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1

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

PubMed Central

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

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

2011-01-01

2

Ventilation with end-expiratory pressure in acute lung disease  

PubMed Central

In 10 patients with severe, acute respiratory failure we studied the effects of positive end-expiratory pressure when intermittent positive pressure ventilation (IPPV) with inspired oxygen (FIO2) up to 0.5 failed to maintain arterial oxygen tension (PaO2) above 70 torr. Positive end-expiratory pressures (PEEP) of 0, 5, 10, and 15 cm H2O were applied for 30-min periods each and in random order. Blood gas exchange, lung volumes, compliance, and hemodynamics were studied at each level of PEEP. PaO2 (FIO2 = 1.0) rose linearly with elevation of PEEP, the mean increase being from 152 to 347 torr, or 13 torr/cm H2O PEEP. Mean functional residual capacity (FRC) was 1.48±0.78 liters at zero PEEP (i.e., IPPV) and the increase was essentially linear, reaching 2.37 liters at 15 cm H2O PEEP. PaO2 and FRC showed a close correlation. Total and lung static compliance were greater during ventilation with high than with low levels of PEEP. The increase in PaO2 correlated with the specific lung compliance. Dynamic lung compliance decreased progressively with rising levels of PEEP except for an increase with 5 and 10 cm H2O PEEP in patients with initial values of 0.06 liter/cm H2O or higher. Cardiac index fell in some patients and rose in others and there was no correlation of mean cardiac index, systemic blood pressure, or peripheral vascular resistance with level of PEEP. The most probable explanation for the effect of PEEP on PaO2 and compliance is recruitment of gas exchange airspaces and prevention of terminal airway closure. Images PMID:4565164

Falke, Konrad J.; Pontoppidan, Henning; Kumar, Anil; Leith, David E.; Geffin, Bennie; Laver, Myron B.

1972-01-01

3

The Impact of Recurrent Acute Chest Syndrome on the Lung Function of Young Adults with Sickle Cell Disease  

Microsoft Academic Search

The aim of this study was to assess the impact of recurrent acute chest syndrome (ACS) episodes on the lung function of young\\u000a adults with sickle cell disease (SCD). Our prospective study included 80 SCD adults [26 with recurrent acute chest syndrome\\u000a (ACS)] and 80 ethnically matched controls aged between 18 and 28 years. Lung function (spirometry and lung volumes)

Jennifer M. Knight-Madden; Terrence S. Forrester; Norma A. Lewis; Anne Greenough

2010-01-01

4

Adalimumab-induced acute interstitial lung disease in a patient with rheumatoid arthritis*  

PubMed Central

The use of immunobiological agents for the treatment of autoimmune diseases is increasing in medical practice. Anti-TNF therapies have been increasingly used in refractory autoimmune diseases, especially rheumatoid arthritis, with promising results. However, the use of such therapies has been associated with an increased risk of developing other autoimmune diseases. In addition, the use of anti-TNF agents can cause pulmonary complications, such as reactivation of mycobacterial and fungal infections, as well as sarcoidosis and other interstitial lung diseases (ILDs). There is evidence of an association between ILD and the use of anti-TNF agents, etanercept and infliximab in particular. Adalimumab is the newest drug in this class, and some authors have suggested that its use might induce or exacerbate preexisting ILDs. In this study, we report the first case of acute ILD secondary to the use of adalimumab in Brazil, in a patient with rheumatoid arthritis and without a history of ILD. PMID:24626274

Dias, Olívia Meira; Pereira, Daniel Antunes Silva; Baldi, Bruno Guedes; Costa, André Nathan; Athanazio, Rodrigo Abensur; Kairalla, Ronaldo Adib; Carvalho, Carlos Roberto Ribeiro

2014-01-01

5

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 ...

6

Linking Acute Infection to Chronic Lung Disease. The Role of IL-33-Expressing Epithelial Progenitor Cells.  

PubMed

Respiratory infection is a common feature of the major human airway diseases, such as asthma and chronic obstructive pulmonary disease, but the precise link between acute infection and chronic lung disease is still undefined. In a mouse model of this process, parainfluenza virus infection is followed by long-term induction of IL-33 expression and release and in turn innate immune cell generation of IL-13 and consequent airway disease signified by excess mucus formation. IL-33 induction was traceable to a subset of secretoglobin-positive airway epithelial cells linked to progenitor/stem cell function. In corresponding studies of humans with chronic obstructive pulmonary disease, an increase in IL-33 production was also detected in concert with up-regulation of IL-13 and airway mucus formation. In this case, increased IL-33 production was localized to a subset of airway basal cells that maintain an endogenous capacity for increased pluripotency and ATP-regulated release of IL-33 even ex vivo. The results provide evidence of a sustainable epithelial cell population that may be activated by environmental danger signals to release IL-33 and thereby lead to IL-13-dependent disease. The progenitor nature of this IL-33-expressing ATP-responsive cell population could explain an acquired susceptibility to chronic airway disease. The findings may therefore provide a new paradigm to explain the role of viral infection and the innate immune system in chronic lung disease based on the influence of long-term epithelial progenitor cells programmed for excess IL-33 production. Further studies are needed to address the basis for this type of postviral reprogramming and the means to correct it and thereby restore airway mucosal immune function to normal. PMID:25525734

Holtzman, Michael J; Byers, Derek E; Brett, Jennifer-Alexander; Patel, Anand C; Agapov, Eugene; Jin, Xiaohua; Wu, Kangyun

2014-12-01

7

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) ...

8

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

9

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

PubMed Central

Sex-specific differences in pulmonary morbidity in humans are well documented. Hyperoxia contributes to lung injury in experimental animals and humans. The mechanisms responsible for sex differences in the susceptibility towards hyperoxic lung injury remain largely unknown. In this investigation, we tested the hypothesis that mice will display sex-specific differences in hyperoxic lung injury. Eight week-old male and female mice (C57BL/6J) were exposed to 72 h of hyperoxia (FiO2>0.95). After exposure to hyperoxia, lung injury, levels of 8-iso-prostaglandin F2 alpha (8-iso-PGF 2?) (LC-MS/MS), apoptosis (TUNEL) and inflammatory markers (suspension bead array) were determined. CytochromeP450 (CYP)1A expression in the lung was assessed using immunohistochemistry and western blotting. After exposure to hyperoxia, males showed greater lung injury, neutrophil infiltration and apoptosis, compared to air-breathing controls than females. Pulmonary 8-iso-PGF 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. PMID:23792423

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

2014-01-01

10

Genetic polymorphisms associated with acute lung injury  

PubMed Central

Acute lung injury and acute respiratory distress syndrome are the result of intense inflammation in the lungs leading to respiratory failure. The causes of acute lung injury/acute respiratory distress syndrome are numerous (e.g., pneumonia, sepsis and trauma) but the reasons why certain individuals develop lung injury in response to these stimuli and others do not are not well understood. There is ample evidence in the literature that gene–host and gene–environment interactions may play a large role in the morbidity and mortality associated with this syndrome. In this review, we initially discuss methods for identification of candidate acute lung injury/acute respiratory distress syndrome susceptibility genes using a number of model systems including in vitro cell systems and inbred mice. We then describe examples of polymorphisms in genes that have been associated with the pathogenesis of acute lung injury/acute respiratory distress syndrome in human case–control studies. Systematic bench to bedside approaches to understand the genetic contribution to acute lung injury/acute respiratory distress syndrome have provided important insight to this complex disease and continuation of these investigations could lead to the development of novel prevention or intervention strategies. PMID:19761373

Reddy, Anita J; Kleeberger, Steven R

2009-01-01

11

Interstitial Lung Disease  

MedlinePLUS

... MS Dept. of Medicine View full profile Interstitial Lung Disease (ILD): Overview Interstitial lung disease (ILD) is ... they may make informed decisions Learn more. Interstitial Lung Disease Program As a center specializing in the ...

12

Farmer's Lung Disease  

PubMed Central

Farmer's lung disease (FLD) is a hypersensitivity pneumonitis secondary to the inhalation of moldy hay spores. Its prevalence is likely underestimated despite the fact it may result in significant acute and chronic respiratory disability. The immunologic mechanisms are best explained as Gell and Coombs Type III & IV reactions. FLD is usually recognized by history and appropriate laboratory confirmation. Therapy requires removal of the patient from the offending antigens, although corticosteroids may be useful for constitutional symptoms. PMID:21286564

Dales, Robert E.; Munt, Peter W.

1982-01-01

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 disease  

MedlinePLUS

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

16

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

17

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

18

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

19

Understanding Pneumoconiosis (Black Lung Disease)  

MedlinePLUS

... Disparities Reports Lung Disease Finder Lung Disease List Lung HelpLine Questions about your lung health? Need help ... treatment of pneumoconiosis . A A A Share Print Lung Cancer Education Resource Online Caregiving Coordination Service Bring ...

20

Interstitial lung disease.  

PubMed

This article reviews the most important articles published in interstitial lung disease, as reviewed during the Clinical Year in Review session at the 2012 annual European Respiratory Society Congress in Vienna, Austria. Since the recent international guidelines for the management of idiopathic pulmonary fibrosis (IPF), important new evidence is available. The anti-fibrotic drug pirfenidone has been recently approved in Europe. Other pharmacological agents, especially nintedanib, are still being tested. The so-called triple combination therapy, anticoagulation therapy and endothelin receptor antagonists, especially ambrisentan, are either harmful or ineffective in IPF and are not recommended as treatment. Although the clinical course of IPF is highly variable, novel tools have been developed for individual prediction of prognosis. Acute exacerbations of IPF are associated with increased mortality and may occur with higher frequency in IPF patients with associated pulmonary hypertension. Interstitial lung disease associated with connective tissue disease has been definitely established to have a better long-term survival than IPF. A subset of patients present with symptoms and/or biological autoimmune features, but do not fulfil diagnostic criteria for a given autoimmune disease; this condition is associated with a higher prevalence of nonspecific interstitial pneumonia pattern, female sex and younger age, although survival relevance is unclear. PMID:23457161

Cottin, Vincent

2013-03-01

21

[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

22

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); Michael Koeppen (University of Colorado Denver Anesthesiology); Holger K. Eltzschig (University of Colorado Denver Anesthesiology)

2009-10-01

23

Lung Diseases and Conditions  

MedlinePLUS

... lead to a disease called COPD (chronic obstructive pulmonary disease). COPD prevents proper airflow in and out of your lungs and can hinder gas exchange in the air sacs. An important ... blood clot called a pulmonary embolism (PE) to block a lung artery. A ...

24

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 ...

25

Acute small bowel obstruction owing to undiagnosed lung cancer.  

PubMed

Lung cancer is the leading cause of cancer related deaths in the United States. Most patients with lung cancer present with advanced disease at the time of diagnosis owing to multiple metastases. However, metastases to the duodenum are extremely rare. We present a case of acute small bowel obstruction in a patient owing to metastatic disease to the duodenum from previously undiagnosed lung adenocarcinoma. PMID:25372366

Erokhina, Katerina; Sharak, Nazar; Cai, Wayne; Pierre, Berry; Schultz, Allen

2014-08-01

26

Adalimumab (Humira) induced acute lung injury  

PubMed Central

Patient: Male, 78 Final Diagnosis: Acute lung injury due to Adalimumab Symptoms: — Medication: Adalimumab Clinical Procedure: Intubated and put on mechanical ventilation Specialty: Pulmonology Objective: Unusual or unexpected effect of treatment Background: Adalimumab is a recombinant human monoclonal antibody that blocks the effects of tumor necrosis factor-alpha. Adalimumab related acute lung injury is a rare form of acute respiratory distress syndrome of possible immune etiology that develops immediately after an infusion. Case Report: We describe a 78 year old, male with no previous cardiac comorbidities, who developed acute lung injury (ALI) within one hour of administration of adalimumab. He was successfully treated with mechanical ventilatory support and adjuvant therapy. Conclusions: TNF? antagonists are a part of a new and revolutionary treatment for severe and difficult-to-treat autoimmune and inflammatory diseases. This report emphasizes that this fatal complication may occur with use of this drug. Clinicians need to be aware of this condition as prompt recognition and supportive management can prevent unwanted morbidity and mortality. PMID:23826460

Kohli, Ritesh; Namek, Karim

2013-01-01

27

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

28

Human Respiratory Syncytial Virus Memphis 37 Causes Acute Respiratory Disease in Perinatal Lamb Lung  

PubMed Central

Abstract Respiratory syncytial virus (RSV) is the leading cause of hospitalization due to respiratory illness among infants and young children of industrialized countries. There is a lack of understanding of the severe disease mechanisms as well as limited treatment options, none of which are fully satisfactory. This is partly due to lack of a relevant animal model of perinatal RSV infection that mimics moderate to severe disease in infants. We and others have shown mild disease in perinatal lambs with either a bovine or a human A2 strain of RSV. The Memphis 37 clinical strain of human RSV has been used to produce mild to moderate upper respiratory disease in healthy adult volunteers. We hypothesized that the Memphis 37 strain of RSV would infect perinatal lambs and produce clinical disease similar to that in human infants. Perinatal (3- to 5-day-old) lambs were inoculated intranasally with 2?mL/nostril of 1×105 focus-forming units (FFU)/mL (n=2) or 2.1×108 FFU/mL (n=3) of RSV Memphis 37. Clinical signs, gross and histological lesions, and immune and inflammatory responses were assessed. Memphis 37 caused moderate to severe gross and histologic lesions along with increased mRNA expression of macrophage inflammatory protein. Clinically, four of the five infected lambs had a mild to severe increase in expiratory effort. Intranasally administered RSV strain Memphis 37 infects neonatal lambs with gross, histologic, and immune responses similar to those observed in human infants. PMID:24804166

van Geelen, Albert; Gallup, Jack M.; Kienzle, Thomas; Shelly, Daniel A.; Cihlar, Tomas; King, Robert R.; Ackermann, Mark R.

2014-01-01

29

Human respiratory syncytial virus memphis 37 causes acute respiratory disease in perinatal lamb lung.  

PubMed

Respiratory syncytial virus (RSV) is the leading cause of hospitalization due to respiratory illness among infants and young children of industrialized countries. There is a lack of understanding of the severe disease mechanisms as well as limited treatment options, none of which are fully satisfactory. This is partly due to lack of a relevant animal model of perinatal RSV infection that mimics moderate to severe disease in infants. We and others have shown mild disease in perinatal lambs with either a bovine or a human A2 strain of RSV. The Memphis 37 clinical strain of human RSV has been used to produce mild to moderate upper respiratory disease in healthy adult volunteers. We hypothesized that the Memphis 37 strain of RSV would infect perinatal lambs and produce clinical disease similar to that in human infants. Perinatal (3- to 5-day-old) lambs were inoculated intranasally with 2?mL/nostril of 1×10(5) focus-forming units (FFU)/mL (n=2) or 2.1×10(8) FFU/mL (n=3) of RSV Memphis 37. Clinical signs, gross and histological lesions, and immune and inflammatory responses were assessed. Memphis 37 caused moderate to severe gross and histologic lesions along with increased mRNA expression of macrophage inflammatory protein. Clinically, four of the five infected lambs had a mild to severe increase in expiratory effort. Intranasally administered RSV strain Memphis 37 infects neonatal lambs with gross, histologic, and immune responses similar to those observed in human infants. PMID:24804166

Derscheid, Rachel J; van Geelen, Albert; Gallup, Jack M; Kienzle, Thomas; Shelly, Daniel A; Cihlar, Tomas; King, Robert R; Ackermann, Mark R

2014-04-01

30

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

31

NOD-Like Receptors in Lung Diseases.  

PubMed

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

32

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

33

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

34

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

35

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

36

Congenital Cystic Lung Diseases  

PubMed Central

Congenital cystic diseases of the lung are a rare but significant cause of morbidity in children and young adults presenting with respiratory distress and repeated chest infections. They consist of cystic adenomatoid malformation, bronchogenic cyst, pulmonary sequestration, and congenital lobar emphysema. Surgical treatment is a safe and an effective method of treatment. Chest X-ray and computed tomography are the key imaging modalities used for diagnosis. PMID:23607074

Jain, Aditi; Anand, K; Singla, Saurabh; Kumar, Ashok

2013-01-01

37

Congenital cystic lung diseases.  

PubMed

Congenital cystic diseases of the lung are a rare but significant cause of morbidity in children and young adults presenting with respiratory distress and repeated chest infections. They consist of cystic adenomatoid malformation, bronchogenic cyst, pulmonary sequestration, and congenital lobar emphysema. Surgical treatment is a safe and an effective method of treatment. Chest X-ray and computed tomography are the key imaging modalities used for diagnosis. PMID:23607074

Jain, Aditi; Anand, K; Singla, Saurabh; Kumar, Ashok

2013-01-01

38

Interstitial Lung Disease (ILD): Treatment  

MedlinePLUS

... MS 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 ...

39

Early activation of pulmonary TGF-?1/Smad2 signaling in mice with acute pancreatitis-associated acute lung injury.  

PubMed

Acute lung injury is caused by many factors including acute pancreatitis. There is no specific therapy directed at underlying pathophysiological mechanisms for acute lung injury. Transforming growth factor-? (TGF-?) is involved in the resolution of lung injury in later phases of the disease. Some evidence exists demonstrating that TGF-? not only is involved in the late stages, but also contributes to lung injury early on in the progress of the disease. Acute pancreatitis was induced using ductal ligation in mice. TGF-?1, 2, and 3, T?RII, ALK-5, Smad2, 3, 4, and 7, and P-Smad2 expression in the lungs were analyzed at 9 and 24?h. We demonstrate that TGF- ?1 levels in the lungs of mice with acute pancreatitis increase as early as 9?h after induction. We observed an increased expression of ALK-5 in acute pancreatitis at both 9 and 24?h. Inhibitory Smad7 expression was transiently increased at 9?h in acute pancreatitis, but reduced later at 24?h, with a concomitant increased nuclear translocation of phosphorylated Smad2. Our findings demonstrate activation of TGF-? signaling in the lungs as early as 24?h after acute pancreatitis, suggesting that TGF-? may represent a potential therapeutic candidate in acute pancreatitis-induced acute lung injury. PMID:24688224

Akbarshahi, Hamid; Sam, Asha; Chen, Chaolei; Rosendahl, Ann H; Andersson, Roland

2014-01-01

40

Early Activation of Pulmonary TGF-?1/Smad2 Signaling in Mice with Acute Pancreatitis-Associated Acute Lung Injury  

PubMed Central

Acute lung injury is caused by many factors including acute pancreatitis. There is no specific therapy directed at underlying pathophysiological mechanisms for acute lung injury. Transforming growth factor-? (TGF-?) is involved in the resolution of lung injury in later phases of the disease. Some evidence exists demonstrating that TGF-? not only is involved in the late stages, but also contributes to lung injury early on in the progress of the disease. Acute pancreatitis was induced using ductal ligation in mice. TGF-?1, 2, and 3, T?RII, ALK-5, Smad2, 3, 4, and 7, and P-Smad2 expression in the lungs were analyzed at 9 and 24?h. We demonstrate that TGF-?1 levels in the lungs of mice with acute pancreatitis increase as early as 9?h after induction. We observed an increased expression of ALK-5 in acute pancreatitis at both 9 and 24?h. Inhibitory Smad7 expression was transiently increased at 9?h in acute pancreatitis, but reduced later at 24?h, with a concomitant increased nuclear translocation of phosphorylated Smad2. Our findings demonstrate activation of TGF-? signaling in the lungs as early as 24?h after acute pancreatitis, suggesting that TGF-? may represent a potential therapeutic candidate in acute pancreatitis-induced acute lung injury. PMID:24688224

Sam, Asha; Chen, Chaolei; Rosendahl, Ann H.

2014-01-01

41

[HRCT patterns of the most important interstitial lung diseases].  

PubMed

Interstitial lung diseases are a mixed group of diffuse parenchymal lung diseases which can have an acute or chronic course. Idiopathic diseases and diseases with an underlying cause (e.g. collagen vascular diseases) share the same patterns. Thin section computed tomography (CT) plays a central role in the diagnostic work-up. The article describes the most important interstitial lung diseases following a four pattern approach with a predominant nodular or reticular pattern or a pattern with increased or decreased lung density. PMID:25503518

Schaefer-Prokop, C

2014-12-01

42

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 ...

43

Types of Childhood Interstitial Lung Disease  

MedlinePLUS

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

44

Lung pathology of fatal severe acute respiratory syndrome  

Microsoft Academic Search

1 Summary Background Severe acute respiratory syndrome (SARS) is a novel infectious disease with global impact. A virus from the family Coronaviridae has been identified as the cause, but the pathogenesis is still unclear. Methods Post-mortem tissue samples from six patients who died from SARS in February and March, 2003, and an open lung biopsy from one of these patients

John M Nicholls; Leo L M Poon; Kam C Lee; Wai F Ng; Sik T Lai; Chung Y Leung; Chung M Chu; Pak K Hui; Kong L Mak; Wilina Lim; Kin W Yan; Kwok H Chan; Ngai C Tsang; Yi Guan; Kwok Y Yuen; J S Malik Peiris

2003-01-01

45

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

46

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

47

Nodular amiodarone lung disease.  

PubMed

The antiarrhythmic drug amiodarone accumulates in many organs of the body. Amiodarone lung disease (ALD) most commonly manifests clinically as an interstitial pneumonitis. The few reports of nodular ALD generally have been in the clinical and radiographic literature. No detailed histopathologic analysis of nodular ALD is available. We report 4 patients with nodular ALD, all of whom had excision of a nodule and none had a preoperative diagnosis of ALD. The radiographic suspicion before excisional biopsy in all 4 cases was malignancy. The initial pathologic suspicion in all 4 cases was either an abscess or vasculitis. In 3 of the 4 cases, where the dosages were known, each patient received 800 mg/d for 7 or more months. All cases have strikingly similar histopathology, with vacuolated histiocytes massed within alveoli to form macroscopic nodules with tissue breakdown. Ultrastructural examination of lung and peripheral nerve in 1 case showed the characteristic inclusions of amiodarone in the cytoplasm of swollen histiocytes. Vacuolated histiocytes filled with these inclusions indicate the effect of the drug, but in these 4 cases there was tissue destruction, which indicated disease. The necrotizing nature of the massed histiocytes in the absence of infection or obstruction suggests the correct etiologic diagnosis even when the history of administration of the drug is not available at initial review. PMID:18753942

Ruangchira-Urai, Ruchira; Colby, Thomas V; Klein, Julianne; Nielsen, G Petur; Kradin, Richard L; Mark, Eugene J

2008-11-01

48

Occupational Interstitial Lung Disease Update  

Microsoft Academic Search

Overview Occupational exposures produce a wide range of interstitial lung disorders. Occupational etiologies account for a significant portion of all interstitial lung disease (ILD), and new causes continue to be described. All of these disorders are preventable with the reduction or elimination of workplace exposure. This chapter highlights the common, persistent diseases that continue to plague workers globally, as well

Lee S. Newman

49

Cigarette smoking and diffuse lung disease.  

PubMed

Cigarette smoke, a toxic collection of more than 4000 chemicals generated from combustion of tobacco plant leaves, is known to cause several respiratory ailments, including chronic bronchitis, emphysema and lung cancer, and is associated with an increase in respiratory infections. In addition, cigarette smoking is considered a principal aetiological factor responsible for the development of certain diffuse interstitial and bronchiolar lung diseases, namely respiratory bronchiolitis-interstitial lung disease (RB-ILD), desquamative interstitial pneumonia (DIP) and adult pulmonary Langerhans' cell histiocytosis (PLCH). Although not exclusively seen in cigarette smokers, substantial clinical and epidemiological data support a central role for smoking as the primary causative agent of most RB-ILD, DIP and PLCH. Additional evidence in support of cigarette smoke as a primary aetiological agent in RB-ILD, DIP and PLCH is the observation that smoking cessation may lead to disease improvement, while recurrence of these disorders has been observed to occur in the transplanted lung upon re-exposure to tobacco smoke. Furthermore, histopathological changes of respiratory bronchiolitis, DIP and PLCH (with or without co-existent emphysema) may be found on lung biopsy in the same individual, implicating smoking as a common inciting agent of these diverse lesions. Recent studies also suggest a role for cigarette smoking as a potential co-factor in the development of acute eosinophilic pneumonia, usual interstitial pneumonia and rheumatoid arthritis-associated interstitial lung disease. In the current review, we propose a novel classification that takes into account the complex relationship between cigarette smoking and diffuse lung diseases. Investigation on the role of smoking as a potential causative factor or modifier of these diverse diffuse lung diseases is important, as smoking cessation utilizing state-of-the-art tobacco cessation efforts should be a central part of therapy, while pharmacotherapy with corticosteroids or other immune modifying agents should be reserved for selected patients. PMID:18627208

Patel, Rajesh R; Ryu, Jay H; Vassallo, Robert

2008-01-01

50

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

51

Acute lung injury. Pathogenesis of intraalveolar fibrosis.  

PubMed Central

In patients dying with acute lung injury, interstitial mesenchymal cells migrate into the airspace where they replicate and deposit connective tissue. We therefore hypothesized that peptides capable of promoting mesenchymal cell migration and replication would be present in the alveolar airspace. To examine this hypothesis, patients with severe acute diffuse lung injury (n = 26) underwent bronchoalveolar lavage. Acutely ill patients without lung injury served as controls (n = 12). Recovered effluent was examined for mesenchymal cell growth-promoting and migration-promoting activity. Lavage cell supernates from both patients and controls were devoid of bioactivity. However, substantial growth-promoting and migration-promoting activity was present in lavage fluid from nearly every patient, whereas little or none was present in fluid from controls. Characterization of the bioactivity indicated a significant proportion consisted of three peptides related to PDGF: (a) a 14-kD peptide that shared with PDGF several biophysical, biochemical, receptor-binding, and antigenic properties; (b) a 29-kD peptide that appeared identical to PDGF of platelet origin; and (c) a 38-kD peptide that was biophysically and antigenically similar to PDGF. These data indicate that peptide moieties are present in the airspace of patients after acute lung injury that can signal mesenchymal cell migration and replication. Images PMID:1864975

Snyder, L S; Hertz, M I; Peterson, M S; Harmon, K R; Marinelli, W A; Henke, C A; Greenheck, J R; Chen, B; Bitterman, P B

1991-01-01

52

Surfactant for Pediatric Acute Lung Injury  

PubMed Central

Synopsis This article reviews exogenous surfactant therapy and its use in mitigating acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) in infants, children, and adults. Biophysical and animal research documenting surfactant dysfunction in ALI/ARDS is described, and the scientific rationale for treatment with exogenous surfactant is discussed. Major emphasis is on reviewing clinical studies of surfactant therapy in pediatric and adult patients with ALI/ARDS. Particular advantages from surfactant therapy in direct pulmonary forms of these syndromes are described. Also discussed are additional factors affecting the efficacy of exogenous surfactants in ALI/ARDS, including the multifaceted pathology of inflammatory lung injury, the effectiveness of surfactant delivery in injured lungs, and composition-based activity differences among clinical exogenous surfactant preparations. PMID:18501754

Willson, Douglas F.; Chess, Patricia R.; Notter, Robert H.

2008-01-01

53

[Interstitial lung diseases. The pattern is important].  

PubMed

Interstitial lung diseases (ILDs) comprise a number of rare entities with an estimated incidence of 10-25 per 100,000 inhabitants but the incidence greatly increases beyond the age of 65 years. The prognosis depends on the underlying cause. The fibrotic disorders show a set of radiological and histopathological patterns that are distinct but not entirely specific. In the absence of a clear clinical picture and consistent high resolution computed tomography (HRCT) findings, patients are advised to undergo surgical lung biopsies from two or three lung lobes (or transbronchial biopsies) to determine the histopathological pattern. The ILDs are differentiated into disorders of known causes (e.g. collagen vascular disease, drug-related), idiopathic interstitial pneumonia (IIP), granulomatous ILDs (e.g. sarcoidosis) and other forms of ILD (e.g. Langerhans' cell histiocytosis). The IIPs encompass idiopathic pulmonary fibrosis (IPF), non-specific interstitial pneumonia, desquamative interstitial pneumonia, respiratory bronchiolitis-interstitial lung disease, cryptogen organizing pneumonia, lymphocytic interstitial pneumonia and acute interstitial pneumonia. Additionally, a category of unclassified interstitial pneumonia exists. The pathologist has to recognize and address the histopathological pattern. In a multidisciplinary discussion the disorder is allocated to a clinicopathological entity and the histopathological pattern plays a major role in the classification of the entity. Recognition of the underlying pattern and the respective histopathological differential diagnoses is important as the therapy varies depending on the cause and ranges from elimination of the stimulus (if possible) to antifibrotic drug therapy up to preparation for lung transplantation. PMID:25319226

Fink, L

2014-11-01

54

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

55

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

56

Drug Induced Interstitial Lung Disease  

PubMed Central

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

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

2012-01-01

57

Overview of current lung imaging in acute respiratory distress syndrome.  

PubMed

Imaging plays a key role in the diagnosis and follow-up of acute respiratory distress syndrome (ARDS). Chest radiography, bedside lung ultrasonography and computed tomography scans can provide useful information for the management of patients and detection of prognostic factors. However, imaging findings are not specific and several possible differential diagnoses should be taken into account. Herein we will review the role of radiological techniques in ARDS, highlight the plain radiological and computed tomography findings according to the pathological stage of the disease (exudative, inflammatory and fibroproliferative), and summarise the main points for the differential diagnosis with cardiogenic oedema, which is still challenging in the acute stage. PMID:25445951

Zompatori, Maurizio; Ciccarese, Federica; Fasano, Luca

2014-12-01

58

Complement system in lung disease.  

PubMed

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

Pandya, Pankita H; Wilkes, David S

2014-10-01

59

Aspiration-related lung diseases.  

PubMed

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

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

2014-09-01

60

Acute Lung Injury Regulation by Hyaluronan  

PubMed Central

Summary Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS), have high mortality rates with few treatment options. An important regulatory factor in the pathology observed in ALI/ARDS is a disruption of the pulmonary endothelial barrier which, in combination with epithelial barrier disruption, causes leakage of fluid, protein and cells into lung airspaces. Degradation of the glycosaminoglycan, hyaluronan (HA), is involved in reduction of the endothelial glycocalyx, disruption of endothelial cell-cell contacts and activation of HA binding proteins upregulated in ALI/ARDS which promote a loss of pulmonary vascular integrity. In contrast, exogenous administration of high molecular weight HA has been shown to be protective in several models of ALI. This review focuses on the dichotomous role of HA to both promote and inhibit ALI based on its size and the HA binding proteins present. Further, potential therapeutic applications of high molecular weight HA in treating ALI/ARDS are discussed. PMID:24244887

Singleton, Patrick A.; Lennon, Frances E.

2013-01-01

61

Diagnostic Invasive Procedures in Diffuse Infiltrative Lung Diseases  

Microsoft Academic Search

The diagnosis of infiltrative diffuse lung disease may require invasive procedures after all noninvasive tools have failed. The clinical context in which these diseases develop and the radiological patterns are crucial for defining the timing and the methods to be used. Immunocompromised hosts are usually acutely ill with fever, cough, shortness of breath, and often with progressive hypoxemia. In this

Venerino Poletti; Marco Chilosi; Dario Olivieri

2004-01-01

62

Interstitial lung diseases in collagen vascular diseases.  

PubMed

In this review, a clinical update is presented of the most important collagen vascular diseases (CVDs) and the different types of interstitial lung disease (ILD) encountered in these CVDs. These CVDs represent a heterogenous group of immunologically mediated inflammatory disorders with a large variety of affected organs besides the lungs. The frequency, clinical presentation, prognosis and response to therapy vary depending on the histological pattern (usual interstitial pneumonia, desquamative interstitial pneumonia, organising pneumonia, diffuse alveolar damage, nodular lesions, etc.), as well as on the underlying CVD (scleroderma, rheumatoid arthritis, systemic lupus erythematosus, dermatopolymyositis, Sjogren's syndrome or mixed connective tissue disease). The diagnosis of most of these CVDs is based on a number of criteria; in several of these, however, lung involvement is not part of the diagnostic criteria. In addition, there may be overlaps between several of these CVDs. Optimal treatment varies depending on the type of collagen vascular disease and the presence of interstitial lung disease, although in many cases, a combination of corticosteroids and cytostatic drugs are given. PMID:11816826

Lamblin, C; Bergoin, C; Saelens, T; Wallaert, B

2001-09-01

63

Cannabidiol improves lung function and inflammation in mice submitted to LPS-induced acute lung injury.  

