Note: This page contains sample records for the topic acute lung disease from Science.gov.
While these samples are representative of the content of Science.gov,
they are not comprehensive nor are they the most current set.
We encourage you to perform a real-time search of Science.gov
to obtain the most current and comprehensive results.
Last update: August 15, 2014.
1

Manipulation of acute inflammatory lung disease  

Microsoft Academic Search

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

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

2008-01-01

2

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

PubMed Central

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

de Abreu, Krasnalhia Livia Soares; da Silva Junior, Geraldo Bezerra; Muniz, Thalita Diogenes; Barreto, Adller Goncalves Costa; Lima, Rafael Siqueira Athayde; Holanda, Marcelo Alcantara; Pereira, Eanes Delgado Barros; Liborio, Alexandre Braga; Daher, Elizabeth de Francesco

2013-01-01

3

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.

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, Gyorgy; Kato, Harubumi

2011-01-01

4

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 ...

5

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.

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

2014-01-01

6

Interstitial lung disease  

Microsoft Academic Search

Idiopathic interstitial pneumonias represent an important group of interstitial lung diseases, encompassing seven entities: (1) usual interstitial pneumonia (UIP)\\/idiopathic pulmonary fibrosis; (2) non-specific interstitial pneumonia (NSIP); (3) organizing pneumonia\\/cryptogenic organizing pneumonia (COP); (4) diffuse alveolar damage (DAD)\\/acute interstitial pneumonia (AIP); (5) respiratory bronchiolitis (RB)\\/respiratory bronchiolitis–interstitial lung disease (RB–ILD); (6) desquamative interstitial pneumonia (DIP); and (7) lymphocytic interstitial pneumonia (LIP). The

William D. Travis

2008-01-01

7

Lung disease - resources  

MedlinePLUS

Resources - lung disease ... The following organizations are good resources for information on lung disease : American Lung Association - www.lungusa.org National Heart, Lung, and Blood Institute - www.nhlbi.nih.gov ...

8

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

PubMed

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. 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. PMID:23792423

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

2013-10-15

9

Acute exacerbation in rheumatoid arthritis-associated interstitial lung disease: a retrospective case control study  

PubMed Central

Objectives To investigate the risk factors and prognosis associated with acute exacerbation (AE) in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Design A retrospective case–control study. Setting A single academic hospital. Participants 51 consecutive patients diagnosed with RA-ILD between 1995 and 2012. All patients fulfilled the diagnostic criteria of the American College of Rheumatology for RA. ILD was diagnosed on the basis of clinical presentation, pulmonary function tests, high-resolution CT (HRCT) findings and lung biopsy findings. Main outcome measures Overall survival and cumulative AE incidence were analysed using Kaplan-Meier method. Cox hazards analysis was used to determine significant variables associated with AE occurrence and survival status. Results A total of 11 patients (22%) developed AE, with an overall 1-year incidence of 2.8%. Univariate analysis revealed that older age at ILD diagnosis (HR 1.11; 95% CI 1.02 to 1.21; p=0.01), usual interstitial pneumonia (UIP) pattern on HRCT (HR 1.95; 95% CI 1.07 to 3.63; p=0.03) and methotrexate usage (HR 3.04; 95% CI 1.62 to 6.02; p=0.001) were associated with AE. Of 11 patients who developed AE during observation period, 7 (64%) died of initial AE. In survival, AE was a prognostic factor for poor outcome (HR 2.47; 95% CI 1.39 to 4.56; p=0.003). Conclusions In patients with RA-ILD, older age at ILD diagnosis, UIP pattern on HRCT and methotrexate usage are associated with the development of AE. Furthermore, AE has a serious impact on their survival.

Hozumi, Hironao; Nakamura, Yutaro; Johkoh, Takeshi; Sumikawa, Hiromitsu; Colby, Thomas V; Kono, Masato; Hashimoto, Dai; Enomoto, Noriyuki; Fujisawa, Tomoyuki; Inui, Naoki; Suda, Takafumi; Chida, Kingo

2013-01-01

10

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 ...

11

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.

Dales, Robert E.; Munt, Peter W.

1982-01-01

12

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 ...

13

Lung Diseases  

MedlinePLUS

... airways resulting in poor air flow. Others, including pulmonary fibrosis http://www.nhlbi.nih.gov/health/health-topics/topics/ipf/ , pneumonia Dictionary of Environmental Health and lung cancer, are caused by a loss of elasticity ...

14

Pertechnegas lung clearance in different forms of interstitial lung disease  

Microsoft Academic Search

Pertechnegas lung clearance in different forms of interstitial lung disease. M.J. Thomeer, B. Dehaes, L. Mortelmans, M. Demedts. #ERS Journals Ltd 2002. ABSTRACT: Interstitial lung diseases (ILD) are characterized by an acute or chronic inflammation of the alveolar capillary membrane, which affects the permeability of this membrane. A possible way to measure the permeability of the membrane is by radionuclide

M. J. Thomeer; B. Dehaes; L. Mortelmans; M. Demedts

2002-01-01

15

[Pneumococcus serotypes in acute and chronic inflammatory lung disease (1978-1980)].  

PubMed

The comparison of the antigenic structure of the polysaccharide capsule in 342 pneumococcal strains isolated in Leningrad from the bronchial contents of patients with acute and chronic inflammatory pulmonary diseases indicated that during 1978-1980 a change in the composition of the prevailing groups of serotypes occurred every year. The comparison of the groups of prevailing pneumococcal serotypes isolated from children and adults has revealed no statistically significant differences in the specific prominence of different types, with the exception of serotype 15. Serotypes 6, 7 and 2 have been found to occur most frequently in acute pneumonia, and serotypes 23, 3, 9, 6, 15, 29 and 34 in chronic inflammatory pulmonary diseases. The preliminary data on the differences in the composition of the prevailing pneumococcal serotypes causing acute pneumonia in Leningrad and Kaunas have been obtained. PMID:6460398

Vishniakova, L A; Vasil'eva, M G; Veselova, T A; Sakalauskas, R; Faustova, M E

1981-12-01

16

Particles causing lung disease.  

PubMed Central

The lung has a limited number of patterns of reaction to inhaled particles. The disease observed depends upon the location: conducting airways, terminal bronchioles and alveoli, and upon the nature of inflammation induced: acute, subacute or chronic. Many different agents cause narrowing of conducting airways (asthma) and some of these cause permanent distortion or obliteration of airways as well. Terminal bronchioles appear to be particularly susceptible to particles which cause goblet cell metaplasia, mucous plugging and ultimately peribronchiolar fibrosis. Cancer is the last outcome at the bronchial level and appears to depend upon continuous exposure to or retention of an agent in the airway and failure of the affected cells to be exfoliated which may be due to squamous metaplasia. Alveoli are populated by endothelial cells, Type I or pavement epithelial cells and metabolically active cuboidal Type II cells that produce the lungs specific surfactant, dipalmytol lecithin. Disturbances of surfactant lead to edema in distal lung while laryngeal edema due to anaphylaxis or fumes may produce asphyxia. Physical retention of indigestible particles or retention by immune memory responses may provoke hyaline membranes, stimulate alveolar lipoproteinosis and finally fibrosis. This later exuberant deposition of connective tissue has been best studied in the occupational pneumoconioses especially silicosis and asbestosis. In contrast emphysema a catabolic response, appears frequently to result from leakage or release of lysosomal proteases into the lung during processing of cigarette smoke particles. The insidious and probably most important human lung disease due to particles is bronchiolar obstruction and obliteration, producing progressive impairment of air flow. The responsible particle is the complex combination of poorly digestive lipids and complex carbohydrates with active chemicals which we call cigarette smoke. More research is needed to perfect, correct and quantify our preliminary picture of the pathogenesis of lung disease by particles, but a useful start has been made. Images FIGURE 1.

Kilburn, K H

1984-01-01

17

Hyperoxic Acute Lung Injury  

PubMed Central

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

Kallet, Richard H; Matthay, Michael A

2013-01-01

18

Lymphatics in Lung Disease  

PubMed Central

The lymphatic circulation appears to be a vital component in lung biology in health and in disease. Animal models have established the role of the lymphatic circulation in neoplastic and inflammatory diseases of the lung, such as asthma and cancer, and allowed for the understanding of the molecular controls of lymphangiogenesis in normal lung development. Understanding the role of lymphatics in human lung disease appears likely to contribute to the understanding of the pathogenesis of disease and the development of novel therapeutic targets.

El-Chemaly, Souheil; Levine, Stewart J.; Moss, Joel

2010-01-01

19

Rituximab treatment in a case of antisynthetase syndrome with severe interstitial lung disease and acute respiratory failure.  

PubMed

We present a case of severe interstitial pneumonitis, mild polyarthritis and polymyositis, and Raynaud's syndrome with the presence of anti-Jo-1 antibodies, which had been diagnosed as anti-synthetase syndrome. The presence, however, of anti-Ro/SSA antibodies led us to understand that we were dealing here with a more severe form of interstitial lung disease. The patient was treated for acute respiratory failure but he showed resistance to glucocorticoids and cyclosporine. Thus, he was treated with infusions of anti-CD20 therapy (rituximab): his clinical conditions improved very rapidly and a significant decrease in the activity of pulmonary disease was detected using high-resolution computerized tomography (HRCT) of the thorax and pulmonary function tests. PMID:22958322

Zappa, Maria Cristina; Trequattrini, Tiziana; Mattioli, Francesco; Rivitti, Rosario; Vigliarolo, Rossana; Marcoccia, Antonella; D'Arcangelo, Giovanni

2011-01-01

20

Rituximab treatment in a case of antisynthetase syndrome with severe interstitial lung disease and acute respiratory failure  

PubMed Central

We present a case of severe interstitial pneumonitis, mild polyarthritis and polymyositis, and Raynaud's syndrome with the presence of anti-Jo-1 antibodies, which had been diagnosed as anti-synthetase syndrome. The presence, however, of anti-Ro/SSA antibodies led us to understand that we were dealing here with a more severe form of interstitial lung disease. The patient was treated for acute respiratory failure but he showed resistance to glucocorticoids and cyclosporine. Thus, he was treated with infusions of anti-CD20 therapy (rituximab): his clinical conditions improved very rapidly and a significant decrease in the activity of pulmonary disease was detected using high-resolution computerized tomography (HRCT) of the thorax and pulmonary function tests.

2011-01-01

21

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

22

Lung Diseases and Conditions  

MedlinePLUS

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

23

Lung disease in farmers.  

PubMed Central

Lung diseases in farmers attributable to their occupation include (a) farmer's lung, caused by exposure to mouldy hay, (b) the asthma caused by exposure to grain dust and (c) silo-filler's disease. Their prevalence in Canada is unknown. Farmer's lung results from inhalation of mould spores in hay; the mechanism is immunologic. The exact cause and mechanism of grain dust asthma are unknown but may be immunologic. Silo-filler's disease is caused by the toxic effects of inhaled nitrogen dioxide.

Warren, C. P.

1977-01-01

24

[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

25

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

26

Statins and Acute Lung Injury  

Microsoft Academic Search

\\u000a The development of acute lung injury (ALI), with progression to acute respiratory distress syndrome (ARDS), is associated\\u000a with an in-hospital mortality as high as 38%. The ageadjusted incidence of ALI and ARDS is reported to be as high as 86.2\\u000a per 100,000 person-years, with approximately 74,500 deaths in the USA each year. Although the ultimate cause of death in patients

Amit K. Mahajan; Jeffrey R. Jacobson

27

Acute lung injury after thoracic surgery.  

PubMed

In this review, the authors discussed criteria for diagnosing ALI; incidence, etiology, preoperative risk factors, intraoperative management, risk-reduction strategies, treatment, and prognosis. The anesthesiologist needs to maintain an index of suspicion for ALI in the perioperative period of thoracic surgery, particularly after lung resection on the right side. Acute hypoxemia, imaging analysis for diffuse infiltrates, and detecting a noncardiogenic origin for pulmonary edema are important hallmarks of acute lung injury. Conservative intraoperative fluid administration of neutral to slightly negative fluid balance over the postoperative first week can reduce the number of ventilator days. Fluid management may be optimized with the assistance of new imaging techniques, and the anesthesiologist should monitor for transfusion-related lung injuries. Small tidal volumes of 6 mL/kg and low plateau pressures of < or =30 cmH2O may reduce organ and systemic failure. PEEP may improve oxygenation and increases organ failure-free days but has not shown a mortality benefit. The optimal mode of ventilation has not been shown in perioperative studies. Permissive hypercapnia may be needed in order to reduce lung injury from positive-pressure ventilation. NO is not recommended as a treatment. Strategies such as bronchodilation, smoking cessation, steroids, and recruitment maneuvers are unproven to benefit mortality although symptomatically they often have been shown to help ALI patients. Further studies to isolate biomarkers active in the acute setting of lung injury and pharmacologic agents to inhibit inflammatory intermediates may help improve management of this complex disease. PMID:20060320

Eichenbaum, Kenneth D; Neustein, Steven M

2010-08-01

28

Occupational Lung Diseases  

MedlinePLUS

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

29

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.

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

2014-01-01

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.

McCubbrey, Alexandra L.

2013-01-01

31

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.

Kohli, Ritesh; Namek, Karim

2013-01-01

32

Pharmacotherapy of Acute Lung Injury and Acute Respiratory Distress Syndrome  

PubMed Central

Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) are characterized by rapid-onset respiratory failure following a variety of direct and indirect insults to the parenchyma or vasculature of the lungs. Mortality from ALI/ARDS is substantial, and current therapy primarily emphasizes mechanical ventilation and judicial fluid management plus standard treatment of the initiating insult and any known underlying disease. Current pharmacotherapy for ALI/ARDS is not optimal, and there is a significant need for more effective medicinal chemical agents for use in these severe and lethal lung injury syndromes. To facilitate future chemical-based drug discovery research on new agent development, this paper reviews present pharmacotherapy for ALI/ARDS in the context of biological and biochemical drug activities. The complex lung injury pathophysiology of ALI/ARDS offers an array of possible targets for drug therapy, including inflammation, cell and tissue injury, vascular dysfunction, surfactant dysfunction, and oxidant injury. Added targets for pharmacotherapy outside the lungs may also be present, since multiorgan or systemic pathology is common in ALI/ARDS. The biological and physiological complexity of ALI/ARDS requires the consideration of combined-agent treatments in addition to single-agent therapies. A number of pharmacologic agents have been studied individually in ALI/ARDS, with limited or minimal success in improving survival. However, many of these agents have complementary biological/biochemical activities with the potential for synergy or additivity in combination therapy as discussed in this article.

Raghavendran, Krishnan; Pryhuber, Gloria S.; Chess, Patricia R.; Davidson, Bruce A.; Knight, Paul R.; Notter, Robert H.

2009-01-01

33

Mitochondria in lung diseases.  

PubMed

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, chronic obstructive pulmonary disease, 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

2013-12-01

34

Acute inflammatory surgical disease.  

PubMed

Infectious and inflammatory diseases comprise some of the most common gastrointestinal disorders resulting in hospitalization in the United States. Accordingly, they occupy a significant proportion of the workload of the acute care surgeon. This article discusses the diagnosis, management, and treatment of appendicitis, acute cholecystitis/cholangitis, acute pancreatitis, diverticulitis, and Clostridium difficile colitis. PMID:24267493

Fagenholz, Peter J; de Moya, Marc A

2014-02-01

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.

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

2013-01-01

37

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

PubMed Central

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

2014-01-01

38

Macrophages and Allergic Lung Disease  

Microsoft Academic Search

Allergic lung diseases such as atopic asthma and extrinsic allergic alveolitis are now recognized as chronic inflammatory lung diseases promoted by dysregulation of T cell-mediated immune mechanisms. The basis of this regulation and the impact of the atopic status of these individuals on this chronic inflammatory disease have yet to be fully explained. The studies described in this paper reveal

L. W. Poulter; C. M. Burke

1996-01-01

39

Combination of lung ultrasound (a comet-tail sign) and N-terminal pro-brain natriuretic peptide in differentiating acute heart failure from chronic obstructive pulmonary disease and asthma as cause of acute dyspnea in prehospital emergency setting  

PubMed Central

Introduction We studied the diagnostic accuracy of bedside lung ultrasound (the presence of a comet-tail sign), N-terminal pro-brain natriuretic peptide (NT-proBNP) and clinical assessment (according to the modified Boston criteria) in differentiating heart failure (HF)-related acute dyspnea from pulmonary (chronic obstructive pulmonary disease (COPD)/asthma)-related acute dyspnea in the prehospital setting. Methods Our prospective study was performed at the Center for Emergency Medicine, Maribor, Slovenia, between July 2007 and April 2010. Two groups of patients were compared: a HF-related acute dyspnea group (n = 129) and a pulmonary (asthma/COPD)-related acute dyspnea group (n = 89). All patients underwent lung ultrasound examinations, along with basic laboratory testing, rapid NT-proBNP testing and chest X-rays. Results The ultrasound comet-tail sign has 100% sensitivity, 95% specificity, 100% negative predictive value (NPV) and 96% positive predictive value (PPV) for the diagnosis of HF. NT-proBNP (cutoff point 1,000 pg/mL) has 92% sensitivity, 89% specificity, 86% NPV and 90% PPV. The Boston modified criteria have 85% sensitivity, 86% specificity, 80% NPV and 90% PPV. In comparing the three methods, we found significant differences between ultrasound sign and (1) NT-proBNP (P < 0.05) and (2) Boston modified criteria (P < 0.05). The combination of ultrasound sign and NT-proBNP has 100% sensitivity, 100% specificity, 100% NPV and 100% PPV. With the use of ultrasound, we can exclude HF in patients with pulmonary-related dyspnea who have positive NT-proBNP (> 1,000 pg/mL) and a history of HF. Conclusions An ultrasound comet-tail sign alone or in combination with NT-proBNP has high diagnostic accuracy in differentiating acute HF-related from COPD/asthma-related causes of acute dyspnea in the prehospital emergency setting. Trial registration ClinicalTrials.gov NCT01235182.

2011-01-01

40

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.

Singh, Sonal

2013-01-01

41

Acute lung injury and acute respiratory distress syndrome in malaria.  

PubMed

Malaria is an important treatable cause of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in the tropics and in the returning traveller in the non-endemic areas. ARDS is an important complication in severe, complicated falciparum malaria and has been described in P. vivax and P. ovale malaria also. Malarial ALI/ARDS is more common in adults than in children. Pregnant women and non-immune individuals are more prone to develop this condition. Increased alveolar capillary permeability resulting in intravascular fluid loss into the lungs appears to be the key pathophysiologic mechanism. In malaria, ARDS can develop either at initial presentation or after initiation of treatment when the parasitaemia is falling and the patient is improving. Patients present with acute onset dysnoea that can rapidly progress to respiratory failure. The diagnosis of malaria is confirmed by slide microscopy supported by the use of rapid antigen tests. Patients with malarial ARDS should be managed in an intensive care unit. Careful attention must be paid to haemodynamic stabilisation and optimising fluid balance. Currently, specific treatment choices for malaria include parenteral artemisinins or intravenous quinine along with doxycycline. Respiratory failure requires endotracheal intubation and assisted mechanical ventilation. Co-existent bacterial sepsis is frequently present in patients with malarial ARDS eventhough an obvious focus may not be evident. Appropriate broad spectrum antibiotic therapy must be started when there is a clinical suspicion after procuring the microbiological specimens. ARDS in malaria is a disease with a high mortality. Early diagnosis, institution of specific antimalarial treatment and assisted ventilation can be life-saving. PMID:18807374

Mohan, Alladi; Sharma, Surendra K; Bollineni, Srinivas

2008-09-01

42

Genomic Medicine and Lung Diseases  

PubMed Central

The recent explosion of genomic data and technology points to opportunities to redefine lung diseases at the molecular level; to apply integrated genomic approaches to elucidate mechanisms of lung pathophysiology; and to improve early detection, diagnosis, and treatment of lung diseases. Research is needed to translate genomic discoveries into clinical applications, such as detecting preclinical disease, predicting patient outcomes, guiding treatment choices, and most of all identifying potential therapeutic targets for lung diseases. The Division of Lung Diseases in the National Heart, Lung, and Blood Institute convened a workshop, “Genomic Medicine and Lung Diseases,” to discuss the potential for integrated genomics and systems approaches to advance 21st century pulmonary medicine and to evaluate the most promising opportunities for this next phase of genomics research to yield clinical benefit. Workshop sessions included (1) molecular phenotypes, molecular biomarkers, and therapeutics; (2) new technology and opportunity; (3) integrative genomics; (4) molecular anatomy of the lung; (5) novel data and information platforms; and (6) recommendations for exceptional research opportunities in lung genomics research.

Center, David M.; Schwartz, David A.; Solway, Julian; Gail, Dorothy; Laposky, Aaron D.

2012-01-01

43

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.

Laratta, Cheryl R.; van Eeden, Stephan

2014-01-01

44

Transfusion-related acute lung injury.  

PubMed

Transfusion-related acute lung injury (TRALI) refers to a clinical syndrome of acute lung injury that occurs in a temporal relationship with the transfusion of blood products. Because of the difficulty in making its diagnosis, TRALI is often underreported. Three not necessarily mutually exclusive hypotheses have been described to explain its etiogenesis: antibody mediated, non-antibody mediated, and two hit mechanisms. Treatment is primarily supportive and includes supplemental oxygen. Diuretics are generally not indicated, as hypovolemia should be avoided. Compared with many other forms of acute lung injury, including the acute respiratory distress syndrome, TRALI is generally transient, reverses spontaneously, and carries a better prognosis. A variety of prevention strategies have been proposed, ranging from restrictive transfusion strategies to using plasma derived only from males. PMID:18372350

Jawa, Randeep S; Anillo, Sergio; Kulaylat, Mahmoud N

2008-01-01

45

Oxidative stress: acute and progressive lung injury.  

PubMed

Oxidative stress in lung often occurs in humans during acute lung injury (ALI) and in the acute respiratory distress syndrome. The lung inflammatory response may proceed to the development of pulmonary fibrosis, a devastating complication that occurs in premature infants after prolonged exposure to high oxygen concentrations. Oxidant-related ALI can be induced by airway deposition of lipopolysaccharide or IgG immune complexes, resulting in activation of recruited neutrophils and residential macrophages, whose oxidants and proteases produce reversible ALI. In the presence of a powerful trigger of leukocytes (phorbol myristate acetate), or following intrapulmonary deposition of enzymes that generate oxidants, extensive endothelial and epithelial damage and destruction occurs, overwhelming repair mechanisms of lung and resulting in pulmonary fibrosis. How residential or circulating stem cells participate in regeneration of damaged/destroyed cells may provide clues regarding therapy in humans who are experiencing lung inflammatory damage. PMID:20716283

Ward, Peter A

2010-08-01

46

[Preoperative assessment of the patient with restrictive lung disease].  

PubMed

Restrictive lung disease is characterized by a reduction in total lung capacity. Pulmonary conditions such as interstitial lung disease related to connective tissue disease, idiopathic interstitial pneumonia (IIP), lung resection, and pulmonary fibrosis could cause restrictive disease. In addition, extrapulmonary disorders are caused by chest wall limitations, muscle dysfunction, or pleural disease. Preoperative medical history of associated diseases or symptoms prompts the anesthesiologist to the directed evalution. With regard to the restrictive lung disease, IIP is the most important disease for an anesthesiologist to know. IIP is known to be combined with primary lung cancer and is associated with an increased risk of postoperative acute exacerbation. Acute exacerbation of IIP is a serious postoperative complication and the consequence is extremely poor. Therefore, both surgeons and anesthesiologists must aim to prevent acute exacerbation of IIP Although it is difficult to predict the development of acute exacerbation of IIP, we should avoid or postpone the surgery in patients demonstrating an active phase of IIP. Besides, we should give enough explanation of the risk of postoperative acute exacerbation to the patient with IIP. PMID:20662280

Fukuoka, Naokazu; Iida, Hiroki

2010-07-01

47

Claudins in lung diseases  

PubMed Central

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

2011-01-01

48

TOLL LIKE RECEPTORS IN DISEASES OF THE LUNG  

PubMed Central

The lung is in continuous contact with a diverse array of infectious agents, foreign antigens, and host-derived danger signals. To sample this expansive internal and external milieu, both resident myeloid and stromal/structure cells of the lung express a full complement of toll like receptors (TLRs) which recognize pathogen-associated molecular patterns (PAMPs) and endogenous danger-associated molecular patterns (DAMPs). TLRs play a vital role in immune host defense against bacterial, mycobacterial, fungal, and viral pathogens of the lung. Additionally, TLRs contribute to disease pathogenesis in non-infectious pulmonary disorders, including airways disease, acute lung injury, and interstitial lung disease. In this review, TLR biology in the context of experimental infectious and non-infectious lung disease is discussed, and correlates to human lung disease, including therapeutic implications of these findings, are defined.

