhibits cigarette smoke-induced acute lung inflammation in a murine model of COPD.  

PubMed

Glycopyrronium bromide (GB) is a muscarinic receptor antagonist that has been used as a long-acting bronchodilator in chronic obstructive pulmonary disease (COPD) patients. The aim of this study was to investigate the anti-inflammatory activity of inhaled GB in a cigarette smoke-induced acute lung inflammation mouse model. We found that aerosol pre-treatment with GB suppresses the accumulation of neutrophils and macrophages in the bronchoalveolar lavage fluid (BALF) in cigarette smoke (CS)-exposed mice. GB at doses of 300 and 600 ?g/ml significantly inhibited the CS-induced increases in the mRNA and protein expression levels of interleukin (IL)-1?, tumor necrosis factor (TNF)-?, monocyte chemotactic protein (MCP)-1 and transforming growth factor (TGF)-?1 in lung tissues and the BALF. Moreover, GB at a dose of 600 ?g/ml significantly inhibited the CS-induced changes in glutathione (GSH) and myeloperoxidase (MPO) activities in the BALF, decreased the CS-induced expression of matrix metalloproteinases (MMP)-9, and increased the CS-induced expression of tissue inhibitor of metalloproteinases (TIMP)-1, as determined through the immunohistochemical staining of lung tissue. Our results demonstrate the beneficial effects of inhaled GB on the inflammatory reaction in COPD. PMID:24389380

Shen, Liang-liang; Liu, Ya-nan; Shen, Hui-juan; Wen, Chong; Jia, Yong-liang; Dong, Xin-wei; Jin, Fang; Chen, Xiao-ping; Sun, Yun; Xie, Qiang-min

2014-02-01

384

Pulmonary Hypertension and Right Heart Dysfunction in Chronic Lung Disease  

PubMed Central

Group 3 pulmonary hypertension (PH) is a common complication of chronic lung disease (CLD), including chronic obstructive pulmonary disease (COPD), interstitial lung disease, and sleep-disordered breathing. Development of PH is associated with poor prognosis and may progress to right heart failure, however, in the majority of the patients with CLD, PH is mild to moderate and only a small number of patients develop severe PH. The pathophysiology of PH in CLD is multifactorial and includes hypoxic pulmonary vasoconstriction, pulmonary vascular remodeling, small vessel destruction, and fibrosis. The effects of PH on the right ventricle (RV) range between early RV remodeling, hypertrophy, dilatation, and eventual failure with associated increased mortality. The golden standard for diagnosis of PH is right heart catheterization, however, evidence of PH can be appreciated on clinical examination, serology, radiological imaging, and Doppler echocardiography. Treatment of PH in CLD focuses on management of the underlying lung disorder and hypoxia. There is, however, limited evidence to suggest that PH-specific vasodilators such as phosphodiesterase-type 5 inhibitors, endothelin receptor antagonists, and prostanoids may have a role in the treatment of patients with CLD and moderate-to-severe PH. PMID:25165714

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

2014-01-01

385

Mechanisms of Physical Activity Limitation in Chronic Lung Diseases  

PubMed Central

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

Vogiatzis, Ioannis; Zakynthinos, George; Andrianopoulos, Vasileios

2012-01-01

386

Toxic Inhalational Injury-Associated Interstitial Lung Disease in Children  

PubMed Central

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

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

387

Hydroxysafflor yellow A suppress oleic acid-induced acute lung injury via protein kinase A  