PubMed

Abstract We have previously shown that the prophylactic treatment with cannabidiol (CBD) reduces inflammation in a model of acute lung injury (ALI). In this work we analyzed the effects of the therapeutic treatment with CBD in mice subjected to the model of lipopolysaccharide (LPS)-induced ALI on pulmonary mechanics and inflammation. CBD (20 and 80?mg/kg) was administered (i.p.) to mice 6?h after LPS-induced lung inflammation. One day (24?h) after the induction of inflammation the assessment of pulmonary mechanics and inflammation were analyzed. The results show that CBD decreased total lung resistance and elastance, leukocyte migration into the lungs, myeloperoxidase activity in the lung tissue, protein concentration and production of pro-inflammatory cytokines (TNF and IL-6) and chemokines (MCP-1 and MIP-2) in the bronchoalveolar lavage supernatant. Thus, we conclude that CBD administered therapeutically, i.e. during an ongoing inflammatory process, has a potent anti-inflammatory effect and also improves the lung function in mice submitted to LPS-induced ALI. Therefore the present and previous data suggest that in the future cannabidiol might become a useful therapeutic tool for the attenuation and treatment of inflammatory lung diseases. PMID:25356537

Ribeiro, A; Almeida, V I; Costola-de-Souza, C; Ferraz-de-Paula, V; Pinheiro, M L; Vitoretti, L B; Gimenes-Junior, J A; Akamine, A T; Crippa, J A; Tavares-de-Lima, W; Palermo-Neto, J

2015-02-01

64

[Transfusion-related acute lung injury (TRALI)].  

PubMed

Transfusion-related acute lung injury (TRALI) is primarily caused by transfusion of fresh frozen plasma or platelet concentrates and occurs by definition within 6 hours after transfusion with acute shortness of breath, hypoxemia and radiographically detectable bilateral infiltrates of the lung. Mostly leucocyte antibodies in the plasma of the blood donor (immunogenic TRALI) are responsible. Apart from antibodies, other substances such as biologically active lipids, mainly arising from the storage of platelet and red blood cell concentrates, can activate neutrophilic granulocytes and trigger a non-immunogenic TRALI. Pathophysiologically, granulocytes in the capillaries of the lung vessels release oxygen radicals and enzymes which damage the endothelial cells and cause pulmonary edema. Therapeutically, nasal oxygen administration may be sufficient. In severe cases, mechanical ventilation, invasive hemodynamic monitoring and fluid intake are required. Diuretics should be avoided. The administration of glucocorticoids is controversial. Antibody-related TRALI reactions occurred mainly after transfusion of fresh frozen plasma, which had been obtained from womenimmunized during pregnancy against leukocyte antigens. Therefore, in Germany, since 2009 only plasma from female donors without a history of prior or current pregnancy or negative testing for antibodies against HLA I, II or HNA has been used with the result that since then no TRALI-related death has been registered. PMID:25046684

Schweisfurth, H; Sopivnik, I; Moog, R

2014-09-01

65

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

66

Polymyositis-dermatomyositis-associated interstitial lung disease.  

PubMed

We report findings in 70 patients with both diffuse interstitial lung disease and either polymyositis (PM) or dermatomyositis (DM). Initial presentations were most commonly either musculoskeletal (arthralgias, myalgias, and weakness) or pulmonary (cough, dyspnea, and fever) symptoms alone; in only 15 patients (21.4%) did both occur simultaneously. Pulmonary disease usually took the form of acute to subacute antibiotic-resistant community-acquired pneumonia. Chest radiographs and computed tomography most commonly demonstrated bilateral irregular linear opacities involving the lung bases; occasionally consolidation was present. Jo-1 antibody was present in 19 (38%) of 50 patients tested. Synchronous associated malignancy was present in 4 of 70 patients (5.7%). Surgical lung biopsies disclosed nonspecific interstitial pneumonia (NSIP) in 18 of 22 patients (81.8%), organizing diffuse alveolar damage (DAD) in 2, bronchiolitis obliterans organizing pneumonia (BOOP) in 1, and usual interstitial pneumonia (UIP) in 1. Treatment usually included prednisone in 40-60 mg/d dosages for initial control, followed by lower dose prednisone plus an immunosuppressive agent such as azathioprine or methotrexate for disease suppression. Survival was significantly better than that observed for historical control subjects with idiopathic UIP, and was more consistent with survival previously reported in idiopathic NSIP. There was no difference in survival between Jo-1 positive and Jo-1 negative groups. PMID:11673206

Douglas, W W; Tazelaar, H D; Hartman, T E; Hartman, R P; Decker, P A; Schroeder, D R; Ryu, J H

2001-10-01

67

Transfusion-Related Acute Lung Injury: The Work of DAMPs*  

PubMed Central

Current notions in immunology hold that not only pathogen-mediated tissue injury but any injury activates the innate immune system. In principle, this evolutionarily highly conserved, rapid first-line defense system responds to pathogen-induced injury with the creation of infectious inflammation, and non-pathogen-induced tissue injury with ‘sterile’ tissue inflammation. In this review, evidence has been collected in support of the notion that the transfusion-related acute lung injury induces a ‘sterile’ inflammation in the lung of transfused patients in terms of an acute innate inflammatory disease. The inflammatory response is mediated by the patient's innate immune cells including lung-passing neutrophils and pulmonary endothelial cells, which are equipped with pattern recognition receptors. These receptors are able to sense injury-induced, damage-associated molecular patterns (DAMPs) generated during collection, processing, and storage of blood/blood components. The recognition process leads to activation of these innate cells. A critical role for a protein complex known as the NLRP3 inflammasome has been suggested to be at the center of such a scenario. This complex undergoes an initial ‘priming’ step mediated by 1 class of DAMPs and then an ‘activating’ step mediated by another class of DAMPs to activate interleukin-1beta and interleukin-18. These 2 cytokines then promote, via transactivation, the formation of lung inflammation. PMID:23637644

Land, Walter G.

2013-01-01

68

Acute- or subacute-onset lung complications in treating patients with rheumatoid arthritis.  

PubMed

Rheumatoid arthritis (RA) is a common systemic disease that manifests as inflammatory arthritis of multiple joints and produces a wide variety of intrathoracic lesions, including pleural diseases, diffuse interstitial pneumonia, rheumatoid nodules, and airway disease. Patients treated for RA can have associated lung disease that commonly manifests as diffuse interstitial pneumonia, drug-induced lung injury, and infection. The purpose of this pictorial review is to illustrate the radiographic and clinical features of lung complications of acute or subacute onset in patients treated for RA and to show the computed tomography features of these complications. PMID:22704786

Nakajima, Reiko; Sakai, Fumikazu; Mimura, Toshihide; Tokuda, Hitoshi; Takahashi, Masahiro; Kimura, Fumiko

2013-08-01

69

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 âÂÂadmitted for acute worsening of his respiratory status and liver failure.â The patientâÂÂs history includes end-stage restrictive lung disease and end-stage liver disease. The âÂÂGross Descriptionâ and âÂÂMicroscopic Descriptionâ sections provide key information and images that contributed to the patientâÂÂs diagnosis. Clicking on the âÂÂFinal Diagnosisâ provides a thorough explanation of the diagnosis and illness from the contributing doctors.

Johnson, Douglas R.

2009-08-20

70

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

71

Chapter 17: Occupational immunologic lung disease.  

PubMed

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

Sabin, Bradley R; Grammer, Leslie C

2012-01-01

72

FXR Protects Lung from Lipopolysaccharide-Induced Acute Injury  

PubMed Central

Acute lung injury and its more severe form, acute respiratory distress syndrome, are characterized by an acute inflammatory response in the airspaces and lung parenchyma. The nuclear receptor farnesoid X receptor (FXR) is expressed in pulmonary artery endothelial cells. Here, we report a protective role of FXR in a lipopolysaccharide-induced mouse model of acute lung injury. Upon intratracheal injection of lipopolysaccharide, FXR?/? mice showed higher lung endothelial permeability, released more bronchoalveolar lavage cells to the alveoli, and developed acute pneumonia. Cell adhesion molecules were expressed at higher levels in FXR?/? mice as compared with control mice. Furthermore, lung regeneration was much slower in FXR?/? mice. In vitro experiments showed that FXR activation blocked TNF?-induced expression of P-selectin but stimulated proliferation of lung microvascular endothelial cells through up-regulation of Foxm1b. In addition, expression of a constitutively active FXR repressed the expression of proinflammatory genes and improved lung permeability and lung regeneration in FXR?/? mice. This study demonstrates a critical role of FXR in suppressing the inflammatory response in lung and promoting lung repair after injury. PMID:22135065

Zhang, Lisheng; Li, Tao; Yu, Donna; Forman, Barry M.

2012-01-01

73

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. Expected final online publication date for the Annual Review of Physiology Volume 77 is February 10, 2015. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates. PMID:25386990

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

2014-10-29

74

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

75

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

76

Interstitial lung diseases in children  

PubMed Central

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

2010-01-01

77

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, Egypt. Abstract--Chronic Obstructive Pulmonary Disease (COPD) refers to a group of lung diseases bronchitis. Pulmonary emphysema is defined as a lung disease characterized by "abnormal enlargement

Paris-Sud XI, Université de

78

Pulmonary nuclear medicine: Techniques in diagnosis of lung disease  

SciTech Connect

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

Atkins, H.L.

1984-01-01

79

Lung Cancer and Interstitial Lung Diseases: A Systematic Review  

PubMed Central

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

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

2012-01-01

80

Lung cancer and interstitial lung diseases: a systematic review.  

PubMed

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

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

2012-01-01

81

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

82

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

PubMed

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; Song, Jin Woo

2014-08-01

83

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

84

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

85

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 ...

86

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

87

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

88

Activator protein-1 activation in acute lung injury.  

PubMed

The role of activator protein-1 (AP-1) in inflammation is primarily unknown. AP-1 was evaluated in nuclear extracts from alveolar macrophages and whole lung nuclear extracts during acute lung injury after deposition of IgG immune complexes. AP-1 activation occurred in macrophages and in whole lung extracts, but with distinctly different time courses. Low levels of constitutive AP-1 were observed in normal rat lung as determined by the electrophoretic mobility shift assay. Increased AP-1 was detected 2 hours after initiation of the inflammatory response in lung with a further increase by 4 hours, while AP-1 activation was found in alveolar macrophages 0.5 hour after onset of the inflammatory response. mRNAs and proteins for c-fos, c-jun, jun-B, and jun-D were all up-regulated in whole lung tissues and in alveolar macrophages during acute lung injury induced by IgG immune complex deposition. Depletion of lung macrophages sharply reduced AP-1 activation, as did anti-tumor necrosis factor-alpha, whereas complement depletion showed no effect on lung AP-1 activation. The data suggest that activation of AP-1 occurs in both alveolar macrophages and in the lung, and this activation process is macrophage- and tumor necrosis factor-alpha-dependent. PMID:12107112

Guo, Ren-Feng; Lentsch, Alex B; Sarma, J Vidya; Sun, Lei; Riedemann, Niels C; McClintock, Shannon D; McGuire, Stephanie R; Van Rooijen, Nico; Ward, Peter A

2002-07-01

89

Asbestos-induced lung disease.  

PubMed Central

This review attempts to deal with two major questions concerning asbestos-induced lung disease: How does inhaled asbestos cause cell proliferation and fibrosis? and Will there continue to be risk from exposure to asbestos in schools and public buildings? The first is a scientific question that has spawned many interesting new experiments over the past 10 years, and there appear to be two hypothetical schemes which could explain, at least in part, the fibroproliferative effects of asbestos fibers. One supports the view that toxic oxygen radicals generated on fiber surfaces and/or intracellularly are the central mediators of disease. The second hypothesis is not mutually exclusive of the first, but, in my opinion, may be integral to it, i.e., the cellular injury induced by oxygen radicals stimulates the elaboration of multiple varieties of growth factors and cytokines that mediate the pathogenesis of asbestosis. There is increasing evidence that molecules such as platelet-derived growth factor and transforming growth factor beta, both synthesized and secreted by activated lung macrophages, are responsible, respectively, for the increased interstitial cell populations and extracellular matrix proteins that are the hallmarks of asbestos-induced fibrosis. The challenge today is to establish which combinations of the many factors released actually are playing a role in disease pathogenesis. The issue of continued risk currently is more a question of policy and perception than science because a sufficient database has not yet been established to allow full knowledge of the circumstances under which asbestos in buildings constitutes an ongoing health hazard. The litigious nature of this question does not help its resolution. In as much as public policy statements and risk assessment are not within my purview, I have focused on the state-of-the-art of asbestos as a complete carcinogen. It appears to be generally nongenotoxic, but all asbestos fiber types can induce chromosomal mutations and aneuploidy, perhaps through their ability to disrupt normal chromosome segregation. Images FIGURE 1. 1a FIGURE 1. 1b FIGURE 2. FIGURE 3. FIGURE 4. 4a FIGURE 4. 4b FIGURE 5. 5a FIGURE 5. 5b FIGURE 6. PMID:8354168

Brody, A R

1993-01-01

90

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

91

Imaging of macrophage-related lung diseases  

Microsoft Academic Search

Macrophage-related pulmonary diseases are a heterogeneous group of disorders characterized by macrophage accumulation, activation or dysfunction. These conditions include smoking-related interstitial lung diseases, metabolic disorders such as Niemann–Pick or Gaucher disease, and rare primary lung tumors. High-resolution computed tomography abnormalities include pulmonary ground-glass opacification secondary to infiltration by macrophages, centrilobular nodules or interlobular septal thickening reflecting peribronchiolar or septal macrophage

Katharina Marten; David M. Hansell

2005-01-01

92

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

93

Elastic pressure-volume curves in acute lung injury and acute respiratory distress syndrome  

Microsoft Academic Search

BackgroundThe principal features of elastic pressure-volume curves of lungs or the respiratory system (P el\\/V curves) recorded during reexpansion of collapsed lungs and subsequent deflation have been known since the 1950s. In acute respiratory failure and acute respiratory distress syndrome such curves have recently attracted increasing interest because new knowledge can be acquired from them, and because such curves may

Björn Jonson

2005-01-01

94

Elastic pressure-volume curves in acute lung injury and acute respiratory distress syndrome  

Microsoft Academic Search

\\u000a \\u000a Background  The principal features of elastic pressure-volume curves of lungs or the respiratory system (Pel\\/V curves) recorded during reexpansion of collapsed lungs and subsequent deflation have been known since the 1950s. In acute\\u000a respiratory failure and acute respiratory distress syndrome such curves have recently attracted increasing interest because\\u000a new knowledge can be acquired from them, and because such curves may be

Björn Jonson

95

Pathophysiology of pulmonary hypertension in acute lung injury  

PubMed Central

Acute lung injury (ALI) and acute respiratory distress syndrome are characterized by protein rich alveolar edema, reduced lung compliance, and acute severe hypoxemia. A degree of pulmonary hypertension (PH) is also characteristic, higher levels of which are associated with increased morbidity and mortality. The increase in right ventricular (RV) afterload causes RV dysfunction and failure in some patients, with associated adverse effects on oxygen delivery. Although the introduction of lung protective ventilation strategies has probably reduced the severity of PH in ALI, a recent invasive hemodynamic analysis suggests that even in the modern era, its presence remains clinically important. We therefore sought to summarize current knowledge of the pathophysiology of PH in ALI. PMID:22246001

Price, Laura C.; McAuley, Danny F.; Marino, Philip S.; Finney, Simon J.; Griffiths, Mark J.

2012-01-01

96

Hard metal lung disease and pneumothorax.  

PubMed

This case report describes a case of spontaneous pneumothorax in a metal grinder that failed to resolve with medical management. A lung biopsy taken during the subsequent thoracotomy revealed changes that were characteristic of giant cell interstitial pneumonia, as seen in hard metal disease. Pneumothorax has been described in many forms of interstitial lung disease but not in this type of occupational disease. Awareness of this possible association can result in: (1) the removal of an affected worker from his adverse work environment before advanced disease develops; and (2) the safe control of the work environment, to the advantage of other similarly exposed workers. PMID:9122508

Wahbi, Z K; Arnold, A G; Taylor, A J

1997-02-01

97

The role of platelets in acute lung injury (ALI)  

PubMed Central

Acute lung injury (ALI) is a common syndrome associated with a high mortality rate. Better understanding of the pathophysiology of acute lung injury and progress in supportive care and mechanical ventilation have led to slightly improved clinical outcomes. New evidence shows that the interplay between platelets, leukocytes and endothelial cells is critical in the pathogenesis of ALI. Key molecules involved in this interaction include P-selectin (Selp) and the eicosanoid thromboxane A2 (TXA2), suggesting potential new targets for pharmacological intervention. In this review, we summarize the aspects of the interactions between platelets, leukocytes, and endothelial cells that are relevant for the pathogenesis of ALI. PMID:19273059

Zarbock, Alexander; Ley, Klaus

2009-01-01

98

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

PubMed

Eosinophilic lung diseases are a diverse group of pulmonary disorders associated with peripheral or tissue eosinophilia. They are classified as eosinophilic lung diseases of unknown cause (simple pulmonary eosinophilia [SPE], acute eosinophilic pneumonia [AEP], chronic eosinophilic pneumonia [CEP], idiopathic hypereosinophilic syndrome [IHS]), eosinophilic lung diseases of known cause (allergic bronchopulmonary aspergillosis [ABPA], bronchocentric granulomatosis [BG], parasitic infections, drug reactions), and eosinophilic vasculitis (allergic angiitis, granulomatosis [Churg-Strauss syndrome]). The percentages of eosinophils in peripheral blood and bronchoalveolar lavage fluid are essential parts of the evaluation. Chest computed tomography (CT) demonstrates a more characteristic pattern and distribution of parenchymal opacities than does conventional chest radiography. At CT, SPE and IHS are characterized by single or multiple nodules with a surrounding ground-glass-opacity halo, AEP mimics radiologically hydrostatic pulmonary edema, and CEP is characterized by nonsegmental airspace consolidations with peripheral predominance. ABPA manifests with bilateral central bronchiectasis with or without mucoid impaction. The CT manifestations of BG are nonspecific and consist of a focal mass or lobar consolidation with atelectasis. The most common CT findings in Churg-Strauss syndrome include sub-pleural consolidation with lobular distribution, centrilobular nodules, bronchial wall thickening, and interlobular septal thickening. The integration of clinical, radiologic, and pathologic findings facilitates the initial and differential diagnoses of various eosinophilic lung diseases. PMID:17495282

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

2007-01-01

99

[Local use of recombinant interleukin-1 beta in the complex treatment of patients with acute lung abscess].  

PubMed

An analysis of results of examination and treatment of 59 patients with a prolonged duration of acute abscesses of the lungs has shown the influence of immune disorders on the dynamics of the development and outcome of pyo-destructive disease in the lung. The indications to local immunosubstituting therapy were determined. A new original method of administration and a scheme of prescription of the medicine Betaleukin are proposed. Clinical efficiency of the method proposed is shown. The local immunocorrection used in the complex treatment of patients with acute abscesses of the lungs allows to get recovery of 89% of the patients. PMID:11517783

Bisenkov, L N; Simbirtsev, A S; Zolotarev, D V; Salamatov, A V; Variushina, E A

2001-01-01

100

[Drug-induced interstitial lung diseases].  

PubMed

Drug-induced infiltrative lung disease may manifest as variable clinical radiological patterns, including subacute or chronic interstitial pneumonia, pulmonary fibrosis, eosinophilic pneumonia, organising pneumonia, pulmonary edema, or sarcoidosis. A large amount of drugs have been incriminated, including those used in cardiovascular diseases (amiodarone, statins and angiotensin converting enzyme inhibitors), antibiotics (minocycline, nitrofurantoin), most of anticancer drugs (and especially chemotherapy and chest radiation), treatment of rheumatoid arthritis, as well as more recent drugs. A high index of suspicion is therefore required in any patient with infiltrative lung disease and the web-based tool www.pneumotox.com will help to list possible causative drugs. The following steps are necessary: history and timing of drug exposure, clinical and imaging pattern, exclusion of other causes of infiltrative lung disease, improvement following drug discontinuation. Rechallenge, dangerous, is not recommended. PMID:25362778

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

2014-09-01

101

Pyrrolidine Dithiocarbamate Attenuates Endotoxin-induced Acute Lung Injury  

Microsoft Academic Search

Lung injury in the acute respiratory distress syndrome (ARDS) is in part due to polymorphonuclear leuko- cyte (PMN)-mediated oxidative tissue damage. By means of nuclear factor- k B (NF- k B) activation, oxi- dants may also induce several genes implicated in the inflammatory response. The dithiocarbamates are antioxidants with potent inhibitory effects on NF- k B. We postulated that the

Avery B. Nathens; Richard Bitar; Christopher Davreux; Michael Bujard; John C. Marshall; Alan P. B. Dackiw; Ronald W. G. Watson; Ori D. Rotstein

1997-01-01

102

Common lung conditions: environmental pollutants and lung disease.  

PubMed

Exposure to environmental pollutants can have short- and long-term effects on lung health. Sources of air pollution include gases (eg, carbon monoxide, ozone) and particulate matter (eg, soot, dust). In the United States, the Environmental Protection Agency regulates air pollution. Elevated ozone concentrations are associated with increases in lung-related hospitalizations and mortality. Elevated particulate matter pollution increases the risk of cardiopulmonary and lung cancer mortality. Occupations with high exposures to pollutants (eg, heavy construction work, truck driving, auto mechanics) pose higher risk of chronic obstructive lung disease. Some industrial settings (eg, agriculture, sawmills, meat packing plants) also are associated with higher risks from pollutants. The Environmental Protection Agency issues an air quality index for cities and regions in the United States. The upper levels on the index are associated with increases in asthma-related emergency department visits and hospitalizations. Damp and moldy housing might make asthma symptoms worse; individuals from lower socioeconomic groups who live in lower quality housing are particularly at risk. Other household exposures that can have negative effects on lung health include radon, nanoparticles, and biomass fuels. PMID:23767420

Delzell, John E

2013-06-01

103

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

104

Assessment of Lung Inflammation With 18F-FDG PET During Acute Lung Injury  

PubMed Central

Objective The purpose of this review is to describe the current experimental and clinical data regarding the fundamentals and applications of 18F-FDG PET during acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Conclusion Lung inflammation is a key feature of ALI. During ALI, FDG PET can be used to monitor lung neutrophils, which are essential cells in the pathophysiologic mechanisms of ALI. Pulmonary FDG kinetics are altered during experimental and human ALI and are associated with regional lung dysfunction, histologic abnormalities, and prognosis. FDG PET may be a valuable noninvasive method for gaining comprehensive understanding of the mechanisms of ALI/ARDS and for evaluating therapeutic interventions. PMID:20651183

de Prost, Nicolas; Tucci, Mauro R.; Vidal Melo, Marcos F.

2011-01-01

105

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

2014-10-13

106

Nitric Oxide and Nitrotyrosine in the Lungs of Patients with Acute Respiratory Distress Syndrome  

Microsoft Academic Search

Nitric oxide (NO) end-products (nitrate and nitrite) are present in bronchoalveolar lavage (BAL) fluid of patients with inflammatory lung diseases. Reactive oxygen-nitrogen intermediates damage macro- molecules by oxidation or nitration of critical residues in proteins. The goal of this study was to measure NO end-products (nitrate 1 nitrite), in BAL fluid before and after the onset of acute respiratory distress

CHANCHAI SITTIPUNT; KENNETH P. STEINBERG; JOHN T. RUZINSKI; CARPANTATO MYLES; SHA ZHU; RICHARD B. GOODMAN; LEONARD D. HUDSON; SADIS MATALON; THOMAS R. MARTIN

2001-01-01

107

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=35-45mmHg), ventilated with 0.03%CO2+21%O2+balancedN2; (2) hypercapnic acidosis (HC, PaCO2=60-70mmHg), 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

108

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

109

Acute Lung Function Response to Dust in Street Sweepers  

PubMed Central

Background: Sweepers are chronically exposed to dust raised during sweeping. Dust is regarded as the most influential agent and it is perceived as a frequent cause of respiratory system illness and may cause acute and chronic lung function impairment. Aims: The aim of this study was to determine the acute lung function changes in sweepers exposed to dust generated from street sweeping. Material and Methods: This study was conducted in central Karnataka, India, on 25 female sweepers and 25 healthy female control subjects who were comparable in age, height and weight. The pulmonary function test was performed in controls, sweepers before and after sweeping, by using RMS medspiror and results were compared by Student’s unpaired ‘t’ test. Results: The results showed a significant reduction in percent predicted values and mean values of FVC, FEV1, PEFR, FEF25-75% and FEF 200-1200 between sweepers and their matched controls. Pulmonary function after sweeping also showed a significant decrease. Conclusions: On comparing the pulmonary functions of sweepers before and after sweeping, it was concluded that inhalation of dust acutely affected the lung function of sweepers in India and that sweepers were at a risk of developing occupation related lung function impairment. We recommend that the workers should use protective face masks and do wet sweeping instead of dry sweeping during sweeping activity. PMID:24298455

Johncy S., Smilee; G., Dhanyakumar; Samuel T., Vivian; K.T., Ajay; Bondade, Suresh Y.

2013-01-01

110

Lung function after acute chlorine exposure.  

PubMed

Chlorine gas, spreading from a train derailment, caused the deaths of 8 persons and the hospitalization of 23 with sublethal respiratory injuries. Twenty-five others had at least one sign of lower respiratory abnormality but were not hospitalized. One hundred thirteen who were examined for gas effects in the forty-eight hours after exposure, including 20 of 23 of those hospitalized and 21 of 25 of those not hospitalized but with respiratory abnormality, participated in follow-up studies. Probability of admission to hospital was related to distance from the spill, but by 3 wk after exposure there was no detectable difference in lung function relating to distance or apparent severity of injury. In 60 adults tested multiple times over the following 6 yr, longitudinal change in lung function showed expected differences related to smoking but none related to distance or severity of injury. The average annual change in FEV was -34 ml/yr in current smokers and -18 ml/yr in ex and never-smokers. The lack of a discernible chlorine effect in this cohort accords with the findings in most previous studies. Without pre-exposure measurements, a single, lasting reduction in lung function cannot be excluded, but there is no evidence for a persisting abnormal rate of decline. PMID:3789518

Jones, R N; Hughes, J M; Glindmeyer, H; Weill, H

1986-12-01

111

Stevioside protects LPS-induced acute lung injury in mice.  

PubMed

Stevioside, a diterpene glycoside component of Stevia rebaudiana, has been known to exhibit anti-inflammatory properties. To evaluate the effect and the possible mechanism of stevioside in lipopolysaccharide (LPS)-induced acute lung injury, male BALB/c mice were pretreated with stevioside or dexamethasone 1 h before intranasal instillation of LPS. Seven hours later, tumor necrosis factor-?, interleukin-1?, and interleukin-6 in bronchoalveolar lavage fluid (BALF) were measured by using enzyme-linked immunosorbent assay. The number of total cells, neutrophils, and macrophages in the BALF were also determined. The right lung was excised for histological examination and analysis of myeloperoxidase activity and nitrate/nitrite content. Cyclooxygenase 2 (COX-2), inducible NO synthase (iNOS), nuclear factor-kappa B (NF-?B), inhibitory kappa B protein were detected by western blot. The results showed that stevioside markedly attenuated the LPS-induced histological alterations in the lung. Stevioside inhibited the production of pro-inflammatory cytokines and the expression of COX-2 and iNOS induced by LPS. In addition, not only was the wet-to-dry weight ratio of lung tissue significantly decreased, the number of total cells, neutrophils, and macrophages in the BALF were also significantly reduced after treatment with stevioside. Moreover, western blotting showed that stevioside inhibited the phosphorylation of I?B-? and NF-?B caused by LPS. Taken together, our results suggest that anti-inflammatory effect of stevioside against the LPS-induced acute lung injury may be due to its ability of inhibition of the NF-?B signaling pathway. Stevioside may be a promising potential therapeutic reagent for acute lung injury treatment. PMID:22968433

Yingkun, Nie; Zhenyu, Wang; Jing, Lin; Xiuyun, Lu; Huimin, Yu

2013-02-01

112

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

113

Long-Term Control Medications for Lung Diseases  

MedlinePLUS

... Term Control Medications Long-Term Control Medications for Lung Diseases Long-term control medications are taken daily to control and prevent lung disease symptoms. These medicines should be taken every ...

114

Genetic polymorphisms and susceptibility to lung disease.  

PubMed

Susceptibility to infection by bacterium such as Bacillus anthracis has a genetic basis in mice and may also have a genetic basis in humans. In the limited human cases of inhalation anthrax, studies suggest that not all individuals exposed to anthrax spores were infected, but rather, individuals with underlying lung disease, particularly asthma, sarcoidosis and tuberculosis, might be more susceptible. In this study, we determined if polymorphisms in genes important in innate immunity are associated with increased susceptibility to infectious and non-infectious lung diseases, particularly tuberculosis and sarcoidosis, respectively, and therefore might be a risk factor for inhalation anthrax. Examination of 45 non-synonymous polymorphisms in ten genes: p47phox (NCF1), p67phox (NCF2), p40phox (NCF4), p22phox (CYBA), gp91phox (CYBB), DUOX1, DUOX2, TLR2, TLR9 and alpha 1-antitrypsin (AAT) in a cohort of 95 lung disease individuals and 95 control individuals did not show an association of these polymorphisms with increased susceptibility to lung disease. PMID:16608528

Lee, Pauline L; West, Carol; Crain, Karen; Wang, Lei

2006-01-01

115

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

116

Experimental Models of Transfusion-Related Acute Lung Injury (TRALI)  

PubMed Central

Transfusion-related acute lung injury (TRALI) is defined clinically as acute lung injury occurring within six hours of the transfusion of any blood product. It is the leading cause of transfusion-related death in the United States, but under-recognition and diagnostic uncertainty have limited clinical research to smaller case control studies. In this review we will discuss the contribution of experimental models to the understanding of TRALI pathophysiology and potential therapeutic approaches. Experimental models suggest that TRALI occurs when a host, with a primed immune system, is exposed to an activating agent such as anti-leukocyte antibody or a biologic response modifier such as lysophosphatidylcholines. Recent work has suggested a critical role for platelets in antibody-based experimental models and identified potential therapeutic strategies for TRALI. PMID:21134622

Gilliss, Brian M.; Looney, Mark R.

2010-01-01

117

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

Microsoft Academic Search

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

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

2008-01-01

118

Identification of Early Interstitial Lung Disease in Smokers from the  

E-print Network

interstitial lung disease (ILD) on chest computed tomographic (CT) scans. Materials and Methods: The CT scans: Early interstitial lung disease; CT scan; smoker. ªAUR, 2010 I diopathic pulmonary fibrosis (IPFIdentification of Early Interstitial Lung Disease in Smokers from the COPDGene Study George R

119

Presumptive acute lung injury following multiple surgeries in a cat  

PubMed Central

A 12-year-old, 3.5-kg spayed female domestic shorthair cat had a tracheal mass identified as malignant B-cell lymphoma. The cat had tracheal resection and subsequently developed laryngeal paralysis. Due to multiple episodes of respiratory distress the cat subsequently had tracheal surgeries. Finally, the cat had a sudden onset of severe respiratory distress and collapsed. Computed tomography imaging and arterial blood gas analysis supported a diagnosis of acute lung injury. PMID:24082167

Katayama, Masaaki; Okamura, Yasuhiko; Katayama, Rieko; Sasaki, Jun; Shimamura, Shunsuke; Uzuka, Yuji; Kamishina, Hiroaki; Nezu, Yoshinori

2013-01-01

120

Acute Respiratory Distress Syndrome Caused by Pulmonary and Extrapulmonary Disease Different Syndromes?  

Microsoft Academic Search

To assess the possible differences in respiratory mechanics between the acute respiratory distress syndrome (ARDS) originating from pulmonary disease (ARDS p ) and that originating from extrapul- monary disease (ARDS exp ) we measured the total respiratory system (Est,rs), chest wall (Est,w) and lung (Est,L) elastance, the intra-abdominal pressure (IAP), and the end-expiratory lung volume (EELV) at 0, 5, 10,

LUCIANO GATTINONI; PAOLO PELOSI; PETER M. SUTER; ALESSIA PEDOTO; PAOLA VERCESI; ALFREDO LISSONI

121

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

122

Lung disease modifier genes in cystic fibrosis.  