Kovach, Melissa A.; Standiford, Theodore J.

2013-01-01

49

Animal models of acute lung injury  

PubMed Central

Acute lung injury in humans is characterized histopathologically by neutrophilic alveolitis, injury of the alveolar epithelium and endothelium, hyaline membrane formation, and microvascular thrombi. Different animal models of experimental lung injury have been used to investigate mechanisms of lung injury. Most are based on reproducing in animals known risk factors for ARDS, such as sepsis, lipid embolism secondary to bone fracture, acid aspiration, ischemia-reperfusion of pulmonary or distal vascular beds, and other clinical risks. However, none of these models fully reproduces the features of human lung injury. The goal of this review is to summarize the strengths and weaknesses of existing models of lung injury. We review the specific features of human ARDS that should be modeled in experimental lung injury and then discuss specific characteristics of animal species that may affect the pulmonary host response to noxious stimuli. We emphasize those models of lung injury that are based on reproducing risk factors for human ARDS in animals and discuss the advantages and disadvantages of each model and the extent to which each model reproduces human ARDS. The present review will help guide investigators in the design and interpretation of animal studies of acute lung injury.

Matute-Bello, Gustavo; Frevert, Charles W.; Martin, Thomas R.

2008-01-01

50

Modulation of acute lung injury by integrins.  

PubMed

Acute lung injury is a common disorder with a high mortality rate, but previous efforts to develop drugs to treat this disorder have been unsuccessful. In an effort to develop more effective treatments, we have been studying the molecular pathways that regulate the dysfunction of alveolar epithelial cells and endothelial cells that serve as a final common pathway leading to alveolar flooding. Using integrin subunit knockout mice and antibodies we developed by immunizing these mice, we have found important and distinct roles for the ?v?6 integrin on epithelial cells and the ?v?5 integrin on endothelial cells in mediating increases in alveolar permeability in multiple models of acute lung injury. We have also found therapeutic effects of ?v?5 inhibition in two models of septic shock even when the antibody was administered to animals that were obviously ill. These results identify ?v?6 and ?v?5 as promising therapeutic targets for the treatment of acute lung injury and septic shock. PMID:22802286

Sheppard, Dean

2012-07-01

51

Serum ferritin correlates with activity of anti-MDA5 antibody-associated acute interstitial lung disease as a complication of dermatomyositis.  

PubMed

Dermatomyositis (DM) is occasionally complicated by interstitial lung disease. Acute/subacute interstitial pneumonia (A/SIP) with DM is intractable and life threatening. Clinically amyopathic dermatomyositis (C-ADM) is also reported to be complicated with A/SIP, especially in those patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody. In the present cases, we indicate that serum ferritin level correlated with activity of A/SIP with DM. Two patients, a 65-year-old woman and a 30-year-old woman, were diagnosed with anti-MDA5 antibody-associated A/SIP with DM. Serum ferritin was high, 1600 and 770 mg/dl, respectively, on admission. Immunosuppressive therapy ameliorated A/SIP in both cases. Similarly, serum ferritin was also decreasing. However, A/SIP was recurrent and progressive, and serum ferritin was also increasing again in one case. In conclusion, serum ferritin correlates with disease activity of anti-MDA5 antibody-associated A/SIP with DM. Intensity of treatment may be decided according to serum ferritin level. PMID:21052763

Gono, Takahisa; Kawaguchi, Yasushi; Ozeki, Eri; Ota, Yuko; Satoh, Takashi; Kuwana, Masataka; Hara, Masako; Yamanaka, Hisashi

2011-04-01

52

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.

Kirkhorn, S R; Garry, V F

2000-01-01

53

Military service and lung disease.  

PubMed

Military personnel can be exposed to toxicants and conditions that can contribute to lung diseases. This article describes what is known about these exposures and diseases, focusing on the Iraq and Afghanistan wars. Adverse lung health outcomes have been reported in US military personnel deployed to Iraq and/or Afghanistan. Most studies to date have been hindered by limited deployment-specific exposure assessment, lack of baseline lung health information, and variable medical evaluations and case definitions. Further research is warranted. Medical surveillance has been recommended for returning troops, but the challenges are substantial. PMID:23153610

Rose, Cecile S

2012-12-01

54

[Interstitial lung disease].  

PubMed

This concise article summarizes recent advances in the field of interstitial lung disease (ILD) with particular focus on clinically relevant findings. As a novel treatment option for idiopathic pulmonary fibrosis (IPF), pirfenidone has been granted marketing authorization in the European Union for the treatment of mild to moderate IPF. In contrast, the FDA refused to approve pirfenidone for the US market. Promising study results for the treatment of IPF were published for the triple tyrosine kinase inhibitor intedanib, other drugs such as the endothelin receptor antagonist (ERA) macitentan are currently investigated in clinical trials. Further studies that investigated the ERA bosentan, the phosphodiesterase 5 inhibitor sildenafil, or the tyrosine kinase inhibitor imatinib in IPF failed to show a benefit for the pertinent primary endpoint. Additionally, an evidence-based guideline for the diagnosis and management of IPF has very recently been published. The European Respiratory Society established a guideline for the management of lymphangioleiomyomatosis (LAM), while another study showed the cost effectiveness of HRCT screening for LAM in selected female patients suffering from spontaneous pneumothorax. Data from a scleroderma-ILD study show the prognostic relevance of antitopoisomerase antibodies in the progression of this form of ILD. Bosentan treatment did not significantly enhance exercise capacity in patients with scleroderma-ILD in the absence of pulmonary hypertension. With regard to sarcoidosis with mediastinal lymphadenopathy the diagnostic sensitivity can be significantly improved by endobronchial ultrasonography-guided transbronchial needle aspiration vs. conventional needle aspiration. As a possible future treatment option for sarcoidosis vasointestinal peptide has been successfully evaluated in a phase 2 tolerability trial. PMID:21611927

von der Beck, D; Günther, A; Markart, P

2011-06-01

55

Reflux and Lung Disease  

MedlinePLUS

... to learn what's in the air. You are here: Health Information > Healthy Lifestyle > Nutrition > Reflux and Lung ... weight and dietary habits can contribute to reflux. Here are a few recommendations to decrease the risk ...

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.

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

2012-01-01

57

[Spontaneous lung torsion after acute pleuropneumonia].  

PubMed

We report on a case of spontaneous torsion of the right lung in a 59 years old woman which occurred after an acute pneumonia followed by chronic empyema and progressive dyspnea with marked respiratory disability. Despite extensive diagnostic procedures including bronchoscopy and bronchography the true diagnosis could be established only by thoracotomy performed in order to cure the chronic empyema. The abnormal hilar rigidity by preexisting calcified sarcoidosis of the lymph-nodes is suggested to be a major risk factor for developing lung torsion as it has been emphasized in a few similar reports from the literature. Surgical reposition of the displaced lung is the most effective treatment and can save and restitute lung structure and function even in patients with prolonged course and delayed diagnosis. PMID:1494581

Hufschmid, P; Keller, R; Aeberhard, P

1992-12-01

58

Hard Metal Interstitial Lung Disease  

Microsoft Academic Search

Hard metal lung disease is an unusual disease which can occur in individuals exposed to hard metals. Clinically, the condition resembles hypersensitivity pneumonitis depending mainly on individual susceptibility, which eventually progresses to pulmonary fibrosis. We present two patients with pulmonary fibrosis, who were actually diagnosed after an exhaustive anamnesis and examination of the tissue by scanning microscope to discard hard

M. Ángeles Montero; Javier de Gracia; Ferràn Morell

2010-01-01

59

An Acute Change in Lung Allocation Score and Survival After Lung Transplantation A Cohort Study  

PubMed Central

Background Lung transplantation is an effective treatment for patients with advanced lung disease. In the United States, lungs are allocated on the basis of the lung allocation score (LAS), a composite measure of transplantation urgency and utility. Clinical deteriorations result in increases to the LAS; however, whether the trajectory of the LAS has prognostic significance is uncertain. Objective To determine whether an acute increase in the LAS before lung transplantation is associated with reduced posttransplant survival. Design Retrospective cohort study of adult lung transplant recipients listed for at least 30 days between 4 May 2005 (LAS implementation) and 31 December 2010 in the United Network for Organ Sharing registry. An acute increase in the LAS was defined as an LAS change (LAS?) greater than 5 units between the 30 days before and the time of transplantation. Multivariable Cox proportional hazards models were used to examine the relationship between an LAS? >5 and posttransplant graft survival. Setting All U.S. lung transplantation centers. Patients 5749 lung transplant recipients. Measurements Survival time after lung transplantation. Results 702 (12.2%) patients experienced an LAS? >5. These patients had significantly worse posttransplant survival (hazard ratio, 1.31 [95% CI, 1.11 to 1.54]; P = 0.001]) after adjustment for the LAS at transplantation and other clinical covariates. The effect of an LAS? >5 was independent of the LAS at transplantation, underlying diagnosis, center volume, or donor characteristics. Limitation Analysis was based on center-reported data. Conclusion An acute increase in LAS before transplantation is associated with posttransplant survival after adjustment for LAS at transplantation. Further emphasis on serial assessment of the LAS could improve prognostication after transplantation.

Copeland, C. Ashley Finlen; Lederer, David J.; Palmer, Scott M.

2013-01-01

60

Genomics of Acute Lung Injury and Vascular Barrier Dysfunction  

Microsoft Academic Search

\\u000a Acute lung injury (ALI) is a devastating ­syndrome of diffuse alveolar damage that develops via a variety of local and systemic\\u000a insults such as sepsis, trauma, ­pneumonia, and aspiration. It is interestingly to note that only a subset of individuals\\u000a exposed to potential ALI-inciting insults develop the disorder and the severity of the disease varies from complete resolution\\u000a to death.

Roberto F. Machado; Joe G. N. Garcia

61

Potential application of mesenchymal stem cells in acute lung injury  

PubMed Central

Despite extensive research into the pathogenesis of acute lung injury and the acute respiratory distress syndrome (ALI/ARDS), mortality remains high at approximately 40%. Current treatment is primarily supportive, with lung-protective ventilation and a fluid conservative strategy. Pharmacologic therapies that reduce the severity of lung injury in experimental studies have not yet been translated into effective clinical treatment options. Therefore, innovative therapies are needed. Recent studies have suggested that bone-marrow-derived multipotent mesenchymal stem cells (MSC) may have therapeutic applications in multiple clinical disorders including myocardial infarction, diabetes, sepsis, hepatic and acute renal failure. Recently, MSC have been studied in several in vivo models of lung disease. This review focuses on first describing the existing experimental literature that has tested the use of MSC in models of ALI/ARDS, and then the potential mechanisms underlying their therapeutic use with an emphasis on secreted paracrine soluble factors. The review concludes with a discussion of future research directions required for potential clinical trials.

Lee, Jae Woo; Gupta, Naveen; Serikov, Vladimir; Matthay, Michael A

2010-01-01

62

Gaseous therapeutics in acute lung injury.  

PubMed

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) remain major causes of morbidity and mortality in critical care medicine despite advances in therapeutic modalities. ALI can be associated with sepsis, trauma, pharmaceutical or xenobiotic exposures, high oxygen therapy (hyperoxia), and mechanical ventilation. Of the small gas molecules (NO, CO, H?S) that arise in human beings from endogenous enzymatic activities, the physiological significance of NO is well established, whereas that of CO or H?S remains controversial. Recent studies have explored the potential efficacy of inhalation therapies using these small gas molecules in animal models of ALI. NO has vasoregulatory and redox-active properties and can function as a selective pulmonary vasodilator. Inhaled NO (iNO) has shown promise as a therapy in animal models of ALI including endotoxin challenge, ischemia/reperfusion (I/R) injury, and lung transplantation. CO, another diatomic gas, can exert cellular tissue protection through antiapoptotic, anti-inflammatory, and antiproliferative effects. CO has shown therapeutic potential in animal models of endotoxin challenge, oxidative lung injury, I/R injury, pulmonary fibrosis, ventilator-induced lung injury, and lung transplantation. H?S, a third potential therapeutic gas, can induce hypometabolic states in mice and can confer both pro- and anti-inflammatory effects in rodent models of ALI and sepsis. Clinical studies have shown variable results for the efficacy of iNO in lung transplantation and failure for this therapy to improve mortality in ARDS patients. No clinical studies have been conducted with H?S. The clinical efficacy of CO remains unclear and awaits further controlled clinical studies in transplantation and sepsis. PMID:23737166

Ryter, Stefan W; Choi, Augustine M K

2011-01-01

63

Transfusion-related acute lung injury in multiple traumatized patients  

PubMed Central

Background: Many of the multiple traumatized patients who refer to the hospital need transfusion. Transfusion-related acute lung injury (TRALI) is a serious clinical syndrome associated with the transfusion of plasma-containing blood components. In the article, we present a case of TRALI following transfusion of packed red blood cells Case Presentation: A 24 year old male referred to Shahid Beheshti Hospital due to multiple trauma with left femoral and humerus fractures. Due to severe anemia he received 3 units of packed red blood cells. The symptoms of TRALI began 2 hours after transfusion. He was transferred to intensive care unit (ICU) due to metabolic acidosis and severe hypoxia. The TRALI was confirmed after ruling out the other probable pulmonary diseases. He recovered and was discharged. Conclusion: Transfusion related acute lung injury should be considered in any case receiving transfusion of plasma containing blood components.

Alijanpour, Ebrahim; Jabbari, Ali; Hoseini, Fahimeh; Tabasi, Shabnam

2012-01-01

64

Restrictive lung disease in pregnancy.  

PubMed

Restrictive lung disease is uncommon in pregnancy. We reviewed 15 pregnancies in 12 women with restrictive disease due to kyphoscoliosis, neuromuscular disease, or parenchymal lung disease. Median FVC was 40% predicted, and six women (50%) had an FVC < 1.0 L. In the 14 pregnancies in which at least two spirometry readings were available, FVC increased in three pregnancies, decreased in three, and remained stable in eight, with maximal changes of 0.4 L. Three women required supplemental oxygen, and one woman with neuromuscular disease required noninvasive ventilation. Premature delivery occurred in nine pregnancies (60%), and 10 deliveries (67%) were by cesarean section. Neuraxial anesthesia was used in 10 of 15 deliveries but was limited in the others by difficult spinal anatomy. There was no maternal or neonatal mortality. Women with restrictive lung disease tolerate pregnancy reasonably well, but many have premature delivery. A multidisciplinary approach is essential, with monitoring of spirometry and oxygenation and planning for labor and delivery. PMID:24493511

Lapinsky, Stephen E; Tram, Carolyn; Mehta, Sangeeta; Maxwell, Cynthia V

2014-02-01

65

Expression Profiling in Granulomatous Lung Disease  

Microsoft Academic Search

The application of expression profiling to granulomatous lung disease is in its infancy. Sarcoidosis, hypersensitivity pneumonitis (HP), Wegener's granulomatosis (WG), and chronic beryllium- induced lung disease (CBD) have been the targets of a limited number of genomic and proteomic studies. In contrast, mycobac- terial disease represents an infectious granulomatous lung dis- ease that has been the subject of more intense

Edward S. Chen; David R. Moller

2007-01-01

66

Ureaplasma urealyticum and chronic lung disease  

Microsoft Academic Search

Neonatal lower respiratory tract colonisation with mycoplasma organisms was examined for an association with chronic lung disease.Ureaplasma urealyticum colonised 9\\/70 (13%) infants less than 1500 g. Seven (78%) colonised and 33 (54%) non-colonised infants developed chronic lung disease. Logistic regression analyses revealed early gestation, but not mycoplasma colonisation, was independently associated with chronic lung disease.

A. R. Smyth; N. J. Shaw; B. C. Pratt; A. M. Weindling

1993-01-01

67

[Lung biopsy for the diagnosis of interstitial lung disease].  

PubMed

The objective of this study was to determine the morbidity, mortality and diagnostic yield of video assisted thoracoscopy (VATS) and thoracotomy lung biopsy in interstitial lung disease (ILD). Clinical records of 71 patients were retrospectively analyzed. There was no difference in mean hospital stay, intensive care unit stay and duration of chest tube drainage in patients with VATS (n = 52) compared with those undergoing open thoracotomy (n = 17). Complications rate (22.2% vs. 21.0%, p = 1.0000) and operating mortality (9.2 vs. 15.7%, p = 0.2738) were also similar. Overall, complications occurred in 16 patients (22.5%). Thirty-day mortality rate was 11.2% (n = 8). Prevalence of immunosupression (4/8 vs. 9/63, p = 0.0325) was significantly higher in the group of patients who died. No surviving patients had higher values of plasmatic urea (50 +/- 20.1 mg/dl vs. 31.2 +/- 10.3 mg/dl, p = 0.0013) or lower values of preoperative oxygen saturation (SaO2): 82.7 +/- 14.8% vs. 92.8 +/- 3.4%, (p = 0.0009). Eleven patients had an acute illness. Those patients did not show a higher complication rate (4/11 vs. 10/45, p = 0.4390) but mortality was significantly higher (4/11, 36.3% vs. 3/45, 7.1%, p = 0.0223). Biopsy allowed a specific histologic diagnosis in 100% of patients and changed therapy in 66.7%. We conclude that surgical lung biopsy is a safe and useful procedure in patients with ILD. However the higher mortality rate in patients with acute symptoms, immunocompromise, or in respiratory failure must be balanced against potential benefits of altering treatment decisions. PMID:18422059

Quadrelli, Silvia; Lyons, Gustavo; Ciallella, Lorena; Iotti, Alejandro; Chertcoff, Julio

2007-01-01

68

Genetically manipulated mouse models of lung disease: potential and pitfalls  

PubMed Central

Gene targeting in mice (transgenic and knockout) has provided investigators with an unparalleled armamentarium in recent decades to dissect the cellular and molecular basis of critical pathophysiological states. Fruitful information has been derived from studies using these genetically engineered mice with significant impact on our understanding, not only of specific biological processes spanning cell proliferation to cell death, but also of critical molecular events involved in the pathogenesis of human disease. This review will focus on the use of gene-targeted mice to study various models of lung disease including airways diseases such as asthma and chronic obstructive pulmonary disease, and parenchymal lung diseases including idiopathic pulmonary fibrosis, pulmonary hypertension, pneumonia, and acute lung injury. We will attempt to review the current technological approaches of generating gene-targeted mice and the enormous dataset derived from these studies, providing a template for lung investigators.

Choi, Alexander J. S.; Owen, Caroline A.; Choi, Augustine M. K.

2012-01-01

69

Perception of dyspnoea during acute changes in lung function in patients with either asthma or COPD  

Microsoft Academic Search

The aim of the study was to evaluate the relationship between several lung function indices and perceived dyspnoea during bronchoconstriction. Acute changes in lung function were induced by inhaled histamine followed by terbutaline, in 12 asthmatics and 12 subjects with chronic obstructive pulmonary disease (COPD). A bipolar visual analogue scale (VAS), allowing subjects to report either improvement or worsening when

A. Noseda; J. Schmerber; T. Prigogine; V. de Maertelaer; J. C. Yernault

1995-01-01

70

Acute Lung Injury in the Medical ICU Comorbid Conditions, Age, Etiology, and Hospital Outcome  

Microsoft Academic Search

The independent effects of chronic disease, age, severity of illness, lung injury score (LIS) and etiol- ogy, and preceding nonpulmonary organ-system dysfunction (OSD) on the outcome of acute lung in- jury (ALI) have not been examined in an exclusively medical-intensive-care-unit (MICU) population. Therefore, 107 consecutive MICU patients with ALI (76% with acute respiratory distress syndrome (ARDS)) were prospectively investigated. The

MARYA D. ZILBERBERG; SCOTT K. EPSTEIN

71

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

72

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.

Sanderson, Michael J.

2011-01-01

73

Lung ultrasonography for the diagnosis of neonatal lung disease.  

PubMed

Ultrasound has recently become an important method for diagnostic examination and monitoring of lung disease. Many lung diseases, such as respiratory distress syndrome, transient tachypnea of the newborn, pneumonia, atelectasis and pneumothorax were diagnosed by chest X-ray or CT scan in the past, but can now easily be diagnosed with lung ultrasound. Lung ultrasound has many advantages over X-ray and CT scan including accuracy, reliability, low-cost and simplicity, as well as the fact that ultrasound incurs no risk of radiation damage. It is therefore feasible and convenient to perform at the bedside in a neonatal ward. This review focuses on features of bedside lung ultrasound and diagnosis features of common lung diseases in newborn infants, culminating in suggestions for improving the application of ultrasound in the neonatal field. PMID:24028601

Liu, Jing

2014-05-01

74

Radiographic measurement of total lung capacity in acute asthma  

Microsoft Academic Search

The thoracic cage appears to be large during attacks of asthma. Lung volume measurements by body plethysmography and helium dilution have suggested that total lung capacity may be increased during an acute attack of asthma, but doubt has been cast on the accuracy of these measurements in the presence of airflow obstruction. The change in total lung capacity has therefore

M S Rothstein; M N Zelefsky; P Q Eichacker; D J Rudolph; M H Williams

1989-01-01

75

Does leflunomide attenuate the sepsis-induced acute lung injury?  

Microsoft Academic Search

The organ that is affected first and most severely in intraabdominal sepsis is the lung. Oxygen radicals and active neutrophils\\u000a in the lung are important sources for severe pulmonary inflammation leading to acute lung injury (ALI)\\/acute respiratory distress\\u000a syndrome. The aim of this study was to investigate the effects of leflunomide, an immunomodulatory agent, on oxidant\\/antioxidant\\u000a status with nitric oxide

Erdogan Ozturk; Semra Demirbilek; Zekine Begec; Murat Surucu; Ersin Fadillioglu; Hale K?r?ml?oglu; M. Ozcan Ersoy

2008-01-01

76

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.

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

2012-01-01

77

Prolonged acute kidney injury exacerbates lung inflammation at 7 days post-acute kidney injury.  

PubMed

Patients with acute kidney injury (AKI) have increased mortality; data suggest that the duration, not just severity, of AKI predicts increased mortality. Animal models suggest that AKI is a multisystem disease that deleteriously affects the lungs, heart, brain, intestine, and liver; notably, these effects have only been examined within 48 h, and longer term effects are unknown. In this study, we examined the longer term systemic effects of AKI, with a focus on lung injury. Mice were studied 7 days after an episode of ischemic AKI (22 min of renal pedicle clamping and then reperfusion) and numerous derangements were present including (1) lung inflammation; (2) increased serum proinflammatory cytokines; (3) liver injury; and (4) increased muscle catabolism. Since fluid overload may cause respiratory complications post-AKI and fluid management is a critical component of post-AKI care, we investigated various fluid administration strategies in the development of lung inflammation post-AKI. Four different fluid strategies were tested - 100, 500, 1000, or 2000 ?L of saline administered subcutaneously daily for 7 days. Interestingly, at 7 days post-AKI, the 1000 and 2000 ?L fluid groups had less severe AKI and less severe lung inflammation versus the 100 and 500 ?L groups. In summary, our data demonstrate that appropriate fluid management after an episode of ischemic AKI led to both (1) faster recovery of kidney function and (2) significantly reduced lung inflammation, consistent with the notion that interventions to shorten AKI duration have the potential to reduce complications and improve patient outcomes. PMID:25052489

Andres-Hernando, Ana; Altmann, Christopher; Bhargava, Rhea; Okamura, Kayo; Bacalja, Jasna; Hunter, Brandi; Ahuja, Nilesh; Soranno, Danielle; Faubel, Sarah

2014-07-01

78

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.

2010-01-01

79

Apoptosis in Lung Injury and Disease  

Microsoft Academic Search

Pulmonary cell death may contribute significantly to acute and chronic lung injuries caused by various adverse environmental\\u000a agents. Pulmonary cells may die by necrosis, apoptosis, and other forms of regulated cell death. Apoptosis exerts a homeostatic\\u000a function in lung defense and development, through the removal of dysfunctional cells and by regulating cellular proliferation.\\u000a Lung cell apoptosis can occur as a

Stefan W. Ryter; Hong Pyo Kim; Augustine M. K. Choi

80

Infiltrative lung diseases in pregnancy.  

PubMed

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

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

2011-03-01

81

Patterns and etiology of acute and chronic lung injury: insights from experimental evidence.  