SciTech Connect

Inflammation response and oxidative stress play important roles in acute lung injury (ALI). Activation of the cAMP/protein kinase A (PKA) signaling pathway may attenuate ALI by suppressing immune responses and inhibiting the generation of reactive oxygen species (ROS). Hydroxysafflor yellow A (HSYA) is a natural flavonoid compound that reduces oxidative stress and inflammatory cytokine-mediated damage. In this study, we examined whether HSYA could protect the lungs from oleic acid (OA)-induced injury, which was used to mimic ALI, and determined the role of the cAMP/PKA signaling pathway in this process. Arterial oxygen tension (PaO{sub 2}), carbon dioxide tension, pH, and the PaO{sub 2}/fraction of inspired oxygen ratio in the blood were detected using a blood gas analyzer. We measured wet/dry lung weight ratio and evaluated tissue morphology. The protein and inflammatory cytokine levels in the bronchoalveolar lavage fluid and serum were determined using enzyme-linked immunoassay. The activities of superoxide dismutase, glutathione peroxidase, PKA, and nicotinamide adenine dinucleotide phosphate oxidase, and the concentrations of cAMP and malondialdehyde in the lung tissue were detected using assay kits. Bcl-2, Bax, caspase 3, and p22{sup phox} levels in the lung tissue were analyzed using Western blotting. OA increased the inflammatory cytokine and ROS levels and caused lung dysfunction by decreasing cAMP synthesis, inhibiting PKA activity, stimulating caspase 3, and reducing the Bcl-2/Bax ratio. H-89 increased these effects. HSYA significantly increased the activities of antioxidant enzymes, inhibited the inflammatory response via cAMP/PKA pathway activation, and attenuated OA-induced lung injury. Our results show that the cAMP/PKA signaling pathway is required for the protective effect of HSYA against ALI. - Highlights: • Oleic acid (OA) cause acute lung injury (ALI) via inhibiting cAMP/PKA signal pathway. • Blocking protein kinase A (PKA) activation may enhance Cytokine release, increase NADPH oxidase activation and reduce activities of antioxidant enzymes. • Hydroxysafflor yellow A (HSYA) up regulate cAMP/PKA signal pathway in lung tissue induced by OA. • HSYA attenuate OA mediated lung injury via reducing inflammatory cytokine release and improving antioxidant capacity.

Wang, Chaoyun [School of Pharmaceutical Sciences, Binzhou Medical University, Yantai, Shandong 264003 (China); Huang, Qingxian [Department of Hepatobiliary Surgery, Yantai Yuhuangding Hospital, Yantai, Shandong 264000 (China); Wang, Chunhua; Zhu, Xiaoxi; Duan, Yunfeng; Yuan, Shuai [School of Pharmaceutical Sciences, Binzhou Medical University, Yantai, Shandong 264003 (China); Bai, Xianyong, E-mail: xybai2012@163.com [School of Pharmaceutical Sciences, Binzhou Medical University, Yantai, Shandong 264003 (China)

2013-11-01

388

Return to play after acute infectious disease in football players.  

PubMed

Acute infectious diseases are common in athletes and can impair their ability to train and to compete. Furthermore, continuing exercise during infectious diseases may lead to prolongation or aggravation of illness with severe acute or chronic organ manifestations. Therefore, even simple infectious diseases require a sufficient period of convalescence and recovery, during which exercise may be not allowed. Nowadays, especially in professional football with high pressures on players, staff and clubs due to broad public interests as well as financial constraints, the return-to-play decision is of utmost significance. Based on previous suggestions and our own experience within amateur and professional athletes and football players, this article aims to give a short overview on return-to-play decisions after common acute infectious diseases in football players. PMID:24784357

Scharhag, Jürgen; Meyer, Tim

2014-01-01

389

USE OF REPEATED BRONCHOALVEOLAR LAVAGE IN RABBITS TO ASSESS POLLUTANT-INDUCED LUNG CHANGES IN AN ANIMAL MODEL OF CARDIOVASCULAR (CV) DISEASE.  

EPA Science Inventory

Animal models of coronary heart disease (e.g., hyperlipidemic rabbits) are being used to investigate epidemiologic associations between higher levels of air pollution and adverse CV consequences. Mechanisms by which pollutant-induced lung or systemic inflammation leads to acute C...

390

Acute Lung Injury in Patients with Severe Brain Injury: A Double Hit Model  

Microsoft Academic Search

The presence of pulmonary dysfunction after brain injury is well recognized. Acute lung injury (ALI) occurs in 20% of patients\\u000a with isolated brain injury and is associated with a poor outcome. The “blast injury” theory, which proposes combined “hydrostatic”\\u000a and “high permeability” mechanisms for the formation of neurogenic pulmonary edema, has been challenged recently by the observation\\u000a that a systemic

Luciana Mascia

2009-01-01

391

Ghrelin attenuates sepsis-induced acute lung injury and mortality in rats  

Microsoft Academic Search

Rationale: Our study has shown that plasma levels of ghrelin, a stomach-derived peptide, are significantly reduced in sepsis, and that ghrelin administration improves organ blood flow via a nuclear factor (NF)-kB-dependent pathway. However, it remains unknown whether ghrelin has any protective effects on severesepsis-induced acute lung injury (ALI) and, if so, whether inhibition of NF-kB plays any role in it.