PubMed

Cystic fibrosis (CF) is recognized as a single gene disorder. However, a considerable diversity in its clinical phenotype has been documented since the description of the disease. Identification of additional gene alleles, so called "modifier genes" that directly influence the phenotype of CF disease became a challenge in the late '90ies, not only for the insight it provides into the CF pathophysiology, but also for the development of new potential therapeutic targets. One of the most studied phenotype has been the lung disease severity as lung dysfunction is the major cause of morbidity and mortality in CF. This review details the results of two main genetic approaches that have mainly been explored so far: (1) an "a priori" approach, i.e. the candidate gene approach; (2) a "without a priori" approach, analyzing the whole genome by linkage and genome-wide association studies (GWAS), or the whole exome by exome sequencing. PMID:24569122

Guillot, Loic; Beucher, Julie; Tabary, Olivier; Le Rouzic, Philippe; Clement, Annick; Corvol, Harriet

2014-07-01

123

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

124

Enrichment of Murine CD68+CCR2+ and CD68+CD206+ Lung Macrophages in Acute Pancreatitis-Associated Acute Lung Injury  

PubMed Central

Acute lung injury (ALI) is an important cause of mortality in critically ill patients. Acute pancreatitis (AP) is one of the risk factors for developing this syndrome. Among the inflammatory cells, macrophages have a key role in determining the severity of the acute lung injury. In the lungs, macrophages constitute a heterogeneous cell population distributed in different compartments. Changes in not only the macrophage count, but also in their phenotype have been seen during the course of lung injury. A murine ductal ligation model of acute pancreatitis showed substantial morphological changes in the pancreas and lungs. Immunohistochemistry showed neutrophil recruitment into both organs after 9 hours and later on. F4/80+ cells in the pancreas increased in the ligated animals, though there was not a significant difference in their number in the lungs as compared to sham operated animals. Flow cytometry analysis of lung macrophages demonstrated an enrichment of F4/80? CD68+CCR2+ and F4/80? CD68+CD206+ lung macrophages in ligated animals (AP) as compared to the sham operated group. The level of interleukin-6 in plasma increased 3 hours after ligation compared to the sham operated group, as a first indicator of a systemic inflammatory response. This study suggests a role for F4/80? CD68+ macrophages in the pathogenesis of acute lung injury in acute pancreatitis. Studying lung macrophages for different phenotypic markers, their polarization, activation and recruitment, in the context of acute lung injury, is a novel area to potentially identify interventions which may improve the outcome of acute lung injury. PMID:23110041

Akbarshahi, Hamid; Menzel, Mandy; Posaric Bauden, Monika; Rosendahl, Ann; Andersson, Roland

2012-01-01

125

Gene therapy for acute lung injury  

Microsoft Academic Search

The remarkable transition of biological science into the age of molecular biology held great promise for development of new therapies for treatment of human disease. The fact that the technology exists for analyzing genetic material in exquisite detail and constructing DNA in virtually any desired form was the basis for promising rapid translation into clinical medicine and the final cure

K. L. Brigham; A. A. Stecenko

2000-01-01

126

[Interstitial lung disease related to systemic connective tissue diseases].  

PubMed

Interstitial lung disease (ILD) is one of the most frequent and most serious complications of connective tissue diseases such as systemic sclerosis, systemic lupus erythematosus, dermato- and polymyositis, Sjogren's syndrome, or mixed connective tissue disease. Diagnosis of ILD is often delayed in patients with connective tissue diseases because of the systemic character of the primary condition, restricted physical activity of the patient and insufficient awareness of the physycian. The aim of the current review is to present the up-to-date information on ethiopathology, classification, diagnosis and treatment of ILD in patients with connective tissue diseases. PMID:16786776

Fiedorczyk, Ma?gorzata; Rojewska, Joanna; Kowal-Bielecka, Otylia; Sierakowski, Stanis?aw

2005-01-01

127

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

128

Incidence and outcome of acute lung injury and acute respiratory distress syndrome in the surgical intensive care unit  

PubMed Central

Introduction: To determine the incidence and mortality of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in a cohort of patients with risk factors admitted to the Surgical Intensive Care Unit (SICU). Materials and Methods: A prospective observational inception cohort study with no intervention was conducted over 12 months. All patients with at least one known risk factor for ALI/ARDS admitted to the SICU were included in the study. The APACHE II severity of disease classification system scoring was performed within 1 h of admission. The ventilatory parameters and chest radiographs were recorded every 24 h. The P/F ratio, PEEP and Lung Injury Score were calculated each day until the day of discharge from the Intensive Care Unit or for the first 7 days of admission, whichever was shorter. Results: The incidence of ARDS among those who were mechanically ventilated was 11.4%. Sepsis was the most common (34.6%) etiology. Among those with risk factors, the incidence of ARDS was 30% and that of ALI was 32.7%. The mortality in those with ARDS was 41.8%. Those who develop ARDS had higher APACHE II scores, lower pH and higher PaCO2 at admission compared with those who developed ALI or no lung injury. Conclusion: The incidence and mortality of ARDS was similar to other studies. Identifying those with risk factors for ARDS or mortality will enable appropriate interventional measures. PMID:25316976

Singh, Georgene; Gladdy, George; Chandy, Tony Thomson; Sen, Nagamani

2014-01-01

129

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

130

Attenuation of IgG immune complex-induced acute lung injury by silencing C5aR in lung epithelial cells  

PubMed Central

Acute lung injury (ALI) in mouse lung occurs after distal airway deposition of IgG immune complexes (IgGICs), resulting in a breakdown of the vascular-airway barrier, causing intrapulmonary edema, hemorrhage, and accumulation of neutrophils [polymorphonuclear leukocytes (PMNs)] in the alveolar compartment, these changes being complement (C5a) and C5a receptor (C5aR) dependent. In this ALI model, C5aR expression (protein) was found to occur on upper (bronchial) and lower (alveolar) airway epithelial cells. An adenovirus construct (siRNA) was used to silence mRNA for C5aR in the lung. Under such conditions, C5aR protein was markedly reduced on lung epithelial cells, resulting in much reduced leakage of albumin into the lung, diminished buildup of PMNs, and lower levels of proinflammatory mediators in bronchoalveolar lavage fluids. These studies indicate that bronchial and alveolar epithelial cell C5aR is up-regulated and greatly contributes to inflammation and injury in the lung. The use of siRNA administered into the airways avoids systemic suppression of C5aR, which might compromise innate immunity. It is possible that such an intervention might be employed in humans with ALI or acute respiratory distress syndrome as well as in upper-airway inflammatory diseases, such as chronic obstructive pulmonary disease and asthma, where there is evidence for complement activation and buildup of PMNs.—Sun, L., Guo, R.-F., Gao, H., Sarma, J. V., Zetoune, F. S., Ward, P. A. Attenuation of IgG immune complex-induced acute lung injury by silencing C5aR in lung epithelial cells. PMID:19620403

Sun, Lei; Guo, Ren-Feng; Gao, Hongwei; Sarma, J. Vidya; Zetoune, Firas S.; Ward, Peter A.

2009-01-01

131

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

132

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

133

Adult Stem Cells for Acute Lung Injury: Remaining Questions & Concerns  

PubMed Central

Acute lung injury (ALI) or acute respiratory distress syndrome remains a major cause of morbidity and mortality in hospitalized patients. The pathophysiology of ALI involves complex interactions between the inciting event, such as pneumonia, sepsis or aspiration, and the host immune response resulting in lung protein permeability, impaired resolution of pulmonary edema, an intense inflammatory response in the injured alveolus and hypoxemia. In multiple pre-clinical studies, adult stem cells have been shown to be therapeutic due to both the ability to mitigate injury and inflammation through paracrine mechanisms and perhaps to regenerate tissue by virtue of their multi-potency. These characteristics have stimulated intensive research efforts to explore the possibility of using stem or progenitor cells for the treatment of lung injury. A variety of stem or progenitor cells have been isolated, characterized, and tested experimentally in pre-clinical animal models of ALI. However, questions remain concerning the optimal dose, route and the adult stem or progenitor cell to use. Here, we review current mechanisms underlying the therapeutic effect of stem cells in ALI as well as the questions that will arise as clinical trials for ALI are planned. PMID:23578018

Zhu, Ying-gang; Hao, Qi; Monsel, Antoine; Feng, Xiao-mei

2013-01-01

134

Genetic Predisposition to Respiratory Diseases: Infiltrative Lung Diseases  

Microsoft Academic Search

The availability of high-throughput genotyping and large collaborative clinical networks creating well-characterized patient populations with DNA repositories has facilitated genome-wide scans and candidate gene studies to identify susceptibility alleles for the development of interstitial lung disease. The association of pulmonary fibrosis with rare inherited disorders, and the variable susceptibility of inbred mouse strains to this disease indicate that pulmonary fibrosis

Mark P. Steele; Kevin K. Brown

2007-01-01

135

[Interstitial lung disease in connective tissue disorders].  

PubMed

After immunosuppressive-induced infections, interstitial lung disease (ILD) is one of the most serious pulmonary complications associated with connective tissue diseases (CTD). Although it is common for ILD to be diagnosed concurrent with or after CTD, some patients will present with ILD years prior to receiving a diagnosis of CTD. The clinical approach involves an examination of the extrathoracic symptoms (suggestive of CTD) and the evaluation of respiratory disability. Nonspecific interstitial pneumonia is the most common histological finding in patients with CTD. The management of patients with CTD-associated ILD is optimized by multidisciplinary collaboration. ILD-CTD are treated through anti-inflammatory medication, immunosuppressants and biological agents. PMID:25362775

Carmier, Delphine; Diot, Élisabeth; Guilleminault, Laurent; Marchand-Adam, Sylvain

2014-09-01

136

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

137

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

138

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

139

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.

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

2014-01-01

140

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

141

Tetrahydrocoptisine protects rats from LPS-induced acute lung injury.  

PubMed

Recent studies show that nuclear factor-kappa B (NF-?B) signaling pathway plays a key role in contributing to the development of lipopolysaccharide (LPS)-induced acute lung injury (ALI). Tetrahydrocoptisine is one of the main active components of Chelidonium majus L. and has been described to be effective in suppressing inflammation. The aim of the present study is to evaluate the protective effect of tetrahydrocoptisine on LPS-induced ALI in rats and clarify its underlying mechanisms of action. We found that in vivo pretreatment with tetrahydrocoptisine to rats 30 min before inducing ALI by LPS markedly decreased the mortality rate, lung wet weight to dry weight ratio, and ameliorated lung pathological changes. Meanwhile, tetrahydrocoptisine significantly inhibited the increase of the amounts of inflammatory cells, total protein content, tumor necrosis factor-? (TNF-?) and interleukin-6 (IL-6) secretion in the bronchoalveolar lavage fluids (BALFs). Furthermore, tetrahydrocoptisine inhibited myeloperoxidase (MPO) accumulation in lung tissue and alleviated TNF-? and IL-6 production in serum. Additionally, immunohistochemistry showed that tetrahydrocoptisine efficiently reduced nuclear factor-kappa B (NF-?B) activation by inhibiting the translocation of NF-?Bp65. In conclusion, our results demonstrate that tetrahydrocoptisine possesses a protective effect on LPS-induced ALI through inhibiting of NF-?B signaling pathways, which may involve the inhibition of pulmonary inflammatory process. PMID:24928630

Li, Weifeng; Huang, Huimin; Niu, Xiaofeng; Fan, Ting; Hu, Hua; Li, Yongmei; Yao, Huan; Li, Huani; Mu, Qingli

2014-12-01

142

Longitudinal alignment of disease progression in fibrosing interstitial lung disease.  

PubMed

Generating disease progression models from longitudinal medical imaging data is a challenging task due to the varying and often unknown state and speed of disease progression at the time of data acquisition, the limited number of scans and varying scanning intervals. We propose a method for temporally aligning imaging data from multiple patients driven by disease appearance. It aligns follow- up series of different patients in time, and creates a cross-sectional spatio-temporal disease pattern distribution model. Similarities in the disease distribution guide an optimization process, regularized by temporal rigidity and disease volume terms. We demonstrate the benefit of longitudinal alignment by classifying instances of different fibrosing interstitial lung diseases. Classification results (AUC) of Usual Interstitial Pneumonia (UIP) versus non-UIP improve from AUC = 0.71 to 0.78 following alignment, classification of UIP vs. Extrinsic Allergic Alveolitis (EAA) improves from 0.78 to 0.88. PMID:25485367

Vogl, Wolf-Dieter; Prosch, Helmut; Müller-Mang, Christina; Schmidt-Erfurth, Ursula; Langs, Georg

2014-01-01

143

TGF-? is a critical mediator of acute lung injury  

PubMed Central

We have shown that the integrin ?v?6 activates latent TGF-? in the lungs and skin. We show here that mice lacking this integrin are completely protected from pulmonary edema in a model of bleomycin-induced acute lung injury (ALI). Pharmacologic inhibition of TGF-? also protected wild-type mice from pulmonary edema induced by bleomycin or Escherichia coli endotoxin. TGF-? directly increased alveolar epithelial permeability in vitro by a mechanism that involved depletion of intracellular glutathione. These data suggest that integrin-mediated local activation of TGF-? is critical to the development of pulmonary edema in ALI and that blocking TGF-? or its activation could be effective treatments for this currently untreatable disorder. PMID:11413161

Pittet, Jean-Francois; Griffiths, Mark J.D.; Geiser, Tom; Kaminski, Naftali; Dalton, Stephen L.; Huang, Xiaozhu; Brown, Lou Anne S.; Gotwals, Phillip J.; Koteliansky, Victor E.; Matthay, Michael A.; Sheppard, Dean

2001-01-01

144

Immunodetection of occult eosinophils in lung tissue biopsies may help predict survival in acute lung injury  

PubMed Central

Background Acute lung injury (ALI) is a serious respiratory disorder for which therapy is primarily supportive once infection is excluded. Surgical lung biopsy may rule out other diagnoses, but has not been generally useful for therapy decisions or prognosis in this setting. Importantly, tissue and peripheral blood eosinophilia, the hallmarks of steroid-responsive acute eosinophilic pneumonia, are not commonly linked with ALI. We hypothesized that occult eosinophilic pneumonia may explain better outcomes for some patients with ALI. Methods Immunohistochemistry using a novel monoclonal antibody recognizing eosinophil peroxidase (EPX-mAb) was used to assess intrapulmonary eosinophil accumulation/degranulation. Lung biopsies from ALI patients (n = 20) were identified following review of a pathology database; 45% of which (i.e., 9/20) displayed classical diffuse alveolar damage (ALI-DAD). Controls were obtained from uninvolved tissue in patients undergoing lobectomy for lung cancer (n = 10). Serial biopsy sections were stained with hematoxylin and eosin (H&E) and subjected to EPX-mAb immunohistochemistry. Results EPX-mAb immunohistochemistry provided a >40-fold increased sensitivity to detect eosinophils in the lung relative to H&E stained sections. This increased sensitivity led to the identification of higher numbers of eosinophils in ALI patients compared with controls; differences using H&E staining alone were not significant. Clinical assessments showed that lung infiltrating eosinophil numbers were higher in ALI patients that survived hospitalization compared with non-survivors. A similar conclusion was reached quantifying eosinophil degranulation in each biopsy. Conclusion The enhanced sensitivity of EPX-mAb immunohistochemistry uniquely identified eosinophil accumulation/degranulation in patients with ALI relative to controls. More importantly, this method was a prognostic indicator of patient survival. These observations suggest that EPX-mAb immunohistochemistry may represent a diagnostic biomarker identifying a subset of ALI patients with improved clinical outcomes. PMID:21871108

2011-01-01

145

Cystic lung disease in tuberculosis: An unusual presentation  

PubMed Central

Cysts in the lung can arise due to large number of causes out of which tuberculosis is very rare, We report a case of tuberculosis in a young female presenting as a febrile illness and respiratory failure with radiological features of cystic lung disease. With treatment,fever and respiratory distress subsided and cysts in the lungs showed partial regression. We highlight the need to consider tuberculosis in the differential diagnoses of cystic lung disease under appropriate circumstances. PMID:24339498

Ray, Animesh; Suri, J. C.; Sen, M. K.; Khanna, Arjun

2013-01-01

146

Acute lung injury and acute respiratory distress syndrome: experimental and clinical investigations  

PubMed Central

Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) can be associated with various disorders. Recent investigation has involved clinical studies in collaboration with clinical investigators and pathologists on the pathogenetic mechanisms of ALI or ARDS caused by various disorders. This literature review includes a brief historical retrospective of ALI/ARDS, the neurogenic pulmonary edema due to head injury, the long-term experimental studies and clinical investigations from our laboratory, the detrimental role of NO, the risk factors, and the possible pathogenetic mechanisms as well as therapeutic regimen for ALI/ARDS. PMID:22783284

Chen, Hsing I

2011-01-01

147

Review series: Aspects of interstitial lung disease: connective tissue disease-associated interstitial lung disease: how does it differ from IPF? How should the clinical approach differ?  

PubMed

The lung is frequently involved in connective tissue diseases (CTDs), although the frequency of lung manifestations varies according to the type of CTD. Interstitial lung diseases (ILD) are frequently seen in CTDs, particularly systemic sclerosis (SSc), polymyositis/dermatomyositis (PM/DM) and rheumatoid arthritis (RA), accounting for a significant proportion of deaths. A large percentage of patients with CTD-associated ILD has limited and stable disease, not requiring treatment. However, a significant minority has severe and/or progressive disease, necessitating prompt initiation of treatment. CTD-ILD histological patterns include non-specific interstitial pneumonia (NSIP), usual interstitial pneumonia (UIP), organizing pneumonia (OP), diffuse alveolar damage (DAD) and lymphocytic interstitial pneumonia (LIP). NSIP is the most common pattern in all CTDs, except for RA, characterized by a higher frequency of UIP. ILD can present acutely or chronically, with acute presentations being more common in systemic lupus erythematosus and PM/DM. Idiopathic pulmonary fibrosis (IPF) is a progressively worsening ILD characterized by inflammation and fibrosis. The characteristic histological pattern of IPF is UIP. Interestingly, a UIP pattern is associated with a significantly better survival in CTD-related disease compared to the idiopathic variety. Prognosis in IPF is dismal, with a median survival since diagnosis of 2-3 years. No treatment regimen has been shown to improve survival in IPF. By contrast, although there have been only two randomized placebo-controlled trials investigating the effect of immunosuppressive treatment in SSc-associated ILD, clinical experience suggests that immunosuppressive drugs in CTD-related ILDs are capable of benefiting a significant proportion of patients, particularly those with certain histological patterns of disease. This review will essentially focus on CTD-associated ILD and will compare aspects of clinical presentation and management to those of IPF. PMID:21339375

de Lauretis, Angelo; Veeraraghavan, Srihari; Renzoni, Elisabetta

2011-01-01

148

Lung Stem and Progenitor Cells in Tissue Homeostasis and Disease  

PubMed Central

The mammalian lung is a complex organ containing numerous putative stem/progenitor cell populations that contribute to region-specific tissue homeostasis and repair. In this review, we discuss recent advances in identifying and studying these cell populations in the context of lung homeostasis and disease. Genetically engineered mice now allow for lineage tracing of several lung stem and progenitor cell populations in vivo during different types of lung injury repair. Using specific sets of cell surface markers, these cells can also be isolated from murine and human lung and tested in 3D culture systems and in vivo transplant assays. The pathology of devastating lung diseases, including lung cancers, is likely in part due to dysregulation and dysfunction of lung stem cells. More precise characterization of stem cells with identification of new, unique markers; improvement in isolation and transplant techniques; and further development of functional assays will ultimately lead to new therapies for a host of human lung diseases. In particular, lung cancer biology may be greatly informed by findings in normal lung stem cell biology as evidence suggests that lung cancer is a disease that begins in, and may be driven by, neoplastic lung stem cells. PMID:24439808

Kim, Carla F.

2014-01-01

149

Genetic testing in diffuse parenchymal lung disease  

PubMed Central

Diffuse parenchymal lung diseases (DPLD) represent a diverse group of disorders affecting the distal lung parenchyma, specifically the tissue and spaces surrounding the alveoli, which may be filled with inflammatory cells, proliferating fibroblasts or established fibrosis, often leading to architectural distortion and impaired gas exchange. While the underlying pathogenetic mechanisms are known or inferred for some DPLD (such as sarcoidosis, silicosis, drug reactions and collagen vascular diseases), the pathogenesis of the majority of these entities - particularly those characterized by progressive fibrosis - is poorly understood. Several lines of evidence indicate that the development of pulmonary fibrosis is genetically determined. They include: 1. familial clustering; 2. the occurrence of pulmonary fibrosis in the context of rare inherited disorders; 3. substantial variability in the development of pulmonary fibrosis amongst individuals exposed to organic or inorganic dusts; 4. difference in susceptibility to fibrogenic stimuli amongst inbred strains of mice. This review focuses on idiopathic pulmonary fibrosis (IPF) and sarcoidosis, the two most common DPLD and the two entities for which there is stronger evidence of a genetic predisposition, although how aberrant genes interact with each other and with environmental factors, such as smoking in IPF and infectious agents in sarcoidosis, in determining disease susceptibility and clinical phenotypes is largely unknown. Finally, we discuss practical issues and implications for both patients and physicians of recent advances in the genetics of sarcoidosis and IPF. PMID:23075428

2012-01-01

150

Ventilator-associated lung injury in patients without acute lung injury at the onset of mechanical ventilation  

Microsoft Academic Search

of mechanical ventilation. When expressed per predicted body weight, women were ventilated with larger tidal volume than men (mean 11.4 vs. 10.4 mL\\/kg predicted body weight, p < .001) and tended to develop acute lung injury more often (29% vs. 20%, p .068). In a multivariate analysis, the main risk factors associated with the development of acute lung injury were

Ognjen Gajic; Saqib I. Dara; Jose L. Mendez; Adebola O. Adesanya; Emir Festic; Sean M. Caples; Rimki Rana; Jennifer L. St. Sauver; James F. Lymp; Bekele Afessa; Rolf D. Hubmayr

2004-01-01

151

Elemental analysis of occupational and environmental lung diseases by electron probe microanalyzer with wavelength dispersive spectrometer.  

PubMed

Occupational and environmental lung diseases are a group of pulmonary disorders caused by inhalation of harmful particles, mists, vapors or gases. Mineralogical analysis is not generally required in the diagnosis of most cases of these diseases. Apart from minerals that are encountered rarely or only in specific occupations, small quantities of mineral dusts are present in the healthy lung. As such when mineralogical analysis is required, quantitative or semi-quantitative methods must be employed. An electron probe microanalyzer with wavelength dispersive spectrometer (EPMA-WDS) enables analysis of human lung tissue for deposits of elements by both qualitative and semi-quantitative methods. Since 1993, we have analyzed 162 cases of suspected occupational and environmental lung diseases using an EPMA-WDS. Our institute has been accepting online requests for elemental analysis of lung tissue samples by EPMA-WDS since January 2011. Hard metal lung disease is an occupational interstitial lung disease that primarily affects workers exposed to the dust of tungsten carbide. The characteristic pathological findings of the disease are giant cell interstitial pneumonia (GIP) with centrilobular fibrosis, surrounded by mild alveolitis with giant cells within the alveolar space. EPMA-WDS analysis of biopsied lung tissue from patients with GIP has demonstrated that tungsten and/or cobalt is distributed in the giant cells and centrilobular fibrosing lesion in GIP. Pneumoconiosis, caused by amorphous silica, and acute interstitial pneumonia, associated with the giant tsunami, were also elementally analyzed by EPMA-WDS. The results suggest that commonly found elements, such as silicon, aluminum, and iron, may cause occupational and environmental lung diseases. PMID:24388365

Takada, Toshinori; Moriyama, Hiroshi; Suzuki, Eiichi

2014-01-01

152

The ubiquitin-CXCR4 axis plays an important role in acute lung-infection-enhanced lung tumor metastasis  

PubMed Central

Purpose Our goals are to test the effect of acute lung infection on tumor metastasis and to investigate the underlying mechanisms. Experimental Design We combined bacteria- and lipopolysaccharide (LPS)-induced acute lung injury/inflammation (ALI) mouse models with mouse metastatic models to study the effect of acute inflammation on lung metastasis in mice. The mechanisms were invested in ex vivo, in vitro, and in vivo studies. Results Both bacteria- and LPS-induced acute lung injury/inflammation significantly enhanced lung metastasis of four tail vein-injected mouse tumor cell lines. Bacteria also enhanced lung metastasis when 4T1 cells orthotopically injected. The broncheoalveolar lavage fluid (BALF) from LPS- or bacteria- injected mice stimulated migration of tumor cells. In vivo tracking of metastatic RM-9 cells showed that bacterial injection enhanced early dissemination of tumor cells to the lung. The majority of the BALF migratory activity could be blocked by AMD3100, a CXCR4 inhibitor. All tested cell lines expressed CXCR4. The levels of extracellular ubiquitin (Ub), but not SDF-1, in BALF were significantly increased by LPS. Ub was able to induce AMD3100-sensitive migration of tumor cells. Finally, the anti-bacterial amoxicillin and AMD3100 blocked the enhancement effect of bacterial infection on tumor metastasis. Conclusions Acute lung infection dramatically increased cancer cell homing to the lung and lung metastasis. This may be due to an alteration of the lung microenvironment and preparation of a favorable metastatic “niche”. This effect was seen in multiple cancer types and thus may have broad applications for cancer patients in prevention and/or treatment of metastasis. PMID:23690484

Yan, Libo; Cai, Qingchun; Xu, Yan

2013-01-01

153

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

154

Fatal interstitial lung disease associated with icotinib.  

PubMed

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; Chen, Rongchang

2014-12-01

155

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

156

Role of Stromelysin 1 and Gelatinase B in Experimental Acute Lung Injury  

Microsoft Academic Search

Matrix metalloproteinases (MMPs) are upregulated locally in sites of inflammation, including the lung. Several MMP activi- ties are upregulated in acute lung injury models but the exact role that these MMPs play in the development of the lung in- jury is unclear due to the absence of specific inhibitors. To de- termine the involvement of individual MMPs in the develop-

Roscoe L. Warner; Luis Beltran; Ellen M. Younkin; Clarence S. Lewis; Stephen J. Weiss; James Varani; Kent J. Johnson

157

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

158

Natural Killer Cells Are Involved in Acute Lung Immune Injury Caused by Respiratory Syncytial Virus Infection  

PubMed Central

It is known that respiratory syncytial virus (RSV) is the main cause of bronchiolitis and pneumonia in young children. RSV infection often leads to severe acute lung immunopathology, but the underlying immune mechanisms are not yet fully elucidated. Here, we found that RSV infection induced severe acute lung immune injury and promoted the accumulation and activation of lung natural killer (NK) cells at the early stage of infection in BALB/c mice. Activated lung NK cells highly expressed activating receptors NKG2D and CD27 and became functional NK cells by producing a large amount of gamma interferon (IFN-?), which was responsible for acute lung immune injury. NK cell depletion significantly attenuated lung immune injury and reduced infiltration of total inflammatory cells and production of IFN-? in bronchoalveolar lavage fluid (BALF). These data show that NK cells are involved in exacerbating the lung immune injury at the early stage of RSV infection via IFN-? secretion. PMID:22171263

Li, Fengqi; Zhu, Hanqing; Sun, Rui; Wei, Haiming

2012-01-01

159

Rikkunshito ameliorates bleomycin-induced acute lung injury in a ghrelin-independent manner.  

PubMed

Acute lung injury (ALI) is a critical syndrome consisting of acute respiratory failure associated with extensive pulmonary infiltrates. The pathological characterization of ALI includes injuries of alveolar epithelial cells (AECs), alveolar neutrophilic infiltration, and increases in proinflammatory cytokines, which cause destruction of the alveolar capillary barrier and subsequent devastating lung fibrosis. Rikkunshito (RKT), a traditional Japanese herbal medicine, is widely used for the treatment of patients with gastrointestinal symptoms and is known to stimulate ghrelin secretion. The therapeutic effects of RKT on organ inflammation and fibrosis remain unknown. We investigated the pharmacological potential of RKT in the treatment of ALI by using a bleomycin-induced ALI model in mice. RKT or distilled water (DW) was given to mice daily starting 12 h after bleomycin administration. The RKT-treated mice showed a definitively higher survival rate than the DW-treated mice after injury. They also had smaller reductions in body weight and food intake. The amelioration of neutrophil alveolar infiltration, pulmonary vascular permeability, induction of proinflammatory cytokines, activation of the NF-?B pathway, apoptosis of AECs, and subsequent lung fibrosis were notable in the RKT-treated mice. RKT administration increased the plasma ghrelin levels in wild-type mice, and it also mitigated the ALI response in both ghrelin-deficient mice and growth hormone secretagogue receptor-deficient mice after lung injury. Our results indicate that RKT administration exerts protective effects against ALI by protecting the AECs and regulating lung inflammation independently of the ghrelin system, and they highlight RKT as a promising therapeutic agent for the management of this intractable disease. PMID:24285267

Tsubouchi, Hironobu; Yanagi, Shigehisa; Miura, Ayako; Iizuka, Seiichi; Mogami, Sachiko; Yamada, Chihiro; Hattori, Tomohisa; Nakazato, Masamitsu

2014-02-01

160

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

161

Stem Cells and Regenerative Medicine in Lung Biology and Diseases  

PubMed Central

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

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

2012-01-01

162

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

163

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

164

Inhaled nitric oxide exacerbated phorbol-induced acute lung injury in rats.  

PubMed

In this study, we determined the effect of inhaled nitric oxide (NO) on the acute lung injury induced by phorbol myristate acetate (PMA) in isolated rat lung. Typical acute lung injury was induced successfully by PMA during 60 min of observation. PMA (2 microg/kg) elicited a significant increase in microvascular permeability, (measured using the capillary filtration coefficient Kfc), lung weight gain, lung weight/body weight ratio, pulmonary arterial pressure (PAP) and protein concentration of the bronchoalveolar lavage fluid. Pretreatment with inhaled NO (30 ppm) significantly exacerbated acute lung injury. All of the parameters reflective of lung injury increased significantly except PAP (P<0.05). Coadministration of Nomega-nitro-L-arginine methyl ester (L-NAME) (5 mM) attenuated the detrimental effect of inhaled NO in PMA-induced lung injury, except for PAP. In addition, L-NAME (5 mM) significantly attenuated PMA-induced acute lung injury except for PAP. These experimental data suggest that inhaled NO significantly exacerbated acute lung injury induced by PMA in rats. L-NAME attenuated the detrimental effect of inhaled NO. PMID:14643171

Lin, Hen I; Chu, Shi Jye; Hsu, Kang; Wang, David

2004-01-01

165

Therapeutic Modulation of Coagulation and Fibrinolysis in Acute Lung Injury and the Acute Respiratory Distress Syndrome  

PubMed Central

Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are characterized by excessive intra-alveolar fibrin deposition, driven, at least in part by inflammation. The imbalance between activation of coagulation and inhibition of fibrinolysis in patients with ALI/ARDS favors fibrin formation and appears to occur both systemically and in the lung and airspace. Tissue factor (TF), a key mediator of the activation of coagulation in the lung, has been implicated in the pathogenesis of ALI/ARDS. As such, there have been numerous investigations modulating TF activity in a variety of experimental systems in order to develop new therapeutic strategies for ALI/ARDS. This review will summarize current understanding of the role of TF and other proteins of the coagulation cascade as well the fibrinolysis pathway in the development of ALI/ARDS with an emphasis on the pathways that are potential therapeutic targets. These include the TF inhibitor pathway, the protein C pathway, antithrombin, heparin, and modulation of fibrinolysis through plasminogen activator-1 (PAI-1) or plasminogen activators (PA). Although experimental studies show promising results, clinical trials to date have proven unsuccessful in improving patient outcomes. Modulation of coagulation and fibrinolysis has complex effects on both hemostasis and inflammatory pathways and further studies are needed to develop new treatment strategies for patients with ALI/ARDS. PMID:21401517

Sebag, Sara C.; Bastarache, Julie A.; Ware, Lorraine B.

2013-01-01

166

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

167

Overview of the Pathology of Three Widely Used Animal Models of Acute Lung Injury  

Microsoft Academic Search

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are syndromes of acute diffuse damage to the pulmonary parenchyma by a variety of local or systemic insults. Increased alveolar capillary membrane permeability was recognized as the common end organ injury and a central feature in all forms of ALI\\/ARDS. Although great strides have been made in understanding the pathogenesis

H. M. Wang; M. Bodenstein; K. Markstaller

2008-01-01

168

Dual role of inducible nitric oxide synthase in acute asbestos-induced lung injury.  