PubMed

Adequate pulmonary function is pivotal for preterm infants. Besides being structurally immature, the preterm lung is susceptible to injury resulting from different prenatal conditions and postnatal insults. Lung injury might result in impaired postnatal lung development, contributing to chronic lung disease of prematurity, bronchopulmonary dysplasia (BPD). This review focuses on lung injury mediated by and related to inflammatory changes in the lung. We give an overview on experimental models which have helped to elucidate mechanisms of pulmonary inflammation in prematurity. We describe experimental data linking acute and chronic chorioamnionitis with intrapulmonary inflammation, lung maturation and surfactant production in various animal models. In addition, experimental data has shown that fetal inflammatory response is modulated by the fetus himself. Experimental data has therefore helped to understand differential effects on lung function and lung maturation exerted by maternal administration of potentially anti-inflammatory substances like glucocorticosteroids (GCS). New approaches of modulation of pulmonary inflammation/injury caused by postnatal interventions during resuscitation and mechanical ventilation have been studied in animal models. Postnatal therapeutic interventions with widely used drugs like oxygen, steroids, surfactant, caffeine and vitamin A have been experimentally and mechanistically assessed regarding their effect on pulmonary inflammation and lung injury. Carefully designed experiments will help to elucidate the complex interaction between lung injury, lung inflammation, repair and altered lung development, and will help to establish a link between lung alterations originating in this early period of life and long-term adverse respiratory effects. PMID:24856991

Hütten, Matthias C; Kramer, Boris W

2014-05-01

82

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.

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

2012-01-01

83

[Transfusion-related acute lung injury].  

PubMed

Transfusion-related acute lung injury (TRALI) developed into the leading cause of transfusion-related morbidity and mortality after the first description by Popovsky et al. approximately three decades ago. It was the most frequent reason for transfusion-related fatalities worldwide before implementation of risk minimization strategies by donor selection. Plasma-rich blood products, such as fresh frozen plasma and apheresis platelets seem to be the leading triggers of TRALI. Hypoxemia and development of pulmonary edema within 6 h of transfusion are the diagnostic criteria for TRALI. The differentiation between cardiac failure and other transfusion-related lung injuries, such astransfusion-associated circulatory overload ( TACO) is difficult and causal treatment is not available. Therapy is based on supportive measures, such as oxygen insufflationor mechanical ventilation. The exactly pathogenesis is still unknown but the most propagated hypothesis is the two-event-model. Neutrophils are primed by the underlying condition, e.g. sepsis or trauma during the first event and these primed neutrophils are activated by transfused leukoagglutinating antibodies (immunogen) or bioreactive mediators (non-immunogen) during the second-event. Transfusion of leukoagglutinating antibodies from female donors with one or more previous pregnancies is the most frequent reason. No more TRALI fatalities were reported after implementation of the donor selection in Germany in 2009. PMID:23558721

Tank, S; Sputtek, A; Kiefmann, R

2013-04-01

84

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

PubMed

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 ischaemia-reperfusion and overventilation-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

Jia, Yanlin; Chen, Ken; Lin, Peihui; 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

85

The role of matrix metalloproteases in cystic fibrosis lung disease  

PubMed Central

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

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

2014-01-01

86

Inhibition of the phosphatase PTEN protects mice against oleic acid-induced acute lung injury  

PubMed Central

Background and purpose Injury to the lung parenchyma is a constitutional feature shared by many lung diseases. The protein, phosphatase and tensin homologue deleted on chromosome Ten (PTEN) is a major suppressor of phosphoinositide-3 kinase/Akt signalling, a vital survival pathway in lung parenchymal cells. Based on this, we hypothesized that PTEN inhibition in vivo would enhance cell tolerance to stress thereby preventing acute lung injury. Experimental approach We evaluated the ability of a PTEN inhibitor, potassium bisperoxo (1,10-phenanthroline) oxovanadate [bpV(phen)], to prevent acute lung injury induced by oleic acid (OA) in adult C57BL/6 mice. Lung assessments included bronchoalveolar lavage, tissue morphology, immunostaining for markers of cell death, cell identity, phospho-Akt and phospho-ERK levels and oximetry. Key results OA induced acute lung injury in a dose- and time-dependent manner. No injury was observed in the vehicle control or bpV(phen) treatment groups. PTEN inhibition by bpV(phen) increased lung tissue levels of phospho-Akt and ERK and but not focal adhesion kinase. This occurred in conjunction with a statistically significant reduction in protein content, lactate dehydrogenase, as well as tumour necrosis factor-? and chemokines in bronchoalveolar lavage fluid when compared with OA treatment alone. The incidence of alveolar lesions, consistent with acute lung injury, and terminal uridine deoxynucleotidyl transferase dUTP nick end labelling (TUNEL)-positive cells was also significantly reduced. Importantly, PTEN suppression maintained pulmonary function. Conclusions and implications Treatment with bpV(phen) significantly reduced the severity of acute lung injury in mice indicating that additional investigation is warranted to understand the important role that this phosphatase may play in the lung.

Lai, Ju-Ping; Bao, Shengying; Davis, Ian C; Knoell, Daren L

2009-01-01

87

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.

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

2012-01-01

88

[Interstitial lung diseases in sarcoidosis].  

PubMed

Sarcoidosis is a multisystem disorder of unknown aetiology characterized by immune granuloma in involved tissue with predilection for lung and lymphoid system. The sarcoidosis aetiology remains unknown. It could result of genetic predisposition and exposure to specific enviromental factors. The chest X-ray is abnormal in 90% of cases with adenopathies and/or massive pulmonary infiltration with or without fibrosis. The different aspects are classified in 4 stages. The diagnosis is done when clinical and radiological usual signs are present with histological granuloma without caseum and in the absence of any other granulomatous disease. Most of the time, sarcoidosis spontaneously heals in 2 to 3 years. 10 to 30% of cases are chronic and often more severe. The disease could lastly generate a pulmonary fibrosis with a potential respiratory insufficiency, cor pulmonale, or aspergillus infection. Cardiac, neurologic, throat, kidney or ophthalmologic lesions or hypercalcemia may also be of bad prognosis. Sarcoidosis is lethal in 0.5 to 5% of cases. Mild disease does not need to be treated. Systemic corticosteroid for 12 months at least is the treatment for more severe diseases. Antimalarials drugs and immunomodulatory agents may be used if corticosteroids cannot be used or failed. TNFalpha recently proposed is currently evaluated. PMID:18320746

Bouvry, Diane; Naccache, Jean-Marc; Valeyre, Dominique

2007-12-31

89

Interstitial Lung Diseases: Respiratory Review of 2013  

PubMed Central

Interstitial lung diseases are heterogeneous entities with diverse clinical presentations. Among them, idiopathic pulmonary fibrosis and connective tissue disease-associated interstitial lung disease are specific categories that pulmonologists are most likely to encounter in the clinical field. Despite the accumulated data from extensive clinical trial and observations, we continue to have many issues which need to be resolved in this field. In this update, we present the review of several articles regarding the clinical presentation, prognosis and treatment of patients with idiopathic pulmonary fibrosis or connective tissue disease-associated interstitial lung disease.

Kim, Yong Hyun

2013-01-01

90

[Fahr's disease accompanying to lung cancer].  

PubMed

Fahr's disease occurs in relation with many metabolic disorders especially with hypoparathyroidism. Imbalance of the coordination system and dysarthria were seen at the end of the treatment in a lung cancer patient treated with radiotherapy and chemotherapy. Fahr's disease was diagnosed by diffuse symmetric calcifications at white matter and basal ganglia of cerebrum and cerebellum in cranial computed tomography. Disease was thought to be caused by hypoparathyroidism with lower calcium and parathyroid hormone levels. Possible factor that caused hipoparathyroidism and also of Fahr's disease was radiotherapy performed to a wide area because of lung cancer. This case is the first Fahr's disease that was diagnosed concurrently with lung cancer. PMID:21038145

Erbaycu, Ahmet Emin; Edibo?lu, Hakan; Mavi?, Ahmet Vedit; Ozantürk, Murat Erdal; Tuksavul, Fevziye; Gürsoy, Soner; Güçlü, Salih Zeki

2010-01-01

91

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 ...

92

Susceptibility to nontuberculous mycobacterial lung disease  

Microsoft Academic Search

The nontuberculous mycobacteria (NTM) exhibit heterogeneous pathogenicity in humans. Articles on known and potential human factors capable of producing susceptibility to NTM lung disease (NTMLD) were identified by a systematic search of the medical literature, and are reviewed in the present study. Patients with pre-existing structural lung disease are known to be at risk of NTMLD. Other susceptible groups have

P. Sexton; A. C. Harrison

2008-01-01

93

Neurotrophins in lung health and disease  

PubMed Central

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

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

2010-01-01

94

Drug-Associated Acute Lung Injury  

PubMed Central

Background: A number of drugs have been reported as risk factors for acute lung injury (ALI) and ARDS. However, evidence is largely limited to case reports, and there is a paucity of data on the incidence and outcome of drug-associated ALI (DALI). Methods: Using a population-based retrospective cohort study design, critically ill patients with a diagnosis of ALI were studied. These patients were classified as having DALI or non-DALI, based on whether they were exposed to prespecified drugs prior to development of ALI. Outcomes were compared between the two groups and frequencies and incidences reported. Results: Among 514 patients with ALI, 49 (9.5%) had DALI with an estimated population-based incidence of 6.6 (95% CI, 4.8-8.5) per 100,000 person-years. Of the 49 patients with DALI, 36 received chemotherapeutic/antiinflammatory agents, and 14 received amiodarone. Twelve patients had no additional risk factors for ALI (probable DALI), whereas 37 had alternative risk factors (possible DALI). Patients with and without DALI had similar baseline characteristics. However, the APACHE (Acute Physiology and Chronic Health Evaluation) III scores (median, 83 vs 70, P = .03), ICU mortality (35% vs 20%, P = .03), and hospital mortality (63% vs 32%, P < .001) were significantly higher in the DALI group compared with those of the non-DALI group. Hospital mortality remained significantly higher after adjusting for APACHE III score on admission and the presence of malignancy in logistic regression analysis (OR, 2.8; 95% CI, 1.3-6.4; P = .009). Conclusions: Drugs are important risk factors for ALI, and recognizing them as such may have important implications for early identification of patients at risk, discontinuation of the offending agent, and prognosis.

Li, Guangxi; Schmickl, Christopher N.; Kashyap, Rahul; Assudani, Jyoti; Limper, Andrew H.; Gajic, Ognjen

2012-01-01

95

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

96

Malignant disease and the lung  

Microsoft Academic Search

Primary lung tumours in childhood are rare. However, cancer in a child may have an impact on the lung in a number of ways. Chemotherapy and radiotherapy may be directly toxic to the lung. Young children are particularly sensitive to the effects of radiotherapy, which can cause impairment of growth of muscle, skin and bone, in addition to its direct

M. E. M. Jenney

2000-01-01

97

Acute lung injury and pulmonary vascular permeability: use of transgenic models.  

PubMed

Acute lung injury is a general term that describes injurious conditions that can range from mild interstitial edema to massive inflammatory tissue destruction. This review will cover theoretical considerations and quantitative and semi-quantitative methods for assessing edema formation and increased vascular permeability during lung injury. Pulmonary edema can be quantitated directly using gravimetric methods, or indirectly by descriptive microscopy, quantitative morphometric microscopy, altered lung mechanics, high-resolution computed tomography, magnetic resonance imaging, positron emission tomography, or x-ray films. Lung vascular permeability to fluid can be evaluated by measuring the filtration coefficient (Kf) and permeability to solutes evaluated from their blood to lung clearances. Albumin clearances can then be used to calculate specific permeability-surface area products (PS) and reflection coefficients (?). These methods as applied to a wide variety of transgenic mice subjected to acute lung injury by hyperoxic exposure, sepsis, ischemia-reperfusion, acid aspiration, oleic acid infusion, repeated lung lavage, and bleomycin are reviewed. These commonly used animal models simulate features of the acute respiratory distress syndrome, and the preparation of genetically modified mice and their use for defining specific pathways in these disease models are outlined. Although the initiating events differ widely, many of the subsequent inflammatory processes causing lung injury and increased vascular permeability are surprisingly similar for many etiologies. PMID:23737205

Parker, James C

2011-04-01

98

A Reconsideration of Acute Beryllium Disease  

PubMed Central

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

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

2009-01-01

99

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.

2010-01-01

100

Inhaled Corticosteroids in Lung Diseases  

PubMed Central

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

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

2013-01-01

101

Alcohol, smoking and lung disease.  

PubMed

Alcohol and smoking are two well-known health hazards. Alcohol and tobacco consumption are strongly correlated and heavy drinkers have more trouble quitting smoking than do light drinkers. Death from tobacco-related causes was more common than alcohol-related death in a follow-up study on patients admitted to an addiction programme for treatment of alcoholism and non-nicotine drug dependence. In British male doctors in the middle and elderly age group, a protective effect of light and moderate alcohol consumption (1-3 British units of alcohol per day) compared with abstinence has been shown in one large survey. This protective effect was shown in overall mortality as well as in mortality from respiratory disease. Higher alcohol intakes were associated with an increase in mortality. This characteristic U-formed, or J-formed, dose-response curve has been found in most studies with an apparent beneficial effect of modest alcohol intake and a harmful effect of high intakes. The anti-inflammatory effect of alcohol has been considered to be responsible for its limited protective effect on smoking-related lung function decline. Recently, a hitherto unconfirmed report suggests that the beneficial effect of alcohol on lung function in men is restricted to subjects with Lewis-negative blood group (10% of the Caucasian population). On the other hand, the protective effect in those individuals is large enough to be clinically relevant. Prospective investigations including both men and women are needed to elucidate which individuals have a protective effect of light and moderate alcohol intake. The major deleterious effect of smoking, including passive smoking, must be kept in mind-drinking alcohol surrounded by cigarette smoke might not be beneficial for respiratory health. PMID:20575766

Ström, K

1999-01-01

102

Emerging roles for cholesterol and lipoproteins in lung disease.  

PubMed

Dyslipidemia, the condition of elevated serum triglycerides, elevated low-density lipoprotein cholesterol, and/or low high-density lipoprotein cholesterol, is a public health problem of growing concern. Dyslipidemia clusters with other disorders of the metabolic syndrome that together influence, and may derive from, chronic inflammation. While best recognized as a risk factor for atherosclerotic cardiovascular disease, lipid dysregulation has recently been shown to influence a variety of disease processes in several organ systems. This review highlights our current understanding of the role of cholesterol and its homeostatic trafficking in pulmonary physiology and pathophysiology. Gene-targeted mice deficient in regulatory proteins that govern reverse cholesterol transport (e.g., ATP Binding Cassette transporter G1, apolipoprotein E) have recently been shown to have abnormal lung physiology, including dysregulated pulmonary innate and adaptive immune responses to the environment. It has also recently been shown that diet-induced dyslipidemia alters trafficking of immune cells to the lung in a manner that may have important implications for the pathogenesis of acute lung injury, asthma, pneumonia, and other lung disorders. Conversely, cholesterol-targeting pharmacologic agents, such as statins, apolipoprotein mimetic peptides, and Liver X Receptor agonists, have shown early promise in the treatment of several lung disorders. An improved understanding of the precise molecular mechanisms by which cholesterol and its trafficking modify pulmonary immunity will be required before the full implications of dyslipidemia as a lung disease modifier, and the full potential of lipid-targeting agents as pulmonary therapeutics, can be realized. PMID:22706330

Gowdy, Kymberly M; Fessler, Michael B

2013-08-01

103

Cytokines and ventilator-induced acute lung injury  

Microsoft Academic Search

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

Bing HAN; Mingyao LIU

2002-01-01

104

Interstitial lung disease: progress and problems  

PubMed Central

Interstitial lung disease involves all areas of medicine as it often occurs in patients with comorbidities or as a consequence of systemic diseases and their treatment. Typically the physician is faced with a breathless patient, a diffusely abnormal chest radiograph, and a wide differential diagnosis. Progress has been made in using high resolution computed tomography as the key investigation in characterising the pattern and extent of the disease. Bronchoalveolar lavage is particularly important in excluding infection as a cause of diffuse lung infiltrates. Surgical lung biopsies have led to a new classification system for the range of histopathological patterns of disease that were previously known by the collective term cryptogenic fibrosing alveolitis. Problems persist in deciding when a surgical lung biopsy is clinically justified, in understanding the pathogenesis of these diseases, and in finding more effective treatments.

Bourke, S J

2006-01-01

105

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

Microsoft Academic Search

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

Jörg Reutershan; Klaus Ley

2004-01-01

106

Pathogenesis of Lung Disease in Cystic Fibrosis  

Microsoft Academic Search

Lung disease in cystic fibrosis is primarily due to a defect in the cystic fibrosis transmembrane regulating protein (CFTR). This results in abnormal chloride transfer across epithelial membranes causing an excessively viscid mucus lining of the airways. Bacterial invasion particularly with Staphylococcus aureus, Haemophilus influenzae and Pseudomonas aeruginosa stimulates a vigorous and excessive primarily neutrophil-driven inflammatory response throughout the lungs.

R. Dinwiddie

2000-01-01

107

NET balancing: a problem in inflammatory lung diseases.  

PubMed

Neutrophil extracellular traps (NETs) are beneficial antimicrobial defense structures that can help fight against invading pathogens in the host. However, recent studies reveal that NETs exert adverse effects in a number of diseases including those of the lung. Many inflammatory lung diseases are characterized with a massive influx of neutrophils into the airways. Neutrophils contribute to the pathology of these diseases. To date, NETs have been identified in the lungs of cystic fibrosis (CF), acute lung injury (ALI), allergic asthma, and lungs infected with bacteria, virus, or fungi. These microbes and several host factors can stimulate NET formation, or NETosis. Different forms of NETosis have been identified and are dependent on varying types of stimuli. All of these pathways however appear to result in the formation of NETs that contain DNA, modified extracellular histones, proteases, and cytotoxic enzymes. Some of the NET components are immunogenic and damaging to host tissue. Innate immune collectins, such as pulmonary surfactant protein D (SP-D), bind NETs, and enhance the clearance of dying cells and DNA by alveolar macrophages. In many inflammatory lung diseases, bronchoalveolar SP-D levels are altered and its deficiency results in the accumulation of DNA in the lungs. Some of the other therapeutic molecules under consideration for treating NET-related diseases include DNases, antiproteases, myeloperoxidase (MPO) inhibitors, peptidylarginine deiminase-4 inhibitors, and anti-histone antibodies. NETs could provide important biological advantage for the host to fight against certain microbial infections. However, too much of a good thing can be a bad thing. Maintaining the right balance of NET formation and reducing the amount of NETs that accumulate in tissues are essential for harnessing the power of NETs with minimal damage to the hosts. PMID:23355837

Cheng, Olivia Z; Palaniyar, Nades

2013-01-01

108

NET balancing: a problem in inflammatory lung diseases  

PubMed Central

Neutrophil extracellular traps (NETs) are beneficial antimicrobial defense structures that can help fight against invading pathogens in the host. However, recent studies reveal that NETs exert adverse effects in a number of diseases including those of the lung. Many inflammatory lung diseases are characterized with a massive influx of neutrophils into the airways. Neutrophils contribute to the pathology of these diseases. To date, NETs have been identified in the lungs of cystic fibrosis (CF), acute lung injury (ALI), allergic asthma, and lungs infected with bacteria, virus, or fungi. These microbes and several host factors can stimulate NET formation, or NETosis. Different forms of NETosis have been identified and are dependent on varying types of stimuli. All of these pathways however appear to result in the formation of NETs that contain DNA, modified extracellular histones, proteases, and cytotoxic enzymes. Some of the NET components are immunogenic and damaging to host tissue. Innate immune collectins, such as pulmonary surfactant protein D (SP-D), bind NETs, and enhance the clearance of dying cells and DNA by alveolar macrophages. In many inflammatory lung diseases, bronchoalveolar SP-D levels are altered and its deficiency results in the accumulation of DNA in the lungs. Some of the other therapeutic molecules under consideration for treating NET-related diseases include DNases, antiproteases, myeloperoxidase (MPO) inhibitors, peptidylarginine deiminase-4 inhibitors, and anti-histone antibodies. NETs could provide important biological advantage for the host to fight against certain microbial infections. However, too much of a good thing can be a bad thing. Maintaining the right balance of NET formation and reducing the amount of NETs that accumulate in tissues are essential for harnessing the power of NETs with minimal damage to the hosts.

Cheng, Olivia Z.; Palaniyar, Nades

2013-01-01

109

Pulmonary Hypertension Associated with Interstitial Lung Disease  

Microsoft Academic Search

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

Mary E. Strek; Julian Solway

110

Acute Rejection and Humoral Sensitization in Lung Transplant Recipients  

PubMed Central

Despite the recent introduction of many improved immunosuppressive agents for use in transplantation, acute rejection affects up to 55% of lung transplant recipients within the first year after transplant. Acute lung allograft rejection is defined as perivascular or peribronchiolar mononuclear inflammation. Although histopathologic signs of rejection often resolve with treatment, the frequency and severity of acute rejections represent the most important risk factor for the subsequent development of bronchiolitis obliterans syndrome (BOS), a condition of progressive airflow obstruction that limits survival to only 50% at 5 years after lung transplantation. Recent evidence demonstrates that peribronchiolar mononuclear inflammation (also known as lymphocytic bronchiolitis) or even a single episode of minimal perivascular inflammation significantly increase the risk for BOS. We comprehensively review the clinical presentation, diagnosis, histopathologic features, and mechanisms of acute cellular lung rejection. In addition, we consider emerging evidence that humoral rejection occurs in lung transplantation, characterized by local complement activation or the presence of antibody to donor human leukocyte antigens (HLA). We discuss in detail methods for HLA antibody detection as well as the clinical relevance, the mechanisms, and the pathologic hallmarks of humoral injury. Treatment options for cellular rejection include high-dose methylprednisolone, antithymocyte globulin, or alemtuzumab. Treatment options for humoral rejection include intravenous immunoglobulin, plasmapheresis, or rituximab. A greater mechanistic understanding of cellular and humoral forms of rejection and their role in the pathogenesis of BOS is critical in developing therapies that extend long-term survival after lung transplantation.

Martinu, Tereza; Chen, Dong-Feng; Palmer, Scott M.

2009-01-01

111

Acute antibody-mediated rejection after lung transplantation.  

PubMed

The role of humoral immunity after lung transplantation remains unclear. In this report, we describe the pathologic findings and clinical course of a case of acute antibody-mediated rejection (AMR) after lung transplantation. After an uncomplicated early course, a 31-year-old man with cystic fibrosis developed acute graft dysfunction 1 month after bilateral lung transplantation. Lung biopsies showed acute pneumonitis with capillary injury, neutrophilic infiltration and nuclear dust. Immunostaining for C4d demonstrated endothelial cell deposition, and circulating donor-specific human leukocyte antigen (HLA) antibodies were identified. Despite severe hypoxemic respiratory failure, he responded well to a regimen consisting of methylprednisolone, plasma exchange, intravenous immunoglobulin and rituximab therapy. He completely recovered clinically although donor-specific HLA antibodies have remained detectable. The incidence of acute AMR after lung transplantation is unknown, but this case fulfills all of the consensus diagnostic criteria, and we suggest that AMR could be an under-recognized cause of acute graft dysfunction. PMID:19134538

Morrell, Matthew R; Patterson, G Alexander; Trulock, Elbert P; Hachem, Ramsey R

2009-01-01

112

Is acute recurrent pancreatitis a chronic disease?  

Microsoft Academic Search

Whether acute recurrent pancreatitis is a chronic disease is still debated and a consensus is not still reached as demonstrated by differences in the classification of acute recurrent pancreatitis. There is major evidence for considering alcoholic pancreatitis as a chronic disease ab initio while chronic pancreatitis lesions detectable in biliary acute recurrent pancreatitis (ARP) seem a casual association. Cystic fibrosis

Alberto Mariani; Pier Alberto Testoni

2008-01-01

113

Computed tomography assessment of exogenous surfactant-induced lung reaeration in patients with acute lung injury  

PubMed Central

Introduction Previous randomized trials failed to demonstrate a decrease in mortality of patients with acute lung injury treated by exogenous surfactant. The aim of this prospective randomized study was to evaluate the effects of exogenous porcine-derived surfactant on pulmonary reaeration and lung tissue in patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS). Methods Twenty patients with ALI/ARDS were studied (10 treated by surfactant and 10 controls) in whom a spiral thoracic computed tomography scan was acquired before (baseline), 39 hours and 7 days after the first surfactant administration. In the surfactant group, 3 doses of porcine-derived lung surfactant (200 mg/kg/dose) were instilled in both lungs at 0, 12 and 36 hours. Each instillation was followed by recruitment maneuvers. Gas and tissue volumes were measured separately in poorly/nonaerated and normally aerated lung areas before and seven days after the first surfactant administration. Surfactant-induced lung reaeration was defined as an increase in gas volume in poorly/non-aerated lung areas between day seven and baseline compared to the control group. Results At day seven, surfactant induced a significant increase in volume of gas in poorly/non-aerated lung areas (320 ± 125 ml versus 135 ± 161 ml in controls, P = 0.01) and a significant increase in volume of tissue in normally aerated lung areas (189 ± 179 ml versus -15 ± 105 ml in controls, P < 0.01). PaO2/FiO2 ratio was not different between the surfactant treated group and control group after surfactant replacement. Conclusions Intratracheal surfactant replacement induces a significant and prolonged lung reaeration. It also induces a significant increase in lung tissue in normally aerated lung areas, whose mechanisms remain to be elucidated. Trial registration NCT00742482.