Rongqian Wu; Weifeng Dong; Mian Zhou; Fangming Zhang; Corrado P. Marini; S. Ravikumar; Ping Wang

2007-01-01

392

Delayed Production of IL18 in Lungs and Pancreas of Rats with Acute Pancreatitis  

Microsoft Academic Search

Background\\/Aims: During acute pancreatitis, tumor necrosis factor (TNF)-?, interleukin (IL)-1 and IL-6 play a pivotal role in promoting injury in the pancreas and remote organs. IL- 18 is a more recently discovered proinflammatory cytokine whose expression is also increased in serum. However, the profile of IL-18 expression in the pancreas and lung is unknown, and the aim of our study

Catherine M. Pastor; Denis R. Morel; Alain Vonlaufen; Eduardo Schiffer; Pierre Lescuyer; Jean-Louis Frossard

2010-01-01

393

[A case of acute respiratory distress syndrome (ARDS) induced by docetaxel administration for lung metastases from oral cancer].  

PubMed

We reported a case of acute respiratory distress syndrome (ARDS) induced by docetaxel in treating lung metastases from oral cancer. The patient was an 84-year-old man who had undergone partial mandibulectomy and radical neck dissection for lower gingival carcinoma. The patient developed ARDS after docetaxel administration (40 mg/body) for multiple lung metastases. PMID:17687210

Mese, Hiroshi; Yoshihama, Yasuto; Nakayama, Shuko; Ibaragi, Soichiro; Sasaki, Akira

2007-08-01

394

Protective effects of aerobic exercise on acute lung injury induced by LPS in mice  

PubMed Central

Introduction The regular practice of physical exercise has been associated with beneficial effects on various pulmonary conditions. We investigated the mechanisms involved in the protective effect of exercise in a model of lipopolysaccharide (LPS)-induced acute lung injury (ALI). Methods Mice were divided into four groups: Control (CTR), Exercise (Exe), LPS, and Exercise + LPS (Exe + LPS). Exercised mice were trained using low intensity daily exercise for five weeks. LPS and Exe + LPS mice received 200 µg of LPS intratracheally 48 hours after the last physical test. We measured exhaled nitric oxide (eNO); respiratory mechanics; neutrophil density in lung tissue; protein leakage; bronchoalveolar lavage fluid (BALF) cell counts; cytokine levels in BALF, plasma and lung tissue; antioxidant activity in lung tissue; and tissue expression of glucocorticoid receptors (Gre). Results LPS instillation resulted in increased eNO, neutrophils in BALF and tissue, pulmonary resistance and elastance, protein leakage, TNF-alpha in lung tissue, plasma levels of IL-6 and IL-10, and IL-1beta, IL-6 and KC levels in BALF compared to CTR (P ?0.02). Aerobic exercise resulted in decreases in eNO levels, neutrophil density and TNF-alpha expression in lung tissue, pulmonary resistance and elastance, and increased the levels of IL-6, IL-10, superoxide dismutase (SOD-2) and Gre in lung tissue and IL-1beta in BALF compared to the LPS group (P ?0.04). Conclusions Aerobic exercise plays important roles in protecting the lungs from the inflammatory effects of LPS-induced ALI. The effects of exercise are mainly mediated by the expression of anti-inflammatory cytokines and antioxidants, suggesting that exercise can modulate the inflammatory-anti-inflammatory and the oxidative-antioxidative balance in the early phase of ALI. PMID:23078757

2012-01-01

395

Inhibition of extracellular HMGB1 attenuates hyperoxia-induced inflammatory acute lung injury.  

PubMed

Prolonged exposure to hyperoxia results in acute lung injury (ALI), accompanied by a significant elevation in the levels of proinflammatory cytokines and leukocyte infiltration in the lungs. However, the mechanisms underlying hyperoxia-induced proinflammatory ALI remain to be elucidated. In this study, we investigated the role of the proinflammatory cytokine high mobility group box protein 1 (HMGB1) in hyperoxic inflammatory lung injury, using an adult mouse model. The exposure of C57BL/6 mice to ?99% O2 (hyperoxia) significantly increased the accumulation of HMGB1 in the bronchoalveolar lavage fluids (BALF) prior to the onset of severe inflammatory lung injury. In the airways of hyperoxic mice, HMGB1 was hyperacetylated and existed in various redox forms. Intratracheal administration of recombinant HMGB1 (rHMGB1) caused a significant increase in leukocyte infiltration into the lungs compared to animal treated with a non-specific peptide. Neutralizing anti-HMGB1 antibodies, administrated before hyperoxia significantly attenuated pulmonary edema and inflammatory responses, as indicated by decreased total protein content, wet/dry weight ratio, and numbers of leukocytes in the airways. This protection was also observed when HMGB1 inhibitors were administered after the onset of the hyperoxic exposure. The aliphatic antioxidant, ethyl pyruvate (EP), inhibited HMGB1 secretion from hyperoxic macrophages and attenuated hyperoxic lung injury. Overall, our data suggest that HMGB1 plays a critical role in mediating hyperoxic ALI through the recruitment of leukocytes into the lungs. If these results can be translated to humans, they suggest that HMGB1 inhibitors provide treatment regimens for oxidative inflammatory lung injury in patients receiving hyperoxia through mechanical ventilation. PMID:24563849