PubMed

Reactive oxygen and nitrogen species have been implicated in the pathogenesis of asbestos fibers-associated pulmonary diseases. By comparing the responses of inducible nitric oxide synthase (iNOS) knockout and wild-type mice we investigated the consequences of iNOS expression for the development of the inflammatory response and tissue injury upon intratracheal instillation of asbestos fibers. Exposure to asbestos fibers resulted in an increased iNOS mRNA and protein expression in the lungs from wild-type mice. Moreover, iNOS knockout mice exhibited an exceeded pulmonary expression and production of TNF-alpha as well as a higher influx of neutrophils into the alveolar space than wild-type mice. In contrast, iNOS knockout animals displayed an attenuated oxidant-related tissue injury reflected in a decrease in protein leakage and LDH release into the alveolar space as well as weaker nitrotyrosine staining of lung tissue compared to wild-type mice. Data presented here indicate that iNOS-derived NO exerts a dichotomous role in acute asbestos-induced lung injury in that iNOS deficiency resulted in an exacerbated inflammatory response but improved oxidant-promoted lung tissue damage. PMID:12160931

Dörger, Martina; Allmeling, Anne-Marie; Kiefmann, Rainer; Schropp, Alke; Krombach, Fritz

2002-08-15

169

IL-17 response mediates acute lung injury induced by the 2009 Pandemic Influenza A (H1N1) Virus  

PubMed Central

The 2009 flu pandemic involved the emergence of a new strain of a swine-origin H1N1 influenza virus (S-OIV H1N1) that infected almost every country in the world. Most infections resulted in respiratory illness and some severe cases resulted in acute lung injury. In this report, we are the first to describe a mouse model of S-OIV virus infection with acute lung injury and immune responses that reflect human clinical disease. The clinical efficacy of the antiviral oseltamivir (Tamiflu) administered in the early stages of S-OIV H1N1 infection was confirmed in the mouse model. Moreover, elevated levels of IL-17, Th-17 mediators and IL-17-responsive cytokines were found in serum samples of S-OIV-infected patients in Beijing. IL-17 deficiency or treatment with monoclonal antibodies against IL-17-ameliorated acute lung injury induced by the S-OIV H1N1 virus in mice. These results suggest that IL-17 plays an important role in S-OIV-induced acute lung injury and that monoclonal antibodies against IL-17 could be useful as a potential therapeutic remedy for future S-OIV H1N1 pandemics. PMID:22025253

Li, Chenggang; Yang, Penghui; Sun, Yang; Li, Taisheng; Wang, Chen; Wang, Zhong; Zou, Zhen; Yan, Yiwu; Wang, Wei; Wang, Chen; Chen, Zhongwei; Xing, Li; Tang, Chong; Ju, Xiangwu; Guo, Feng; Deng, Jiejie; Zhao, Yan; Yang, Peng; Tang, Jun; Wang, Huanling; Zhao, Zhongpeng; Yin, Zhinan; Cao, Bin; Wang, Xiliang; Jiang, Chengyu

2012-01-01

170

[Drug induced interstitial lung disease in systemic diseases].  

PubMed

Immunosuppressants and immunomodulators are designed to regulate excessive immune response responsible for inflammatory lesions and are prescribed more and more in internal medicine. These drugs are known for their efficiency but with a significant toxicity including interstitial lung disease (ILD). Some factors liable to pulmonary toxicity include advanced age, genetic polymorphism and the existence of prior pulmonary disease. Cytotoxicity and hypersensitivity are the main mechanisms of pulmonary toxicity. There is no universal classification of drug induced-lung disease. Theoretically, drugs may be responsible for all histological aspects of ILD. Methotrexate is the most well-known drug as a provider of ILD with a prevalence of 0.3 to 11.6%. Some cases of ILD have also been reported with the new biologics used in systemic diseases. The diagnostic approach to the suspicion of drug ILD is to eliminate non-medicinal causes of pneumonia including infections and tumors before exploring the clinical symptomatology and the results of imaging and bronchoalveolar lavage cell profile. The analysis of the clinical symptomatology check the compatibility of the chronology of clinical and/or radiological pneumonia with the medication suspected. Subsequently, data from the clinical case are compared with those of the literature. Treatment involves stopping the suspected drug. The use of corticosteroids may be required in case of signs of severity or a lingering evolution. PMID:24183295

Essaadouni, L; Benjilali, L

2013-12-01

171

Acute effects of thoracic irradiation on lung function and structure in awake sheep  

Microsoft Academic Search

To investigate the acute physiological and structural changes after lung irradiation, the effects of whole-lung irradiation were investigated in fourteen sheep. Ten sheep were prepared with vascular and chronic lung lymph catheters, then a week later were given 1,500 rad whole-lung radiation and monitored for 2 days. Four sheep were given the same dose of radiation and were killed 4

J. E. Loyd; J. M. Bolds; J. R. Sheller; S. S. Duke; A. W. Gillette; A. W. Malcolm; B. O. Meyrick; K. L. Brigham

1987-01-01

172

Ethical aspects of palliative care in lung cancer and end stage lung disease  

Microsoft Academic Search

Over 50 000 people die per year in England and Wales from lung cancer and chronic obstructive pulmonary disease (COPD). Current National Institute for Clinical Evidence guidelines for lung cancer and COPD recommend provision of palliative care for those that need it. Palliative care historically has accepted patients with cancer, but access to patients with non-malignant disease has been more

J Neerkin; J Riley

2006-01-01

173

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...

174

Hard metal lung disease in an oil industry worker.  

PubMed

Hard metal lung disease, which manifests as giant cell interstitial pneumonia, is caused by exposure to hard metal dust. We report the case of an oil industry worker diagnosed with hard metal lung disease. The diagnosis was based on the clinical, radiological and anatomopathological analysis, as well as on pulmonary function testing. PMID:20126930

Bezerra, Patrícia Nunes; Vasconcelos, Ana Giselle Alves; Cavalcante, Lílian Loureiro Albuquerque; Marques, Vanessa Beatriz de Vasconcelos; Nogueira, Teresa Neuma Albuquerque Gomes; Holanda, Marcelo Alcantara

2009-12-01

175

Work-Related Lung Disease: All Pneumoconioses and Related Exposures  

MedlinePLUS

... visit this page: About CDC.gov . Work-Related Lung Disease Surveillance System (eWoRLD) NIOSH > Workplace Safety and Health ... Share Compartir Welcome to eWoRLD The Work-Related Lung Disease Surveillance System (eWoRLD) presents data on selected work- ...

176

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

177

Sulfur dioxide attenuates LPS-induced acute lung injury via enhancing polymorphonuclear neutrophil apoptosis  

PubMed Central

Aim: We speculated that the enhanced apoptosis of polymorphonuclear neutrophil (PMN) might be responsible for the inhibition of PMN infiltration in the lung. This study was designed to investigate the effects of sulfur dioxide (SO2) on PMN apoptosis in vivo and in vitro, which may mediate the protective action of SO2 on pulmonary diseases. Methods: Acute lung injury (ALI) was induced by intratracheally instillation of lipopolysaccharide (LPS, 100 ?g/100 g, in 200 ?L saline) in adult male SD rats. SO2 solution (25 ?mol/kg) was administered intraperitoneally 30 min before LPS treatment. The rats were killed 6 h after LPS treatment. Lung tissues were collected for histopathologic study and SO2 concentration assay. Bronchoalveolar lavage fluid (BALF) was collected for the measurement of PMN apoptosis. For in vitro experiments, rat peripheral blood PMNs were cultured and treated with LPS (30 mg/L) and SO2 (10, 20 and 30 ?mol/L) for 6 h, and apoptosis-related protein expression was detected by Western blotting, and apoptosis rate was measured with flow cytometry. Results: LPS treatment significantly reduced the SO2 concentrations in the lung tissue and peripheral blood, as compared with the control group. Pretreatment with SO2 prevented LPS-induced reduction of the SO2 concentration in the lung tissue and peripheral blood. LPS treatment significantly reduced PMN apoptosis both in vivo and in vitro, which could be prevented by the pretreatment with SO2. The protein levels of Caspase-3 and Bax was significantly increased, but Bcl-2 was decreased by the pretreatment with SO2, as compared with LPS administration alone. Conclusion: SO2 plays an important role as the modulator of PMN apoptosis during LPS-induced ALI, which might be one of the mechanisms underlying the protective action of SO2 on pulmonary diseases. PMID:22796764

Ma, Hui-jie; Huang, Xin-li; Liu, Yan; Fan, Ya-min

2012-01-01

178

Clinical review: Lung imaging in acute respiratory distress syndrome patients - an update  

PubMed Central

Over the past 30 years lung imaging has greatly contributed to the current understanding of the pathophysiology and the management of acute respiratory distress syndrome (ARDS). In the past few years, in addition to chest X-ray and lung computed tomography, newer functional lung imaging techniques, such as lung ultrasound, positron emission tomography, electrical impedance tomography and magnetic resonance, have been gaining a role as diagnostic tools to optimize lung assessment and ventilator management in ARDS patients. Here we provide an updated clinical review of lung imaging in ARDS over the past few years to offer an overview of the literature on the available imaging techniques from a clinical perspective. PMID:24238477

2013-01-01

179

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

180

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

181

Kawasaki disease resembling acute colitis  

PubMed Central

This report presents a case of atypical Kawasaki disease (KD) in a 4-year-old boy developing with severe colitis accompanied by frequent diarrhoea and hypokalemic dehydration. Abdominal ultrasonography showed findings of left colon mucosal thickening and prominent dilatation of the colon. Antibiotic treatment was not effective. Some symptoms of KD appeared with progression of the illness. Intravenous immunoglobulin (IVIG) was administered based on a diagnosis of incomplete KD on the ninth day of the illness. The patient became afebrile soon after IVIG therapy. Diarrhoea and other symptoms dramatically subsided. The patient has recovered during the 3-month follow-up and repeated echocardiograms were normal. PMID:23291810

Miyahara, Masazumi; Hirayama, Masahiro

2013-01-01

182

Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury.  

PubMed

Multiple lung pathogens such as chemical agents, H5N1 avian flu, or SARS cause high lethality due to acute respiratory distress syndrome. Here we report that Toll-like receptor 4 (TLR4) mutant mice display natural resistance to acid-induced acute lung injury (ALI). We show that TLR4-TRIF-TRAF6 signaling is a key disease pathway that controls the severity of ALI. The oxidized phospholipid (OxPL) OxPAPC was identified to induce lung injury and cytokine production by lung macrophages via TLR4-TRIF. We observed OxPL production in the lungs of humans and animals infected with SARS, Anthrax, or H5N1. Pulmonary challenge with an inactivated H5N1 avian influenza virus rapidly induces ALI and OxPL formation in mice. Loss of TLR4 or TRIF expression protects mice from H5N1-induced ALI. Moreover, deletion of ncf1, which controls ROS production, improves the severity of H5N1-mediated ALI. Our data identify oxidative stress and innate immunity as key lung injury pathways that control the severity of ALI. PMID:18423196

Imai, Yumiko; Kuba, Keiji; Neely, G Greg; Yaghubian-Malhami, Rubina; Perkmann, Thomas; van Loo, Geert; Ermolaeva, Maria; Veldhuizen, Ruud; Leung, Y H Connie; Wang, Hongliang; Liu, Haolin; Sun, Yang; Pasparakis, Manolis; Kopf, Manfred; Mech, Christin; Bavari, Sina; Peiris, J S Malik; Slutsky, Arthur S; Akira, Shizuo; Hultqvist, Malin; Holmdahl, Rikard; Nicholls, John; Jiang, Chengyu; Binder, Christoph J; Penninger, Josef M

2008-04-18

183

Evolution of endotoxin induced acute lung injury in the rat.  

PubMed

To clarify the evolution of acute lung injury induced by endotoxin, the progression of lung damage in 26 rats submitted to intratracheal instillation of 5 mg/kg body weight endotoxin was examined by blood gas analysis, computerized tomography, light and electron microscopy. Hypoxaemia, hypercapnia, acidosis and inhomogeneous bilateral infiltrates developed gradually within 48 hours. Monocytes appeared within blood capillaries and the instertitium by 12 hours after treatment, then migrated into alveoli and underwent progressive differentiation into macrophages by 24 hours after treatment. Granulocytes were found within blood capillaries at an early stage, but outside capillaries only at 48 hours. Hyperplasia of type II pneumocytes and hypertrophy of interstitial fibroblasts also occurred at 48 hours. These data suggest that the pathogenesis of endotoxin induced pulmonary injury proceeds through an early phase of granulocyte migration inside capillaries and monocyte extravasation, an intermediate phase of monocyte differentiation into macrophages inside alveoli and a late phase of diffuse infiltration of alveoli by newly differentiated macrophages and late-extravasated neutrophils. PMID:7488552

Domenici-Lombardo, L; Adembri, C; Consalvo, M; Forzini, R; Meucci, M; Romagnoli, P; Novelli, G P

1995-10-01

184

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

PubMed

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. PMID:24920450

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

2014-01-01

185

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

186

Bronchoscopic Cryobiopsy for the Diagnosis of Diffuse Parenchymal Lung Disease  

PubMed Central

Background Although in some cases clinical and radiographic features may be sufficient to establish a diagnosis of diffuse parenchymal lung disease (DPLD), surgical lung biopsy is frequently required. Recently a new technique for bronchoscopic lung biopsy has been developed using flexible cryo-probes. In this study we describe our clinical experience using bronchoscopic cryobiopsy for diagnosis of diffuse lung disease. Methods A retrospective study of subjects who had undergone bronchoscopic cryobiopsy for evaluation of DPLD at an academic tertiary care center from January 1, 2012 through January 15, 2013 was performed. The procedure was performed using a flexible bronchoscope to acquire biopsies of lung parenchyma. H&E stained biopsies were reviewed by an expert lung pathologist. Results Twenty-five eligible subjects were identified. With a mean area of 64.2 mm2, cryobiopsies were larger than that typically encountered with traditional transbronchial forceps biopsy. In 19 of the 25 subjects, a specific diagnosis was obtained. In one additional subject, biopsies demonstrating normal parenchyma were felt sufficient to exclude diffuse lung disease as a cause of dyspnea. The overall diagnostic yield of bronchoscopic cryobiopsy was 80% (20/25). The most frequent diagnosis was usual interstitial pneumonia (UIP) (n?=?7). Three of the 25 subjects ultimately required surgical lung biopsy. There were no significant complications. Conclusion In patients with suspected diffuse parenchymal lung disease, bronchoscopic cryobiopsy is a promising and minimally invasive approach to obtain lung tissue with high diagnostic yield. PMID:24265706

Kropski, Jonathan A.; Pritchett, Jason M.; Mason, Wendi R.; Sivarajan, Lakshmi; Gleaves, Linda A.; Johnson, Joyce E.; Lancaster, Lisa H.; Lawson, William E.; Blackwell, Timothy S.; Steele, Mark P.; Loyd, James E.; Rickman, Otis B.

2013-01-01

187

Heat stress attenuates air bubble-induced acute lung injury: a novel mechanism of diving acclimatization.  

PubMed

Diving acclimatization refers to a reduced susceptibility to acute decompression sickness (DCS) in individuals undergoing repeated compression-decompression cycles. We postulated that mechanisms responsible for the acclimatization are similar to that of a stress preconditioning. In this study, we investigated the protective effect of prior heat shock treatment on air embolism-induced lung injury and on the incidence of DCS in rats. We exposed rats (n = 31) to a pressure cycle that induced signs of severe DCS in 48% of the rats, greater wet-to-dry ratio (W/D) of lung weight compared with the control group (5.48 +/- 0.69 vs. 4.70 +/- 0.17), and higher protein concentration in bronchoalveolar lavage (BAL) fluid (362 +/- 184 vs. 209 +/- 78 mg/l) compared with the control group. Rats with DCS expressed more heat shock protein 70 (HSP70) in the lungs than those without signs of disease. Prior heat shock (n = 12) increased the expression of HSP70 in the lung and attenuated the elevation of W/D of lung weight (5.03 +/- 0.17) after the identical decompression protocol. Prior heat shock reduced the incidence of severe DCS by 23%, but this failed to reach statistical significant (chi(2) = 1.94, P = 0.163). Venous air infusion (1.0 ml/40 min) caused profound hypoxemia (54.5 +/- 3.8 vs. 83.8 +/- 3.2 Torr at baseline; n = 6), greater W/D of lung weight (5.98 +/- 0.45), and high protein concentration in BAL fluid (595 +/- 129 mg/l). Prior heat shock (n = 6) did not alter the level of hypoxemia caused by air embolism, but it accelerated the recovery to normoxemia after air infusion was stopped. Prior heat shock also attenuated the elevation of W/D of lung weight (5.19 +/- 0.40) and the increase in BAL protein (371 +/- 69 mg/l) in air embolism group. Our results showed that the occurrence of DCS after rapid decompression is associated with increased expression of a stress protein (HSP70) and that prior heat shock exposure attenuates the air bubble-induced lung injury. These results suggest that bubble formation in tissues activates a stress response and that stress preconditioning attenuates lung injury on subsequent stress, which may be the mechanism responsible for diving acclimatization. PMID:12482763

Huang, Kun-Lun; Wu, Chin-Pyng; Chen, Yin-Li; Kang, Bor-Hwang; Lin, Yu-Chong

2003-04-01

188

Connective Tissue Disease-associated Interstitial Lung Disease: A review  

PubMed Central

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

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

2012-01-01

189

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

PubMed

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

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

2012-09-21

190

Prevalence of Aspergillosis in chronic lung diseases.  

PubMed

Eighty eight patients of chronic lung diseases (CLD) attending TB and Chest department of J.N. Medical college Hospital were studied to find out the prevalence of Aspergillus in Broncho-alveolar Lavage (BAL) and anti- aspergillus antibodies in their sera. Direct microscopy and fungal culture of BAL was done. Antibodies were studied by immunodiffusion (ID) and Enzyme linked immunosorbent assay (ELISA). Dot blot assay for anti-aspergillus antibodies was also performed in sera of patients which were either positive by ID or by ELISA. Aspergillus was isolated in culture from 13(14.7%) cases of CLD, while, 30.6% cases showed anti-aspergillus antibodies by serological methods. Aspergillus fumigatus was the predominant species isolated. 17(19.3%) cases of CLD showed antibody against Aspergillus by ID, 22(25%) by ELISA, while 19 of 27 seropositive cases also showed positive results by Dot Blot assay. In cases of bronchogenic carcinoma and pulmonary tuberculosis, anti-aspergillus antibodies were detected equally by ID and ELISA in 21.42% and 21.05% cases respectively. In bronchial asthma, the antibodies could be detected in 60% cases by ELISA, while, in only 10% cases by ID. ELISA was found more sensitive than ID for detection of anti-aspergillus antibodies. The sensitivity of Dot Blot lies some what between ID and ELISA. It is concluded that prevalence of Aspergillosis is quite high in chronic lung diseases, culture and serological test should be performed in conjunction and more than one type of serological tests should be performed to establish the diagnosis. PMID:17664833

Shahid, M; Malik, A; Bhargava, R

2001-01-01

191

Lung Surfactant Protein D (SP-D) Response and Regulation During Acute and Chronic Lung Injury  

PubMed Central

Background Surfactant protein D (SP-D) is a collection that plays important roles in modulating host defense functions and maintaining phospholipid homeostasis in the lung. The aim of current study was to characterize comparatively the SP-D response in bronchoalveolar lavage (BAL) and serum in three murine models of lung injury, using a validated ELISA technology for estimation of SP-D levels. Methods Mice were exposed to lipopolysaccharide, bleomycin, or Pneumocystis carinii (Pc) and sacrificed at different time points. Results In lipopolysaccharide-challenged mice, the level of SP-D in BAL increased within 6 h, peaked at 51 h (4,518 ng/ml), and returned to base level at 99 h (612 ng/ml). Serum levels of SP-D increased immediately (8.6 ng/ml), peaked at 51 h (16 ng/ml), and returned to base levels at 99 h (3.8 ng/ml). In a subacute bleomycin inflammation model, SP-D levels were 4,625 and 367 ng/ml in BAL and serum, respectively, 8 days after exposure. In a chronic Pc inflammation model, the highest level of SP-D was observed 6 weeks after inoculation, with BAL and serum levels of 1,868 and 335 ng/ml, respectively. Conclusions We conclude that serum levels of SP-D increase during lung injury, with a sustained increment during chronic inflammation compared with acute inflammation. A quick upregulation of SP-D in serum in response to acute airway inflammation supports the notion that SP-D translocates from the airways into the vascular system, in favor of being synthesized systemically. The study also confirms the concept of using increased SP-D serum levels as a biomarker of especially chronic airway inflammation. PMID:23435873

Rasmussen, Karina Juhl; Beers, Michael F.; Atochina-Vasserman, Elena N.; Hansen, Soren

2014-01-01

192

Transbronchial Lung Cryobiopsy in the Diagnosis of Fibrotic Interstitial Lung Diseases  

PubMed Central

Background Histology is a key element for the multidisciplinary diagnosis of fibrotic diffuse parenchymal lung diseases (f-DPLD) when the clinical-radiological picture is nondiagnostic. Transbronchial lung cryobiopsy (TBLC) have been shown to be useful for obtaining large and well-preserved biopsies of lung parenchyma, but experience with TBLC in f-DPLD is limited. Objectives To evaluate safety, feasibility and diagnostic yield of TBLC in f-DPLD. Method Prospective study of 69 cases of TBLC using flexible cryoprobe in the clinical-radiological setting of f-DPLD with nondiagnostic high resolution computed tomography (HRCT) features. Results Safety: pneumothorax occurred in 19 patients (28%). One patient (1.4%) died of acute exacerbation. Feasibility: adequate cryobiopsies were obtained in 68 cases (99%). The median size of cryobiopsies was 43.11 mm2 (range, 11.94–76.25). Diagnostic yield: among adequate TBLC the pathologists were confident (“high confidence”) that histopathologic criteria sufficient to define a specific pattern in 52 patients (76%), including 36 of 47 with UIP (77%) and 9 nonspecific interstitial pneumonia (6 fibrosing and 3 cellular), 2 desquamative interstitial pneumonia/respiratory bronchiolitis–interstitial lung disease, 1 organizing pneumonia, 1 eosinophilic pneumonia, 1 diffuse alveolar damage, 1 hypersensitivity pneumonitis and 1 follicular bronchiolitis. In 11 diagnoses of UIP the pathologists were less confident (“low confidence”). Agreement between pathologists in the detection of UIP was very good with a Kappa coefficient of 0.83 (95% CI, 0.69–0.97). Using the current consensus guidelines for clinical-radiologic-pathologic correlation 32% (20/63) of cases were classified as Idiopathic Pulmonary Fibrosis (IPF), 30% (19/63) as possible IPF, 25% (16/63) as other f-DPLDs and 13% (8/63) were unclassifiable. Conclusions TBLC in the diagnosis of f-DPLD appears safe and feasible. TBLC has a good diagnostic yield in the clinical-radiological setting of f-DPLD without diagnostic HRCT features of usual interstitial pneumonia. Future studies should consider TBLC as a potential alternative to SLBx in f-DPLD. PMID:24586252

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

2014-01-01

193

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

194

Rheumatoid arthritis and lung disease: from mechanisms to a practical approach.  

PubMed

Rheumatoid arthritis (RA) is a common chronic systemic autoimmune disease characterized by joint inflammation and, in a proportion of patients, extra-articular manifestations (EAM). Lung disease, either as an EAM of the disease, related to the drug therapy for RA, or related to comorbid conditions, is the second commonest cause of mortality. All areas of the lung including the pleura, airways, parenchyma, and vasculature may be involved, with interstitial and pleural disease and infection being the most common problems. High-resolution computed tomography of the chest forms the basis of investigation and when combined with clinical information and measures of physiology, a multidisciplinary team can frequently establish the diagnosis without the need for an invasive biopsy procedure. The most frequent patterns of interstitial lung disease (ILD) are usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP), with some evidence for the prognosis being better than for the idiopathic equivalents. Risk factors depend on the type of disease but for ILD (mainly UIP and NSIP) include smoking, male gender, human leukocyte antigen haplotype, rheumatoid factor, and anticitrullinated protein antibodies (ACPAs). Citrullination of proteins in the lung, frequently thought to be incited by smoking, and the subsequent development of ACPA appear to play an important role in the development of lung and possibly joint disease. The biologic and nonbiological disease modifying antirheumatic drugs (DMARDs) have had a substantial impact on morbidity and mortality from RA, and although there multiple reports of drug-related lung toxicity and possible exacerbation of underlying ILD, overall these reactions are rare and should only preclude the use of DMARDs in a minority of patients. Common scenarios facing pulmonologists and rheumatologists are addressed using the current best evidence; these include screening the new patient; monitoring and choosing RA treatment in the presence of subclinical disease; treating deteriorating ILD; and establishing a diagnosis in a patient with an acute respiratory presentation. PMID:24668537

Lake, Fiona; Proudman, Susanna

2014-04-01

195

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

196

Biomarkers in connective tissue disease-associated interstitial lung disease.  

PubMed

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

Bonella, Francesco; Costabel, Ulrich

2014-04-01

197

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

198

CT appearance of acute radiation-induced injury in the lung  

SciTech Connect

To determine how soon radiation-induced lung injury is detectable, to compare the CT findings with those on chest radiographs, and to observe the appearance of the abnormality during the acute phase, we performed 83 CT studies in 17 radiotherapy patients at relatively short intervals. All 17 patients received fractionated radiotherapy to the thorax with a large irradiated lung volume. The CT findings were variable; pulmonary infiltrates were homogeneous, patchy, or discrete. CT abnormalities were evident in 15 of 17 cases within 16 weeks after radiotherapy; in 13 of these it was detected within 4 weeks. In three of these 15 cases, no abnormality was detected on chest radiographs, and in three other cases, the change was observed much later on chest radiographs than on CT scans. In the other nine cases, abnormalities were detected simultaneously on CT scans and chest radiographs. In four cases, extensive radiation pneumonitis was observed on CT, but in two of these, the change was misdiagnosed on the chest radiograph. We conclude that CT is useful in the detection of acute radiation-induced pulmonary disease.

Ikezoe, J.; Takashima, S.; Morimoto, S.; Kadowaki, K.; Takeuchi, N.; Yamamoto, T.; Nakanishi, K.; Isaza, M.; Arisawa, J.; Ikeda, H.

1988-04-01

199

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

200

Significance of the microbiome in obstructive lung disease  

PubMed Central

The composition of the lung microbiome contributes to both health and disease, including obstructive lung disease. Because it has been estimated that over 70% of the bacterial species on body surfaces cannot be cultured by currently available techniques, traditional culture techniques are no longer the gold standard for microbial investigation. Advanced techniques that identify bacterial sequences, including the 16S ribosomal RNA gene, have provided new insights into the depth and breadth of microbiota present both in the diseased and normal lung. In asthma, the composition of the microbiome of the lung and gut during early childhood development may play a key role in the development of asthma, while specific airway microbiota are associated with chronic asthma in adults. Early bacterial stimulation appears to reduce asthma susceptibility by helping the immune system develop lifelong tolerance to innocuous antigens. By contrast, perturbations in the microbiome from antibiotic use may increase the risk for asthma development. In chronic obstructive pulmonary disease, bacterial colonisation has been associated with a chronic bronchitic phenotype, increased risk of exacerbations, and accelerated loss of lung function. In cystic fibrosis, studies utilising culture-independent methods have identified associations between decreased bacterial community diversity and reduced lung function; colonisation with Pseudomonas aeruginosa has been associated with the presence of certain CFTR mutations. Genomic analysis of the lung microbiome is a young field, but has the potential to define the relationship between lung microbiome composition and disease course. Whether we can manipulate bacterial communities to improve clinical outcomes remains to be seen. PMID:22318161

Han, MeiLan K; Huang, Yvonne J; LiPuma, John J; Boushey, Homer A; Boucher, Richard C; Cookson, William O; Curtis, Jeffrey L; Erb-Downward, John; Lynch, Susan V; Sethi, Sanjay; Toews, Galen B; Young, Vincent B; Wolfgang, Matthew C; Huffnagle, Gary B; Martinez, Fernando J

2012-01-01

201

Inhibition of Pyk2 blocks lung inflammation and injury in a mouse model of acute lung injury  

PubMed Central

Background Proline-rich tyrosine kinase 2 (Pyk2) is essential in neutrophil degranulation and chemotaxis in vitro. However, its effect on the process of lung inflammation and edema formation during LPS induced acute lung injury (ALI) remains unknown. The goal of the present study was to determine the effect of inhibiting Pyk2 on LPS-induced acute lung inflammation and injury in vivo. Methods C57BL6 mice were given either 10 mg/kg LPS or saline intratracheally. Inhibition of Pyk2 was effected by intraperitoneal administration TAT-Pyk2-CT 1 h before challenge. Bronchoalveolar lavage analysis of cell counts, lung histology and protein concentration in BAL were analyzed at 18 h after LPS treatment. KC and MIP-2 concentrations in BAL were measured by a mouse cytokine multiplex kit. The static lung compliance was determined by pressure-volume curve using a computer-controlled small animal ventilator. The extravasated Evans blue concentration in lung homogenate was determined spectrophotometrically. Results Intratracheal instillation of LPS induced significant neutrophil infiltration into the lung interstitium and alveolar space, which was attenuated by pre-treatment with TAT-Pyk2-CT. TAT-Pyk2-CT pretreatment also attenuated 1) myeloperoxidase content in lung tissues, 2) vascular leakage as measured by Evans blue dye extravasation in the lungs and the increase in protein concentration in bronchoalveolar lavage, and 3) the decrease in lung compliance. In each paradigm, treatment with control protein TAT-GFP had no blocking effect. By contrast, production of neutrophil chemokines MIP-2 and keratinocyte-derived chemokine in the bronchoalveolar lavage was not reduced by TAT-Pyk2-CT. Western blot analysis confirmed that tyrosine phosphorylation of Pyk2 in LPS-challenged lungs was reduced to control levels by TAT-Pyk2-CT pretreatment. Conclusions These results suggest that Pyk2 plays an important role in the development of acute lung injury in mice and that pharmacological inhibition of Pyk2 might provide a potential therapeutic strategy in the pretreatment for patients at imminent risk of developing acute lung injury. PMID:22257498

2012-01-01

202

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

203

Sex Differences and Sex Steroids in Lung Health and Disease  

PubMed Central

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

Townsend, Elizabeth A.; Miller, Virginia M.

2012-01-01

204

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

205

Proteomic Analysis of Lung Tissue in a Rat Acute Lung Injury Model: Identification of PRDX1 as a Promoter of Inflammation  

PubMed Central

Acute respiratory distress syndrome (ARDS) remains a high morbidity and mortality disease entity in critically ill patients, despite decades of numerous investigations into its pathogenesis. To obtain global protein expression changes in acute lung injury (ALI) lung tissues, we employed a high-throughput proteomics method to identify key components which may be involved in the pathogenesis of ALI. In the present study, we analyzed lung tissue proteomes of Pseudomonas aeruginosa-induced ALI rats and identified eighteen proteins whose expression levels changed more than twofold as compared to normal controls. In particular, we found that PRDX1 expression in culture medium was elevated by a lipopolysaccharide (LPS) challenge in airway epithelial cells in vitro. Furthermore, overexpression of PRDX1 increased the expression of proinflammatory cytokines interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-? (TNF-?), whereas knockdown of PRDX1 led to downregulated expression of cytokines induced by LPS. In conclusion, our findings provide a global alteration in the proteome of lung tissues in the ALI rat model and indicate that PRDX1 may play a critical role in the pathogenesis of ARDS by promoting inflammation and represent a novel strategy for the development of new therapies against ALI. PMID:25024510

Liu, Dongdong; Mao, Pu; Huang, Yongbo; Liu, Yiting; Liu, Xiaoqing; Pang, Xiaoqing; Li, Yimin

2014-01-01

206

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

207

Clinical potentials of human pluripotent stem cells in lung diseases  

PubMed Central

Lung possesses very limited regenerative capacity. Failure to maintain homeostasis of lung epithelial cell populations has been implicated in the development of many life-threatening pulmonary diseases leading to substantial morbidity and mortality worldwide, and currently there is no known cure for these end-stage pulmonary diseases. Embryonic stem cells (ESCs) and somatic cell-derived induced pluripotent stem cells (iPSCs) possess unlimited self-renewal capacity and great potential to differentiate to various cell types of three embryonic germ layers (ectodermal, mesodermal, and endodermal). Therapeutic use of human ESC/iPSC-derived lung progenitor cells for regeneration of injured or diseased lungs will have an enormous clinical impact. This article provides an overview of recent advances in research on pluripotent stem cells in lung tissue regeneration and discusses technical challenges that must be overcome for their clinical applications in the future. PMID:24995122

2014-01-01

208

Comparison of Two Methods of Diagnostic Lung Lavage in Ventilated Infants with Lung Disease  

Microsoft Academic Search

The methods of nonbronchoscopic lung lavage used for collection of samples of epithelial lining fluid (ELF) in intubated patients are poorly standardized and incompletely validated. In infants with lung disease requiring ventilatory support, we evaluated two techniques of small volume saline lavage for the collection of a specimen suitable for pulmonary surfactant analysis. We aimed to compare appar- ent origin

PETER A. DARGAVILLE; MICHAEL SOUTH; PETER N. McDOUGALL

1999-01-01

209

The epidemiology of interstitial lung disease and its association with lung cancer  

Microsoft Academic Search

The criteria and terminology for diagnosing interstitial lung disease (ILD), a diverse range of pulmonary fibrotic disorders that affect the alveoli of the lungs, have been variable and confusing; however, there have been recent major improvements to an internationally agreed classification. Evidence from recent analyses of populations suggests that the incidence and prevalence rates of ILD are on the increase,

G Raghu; F Nyberg; G Morgan

2004-01-01

210

Chronic Obstructive Pulmonary Disease and Lung Cancer: New Molecular Insights  

Microsoft Academic Search

Both chronic obstructive pulmonary disease (COPD) and lung cancer are major causes of death worldwide. In most cases this reflects cigarette smoke exposure which is able to induce an inflammatory response in the airways of smokers. Indeed, COPD is characterized by lower airway inflammation, and importantly, the presence of COPD is by far the greatest risk factor for lung cancer

Ian M. Adcock; Gaetano Caramori; Peter J. Barnes

2011-01-01

211

Surgical management of Aspergillus colonization associated with lung hydatid disease.  