2010-01-01

114

Acute lung injury and the acute respiratory distress syndrome in the injured patient  

PubMed Central

Acute lung injury and acute respiratory distress syndrome are clinical entities of multi-factorial origin frequently seen in traumatically injured patients requiring intensive care. We performed an unsystematic search using PubMed and the Cochrane Database of Systematic Reviews up to January 2012. The purpose of this article is to review recent evidence for the pathophysiology and the management of acute lung injury/acute respiratory distress syndrome in the critically injured patient. Lung protective ventilation remains the most beneficial therapy. Future trials should compare intervention groups to controls receiving lung protective ventilation, and focus on relevant outcome measures such as duration of mechanical ventilation, length of intensive care unit stay, and mortality.

2012-01-01

115

Proteasomes in lungs from organ donors and patients with end-stage pulmonary diseases.  

PubMed

Proteasomes appear to be involved in the pathophysiology of various acute and chronic lung diseases. Information on the human lung proteasome in health and disease, however, is sparse. Therefore, we studied whether end-stage pulmonary diseases are associated with alterations in lung 20S/26S proteasome content, activity and 20S subunit composition. Biopsies were obtained from donor lungs (n=7) and explanted lungs from patients undergoing lung transplantation because of end stage chronic obstructive pulmonary disease (COPD; n=7), idiopathic pulmonary fibrosis (IPF, n=7) and pulmonary sarcoidosis (n=5). 20S/26S proteasomes in lung extracts were quantified by ELISA, chymotrypsin-like proteasome peptidase activities measured and 20S proteasome beta subunits analyzed by Western blot. As compared with donor lungs, proteasome content was increased in IPF and sarcoidosis, but not in COPD. The relative distribution of free 20S and 26S proteasomes was similar; 20S proteasome was predominant in all extracts. Proteasome peptidase activities in donor and diseased lungs were indistinguishable. All extracts contained a mixed composition of inducible 20S beta immuno-subunits and their constitutive counterparts; a disease associated distribution could not be identified. A higher content of lung proteasomes in IPF and pulmonary sarcoidosis may contribute to the pathophysiology of human fibrotic lung diseases. PMID:24564596

Baker, T A; Bach, H H; Gamelli, R L; Love, R B; Majetschak, M

2014-07-16

116

Aggressive and acute periodontal diseases.  

PubMed

Inflammatory periodontal diseases are highly prevalent, although most of these diseases develop and progress slowly, often unnoticed by the affected individual. However, a subgroup of these diseases include aggressive and acute forms that have a relatively low prevalence but show a rapid-course, high rate of progression leading to severe destruction of the periodontal tissues, or cause systemic symptoms that often require urgent attention from healthcare providers. Aggressive periodontitis is an early-onset, destructive disease that shows a high rate of periodontal progression and distinctive clinical features. A contemporary case definition of this disease is presented. Population studies show that the disease is more prevalent in certain geographic regions and ethnic groups. Aggressive periodontitis is an infectious disease, and recent data show that in affected subjects the subgingival microbiota is composed of a mixed microbial infection, with a wide heterogeneity in the types and proportions of microorganisms recovered. Furthermore, there are significant differences in the microbiota of the disease among different geographic regions and ethnicities. There is also evidence that the Aggregatibacter actinomycetemycomitans-JP2 clone may play an important role in the development of the disease in certain populations. The host response plays an important role in the susceptibility to aggressive periodontitis, where the immune response may be complex and involve multiple mechanisms. Also, genetic factors seem to play an important role in the pathogenesis of this disease, but the mechanisms of increased susceptibility are complex and not yet fully understood. The available data suggest that aggressive periodontitis is caused by mutations either in a few major genes or in multiple small-effect genes, and there is also evidence of gene-gene and gene-environment interaction effects. Diagnostic methods for this disease, based on a specific microbiologic, immunologic or genetic profile, currently do not exist. Genetic markers have the potential to be implemented as screening tools to identify subjects at risk. This approach may significantly enhance treatment outcome through the early detection and treatment of affected subjects, as well as using future approaches based on gene therapy. At present, the treatment of this disease is directed toward elimination of the subgingival bacterial load and other local risk factors. Adjunctive use of appropriate systemic antibiotics is recommended and may contribute to a longer suppression of the microbial infection. Other aggressive forms of periodontal diseases occur in patients who are affected with certain systemic diseases, including the leukocyte adhesion deficiency syndrome, Papillon-Lefèvre syndrome, Chediak-Higashi syndrome and Down syndrome. Management of the periodontal component of these diseases is very challenging. Acute gingival and periodontal lesions include a group of disorders that range from nondestructive to destructive forms, and these lesions are usually associated with pain and are a common reason for emergency dental consultations. Some of these lesions may cause a rapid and severe destruction of the periodontal tissues and loss of teeth. Oral infections, particularly acute infections, can spread to extra-oral sites and cause serious medical complications, and even death. Hence, prompt diagnosis and treatment are paramount. PMID:24738583

Albandar, Jasim M

2014-06-01

117

Interstitial Lung Disease in Idiopathic Inflammatory Myopathy  

PubMed Central

The lung is one of the most common extra-muscular targets in idiopathic inflammatory myopathies (IIM) and interstitial lung disease (ILD) is a prevalent and often devastating manifestation of IIM. IIM-associated ILD (IIM-ILD) contributes to nearly 80% of the mortality in IIM with a reported prevalence of 65% of newly diagnosed IIM cases. Although ILD frequently accompanies clinical and laboratory findings of myositis, overt signs of muscle disease may be absent in the setting of significant lung disease. Understanding the varied scope of presentation of these diseases is essential to providing optimal patient care. This review will provide an in depth examination of ILD in IIM both from a rheumatologic and pulmonary perspective and will discuss the scope of disease, presenting features, genetic associations, pathogenesis, diagnosis, radiographic and histopathologic findings, along with biomarker assessment and a rationale for therapeutic intervention.

Saketkoo, Lesley Ann; Ascherman, Dana P.; Cottin, Vincent; Christopher-Stine, Lisa; Danoff, Sonye K.; Oddis, Chester V.

2011-01-01

118

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

PubMed Central

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

Watanabe, Atsushi; Kawaharada, Nobuyoshi; Higami, Tetsuya

2011-01-01

119

Consumption of hydrogen water reduces paraquat-induced acute lung injury in rats.  

PubMed

Exposure to paraquat leads to acute lung injury and oxidative stress is widely accepted as a contributor to paraquat-induced acute lung injury. Recent studies have reported that consumption of water with dissolved molecular hydrogen to a saturated level (hydrogen water) prevents oxidative stress-induced diseases. Here, we investigated whether consumption of saturated hydrogen saline protects rats against paraquat-induced acute lung injury. Adult male Sprague-Dawley (SD) rats were randomly divided into four groups: Control group; hydrogen water-only group (HW group); paraquat-only group (PQ group); paraquat and hydrogen water group (PQ + HW group). The rats in control group and HW group drank pure water or hydrogen water; the rats in PQ group and PQ + HW group were intraperitonealy injected with paraquat (35?mg/kg) and then provided pure water or hydrogen water. Both biochemical and histological lung alterations were measured. The results showed that hydrogen water ameliorated these alterations, demonstrating that hydrogen water alleviated paraquat-induced acute lung injury possibly by inhibition of oxidative damage. PMID:21318114

Liu, Shulin; Liu, Kan; Sun, Qiang; Liu, Wenwu; Xu, Weigang; Denoble, Petar; Tao, Hengyi; Sun, Xuejun

2011-01-01

120

Lung Parenchyma Remodelling in the Acute Respiratory Distress Syndrome  

Microsoft Academic Search

The acute respiratory distress syndrome (ARDS) is a catastrophic condition with exudation, inflammation and often fibrosis\\u000a throughout the lung [1]. Interestingly, despite the extensive damage, it can be fully repaired [2]. This recovery requires the resolution of inflammation, clearance of inflammatory cells and oedema and reversal of fibrosis,\\u000a allowing the lung tissue to return to its normal structure and function.

A. B. Souza-Fernandes; P. R. M. Rocco; W. A. Zin

121

HIV-associated Obstructive Lung Diseases  

PubMed Central

In the era of effective antiretroviral therapy (ART), epidemiologic studies have found that HIV-infected persons have a higher prevalence and incidence of chronic obstructive pulmonary disease than HIV-uninfected persons. Recently, pulmonary function studies in HIV-infected persons have shown a high prevalence of airway obstruction, bronchodilator reversibility, and impaired diffusing capacity. In comparison to HIV-uninfected persons and those with well-controlled HIV disease, HIV-infected persons with poor viral control or lower CD4 cell count have more airflow obstruction, a greater decline in lung function, and possibly more severe diffusing impairment. This chapter will review the evidence linking HIV infection to obstructive lung disease and discuss management issues related to the treatment of obstructive lung disease in HIV-infected patients.

Gingo, Matthew R.; Morris, Alison; Crothers, Kristina

2013-01-01

122

NADPH oxidases in lung health and disease.  

PubMed

Abstract Significance: The evolution of the lungs and circulatory systems in vertebrates ensured the availability of molecular oxygen (O2; dioxygen) for aerobic cellular metabolism of internal organs in large animals. O2 serves as the physiologic terminal acceptor of mitochondrial electron transfer and of the NADPH oxidase (Nox) family of oxidoreductases to generate primarily water and reactive oxygen species (ROS), respectively. Recent advances: The purposeful generation of ROS by Nox family enzymes suggests important roles in normal physiology and adaptation, most notably in host defense against invading pathogens and in cellular signaling. Critical issues: However, there is emerging evidence that, in the context of chronic stress and/or aging, Nox enzymes contribute to the pathogenesis of a number of lung diseases. Future Directions: Here, we review evolving functions of Nox enzymes in normal lung physiology and emerging pathophysiologic roles in lung disease. Antioxid. Redox Signal. 20, 2838-2853. PMID:24093231

Bernard, Karen; Hecker, Louise; Luckhardt, Tracy R; Cheng, Guangjie; Thannickal, Victor J

2014-06-10

123

Respiratory muscle function in interstitial lung disease.  

PubMed

Interstitial lung diseases limit daily activities, impair quality of life and result in (exertional) dyspnoea. This has mainly been attributed to a decline in lung function and impaired gas exchange. However, the contribution of respiratory muscle dysfunction to these limitations remains to be conclusively investigated. Interstitial lung disease patients and matched controls performed body plethysmography, a standardised 6-min walk test, volitional tests (respiratory drive (P0.1), global maximal inspiratory mouth occlusion pressure (PImax), sniff nasal pressure (SnPna) and inspiratory muscle load) and nonvolitional tests on respiratory muscle function and strength (twitch mouth and transdiaphragmatic pressure during bilateral magnetic phrenic nerve stimulation (TwPmo and TwPdi)). 25 patients and 24 controls were included in the study. PImax and SnPna remained unaltered (both p>0.05), whereas P0.1 and the load on the inspiratory muscles were higher (both p<0.05) in interstitial lung disease patients compared with controls. TwPmo and TwPdi were lower in interstitial lung disease patients (mean±sd TwPmo 0.86±0.4 versus 1.32±0.4, p<0.001; TwPdi 1.34±0.6 versus 1.88±0.5, p=0.022). Diaphragmatic force generation seems to be impaired in this cohort of interstitial lung disease patients while global respiratory muscle strength remains preserved. Central respiratory drive and the load imposed on the inspiratory muscles are increased. Whether impaired respiratory muscle function impacts morbidity and mortality in interstitial lung disease patients needs to be investigated in future studies. PMID:23258788

Walterspacher, Stephan; Schlager, Daniel; Walker, David J; Müller-Quernheim, Joachim; Windisch, Wolfram; Kabitz, Hans-Joachim

2013-07-01

124

Acute Chagas Disease in a Returning Traveler  

PubMed Central

Acute Chagas disease is rarely recognized, and the risk for acquiring the disease is undefined in travelers to Central America. We describe a case of acute Chagas disease in a traveler to Costa Rica and highlight the need for increased awareness of this infection in travelers to Chagas-endemic areas.

Carter, Yvonne L.; Juliano, Jonathan J.; Montgomery, Susan P.; Qvarnstrom, Yvonne

2012-01-01

125

Outcomes in Systemic Sclerosis-related Lung Disease following Lung Transplantation  

PubMed Central

Background Lung disease (LD) is the leading cause of death in systemic sclerosis (SSc). The diagnosis of SSc-related LD (SSc-LD) is often a contraindication to lung transplantation (LT) due to concerns that extra-pulmonary involvement will yield worse outcomes. We sought to evaluate post-transplant outcomes in persons with SSc-LD with esophageal involvement compared to persons with non-connective tissue disease related interstitial lung disease (nCTD-ILD). Methods From 1998-2012, persons undergoing LT for SSc-LD were age and gender matched in a 2:1 fashion to controls undergoing LT for nCTD-ILD. Esophageal function was assessed by pH testing and manometry. We defined esophageal dysfunction as the presence of a DeMeester score >14 or dysmotility more severe than “mild non-specific disorder”. The primary outcome was post-transplant survival. Secondary outcomes included freedom from bronchiolitis obliterans syndrome (fBOS) and rates of acute rejection. Survival and fBOS were estimated with Kaplan-Meier methods. Acute rejection was compared with Students t-test. Results Survival was similar in 23 persons with SSc-LD and 46 controls who underwent LT (p=0.47). For the SSc-LD group, 1- and 5-year survival was 83% and 76% compared to 91% and 64% in the nCTD-ILD group. There were no differences in fBOS (p=0.83). Rates of acute rejection were less in SSc-ILD (p=0.05). Esophageal dysfunction was not associated with worse outcomes (p>0.55). Conclusions Persons with SSc-LD appear to have similar survival and fBOS as persons transplanted for nCTD-ILD. The risk of acute rejection after transplant may be reduced in persons with SSc-LD. Esophageal involvement does not appear to impact outcomes.

Sottile, Peter D; Iturbe, David; Katsumoto, Tamiko R; Connolly, M Kari; Collard, Harold R; Leard, Lorriana A; Hays, Steven; Golden, Jeffrey A; Hoopes, Charles; Kukreja, Jasleen; Singer, Jonathan P

2013-01-01

126

Kidney-lung cross-talk and acute kidney injury.  

PubMed

There is a growing appreciation for the role that acute kidney injury (AKI) plays in the propagation of critical illness. In children, AKI is not only an independent predictor of morbidity and mortality, but is also associated with especially negative outcomes when concurrent with acute lung injury (ALI). Experimental data provide evidence that kidney-lung crosstalk occurs and can be bidirectionally deleterious, although details of the precise molecular mechanisms involved in the AKI-ALI interaction remain incomplete. Clinically, ALI, and the subsequent clinical interventions used to stabilize gas exchange, carry consequences for the homeostasis of kidney function. Meanwhile, AKI negatively affects lung physiology significantly by altering the homeostasis of fluid balance, acid-base balance, and vascular tone. Experimental AKI research supports an "endocrine" role for the kidney, triggering a cascade of extra-renal inflammatory responses affecting lung homeostasis. In this review, we will discuss the pathophysiology of kidney-lung crosstalk, the multiple pathways by which AKI affects kidney-lung homeostasis, and discuss how these phenomena may be unique in critically ill children. Understanding how AKI may affect a "balance of communication" that exists between the kidneys and the lungs is requisite when managing critically ill children, in whom imbalance is the norm. PMID:23334385

Basu, Rajit K; Wheeler, Derek S

2013-12-01

127

Acute pancreatitis: a multisystem disease.  

PubMed

Proteolytic enzymes, lipase, kinins, and other active peptides liberated from the inflamed pancreas convert inflammation of the pancreas, a single-organ disease of the retroperitoneum, to a multisystem disease. Adult respiratory distress syndrome, in addition to being secondary to microvascular thrombosis, may be the result of active phospholipase A (lecithinase), which digests lecithin, a major component of surfactant. Myocardial depression and shock are suspected to be secondary to vasoactive peptides and a myocardial depressant factor. Coagulation abnormalities may range from scattered intravascular thrombosis to severe disseminated intravascular coagulation. Acute renal failure has been explained on the basis of hypovolemia and hypotension. The renin-angiotensin alterations in acute pancreatitis (AP) as mediators of renal failure need to be studied. Metabolic complications include hypocalcemia, hyperlipemia, hyperglycemia, hypoglycemia, and diabetic ketoacidosis, of which hypocalcemia has been long recognized as an indicator of poor prognosis. The pathogenesis of hypocalcemia is multifactorial and includes calcium-soap formation, hormonal imbalances (e.g., parathyroid hormone, calcitonin, glucagon), binding of calcium by free fatty acid-albumin complexes, and intracellular translocation of calcium. Subcutaneous fat necrosis, arthritis, and Purtscher's retinopathy are rare. The various prognostic criteria of AP and other associated laboratory abnormalities are manifestations of systemic effects. Early recognition and appropriated management of these complications have resulted in improved prognosis of severe AP. PMID:8049885

Agarwal, N; Pitchumoni, C S

1993-06-01

128

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

129

Previous lung diseases and lung cancer risk: a pooled analysis from the International Lung Cancer Consortium.  

PubMed

To clarify the role of previous lung diseases (chronic bronchitis, emphysema, pneumonia, and tuberculosis) in the development of lung cancer, the authors conducted a pooled analysis of studies in the International Lung Cancer Consortium. Seventeen studies including 24,607 cases and 81,829 controls (noncases), mainly conducted in Europe and North America, were included (1984-2011). Using self-reported data on previous diagnoses of lung diseases, the authors derived study-specific effect estimates by means of logistic regression models or Cox proportional hazards models adjusted for age, sex, and cumulative tobacco smoking. Estimates were pooled using random-effects models. Analyses stratified by smoking status and histology were also conducted. A history of emphysema conferred a 2.44-fold increased risk of lung cancer (95% confidence interval (CI): 1.64, 3.62 (16 studies)). A history of chronic bronchitis conferred a relative risk of 1.47 (95% CI: 1.29, 1.68 (13 studies)). Tuberculosis (relative risk = 1.48, 95% CI: 1.17, 1.87 (16 studies)) and pneumonia (relative risk = 1.57, 95% CI: 1.22, 2.01 (12 studies)) were also associated with lung cancer risk. Among never smokers, elevated risks were observed for emphysema, pneumonia, and tuberculosis. These results suggest that previous lung diseases influence lung cancer risk independently of tobacco use and that these diseases are important for assessing individual risk. PMID:22986146

Brenner, Darren R; Boffetta, Paolo; Duell, Eric J; Bickeböller, Heike; Rosenberger, Albert; McCormack, Valerie; Muscat, Joshua E; Yang, Ping; Wichmann, H-Erich; Brueske-Hohlfeld, Irene; Schwartz, Ann G; Cote, Michele L; Tjønneland, Anne; Friis, Søren; Le Marchand, Loic; Zhang, Zuo-Feng; Morgenstern, Hal; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Zaridze, David; Rudnai, Peter; Fabianova, Eleonora; Foretova, Lenka; Janout, Vladimir; Bencko, Vladimir; Schejbalova, Miriam; Brennan, Paul; Mates, Ioan N; Lazarus, Philip; Field, John K; Raji, Olaide; McLaughlin, John R; Liu, Geoffrey; Wiencke, John; Neri, Monica; Ugolini, Donatella; Andrew, Angeline S; Lan, Qing; Hu, Wei; Orlow, Irene; Park, Bernard J; Hung, Rayjean J

2012-10-01

130

Previous Lung Diseases and Lung Cancer Risk: A Pooled Analysis From the International Lung Cancer Consortium  

PubMed Central

To clarify the role of previous lung diseases (chronic bronchitis, emphysema, pneumonia, and tuberculosis) in the development of lung cancer, the authors conducted a pooled analysis of studies in the International Lung Cancer Consortium. Seventeen studies including 24,607 cases and 81,829 controls (noncases), mainly conducted in Europe and North America, were included (1984–2011). Using self-reported data on previous diagnoses of lung diseases, the authors derived study-specific effect estimates by means of logistic regression models or Cox proportional hazards models adjusted for age, sex, and cumulative tobacco smoking. Estimates were pooled using random-effects models. Analyses stratified by smoking status and histology were also conducted. A history of emphysema conferred a 2.44-fold increased risk of lung cancer (95% confidence interval (CI): 1.64, 3.62 (16 studies)). A history of chronic bronchitis conferred a relative risk of 1.47 (95% CI: 1.29, 1.68 (13 studies)). Tuberculosis (relative risk = 1.48, 95% CI: 1.17, 1.87 (16 studies)) and pneumonia (relative risk = 1.57, 95% CI: 1.22, 2.01 (12 studies)) were also associated with lung cancer risk. Among never smokers, elevated risks were observed for emphysema, pneumonia, and tuberculosis. These results suggest that previous lung diseases influence lung cancer risk independently of tobacco use and that these diseases are important for assessing individual risk.

Brenner, Darren R.; Boffetta, Paolo; Duell, Eric J.; Bickeboller, Heike; Rosenberger, Albert; McCormack, Valerie; Muscat, Joshua E.; Yang, Ping; Wichmann, H.-Erich; Brueske-Hohlfeld, Irene; Schwartz, Ann G.; Cote, Michele L.; Tj?nneland, Anne; Friis, S?ren; Le Marchand, Loic; Zhang, Zuo-Feng; Morgenstern, Hal; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Zaridze, David; Rudnai, Peter; Fabianova, Eleonora; Foretova, Lenka; Janout, Vladimir; Bencko, Vladimir; Schejbalova, Miriam; Brennan, Paul; Mates, Ioan N.; Lazarus, Philip; Field, John K.; Raji, Olaide; McLaughlin, John R.; Liu, Geoffrey; Wiencke, John; Neri, Monica; Ugolini, Donatella; Andrew, Angeline S.; Lan, Qing; Hu, Wei; Orlow, Irene; Park, Bernard J.; Hung, Rayjean J.

2012-01-01

131

Relationship between neutrophil elastase and acute lung injury in humans  

Microsoft Academic Search

We conducted clinical trials in patients with acute lung injury (ALI) associated with systemic inflammatory response syndrome using a selective neutrophil elastase inhibitor, sivelestat sodium hydrate (Sivelestat), to investigate the involvement of neutrophil elastase in ALI. In the phase III double-blind study (Study 1) in 230 patients, the efficacy of Sivelestat was evaluated with the pulmonary function improvement (PFI) rating

Shouetsu Tamakuma; Michio Ogawa; Naoki Aikawa; Tatsuya Kubota; Hiroyuki Hirasawa; Akitoshi Ishizaka; Nobuyuki Taenaka; Chikuma Hamada; Shozo Matsuoka; Taira Abiru

2004-01-01

132

Hypoxia and chronic lung disease  

Microsoft Academic Search

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

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

2007-01-01

133

Ron receptor deficient alveolar myeloid cells exacerbate LPS-induced acute lung injury in the murine lung  

PubMed Central

Previous studies have shown that the Ron receptor tyrosine kinase is an important regulator of the acute lung inflammatory response induced by intranasal administration of bacterial lipopolysaccharide (LPS). Compared to wild type mice, complete loss of the Ron receptor in all cell types in vivo was associated with increased lung damage as determined by histological analyses and several markers of lung injury including increases in pro-inflammatory cytokines such as TNF?. TNF? is a multifunctional cytokine secreted by macrophages, which plays a major role in inflammation and is a central mediator of several disease states including rheumatoid arthritis and sepsis. Based on increased TNF? production observed in the Ron-deficient mice, we hypothesized that Ron receptor function in the inflammatory cell compartment is essential for the regulating lung injury in vivo. To test this hypothesis we generated myeloid lineage-specific Ron deficient mice. In this study, we report that loss of Ron signaling selectively in myeloid cells results in increased lung injury following intranasal administration of LPS as measured by increases in TNF? production, ensuing neutrophil accumulation and increased lung histopathology. These findings corroborate the role of Ron receptor tyrosine kinase as a negative regulator of inflammation and further demonstrate the in vivo significance of Ron signaling selectively in myeloid cells as a major regulator of this response in vivo. These data authenticate Ron as a potential target in innate immunity and TNF?-mediated pathologies.

Nikolaidis, Nikolaos M.; Kulkarni, Rishikesh M.; Gray, Jerilyn K.; Collins, Margaret H.; Waltz, Susan E.

2014-01-01

134

Focus on acute diarrhoeal disease.  

PubMed

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

2009-07-21

135

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.