Entezari, Maria; Javdan, Mohammad; Antoine, Daniel J; Morrow, Dympna M P; Sitapara, Ravikumar A; Patel, Vivek; Wang, Mao; Sharma, Lokesh; Gorasiya, Samir; Zur, Michelle; Wu, Wenjun; Li, Jianhua; Yang, Huan; Ashby, Charles R; Thomas, Douglas; Wang, Haichao; Mantell, Lin L

2014-01-01

396

Inhibition of extracellular HMGB1 attenuates hyperoxia-induced inflammatory acute lung injury???  

PubMed Central

Prolonged exposure to hyperoxia results in acute lung injury (ALI), accompanied by a significant elevation in the levels of proinflammatory cytokines and leukocyte infiltration in the lungs. However, the mechanisms underlying hyperoxia-induced proinflammatory ALI remain to be elucidated. In this study, we investigated the role of the proinflammatory cytokine high mobility group box protein 1 (HMGB1) in hyperoxic inflammatory lung injury, using an adult mouse model. The exposure of C57BL/6 mice to ?99% O2 (hyperoxia) significantly increased the accumulation of HMGB1 in the bronchoalveolar lavage fluids (BALF) prior to the onset of severe inflammatory lung injury. In the airways of hyperoxic mice, HMGB1 was hyperacetylated and existed in various redox forms. Intratracheal administration of recombinant HMGB1 (rHMGB1) caused a significant increase in leukocyte infiltration into the lungs compared to animal treated with a non-specific peptide. Neutralizing anti-HMGB1 antibodies, administrated before hyperoxia significantly attenuated pulmonary edema and inflammatory responses, as indicated by decreased total protein content, wet/dry weight ratio, and numbers of leukocytes in the airways. This protection was also observed when HMGB1 inhibitors were administered after the onset of the hyperoxic exposure. The aliphatic antioxidant, ethyl pyruvate (EP), inhibited HMGB1 secretion from hyperoxic macrophages and attenuated hyperoxic lung injury. Overall, our data suggest that HMGB1 plays a critical role in mediating hyperoxic ALI through the recruitment of leukocytes into the lungs. If these results can be translated to humans, they suggest that HMGB1 inhibitors provide treatment regimens for oxidative inflammatory lung injury in patients receiving hyperoxia through mechanical ventilation. PMID:24563849

Entezari, Maria; Javdan, Mohammad; Antoine, Daniel J.; Morrow, Dympna M.P.; Sitapara, Ravikumar A.; Patel, Vivek; Wang, Mao; Sharma, Lokesh; Gorasiya, Samir; Zur, Michelle; Wu, Wenjun; Li, JianHua; Yang, Huan; Ashby, Charles R.; Thomas, Douglas; Wang, Haichao; Mantell, Lin L.

2014-01-01

397

Does hydatid disease have protective effects against lung cancer?  

PubMed

We hypothesized that solid tumors rarely occur in patients with hydatid disease. We obtained the serum of 14 patients diagnosed with hydatid disease, the serum of 10 patients who did not have a history of hydatid disease, and the hydatid cyst fluid from six patients. These sera and fluid samples were added at different concentrations to NCI-H209/An1 human lung small cell carcinoma cells and L929 mouse fibroblasts as a control group. Sera of patients with hydatid diseases had cytotoxic effects on NCI-H209/An1 cells, but they did not have cytotoxic effects on fibroblast cells. Sera from healthy subjects did not have a cytotoxic effect on the tumor cell line or control fibroblasts. Cyst fluid, also, did not have toxic effects on the NCI-H209/An1 cell line, but was toxic to fibroblasts up to a 1:32 dilution. Sera from patients with hydatid disease had cytotoxic effects on human small cell lung cancer cells in vitro. PMID:23645038

Karadayi, Sule; Arslan, Sulhattin; Sumer, Zeynep; Turan, Mustafa; Sumer, Haldun; Karadayi, Kursat

2013-08-01

398