PubMed

Colonization with Aspergillus sp. usually occurs in previously formed lung cavities. Cystectomy is a widely used surgical technique for hydatid lung disease that can also leave residual cavities and potentially result in aspergilloma. We present two cases of this rare entity and a case with Aspergillus sp. colonization of an existing ruptured hydatid cyst. PMID:18414351

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

2008-04-01

212

Computational Identification of Key Biological Modules and Transcription Factors in Acute Lung Injury  

Microsoft Academic Search

Rationale: Mechanical ventilation augments the acute lung injury (ALI) caused by bacterial products. The molecular pathogenesis of this synergistic interaction remains incompletely understood. Objective: We sought to develop a computational framework to systematically identify gene regulatory networks activated in ALI. Methods: We have developed a mouse model in which the combina- tionofmechanicalventilationandintratrachealLPSproducessignif- icantly more injury to the lung than either

Sina A. Gharib; W. Conrad Liles; Gustavo Matute-Bello; Robb W. Glenny; Thomas R. Martin; William A. Altemeier

213

CT appearance of acute radiation-induced injury in the lung  

Microsoft Academic Search

To determine how soon radiation-induced lung injury is detectable, to compare the CT findings with those on chest radiographs, and to observe the appearance of the abnormality during the acute phase, we performed 83 CT studies in 17 radiotherapy patients at relatively short intervals. All 17 patients received fractionated radiotherapy to the thorax with a large irradiated lung volume. The

Junpei Ikezoe; Shodayu Takashima; S. Morimoto; Koichi Kadowaki; N. Takeuchi; T. Yamamoto; K. Nakanishi; M. Isaza; J. Arisawa; H. Ikeda

1988-01-01

214

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

PubMed

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

Schluger, Neil W; Koppaka, Ram

2014-03-01

215

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

216

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

217

CXCR4 receptor overexpression in mesenchymal stem cells facilitates treatment of acute lung injury in rats.  

PubMed

Novel therapeutic regimens for tissue renewal incorporate mesenchymal stem cells (MSCs) as they differentiate into a variety of cell types and are a stem cell type that is easy to harvest and to expand in vitro. However, surface chemokine receptors, such as CXCR4, which are involved in the mobilization of MSCs, are expressed only on the surface of a small proportion of MSCs, and the lack of CXCR4 expression may underlie the low efficiency of homing of MSCs toward tissue damage, which results in a poor curative effect. Here, a rat CXCR4 expressing lentiviral vector was constructed and introduced into MSCs freshly prepared from rat bone marrow. The influence of CXCR4 expression on migration, proliferation, differentiation, and paracrine effects of MSCs was examined in vitro. The in vivo properties of CXCR4-MSCs were also investigated in a model of acute lung injury in rats induced by lipopolysaccharide. Expression of CXCR4 in MSCs significantly enhanced the chemotactic and paracrine characteristics of the cells in vitro but did not affect self-renewal or differentiation into alveolar and vascular endothelial cells. In vivo, CXCR4 improved MSC homing and colonization of damaged lung tissue, and furthermore, the transplanted CXCR4-MSCs suppressed the development of acute lung injury in part by modulating levels of inflammatory molecules and the neutrophil count. These results indicated that efficient mobilization of MSCs to sites of tissue injury may be due to CXCR4, and therefore, increased expression of CXCR4 may improve their therapeutic potential in the treatment of diseases where tissue damage develops. PMID:25492872

Yang, Jing-Xian; Zhang, Nan; Wang, Han-Wei; Gao, Peng; Yang, Qing-Ping; Wen, Qing-Ping

2015-01-23

218

Diagnostic Pathology of Diffuse Lung Disease in Children  

PubMed Central

The pathologic classification of diffuse lung disease in children and adolescents has undergone revision in recent years in response to rapid developments and new discoveries in the field. A number of important advancements have been made in the last 10 years including the description of new genetic mutations causing severe lung disease in infants and children, as well as the description of new pathologic entities in infants. These recently described entities, including ABCA3 surfactant disorders, pulmonary interstitial glycogenosis, and neuroendocrine cell hyperplasia of infancy, are being recognized with increasing frequency. This review will include brief discussion of the etiology and pathogenesis of the major groups of diffuse lung disease in children. Histopathologic features are discussed for each of the major categories of diffuse lung disease in children, beginning with the genetic, developmental, and alveolar growth disorders common in infancy, followed by brief discussion of airway diseases, immunologic diseases, and pulmonary vascular diseases seen more commonly in older children. A protocol for handling pediatric wedge lung biopsies is also discussed, which optimizes the diagnostic yield of lung biopsies in this population. PMID:22332032

2010-01-01

219

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

PubMed

Over the past two decades, the secreted protein sonic hedgehog (SHH) has emerged as a critical morphogen during embryonic lung development, regulating the interaction between epithelial and mesenchymal cell populations in the airway and alveolar compartments. There is increasing evidence that the SHH pathway is active in adult lung diseases such as pulmonary fibrosis, asthma, chronic obstructive pulmonary disease, and lung cancer, which raises two questions: (1) What role does SHH signaling play in these diseases? and (2) Is it a primary driver of the disease or a response (perhaps beneficial) to the primary disturbance? In this review we aim to fill the gap between the well-studied period of embryonic lung development and the adult diseased lung by reviewing the hedgehog (HH) pathway during the postnatal period and in adult uninjured and injured lungs. We elucidate the similarities and differences in the epithelial-mesenchymal interplay during the fibrosis response to injury in lung compared with other organs and present a critical appraisal of tools and agents available to evaluate HH signaling. PMID:25068457

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

2015-01-01

220

Amniotic Fluid Stem Cells from EGFP Transgenic Mice Attenuate Hyperoxia-Induced Acute Lung Injury  

PubMed Central

High concentrations of oxygen aggravate the severity of lung injury in patients requiring mechanical ventilation. Although mesenchymal stem cells have been shown to effectively attenuate various injured tissues, there is limited information regarding a role for amniotic fluid stem cells (AFSCs) in treating acute lung injury. We hypothesized that intravenous delivery of AFSCs would attenuate lung injury in an experimental model of hyperoxia-induced lung injury. AFSCs were isolated from EGFP transgenic mice. The in vitro differentiation, surface markers, and migration of the AFSCs were assessed by specific staining, flow cytometry, and a co-culture system, respectively. The in vivo therapeutic potential of AFSCs was evaluated in a model of acute hyperoxia-induced lung injury in mice. The administration of AFSCs significantly reduced the hyperoxia-induced pulmonary inflammation, as reflected by significant reductions in lung wet/dry ratio, neutrophil counts, and the level of apoptosis, as well as reducing the levels of inflammatory cytokine (IL-1?, IL-6, and TNF-?) and early-stage fibrosis in lung tissues. Moreover, EGFP-expressing AFSCs were detected and engrafted into a peripheral lung epithelial cell lineage by fluorescence microscopy and DAPI stain. Intravenous administration of AFSCs may offer a new therapeutic strategy for acute lung injury (ALI), for which efficient treatments are currently unavailable. PMID:24040409

Lai, Cheng-Wei; Yen, Chih-Ching; Lee, Kun-Hsiung; Wu, Shinn-Chih; Chen, Chuan-Mu

2013-01-01

221

Spirometry: Simulations of Obstructive and Restrictive Lung Diseases  

NSDL National Science Digital Library

Description of spirometry exercises that enhance studentsÃÂ 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); PhD Heidi L. Collins (Wayne State Univ. School of Medicine Dept. of Physiology); PhD Stephen M. DiCarlo (Wayne State Univ Sch Med Dept of Physiology)

2002-09-01

222

Vascular endothelial growth factor (VEGF) in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS): paradox or paradigm?  

PubMed Central

Acute respiratory distress syndrome (ARDS), the most severe form of acute lung injury (ALI), remains a devastating condition with a high mortality. It is characterised by alveolar injury and increased pulmonary vascular permeability. Vascular endothelial cell growth factor (VEGF) was identified by its properties to increase permeability and act as a cellular growth factor, hence its potential for a key role in the pathogenesis of ALI/ARDS. This review describes the basic biology of VEGF and its receptors as an essential prerequisite to discussing the available and sometimes paradoxical published data, before considering a paradigm for the role of VEGF in the human lung. PMID:16807391

Medford, A R L; Millar, A B

2006-01-01

223

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

224

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

225

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

226

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

227

Perioperative Management of Interscalene Block in Patients with Lung Disease  

PubMed Central

Interscalene nerve block impairs ipsilateral lung function and is relatively contraindicated for patients with lung impairment. We present a case of an 89-year-old female smoker with prior left lung lower lobectomy and mild to moderate lung disease who presented for right shoulder arthroplasty and insisted on regional anesthesia. The patient received a multimodal perioperative regimen that consisted of a continuous interscalene block, acetaminophen, ketorolac, and opioids. Surgery proceeded uneventfully and postoperative analgesia was excellent. Pulmonary physiology and management of these patients will be discussed. A risk/benefit discussion should occur with patients having impaired lung function before performance of interscalene blocks. In this particular patient with mild to moderate disease, analgesia was well managed through a multimodal approach including a continuous interscalene block, and close monitoring of respiratory status took place throughout the perioperative period, leading to a successful outcome. PMID:24369510

Schwenk, Eric S.; Gandhi, Kishor; Viscusi, Eugene R.

2013-01-01

228

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

229

Clinical and prognostic significance of lung thallium uptake on rest imaging in acute myocardial infarction  

SciTech Connect

Exercise-induced pulmonary uptake of thallium-201 in patients with ischemic heart disease is probably due to transient pulmonary edema and left ventricular failure induced by exercise. The significance of increased lung uptake of thallium-201 at rest after acute myocardial infarction (AMI) has not been described. Ninety-six patients admitted with chest pain for suspected AMI or unstable angina underwent thallium-201 imaging at rest. Using conventional diagnostic criteria, 62 had AMI, 12 had unstable angina and 22 had neither. Increased lung uptake of thallium-201 was present in 24 of the total 96 (25%) patients, 20 of the 62 (32%) patients with AMI and 4 of 34 (13%) patients with no evidence of infarction. In the AMI group, those with increased lung thallium-201 uptake had a higher mean +/- standard deviation segmental thallium-201 defect score (22 +/- 7 vs 12 +/- 8, p less than 0.0001), lower ejection fraction (35 +/- 14 vs 49 +/- 14%, p less than 0.002), higher peak creatine kinase levels (2,410 +/- 1,247 vs 1,496 +/- 1,228 IU/liter, p less than 0.01), higher wall motion abnormality score (25 +/- 13 vs 13 +/- 12, p less than 0.0001), increased incidence of clinical in-hospital heart failure (15 of 20 vs 7 of 42, p less than 0.0001) and higher short-term mortality (4 of 20 vs 1 of 42, p less than 0.02) compared to those without increased lung thallium-201 uptake.

Jain, D.; Lahiri, A.; Raftery, E.B. (Northwick Park Hospital, Harrow, Middlesex (England))

1990-01-15

230

Integrin ?3 mutations with kidney, lung, and skin disease.  

PubMed

Integrin ?(3) is a transmembrane integrin receptor subunit that mediates signals between the cells and their microenvironment. We identified three patients with homozygous mutations in the integrin ?(3) gene that were associated with disrupted basement-membrane structures and compromised barrier functions in kidney, lung, and skin. The patients had a multiorgan disorder that included congenital nephrotic syndrome, interstitial lung disease, and epidermolysis bullosa. The renal and respiratory features predominated, and the lung involvement accounted for the lethal course of the disease. Although skin fragility was mild, it provided clues to the diagnosis. PMID:22512483

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

2012-04-19

231

CATIONIC SHELL CROSSLINKED NANOPARTICLES AS INTRACELLULAR DELIVERY VEHICLES FOR THE DIAGNOSIS AND TREATMENT OF ACUTE LUNG INJURY  

E-print Network

on the development of polymer nanomaterials known as shell crosslinked knedel-like (SCK) nanoparticles to serve as intracellular carriers of genetic material and specifically target injured cells in the lung for the treatment of acute lung injury (ALI). SCK...

Florez, Stephanie

2011-08-08

232

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

233

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

234

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

235

Bench-to-bedside review: Acute respiratory distress syndrome – how neutrophils migrate into the lung  

PubMed Central

Acute lung injury and its more severe form, acute respiratory distress syndrome, are major challenges in critically ill patients. Activation of circulating neutrophils and transmigration into the alveolar airspace are associated with development of acute lung injury, and inhibitors of neutrophil recruitment attenuate lung damage in many experimental models. The molecular mechanisms of neutrophil recruitment in the lung differ fundamentally from those in other tissues. Distinct signals appear to regulate neutrophil passage from the intravascular into the interstitial and alveolar compartments. Entry into the alveolar compartment is under the control of CXC chemokine receptor (CXCR)2 and its ligands (CXC chemokine ligand [CXCL]1–8). The mechanisms that govern neutrophil sequestration into the vascular compartment of the lung involve changes in the actin cytoskeleton and adhesion molecules, including selectins, ?2 integrins and intercellular adhesion molecule-1. The mechanisms of neutrophil entry into the lung interstitial space are currently unknown. This review summarizes mechanisms of neutrophil trafficking in the inflamed lung and their relevance to lung injury. PMID:15566616

Reutershan, Jörg; Ley, Klaus

2004-01-01

236

Mycobacterium abscessus Lung Disease in a Patient with Kartagener Syndrome  

PubMed Central

Primary ciliary dyskinesia (PCD) is characterized by the congenital impairment of mucociliary clearance. When accompanied by situs inversus, chronic sinusitis and bronchiectasis, PCD is known as Kartagener syndrome. The main consequence of impaired ciliary function is a reduced mucus clearance from the lungs, and susceptibility to chronic respiratory infections due to opportunistic pathogens, including nontuberculous mycobacteria (NTM). There has been no report of NTM lung disease combined with Kartagener syndrome in Korea. Here, we report an adult patient with Kartagener syndrome complicated with Mycobacterium abscessus lung disease. A 37-year-old female presented to our hospital with chronic cough and sputum. She was ultimately diagnosed with M. abscessus lung disease and Kartagener syndrome. M. abscessus was repeatedly isolated from sputum specimens collected from the patient, despite prolonged antibiotic treatment. The patient's condition improved and negative sputum culture conversion was achieved after sequential bilateral pulmonary resection. PMID:25309609

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

2014-01-01

237

'Biomass Lung': Primitive Biomass Combustion and Lung Disease  

Microsoft Academic Search

Domestic burning of biomass fuel is one of the most important risk factors for the development of respiratory diseases and infant mortality. The fuel which causes the highest level of disease is dung. In the rural areas of developing countries some 80% of households rely on biomass fuels for cooking and often heating as well and so suffer high indoor

Yusuf Izzettin Bari?; John A. Hoskins; Zehra Seyfikli; Ahmet Demir

2002-01-01

238

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

239

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

240

Animal models of beryllium-induced lung disease.  

PubMed Central

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 micrograms Be/g lung, inhaled Be metal induced benign and/or malignant lung tumors in over 50% of male and female F344 rats surviving > or = 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 micrograms (-300 micrograms 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. PMID:8933044

Finch, G L; Hoover, M D; Hahn, F F; Nikula, K J; Belinsky, S A; Haley, P J; Griffith, W C

1996-01-01

241

The pathology of interstitial lung disease in nylon flock workers.  

PubMed

Flocking is a widely used industrial process in which short lengths of synthetic fibers are applied to backing fabric to produce plush material. In response to an apparent outbreak of interstitial lung disease in flock workers, the Centers for Disease Control hosted a clinical-pathological workshop to identify the defining characteristics of the disease and possible etiologic agents. Six pathologists reviewed 15 biopsies of 15 cases (out of a clinical caseload of 20 patients) and assessed the pattern, extent and degree of pulmonary inflammation, fibrosis, and other changes. A consensus clinical-pathologic diagnosis was reached for each patient and correlated with clinical and radiologic findings. Four of eight open lung biopsies and one of seven closed (transbronchial) lung biopsies demonstrated a characteristic pattern to which the descriptive terminology lymphocytic bronchiolitis and peribronchiolitis with lymphoid hyperplasia was applied. The other biopsies showed nonspecific inflammatory changes, airspace organization, and diffuse alveolar damage. One open lung biopsy demonstrated respiratory bronchiolitis with lymphoid hyperplasia. None of the lung biopsies showed more than mild interstitial fibrosis and no granulomas were identified. The consensus of the workshop was that lymphocytic bronchiolitis and peribronchiolitis with lymphoid hyperplasia was a characteristic and distinctive pattern of injury in the flock workers' lung biopsies. Although the etiology of this disease remains undefined at present, the injury pattern and environmental studies suggest a chronic immunologic response to inhaled material. PMID:10584708

Boag, A H; Colby, T V; Fraire, A E; Kuhn, C; Roggli, V L; Travis, W D; Vallyathan, V

1999-12-01

242

Functional Genomics of Chlorine-induced Acute Lung Injury in Mice  

PubMed Central

Acute lung injury can be induced indirectly (e.g., sepsis) or directly (e.g., chlorine inhalation). Because treatment is still limited to supportive measures, mortality remains high (?74,500 deaths/yr). In the past, accidental (railroad derailments) and intentional (Iraq terrorism) chlorine exposures have led to deaths and hospitalizations from acute lung injury. To better understand the molecular events controlling chlorine-induced acute lung injury, we have developed a functional genomics approach using inbred mice strains. Various mouse strains were exposed to chlorine (45 ppm × 24 h) and survival was monitored. The most divergent strains varied by more than threefold in mean survival time, supporting the likelihood of an underlying genetic basis of susceptibility. These divergent strains are excellent models for additional genetic analysis to identify critical candidate genes controlling chlorine-induced acute lung injury. Gene-targeted mice then could be used to test the functional significance of susceptibility candidate genes, which could be valuable in revealing novel insights into the biology of acute lung injury. PMID:20601635

Leikauf, George D; Pope-Varsalona, Hannah; Concel, Vincent J.; Liu, Pengyuan; Bein, Kiflai; Brant, Kelly A.; Dopico, Richard A.; Di, Y. Peter; Jang, An-Soo; Dietsch, Maggie; Medvedovic, Mario; Li, Qian; Vuga, Louis J.; Kaminski, Naftali; You, Ming; Prows, Daniel R.

2010-01-01

243

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

PubMed

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

2014-11-01

244

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

245

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

246

Prehospitalization Antiplatelet Therapy Is Associated With a Reduced Incidence of Acute Lung Injury  

PubMed Central

Background: Acute lung injury (ALI) is a potentially fatal lung disease with few treatment options. Platelet activation is a key component of ALI pathophysiology and may provide an opportunity for prevention strategies. We examined the association of prehospitalization antiplatelet therapy with development of ALI in critically ill patients. Methods: All Olmsted County, Minnesota, residents with a medical ICU admission in the year 2006 were evaluated. Patients with at least one major risk factor for ALI who did not meet criteria for ALI at the time of hospital admission were included in the analysis. Baseline characteristics, major risk factors for ALI, the presence of antiplatelet therapy at the time of hospitalization, and the propensity to receive this therapy were determined. The primary outcome was ALI or ARDS during the hospitalization. Secondary outcomes were ICU and hospital-free days and ICU and hospital mortality. Results: A total of 161 patients were evaluated. Seventy-nine (49%) were receiving antiplatelet therapy at hospital admission; 33 (21%) developed ALI/ARDS. Antiplatelet therapy was associated with a reduced incidence of ALI/ARDS (12.7% vs 28.0%; OR, 0.37; 95% CI, 0.16-0.84; P = .02). This association remained significant after adjusting for confounding variables. Conclusions: Prehospitalization antiplatelet therapy was associated with a reduced incidence of ALI/ARDS. If confirmed in a more diverse patient population, these results would support the use of antiplatelet agents in an ALI prevention trial. PMID:20688925

Erlich, Jason M.; Talmor, Daniel S.; Cartin-Ceba, Rodrigo; Gajic, Ognjen

2011-01-01

247

Systems biology approaches to identify developmental bases for lung diseases  

PubMed Central

A greater understanding of the regulatory processes contributing to lung development could be helpful to identify strategies to ameliorate morbidity and mortality in premature infants and to identify individuals at risk for congenital and/or chronic lung diseases. Over the past decade, genomics technologies have enabled the production of rich gene expression databases providing information for all genes across developmental time or in diseased tissue. These data sets facilitate systems biology approaches for identifying underlying biological modules and programs contributing to the complex processes of normal development, and those that may be associated with disease states. The next decade will undoubtedly see rapid and significant advances in redefining both lung development and disease at the systems level. PMID:23314295

Bhattacharya, Soumyaroop; Mariani, Thomas J.

2013-01-01

248

Lung Cancer Diseases Diagnostic Asistance Using Gray Color Analysis  

Microsoft Academic Search

Errors in diagnosing the disease is a critical risk that must be faced by any person giving treatment to the hospital. Medical treatment can not always be done with perfect accuracy. Lung cancer is one of the most deadly disease that prone to misdiagnose. In general, some practitioners tend to “read” cancer in x-ray rontgen image as tumor this could

P. Paulus; F. L. Gaol

2010-01-01

249

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...

250

Targeting lethal minimal residual disease in small cell lung cancer  

Microsoft Academic Search

In the last three decades, treatment for small cell lung cancer has improved with advances in chemotherapy and radiotherapy. Almost all patients respond initially to standard chemotherapy, and some patients with limited stage disease are cured with the combination of chemotherapy and thoracic irradiation. Nonetheless, the majority of patients will experience lethal relapse from chemotherapy-resistant micrometastatic disease, and this has

Jyoti D. Patel; Lee M. Krug; Christopher G. Azzoli; Jorge Gomez; Mark G. Kris; Vincent A. Miller

2003-01-01

251

Novel Role for Aldose Reductase in Mediating Acute Inflammatory Responses in the Lung1  

PubMed Central

Exaggerated inflammatory responses and the resultant increases in alveolar-capillary permeability underlie the pathogenesis of acute lung injury during sepsis. This study examined the functions of aldose reductase (AR) in mediating acute lung inflammation. Transgenic mice expressing human AR (ARTg) were used to study the functions of AR since mice have low intrinsic AR activity. In a mild cecal ligation and puncture model, ARTg mice demonstrated an enhanced AR activity and a greater inflammatory response as evaluated by circulating cytokine levels, neutrophil accumulation in the lungs, and activation of Rho kinase in lung endothelial cells (ECs). Compared with WT lung cells, ARTg lung cells produced more IL-6 and showed augmented JNK activation in response to LPS stimulation ex vivo. In human neutrophils, AR activity was required for fMLP-included CD11b activation and up-regulation, respiratory burst, and shape changes. In human pulmonary microvascular ECs, AR activity was required for TNF-?-induced activation of the Rho kinase/MKK4/JNK pathway and IL-6 production, but not p38 activation or ICAM-1 expression. Importantly, AR activity in both human neutrophils and ECs was required for neutrophil adhesion to TNF-?-stimulated ECs. These data demonstrate a novel role for AR in regulating the signaling pathways leading to neutrophil-EC adhesion during acute lung inflammation. PMID:20007578

Ravindranath, Thyyar M.; Mong, Phyllus Y.; Ananthakrishnan, Radha; Li, Qing; Quadri, Nosirudeen; Schmidt, Ann Marie; Ramasamy, Ravichandran; Wang, Qin

2011-01-01

252

Inhaled beta-2 agonist salbutamol and acute lung injury: an association with improvement in acute lung injury  

PubMed Central

Introduction ?2 agonists have several properties that could be beneficial in acute lung injury (ALI). We therefore chose to study the effect of inhaled ?2 agonist use (salbutamol) on duration and severity of ALI. Methods We undertook a retrospective chart review of 86 consecutive mechanically ventilated patients with ALI, who had varying exposure to inhaled salbutamol. The cohort was divided into two groups according to the average daily dose of inhaled salbutamol they received ('high dose' ? 2.2 mg/day and 'low dose' <2.2 mg/day). Severity of ALI and non-pulmonary organ dysfunction was compared between the groups by calculating the days alive and free of ALI and other organ dysfunctions. Results The high dose and low dose groups received a mean of 3.72 mg and 0.64 mg salbutamol per day, respectively. The high dose salbutamol group had significantly more days alive and free of ALI than the low dose group (12.2 ± 4.4 days versus 7.6 ± 1.9 days, p = 0.02). There were no associations between dose of ? agonist and non-pulmonary organ dysfunctions. High dose salbutamol (p = 0.04), APACHE II score (p = 0.02), and cause of ALI (p = 0.02) were independent variables associated with number of days alive and free of ALI in a multivariate linear regression model. Conclusion Our retrospective study suggests that salbutamol, an inhaled ?2 agonist, is associated with a shorter duration and lower severity of ALI. A dose greater than 2.2 mg/day of inhaled salbutamol could be a minimal effective dose to evaluate in a randomized controlled trial. PMID:16420663

Manocha, Sanjay; Gordon, Anthony C; Salehifar, Ebrahim; Groshaus, Horacio; Walley, Keith R; Russell, James A

2006-01-01

253

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

254

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

255

[Acute bacterial meningitis as an occupational disease].  

PubMed

Streptococcus suis is a zoonotic pathogen with worldwide distribution, responsible for more than 700 human cases globally reported. This infection affects mostly men, exposed to pig or pork, which leads to its usual classification as an occupational disease. We report a case of acute bacterial meningitis in a 44 years old male. According to his past medical history, the patient had chronic alcoholism and worked in a restaurant as a piglet roaster. Microbiological examination of blood and CSF revealed S. suis. After 14 days of ceftriaxone the patient fully recovered. The authors review the clinical reports previously described in Portugal. In all of them was possible to identify risk exposition to pork. We alert to this microorganism's importance in Portugal where it is probably underdiagnosed. PMID:25203963

Seixas, Diana; Lebre, Ana; Crespo, Pedro; Ferreira, Eugénia; Serra, José Eduardo; Saraiva da Cunha, José Gabriel

2014-01-01

256

Clinical knowledge-based inference model for early detection of acute lung injury.  

PubMed

Acute lung injury (ALI) is a devastating complication of acute illness and one of the leading causes of multiple organ failure and mortality in the intensive care unit (ICU). The detection of this syndrome is limited due to the complexity of the disease, insufficient understanding of its development and progression, and the large amount of risk factors and modifiers. In this preliminary study, we present a novel mathematical model for ALI detection. It is constructed based on clinical and research knowledge using three complementary techniques: rule-based fuzzy inference systems, Bayesian networks, and finite state machines. The model is developed in Matlab(®)'s Simulink environment and takes as input pre-ICU and ICU data feeds of critically ill patients. Results of the simulation model were validated against actual patient data from an epidemiologic study. By appropriately combining all three techniques the performance attained is in the range of 71.7-92.6% sensitivity and 60.3-78.4% specificity. PMID:22167531

Chbat, Nicolas W; Chu, Weiwei; Ghosh, Monisha; Li, Guangxi; Li, Man; Chiofolo, Caitlyn M; Vairavan, Srinivasan; Herasevich, Vitaly; Gajic, Ognjen

2012-05-01

257

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

258

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

259

Inhaled aerosolized insulin ameliorates hyperglycemia-induced inflammatory responses in the lungs in an experimental model of acute lung injury  

PubMed Central

Introduction Previous studies have shown that patients with diabetes mellitus appear to have a lower prevalence of acute lung injury. We assumed that insulin prescribed to patients with diabetes has an anti-inflammatory property and pulmonary administration of insulin might exert beneficial effects much more than intravenous administration. Methods Twenty-eight mechanically ventilated rabbits underwent lung injury by saline lavage, and then the animals were allocated into a normoglycemia group (NG), a hyperglycemia group (HG), an HG treated with intravenous insulin (HG-VI) group or an HG treated with aerosolized insulin (HG-AI) group with continuous infusion of different fluid solutions and treatments: normal saline, 50% glucose, 50% glucose with intravenous insulin, or 50% glucose with inhaled aerosolized insulin, respectively. After four hours of treatment, the lungs and heart were excised en bloc, and then high-mobility group B1 concentration in bronchoalveolar lavage fluid, interleukin-8 and toll-like receptor 4 mRNA expression in bronchoalveolar lavage fluid cells, and lung myeloperoxidase activity were measured. Results Treatment with both aerosolized insulin and intravenous insulin attenuated toll-like receptor 4 mRNA expressions in the bronchoalveolar lavage fluid cells. Interleukin-8 and toll-like receptor 4 mRNA expression was significantly lower in the HG-AI group than in the HG-IV group. The lung myeloperoxidase activity in the normal healthy group showed significantly lower levels compared to the NG group but not different compared to those of the HG, HG-VI and HG-AI groups. Conclusions The results suggest that insulin attenuates inflammatory responses in the lungs augmented by hyperglycemia in acute lung injury and the insulin's efficacy may be better when administered by aerosol. PMID:23622115

2013-01-01

260

Corticosteroids prevent acute lung dysfunction caused by thoracic irradiation in unanesthetized sheep  

SciTech Connect

We sought to determine the effect of corticosteroid therapy in a new acute model of oxidant lung injury, thoracic irradiation in awake sheep. Sheep were irradiated with 1,500 rads to the whole chest except for blocking the heart and adjacent ventral lung. Seven experimental sheep were given methylprednisolone (1 g intravenously every 6 h for four doses) and thoracic irradiation; control sheep received only irradiation. In irradiated control sheep, lung lymph flow increased from baseline (7.6 ml/h) to peak at 3 h (13.2), and lung lymph protein clearance increased from 5.1 to 9.7 ml/h. Mean pulmonary artery pressure increased in the irradiated control sheep from 19 to 32.4 cm H/sub 2/O, whereas the lung lymph thromboxane concentration increased from 0.09 to 6.51 ng/ml at 3 h. Arterial oxygen tension in irradiated control sheep fell gradually from 86 mm Hg at baseline to 65 mm Hg at 8 h. Methylprednisolone administration significantly prevented the increase in lung lymph protein clearance, mean pulmonary artery pressure, and lung lymph thromboxane concentration. Methylprednisolone also prevented the fall in arterial oxygen tension after thoracic irradiation, but did not prevent a further decrease in lymphocytes in blood or lung lymph after radiation. We conclude that corticosteroid therapy prevents most of the acute physiologic changes caused by thoracic irradiation in awake sheep.

Loyd, J.E.; Bolds, J.M.; Wickersham, N.; Malcolm, A.W.; Brigham, K.L.

1988-11-01

261

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

262

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

SciTech Connect

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

Infante, P.F. (Occupational Safety and Health Administration, Washington, DC); Wagoner, J.K.; Sprince, N.L.

1980-02-01

263

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

264

Body position changes redistribute lung computed-tomographic density in patients with acute respiratory failure.  