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

2009-01-01

136

Lung Compliance and Chronic Obstructive Pulmonary Disease  

PubMed Central

Chronic obstructive pulmonary disease, namely, pulmonary emphysema and chronic bronchitis, is a chronic inflammatory response of the airways to noxious particles or gases, with resulting pathological and pathophysiological changes in the lung. The main pathophysiological aspects of the disease are airflow obstruction and hyperinflation. The mechanical properties of the respiratory system and its component parts are studied by determining the corresponding volume-pressure (P-V) relationships. The consequences of the inflammatory response on the lung structure and function are depicted on the volume-pressure relationships.

Papandrinopoulou, D.; Tzouda, V.; Tsoukalas, G.

2012-01-01

137

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

Microsoft Academic Search

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

LORRAINE B. WARE; MICHAEL A. MATTHAY

2001-01-01

138

Expression Profiling in Granulomatous Lung Disease  

PubMed Central

Granulomatous lung diseases, such as sarcoidosis, hypersensitivity pneumonitis, Wegener's granulomatosis, and chronic beryllium disease, along with granulomatous diseases of known infectious etiologies, such as tuberculosis, are major causes of morbidity and mortality throughout the world. Clinical manifestations of these diseases are highly heterogeneous, and the determinants of disease susceptibility and clinical course (e.g., resolution vs. chronic, progressive fibrosis) are largely unknown. The underlying pathogenic mechanisms of these diseases also remain poorly understood. Within this context, these diseases have been approached using genomic and proteomic technologies to allow us to identify patterns of gene/protein expression that track with clinical disease or to identify new pathways involved in disease pathogenesis. The results from these initial studies highlight the potential for these “-omics” approaches to reveal novel insights into the pathogenesis of granulomatous lung disease and provide new tools to improve diagnosis, clinical classification, course prediction, and response to therapy. Realizing this potential will require collaboration among multidisciplinary groups with expertise in the respective technologies, bioinformatics, and clinical medicine for these complex diseases.

Chen, Edward S.; Moller, David R.

2007-01-01

139

Quantitative stratification of diffuse parenchymal lung diseases.  

PubMed

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

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

2014-01-01

140

Endogenous Nitric Oxide in Acute Lung Injury  

Microsoft Academic Search

\\u000a Nitric oxide (NO) is a ubiquitous signal transduction molecule formed from the oxidative deamination of one of the equivalent\\u000a guanidine nitrogens of the amino acid L-arginine via the activity of at least four known isoforms of NO synthase (1). Within the lung, NO is synthesized by endothelial NO synthase (NOS-3) localized in airway epithelial cells and pulmonary\\u000a vascular endothelial cells,

Neil W. Kooy

141

Hydrocarbon pneumonitis masquerading as acute lung injury  

PubMed Central

Hydrocarbon pneumonitis is an acute, intense pneumonitis resulting from aspiration/inhalation of volatile hydrocarbon compounds with low viscosity and surface tension. The authors describe the case of a 24-year-old male who aspirated diesel while siphoning it from heavy duty crane, developed bilateral pneumonitis and responded to 2-day therapy with non-invasive continuous positive airway pressure ventilation.

Shrivastava, Makardhwaj Sarvadaman; Palkar, Atul Vijay; Karnik, Niteen D

2011-01-01

142

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.

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

143

Role of TNF-? in lung tight junction alteration in mouse model of acute lung inflammation  

PubMed Central

In the present study, we used tumor necrosis factor-R1 knock out mice (TNF-?R1KO) to understand the roles of TNF-? on epithelial function in models of carrageenan-induced acute lung inflammation. In order to elucidate whether the observed anti-inflammatory status is related to the inhibition of TNF-?, we also investigated the effect of etanercept, a TNF-? soluble receptor construct, on lung TJ function. Pharmacological and genetic TNF-? inhibition significantly reduced the degree of (1) TNF-? production in pleural exudates and in the lung tissues, (2) the inflammatory cell infiltration in the pleural cavity as well as in the lung tissues (evaluated by MPO activity), (3) the alteration of ZO-1, Claudin-2, Claudin-4, Claudin-5 and ?-catenin (immunohistochemistry) and (4) apoptosis (TUNEL staining, Bax, Bcl-2 expression). Taken together, our results demonstrate that inhibition of TNF-? reduces the tight junction permeability in the lung tissues associated with acute lung inflammation, suggesting a possible role of TNF-? on lung barrier dysfunction.

Mazzon, Emanuela; Cuzzocrea, Salvatore

2007-01-01

144

Serum biomarkers in interstitial lung diseases  

PubMed Central

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 applications of several new molecules as biologic markers in the research field relevant to interstitial lung diseases (translational research). The scope of this review is to summarize the current state of knowledge about serum biomarkers in interstitial lung diseases and their potential value as prognostic and diagnostic tools and present some of the future perspectives and challenges.

Tzouvelekis, Argyris; Kouliatsis, George; Anevlavis, Stavros; Bouros, Demosthenes

2005-01-01

145

Genetic polymorphisms and susceptibility to lung disease  

PubMed Central

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.

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

2006-01-01

146

Lymphomatoid granulomatosis mimicking interstitial lung disease.  

PubMed

Lymphoid granulomatosis is a rare form of pulmonary angiitis. This case report presents a patient with lymphoid granulomatosis in whom the clinical presentation, radiological features and the partial response to corticosteroid therapy mimicked interstitial lung disease. Lymphoid granulomatosis was only diagnosed at post-mortem examination. The range of reported clinical presentations, diagnostic approaches and outcomes are described. PMID:18699810

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

2008-11-01

147

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.

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

2013-01-01

148

Interstitial lung disease in polymyositis and dermatomyositis  

Microsoft Academic Search

Interstitial lung disease occurs in approximately one-third of patients with polymyositis and dermatomyositis (PM\\/DM) and\\u000a has an adverse effect on survival. It is commonly a component of early PM\\/DM and can precede the onset of muscle or skin disease.\\u000a Its most common histopathology is nonspecific interstitial pneumonia. This is a more benign pattern, with respect to response\\u000a to immunosuppression and

Armin Schnabel; Bernhard Hellmich; Wolf gang Ludwig Gross

2005-01-01

149

Alveolar recruitment maneuvers in acute lung injury/acute respiratory distress syndrome  

PubMed Central

Mechanical ventilation can worsen lung damage in acute lung injury and acute respiratory distress syndrome. The use of low tidal volumes is one of the strategies that has been shown to reduce lung injury and improve outcomes in this situation. However, low tidal volumes may lead to alveolar derecruitment and worsening of hypoxia. Recruitment maneuvers along with positive end-expiratory pressure may help to prevent derecruitment. Although recruitment maneuvers have been shown to improve oxygenation, improved clinical outcomes have not been demonstrated. The optimal recruitment strategy and the type of patients who might benefit are also unclear. This review summarizes the impact of recruitment maneuvers on lung mechanics and physiology, techniques of application, and the clinical situations in which they may be useful.

Chacko, Jose; Rani, Usha

2009-01-01

150

Diabetes, insulin, and development of acute lung injury  

PubMed Central

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

Honiden, Shyoko; Gong, Michelle N.

2009-01-01

151

2 Drugs Offer Hope for Fatal Lung Disease  

MedlinePLUS

... enable JavaScript. 2 Drugs Offer Hope for Fatal Lung Disease Doctors have had little to offer patients ... disease that robs their breath by scarring the lungs, according to clinical trial results. Both drugs, pirfenidone ...

152

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

153

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

154

Undifferentiated Connective Tissue Disease-Associated Interstitial Lung Disease: Changes in Lung Function  

Microsoft Academic Search

Undifferentiated connective tissue disease (UCTD) is a distinct clinical entity that may be accompanied by interstitial lung\\u000a disease (ILD). The natural history of UCTD-ILD is unknown. We hypothesized that patients with UCTD-ILD would be more likely\\u000a to have improvement in lung function than those with idiopathic pulmonary fibrosis (IPF) during longitudinal follow-up. We\\u000a identified subjects enrolled in the UCSF ILD

Brent W. Kinder; Cyrus Shariat; Harold R. Collard; Laura L. Koth; Paul J. Wolters; Jeffrey A. Golden; Ralph J. Panos; Talmadge E. King

2010-01-01

155

New concepts of the pathogenesis of cystic fibrosis lung disease  

Microsoft Academic Search

New concepts of the pathogenesis of cystic fibrosis lung disease. R.C. Boucher. #ERS Journals Ltd 2004. ABSTRACT: Although there has been impressive progress in the elucidation of the genetic and molecular basis of cystic fibrosis (CF), the pathogenesis of CF lung disease remains obscure. The elucidation of the pathogenesis of CF lung disease requires both a full description of normal

R. C. Boucher

2004-01-01

156

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

157

Acute allograft rejection after lung transplantation: diagnosis and therapy.  

PubMed

Acute rejection remains a significant problem after lung transplantation. While it generally is a treatable condition, significant resources and therapies are directed toward its prevention and resolution. Its larger significance undoubtedly rests in its contribution to the pathogenesis of BOS. Significant questions regarding the origins of AR, the role of LBB, alternative histologic appearances of acute allograft injury, and optimal therapy remain. Controversy regarding the utility of surveillance bronchoscopy and preemptive treatment of occult AR persists because of lack of conclusive evidence. Future investigations might resolve these matters and provide more efficacious and less toxic therapies that will hopefully reduce the impact of chronic rejection and improve long-term outcomes. PMID:13678311

Chakinala, Murali M; Trulock, Elbert P

2003-08-01

158

Acute irreversible oxalate nephropathy in a lung transplant recipient treated successfully with a renal transplant.  

PubMed

We report a 29 year old male cystic fibrosis patient with end stage lung disease and normal renal function who underwent a sequential double lung transplant. Medical history included: an ileal resection and pancreatic exocrine dysfunction. The postoperative period was complicated with haemorrhage and repeat surgery, requiring multiple blood transfusions and extensive antibiotic cover. Pancreatic supplements were interrupted. Acute renal failure attributed to haemodynamically-mediated acute tubular necrosis was managed expectantly. He remained dialysis dependent 8 weeks post surgery and was maintained on triple immunosuppression with tacrolimus, mycophenolate and prednisolone. A DTPA study was consistent with ATN. Renal biopsy revealed features consistent with tubular injury due to acute oxalate nephropathy (AON). Further biochemical characterization excluded primary hyperoxaluria but confirmed increased 24 hour urinary oxalate. He was maintained on enhanced frequency HDF and subsequently received an uncomplicated live related renal transplant 10 months post lung transplant with only additional basiliximab. Calcium carbonate was continued to manage post transplant hyperoxaluria and an early renal biopsy excluded recurrent oxalate injury. Enteric hyperoxaluria due to malabsorption in patients with CF especially with ileal resection, in addition to loss of gut Oxalobacter formigenes due to prolonged antimicrobials, increases the risk of AON. Increased awareness of this condition and screening prior to lung transplant is recommended. PMID:22497648

Dheda, Shyam; Swaminathan, Ramyasuda; Musk, Michael; Sinniah, Rajalingam; Lawrence, Sharon; Irish, Ashley

2012-04-01

159

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

PubMed

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

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

2013-04-01

160

E3 ubiquitin ligase Cblb regulates the acute inflammatory response underlying lung injury  

Microsoft Academic Search

The E3 ubiquitin ligase Cblb has a crucial role in the prevention of chronic inflammation and autoimmunity. Here we show that Cblb also has an unexpected function in acute lung inflammation. Cblb attenuates the sequestration of inflammatory cells in the lungs after administration of lipopolysaccharide (LPS). In a model of polymicrobial sepsis in which acute lung inflammation depends on the

Sophie Toya; Xiaopei Gao; Thomas Triantafillou; Sean Garrean; Gye Young Park; Randall S Frey; Stephen Vogel; Richard Minshall; John W Christman; Chinnaswamy Tiruppathi; Asrar B Malik; Kurt Bachmaier

2007-01-01

161

IL-27 is elevated in acute lung injury and mediates inflammation.  

PubMed

Cytokines play a critical role in the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Here we investigated whether IL-27 was elevated in patients with ALI/ARDS and its potential clinical significance. Bronchoalveolar lavage (BAL) and serum samples were obtained from 58 ALI/ARDS patients, and 25 control healthy volunteers. IL-27 and other inflammatory mediators were measured in BAL and serum by ELISA. Besides, a mouse model of cecal ligation and puncture (CLP)-induced lung inflammation/injury was established, and serum, BAL fluid and tissues were collected for analyses in the presence or absence of IL-27 neutralizing antibodies. BAL IL-27 was found to be significantly higher in patients with ALI/ARDS than that in controls, particularly of pulmonary origin; serum IL-27 was also significantly higher. Increased IL-27 was associated with markers of inflammation, and correlated with disease severity of patients in ALI/ARDS. In a mouse model of CLP-induced lung inflammation/injury, elevated IL-27 levels were observed in the lung, serum, and BAL fluids. IL-27 neutralizing antibody treatment reduced pulmonary inflammation and lung injury and improved mouse survival in response to CLP. Therefore, IL-27 is a critical cytokine in ALI/ARDS and inhibition of IL-27 may open a promising approach for ALI/ARDS patients. PMID:23842867

Xu, Fang; Liu, Qiong; Lin, Shihui; Shen, Na; Yin, Yibing; Cao, Ju

2013-10-01

162

Susceptibility to nontuberculous mycobacterial lung disease.  

PubMed

The nontuberculous mycobacteria (NTM) exhibit heterogeneous pathogenicity in humans. Articles on known and potential human factors capable of producing susceptibility to NTM lung disease (NTMLD) were identified by a systematic search of the medical literature, and are reviewed in the present study. Patients with pre-existing structural lung disease are known to be at risk of NTMLD. Other susceptible groups have become recognised since the 1980s, in particular middle-aged nonsmokers without previous lung disease (a group including those with Lady Windermere syndrome) and patients with genetically determined defects of cell-mediated immunity, including abnormalities of the interleukin-12/interferon-gamma axis, certain human leukocyte antigen alleles, cystic fibrosis transmembrane conductance regulator mutations, and polymorphisms of solute carrier 11A1 (or natural resistance-associated macrophage protein 1) and the vitamin D receptor. Information is also accruing about acquired systemic causes of susceptibility to NTMLD, including inhibitory antibodies directed against interferon-gamma, post-menopausal waning of endogenous oestrogen levels, coeliac disease and exposure to use of dietary phyto-oestrogens. It is not known whether immunosuppressive factors, such as oral corticosteroid treatment, chronic renal failure, diabetes mellitus and other known risk factors for pulmonary tuberculosis, are also risk factors for the development of NTMLD. Caution is appropriate in managing such patients. PMID:18515557

Sexton, P; Harrison, A C

2008-06-01

163

OXIDANTS AND THE PATHOGENESIS OF LUNG DISEASES  

PubMed Central

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

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

2009-01-01

164

[Acute lung injury as a consequence of blood transfusion].  

PubMed

Acute lung injury (ALI) has been recognized as a consequence of blood transfusion (BT) since 1978; the Food and Drug Administration, has classified it as the third BT mortality issue, in 2004, and in first place related with ALI. It can be mainly detected as: Acute respiratory distress syndrome (ARDS), transfusion associated circulatory overload (TACO) and transfusion related acute lung injury (TRALI). The clinical onset is: severe dyspnea, bilateral lung infiltration and low oxygen saturation. In USA, ARDS has an incidence of three to 22.4 cases/100 000 inhabitants, with 58.3 % mortality. TACO and TRALI are less frequent; they have been reported according to the number of transfusions: one in 1275 to 6000 for TRALI and one in 356 transfusions for TACO. Mortality is reported from two to 20 % in TRALI and 20 % in TACO. Antileukocyte antibodies in blood donors plasma, caused TRALI in 89 % of cases; also it has been found antigen specificity against leukocyte blood receptor in 59 %. The UCI patients who received a BT have ALI as a complication in 40 % of cases. The capillary pulmonary endothelia is the target of leukocyte antibodies and also plasma biologic modifiers of the stored plasma, most probable like a Sanarelli-Shwar-tzman phenomenon. PMID:21838994

Rodríguez-Moyado, Héctor

2011-01-01

165

Gouty Arthritis in Acute Cerebrovascular Disease  

Microsoft Academic Search

Background: Gouty arthritis is a metabolic disorder associated with several medical diseases and is considered as a high-risk factor of acute myocardial infarction and cardiovascular mortality. Since no study has assessed the frequency of gout attack in acute-stroke patients, a retrospective analysis of gouty arthritis in stroke patients was performed to identify the frequency and characteristics of gouty arthritis in

Ya-Hui Lin; Huan-Lin Hsu; Ying-Chih Huang; Meng Lee; Wen-Yi Huang; Yen-Chu Huang; Tsong-Hai Lee; Jiann-Der Lee

2009-01-01

166

Acute graft-vs-host disease  

Microsoft Academic Search

Acute graft-vs-host disease (GVHD) is a major obstacle to safe allogeneic hematopoietic stem cell transplantation (HSCT), leading to a significant morbidity and mortality. GVHD occurs when transplanted donor T lymphocytes react to foreign host cells. It causes a wide variety of host tissue injuries. This review focuses on the pathobiological basis, clinical aspects, and current management strategies of acute GVHD.

Hakan Goker; Ibrahim C. Haznedaroglu; Nelson J. Chao

2001-01-01

167

Focus on acute diarrhoeal disease  

Microsoft Academic Search

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

Fabio Baldi; Maria Antonia Bianco; Gerardo Nardone; Alberto Pilotto; Emanuela Zamparo; Zamparo E. Focus

2009-01-01

168

Acute myelogenous leukemia associated with Ollier disease.  

PubMed

Ollier disease is a rare disorder characterized by the presence of multiple enchondromas and a propensity to develop malignancies. We report the case of a 7-year-old Caucasian male with Ollier disease who developed acute myelogenous leukemia (AML). This report describes a patient with Ollier disease and AML and may offer a clue into the genetic pathogenesis of these disorders. PMID:16991136

White, Matthew S; Martin, Paul L; McLean, Thomas W

2008-03-01

169

Genetic therapies for cystic fibrosis lung disease.  

PubMed

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

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

2011-04-15

170

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.

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

2012-01-01

171

Human embryonic stem cells recover in vivo acute lung inflammation bleomycin-induced.  

PubMed

Idiopathic pulmonary fibrosis (IPF)  is characterized by alveolar epithelial cell injury, type II cell activation, apoptosis and bronchiolar epithelial cell proliferation, accumulation of extracellular matrix and fibroblasts. No current animal model recapitulates all of these cardinal manifestation of the human disease. However, bleomycin instillation in mice lung by intranasal way (ITN) represents the best experimental model of pulmonary fibrosis in which alveolar pneumocytes type II (ATII) are usually depleted. The aim of this study was to test the possibility to recover acute lung fibrosis after transplantation of human embryonic type II derived-pneumocytes in a murine model of bleomycin-induced damage. Our results indicate the striking "clinical" beneficial effect of differentiated HUES-3 cells into ATII in terms of lung function, weight loss and mortality in injured mice, suggesting this stem cell therapy as a promising, systemic and specific treatment of human pulmonary fibrosis. PMID:24284290

Sangiuolo, Federica; Spitalieri, P; Quitadamo, M C; Orlandi, A; Puxeddu, E; Curradi, G; Sangiuolo, F

2013-10-01

172

Cell proliferation in lung following acute fly ash exposure.  

PubMed

Cell proliferation was examined in the lung parenchyma, the ciliated airway epithelium and the lymph nodes of Fischer-344 rats following a 6-h exposure to fly ash obtained from the baghouse of an experimental fluidized bed combustor. The fly ash concentration was 142 mg/m3 with a mass median aerodynamic diameter (MMAD) of approximately 3.0 micron and a geometric standard deviation (sigma g) of approximately 2.6. Lung deposition of fly ash was measured in the right lung to be 90 +/- 20 and 80 +/- 30 mg for male and female rats, respectively, resulting in a calculated value for male rats of (140 +/- 30 micrograms/animal) and for female rats of 130 +/- 50 micrograms/animal). Autoradiographic methods were used to detect cells that incorporated [3H] thymidine. About a 10-fold increase in labeling of the lung epithelial type II cells was observed following the 6-h fly ash exposure. There was also an increase in [3H] thymidine incorporation into DNA of alveolar macrophages. Labeling activity of macrophages within the lung was increased for up to 4 days following fly ash exposure; however, the size of the macrophage population was not altered. Following exposure, a higher labeling index was also observed in the epithelial cells of the airways. Labeling in the trachea reached a peak at 4 days after exposure while in the bronchi and in small airways (inside diameter of less than 0.35 mm) the highest level of labeling was observed at 1 day after exposure. Labeling in airway epithelial cells was increased 2-4 times above that of sham-exposed animals. Lung-associated lymph nodes accumulated particulate material and had variable amounts of [3H]thymidine incorporation. These results demonstrate that acute inhalation exposure to fly ash initiated cell division or DNA synthesis in several cell populations of lung parenchyma and airways. PMID:6623476

Hackett, N A

1983-01-01

173

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

174

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

175

Antioxidant vitamins and prevention of lung disease.  

PubMed

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, NO2 and O3. The oxidation of lung lipids can be prevented by both vitamins C and E. Vitamin C is more effective in preventing oxidation by NO2, and vitamin E is more effective against O3. Second, multiple species of experimental animals develop lung disease similar to human bronchitis and emphysema from exposure to NO2 and O3, respectively. The development of these diseases occurs over a near lifetime exposure when the levels of NO2 or O3 are at near ambient air pollution values. Third, isolated human cells are protected against oxidative damage from NO2 and O3 by both vitamins C and E. Fourth, the vitamin C level in the lung either declines on exposure to NO2 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. Although animal studies do not provide evidence for complete protection against NO2 or O3, they do illustrate that current recommended daily allowances are inadequate for maximum protection against air pollution levels to which over 100 million Americans are exposed. The problem of air pollution and its effects on humans is truly of global concern. Air pollution is not restricted to North America or Japan where it was first recognized, but is a major public health problem in Europe as well. When data are available, air pollution probably will be shown to be a major public health problem in all urban areas of the world.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1444020

Menzel, D B

1992-09-30

176

Fibrocytes and the pathogenesis of diffuse parenchymal lung disease  

PubMed Central

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

2012-01-01

177

Bronchoalveolar lavage in farmers' lung disease: diagnostic and physiological significance.  

PubMed Central

A group of 92 farmers had clinical evaluation, pulmonary function tests, and bronchoalveolar lavage (BAL). There were 12 patients with acute farmers' lung disease (FLD) (group 1) and 37 farmers who had had acute FLD, of whom 22 were still on their farm (group 2) and 15 had ceased contact (group 3); others were normal dairy farmers, 23 serology positive to Micropolyspora faeni (group 4), 20 serology negative (group 5), and 42 normal controls (group 6). Of the 134 subjects, 59 had an increase in alveolar lymphocytes (greater than 22% lymphocytes in BAL) (12 in group 1, 19 in group 2, six in group 3, 14 in group 4, five in group 5, and three in group 6). Within each group there was no correlation between BAL lymphocytes (% and absolute number) and most pulmonary function tests. It is concluded that although an increase in BAL lymphocytes is always seen in acute FLD it may also be seen in the absence of clinically evident disease and that BAL lymphocytosis does not correlate with physiological changes in FLD.

Cormier, Y; Belanger, J; LeBlanc, P; Laviolette, M

1986-01-01

178

Bronchoalveolar lavage in farmers' lung disease: diagnostic and physiological significance.  

PubMed

A group of 92 farmers had clinical evaluation, pulmonary function tests, and bronchoalveolar lavage (BAL). There were 12 patients with acute farmers' lung disease (FLD) (group 1) and 37 farmers who had had acute FLD, of whom 22 were still on their farm (group 2) and 15 had ceased contact (group 3); others were normal dairy farmers, 23 serology positive to Micropolyspora faeni (group 4), 20 serology negative (group 5), and 42 normal controls (group 6). Of the 134 subjects, 59 had an increase in alveolar lymphocytes (greater than 22% lymphocytes in BAL) (12 in group 1, 19 in group 2, six in group 3, 14 in group 4, five in group 5, and three in group 6). Within each group there was no correlation between BAL lymphocytes (% and absolute number) and most pulmonary function tests. It is concluded that although an increase in BAL lymphocytes is always seen in acute FLD it may also be seen in the absence of clinically evident disease and that BAL lymphocytosis does not correlate with physiological changes in FLD. PMID:3426661

Cormier, Y; Bélanger, J; LeBlanc, P; Laviolette, M

1986-06-01

179

Characterizing aggressiveness and predicting future progression of CF lung disease.  