PubMed

Ten patients with parenchymal acute respiratory failure (ARF) underwent computed tomography (CT) scans while in the supine and prone positions. At equal levels of positive end-expiratory pressure, the authors measured the changes of CT density in dorsal and ventral basilar lung regions induced by the change of position as well as alterations of gas exchange. The level of venous admixture did not change with body position. The CT scan image of each lung was fractionated into ten levels from dorsal to ventral, each constituting 10% of the lung height. After measuring each lung fraction, the volume, the average CT number, its frequency distribution, and the expected normal value, we computed the lung tissue mass, the excess tissue mass, and the fraction of normally inflated tissue (excess tissue mass = amount of "tissue," which includes edema, cells, and blood in excess of the expected normal value). We also estimated the superimposed hydrostatic pressure on each lung region. We found that the excess lung tissue mass is independent of position. However, in patients in the supine position, lung CT density increased and regional inflation decreased from ventral to dorsal, suggesting progressive deflation of gas-containing alveoli along the gravity gradient. A similar ventral-dorsal deflation pattern occurred within 10 min in patients in the prone position. We conclude that the lung in patients with ARF behaves like an elastic body with a diffusely increased mass; dependent lung regions are compressed by the pressure of overlying structures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1986640

Gattinoni, L; Pelosi, P; Vitale, G; Pesenti, A; D'Andrea, L; Mascheroni, D

1991-01-01

265

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

PubMed Central

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

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

2014-01-01

266

Lung function abnormalities in different connective tissue diseases  

Microsoft Academic Search

Summary  \\u000aLung volumes, forced expiratory flow-volume curves, diffusing capacity indexes, and arterial blood gases were measured in 72 non-smoking patients with various connective tissue diseases (13 with rheumatoid arthritis, 17 with systemic lupus erythematosus, 25 with progressive systemic sclerosis, 10 with primary Sjögren's syndrome, 4 with polymyositis, and 3 with mixed connective tissue disease). Small airways disease and a diffusion

C. Vitali; G. Viegi; S. Tassoni; A. Tavoni; P. Paoletti; E. Bibolotti; C. Ferri; S. Bombardieri

1986-01-01

267

Pattern of inspiratory gas delivery affects CO 2 elimination in health and after acute lung injury  

Microsoft Academic Search

Objective  To avoid ventilator induced lung injury, tidal volume should be low in acute lung injury (ALI). Reducing dead space may be\\u000a useful, for example by using a pattern of inspiration that prolongs the time available for gas distribution and diffusion\\u000a within the respiratory zone, the mean distribution time (MDT). A study was conducted to investigate how MDT affects CO2 elimination in pigs

Elisabet Åström; Leif Uttman; Lisbet Niklason; Jerome Aboab; Laurent Brochard; Björn Jonson

2008-01-01

268

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

269

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

270

Pulmonary capillaritis as a manifestation of acute humoral allograft rejection following infant lung transplantation.  

PubMed

Pulmonary capillaritis has been described in adult lung transplant recipients, but has not been previously reported in pediatric recipients. We report a case of posttransplant pulmonary capillaritis in an 8-month-old infant, and demonstrate evidence of C4d deposition and B-lymphocytes in the allograft, donor anti-HLA antibodies in the serum and a clinical and immunohistochemical response to anti-CD20 monoclonal antibody (rituximab) therapy. These findings strongly support the hypothesis that pulmonary capillaritis may represent a form of acute humoral rejection in the lung allograft that is less common than, and clinically and histologically distinct from, typical acute cellular rejection. PMID:19067668

Astor, T L; Galantowicz, M; Phillips, A; Palafox, J; Baker, P

2009-02-01

271

Titanium Dioxide Exposure Induces Acute Eosinophilic Lung Inflammation in Rabbits  

PubMed Central

Titanium dioxide (TiO2) is increasingly widely used in industrial, commercial and home products. TiO2 aggravates respiratory symptoms by induction of pulmonary inflammation although the mechanisms have not been well investigated. We aimed to investigate lung inflammation in rabbits after intratracheal instillation of P25 TiO2. One ml of 10, 50 and 250 µg of P25 TiO2 was instilled into one of the lungs of rabbits, chest computed-tomography was performed, and bronchoalveolar lavage (BAL) fluid was collected before, at 1 and 24 h after P25 TiO2 exposure. Changes in inflammatory cells in the BAL fluids were measured. Lung pathological assay was also carried out at 24 h after P25 TiO2 exposure. Ground glass opacities were noted in both lungs 1 h after P25 TiO2 and saline (control) instillation. Although the control lung showed complete resolution at 24 h, the lung exposed to P25 TiO2 showed persistent ground glass opacities at 24 h. The eosinophil counts in BAL fluid were significantly increased after P25 TiO2 exposure. P25 TiO2 induced a dose dependent increase of eosinophils in BAL fluid but no significant differences in neutrophil and lymphocyte cell counts were detected. The present findings suggest that P25 TiO2 induces lung inflammation in rabbits which is associated with eosinophilic inflammation. PMID:24705802

CHOI, Gil Soon; OAK, Chulho; CHUN, Bong-Kwon; WILSON, Donald; JANG, Tae Won; KIM, Hee-Kyoo; JUNG, Mannhong; TUTKUN, Engin; PARK, Eun-Kee

2014-01-01

272

Smoking-Related "Interstitial" Lung Disease.  

PubMed

Context .- Emphysema, respiratory bronchiolitis, desquamative interstitial pneumonia, pulmonary Langerhans' cell histiocytosis, small-airway injury including submucosal and adventitial fibrosis, increased bronchus-associated lymphoid tissue, and small artery/arteriolar wall thickening are recognized histologic findings in cigarette smokers. It has only recently been acknowledged that the range of lung injury from cigarette smoke is wider than generally accepted, in particular, there is increasing recognition that fibrosis of alveolar walls occurs in smokers. Objectives .- To review the literature that describes the range of histologic findings in cigarette smokers and that links cigarette smoke exposure to the development of alveolar wall fibrosis. Data Sources .- Relevant peer-reviewed literature indexed in PubMed (National Library of Medicine) form the basis of this review. Conclusions .- Smokers demonstrate a wide range of lung injury at biopsy that defies simple placement within single categories, and the current categories do not adequately take into account the importance of alveolar wall and airway fibrosis. PMID:25415179

Franks, Teri J; Galvin, Jeffrey R

2014-11-21

273

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 Søs; Kyjovska, Zdenka O; Halappanavar, Sabina; Yauk, Carole L; Wallin, Håkan; Vogel, Ulla

2014-01-01

274

Therapeutic Effect of Intravenous Infusion of Perfluorocarbon Emulsion on LPS-Induced Acute Lung Injury in Rats  

PubMed Central

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

Lv, Qi; Yin, Xiaofeng; Song, Jianqi; Landén, Ning Xu; Fan, Haojun

2014-01-01

275

Hyperbaric oxygen preconditioning protects lung against hyperoxic acute lung injury in rats via heme oxygenase-1 induction.  

PubMed

Hyperoxic acute lung injury (HALI) is a clinical syndrome as a result of prolonged supplement of high concentrations of oxygen. Previous studies have shown hyperbaric oxygen preconditioning (HBO-PC) had a protective effect on oxidative injury. In the present study, we investigated the effect of HBO-PC on HALI in rats. The results demonstrated that HBO-PC ameliorated the lung biochemical and histological alterations induced by hyperoxia, decreased oxidative products but increased antioxidant enzymes. Furthermore, HBO-PC up-regulated heme oxygenase-1 (HO-1) mRNA and activity in lung tissues. The administration of HO-1 inhibitor, Zinc protoporphyrin IX, abolished its protective effects. The data showed that HBO-PC could protect rats against HALI and the anti-oxidative effect may be related to the up-regulation of HO-1. PMID:25264201

Feng, Ying; Zhang, Zinan; Li, Qiang; Li, Weihao; Xu, Jing; Cao, Huifang

2015-01-01

276

Mechanical ventilation with high tidal volume induces inflammation in patients without lung disease  

Microsoft Academic Search

INTRODUCTION: Mechanical ventilation (MV) with high tidal volumes may induce or aggravate lung injury in critical ill patients. We compared the effects of a protective versus a conventional ventilatory strategy, on systemic and lung production of tumor necrosis factor-? (TNF-?) and interleukin-8 (IL-8) in patients without lung disease. METHODS: Patients without lung disease and submitted to mechanical ventilation admitted to

Roselaine Pinheiro de Oliveira; Marcio Pereira Hetzel; Mauro dos Anjos Silva; Daniele Dallegrave; Gilberto Friedman

2010-01-01

277

Drug induced lung disease--amiodarone in focus.  

PubMed

More than 380 medications are known to cause pulmonary toxicity. Selected drugs that are important causes of pulmonary toxicity fall into the following classes: cytotoxic, cardiovascular, anti-inflammatory, antimicrobial, illicit drugs, miscellaneous. The adverse reactions can involve the pulmonary parenchyma, pleura, the airways, pulmonary vascular system, and mediastinum. Drug-induced lung diseases have no pathognomonic clinical, laboratory, physical, radiographic or histological findings. A drug-induced lung disease is usually considered a diagnosis of exclusion of other diseases. The diagnosis of drug-mediated pulmonary toxicity is usually made based on clinical findings. In general, laboratory analyses do not help in establishing the diagnosis. High-resolution computed tomography scanning is more sensitive than chest radiography for defining radiographic abnormalities. The treatment of drug-induced lung disease consists of immediate discontinuation of the offending drug and appropriate management of the pulmonary symptoms. Glucocorticoids have been associated with rapid improvement in gas exchange and reversal of radiographic abnormalities. Before starting any medication, patients should be educated about the potential adverse effects of the drug. Amiodarone is an antiarrhythmic agent used in the treatment of many types of tachyarrhythmia. Amiodarone-caused pulmonary toxicity is a well-known side effect (complication) of this medication. The incidence of amiodarone-induced lung disease is approximately 5-7%. PMID:25546981

Vasi?, Nada R; Milenkovi?, Branislava A; Pešut, Dragica P; Stevi?, Ruža S; Jovanovi?, Dragana M

2014-01-01

278

Therapeutic potential of heme oxygenase-1/carbon monoxide in lung disease.  

PubMed

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

279

Acute effects of estradiol on lung inflammation due to intestinal ischemic insult in male rats.  

PubMed

Intestinal ischemia and reperfusion (intestinal I/R) causes acute lung inflammation that is characterized by leukocyte migration, increased lung microvascular permeability, and, in severe forms, noncardiogenic pulmonary edema and acute respiratory distress syndrome. Female sex hormones interfere with immune response, and experimental and clinical evidence shows that females are more resistant than males to organ injury caused by gut trauma. To reduce the lung inflammation caused by intestinal I/R, we have acutely treated male rats with estradiol. Intestinal I/R was performed by the clamping (45 min) of the superior mesenteric artery (SMA), followed by 2 h of intestinal reperfusion (unclamping SMA). Groups of rats received 17? estradiol (E2, 280 µg/kg, i.v., single dose) 30 min after the SMA occlusion (ischemia period) or 1 h after the unclamping of SMA (reperfusion period). Leukocytes influx into the lung and microvascular leakage were assessed by lung myeloperoxidase activity and Evans blue dye extravasation, respectively. The lung expression of adhesion molecules (intercellular adhesion molecule 1, platelet endothelial cell adhesion molecule 1, and vascular cell adhesion molecule [VCAM]) was evaluated by immunohistochemistry. Interleukin 1? (IL-1?), IL-10, and NOx concentrations were quantified in supernatants of cultured lung tissue. We have found that intestinal I/R increased the lung myeloperoxidase activity and Evans blue dye extravasation, which were reduced by treatment of rats with E2. Intestinal I/R increased ICAM-1 expression only, and it was decreased by E2 treatment. However, E2 treatment reduced the basal expression of platelet endothelial cell adhesion molecule 1. E2 treatment during intestinal ischemia was effective to reduce the levels of IL-10 and IL-1? in explant supernatant, but only IL-10 levels were reduced by E2 at reperfusion phase. The treatment with E2 did not affect NOx concentration. Taken together, our data suggest that estradiol modulates the lung inflammatory response induced by lung injury, likely by acute effects. Thus, acute estradiol treatment could be considered as a potential therapeutic agent in ischemic events. PMID:24220282

Breithaupt-Faloppa, Ana Cristina; Thais Fantozzi, Evelyn; Romero, Daniel Cancelli; Rodrigues, Adriana da Silva; de Sousa, Paulo Thales Rocha; Lino Dos Santos Franco, Adriana; Oliveira-Filho, Ricardo Martins; Boris Vargaftig, Bernardo; Tavares de Lima, Wothan

2014-03-01

280

Fibrocytes in chronic lung disease--facts and controversies.  

PubMed

Fibrocytes are bone marrow-derived mesenchymal cell precursors, defined primarily by their ability to co-express markers of both haematopoietic (e.g. CD45 or CXCR4) and stromal (e.g. collagen) lineages. Fibrocytes in culture also have ultrastructural cell surface features that distinguish them from other leukocytes. Extensive efforts have helped to characterise fibrocytes phenotypically and functionally, but it is still unclear exactly how these cells contribute to tissue repair and/or pathologic fibrosis. Nevertheless, the varied levels of fibrocytes in blood have raised considerable interest as a biomarker of disease activity, such as chronic lung diseases, including pulmonary fibrosis, asthma and pulmonary hypertension. These cells also may become a novel therapeutic target for these difficult to treat disorders. This review will briefly summarize the current knowledge about fibrocytes in human lung disease and in animal disease models and highlight areas of consensus as well as issues that remain controversial to date. PMID:21951688

Maharaj, Shyam S; Baroke, Eva; Gauldie, Jack; Kolb, Martin R J

2012-08-01

281

Pulmonary functional magnetic resonance imaging for paediatric lung disease.  

PubMed

A better understanding of the anatomic structure and physiological function of the lung is fundamental to understanding the pathogenesis of pulmonary disease and how to design and deliver better treatments and measure response to intervention. Magnetic resonance imaging (MRI) with the hyperpolarised noble gases helium-3 ((3)He) and xenon-129 ((129)Xe) provides both structural and functional pulmonary measurements, and because it does not require the use of x-rays or other ionising radiation, offers the potential for intensive serial and longitudinal studies in paediatric patients. These facts are particularly important in the evaluation of chronic lung diseases such as asthma and cystic fibrosis- both of which can be considered paediatric respiratory diseases with unmet therapy needs. This review discusses MRI-based imaging methods with a focus on hyperpolarised gas MRI. We also discuss the strengths and limitations as well as the future work required for clinical translation towards paediatric respiratory disease. PMID:23522599

Kirby, Miranda; Coxson, Harvey O; Parraga, Grace

2013-09-01

282

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 ...

283

Rheumatoid interstitial lung disease presenting as cor pulmonale  

PubMed Central

Rheumatiod arthritis (RA) is a multisystem connective tissue disorder. The predominant presentation is polyarticular, symmetric peripheral arthritis with relative sparing of axial skeleton. Inflammatory synovitis is the pathologic hallmark. Extra-articular manifestations of RA can involve several other organ systems and amongst them pulmonary manifestations occur commonly. We report a case of rheumatoid interstitial lung disease presenting as cor pulmonale. PMID:21139729

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

2010-01-01

284

Relative importance of cigarette smoking in occupational lung disease  

Microsoft Academic Search

Since 1900 respiratory disease has remained a constant serious cause of chronic ill health and premature death in Britain. The falling importance of tuberculosis and pneumonia has been off-set by the rise in lung cancer. Bronchitis morbidity and mortality have fallen only slightly since 1935. To produce any real improvement in the future existing information as to cause must be

P C Elmes

1981-01-01

285

The radiology of chronic lung disease in children  

Microsoft Academic Search

Chronic lung disease (CLD) in children represents a heterogeneous group of many distinct clinicopathological entities. The prevalence of CLD has increased in the past decade because of the more advanced and intensive respiratory support provided for compromised children and additionally the overall improved survival of preterm babies. The disorders which constitute CLD generally have a slow tempo of progression over

U G Rossi; C M Owens

2005-01-01

286

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

2014-11-15

287

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

288

Serum biomarkers in interstitial lung diseases  

Microsoft Academic Search

The use of biomarkers in medicine lies in their ability to detect disease and support diagnostic and therapeutic decisions. New research and novel understanding of the molecular basis of the disease reveals an abundance of exciting new biomarkers who present a promise for use in the everyday clinical practice. The past fifteen years have seen the emergence of numerous clinical

Argyris Tzouvelekis; George Kouliatsis; Stavros Anevlavis; Demosthenes Bouros

2005-01-01

289

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 ...

290

Identification of Patients with Acute Lung Injury from Free-Text Chest X-Ray Reports  

E-print Network

Identification of Patients with Acute Lung Injury from Free-Text Chest X-Ray Reports Meliha on the information available in free-text chest x-ray reports. To increase the classification performance we enhanced are positive for ALI based only on the free-text chest x-ray re- ports. 2 Related Work Several studies

Yetisgen-Yildiz, Meliha

291

Lipid Mediators as Agonists for the Resolution of Acute Lung Inflammation and Injury  

Microsoft Academic Search

Resolution of acute lung inflammation and injury is an active pro- cess; it is not merely the absence of proinflammatory signals. Resto- ration of homeostasis is coordinated by specific mediators and cellular events. In response to injury and inflammatory stimuli, infiltrating leukocytes and tissue-resident cells interact to generate lipoxins (LXs), which are bioactive eicosanoids derived from arachi- donic acid. In

Caroline Bonnans; Bruce D. Levy

292

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 ...

293

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

294

Respiratory syncytial virus-induced acute and chronic airway disease is independent of genetic background: An experimental murine model  

Microsoft Academic Search

BACKGROUND: Respiratory syncytial virus (RSV) is the leading respiratory viral pathogen in young children worldwide. RSV disease is associated with acute airway obstruction (AO), long-term airway hyperresponsiveness (AHR), and chronic lung inflammation. Using two different mouse strains, this study was designed to determine whether RSV disease patterns are host-dependent. C57BL\\/6 and BALB\\/c mice were inoculated with RSV and followed for

Susana Chávez-Bueno; Asunción Mejías; Ana M Gómez; Kurt D Olsen; Ana M Ríos; Mónica Fonseca-Aten; Octavio Ramilo; Hasan S Jafri

2005-01-01

295

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

296

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

297

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

298

Clinical course of acute chemical lung injury caused by 3-chloropentafluoropene.  

PubMed

Perfluoroallyl chloride (PFAC), a fluorine-containing compound, has very severe toxicity, but this toxicity is not well characterised. We report a fatal case of acute chemical lung injury caused by the inhalation of PFAC. A 39-year-old man, working at a chemical factory, inhaled PFAC gas and died 16 days later of acute lung injury with severe pneumothorax. We present his clinical course together with thoracic CT findings, autopsy and analysis of PFAC in blood and urine samples with gas chromatograph-mass spectrometry. Previously, a fatal case of PFAC was reported in 1981 but PFAC was not identified in any of the patient's samples. In our patient, we identified PFAC in both blood and urine samples. Our toxicological analysis may be used as a reference to detect PFAC toxicity in the future. Our study should be helpful for diagnosing lung injury induced by a highly toxic gas, such as PFAC. PMID:24311414

Morita, Satomu; Takimoto, Takayuki; Kawahara, Kunimitsu; Nishi, Katsuji; lino, Morio

2013-01-01

299

Relationships between lung computed tomographic density, gas exchange, and PEEP in acute respiratory failure.  

PubMed

Twenty-two patients with acute respiratory failure underwent lung computed tomography (CT) and physiological measurements at 5, 10, and 15 cm H2O positive end-expiratory pressure (PEEP) to investigate the relationship between morphology and function. Lung densities were primarily concentrated in the dependent regions. From the frequency distribution of CT numbers (difference in x-ray attenuation between water and lung) and lung gas volume measurements the authors obtained a quantitative estimate of normally inflated, poorly inflated, and non-inflated lung tissue weight. This estimated average lung weight was increased twofold above normal and excess lung weight correlated with the mean pulmonary artery pressure (P less than 0.01). Venous admixture correlated with the non-inflated tissue mass (P less than 0.01). Increasing PEEP caused progressive clearing of radiographic densities and increased the mass of normally inflated tissue (anatomic recruitment), while reducing venous admixture. The cardiac index decreased after increasing PEEP while oxygen delivery was unchanged. The authors conclude that CT scan lung density and oxygen exchange efficiency are correlated; the main effect of augmenting PEEP is to recruit perfused alveolar units that were previously collapsed. PMID:3057937

Gattinoni, L; Pesenti, A; Bombino, M; Baglioni, S; Rivolta, M; Rossi, F; Rossi, G; Fumagalli, R; Marcolin, R; Mascheroni, D

1988-12-01

300

Derivation and Validation of Automated Electronic Search Strategies to Identify Pertinent Risk Factors for Postoperative Acute Lung Injury  

PubMed Central

OBJECTIVE: To develop and validate time-efficient automated electronic search strategies for identifying preoperative risk factors for postoperative acute lung injury. PATIENTS AND METHODS: This secondary analysis of a prospective cohort study included 249 patients undergoing high-risk surgery between November 1, 2005, and August 31, 2006. Two independent data-extraction strategies were compared. The first strategy used a manual review of medical records and the second a Web-based query-building tool. Web-based searches were derived and refined in a derivation cohort of 83 patients and subsequently validated in an independent cohort of 166 patients. Agreement between the 2 search strategies was assessed with percent agreement and Cohen ? statistics. RESULTS: Cohen ? statistics ranged from 0.34 (95% confidence interval, 0.00-0.86) for amiodarone to 0.85 for cirrhosis (95% confidence interval, 0.57-1.00). Agreement between manual and automated electronic data extraction was almost complete for 3 variables (diabetes mellitus, cirrhosis, H2-receptor antagonists), substantial for 3 (chronic obstructive pulmonary disease, proton pump inhibitors, statins), moderate for gastroesophageal reflux disease, and fair for 2 variables (restrictive lung disease and amiodarone). Automated electronic queries outperformed manual data collection in terms of sensitivities (median, 100% [range, 77%-100%] vs median, 87% [range, 0%-100%]). The specificities were uniformly high (?96%) for both search strategies. CONCLUSION: Automated electronic query building is an iterative process that ultimately results in accurate, highly efficient data extraction. These strategies may be useful for both clinicians and researchers when determining the risk of time-sensitive conditions such as postoperative acute lung injury. PMID:21531881

Alsara, Anas; Warner, David O.; Li, Guangxi; Herasevich, Vitaly; Gajic, Ognjen; Kor, Daryl J.

2011-01-01

301

Role of platelet-activating factor in pancreatitis-associated acute lung injury in the rat.  

PubMed Central

Acute necrotizing pancreatitis induced by infusion of bile salt into the pancreatic duct in rats is consistently associated with acute lung injury similar to the adult respiratory distress syndrome. The role of platelet-activating factor (PAF) in this pancreatitis-associated remote organ failure (lung injury) was investigated. Pulmonary tissue levels of PAF were increased gradually and reached a level of 1345 +/- 455 pg/g (6 times the control level) at 12 hours after induction of pancreatitis, whereas pancreatic PAF levels were undetectable and blood PAF remained unchanged. This local pulmonary PAF accumulation occurred at approximately the same time as the progression of lung injury. Pulmonary responses detected (i.e., eicosanoid production, leukocytic infiltration, Evan's blue extravasation, beta-glucuronidase release) were attenuated to varying degrees by treatment of rats in which pancreatitis was initiated with the PAF receptor antagonists (WEB2170 and BN52021). Rat lung lavages were examined after a 12-hour course of pancreatitis and no changes in PAF concentration, surfactant content, and phospholipase A2 (PLA2) activity were noted. Intravenous administration of PLA2 promoted pulmonary PAF production in experimental rats with pancreatitis but not in normal rats. This observation indicates that PLA2, which was determined to be elevated in plasma during pancreatitis, may be responsible for the accumulation of PAF in the lung. In conclusion, pancreatitis-associated lung injury appears to result from an endogenous inflammatory response in which PAF may play an important role. Images Figure 1 PMID:1562055

Zhou, W.; McCollum, M. O.; Levine, B. A.; Olson, M. S.

1992-01-01

302

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

303

Discrimination between two lung diseases using chest radiographs.  

PubMed

Economic considerations make the conventional chest radiograph (X-ray) film an important ingredient in the diagnostic process. An initial clinical investigation for patients with suspected lung ailments is the study of the chest X-rays. The problem of detection for diseases in their early stages are well known using X-ray. A technique involving wavelets coefficient as the feature vector and Andrew's Curve has been proposed for detection of Mycobacterium Tuberculosis (MTB). This paper presents new and important results whereby lung cancer (LC) may be detected and differentiated from MTB. A method to calculate misclassification probabilities is given. PMID:17282956

Mohd Noor, Norliza; Mohd Rijal, Omar; Shaban, Hamidah; Ee Ling, Ong

2005-01-01

304

A Case of Venlafaxine-Induced Interstitial Lung Disease  

PubMed Central

A patient treated with venlafaxine for major depression developed an interstitial lung disease (ILD) with the characteristic clinical, radiological and pathological features of chronic hypersensitivity pneumonitis. A high resolution computed tomography scan demonstrated ground glass opacity, mosaic perfusion with air-trapping and traction bronchiectasis in both lungs. The pathological findings were consistent with a nonspecific interstitial pneumonia pattern. Clinical and radiological improvements were noted after the discontinuation of venlafaxine and the administration of a corticosteroid. This report provides further evidence that the anti-depressant venlafaxine can cause ILD. PMID:25237379

Oh, Serim; Kim, Hyera; Kim, Minjung; Choi, Sun Ha; Seo, Hyewon; Park, Tae-In

2014-01-01

305

Granulomatous lung disease in a patient with a family history of hematological disorders.  

PubMed

A 29-year old patient presented with granulomatous lung disease and a family history of myelodysplastic syndrome/acute myeloid leukemia. She appeared to be a carrier of a mutation in the transcription factor GATA2. The case adds to the recent described heterogeneous clinical manifestations and syndromes in which, against a background of hematologic disorders, GATA2 mutations have been demonstrated, such as the Monomac and Emberger syndromes. In patients with a granulomatous disease and a history of (familial) hematologic disorders, the occurence of GATA2 mutations should be considered, as to gain further insight in the occurrence of granulomatous disease in a possible distinct phenotype among GATA2 mutation carriers. PMID:25591147

Overbeek, Maria; Van de Loosdrecht, Arjen; Vonk-Noordegraaf, Anton

2015-01-01

306

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

307

Human multipotent stromal cells attenuate lipopolysaccharide-induced acute lung injury in mice via secretion of tumor necrosis factor-?-induced protein 6  

Microsoft Academic Search

Introduction  Multipotent stromal cells (MSCs) are currently in clinical trials for a number of inflammatory diseases. Recent studies have\\u000a demonstrated the ability of MSCs to attenuate inflammation in rodent models of acute lung injury (ALI) suggesting that MSCs\\u000a may also be beneficial in treating ALI.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  To better understand how human MSCs (hMSCs) may act in ALI, the lungs of immunocompetent mice

Svitlana Danchuk; Joni H Ylostalo; Fokhrul Hossain; Randy Sorge; Austin Ramsey; Ryan W Bonvillain; Joseph A Lasky; Bruce A Bunnell; David A Welsh; Darwin J Prockop; Deborah E Sullivan

2011-01-01

308

[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

309

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

310

Immunoglobulin G4-related lung disease: A disease with many different faces  

PubMed Central

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, Philip; Mattman, André; Wilcox, Pearce G; Wright, Joanne L; Sin, Don D

2013-01-01

311

Phospholipase A2 mediates nitric oxide production by alveolar macrophages and acute lung injury in pancreatitis.  

PubMed Central

OBJECTIVE: Reportedly, nitric oxide (NO) derived from alveolar macrophages (AMs) and increased serum phospholipase A2 (PLA2) activity are associated with the pathogenesis of lung injury in acute pancreatitis. The authors examined the possibility that PLA2 causes, in part, the induction of NO production by AMs in pancreatitis. METHODS: Pancreatitis was induced in rats by selective pancreatic duct ligation (SPL). AMs were stimulated with PLA2 or SPL rat serum, with or without administration of the PLA2 inhibitor quinacrine. Then NO production from the AMs was measured by the Griess method, inducible NO synthase mRNA expression of AMs was analyzed by the reverse transcription-polymerase chain reaction, and cytotoxic effects of AMs on human umbilical vein endothelial cells was examined by a 51Cr release assay. In vivo, the effect of quinacrine on lung injury was determined by measuring the arterial blood oxygen pressure (PaO2), lung weight, and lung permeability using Evans blue dye concentration of SPL rat. RESULTS: In vitro, the serum with high PLA2 activity induced NO production by rat AMs. PLA2 (50 ng/ml) induced significant amounts of NO production, inducible NO synthase mRNA expression, and cytotoxicity toward the human umbilical vein endothelial cells in normal rat AMs, and these activities were significantly inhibited by quinacrine. In vivo, rats with pancreatitis that were given quinacrine showed decreased concentrations of NO2- and NO3- in the bronchoalveolar lavage fluid, and the PaO2, lung edema, and lung permeability were improved significantly. CONCLUSION: PLA2 induces AMs to release NO, which contributes to lung injury in acute pancreatitis. This lung injury was prevented by the administration of the PLA2 inhibitor quinacrine. Images Figure 4. PMID:10077051

Tsukahara, Y; Morisaki, T; Horita, Y; Torisu, M; Tanaka, M

1999-01-01

312

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

SciTech Connect

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

Vallyathan, V.; Shi, Xianglin [National Inst. for Occupational Safety and Health, Morgantown, WV (United States)

1997-02-01

313

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

PubMed Central

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

Vallyathan, V; Shi, X

1997-01-01

314

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

315

Morphologic changes leading to bronchiolitis obliterans in a patient with delayed non-infectious lung disease after allogeneic bone marrow transplantation  

Microsoft Academic Search

A 37-year-old man developed delayed non-infectious lung disease after undergoing bone marrow transplantation (BMT) for acute myeloid leukaemia. Over a 15-month period, the progression of morphologic changes from cellular interstitial pneumonia to bronchiolitis obliterans organizing pneumonia and cicatricial bronchiolitis obliterans was documented. Pulmonary function tests, high-resolution CT, bronchoalveolar lavage, lung biopsy and extensive microbiological studies were used as diagnostic tools

R Trisolini; G Bandini; M Stanzani; M Chilosi; A Cancellieri; M Boaron; V Poletti

2001-01-01

316

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. ...

317

Low molecular weight heparin may prevent acute lung injury induced by sepsis in rats.  

PubMed

The purpose of this study was to assess the protective effect of low molecular weight heparin (LMWH) on acute lung injury (ALI) in rats induced by sepsis. Rat ALI model was reproduced by cecal ligation and puncture (CLP). All rats were randomly divided into three groups (n=50): control group (A), ALI group (B), and LMWH-treated group (C). Group A received a sham operation and the other groups underwent CLP operation. Groups A and B accepted intraperitoneal injection (i.p.) of normal saline (NS) at a dose of 2.0mlkg(-1) and ceftriaxone (30mgkg(-1)), group C was intraperitoneally injected with additional LMWH (150Ukg(-1)) except saline and ceftriaxone. Blood was collected and lung tissue was harvested at the designated time points for analysis. The lung specimens were harvested for morphological studies, immunohistochemistry examination. Lung tissue edema was evaluated by tissue water content. The levels of lung tissue myeloperoxidase (MPO) were determined. Meanwhile, the nuclear factor-kappa B (NF-?B) activation, tumor necrosis factor-? (TNF-?), interleukin-1? (IL-1?) levels, high mobility group box 1 (HMGB1) and intercellular adhesion molecule-1 (ICAM-1) protein levels in the lung were studied. There was a significant difference in each index between groups A and B (P<0.05). Treatment with LMWH significantly decreased the expression of TNF-?, IL-1?, HMGB1 and ICAM-1 in the lungs of ALI rats. Similarly, treatment with LMWH dramatically diminished sepsis-induced neutrophil sequestration and markedly reduced the enhanced lung permeability. In the present study, LMWH administration inhibited the nuclear translocation of NF-?B in the lungs. These data suggest that LMWH attenuates inflammation and ameliorates lung pathology in CLP-induced sepsis in a rat model. PMID:25497831

Ning, Fangyu; Wang, Xiaozhi; Shang, Li; Wang, Tao; Lv, Changjun; Qi, Zhijiang; Wu, Dawei

2015-02-15

318

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

PubMed Central

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

Lippmann, M

1990-01-01

319

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

PubMed

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

Lippmann, M

1990-08-01

320

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

321

[Protective effect against monoammonium glycyrrhizinate on lipopolysaccharide-induced acute lung injury in mice].  

PubMed

The aim of this study is to investigate the effect of monoammonium glycyrrhizinate (MAG) on lipopolysaccharide (LPS) -induced acute lung injury (ALI) and its anti-inflammatory mechanism in mice. All male ICR mice were randomly divided into six groups: LPS group; control group; MAG 3, 10, and 30 mg x kg(-1) groups; and dexamethasone (DXM) 5 mg x kg(-1) group. Lung dry weight and wet weight percentage and permeability were detected. Neutrophil infiltration in bronchoalveolar lavage fluid (BALF) and lung tissues was detected by cell count and morphological analysis. The levels of TNF-alpha and IL-10 in lung were detected by ELISA. MPO activity was determined followed the specification. MAG induced a decrease in lung wet weight/dry weight ratio, and significantly decreased in total leucocyte number and neutrophil percentage in the BALF, and MPO activity of lung in a dose-dependent manner. Importantly, It could up-regulate the IL-10 level and down-regulate the TNF-alpha level in the lung tissue of ALI mice. These results suggested that the protective effect of MAG in mice on LPS induced ALI was associated with the regulation of TNF-alpha/IL-10 balance, and MAG maybe a potentially treatment for ALI/ARDS. PMID:18050737

Tang, Hui-Fang; Mao, Lian-Gen; Jiang, Ruo-An; Qian, Yun; Chen, Ji-Qiang

2007-09-01

322

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

323

Oxygenation effect of interventional lung assist in a lavage model of acute lung injury: a prospective experimental study  

PubMed Central

Introduction The aim of the study was to test the hypothesis that a pumpless arteriovenous extracorporeal membrane oxygenator (interventional lung assist (ILA)) does not significantly improve oxygenation in a lavage model of acute lung injury. Methods The study was designed as a prospective experimental study. The experiments were performed on seven pigs (48–60 kg body weight). The pigs were anesthetized and mechanically ventilated. Both femoral arteries and one femoral vein were cannulated and connected with ILA. Acute lung injury was induced by repeated bronchoalveolar lavage until the arterial partial pressure of O2 was lower than 100 Torr for at least 30 minutes during ventilation with 100% O2. Results ILA was applied with different blood flow rates through either one or both femoral arteries. Measurements were repeated at different degrees of pulmonary gas exchange impairment with the pulmonary venous admixture ranging from 35.0% to 70.6%. The mean (± standard deviation) blood flow through ILA was 15.5 (± 3.9)% and 21.7 (± 4.9)% of cardiac output with one and both arteries open, respectively. ILA significantly increased the arterial partial pressure of O2 from 64 (± 13) Torr to 71 (± 14) Torr and 74 (± 17) Torr with blood flow through one and both femoral arteries, respectively. O2 delivery through ILA increased with extracorporeal shunt flow (36 (± 14) ml O2/min versus 47 (± 17) ml O2/min) and reduced arterialization of the inlet blood. Pulmonary artery pressures were significantly reduced when ILA was in operation. Conclusion Oxygenation is increased by ILA in severe lung injury. This effect is significant but small. The results indicate that the ILA use may not be justified if the improvement of oxygenation is the primary therapy goal. PMID:16606436

Zick, Günther; Frerichs, Inéz; Schädler, Dirk; Schmitz, Gunnar; Pulletz, Sven; Cavus, Erol; Wachtler, Felix; Scholz, Jens; Weiler, Norbert

2006-01-01

324

Terminology in chronic obstructive lung diseases.  

PubMed Central

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

Fletcher, C H

1978-01-01

325

Vitamin D Deficiency and the Lung: Disease Initiator or Disease Modifier?  

PubMed Central

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.

2013-01-01

326

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

327

Trace metal lung disease: in vitro interaction of hard metals with human lung and plasma components.  

PubMed

Hard metal pneumoconiosis is an occupational pulmonary disease caused by long-term exposure to dust produced in the hard metal industry. In vitro experiments have been carried out to study the solubility and metabolic behaviour in human lung tissue and plasma of hard metal alloy constituents such as cobalt, tungsten, tantalum, titanium and niobium. The experiments were carried out using 60Co, 187W, 182Ta, 44Ti and 95Nb radiotracers in combination with neutron activation, radio-release tests and gel filtration techniques. Leaching experiments from neutron-irradiated hard metal dust showed that cobalt was highly soluble, especially in the lung cytosol and plasma, in comparison with tantalum and tungsten. The gel filtration experiments showed three biochemical pools of cobalt in both lung and plasma components, in accordance with the hypothesis that cobalt represents the allergic factor in the development of hard metal disease. High affinity for proteins was observed for Nb, Ta and Ti, but not for W, in agreement with the dissimilar biological half-lives of these elements in the body. The different ability of the metals to interact with biochemical components and to be solubilized in biological media may explain the various degrees of retention in the lung, which would influence the metabolic pathways. This would explain the presence of Co, Ta and W in body fluids, as well as in the public hair and toenails of hard metal workers. PMID:2205918

Edel, J; Sabbioni, E; Pietra, R; Rossi, A; Torre, M; Rizzato, G; Fraioli, P

1990-06-01

328

Protective effect of U74500A on phorbol myristate acetate-induced acute lung injury.  

PubMed

1. The present study was designed to determine whether U74500A could ameliorate acute lung injury (ALI) induced by phorbol myristate acetate (PMA) in our rat isolated lung model compared with any amelioration induced by dimethylthiourea (DMTU), superoxide dismutase (SOD) and catalase. 2. Acute lung injury was induced successfully by PMA during 60 min of observation. At 2 microg/kg, PMA elicited a significant increase in microvascular permeability (measured using the capillary filtration coefficient Kfc), lung weight gain, the lung weight/bodyweight ratio, pulmonary arterial pressure and protein concentration of the bronchoalveolar lavage fluid. 3. Pretreatment with 1.5 mg/kg U74500A significantly attenuated ALI; there was no significant increase in any parameters measured, except for pulmonary arterial pressure. The protective effect of U74500A was approximately the same as that of 600 mg/kg DMTU. However, 6000 U/kg SOD, 50,000 U/kg catalase and 6000 U/kg SOD + 50,000 U/kg catalase had no protective effect. 4. These experimental data suggest that U74500A significantly ameliorates ALI induced by PMA in rats. PMID:15298545

Chu, Shi-Jye; Chang, Deh-Ming; Wang, David; Lin, Hen-I; Lin, Shih-Hua; Hsu, Kang

2004-08-01

329

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

330

NLRP3 Inflammasome Activation Is Essential for Paraquat-Induced Acute Lung Injury.  

PubMed

The innate immune response is important in paraquat-induced acute lung injury, but the exact pathways involved are not elucidated. The objectives of this study were to determine the specific role of the NLRP3 inflammasome in the process. Acute lung injury was induced by administering paraquat (PQ) intraperitoneally. NLRP3 inflammasome including NLRP3, ASC, and caspase-1 mRNA and protein expression in lung tissue and IL-1? and IL-18 levels in BALF were detected at 4, 8, 24, and 72 h after PQ administration in rats. Moreover, rats were pretreated with 10, 30, and 50 mg/kg NLRP3 inflammasome blocker glybenclamide, respectively, 1 h before PQ exposure. At 72 h after PQ administration, lung histopathology changes, NLRP3, ASC, and caspase-1 protein expression, as well as secretion of cytokines including IL-1? and IL-18 in BALF were investigated. The NLRP3 inflammasome including NLRP3, ASC, caspase-1 expression, and cytokines IL-1? and IL-18 levels in PQ poisoning rats were significantly higher than that in the control group. NLRP3 inflammasome blocker glybenclamide pretreatment attenuated lung edema, inhibited the NLRP3, ASC, and caspase-1 activation, and reduced IL-1? and IL-18 levels in BALF. In the in vitro experiments, IL-1? and IL-18 secreted from RAW264.7 mouse macrophages treated with paraquat were attenuated by glybenclamide. In conclusion, paraquat can induce IL-1?/IL-18 secretion via NLRP3-ASC-caspase-1 pathway, and the NLRP3 inflammasome is essential for paraquat-induced acute lung injury. PMID:25338942

Liu, Zhenning; Zhao, Hongyu; Liu, Wei; Li, Tiegang; Wang, Yu; Zhao, Min

2015-02-01

331

Bradykinin inducible receptor is essential to lipopolysaccharide-induced acute lung injury in mice.  

PubMed

Lipopolysaccharides from gram-negative bacteria are amongst the most common causative agents of acute lung injury, which is characterized by an inflammatory response, with cellular infiltration and the release of mediators/cytokines. There is evidence that bradykinin plays a role in lung inflammation in asthma but in other types of lung inflammation its role is less clear. In the present study we evaluated the role of the bradykinin B1 receptor in acute lung injury caused by lipopolysaccharide inhalation and the mechanisms behind bradykinin actions participating in the inflammatory response. We found that in C57Bl/6 mice, the bradykinin B1 receptor expression was up-regulated 24h after lipopolysaccharide inhalation. At this time, the number of cells and protein concentration were significantly increased in the bronchoalveolar lavage fluid and the mice developed airway hyperreactivity to methacholine. In addition, there was an increased expression of tumor necrosis factor-alpha, interleukin-1 beta and interferon-gamma and chemokines (monocytes chemotactic protein-1 and KC) in the bronchoalveolar lavage fluid and in the lung tissue. We then treated the mice with a bradykinin B1 receptor antagonist, R-954 (Ac-Orn-[Oic2, alpha-MePhe5, D-betaNal7, Ile8]desArg9-bradykinin), 30 min after lipopolysaccharide administration. We observed that this treatment prevented the airway hyperreactivity as well as the increased cellular infiltration and protein content in the bronchoalveolar lavage fluid. Moreover, R-954 inhibited the expression of cytokines/chemokines. These results implicate bradykinin, acting through B1 receptor, in the development of acute lung injury caused by lipopolysaccharide inhalation. PMID:20153312

Campanholle, Gabriela; Landgraf, Richardt G; Borducchi, Erica; Semedo, Patricia; Wang, Pamela H M; Amano, Mariane T; Russo, Momtchilo; Pacheco-Silva, Alvaro; Jancar, Sonia; Camara, Niels O S

2010-05-25

332

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

333

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

334

Cytokine levels in pleural fluid as markers of acute rejection after lung transplantation*  

PubMed Central

Our objective was to determine the levels of lactate dehydrogenase, IL-6, IL-8, and VEGF, as well as the total and differential cell counts, in the pleural fluid of lung transplant recipients, correlating those levels with the occurrence and severity of rejection. We analyzed pleural fluid samples collected from 18 patients at various time points (up to postoperative day 4). The levels of IL-6, IL-8, and VEGF tended to elevate in parallel with increases in the severity of rejection. Our results suggest that these levels are markers of acute graft rejection in lung transplant recipients. PMID:25210966

de Camargo, Priscila Cilene León Bueno; Afonso, José Eduardo; Samano, Marcos Naoyuki; Acencio, Milena Marques Pagliarelli; Antonangelo, Leila; Teixeira, Ricardo Henrique de Oliveira Braga

2014-01-01

335

Update in diffuse parenchymal lung disease 2013.  

PubMed

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

Rosas, Ivan O; Kaminski, Naftali

2015-02-01

336

Vitamin D to prevent acute lung injury following oesophagectomy (VINDALOO): study protocol for a randomised placebo controlled trial  

PubMed Central

Background Acute lung injury occurs in approximately 25% to 30% of subjects undergoing oesophagectomy. Experimental studies suggest that treatment with vitamin D may prevent the development of acute lung injury by decreasing inflammatory cytokine release, enhancing lung epithelial repair and protecting alveolar capillary barrier function. Methods/Design The ‘Vitamin D to prevent lung injury following oesophagectomy trial’ is a multi-centre, randomised, double-blind, placebo-controlled trial. The aim of the trial is to determine in patients undergoing elective transthoracic oesophagectomy, if pre-treatment with a single oral dose of vitamin D3 (300,000 IU (7.5 mg) cholecalciferol in oily solution administered seven days pre-operatively) compared to placebo affects biomarkers of early acute lung injury and other clinical outcomes. The primary outcome will be change in extravascular lung water index measured by PiCCO® transpulmonary thermodilution catheter at the end of the oesophagectomy. The trial secondary outcomes are clinical markers indicative of lung injury: PaO2:FiO2 ratio, oxygenation index; development of acute lung injury to day 28; duration of ventilation and organ failure; survival; safety and tolerability of vitamin D supplementation; plasma indices of endothelial and alveolar epithelial function/injury, plasma inflammatory response and plasma vitamin D status. The study aims to recruit 80 patients from three UK centres. Discussion This study will ascertain whether vitamin D replacement alters biomarkers of lung damage following oesophagectomy. Trial registration Current Controlled Trials ISRCTN27673620 PMID:23782429

2013-01-01

337

Acute myeloid leukemia developing in patients with autoimmune diseases  

PubMed Central

Therapy-related acute myeloid leukemia is an unfortunate complication of cancer treatment, particularly for patients with highly curable primary malignancies and favorable life expectancy. The risk of developing therapy-related acute myeloid leukemia also applies to patients with non-malignant conditions, such as autoimmune diseases treated with cytotoxic and/or immunosuppressive agents. There is considerable evidence to suggest that there is an increased occurrence of hematologic malignancies in patients with autoimmune diseases compared to the general population, with a further increase in risk after exposure to cytotoxic therapies. Unfortunately, studies have failed to reveal a clear correlation between leukemia development and exposure to individual agents used for the treatment of autoimmune diseases. Given the dismal outcome of secondary acute myeloid leukemia and the wide range of available agents for treatment of autoimmune diseases, an increased awareness of this risk and further investigation into the pathogenetic mechanisms of acute leukemia in autoimmune disease patients are warranted. This article will review the data available on the development of acute myeloid leukemia in patients with autoimmune diseases. Possible leukemogeneic mechanisms in these patients, as well as evidence supporting the association of their primary immunosuppressive status and their exposure to specific therapies, will also be reviewed. This review also supports the idea that it may be misleading to label leukemias that develop in patients with autoimmune diseases who are exposed to cytotoxic agents as ‘therapy-related leukemias’. A better understanding of the molecular defects in autoimmune disease patients who develop acute leukemia will lead to a better understanding of the association between these two diseases entities. PMID:22180424

Ramadan, Safaa M.; Fouad, Tamer M; Summa, Valentina; Hasan, Syed KH; Lo-Coco, Francesco

2012-01-01

338

Sleep disordered breathing in interstitial lung disease: A review  

PubMed Central

Patients with interstitial lung disease commonly exhibit abnormal sleep architecture and increased sleep fragmentation on polysomnography. Fatigue is a frequent complaint, and it is likely that poor sleep quality is a significant contributor. A number of studies have shown that sleep disordered breathing is prevalent in this population, particularly in the idiopathic pulmonary fibrosis subgroup. The factors that predispose these patients to obstructive sleep apnoea are not well understood, however it is believed that reduced caudal traction on the upper airway can enhance collapsibility. Ventilatory control system instability may also be an important factor, particularly in those with increased chemo-responsiveness, and in hypoxic conditions. Transient, repetitive nocturnal oxygen desaturation is frequently observed in interstitial lung disease, both with and without associated obstructive apnoeas. There is increasing evidence that sleep-desaturation is associated with increased mortality, and may be important in the pathogenesis of pulmonary hypertension in this population. PMID:25516856

Troy, Lauren K; Corte, Tamera J

2014-01-01

339

Staphylococcal enterotoxin B-induced microRNA-155 targets SOCS1 to promote acute inflammatory lung injury.  

PubMed

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; Rieder, Sadiye Amcaoglu; Nagarkatti, Prakash; Nagarkatti, Mitzi

2014-07-01

340

A Comparative Analysis of Bronchial Stricture Following Lung Transplantation in Recipients With and Without Early Acute Rejection  

PubMed Central

Background Risk factors and outcomes of bronchial stricture following lung transplantation are not well defined. An association between acute rejection and development of stricture has been suggested in small case series. We evaluated this relationship using a large, national registry. Methods All lung transplants between 04/1994 and 12/2008 per the United Network for Organ Sharing database were analyzed. Generalized linear models were used to determine the association between early rejection and development of stricture after adjusting for potential confounders. The association of stricture with postoperative lung function and overall survival was also evaluated. Results 9,335 patients were included for analysis. The incidence of stricture was 11.5% (=1,077/9,335) with no significant change in incidence during the study period (p=0.13). Early rejection was associated with a significantly greater incidence of stricture [adjusted odds ratio (AOR) 1.40, 95% confidence interval (CI) 1.22 - 1.61; p<0.0001]. Male gender, restrictive lung disease, and pre-transplant requirement for hospitalization were also associated with stricture. Those who developed stricture had and a lower postoperative peak percent predicted forced expiratory volume at one second (median 74% vs. 86% for bilateral transplants only, p<0.0001), shorter unadjusted survival (median 6.09 vs. 6.82 years, p<0.001) and increased risk of death after adjusting for potential confounders (adjusted hazard ratio 1.13, CI 1.03 - 1.23, p=0.007). Conclusions Early rejection is associated with an increased incidence of stricture. Recipients with stricture demonstrate worse postoperative lung function and survival. Prospective studies may be warranted to further assess causality and the potential for coordinated rejection and stricture surveillance strategies to improve postoperative outcomes. PMID:23870829

Castleberry, Anthony W.; Worni, Mathias; Kuchibhatla, Maragatha; Lin, Shu S.; Snyder, Laurie D.; Shofer, Scott L.; Palmer, Scott M.; Pietrobon, Ricardo S.; Davis, R. Duane; Hartwig, Matthew G.

2014-01-01

341

Involvement of Rho kinase (ROCK) in sepsis-induced acute lung injury  

PubMed Central

Indirect acute lung injury is associated with high morbidity and mortality. We investigated the link between Rho kinase (ROCK) activation and apoptotic cell death in sepsis induced acute lung injury. This hypothesis was tested by administering a specific, selective inhibitor of ROCK (Y-27632) to rats subjected to cecal ligation and puncture (CLP). Rats were randomly divided into 4 groups as; sham-operated, sham + Y-27632, CLP and CLP + Y-27632. Twenty-four hours later, each experiment was terminated and lungs analyzed. Histopathology was assessed by hematoxylin-eosin staining and the presence of apoptosis was evaluated through the TUNEL assay. Pulmonary activity of caspase 3 and ROCK 1 & 2 were measured by western blot. Interstitial edema, severely damaged pulmonary architecture with massive infiltration of the inflammatory cells and an increase in lung tissue TBARS levels as well as 3-NT to total tyrosine ratios were observed in untreated CLP animals. Pretreatment of animals with Y-27632, reduced lung injury in the CLP induced septic rats in each of these parameters of lung injury (p<0.05). Western immunoblot revealed active caspase cleavage and increased expression of active fragment of ROCK 1 & 2 in the CLP group. TUNEL assay showed an increase in percentage of apoptotic cells when comparing the CLP group with the CLP + Y-27632 group. These results suggest an important role of Rho kinase in sepsis induced lung injury by a mechanism that might be related to oxidative and/or nitrosative stress mediated caspase cleavage leading to apoptosis. PMID:22295165

Cinel, Ismail; Ark, Mustafa; Dellinger, Phillip; Karabacak, Tuba; Tamer, Lulufer; Cinel, Leyla; Michael, Paul; Hussein, Shaimaa; Parrillo, Joseph E.; Kumar, Anand; Kumar, Aseem

2012-01-01

342

Outcome of lung cancer patients admitted to the intensive care unit with acute respiratory failure  

PubMed Central

Background: Previous studies have shown that the outcome of lung cancer patients who were admitted to the Intensive Care Unit (ICU), especially those requiring mechanical ventilation, is extremely poor. The present study was conducted in order to assess the outcome of a recent cohort of lung cancer patients admitted to the ICU with acute respiratory failure. Methods: A retrospective analysis of the medical records of 105 lung cancer patients who were admitted to the ICU between January 2008 and January 2011 was performed. Severity of illness on the first day of ICU admission was assessed using the acute physiology and chronic health evaluation (APACHE) II and the sequential organ failure assessment (SOFA) scoring systems. Associated organ failure was determined according to the Knaus criteria. Results: Eighty four (80%) patients were diagnosed with non-small cell lung cancer, 14 (13.3%) with small cell lung cancer, one patient with mesothelioma, and in the remaining 6 patients, the type of lung cancer could not be determined. Significant factors on admission were APACHE II and SOFA scores, poor performance status and severe comorbidity. During ICU stay, the main risk factors for poor outcome were the long term mechanical ventilation duration, use of vasopressors, more than two organ system failures and septic condition. The overall ICU, hospital and 6-month mortality rates were 44.7% (47/105), 56.1% (59/105) and 77.1% (81/105) respectively. Conclusions: The present data show that the medical intensive care unit outcome of lung cancer patients is improving. Further studies of patients selected to ICU admission are needed to assess long-term mortality, quality of life, ability to continue chemotherapy and economic cost. PMID:23935346

Anisoglou, S; Asteriou, C; Barbetakis, N; Kakolyris, S; Anastasiadou, G; Pnevmatikos, I

2013-01-01

343

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

344

Acute infectious bursal disease in poultry: A review  

Microsoft Academic Search

This review is focused on the acute form of infectious bursal disease (IBD) caused by very virulent IBD virus (vvIBDV). First described in Europe about 10 years ago, this new form of the disease has rapidly spread all over the world, causing dramatic losses; after a decade, it still represents a considerable threat to the poultry industry. Emergence of the

Thierry P. Van Den Berg

2000-01-01

345

[The coincidence of acute intermittent porphyria and Crohn's disease].  

PubMed

In the course of four weeks, tetraparesis developed in a 28-year-old man with Crohn's disease for the last six years, treated with glucocorticoids and sulphasalazine. The cause was acute intermittent porphyria which had been previously overlooked because of the similar abdominal symptoms of Crohn's disease. Treatment with glucose, propranolol and haemarginate failed to bring about any improvement, but there was a remission of the porphyria. This case demonstrates that diagnosis of acute intermittent porphyria in the presence of Crohn's disease is difficult, and if delayed therapeutic measures in the face of persisting neurological complications are of little benefit. PMID:2340805

Beckh, K; Sieg, I; Stellwaag, M; Blanke, H; Arnold, R; Doss, M

1990-05-25

346

Supportive and Palliative Care of Advanced Nonmalignant Lung Disease  

Microsoft Academic Search

Supportive and palliative care is an interdisciplinary challenge with the aims of symptom relief and improvement of quality of life in end-stage patients. Main complaints of patients with advanced nonmalignant lung disease are depression and anxiety, dyspnea, pain, and coughing. The discomfort of many physicians, caregivers, and family members with discussions about end-of-life care is one obstacle for the timely

Michael Kreuter; Felix J. F. Herth

2011-01-01

347

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

348

Childhood Interstitial Lung Diseases: An 18-year Retrospective Analysis  

PubMed Central

OBJECTIVE: Childhood interstitial lung diseases (ILD) occur in a variety of clinical contexts. Advances in the understanding of disease pathogenesis and use of standardized terminology have facilitated increased case ascertainment. However, as all studies have been performed at specialized referral centers, the applicability of these findings to general pulmonary practice has been uncertain. The objective of this study was to determine the historical occurrence of childhood ILD to provide information reflecting general pediatric pulmonary practice patterns. METHODS: Childhood ILD cases seen at Vanderbilt Children’s Hospital from 1994 to 2011 were retrospectively reviewed and classified according to the current pediatric diffuse lung disease histopathologic classification system. RESULTS: A total of 93 cases were identified, of which 91.4% were classifiable. A total of 68.8% (64/93) of subjects underwent lung biopsy in their evaluations. The largest classification categories were disorders related to systemic disease processes (24.7%), disorders of the immunocompromised host (24.7%), and disorders more prevalent in infancy (22.6%). Eight cases of neuroendocrine cell hyperplasia of infancy (NEHI) were identified, including 5 that were previously unrecognized before this review. CONCLUSIONS: Our findings demonstrate the general scope of childhood ILD and that these cases present within a variety of pediatric subspecialties. Retrospective review was valuable in recognizing more recently described forms of childhood ILD. As a significant portion of cases were classifiable based on clinical, genetic, and/or radiographic criteria, we urge greater consideration to noninvasive diagnostic approaches and suggest modification to the current childhood ILD classification scheme to accommodate the increasing number of cases diagnosed without lung biopsy. PMID:24081995

Soares, Jennifer J.; Deutsch, Gail H.; Moore, Paul E.; Fazili, Mohammad F.; Austin, Eric D.; Brown, Rebekah F.; Sokolow, Andrew G.; Hilmes, Melissa A.

2013-01-01

349

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

350

[Echocardiographic grading of cor pulmonale in chronic lung diseases].  

PubMed

The extent of right heart strain determines the prognosis of chronic lung disease. The value of a simple semiquantitative echocardiographic grading system for cor pulmonale was assessed in 69 patients (24 females, 45 males, age 61 +/- 12 years, ranging from 28-82 years) suffering from chronic lung disease. The patients were classified by echocardiography into four groups, Grade 0 consisting of those without evidence of right heart strain and three groups showing increasing severity of change (Grade I: right ventricular hypertrophy; Grade II: I + right ventricular dilation; Grade III: II + Dilation of the inferior vena cava). Echocardiographic investigation, at least from the subcostal view, and grading was possible in all patients. A correlation was found between the echocardiographic grading and the mean pulmonary artery pressure (PAP)-normal echo study 15.7 +/- 4.8; grade I 21.1 +/- 5.6; grade II 28.8 +/- 10.2; grade III 39.4 +/- 9.4 mmHg. In addition, patients with stress-induced pulmonary hypertension (PHT) were detected by Doppler echocardiography. 6 of 11 patients with latent PHT already showed evidence of cor pulmonale (4 Grade I and 2 Grade II). In 42 patients (61%) the systolic PAP was estimated by measuring the velocity of the tricuspid insufficiency jet with Doppler, and these data correlated closely with the invasive data (p < 0.001; r = 0.81). Doppler echocardiography for evaluation of cor pulmonale is feasible even in patients with chronic lung disease and limited acoustic windows. Semiquantitative grading correlates well with invasive data. Here, this technique is useful as a baseline study as well as for the follow-up of patients with chronic lung disease. PMID:7732691

Weihs, W; Picha, R; Schuchlenz, H; Harb, S; Anelli-Monti, B; Harnoncourt, K

1995-01-01

351

Lung Dendritic Cells: Targets for Therapy in Allergic Disease  

Microsoft Academic Search

Dendritic cells (DCs) are crucial in determining the functional outcome of allergen encounter in the lung. Antigen presentation\\u000a by myeloid DCs leads to Th2 sensitization typical of allergic disease, whereas antigen presentation by plas-macytoid DCs serves\\u000a to dampen inflammation. It is increasingly clear that DCs have an antigen presenting function beyond sensitisation. DCs therefore\\u000a constitute a novel target for the

Bart N. Lambrecht; Hamida Hammad

352

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

353

HIF2? signaling inhibits adherens junctional disruption in acute lung injury.  

PubMed

Vascular endothelial barrier dysfunction underlies diseases such as acute respiratory distress syndrome (ARDS), characterized by edema and inflammatory cell infiltration. The transcription factor HIF2? is highly expressed in vascular endothelial cells (ECs) and may regulate endothelial barrier function. Here, we analyzed promoter sequences of genes encoding proteins that regulate adherens junction (AJ) integrity and determined that vascular endothelial protein tyrosine phosphatase (VE-PTP) is a HIF2? target. HIF2?-induced VE-PTP expression enhanced dephosphorylation of VE-cadherin, which reduced VE-cadherin endocytosis and thereby augmented AJ integrity and endothelial barrier function. Mice harboring an EC-specific deletion of Hif2a exhibited decreased VE-PTP expression and increased VE-cadherin phosphorylation, resulting in defective AJs. Mice lacking HIF2? in ECs had increased lung vascular permeability and water content, both of which were further exacerbated by endotoxin-mediated injury. Treatment of these mice with Fg4497, a prolyl hydroxylase domain 2 (PHD2) inhibitor, activated HIF2?-mediated transcription in a hypoxia-independent manner. HIF2? activation increased VE-PTP expression, decreased VE-cadherin phosphorylation, promoted AJ integrity, and prevented the loss of endothelial barrier function. These findings demonstrate that HIF2? enhances endothelial barrier integrity, in part through VE-PTP expression and the resultant VE-cadherin dephosphorylation-mediated assembly of AJs. Moreover, activation of HIF2?/VE-PTP signaling via PHD2 inhibition has the potential to prevent the formation of leaky vessels and edema in inflammatory diseases such as ARDS. PMID:25574837

Gong, Haixia; Rehman, Jalees; Tang, Haiyang; Wary, Kishore; Mittal, Manish; Chatturvedi, Pallavi; Zhao, Youyang; Komorova, Yulia A; Vogel, Stephen M; Malik, Asrar B

2015-02-01

354

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

PubMed Central

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

Rom, William N.; Weiden, Michael D.

2014-01-01

355

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

356

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

357

Large ABCA3 and SFTPC Deletions Resulting in Lung Disease  

PubMed Central

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

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

2013-01-01

358

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...

359

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

PubMed

Pulmonary complications are an important extra-articular feature of autoimmune rheumatic diseases and a major cause of mortality. The underlying pathogenesis probably involves multiple cellular compartments, including the epithelium, lung fibroblasts, and the innate and adaptive immune system. Heterogeneity in the extent and progression of lung fibrosis probably reflects differences in underlying pathogenic mechanisms. Growing understanding of the key pathogenic drivers of lung fibrosis might lead to the development of more effective targeted therapies to replicate the treatment advances in other aspects of these diseases. Interstitial lung disease (ILD) in connective tissue disease (CTD) is characterized using the classification of the idiopathic interstitial pneumonias. Systemic sclerosis is most frequently associated with ILD and, in most of these patients, ILD manifests as a histological pattern of nonspecific interstitial pneumonia. Conversely, in rheumatoid arthritis, the pattern of ILD is most often usual interstitial pneumonia. The key goals of clinical assessment of patients with both ILD and CTD are the detection of ILD and prognostic evaluation to determine which patients should be treated. Data from treatment trials in systemic sclerosis support the use of immunosuppressive therapy, with the treatment benefit largely relating to the prevention of progression of lung disease. PMID:25266451

Wells, Athol U; Denton, Christopher P

2014-12-01

360

Time-dependence of lung injury in mice acutely exposed to cylindrospermopsin.  