PubMed

Cystic fibrosis (CF) is a life-shortening genetic disease characterized by variability in age of death that is largely due to variability in rate of progression of lung disease, the primary cause of mortality. Recognizing which individuals have more aggressive disease phenotypes and predicting their risk of immediate lung disease progression is a critical step in managing CF lung disease and extending the life expectancy of CF patients. Studies using observational CF patient registries have yielded useful methods for predicting future rate of disease progression and can be used to determine the impact that chronic pulmonary therapies have on slowing rate of lung function decline. PMID:19460682

Konstan, Michael W; Wagener, Jeffrey S; VanDevanter, Donald R

2009-06-01

180

Novel Aspects of Treatment for Interstitial Lung Diseases  

Microsoft Academic Search

Interstitial lung diseases (ILDs) are a heterogenous group of diseases with a complex pathogenesis. Inflammation was noticed first to be a component of ILDs, but anti-inflammatory therapy proved effective only in a subgroup of disease entities with predominant inflammatory features such as nonspecific interstitial pneumonia (NSIP), desquamative interstitial pneumonia (DIP) or cryptogenic organizing pneumonia (COP). In fibrotic lung diseases such

J. Behr

2007-01-01

181

Treatment of Lung Carcinoid by Type and Extent of Disease  

MedlinePLUS

... information for lung carcinoid tumors Treatment of lung carcinoid by type and extent of disease The treatment ... can’t be removed completely (unresectable cancers). Resectable carcinoid tumors Resectable carcinoid tumors haven’t spread far ...

182

Antioxidant Treatment Ameliorates Respiratory Syncytial Virus-induced Disease and Lung Inflammation  

Microsoft Academic Search

Rationale: Respiratory syncytial virus (RSV) is a major cause of lower respiratorytractinfectioninchildren.Notreatmenthasbeenshown to significantly improve the clinical outcome of patients with this infection. Recent evidence suggests that oxidative stress could play an important role in the pathogenesis of acute and chronic lung inflammatory diseases. We do not known whether RSV induces pulmonary oxidative stress and whether antioxidant treatment can modulate

Shawn Monique Castro; Antonieta Guerrero-Plata; Giovanni Suarez-Real; Patrick A. Adegboyega; Giuseppe N. Colasurdo; Amir M. Khan; Roberto P. Garofalo; Antonella Casola

2006-01-01

183

Identification of a Common Gene Expression Response in Different Lung Inflammatory Diseases in Rodents and Macaques  

Microsoft Academic Search

To identify gene expression responses common to multiple pulmonary diseases we collected microarray data for acute lung inflammation models from 12 studies and used these in a meta-analysis. The data used include exposures to air pollutants; bacterial, viral, and parasitic infections; and allergic asthma models. Hierarchical clustering revealed a cluster of 383 up-regulated genes with a common response. This cluster

Jeroen L. A. Pennings; Tjeerd G. Kimman; Riny Janssen; Nina Papavasiliou

2008-01-01

184

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.

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

2013-01-01

185

Propofol attenuates oxidant-induced acute lung injury in an isolated perfused rabbit-lung model  

Microsoft Academic Search

Purpose. Reactive oxygen species have been strongly implicated in the pathogenesis of acute lung injury (ALI). Some animal studies suggest that free radical scavengers inhibit the onset of oxidant-induced ALI. Propofol (2,6-diisopropylphenol) is chemically similar to phenol-based free radical scavengers such as the endogenous antioxidant vitamin E. Both in vivo and in vitro studies have suggested that propofol has antioxidant

Masato Yumoto; Osamu Nishida; Fujio Nakamura; Hirotada Katsuya

2005-01-01

186

Acute cholestatic liver disease protects against glycerol-induced acute renal failure in the rat  

Microsoft Academic Search

Acute cholestatic liver disease protects against glycerol-induced acute renal failure in the rat.BackgroundIt is widely held that liver disease predisposes toward acute tubular necrosis. The present study examines the effect of acute cholestatic liver disease on the susceptibility to glycerol-induced acute tubular necrosis in the rat.MethodsAcute cholestatic liver disease was induced by ligation of the common bile duct, while the

Nelson Leung; Anthony J. Croatt; Jill J. Haggard; Joseph P. Grande; Karl A. Nath

2001-01-01

187

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.

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

2014-01-01

188

Interstitial lung disease in systemic sclerosis.  

PubMed

Interstitial lung disease (ILD) is a common manifestation of systemic sclerosis (SSc) and mainly encountered in patients with diffuse disease and/or anti-topoisomerase 1 antibodies. ILD develops in up to 75% of patients with SSc overall. However, SSc-ILD evolves to end-stage respiratory insufficiency in only a few patients. Initial pulmonary function tests (PFT) with measurement of carbon monoxide diffusing capacity, together with high-resolution computed tomography, allows for early diagnosis of SSc-ILD, before the occurrence of dyspnea. Unlike idiopathic ILD, SSc-ILD corresponds to non-specific interstitial pneumonia in most cases, whereas usual interstitial pneumonia is less frequently encountered. Therefore, the prognosis of SSc-ILD is better than that for idiopathic ILD. Nevertheless, ILD represents one of the two main causes of death in SSc patients. To detect SSc-ILD early, PFT must be repeated regularly, every 6 months to 1 year, depending on disease worsening. Conversely, broncho-alveolar lavage is not needed to evaluate disease activity in SSc-ILD but may be of help in diagnosing opportunistic infection. The treatment of SSc-ILD is not well established. Cyclophosphamide, which has been used for 20 years, has recently been evaluated in two prospective randomized studies that failed to demonstrate a major benefit for lung function. Open studies reported mycophenolate mofetil, azathioprine and rituximab as alternatives to cyclophosphamide. On failure of immunosuppressive agent treatment, lung transplantation can be proposed in the absence of other major organ involvement or severe gastro-esophageal reflux. PMID:20863911

Bussone, Guillaume; Mouthon, Luc

2011-03-01

189

[Protective effect of rupatadine against oleic acid-induced acute lung injury in rabbits].  

PubMed

Acute lung injury (ALI) makes up a spectrum of disease that is commonly defined as "acute non-cardiogenic edematous lung injury". It may contribute to morbidity and mortality in the critically ill patient in the intensive care unit. ALI was induced by oleic acid in rabbits. During the experiment, blood samples were taken from cervical artery and subjected to blood-gas analysis at different time points after oleic acid injection. Shortly after the rabbits were killed at 3 hour after iv OA injection, bronchoalveolar lavage fluid (BALF) was colleted, and the concentrations of protein, platelet-activating factor (PAF), intercellular adhesion molecule-1 (ICAM-1), interleukin 8 (IL-8) in BALF were then measured by ELISA. The ratio of wet to dry weight (W/D) of left lung was calculated to assess alveolar edema. Lung tissue was fixed in formaldehyde and stained with HE, and examined under a light microscope. The OA-induced elevation of arterial blood oxygen pressure was inhibited, as well as PAF, ICAM-1, IL-8 in BALF in rupatadine group. Furthermore, rupatadine also decreased the concentration of protein in BALF and inhibited the increase of the W/D weight ratio significantly. Light microscopic findings showed that the damage in rupatadine groups was far less severe than that in OA model group. Pretreatment with rupatadine has a beneficial effect on acute lung injury induced by oleic acid in rabbits. The ultimate reduction of inflammatory factors was involved, at least in part, in the mechanism of action of rupatadine effects. PMID:17520822

Zhang, Lin-Li; Lu, Jing; Yu, Shu-Qin; He, Jian-Lin; Zhou, Min; Xu, Guang-Lin

2007-03-01

190

Experimental Models and Emerging Hypotheses for Acute Lung Injury  

PubMed Central

Acute Lung Injury (ALI) is a complex illness involving the activation of multiple pathways leading to lung injury, resolution and repair. Since the first description of ALI, a great deal of effort has been devoted to exploring the roles of individual pathways in humans and animal models. These have led to a much greater understanding of the complexity of ALI and the links between ALI and systemic multiorgan failure. Despite progress in many areas, we still do not have an integrated understanding of the initiating factors, the key steps in the progression of ALI, and the central processes involved in repair. Although animal models have suggested a range of new hypotheses for study, the major need is for a better understanding of how pathways interact to explain the complexity of the human ALI syndrome and how complementary treatments can be used simultaneously or sequentially to modify the onset, severity and outcome of ALI in humans.

Martin, Thomas R.; Matute-Bello, Gustavo

2011-01-01

191

Plasminogen activator inhibitor-1 in acute hyperoxic mouse lung injury.  

PubMed Central

Hyperoxia-induced lung disease is associated with prominent intraalveolar fibrin deposition. Fibrin turnover is tightly regulated by the concerted action of proteases and antiproteases, and inhibition of plasmin-mediated proteolysis could account for fibrin accumulation in lung alveoli. We show here that lungs of mice exposed to hyperoxia overproduce plasminogen activator inhibitor-1 (PAI-1), and that PAI-1 upregulation impairs fibrinolytic activity in the alveolar compartment. To explore whether increased PAI-1 production is a causal or only a correlative event for impaired intraalveolar fibrinolysis and the development of hyaline membrane disease, we studied mice genetically deficient in PAI-1. We found that these mice fail to develop intraalveolar fibrin deposits in response to hyperoxia and that they are more resistant to the lethal effects of hyperoxic stress. These observations provide clear and novel evidence for the pathogenic contribution of PAI-1 in the development of hyaline membrane disease. They identify PAI-1 as a major deleterious mediator of hyperoxic lung injury.

Barazzone, C; Belin, D; Piguet, P F; Vassalli, J D; Sappino, A P

1996-01-01

192

CD4+ T Lymphocytes are Not Necessary for the Acute Rejection of Vascularized Mouse Lung Transplants  

PubMed Central

Acute rejection continues to present a major obstacle to successful lung transplantation. While CD4+ T lymphocytes are critical for the rejection of some solid organ grafts the role of CD4+ T cells in the rejection of lung allografts is largely unknown. In this study we demonstrate in a novel model of orthotopic vascularized mouse lung transplantation that acute rejection of lung allografts is independent of CD4+ T cell-mediated allorecognition pathways. CD4+ T cell-independent rejection occurs in the absence of donor-derived graft-resident hematopoietic antigen presenting cells. Furthermore, blockade of the CD28/B7 costimulatory pathways attenuates acute lung allograft rejection in the absence of CD4+ T cells, but does not delay acute rejection when CD4+ T cells are present. Our results provide new mechanistic insight into the acute rejection of lung allografts and highlight the importance of identifying differences in pathways that regulate the rejection of various organs.

Gelman, Andrew E.; Okazaki, Mikio; Lai, Jiaming; Kornfeld, Christopher G.; Kreisel, Friederike H.; Richardson, Steven B.; Sugimoto, Seiichiro; Tietjens, Jeremy R.; Patterson, G. Alexander; Krupnick, Alexander S.; Kreisel, Daniel

2014-01-01

193

Lower incidence of CMV infection and acute rejections with valganciclovir prophylaxis in lung transplant recipients  

PubMed Central

Background Cytomegalovirus (CMV) is the most common opportunistic infection following lung transplantation. CMV replication in the lung allograft is described as accelerating the development of bronchiolitis obliterans syndrome (BOS). Finding a strategy to prevent CMV infection is an important issue. Methods We performed a retrospective, single-centre study of 114 lung transplant recipients (LTRs) who underwent lung transplantation from January 2001 to December 2006. In a smaller cohort of 88 CMV seropositive (R+) LTRs, three months of valganciclovir prophylaxis (2004-2006) was compared to three months of oral ganciclovir (2001-2003) with respect to the incidence of CMV infection/disease, the severity of CMV disease, acute rejection, BOS-free 4 year survival and 4 year survival. In the whole group of 114 LTRs the impact of CMV infection on long-term survival (BOS free 4 year survival and 6 year survival) was assessed. Results For the cohort of 88 CMV seropositive LTRs, the incidence of CMV infection/disease at one year was lower in the valganciclovir group compared to the ganciclovir group (24% vs. 54%, p?=?0.003). There was a tendency towards reduced CMV disease, from 33% to 20% and a significant lower incidence of asymptomatic CMV infection (22% vs. 4%, p?=?0.005). A lower incidence of acute rejection was observed in the valganciclovir group. However, there was no significant difference between the two groups in BOS free 4 year survival and 4 year survival. For the entire group of 114 LTRs, BOS-free 4 year survival for recipients with CMV disease was (32%, p?=?0.005) and among those with asymptomatic CMV infection (36%, p?=?0.061) as compared with patients without CMV infection (69%). Six year survival was lower among patients with CMV disease, (64%, p?=?0.042) and asymptomatic CMV infection (55%, p?=?0.018) than patients without CMV infection (84%). Conclusions A lower incidence of CMV infection/disease and acute rejections was observed with valganciclovir (3 months) when compared to oral ganciclovir (3 months). The long-term impact of CMV infection/disease was significant for BOS-free survival and survival.

2013-01-01

194

Mannose prevents lipopolysaccharide-induced acute lung injury in rats  

Microsoft Academic Search

.\\u000a Objective:  To investigate the effect of mannose on lipopolysaccharide (LPS) induced acute lung injury (ALI) in rats.\\u000a \\u000a \\u000a \\u000a Methods:  Ten groups of Sprague–Dawley rats were used: 1) the control group received an intratracheal instillation of saline, 2) the LPS group received an intratracheal instillation of LPS (3 mg\\/kg), 3–6) the mannose groups were injected i.v. with 15, 45, 135, and 405 mg\\/kg mannose, 7–9)

X. L. Xu; Q. M. Xie; Y. H. Shen; J. J. Jiang; Y. Y. Chen; H. Y. Yao; J. Y. Zhou

2008-01-01

195

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.

Kim, Carla F.

2014-01-01

196

Lung stem and progenitor cells in tissue homeostasis and disease.  

PubMed

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

Leeman, Kristen T; Fillmore, Christine M; Kim, Carla F

2014-01-01

197

Prognostic Factors for Myositis-Associated Interstitial Lung Disease  

PubMed Central

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

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

2014-01-01

198

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

199

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.

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

2013-01-01

200

Lung recruitment manoeuvres are effective in regaining lung volume and oxygenation after open endotracheal suctioning in acute respiratory distress syndrome  

PubMed Central

Introduction Lung collapse is a contributory factor in the hypoxaemia that is observed after open endotracheal suctioning (ETS) in patients with acute lung injury and acute respiratory distress syndrome. Lung recruitment (LR) manoeuvres may be effective in rapidly regaining lung volume and improving oxygenation after ETS. Materials and method A prospective, randomized, controlled study was conducted in a 15-bed general intensive care unit at a university hospital. Eight consecutive mechanically ventilated patients with acute lung injury or acute respiratory distress syndrome were included. One of two suctioning procedures was performed in each patient. In the first procedure, ETS was performed followed by LR manoeuvre and reconnection to the ventilator with positive end-expiratory pressure set at 1 cmH2O above the lower inflexion point, and after 60 min another ETS (but without LR manoeuvre) was performed followed by reconnection to the ventilator with similar positive end-expiratory pressure; the second procedure was the same as the first but conducted in reverse order. Before (baseline) and over 25 min following each ETS procedure, partial arterial oxygen tension (PaO2) and end-expiratory lung volume were measured. Results After ETS, PaO2 decreased by 4.3(0.9–9.7)kPa (median and range; P < 0.005). After LR manoeuvre, PaO2 recovered to baseline. Without LR manoeuvre, PaO2 was reduced (P = 0.05) until 7 min after ETS. With LR manoeuvre end-expiratory lung volume was unchanged after ETS, whereas without LR manoeuvre end-expiratory lung volume was still reduced (approximately 10%) at 5 and 15 min after ETS (P = 0.01). Discussion A LR manoeuvre immediately following ETS was, as an adjunct to positive end-expiratory pressure, effective in rapidly counteracting the deterioration in PaO2 and lung volume caused by open ETS in ventilator-treated patients with acute lung injury or acute respiratory distress syndrome.

Dyhr, Thomas; Bonde, Jan; Larsson, Anders

2003-01-01

201

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

202

Interstitial lung disease in myositis: clinical subsets, biomarkers, and treatment.  

PubMed

Interstitial lung disease (ILD) is the most frequent organ involvement (found in nearly half) of myositis patients, but it reveals various clinical courses and therapeutic responsiveness according to clinical and serological subsets. Autoantibodies, as well as imaging and histopathological studies, are useful for the classification of ILD in myositis and provide useful information for predicting prognosis and determining treatment. Antisynthetase antibodies are correlated with chronic and recurrent ILD, whereas anti-CADM-140 (MDA5/IFIH1) antibodies are a marker of acute progressive ILD in clinically amyopathic dermatomyositis. Serum KL-6, SP-D, and ferritin are useful biomarkers for monitoring the activity and severity of ILD. Regarding treatment, glucocorticoids are the first-line drug, but additional immunomodulating drugs are also used in refractory patients. Cyclophosphamide and calcineurin inhibitors (cyclosporine and tacrolimus) appear to be the key drugs in the treatment of refractory myositis-ILD. Rituximab may become another candidate if these drugs are not effective. PMID:22367479

Mimori, Tsuneyo; Nakashima, Ran; Hosono, Yuji

2012-06-01

203

Lung protective mechanical ventilation and two year survival in patients with acute lung injury: prospective cohort study  

PubMed Central

Objective To evaluate the association of volume limited and pressure limited (lung protective) mechanical ventilation with two year survival in patients with acute lung injury. Design Prospective cohort study. Setting 13 intensive care units at four hospitals in Baltimore, Maryland, USA. Participants 485 consecutive mechanically ventilated patients with acute lung injury. Main outcome measure Two year survival after onset of acute lung injury. Results 485 patients contributed data for 6240 eligible ventilator settings, as measured twice daily (median of eight eligible ventilator settings per patient; 41% of which adhered to lung protective ventilation). Of these patients, 311 (64%) died within two years. After adjusting for the total duration of ventilation and other relevant covariates, each additional ventilator setting adherent to lung protective ventilation was associated with a 3% decrease in the risk of mortality over two years (hazard ratio 0.97, 95% confidence interval 0.95 to 0.99, P=0.002). Compared with no adherence, the estimated absolute risk reduction in two year mortality for a prototypical patient with 50% adherence to lung protective ventilation was 4.0% (0.8% to 7.2%, P=0.012) and with 100% adherence was 7.8% (1.6% to 14.0%, P=0.011). Conclusions Lung protective mechanical ventilation was associated with a substantial long term survival benefit for patients with acute lung injury. Greater use of lung protective ventilation in routine clinical practice could reduce long term mortality in patients with acute lung injury. Trial registration Clinicaltrials.gov NCT00300248.

2012-01-01

204

Inhibition of Neutrophil Exocytosis Ameliorates Acute Lung Injury in Rats  

PubMed Central

Exocytosis of neutrophil granules contributes to acute lung injury (ALI) induced by infection or inflammation, suggesting that inhibition of neutrophil exocytosis in vivo could be a viable therapeutic strategy. This study was conducted to determine the effect of a cell-permeable fusion protein that inhibits neutrophil exocytosis (TAT-SNAP-23) on ALI using an immune complex deposition model in rats. The effect of inhibition of neutrophil exocytosis by intravenous administration of TAT-SNAP-23 on ALI was assessed by albumin leakage, neutrophil infiltration, lung histology, and proteomic analysis of bronchoalveolar lavage fluid (BALf). Administration of TAT-SNAP-23, but not TAT-Control, significantly reduced albumin leakage, total protein levels in the BALf, and intra-alveolar edema and hemorrhage. Evidence that TAT-SNAP-23 inhibits neutrophil exocytosis included a reduction in plasma membrane CD18 expression by BALf neutrophils and a decrease in neutrophil granule proteins in BALf. Similar degree of neutrophil accumulation in the lungs and/or BALf suggests that TAT-SNAP-23 did not alter vascular endothelial cell function. Proteomic analysis of BALf revealed that components of the complement and coagulation pathways were significantly reduced in BALf from TAT-SNAP-23-treated animals. Our results indicate that administration of a TAT-fusion protein that inhibits neutrophil exocytosis reduces in vivo ALI. Targeting neutrophil exocytosis is a potential therapeutic strategy to ameliorate ALI.

Uriarte, Silvia M.; Rane, Madhavi J.; Merchant, Michael L.; Jin, Shunying; Lentsch, Alex B.; Ward, Richard A.; McLeish, Kenneth R.

2013-01-01

205

Cystic interstitial lung diseases: recognizing the common and uncommon entities.  

PubMed

Cystic lung diseases present a considerable diagnostic challenge because they are less frequently encountered in clinical practice and high-resolution computed tomography findings are often similar in many of these diseases. Here, we review the high-resolution computed tomography findings of cystic lung diseases and their mimics and provide a systematic approach to their diagnosis. Specific diseases that are discussed include pulmonary Langerhans cell histiocytosis, lymphangioleiomyomatosis, Birt-Hogg-Dubé syndrome, lymphocytic interstitial pneumonia, and light chain deposition disease. PMID:24791615

Jawad, Hamza; Walker, Christopher M; Wu, Carol C; Chung, Jonathan H

2014-01-01

206

Systemic administration of FC-77 dampens ischemia-reperfusion-induced acute lung injury in rats.  

PubMed

Systemic administration of perfluorocarbons (PFCs) reportedly attenuates acute lung injury induced by acid aspiration and phorbol myristate acetate. However, the effects of PFCs on ischemia-reperfusion (IR)-induced lung injury have not been investigated. Typical acute lung injury was induced in rats by 60 min of ischemia and 60 min of reperfusion in isolated and perfused rat lung model. Rat lungs were randomly assigned to receive PBS (control), 1 % FC-77, IR only, or IR with different doses of FC-77 (0.1 %, 0.5 %, or 1 %). Subsequently, bronchoalveolar lavage fluid (BALF), perfusate, and lung tissues were collected to evaluate the degree of lung injury. IR caused a significant increase in the following parameters: pulmonary arterial pressure, capillary filtration coefficient, lung weight gain, lung weight/body weight ratio, wet/dry lung weight ratio, and protein concentration in BALF. TNF-? and cytokine-induced neutrophil chemoattractant-1 concentrations in perfusate samples and MDA concentration and MPO activities in lung tissues were also significantly increased. Histopathology showed increased septal thickness and neutrophil infiltration in the lung tissues. Furthermore, NF-?B activity was significantly increased in the lungs. However, pretreatment with 1 % FC-77 prior to IR significantly attenuated the increases in these parameters. In conclusion, our results suggest that systemic FC-77 administration had a protective effect on IR-induced acute lung injury. These protective mechanisms may have been mediated by the inhibition of NF-?B activation and attenuation of subsequent inflammatory response. PMID:23807052

Chu, Shi-Jye; Huang, Kun-Lun; Wu, Shu-Yu; Ko, Fu-Chang; Wu, Geng-Chin; Li, Rui-Ying; Li, Min-Hui

2013-12-01

207

Acute effects of routine firefighting on lung function.  

PubMed

We undertook a study to determine the acute effects of routine firefighting on lung function and the relationship between these acute effects and nonspecific airway responsiveness. For 29 firefighters from a single fire station, we calculated the concentration of methacholine aerosol that caused a 100% increase in specific airway resistance (Pc100). Over an 8-week period we than measured FEV1 and FVC in each firefighter before and after each 24-hr workshift and after every fire. From 199 individual workshifts without fires, we calculated the mean +/- 2 SD across-workshift change in FEV1 and FVC for each firefighter. Eighteen of 76 measurements obtained within 2 hr after a fire (24%) showed a greater than 2 SD fall in FEV1 and/or FVC compared to two of 199 obtained after routine workshifts without fires (1%; p less than .001). On 13 of 18 occasions when spirometry decreased significantly, we obtained repeat spirometry (postshift) 3-18.5 hr after fires, and on four of these occasions FEV1 and/or FVC were still more than 2 SD below baseline. Decrements in spirometry occurred as often in firefighters with high Pc100s as in those with low Pc100s. In two firefighters in whom FEV1 and FVC fell by more than 10% after fires, we repeated measurements of methacholine sensitivity, and it was increased over the prestudy baseline. These findings suggest that routine firefighting is associated with a high incidence of acute decrements in lung function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3518426

Sheppard, D; Distefano, S; Morse, L; Becker, C

1986-01-01

208

Altered mucosal immune response after acute lung injury in a murine model of Ataxia Telangiectasia  

PubMed Central

Background Ataxia telangiectasia (A-T) is a rare but devastating and progressive disorder characterized by cerebellar dysfunction, lymphoreticular malignancies and recurrent sinopulmonary infections. In A-T, disease of the respiratory system causes significant morbidity and is a frequent cause of death. Methods We used a self-limited murine model of hydrochloric acid-induced acute lung injury (ALI) to determine the inflammatory answer due to mucosal injury in Atm (A-T mutated)- deficient mice (Atm-/-). Results ATM deficiency increased peak lung inflammation as demonstrated by bronchoalveolar lavage fluid (BALF) neutrophils and lymphocytes and increased levels of BALF pro-inflammatory cytokines (e.g. IL-6, TNF). Furthermore, bronchial epithelial damage after ALI was increased in Atm-/- mice. ATM deficiency increased airway resistance and tissue compliance before ALI was performed. Conclusions Together, these findings indicate that ATM plays a key role in inflammatory response after airway mucosal injury.

2014-01-01

209

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

210

Biochemical assessment of acute nitrogen dioxide toxicity in rat lung  

SciTech Connect

The early primary biochemical response of lung to NO/sub 2/ was studied separately from the later secondary responses of inflammation and proliferation by measuring several biochemical parameters in lungs of rats immediately following a 4-hr exposure to nitrogen dioxide (NO/sub 2/) at concentrations of 10, 20, 30 and 40 ppm. Cell-free lavage fluid contained elevated amounts of lactate dehydrogenase (LDH), malate dehydrogenase (MDH), isocitrate dehydrogenase (IDH), glucose-6-phosphate dehydrogenase (GDH), acid phosphatase (AP), and aryl sulfatase (AS) after 30 or 40 ppm NO/sub 2/. Total protein and sialic acid were increased in cell-free lavage after 20, 30, or 40 ppm NO/sub 2/. The amounts of protein, sialic acid, and acid phosphatase recovered by airway lavage were equal to the amounts found in 0.7 ml of plasma, consistent with transudation of this volume of plasma into airways as a source of these parameters. The plasma activity of the other parameters measured was too low to account for their increase in lavage fluid by plasma leakage into airways. Decrease in the number and enzyme content of lavagable cells indicated damage to free cells in the airways. The amount of the decrease in enzyme content of the lavagable cell fraction was similar to the increase in the cell-free lavage for all of the measured enzymes except acid phosphatase, suggesting the release of these enzymes into airways as a result of damage to free cells. However, the LDH isoenzyme profile in cell-free lavage after exposure is inconsistent with free cells as the source of this enzyme. This study indicates that initial acute damage to lung by NO/sub 2/ results in translocation of enzymes, proteins, and sialic acid into airways. Plasma is a likely source of translocated protein, sialic acid, and acid phosphatase. The sources of the other enzyme activities remain to be identified, with lung parenchyma and free cells as likely sources.

Guth, D.J.; Mavis, R.D.

1985-01-01

211

Nontuberculous mycobacterial (NTM) lung disease: the top ten essentials.  

PubMed

This review will utilize essential questions about nontuberculous mycobacterial (NTM) lung disease to succinctly address important new developments in the pathogenesis, diagnosis and management of NTM lung disease with a focus on practical information and "bottom line" answers. 1) What do I tell my patients who ask, “where did I get this infection” and, “should I take showers”? 2) What is the connection between bronchiectasis and the acquisition of NTM lung infection? 3) What other factors are important in the pathogenesis of NTM lung disease? 4) Why does it seem that am I seeing more new NTM lung disease patients? 5) Why is the diagnosis of NTM lung disease so complicated and does the diagnosis of NTM lung infection obligate specific treatment? 6) Unlike traditional tuberculosis, what is behind the irrelevance of most in vitro susceptibility testing reports for NTM infections? 7) Is there anything new for the management of patients with Mycobacterium avium complex lung disease? How does the radiographic appearance influence treatment? 8) Is there anything new for the management of patients with Mycobacterium abscessus lung disease? 9) What about the management of other NTM respiratory pathogens? 10) Is there a role for the use of macrolide monotherapy for non-cystic fibrosis bronchiectasis? PMID:24484653

Aksamit, Timothy R; Philley, Julie V; Griffith, David E

2014-03-01

212

Pulmonary hypertension complicating interstitial lung disease and COPD.  

PubMed

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

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

2013-10-01

213

Respiratory failure due to infliximab induced interstitial lung disease.  

PubMed

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

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

2013-01-01

214

Hepatic cryoablation-induced acute lung injury: histopathologic findings.  

PubMed

We have previously shown that hepatic cryoablation (cryo), but not partial hepatectomy, induces a systemic inflammatory response, with distant organ injury and overproduction of NF-kappaB-dependent cytokines. Serum tumor necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein-2 (MIP-2) levels are markedly increased 1 h and beyond after cryo compared with partial hepatectomy where no elevation occurs. NF-kappaB activation (by electrophoretic mobility shift assay) is strikingly increased in the noncryo liver (but not in the lung) at 30 min and in both the liver and lung tissue 1 h after cryo, returning to the baseline by 2 h and beyond. The current study investigated the histopathologic changes associated with cryoablation-induced acute lung injury. Animals underwent 35% hepatic resection or a similar volume hepatic cryo and were sacrificed at 1, 2, 6, and 24 h. Pulmonary histologic features were assessed using hematoxylin and eosin and immunoperoxidase staining with a macrophage-specific antibody (anti-lysozyme, 1:200 dilution, Dako, Carpinteria, CA). The following features were graded semiquantitatively (0-3): perivascular lymphoid cuffs, airspace edema and hemorrhage, margination of neutrophils within pulmonary vasculature, and the presence of macrophages with foamy cytoplasm in the pulmonary interstitium. Hepatic resection (n = 21) resulted in slight perivascular edema at 1, 2, 6, and 24 h post-resection, but there were no other significant changes. Pulmonary findings after hepatic cryo (n = 22) included prominent perivascular lymphoid cuffs 1 and 2 h following hepatic injury that were not present at any other time point (P 0.01). Marginating PMNs and foamy macrophages were more common after cryo at all time points (P<0.05, cryo vs resection). Severe lung injury, as evidenced by airspace edema and parenchymal hemorrhage, was present in four of six (67%) animals at 24 h (P 0.03). In follow-up studies immediate resection (n = 15) of the cryo-treated liver prior to thawing prevented the pulmonary changes. The findings of pulmonary perivascular interstitial macrophages 2 h following hepatic cryo suggests that hepatic cytokine production may induce downstream recruitment of pulmonary macrophages, which may contribute to subsequent severe lung injury. This study suggests that a soluble mediator from direct liver injury leads to neutrophilic lung inflammation and this is associated with the thawing phase of cryoablation. PMID:11120627

Washington, K; Debelak, J P; Gobbell, C; Sztipanovits, D R; Shyr, Y; Olson, S; Chapman, W C

2001-01-01

215

Acute Heart Failure and Systemic Diseases  

Microsoft Academic Search

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

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

216

Acute dysautonomia associated with Hodgkin's disease.  

PubMed Central

A patient is described with acute dysautonomia associated with Hodgkin's disease. Testing of cardiovascular reflex control showed that this patient had a rare manifestation of autonomic cardiovascular neuropathy, namely intact parasympathetic heart rate control in combination with a sympathetic postganglionic lesion affecting the control of the vascular tree.

van Lieshout, J J; Wieling, W; van Montfrans, G A; Settels, J J; Speelman, J D; Endert, E; Karemaker, J M

1986-01-01

217

Predictors of acute relapse of Crohn's disease  

Microsoft Academic Search

Relapses of Crohn's disease appear to be almost random. If these attacks could be reliably predicted, it might be possible to abort them with early treatment. In order to identify laboratory and clinical parameters that would predict an acute relapse, patients who had been assessed clinically in the three months prior to an attack were studied. Published clinical indices as

J. P. Wright; M. N. Alp; G. O. Young; N. Tigler-Wybrandi

1987-01-01

218

Invasive Aspergillus infections in hospitalized patients with chronic lung disease  

PubMed Central

Background Although invasive pulmonary aspergillosis (IPA) is more prevalent in immunocompromised patients, critical care clinicians need to be aware of the occurrence of IPA in the nontraditional host, such as a patient with chronic lung disease. The purpose of this study was to describe the IPA patient with chronic lung disease and compare the data with that of immunocompromised patients. Methods The records of 351 patients with Aspergillus were evaluated in this single-center, retrospective study for evidence and outcomes of IPA. The outcomes of 57 patients with chronic lung disease and 56 immunocompromised patients were compared. Patients with chronic lung disease were defined by one of the following descriptive terms: emphysema, asthma, idiopathic lung disease, bronchitis, bronchiectasis, sarcoid, or pulmonary leukostasis. Results Baseline demographics were similar between the two groups. Patients with chronic lung disease were primarily defined by emphysema (61%) and asthma (18%), and immunocompromised patients primarily had malignancies (27%) and bone marrow transplants (14%). A higher proportion of patients with chronic lung disease had a diagnosis of IPA by bronchoalveolar lavage versus the immunocompromised group (P < 0.03). The major risk factors for IPA were found to be steroid use in the chronic lung disease group and neutropenia and prior surgical procedures in the immunocompromised group. Overall, 53% and 69% of chronic lung disease and immunocompromised patients were cured (P = 0.14); 55% of chronic lung patients and 47% of immunocompromised patients survived one month (P = 0.75). Conclusion Nontraditional patients with IPA, such as those with chronic lung disease, have outcomes and mortality similar to that in the more traditional immunocompromised population.

Wessolossky, Mireya; Welch, Verna L; Sen, Ajanta; Babu, Tara M; Luke, David R

2013-01-01

219

Transfusion-Related Acute Lung Injury in Children with Hematological Malignancies  

Microsoft Academic Search

\\u000a Although uncommon, acute lung injury (ALI) and its more severe form the acute respiratory distress syndrome (ARDS) are serious\\u000a life-threatening complications that may occur during the routine treatment of children with hematological malignancies. ALI\\u000a may be the results of both the treatment of the malignancy or an adverse event related to supportive care, especially transfusion.\\u000a Transfusion-related acute lung injury (TRALI)

Rachel S. Bercovitz; J. Bradley Ball; Marguerite R. Kelher; Christopher C. Silliman

220

Extravascular lung water as an indicator of pulmonary dysfunction in acute hemorrhagic pancreatitis.  

PubMed Central

This study quantifies lung water in acute hemorrhagic pancreatitis to determine the degree to which pulmonary dysfunction occurs subclinically, before alterations in the arterial blood gases can be measured. Pancreatitis was induced in ten dogs by injecting 0.5 ml/kg of bile into the pancreatic ducts, which had been surgically cannulated. Pulmonary and systemic blood gases and blood pressures, heart rate, extravascular lung water, and lung blood flows were studied over 5 hours while cardiac output and mean arterial pressure were maintained at control values by Ringer's lactate infusion. The percentage of water in lung tissue was determined at the time of sacrifice using gravimetric measurements. Mean arterial pressure, cardiac output, and pulmonary capillary wedge pressure, reflecting intravascular volume status, did not change through at the experiment. By contrast, major disturbances were measured in the pulmonary bed with pulmonary artery pressures rising from 15.6 +/- 1.8/8.1 +/- 1.3 mmHg to 22.0 +/- 1.2/15.6 +/- 1.7 mmHg over 5 hours (p less than 0.01). Peripheral vascular resistance rose from 3.6 +/- 0.6 units to 6.6 +/- 0.4 units (p less than 0.05), whereas bronchial blood flow to the lung fell significantly. These changes in pulmonary hemodynamics were not reflected by changes in the arterial blood gases. Arterial oxygenation was maintained during 5 hours of pancreatitis. The partial pressure of carbon dioxide and the serum pH did not change significantly. There was, however, a progressive rise in extravascular lung water measured by the double-dilution technique from 10.2 +/- 0.8 ml/kg at control to 18.1 +/- 2.8 ml/kg (p less than 0.01) at 5 hours. This was confirmed by direct gravimetric measurements, which revealed an increase in the water content of the lung from 78.1 +/- 0.3% to 86.4 +/- 2.4% over the course of the experiment. Arterial blood gases, therefore, do not necessarily reflect the pulmonary deterioration in acute pancreatitis. These data supported a mechanism of lung dysfunction independent of the circulatory compromise, which often accompanies the disease in the clinical setting.

Burnweit, C A; Horton, J W

1988-01-01

221

Contagious caprine pleuropneumonia and Mannheimia haemolytica-associated acute respiratory disease of goats and sheep in Afar Region, Ethiopia  

Microsoft Academic Search

Summary In April 2002, an investigation into an outbreak of acute respiratory disease in goats and sheep in Milae (Afar), Ethiopia was conducted. The investigation involved 4 flocks (722 sheep and 750 goats in total) and comprised the disease history, clinical and post-mortem examination, and microbiological analysis of nasal swabs, lung lesions, and pleural fluid samples. Clinically diseased animals exhibited

G. Shiferaw; S. Tariku; G. Ayelet; Z. Abebe

222

Structure-activity association of flavonoids in lung diseases.  

PubMed

Flavonoids are polyphenolic compounds classified into flavonols, flavones, flavanones, isoflavones, catechins, anthocyanidins, and chalcones according to their chemical structures. They are abundantly found in Nature and over 8,000 flavonoids have from different sources, mainly plant materials, have been described. Recently reports have shown the valuable effects of flavonoids as antiviral, anti-allergic, antiplatelet, antitumor, antioxidant, and anti-inflammatory agents and interest in these compounds has been increasing since they can be helpful to human health. Several mechanisms of action are involved in the biological properties of flavonoids such as free radical scavenging, transition metal ion chelation, activation of survival genes and signaling pathways, regulation of mitochondrial function and modulation of inflammatory responses. The anti-inflammatory effects of flavonoids have been described in a number of studies in the literature, but not frequently associated to respiratory disease. Thus, this review aims to discuss the effects of different flavonoids in the control of lung inflammation in some disorders such as asthma, lung emphysema and acute respiratory distress syndrome and the possible mechanisms of action, as well as establish some structure-activity relationships between this biological potential and chemical profile of these compounds. PMID:24662074

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

2014-01-01

223

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.

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

2012-01-01

224

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

PubMed Central

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

Cornelio Favarin, Daniely; Martins Teixeira, Maxelle; Lemos de Andrade, Edneia; de Freitas Alves, Claudiney; Lazo Chica, Javier Emilio; Arterio Sorgi, Carlos; Paula Rogerio, Alexandre

2013-01-01

225

Perception of dyspnoea during acute changes in lung function in patients with either asthma or COPD.  

PubMed

The aim of the study was to evaluate the relationship between several lung function indices and perceived dyspnoea during bronchoconstriction. Acute changes in lung function were induced by inhaled histamine followed by terbutaline, in 12 asthmatics and 12 subjects with chronic obstructive pulmonary disease (COPD). A bipolar visual analogue scale (VAS), allowing subjects to report either improvement or worsening when moving off from a 'nochange' midpoint, was used to rate shortness of breath. Large swings in ratings were seen in all asthmatics and in seven out of 12 COPD subjects (high perceivers). Using linear regression of VAS rating against parallel change in lung function, on a within-subject basis, the highest degree of correlation between dyspnoea and objective response was found to involve the change in specific inspiratory resistance (sRin) in the asthmatics. In the five low perceivers, the ability to discriminate an increase in airway obstruction, estimated as the VAS/change in lung function slope, was very poor. Using a stepwise multiple regression analysis, the sensation of dyspnoea was found to be significantly related to the FEV1 and the sRin in the asthmatics, to the inspiratory vital capacity and the maximal inspiratory flow at 50% FVC (MIF50) in the COPD subjects with high perception, and to the MIF50 in the COPD subjects with low perception. PMID:7480977

Noseda, A; Schmerber, J; Prigogine, T; de Maertelaer, V; Yernault, J C

1995-08-01

226

Simvastatin Reduces Endotoxin-Induced Acute Lung Injury by Decreasing Neutrophil Recruitment and Radical Formation  

PubMed Central

Introduction Treatment of acute lung injury (ALI) remains an unsolved problem in intensive care medicine. As simvastatin exerts protective effects in inflammatory diseases we explored its effects on development of ALI and due to the importance of neutrophils in ALI also on neutrophil effector functions. Methods C57Bl/6 mice were exposed to aerosolized LPS (500 µg/ml) for 30 min. The count of alveolar, interstitial, and intravasal neutrophils were assessed 4 h later by flow cytometry. Lung permeability changes were assessed by FITC-dextran clearance and albumin content in the BAL fluid. In vitro, we analyzed the effect of simvastatin on neutrophil adhesion, degranulation, apoptosis, and formation of reactive oxygen species. To monitor effects of simvastatin on bacterial clearance we performed phagocytosis and bacterial killing studies in vitro as well as sepsis experiments in mice. Results Simvastatin treatment before and after onset of ALI reduces neutrophil influx into the lung as well as lung permeability indicating the protective role of simvastatin in ALI. Moreover, simvastatin reduces the formation of ROS species and adhesion of neutrophils without affecting apoptosis, bacterial phagocytosis and bacterial clearance. Conclusion Simvastatin reduces recruitment and activation of neutrophils hereby protecting from LPS-induced ALI. Our results imply a potential role for statins in the management of ALI.

Grommes, Jochen; Vijayan, Santosh; Drechsler, Maik; Hartwig, Helene; Morgelin, Matthias; Dembinski, Rolf; Jacobs, Michael; Koeppel, Thomas Andreas; Binnebosel, Marcel; Weber, Christian; Soehnlein, Oliver

2012-01-01

227

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.

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

228

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

Microsoft Academic Search

Treatment with dimethylthiourea (DMTU), a potent Oâ metabolite scavenger, prevented neutrophil-mediated acute edema in lungs of rabbits given phorbol myristate acetate (PMA) and in isolated rabbit lungs perfused with neutrophils and PMA. DMTU-treated rabbits given PMA did not increase their lung weight-to-total body weight ratios (5.0 +\\/- 0.3) or lung lavage albumin concentrations (14 +\\/- 4.6 mg\\/dl) in comparison to

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

1986-01-01

229

[Genetic susceptibility for acute high altitude disease].  

PubMed

Acute high altitude disease(AHAD), which can be divided into acute mountain disease (AMS), high altitude pulmonary edema (HAPE) and high altitude cerebral edema (HACE), is one of the special illnesses occurred at high altitude, commonly encountered by travelers to high altitudes (>2 500 m), which affects people's work capacity and health and could be even a life-threatening disease. Despite extensive investigations over the last century, the pathophysiology of AHAD remains elusive. Nevertheless, numerous researches have confirmed the existence of AHAD susceptibility differences. The aim of this paper was to review the epidemiological evidence for a genetic component to the various forms of AHAD so far, as well as to supply helpful reference to its epidemiological studies. PMID:23448926

Zhou, Wen-Ting; Hu, Yang

2013-02-01

230

Biomarkers in Acute Lung Injury - Marking Forward Progress  

PubMed Central

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

Barnett, Nicolas; Ware, Lorraine B.

2011-01-01

231

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

232

Future Directions in Early Cystic Fibrosis Lung Disease Research  

PubMed Central

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

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

2012-01-01

233

Apolipoprotein e-deficient mice are susceptible to the development of acute lung injury.  

PubMed

Background: Apolipoprotein E (apoE) has been shown to play a pivotal role in the development of cardiovascular disease, attributable to its function in lipid trafficking and immune modulating properties; however, its role in modulating inflammation in the setting of acute lung injury (ALI) is unknown. Objective: To determine whether apoE-deficient mice (apoE-/-) are more susceptible to ALI compared to wild-type (WT) animals. Methods: Two independent models of ALI were employed. Firstly, WT and apoE-/- mice were randomized to acid aspiration (50 ?l of 0.1 N hydrochloric acid) followed by 4 h of mechanical ventilation. Secondly, WT and apoE-/- mice were randomized to 72 h of hyperoxia exposure or room air. Thereafter, the intrinsic responses of WT and apoE-/- mice were assessed using the isolated perfused mouse lung (IPML) setup. Finally, based on elevated levels of oxidized low-density lipoprotein (oxLDL) in apoE-/-, the effect of oxLDL on lung endothelial permeability and inflammation was assessed. Results: In both in vivo models, apoE-/- mice demonstrated greater increases in lung lavage protein levels, neutrophil counts, and cytokine expression (p < 0.05) compared to WT mice. Experiments utilizing the IPML setup demonstrated no differences in intrinsic lung responses to injury between apoE-/- and WT mice, suggesting the presence of a circulating factor as being responsible for the in vivo observations. Finally, the exposure of lung endothelial cells to oxLDL resulted in increased monolayer permeability and IL-6 release compared to native (nonoxidized) LDL. Conclusions: Our findings demonstrate a susceptibility of apoE-/- animals to ALI that may occur, in part, due to elevated levels of oxLDL. © 2014 S. Karger AG, Basel. PMID:24662316

Yamashita, Cory M; Fessler, Michael B; Vasanthamohan, Lakshman; Lac, Joanne; Madenspacher, Jennifer; McCaig, Lynda; Yao, Lijuan; Wang, Lefeng; Puntorieri, Valeria; Mehta, Sanjay; Lewis, Jim F; Veldhuizen, Ruud A W

2014-01-01

234

Lung disease with chronic obstruction in opium smokers in Singapore  

PubMed Central

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

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

1971-01-01

235

Kawasaki disease resembling acute colitis.  

PubMed

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

236

Gene Expression Profiling in Patients with Chronic Obstructive Pulmonary Disease and Lung Cancer  

Microsoft Academic Search

Rationale: Chronic obstructive lung disease (COPD) is a common and disabling lung disease for which there are few therapeutic options. Objectives: We reasoned that gene expression profiling of COPD lungs could reveal previously unidentified disease pathways. Methods: Forty-eight human lung samples were obtained from tis- sue resected from five nonsmokers, 21 GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage

I-Ming Wang; Sergey Stepaniants; Yves Boie; James R. Mortimer; Brian Kennedy; Mark Elliott; Shizu Hayashi; Leanna Loy; Silvija Coulter; Sandra Cervino; Jennifer Harris; Michele Thornton; Richard Raubertas; Chris Roberts; Jim C. Hogg; Michael Crackower; Gary O'Neill; Peter D. Pare

237

Coronary Artery Disease Is Under-diagnosed and Under-treated in Advanced Lung Disease  

PubMed Central

BACKGROUND Coronary artery disease is a potentially treatable comorbidity observed frequently in both chronic obstructive pulmonary disease and interstitial lung disease. The prevalence of angiographically proven coronary artery disease in advanced lung disease is not well described. We sought to characterize the treatment patterns of coronary artery disease complicating advanced lung disease and to describe the frequency of occult coronary artery disease in this population. METHODS We performed a 2-center, retrospective cross-sectional study of patients with either chronic obstructive pulmonary disease or interstitial lung disease evaluated for lung transplantation. Medications and diagnoses before the transplant evaluation were recorded in conjunction with left heart catheterization results. RESULTS Of 473 subjects, 351 had chronic obstructive pulmonary disease, and 122 had interstitial lung disease. In subjects diagnosed clinically with coronary artery disease, medical regimens included a statin in 78%, antiplatelet therapy in 62%, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in 42%, and a beta-blocker in 37%. Ten percent were on no medication from these 4 classes. Fifty-seven percent of these subjects were on an antiplatelet agent as well as a statin, and 13% were on neither. Beta-blockers were less frequently prescribed in chronic obstructive pulmonary disease than interstitial lung disease (23% vs 58%, P = .007). Coronary angiography was available in 322 subjects. It demonstrated coronary artery disease in 60% of subjects, and severe coronary artery disease in 16%. Occult coronary artery disease and severe occult coronary artery disease were found in 53% and 9%, respectively. There were no significant differences in angiographic results between chronic obstructive pulmonary disease and interstitial lung disease, despite imbalanced risk factors. CONCLUSIONS Coronary artery disease is common in patients with advanced lung disease attributable to chronic obstructive pulmonary disease or interstitial lung disease and is under-diagnosed. Guideline-recommended cardioprotective medications are suboptimally utilized in this population.

Reed, Robert M.; Eberlein, Michael; Girgis, Reda E.; Hashmi, Salman; Iacono, Aldo; Jones, Steven; Netzer, Giora; Scharf, Steven

2013-01-01

238

The utility of clinical predictors of acute lung injury: towards prevention and earlier recognition  

PubMed Central

Despite significant advances in our understanding of the pathophysiology of acute lung injury, a lung-protective strategy of mechanical ventilation remains the only therapy with a proven survival advantage. Numerous pharmacologic therapies have failed to show benefit in multicenter clinical trials. The paradigm of early, goal-directed therapy of sepsis suggests greater clinical benefit may derive from initiating therapy prior to the onset of respiratory failure that requires mechanical ventilation. Thus, there is heightened interest in more accurate and complete characterization of high-risk patient populations and identification of patients in the early stage of acute lung injury, prior to the need for mechanical ventilation. This article discusses the growing literature on clinical predictors of acute lung injury (including risk factors for specific subgroups) with an emphasis on transfusion-related risk factors and recent research targeting the early identification of high-risk patients and those with early acute lung injury prior to the onset of respiratory failure.

Levitt, Joseph E; Matthay, Michael A

2011-01-01

239

Minimal acute rejection in pediatric lung transplantation does it matter?  