PubMed

Cylindrospermopsin is a cyanobacterial toxin of increasing environmental importance, as it can lead to disease if orally or intravenously absorbed. However, its in vivo lung impairment has not been documented. Thus, we aimed at verifying whether cylindrospermopsin can induce lung injury and establish its putative dependence on the time elapsed since exposure. BALB/c mice were intratracheally injected with either saline (NaCl 0.9%, 50 ?L, SAL group, n = 12) or a sublethal dose (70 ?g/kg) of semi-purified extract of cylindrospermopsin (CYN groups, n = 52). Lung mechanics, histological and biochemical analyses, and cylindrospermopsin presence in lungs and liver were determined in independent groups at 2, 8, 24, 48, and 96 h after cylindrospermopsin instillation. There was a significant increase in static elastance at 24 and 48 h after exposure to cylindrospermopsin, while viscoelastic component of elastance and viscoelastic pressure rose at 48 h. Alveolar collapse augmented in CYN groups at 8 h. A significant increase in polymorphonuclear influx into lung parenchyma, as well as a higher myeloperoxidase activity started off at 24 h. Exposure to cylindrospermopsin increased lipid peroxidation and superoxide dismutase activity and reduced catalase activity in CYN groups. The toxin was detected in lungs and liver of all CYN mice. In conclusion, cylindrospermopsin exposure impaired lung mechanics, which was preceded by lung parenchyma inflammation and oxidative stress. PMID:22750219

Oliveira, V R; Carvalho, G M C; Avila, M B; Soares, R M; Azevedo, S M F O; Ferreira, T S; Valença, S S; Faffe, D S; Zin, Walter Araujo

2012-10-01

361

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

362

Effect of acute hypoxic hypoxia on the thickness of the lung air-blood barrier  

Microsoft Academic Search

The arithmetic mean and harmonic mean thickness of the air-blood barrier (ABB) of the lungs and the arithmetic mean thickness of its individual layers were studied by morphometric analysis of electron micrographs obtained from rats of different ages under normal conditions and after inhalation of a gas mixture of N2 with 11.2% O2 for 30 min. Acute hypoxic leads to

T. N. Kovalenko; V. P. Pozharov; M. M. Seredenko

1980-01-01

363

Naringin attenuates acute lung injury in LPS-treated mice by inhibiting NF-?B pathway  

Microsoft Academic Search

Naringin has been reported as an effective anti-inflammatory compound. We previously showed that naringin had antitussive effect on experimentally induced cough in guinea pigs. However, the effects and mechanism of naringin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice are not fully understood. In this study, our aim was to evaluate the anti-inflammatory activities of naringin on LPS-induced ALI

Ying Liu; Hao Wu; Yi-chu Nie; Jia-ling Chen; Wei-wei Su; Pei-bo Li

2011-01-01

364

Acute Phase Reactants as Novel Predictors of Cardiovascular Disease  

PubMed Central

Acute phase reaction is a systemic response which usually follows a physiological condition that takes place in the beginning of an inflammatory process. This physiological change usually lasts 1-2 days. However, the systemic acute phase response usually lasts longer. The aim of this systemic response is to restore homeostasis. These events are accompanied by upregulation of some proteins (positive acute phase reactants) and downregulation of others (negative acute phase reactants) during inflammatory reactions. Cardiovascular diseases are accompanied by the elevation of several positive acute phase reactants such as C-reactive protein (CRP), serum amyloid A (SAA), fibrinogen, white blood cell count, secretory nonpancreatic phospholipase 2-II (sPLA2-II), ferritin, and ceruloplasmin. Cardiovascular disease is also accompanied by the reduction of negative acute phase reactants such as albumin, transferrin, transthyretin, retinol-binding protein, antithrombin, and transcortin. In this paper, we will be discussing the biological activity and diagnostic and prognostic values of acute phase reactants with cardiovascular importance. The potential therapeutic targets of these reactants will be also discussed. PMID:24049653

Ahmed, M. S.; Jadhav, A. B.; Hassan, A.; Meng, Qing H.

2012-01-01

365

Comparison of thermodilution measured extravascular lung water with chest radiographic assessment of pulmonary oedema in patients with acute lung injury  

PubMed Central

Background Acute lung injury and the acute respiratory distress syndrome (ALI/ARDS) are characterized by pulmonary oedema, measured as extravascular lung water (EVLW). The chest radiograph (CXR) can potentially estimate the quantity of lung oedema while the transpulmonary thermodilution method measures the amount of EVLW. This study was designed to determine whether EVLW as estimated by a CXR score predicts EVLW measured by the thermodilution method and whether changes in EVLW by either approach predict mortality in ALI/ARDS. Methods Clinical data were collected within 48 hours of ALI/ARDS diagnosis and daily up to 14 days on 59 patients with ALI/ARDS. Two clinicians scored each CXR for the degree of pulmonary oedema, using a validated method. EVLW indexed to body weight was measured using the single indicator transpulmonary thermodilution technique. Results The CXR score had a modest, positive correlation with the EVLWI measurements (r?=?0.35, p?

2013-01-01

366

Rotating Night Shift Work May Raise Risks of Heart Disease, Lung Cancer: Study  

MedlinePLUS

... Shift Work May Raise Risks of Heart Disease, Lung Cancer: Study Research can't prove cause-and-effect, ... a 25 percent higher risk of death from lung cancer, according to the study. The findings are to ...

367

Citral inhibits lipopolysaccharide-induced acute lung injury by activating PPAR-?.  

PubMed

Citral, a component of lemongrass oil, has been reported to have many pharmacological activities such as anti-bacterial and anti-inflammatory effects. However, the effects of citral on acute lung injury (ALI) and the molecular mechanisms have not been reported. The aim of this study was to detect the effects of citral on lipopolysaccharide (LPS)-induced acute lung injury and investigate the molecular mechanisms. LPS-induced acute lung injury model was used to detect the anti-inflammatory effect of citral in vivo. The alveolar macrophages were used to investigate the molecular mechanism of citral in vitro. The results showed that pretreatment with citral remarkably attenuated pulmonary edema, histological severities, TNF-?, IL-6 and IL-1? production in LPS-induced ALI in vivo. In vitro, citral inhibited LPS-induced TNF-?, IL-6 and IL-1? production in alveolar macrophages. LPS-induced NF-?B activation was also inhibited by citral. Furthermore, we found that citral activated PPAR-? and the anti-inflammatory effects of citral can be reversed by PPAR-? antagonist GW9662. In conclusion, this is the first to demonstrate that critral protects LPS-induced ALI in mice. The anti-inflammatory mechanism of citral is associated with activating PPAR-?, thereby inhibiting LPS-induced inflammatory response. PMID:25281205

Shen, Yongbin; Sun, Zhanfeng; Guo, Xiaotong

2015-01-15

368

Effect of methylsulfonylmethane on paraquat-induced acute lung and liver injury in mice.  

PubMed

Methylsulfonylmethane (MSM) is a natural organosulfur compound that exhibits antioxidative and anti-inflammatory effects. This study was carried out to investigate the effect of MSM on paraquat (PQ)-induced acute lung and liver injury in mice. A single dose of PQ (50 mg/kg, i.p.) induced acute lung and liver toxicity. Mice were treated with MSM (500 mg/kg/day, i.p.) for 5 days. At the end of the experiment, animals were euthanized, and lung and liver tissues were collected for histological and biochemical analysis. Tissue samples were used to determine malondialdehyde (MDA), myeloperoxidase (MPO), catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), and tumor necrosis factor-? (TNF-?) levels. Blood samples were used to measure plasma alanine transaminase (ALT), ?-glutamyl transferase (GGT), and alkaline phosphatase (ALP). Histological examination indicated that MSM decreased lung and liver damage caused by PQ. Biochemical results showed that MSM treatment significantly reduced tissue levels of MDA, MPO, and TNF-?, while increased the levels of SOD, CAT, and GSH compared with PQ group. MSM treatment also significantly reduced plasma levels of ALT, GGT, and ALP. These findings suggest that MSM as a natural product attenuates PQ-induced pulmonary and hepatic oxidative injury. PMID:23595869

Amirshahrokhi, Keyvan; Bohlooli, Shahab

2013-10-01

369

Suppression of Acute Lung Inflammation by Intracellular Peptide Delivery of a Nuclear Import Inhibitor  

PubMed Central

Acute lung inflammation is a potentially life-threatening complication of infections due to community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), a worldwide emerging pathogen, which causes necrotizing pneumonia and acute respiratory distress syndrome (ARDS). MRSA virulence factors encompass immunotoxins termed superantigens that contribute to lung inflammation. In this study, we demonstrate that staphylococcal enterotoxin B (SEB)-induced lung inflammation is attenuated by a cell-penetrating peptide nuclear import inhibitor of nuclear factor (NF)-?B and other stress-responsive transcription factors (SRTFs). This inhibitor suppressed production of a wide spectrum of cytokines and chemokines induced by direct SEB airway exposure. Consequently, trafficking of neutrophils, monocytes/macrophages, and lymphocytes to the bronchoalveolar space was significantly reduced while vascular injury, manifested by increased permeability and protein leakage, was attenuated. Moreover, induction of systemic proinflammatory cytokines and chemokines in response to direct SEB airway exposure was reduced. Thus, intracellular delivery of a nuclear import inhibitory peptide suppresses respiratory and systemic expression of key mediators of lung inflammation evoked by SEB. PMID:19259070

Liu, Danya; Zienkiewicz, Jozef; DiGiandomenico, Antonio; Hawiger, Jacek

2009-01-01

370

Integrative assessment of chlorine-induced acute lung injury in mice.  

PubMed

The genetic basis for the underlying individual susceptibility to chlorine-induced acute lung injury is unknown. To uncover the genetic basis and pathophysiological processes that could provide additional homeostatic capacities during lung injury, 40 inbred murine strains were exposed to chlorine, and haplotype association mapping was performed. The identified single-nucleotide polymorphism (SNP) associations were evaluated through transcriptomic and metabolomic profiling. Using ? 10% allelic frequency and ? 10% phenotype explained as threshold criteria, promoter SNPs that could eliminate putative transcriptional factor recognition sites in candidate genes were assessed by determining transcript levels through microarray and reverse real-time PCR during chlorine exposure. The mean survival time varied by approximately 5-fold among strains, and SNP associations were identified for 13 candidate genes on chromosomes 1, 4, 5, 9, and 15. Microarrays revealed several differentially enriched pathways, including protein transport (decreased more in the sensitive C57BLKS/J lung) and protein catabolic process (increased more in the resistant C57BL/10J lung). Lung metabolomic profiling revealed 95 of the 280 metabolites measured were altered by chlorine exposure, and included alanine, which decreased more in the C57BLKS/J than in the C57BL/10J strain, and glutamine, which increased more in the C57BL/10J than in the C57BLKS/J strain. Genetic associations from haplotype mapping were strengthened by an integrated assessment using transcriptomic and metabolomic profiling. The leading candidate genes associated with increased susceptibility to acute lung injury in mice included Klf4, Sema7a, Tns1, Aacs, and a gene that encodes an amino acid carrier, Slc38a4. PMID:22447970

Leikauf, George D; Pope-Varsalona, Hannah; Concel, Vincent J; Liu, Pengyuan; Bein, Kiflai; Berndt, Annerose; Martin, Timothy M; Ganguly, Koustav; Jang, An Soo; Brant, Kelly A; Dopico, Richard A; Upadhyay, Swapna; Di, Y P Peter; Li, Qian; Hu, Zhen; Vuga, Louis J; Medvedovic, Mario; Kaminski, Naftali; You, Ming; Alexander, Danny C; McDunn, Jonathan E; Prows, Daniel R; Knoell, Daren L; Fabisiak, James P

2012-08-01

371

Integrative Assessment of Chlorine-Induced Acute Lung Injury in Mice  

PubMed Central

The genetic basis for the underlying individual susceptibility to chlorine-induced acute lung injury is unknown. To uncover the genetic basis and pathophysiological processes that could provide additional homeostatic capacities during lung injury, 40 inbred murine strains were exposed to chlorine, and haplotype association mapping was performed. The identified single-nucleotide polymorphism (SNP) associations were evaluated through transcriptomic and metabolomic profiling. Using ? 10% allelic frequency and ? 10% phenotype explained as threshold criteria, promoter SNPs that could eliminate putative transcriptional factor recognition sites in candidate genes were assessed by determining transcript levels through microarray and reverse real-time PCR during chlorine exposure. The mean survival time varied by approximately 5-fold among strains, and SNP associations were identified for 13 candidate genes on chromosomes 1, 4, 5, 9, and 15. Microarrays revealed several differentially enriched pathways, including protein transport (decreased more in the sensitive C57BLKS/J lung) and protein catabolic process (increased more in the resistant C57BL/10J lung). Lung metabolomic profiling revealed 95 of the 280 metabolites measured were altered by chlorine exposure, and included alanine, which decreased more in the C57BLKS/J than in the C57BL/10J strain, and glutamine, which increased more in the C57BL/10J than in the C57BLKS/J strain. Genetic associations from haplotype mapping were strengthened by an integrated assessment using transcriptomic and metabolomic profiling. The leading candidate genes associated with increased susceptibility to acute lung injury in mice included Klf4, Sema7a, Tns1, Aacs, and a gene that encodes an amino acid carrier, Slc38a4. PMID:22447970

Pope-Varsalona, Hannah; Concel, Vincent J.; Liu, Pengyuan; Bein, Kiflai; Berndt, Annerose; Martin, Timothy M.; Ganguly, Koustav; Jang, An Soo; Brant, Kelly A.; Dopico, Richard A.; Upadhyay, Swapna; Di, Y. P. Peter; Hu, Zhen; Vuga, Louis J.; Medvedovic, Mario; Kaminski, Naftali; You, Ming; Alexander, Danny C.; McDunn, Jonathan E.; Prows, Daniel R.; Knoell, Daren L.

2012-01-01

372

Expression of neutral endopeptidase activity during clinical and experimental acute lung injury  

PubMed Central

Background Neutral endopeptidase (NEP), an enzyme that cleaves inflammatory bioactive peptides, may play a protective role in the pathogenesis of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). However, its low extracellular activity hinders the precise measurement of changes that take place during ALI/ARDS. The main objective of this study was to clarify the regulation of NEP activity and its expression during ALI/ARDS. Methods In a clinical study, we measured plasma NEP activity in patients who developed postoperative ALI/ARDS, using a HPLC fluorometric system. In an experimental study, we induced ALI by intratracheal instillation of hydrochloric acid (HCl) or lipopolysaccharide (LPS) in mice, and similarly measured NEP activity in plasma, lung tissue, and broncho-alveolar lavage fluid (BALF). We also studied the distribution and measured the amounts of NEP protein, using immuno-histochemical and immunoblot analyses, and measured the levels of NEP mRNA, using real-time reverse transcription-polymerase chain reaction, in the lungs of mice with ALI. Results The plasma NEP activity was significantly lower in patients presenting with ALI/ARDS than in controls. Similarly, the NEP activity in plasma and lung tissue was markedly lower, and lung injuries more severe in LPS- than in HCl-treated mice. In contrast, the activity of NEP in the BALF of LPS-treated mice was increased. The intratracheal instillation of LPS decreased the gene expression of NEP in the lung. Immuno-histochemical and Western immunoblot studies in mice confirmed a) the presence of NEP in the alveolar wall, a critical target in ALI/ARDS, and b) a decrease in its expression in HCl- and LPS-induced ALI. Conclusion In this experimental and clinical study of ALI/ARDS, the activity of NEP was significantly decreased in plasma and increased in the alveolar air space. PMID:21114838

2010-01-01

373

Transcriptome profiling of the newborn mouse lung response to acute ozone exposure.  

PubMed

Ozone pollution is associated with adverse effects on respiratory health in adults and children but its effects on the neonatal lung remain unknown. This study was carried out to define the effect of acute ozone exposure on the neonatal lung and to profile the transcriptome response. Newborn mice were exposed to ozone or filtered air for 3h. Total RNA was isolated from lung tissues at 6 and 24h after exposure and was subjected to microarray gene expression analysis. Compared to filtered air-exposed littermates, ozone-exposed newborn mice developed a small but significant neutrophilic airway response associated with increased CXCL1 and CXCL5 expression in the lung. Transcriptome analysis indicated that 455 genes were down-regulated and 166 genes were up-regulated by at least 1.5-fold at 6h post-ozone exposure (t-test, p < .05). At 24h, 543 genes were down-regulated and 323 genes were up-regulated in the lungs of ozone-exposed, compared to filtered air-exposed, newborn mice (t-test, p < .05). After controlling for false discovery rate, 50 genes were identified as significantly down-regulated and only a few (RORC, GRP, VREB3, and CYP2B6) were up-regulated at 24h post-ozone exposure (q < .05). Gene ontology enrichment analysis revealed that cell cycle-associated functions including cell division/proliferation were the most impacted pathways, which were negatively regulated by ozone exposure, an adverse effect that was associated with reduced bromo-deoxyuridine incorporation. These results demonstrate that acute ozone exposure alters cell proliferation in the developing neonatal lung through a global suppression of cell cycle function. PMID:24336422

Gabehart, Kelsa; Correll, Kelly A; Yang, Jing; Collins, Maureen L; Loader, Joan E; Leach, Sonia; White, Carl W; Dakhama, Azzeddine

2014-03-01

374

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

PubMed Central

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

2013-01-01

375

Molecular Basis of Asbestos-Induced Lung Disease  

PubMed Central

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

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

2013-01-01

376

Beneficial effect of a hydrogen sulphide donor (sodium sulphide) in an ovine model of burn- and smoke-induced acute lung injury  

PubMed Central

Background and purpose: The present study investigated whether the pathophysiological changes induced by burn and smoke inhalation are modulated by parenteral administration of Na2S, a H2S donor. Experimental approach: The study used a total of 16 chronically instrumented, adult female sheep. Na2S was administered 1 h post injury, as a bolus injection at a dose of 0.5 mg·kg?1 and subsequently, as a continuous infusion at a rate of 0.2 mg·kg?1·h?1 for 24 h. Cardiopulmonary variables (mean arterial and pulmonary arterial blood pressure, cardiac output, ventricular stroke work index, vascular resistance) and arterial and mixed venous blood gases were measured. Lung wet-to-dry ratio and myeloperoxidase content and protein oxidation and nitration were also measured. In addition, lung inducible nitric oxide synthase expression and cytochrome c were measured in lung homogenates via Western blotting and enzyme-linked immunosorbent assay (elisa) respectively. Key results: The H2S donor decreased mortality during the 96 h experimental period, improved pulmonary gas exchange and lowered further increase in inspiratory pressure and fluid accumulation associated with burn- and smoke-induced acute lung injury. Further, the H2S donor treatment reduced the presence of protein oxidation and 3-nitrotyrosine formation following burn and smoke inhalation injury. Conclusions and implications: Parenteral administration of the H2S donor ameliorated the pulmonary pathophysiological changes associated with burn- and smoke-induced acute lung injury. Based on the effect of H2S observed in this clinically relevant model of disease, we propose that treatment with H2S or its donors may represent a potential therapeutic strategy in managing patients with acute lung injury. PMID:19845680

Esechie, Aimalohi; Enkhbaatar, Perenlei; Traber, Daniel L; Jonkam, Collette; Lange, Matthias; Hamahata, Atsumori; Djukom, Clarisse; Whorton, Elbert B; Hawkins, Hal K; Traber, Lillian D; Szabo, Csaba

2009-01-01

377

Diffuse pulmonary lymphatic disease presenting as interstitial lung disease in adulthood: report of 3 cases.  

PubMed

Diffuse pulmonary lymphatic diseases are typically diagnosed shortly after birth or in childhood, but rarely may become evident in adulthood. We report 3 adult patients who presented with diffuse interstitial lung disease clinically and radiologically but on biopsy were found to have diffuse pulmonary lymphatic disease (2 cases of pulmonary lymphangiectasis and 1 case of pulmonary lymphangiomatosis). These patients presented with the insidious onset of symptoms including shortness of breath and cough. Imaging studies of the chest showed diffuse pulmonary interstitial opacities, often with a perilymphatic distribution. The clinical differential diagnostic considerations before surgical lung biopsy included infection, neoplasm, and interstitial lung disease. The histopathologic features included abnormal vessels and associated fibrosis following lymphatic routes, namely visceral pleura, bronchovascular bundles, and interlobular septa. Lymphangiectasis was characterized by dilation of normally distributed lymphatic spaces, whereas lymphangiomatosis showed a complex anastamosing proliferation of lymphatic vascular spaces without significant dilatation. The dilated lymphatic spaces often had undergone muscularization, which could easily lead to misclassification as veins. Immunohistochemical staining for the lymphatic endothelial marker D2-40 was helpful in correctly classifying these lesions. Diffuse pulmonary lymphatic disease can rarely present in adulthood, wherein the histologic findings can be subtle and could be overlooked as nonspecific reactive changes or misdiagnosed as an idiopathic interstitial lung disease. Recognition of the characteristic lymphangitic distribution of abnormally dilated or reduplicated lymphatic spaces is key to the correct diagnosis. PMID:22982897

Boland, Jennifer M; Tazelaar, Henry D; Colby, Thomas V; Leslie, Kevin O; Hartman, Thomas E; Yi, Eunhee S

2012-10-01

378

Comparison of reducing effect on lung injury of dexamethasone and bosentan in acute lung injury: an experimental study  

PubMed Central

Background Different medical therapies are employed in acute lung injury (ALI) but there is still a debate about the efficacy of these drugs. Among these therapies steroids are clinically applied and bosentan is experimentally studied. The aim of this study was to evaluate the efficacy of these two drugs to treat inflammation in ALI by histopathological comparison. Methods The five experimental groups (n = 5 per group) were: saline control (Group I); lipopolysaccharide (LPS) + saline (Group II); LPS + dexamethasone (Group III); LPS + 50 mg/kg bosentan (Group IV); and LPS + 100 mg/kg bosentan (Group V). Bosentan was administered orally one hour before and 12 hours after LPS treatment. Dexamethasone was administered intraperitoneally in three doses of 1 mg/kg; one dose was co-administered with LPS and the other two doses were given respectively 30 minutes before and after LPS treatment. Vasodilation-congestion, hemorrhage, polymorphonuclear leukocyte (PMN) infiltration, mononuclear leukocyte (MNL) infiltration, alveolar wall thickening, alveolar destruction/emphysematous appearance, and focal organization were the parameters used as criteria for evaluating inflammation and efficacy of treatment. Results Compared to the LPS-only group (Group II), dexamethasone treatment (Group III) resulted in significant improvements in vasodilation-congestion, hemorrhage, PMN and MNL infiltration, alveolar wall thickening and emphysematous areas. Treatment with 50 mg/kg dose of bosentan (Group IV) also resulted in significant improvements in hemorrhage, PMN and MNL infiltration, alveolar wall thickening and alveolar destruction. Reducing lung injury and reparative effects of 100 mg/kg bosentan were significant in all parameters. Conclusions Bosentan is as effective as dexamethasone for treating lung injury in ALI. Bosentan at 100 mg/kg can be recommended as a first treatment choice based on its significant reducing lung injury and reparative effects. PMID:24342001

2013-01-01

379

Asymptomatic Preclinical Rheumatoid Arthritis-Associated Interstitial Lung Disease  

PubMed Central

Objective. Interstitial lung disease (ILD) is a common extra-articular manifestation of rheumatoid arthritis (RA) and a significant cause of morbidity and mortality. The objective of this study was to define high-resolution chest CT (HRCT) and pulmonary function test (PFT) abnormalities capable of identifying asymptomatic, preclinical forms of RA-ILD that may represent precursors to more severe fibrotic lung disease. Methods. We analyzed chest HRCTs in consecutively enrolled RA patients and subsequently classified these individuals as RA-ILD or RA-no ILD based on the presence/absence of ground glass opacification, septal thickening, reticulation, traction bronchiectasis, and/or honeycombing. Coexisting PFT abnormalities (reductions in percent predicted FEV1, FVC, TLC, and/or DLCO) were also used to further characterize occult respiratory defects. Results. 61% (63/103) of RA patients were classified as RA-ILD based on HRCT and PFT abnormalities, while 39% (40/103) were designated as RA-no ILD. 57/63 RA-ILD patients lacked symptoms of significant dyspnea or cough at the time of HRCT and PFT assessment. Compared with RA-no ILD, RA-ILD patients were older and had longer disease duration, higher articular disease activity, and more significant PFT abnormalities. Conclusion. HRCT represents an effective tool to detect occult/asymptomatic ILD that is highly prevalent in our unselected, university-based cohort of RA patients. PMID:23983768

Shi, YongHong; Wang, XiaoPing; Huang, Heqing

2013-01-01

380

Occupational Lung Diseases among Soldiers Deployed to Iraq and Afghanistan.  

PubMed

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

Szema, Anthony M

2013-01-01

381

The Lung Tissue Microbiome in Chronic Obstructive Pulmonary Disease  

PubMed Central

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

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

2012-01-01

382

INTRODUCTION Acute lung injury is characterized by lesions of both lung  

E-print Network

components, we hypothesized that matrix metalloproteinases (MMPs), especially collagenases, which cleave by the four members of the tissue inhibitor of matrix metalloproteinase (TIMP) family, TIMP-1, -2, -3 and -4 this acute phase, basement membranes are also damaged with deposition of a provisional extracellular matrix

Paris-Sud XI, Université de

383

Biomarkers for oxidative stress in acute lung injury induced in rabbits submitted to different strategies of mechanical ventilation  

Technology Transfer Automated Retrieval System (TEKTRAN)

Oxidative damage has been said to play an important role in pulmonary injury, which is associated with the development and progression of acute respiratory distress syndrome (ARDS). We aimed to identify biomarkers to determine the oxidative stress in an animal model of acute lung injury (ALI) using ...

384

A Case of Acute Cadmium Pneumonitis: Lung Function Tests during a Four-year Follow-up  

Microsoft Academic Search

Experimental animals which survive the acute pneumonitis that follows the inhalation of cadmium fume develop a perivascular and peribronchial fibrosis. Such fibrosis has not yet been described in man.When a severe case of acute cadmium pneumonitis occurred in a welder, lung function tests were performed and chest radiographs were taken during the subsequent four years in order to observe whether

R. H. Townshend

1968-01-01

385

Phanerochaete chrysosporium and granulomatous lung disease in a mulch gardener.  

PubMed

A 50-year-old woman who gardens regularly with rotting bark mulch presented with exertional dyspnea, diffusion impairment, and radiographic abnormalities (centrilobular nodules, tree-in-bud and ground glass opacities, calcified mediastinal and hilar lymph nodes) on a computed tomogram. Moderate lymphocytosis was noted on bronchoalveolar lavage. Surgical biopsy of her lung revealed granulomatous changes, and biopsies grew Phanerochaete chrysosporium, a fungus that causes white rot in tree bark. She was treated with voriconazole and instructed to avoid gardening, which led to radiographic and symptomatic improvement. She had recurrence of symptoms when she started doing yard work again. P. chrysosporium has been demonstrated to cause hypersensitivity pneumonitis in animal models. This case is the first documented report of P. chrysosporium associated with granulomatous lung disease in a human. PMID:25473549

Lanspa, Michael J; Hatton, Nathan D

2014-03-01

386

Graves' disease as an uncommon cause of acute pericarditis.  

PubMed

Acute pericarditis is either dry, fibrinous or effusive, independent of its aetiology. A case is presented involving a 44-year-old man with acute pericarditis. The cause was established to be an aggravation of Graves' disease due to non-compliance with treatment. Pericarditis is an uncommon cardiac complication of Graves' disease and is associated with more recurrent episodes when not detected. Pharmacological treatment should include anti-inflammatory drugs in combination with treatment for hyperthyroidism. The specific pathophysiological link between the two conditions is still to be elucidated. PMID:24769665

Kortekaas, Kirsten A; Kortekaas, Kirsten; van der Lienden, Bas; Jong, Simone; Riezebos, Robert

2014-01-01

387

Oxygen, Gastrin-Releasing Peptide, and Pediatric Lung Disease: Life in the Balance  

PubMed Central

Excessive oxygen (O2) can cause tissue injury, scarring, aging, and even death. Our laboratory is studying O2-sensing pulmonary neuroendocrine cells (PNECs) and the PNEC-derived product gastrin-releasing peptide (GRP). Reactive oxygen species (ROS) generated from exposure to hyperoxia, ozone, or ionizing radiation (RT) can induce PNEC degranulation and GRP secretion. PNEC degranulation is also induced by hypoxia, and effects of hypoxia are mediated by free radicals. We have determined that excessive GRP leads to lung injury with acute and chronic inflammation, leading to pulmonary fibrosis (PF), triggered via ROS exposure or by directly treating mice with exogenous GRP. In animal models, GRP-blockade abrogates lung injury, inflammation, and fibrosis. The optimal time frame for GRP-blockade and the key target cell types remain to be determined. The concept of GRP as a mediator of ROS-induced tissue damage represents a paradigm shift about how O2 can cause injury, inflammation, and fibrosis. The host PNEC response in vivo may depend on individual ROS sensing mechanisms and subsequent GRP secretion. Ongoing scientific and clinical investigations promise to further clarify the molecular pathways and clinical relevance of GRP in the pathogenesis of diverse pediatric lung diseases. PMID:25101250

Sunday, Mary E.

2014-01-01

388

Inflammasome and Lung Pathologies  

Microsoft Academic Search

\\u000a Nonregulated inflammation in the lung often leads to chronic inflammatory diseases such as asthma, chronic obstructive pulmonary\\u000a disease (COPD), and pulmonary fibrosis. Interleukin-1? (IL-1?) and interleukin-1? (IL-1?) are potent mediators of innate immunity\\u000a and IL-1? is processed by large multiprotein complexes called inflammasomes. Using a mice model of lung inflammatory diseases,\\u000a it was shown that acute cigarette smoke exposure induces

Bernhard Ryffel; Dieudonnée Togbe; Isabelle Couillin

389

Suspected Transfusion Related Acute Lung Injury Improving following Administration of Tranexamic Acid: A Case Report  

PubMed Central

A 16-year-old woman with craniofacial injury developed severe acute respiratory failure under the primary reconstructive surgical procedure requiring several units of blood and plasma. A transfusion related acute lung injury (TRALI) was suspected and supportive treatment was initiated. Because of the severity of symptoms, acute extracorporeal membrane oxygenation (ECMO) was planned. During preparation for ECMO, a single intravenous dose, 1?g of tranexamic acid, was administered and a remarkable improvement was observed shortly thereafter. The patient was placed on ECMO for 16 hours. The further course was uncomplicated and the patient was discharged from ICU on the 6th day after admission fully and she recovered. A clinical improvement was observed in a timely fashion following the administration of tranexamic acid. The handling of a suspected TRALI and potential benefit from administration of tranexamic acid are discussed in this case report. PMID:24995132

Ryniak, Stan; Harbut, Piotr; Östlund, Anders; Jakobsson, Jan G.

2014-01-01

390

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

PubMed Central

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

Weiss, Daniel J.

2014-01-01

391

Heart and lung, a dangerous liaison-Tako-tsubo cardiomyopathy and respiratory diseases: A systematic review  

PubMed Central

AIM: To investigate the possible association between Tako-tsubo cardiomyopathy (TTC)-a reversible clinical condition mimicking an acute myocardial infarction characterized by multifactorial pathophysiologic mechanisms- and respiratory system diseases. METHODS: We systematically searched PubMed and EMBASE medical information sources, to identify the different triggering causes, limiting our search to articles in English. The search keywords were: “tako-tsubo cardiomyopathy”, “takotsubo”, “takotsubo cardiomyopathy”, “broken heart syndrome”, “stress-induced cardiomyopathy”, “apical ballooning syndrome”, and “ampulla cardiomyopathy in combination with respiratory diseases, lung, pulmonary disease. For each kind of disease, we registered: author, year and country of study, patient sex, age, concurring situation, and outcome. RESULTS: Out of a total of 1725 articles found, we selected 37 papers reporting a total of 38 patients. As expected, most patients were women (81.6%), mean age was 65 ± 10 years. Outcome was favorable in 100% of cases, and all the patients have been discharged uneventfully in a few days. CONCLUSION: An association between respiratory diseases and TTC is likely to exist. Patients with severe respiratory diseases, due to the high dosages of ?2-agonists used or to the need of invasive procedures, are highly exposed to the risk of developing TTC. PMID:24944763

Manfredini, Roberto; Fabbian, Fabio; Giorgi, Alfredo De; Pala, Marco; Menegatti, Alessandra Mallozzi; Parisi, Claudia; Misurati, Elisa; Tiseo, Ruana; Gallerani, Massimo; Salmi, Raffaella; Bossone, Eduardo

2014-01-01

392

Monoammonium glycyrrhizinate inhibited the inflammation of LPS-induced acute lung injury in mice.  

PubMed

Monoammonium glycyrrhizinate (MAG) was the aglycone of glycyrrhizin derived from licorice. In this study, the anti-inflammatory effects of MAG on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and the possible mechanisms involved in this protection were investigated. Pretreatment with MAG prior to the administration of intratracheal LPS significantly induced a decrease in lung wet weight/dry weight ratio, in total leukocyte number and neutrophil percent in the BALF, and in myeloperoxidase (MPO) activity of lung in dose-dependent manners. At the same time, pretreatment with MAG also significantly improved the super oxide dismutase (SOD) activity and induced the malondialdehyde (MDA) content in the bronchoalveolar lavage fluid (BALF). Importantly, pretreatment with MAG prevented an increase in cyclic adenosine monophosphate-phosphodiesterase (cAMP-PDE) activity of lung in a dose-dependent manner. In addition, it can up-regulate the interleukin-10 (IL-10) level and down-regulate the tumor neurosis factor-? (TNF-?) level in the lung tissue of ALI mice. These results showed that anti-inflammatory effects of MAG against the LPS-induced ALI may be due to its ability of primary inhibition of cAMP-PDE activity, oxidative stress and its regulation of cytokine effects. Thus the results support that use of MAG is beneficial in the treatment of ALI and ARDS. PMID:20637836

Shi, Jian-Rong; Mao, Lian-Gen; Jiang, Ruo-An; Qian, Yun; Tang, Hui-Fang; Chen, Ji-Qiang

2010-10-01

393

Diethylcarbamazine inhibits NF-?B activation in acute lung injury induced by carrageenan in mice.  

PubMed

Diethylcarbamazine citrate (DEC) is widely used to treat lymphatic filariasis and Tr