PubMed Central

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

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

2009-01-01

240

Effects of contrast material on computed tomographic measurements of lung volumes in patients with acute lung injury  

PubMed Central

Background Intravenous injection of contrast material is routinely performed in order to differentiate nonaerated lung parenchyma from pleural effusion in critically ill patients undergoing thoracic computed tomography (CT). The aim of the present study was to evaluate the effects of contrast material on CT measurement of lung volumes in 14 patients with acute lung injury. Method A spiral thoracic CT scan, consisting of contiguous axial sections of 10 mm thickness, was performed from the apex to the diaphragm at end-expiration both before and 30 s (group 1; n = 7) or 15 min (group 2; n = 7) after injection of 80 ml contrast material. Volumes of gas and tissue, and volumic distribution of CT attenuations were measured before and after injection using specially designed software (Lungview®; Institut National des Télécommunications, Evry, France). The maximal artifactual increase in lung tissue resulting from a hypothetical leakage within the lung of the 80 ml contrast material was calculated. Results Injection of contrast material significantly increased the apparent volume of lung tissue by 83 ± 57 ml in group 1 and 102 ± 80 ml in group 2, whereas the corresponding maximal artifactual increases in lung tissue were 42 ± 52 ml and 31 ± 18 ml. Conclusion Because systematic injection of contrast material increases the amount of extravascular lung water in patients with acute lung injury, it seems prudent to avoid this procedure in critically ill patients undergoing a thoracic CT scan and to reserve its use for specific indications.

Bouhemad, Belaid; Richecoeur, Jack; Lu, Qin; Malbouisson, Luiz M; Cluzel, Philippe; Rouby, Jean-Jacques

2003-01-01

241

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

242

Roger S. Mitchell lecture. Uses of expression microarrays in studies of pulmonary fibrosis, asthma, acute lung injury, and emphysema.  

PubMed

Expression microarrays are a powerful tool that could provide new information about the molecular pathways regulating common lung diseases. To exemplify how this tool can be useful, selected examples of informative experiments are reviewed. In studies relevant to asthma, the cytokine interleukin-13 has been shown to produce many of the phenotypic features of this disease, but the cellular targets in the airways and the molecular pathways activated are largely unknown. We have used microarrays to begin to dissect the different transcriptional responses of primary lung cells to this cytokine. In experiments designed to identify global transcriptional programs responsible for regulating lung inflammation and pulmonary fibrosis, we performed microarray experiments on lung tissue from wild-type mice and mice lacking a member of the integrin family know to be involved in activation of latent transforming growth factor (TGF)-beta. In addition to identifying distinct cluster of genes involved in each of these processes, these studies led to the identification of novel pathways by which TGF-beta can regulate acute lung injury and emphysema. Together, these examples demonstrate how careful application and thorough analysis of expression microarrays can facilitate the discovery of novel molecular targets for intervening in common lung diseases. PMID:11893658

Sheppard, Dean

2002-03-01

243

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.

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

244

Protective effect of adenosine receptors against lipopolysaccharide-induced acute lung injury.  

PubMed

Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) affect 200,000 people a year in the USA. Pulmonary vascular and specifically endothelial cell (EC) barrier compromise is a hallmark of these diseases. We have recently shown that extracellular adenosine enhances human pulmonary (EC) barrier via activation of adenosine receptors (ARs) in cell cultures. On the basis of these data, we hypothesized that activation of ARs might exert barrier-protective effects in a model of ALI/ARDS in mice. To test this hypothesis, we examined the effects of pre- and posttreatment of adenosine and 5'-N-ethylcarboxamidoadenosine (NECA), a nonselective stable AR agonist, on LPS-induced lung injury. Mice were given vehicle or LPS intratracheally followed by adenosine, NECA, or vehicle instilled via the internal jugular vein. Postexperiment cell counts, Evans Blue Dye albumin (EBDA) extravasation, levels of proteins, and inflammatory cytokines were analyzed. Harvested lungs were used for histology and myeloperoxidase studies. Mice challenged with LPS alone demonstrated an inflammatory response typical of ALI. Cell counts, EBDA extravasation, as well as levels of proteins and inflammatory cytokines were decreased in adenosine-treated mice. Histology displayed reduced infiltration of neutrophils. NECA had a similar effect on LPS-induced vascular barrier compromise. Importantly, posttreatment with adenosine or NECA recovers lung vascular barrier and reduces inflammation induced by LPS challenge. Furthermore, adenosine significantly attenuated protein degradation of A2A and A3 receptors induced by LPS. Collectively, our results demonstrate that activation of ARs protects and restores vascular barrier functions and reduces inflammation in LPS-induced ALI. PMID:24414256

Gonzales, Joyce N; Gorshkov, Boris; Varn, Matthew N; Zemskova, Marina A; Zemskov, Evgeny A; Sridhar, Supriya; Lucas, Rudolf; Verin, Alexander D

2014-03-15

245

Treatment of Acute Pelvic Inflammatory Disease  

PubMed Central

Pelvic inflammatory disease (PID), one of the most common infections in nonpregnant women of reproductive age, remains an important public health problem. It is associated with major long-term sequelae, including tubal factor infertility, ectopic pregnancy, and chronic pelvic pain. In addition, treatment of acute PID and its complications incurs substantial health care costs. Prevention of these long-term sequelae is dependent upon development of treatment strategies based on knowledge of the microbiologic etiology of acute PID. It is well accepted that acute PID is a polymicrobic infection. The sexually transmitted organisms, Neisseria gonorrhoeae and Chlamydia trachomatis, are present in many cases, and microorganisms comprising the endogenous vaginal and cervical flora are frequently associated with PID. This includes anaerobic and facultative bacteria, similar to those associated with bacterial vaginosis. Genital tract mycoplasmas, most importantly Mycoplasma genitalium, have recently also been implicated as a cause of acute PID. As a consequence, treatment regimens for acute PID should provide broad spectrum coverage that is effective against these microorganisms.

Sweet, Richard L.

2011-01-01

246

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

PubMed

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

Fisher, Aron B

2014-06-15

247

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

248

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

PubMed

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

Goto, Hisatsugu; Mitsuhashi, Atsushi; Nishioka, Yasuhiko

2014-01-01

249

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.

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

250

Congenital cystic lung disease: contemporary antenatal and postnatal management  

Microsoft Academic Search

Congenital cystic lung disease comprises a broad spectrum of rare but clinically significant developmental abnormalities,\\u000a including congenital pulmonary adenomatoid malformations, bronchopulmonary sequestrations, bronchogenic cysts, and congenital\\u000a lobar emphysema that result from perturbations in lung and airway embryogenesis. As congenital lung lesions are now more commonly\\u000a recognized antenatally, mothers require accurate prenatal counseling and appropriate perinatal management. In light of long-term

Richard G. Azizkhan; Timothy M. Crombleholme

2008-01-01

251

Smoking-related interstitial lung diseases: radiologic-pathologic correlation  

Microsoft Academic Search

Smoking-related interstitial lung diseases (SRILD) are a heterogeneous group of entities of unknown cause. These diseases\\u000a include desquamative interstitial pneumonia (DIP), respiratory-bronchiolitis-related interstitial lung disease (RB-ILD), pulmonary\\u000a Langerhans’ cell histiocytosis (LCH) and idiopathic pulmonary fibrosis (IPF). High-resolution CT is highly sensitive in the\\u000a detection of abnormalities in the lung parenchyma and airways. Ground-glass attenuation can occur in DIP and RB-ILD.

Alberto Hidalgo; Tomás Franquet; Ana Giménez; Ramón Bordes; Rosa Pineda; Marta Madrid

2006-01-01

252

Peroxiredoxin 6 differentially regulates acute and chronic cigarette smoke-mediated lung inflammatory response and injury  

PubMed Central

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

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

2011-01-01

253

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.

2014-01-01

254

Interstitial lung disease associated with vindesine and radiation therapy for carcinoma of the lung  

SciTech Connect

Diffuse interstitial lung disease and pulmonary fibrosis occurred after the use of vindesine and radiation therapy in a patient with squamous cell carcinoma of the lung. Clinical improvement occurred after the drug was discontinued and corticosteroid therapy was initiated. Review of the literature reveals no previously reported cases of pulmonary toxicity due to vindesine when used alone or in combination with other therapeutic modalities.

Bott, S.J.; Stewart, F.M.; Prince-Fiocco, M.A.

1986-07-01

255

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

256

Monoacylglycerol Lipase (MAGL) Inhibition Attenuates Acute Lung Injury in Mice  

PubMed Central

Endocannabinoid signaling is terminated by enzymatic hydrolysis, a process that, for 2-Arachidonoylglycerol (2-AG), is mediated by monoacylglycerol lipase (MAGL). The piperidine carbamate, 4-?nitrophenyl- ?4-?(dibenzo[d] [1,3]dioxol-?5-?yl (hydroxy) methyl) piperidine- 1-?carboxylate (JZL184), is a drug that inhibits MAGL and presents high potency and selectivity. Thus, JZL184 increases the levels of 2-AG, an endocannabinoid that acts on the CB1 and CB2 cannabinoid receptors. Here, we investigated the effects of MAGL inhibition, with a single dose (16 mg/kg, intraperitoneally (i.p.)) of JZL184, in a murine model of lipopolysaccharide (LPS) -induced acute lung injury (ALI) 6, 24 and 48 hours after the inflammatory insult. Treatment with JZL184 decreased the leukocyte migration into the lungs as well as the vascular permeability measured through the bronchoalveolar lavage fluid (BAL) and histological analysis. JZL184 also reduced the cytokine and chemokine levels in the BAL and adhesion molecule expression in the blood and BAL. The CB1 and CB2 receptors were considered involved in the anti-inflammatory effects of JZL184 because the AM281 selective CB1 receptor antagonist (1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-4-morpholinyl-1H-pyrazole-3-carboxamide) and the AM630 selective CB2 receptor antagonist ([6-?iodo-?2-?methyl-?1-?[2-?(4-?morpholinyl)ethyl]-?1H-?indol-?3-?yl](4-?methoxyphenyl)-?methanone) blocked the anti-inflammatory effects previously described for JZL184. It was concluded that MAGL inhibition, and consequently the increase in 2-AG levels, produced anti-inflammatory effects in a murine model of LPS-induced ALI, a finding that was considered a consequence of the activation of the CB1 and CB2 receptors.

Costola-de-Souza, Carolina; Ribeiro, Alison; Ferraz-de-Paula, Viviane; Calefi, Atilio Sersun; Aloia, Thiago Pinheiro Arrais; Gimenes-Junior, Joao Antonio; de Almeida, Vinicius Izidio; Pinheiro, Milena Lobao; Palermo-Neto, Joao

2013-01-01

257

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.

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

2014-01-01

258

Alveolar epithelium and Na,K-ATPase in acute lung injury  

Microsoft Academic Search

Active transport of sodium across the alveolar epithelium, undertaken in part by the Na,K-adenosine triphosphatase (Na,K-ATPase),\\u000a is critical for clearance of pulmonary edema fluid and thus the outcome of patients with acute lung injury. Acute lung injury\\u000a results in disruption of the alveolar epithelial barrier and leads to impaired clearance of edema fluid and altered Na,K-ATPase\\u000a function. There has been

István Vadász; Stacy Raviv; Jacob I. Sznajder

2007-01-01

259

Erythropoetin as a novel agent with pleiotropic effects against acute lung injury  

Microsoft Academic Search

Current pharmacotherapy for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is not optimal, and the\\u000a biological and physiological complexity of these severe lung injury syndromes requires consideration of combined-agent treatments\\u000a or agents with pleiotropic action. In this regard, exogenous erythropoietin (EPO) represents a possible candidate since a\\u000a number of preclinical studies have revealed beneficial effects of EPO

Sotirios Kakavas; Theano Demestiha; Panagiotis Vasileiou; Theodoros Xanthos

2011-01-01

260

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

261

Work-Related Lung Disease: All Pneumoconioses and Related Exposures  

MedlinePLUS

... Home Work-Related Lung Disease Surveillance System (eWoRLD) All Pneumoconioses and Related Exposures Thumbnail Table/Figure Title Date Posted All pneumoconioses: Number of deaths, crude and age-adjusted ...

262

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

263

Scientists Spot New Clues to a Deadly Lung Disease  

MedlinePLUS

... on this page, please enable JavaScript. Scientists Spot New Clues to a Deadly Lung Disease Idiopathic pulmonary ... bleak prognosis. Last month, studies revealed that two new medications might offer some hope for the first ...

264

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

SciTech Connect

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

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

1988-01-01

265

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

266

Effect of corticosteroid treatment on cell recovery by lung lavage in acute radiation-induced lung injury  

SciTech Connect

The purpose of this study was to quantitate cell populations recovered by lung lavage up to 6 weeks following thoracic irradiation (24 Gy) as an index of the acute inflammatory response within lung structures. Additionally, rats were treated five times weekly with intraperitoneal saline (0.3 cc) or methylprednisolone (7.5 mg/kg/week). Lung lavage of irradiated rats recovered increased numbers of total cells compared to controls beginning 3 weeks after irradiation (P less than 0.05). The initial increase in number of cells recovered was attributable to an influx of neutrophils (P less than 0.05), and further increases at 4 and 6 weeks were associated with increased numbers of recovered macrophages (P less than 0.05). Lung lavage of steroid-treated rats at 6 weeks after irradiation recovered increased numbers of all cell populations compared to controls (P less than 0.05); however, numbers of recovered total cells, macrophages, neutrophils, and lymphocytes were all significantly decreased compared to saline-treated rats (P less than 0.05). The number of inflammatory cells recovered by lung lavage during acute radiation-induced lung injury is significantly diminished by corticosteroid treatment. Changes in cells recovered by lung lavage can also be correlated with alteration in body weight and respiration rate subsequent to treatment with thoracic irradiation and/or corticosteroids.

Wesselius, L.J.; Floreani, A.A.; Kimler, B.F.; Papasian, C.J.; Dixon, A.Y. (Kansas City Veterans Administration Medical Center, MO (USA))

1989-11-01

267

[Use of enteral immune mixture in program of intensive care for acute parenchimal lung injury].  

PubMed

The article deals with a case of successful acute lung injure syndrome treatment. Patient received enteral nutritive treatment with balanced polysubstrate mixture--immune liquid additionally to antibacterial, infusion, respiratory and symptomatic therapy. The case shows that immune liquid corrects hypermetabolic syndrome and effects on decreasing of organs dysfunctions especially lung dysfunction. PMID:24341001

Iudakova, T N; Girsh, A O

2013-01-01

268

Computed tomography scan assessment of lung disease in primary immunodeficiencies  

Microsoft Academic Search

A wide spectrum of lung disease can complicate primary immunodeficiencies and early recognition influences management and\\u000a prognosis. Computed tomography (CT) especially high resolution computed tomography (HRCT) has been shown to detect lung disease\\u000a in adult immunodeficient patients often when the chest radiograph (CXR) is normal, but this has not been studied in children.\\u000a Twenty-five CT scans [10 HRCT] and CXRs

T. Newson; A. J. Chippindale; A. J. Cant

1999-01-01

269

Evaluation of Mycobacterium avium complex lung disease in women  

Microsoft Academic Search

Mycobacterium avium complex (MAC) is a ubiquitous organism responsible for most pulmonary and disseminated disease caused by non-tuberculosis (NTM) mycobacteria. Though MAC lung disease without predisposing factors is uncommon, in recent years it has been increasingly described in middle-aged and elderly women. Recognition and correct diagnosis, is often delayed due to the indolent nature of the disease. It is unclear

Tracie J Gardner

2004-01-01

270

Acute lung inflammation in rats induced by phorbol myristate acetate (PMA)  

Microsoft Academic Search

Intratracheal administration of PMA produces acute lung injury in part due to the generation of O2-derived free radicals. This study evaluated the role of the antioxidant enzyme superoxide dismutase (SOD) in PMA-induced lung injury in the rat. PMA was instilled into rats intratracheally (20–60 ?g\\/kg), and the lungs were lavaged 4 hr later. Total number of cells recovered from lavage

J. S. Kerr; A. Ciuffetelli; H. D. Hall; T. M. Stevens; N. R. Ackerman; W. M. Mackin

1987-01-01

271

Interleukin1 Causes Acute Lung Injury via v5 and v6 Integrin-Dependent Mechanisms  

Microsoft Academic Search

Interleukin (IL)-1 has previously been shown to be among the most biologically active cytokines in the lungs of patients with acute lung injury (ALI). Furthermore, there is experimental evidence that lung vascular permeability increases after short-term exposure to IL-1 protein, although the exact mechanism is unknown. Therefore, the objective of this study was to determine the mechanisms of IL-1-mediated increase

Michael T. Ganter; Jeremie Roux; Byron Miyazawa; Marybeth Howard; James A. Frank; George Su; Dean Sheppard; Shelia M. Violette; Paul H. Weinreb; Gerald S. Horan; Michael A. Matthay; Jean-Francois Pittet

272

Lung pathology of severe acute respiratory syndrome (SARS): a study of 8 autopsy cases from Singapore  

Microsoft Academic Search

Severe acute respiratory syndrome (SARS) is an infectious condition caused by the SARS-associated coronavirus (SARS-CoV), a new member in the family Coronaviridae. To evaluate the lung pathology in this life-threatening respiratory illness, we studied postmortem lung sections from 8 patients who died from SARS during the spring 2003 Singapore outbreak. The predominant pattern of lung injury in all 8 cases

Teri J Franks; Pek Y Chong; Paul Chui; Jeffrey R Galvin; Raina M Lourens; Ann H Reid; Elena Selbs; Col Peter L Mcevoy; Col Dennis L Hayden; Junya Fukuoka; Jeffery K Taubenberger; William D Travis

2003-01-01

273

Coal mine dust lung disease. New lessons from old exposure.  

PubMed

Coal mining remains a sizable industry, with millions of working and retired coal miners worldwide. This article provides an update on recent advances in the understanding of respiratory health issues in coal miners and focuses on the spectrum of disease caused by inhalation of coal mine dust, termed coal mine dust lung disease. In addition to the historical interstitial lung diseases (coal worker's pneumoconiosis, silicosis, and mixed dust pneumoconiosis), coal miners are at risk for dust-related diffuse fibrosis and chronic airway diseases, including emphysema and chronic bronchitis. Recent recognition of rapidly progressive pneumoconiosis in younger miners, mainly in the eastern United States, has increased the sense of urgency and the need for vigilance in medical research, clinical diagnosis, and exposure prevention. Given the risk for disease progression even after exposure removal, along with few medical treatment options, there is an important role for chest physicians in the recognition and management of lung disease associated with work in coal mining. PMID:23590267

Petsonk, Edward L; Rose, Cecile; Cohen, Robert

2013-06-01

274

Therapeutic effects of Caspase-1 inhibitors on acute lung injury in experimental severe acute pancreatitis  

PubMed Central

AIM: To assess the therapeutic effect of Caspase-1 inhibitors (ICE-I) on acute lung injury (ALI) in experimental severe acute pancreatitis (SAP). METHODS: Forty-two SD rats were randomly divided into 3 groups: healthy controls (HC, n = 6); SAP-S group (n = 18); SAP-ICE-I group (n = 18). SAP was induced by retrograde infusion of 5% sodium taurocholate into the bile-pancreatic duct. HC rats underwent the same surgical procedures and duct cannulation without sodium taurocholate infusion. In SAP-S group, rats received the first intraperitoneal injection of isotonic saline 2 h after induction of acute pancreatitis and a repeated injection after 12 h. In SAP-ICE-I group, the rats were firstly given ICE inhibitors intraperitoneally 2 h after induction of pancreatitis. As in SAP-S group, the injection was repeated at 12 h. Serum IL-1? was measured by ELISA. Intrapulmonary expression of Caspase-1, IL-1? and IL-18 mRNA were detected by semi-quantitative RT-PCR. The wet/dry weight ratios and histopathological changes of the lungs were also evaluated. RESULTS: Serum IL-1? levels in SAP-S group were 276.77 ± 44.92 pg/mL at 6 h, 308.99 ± 34.95 pg/mL at 12 h, and 311.60 ± 46.51 pg/mL at 18 h, which were increased significantly (P < 0.01, vs HC). In SAP-ICE-I group, those values were decreased significantly (P < 0.01, vs SAP-S). Intrapulmonary expression of Caspase-1, IL-1? and IL-18 mRNA were observed in the HC group, while they were increased significantly in the SAP-S group (P < 0.01, vs HC). The expression of IL-1? and IL-18 mRNA were decreased significantly in the SAP-ICE-I group (P < 0.01, vs SAP-S), whereas Caspase-1 mRNA expression had no significant difference (P > 0.05). The wet/dry weight ratios of the lungs in the SAP-S group were increased significantly (P < 0.05 at 6 h, P < 0.01 at 12 h and 18 h, vs HC) and they were decreased significantly in the SAP-ICE-I group (P < 0.05, vs SAP-S). Caspase-1 inhibitors ameliorated the severity of ALI in SAP. CONCLUSION: Caspase-1 activation, and overproduction of IL-1? and IL-18 play an important role in the course of ALI, and Caspase-1 inhibition is effective for the treatment of ALI in experimental SAP.

Zhang, Xiao-Hua; Zhu, Ren-Min; Xu, Wen-An; Wan, Hai-Jun; Lu, Heng

2007-01-01

275

The Association Between BMI and Plasma Cytokine Levels in Patients With Acute Lung Injury  

PubMed Central

Background: Obesity is associated with poor outcomes in many diseases, although recent data suggest that acute lung injury (ALI) is an exception. This is particularly interesting because obesity is marked by increased levels of proinflammatory mediators associated with increased morbidity and mortality in ALI. We hypothesized that cytokine response might be attenuated in patients who are obese and critically ill or that obesity might modify the relationship between plasma cytokines and clinical outcomes in ALI. Methods: We analyzed plasma biomarker levels (interleukin [IL]-6, IL-8, tumor necrosis factor-? receptor 1, surfactant protein D [SP-D], soluble intracellular adhesion molecule, von Willebrand factor (vWF), protein C, and plasminogen activator inhibitor-1) collected at baseline and day 3 in 1,409 participants in prior National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network (ARDSNet) trials. BMI was calculated for each patient, and associations with cytokine levels and ventilator-free days (VFDs), organ failure-free days (OFDs), and mortality were investigated in regression models adjusting for confounders. Results: In adjusted analyses, plasma IL-6 (P = .052), IL-8 (P = .001), and SP-D (P < .001) were inversely related to BMI, whereas vWF (P = .001) and WBC count (P = .042) increased proportionally with BMI. BMI was not associated with increased morbidity or mortality and did not modify the association between baseline biomarker levels and mortality, VFDs, or OFDs. Conclusions: Patients who are obese and have ALI have lower levels of several proinflammatory cytokines, suggesting that the inflammatory response may be altered in patients with ALI and a high BMI. Lower SP-D but higher vWF suggests decreased epithelial and increased endothelial injury in the lung of patients who are obese. Mechanisms by which obesity may modulate innate immunity in critical illness are unclear, and future studies should elucidate such mechanisms.

Dixon, Anne E.; Parsons, Polly E.; Ware, Lorraine B.; Suratt, Benjamin T.

2010-01-01

276

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.

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

2013-01-01

277

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

PubMed

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

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

2014-08-01

278

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

Microsoft Academic Search

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

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

2004-01-01

279

Pharmacokinetic Behavior of Theophylline following PEEP in Critically Ill Patients with Acute Lung Injury  

Microsoft Academic Search

The effect of Positive End Expiratory Pressure (PEEP) on the hepatic elimination of low to moderate extraction ratio drugs has not been clearly defined. We prospectively investigated the effect of PEEP on the clearance of theophylline in 30 (20 males and 10 females) intubated critically ill adult patients with acute lung injury\\/acute respiratory distress syndrome (ALI\\/ARDS). The Mean (±SD) age

Naser Hadavand; Mojtaba Mojtahedzadeh; Sima Sadray; Reza Shariat Moharreri; Bijan Shafaghi; Mohammad Reza Khajavi; Poneh Salari

2004-01-01

280

Advances in the diagnosis of pleural disease in lung cancer.  

PubMed

Pleural disease in lung cancer can be benign or malignant with the latter carrying a grave prognosis. In this review, we describe and discuss the advances in pleural imaging, procedures, and biomarkers for the diagnosis of pleural diseases in lung cancer. Ultrasound and computed tomography are increasingly applied in the planning of pleural procedures to enhance diagnostic accuracy and safety whilst pleuroscopy gives excellent yield in excess of 93% in the evaluation of cytology negative pleural effusions. Invasion beyond the elastic layer of the visceral pleura upstages lung cancer, and may indicate a need for adjuvant chemotherapy. Biomarkers isolated from pleural fluid or tissue may aid in diagnosis and guide treatment in the future. Magnetic resonance imaging, positron emission tomography, narrow band imaging of the pleura and autofluorescence thoracoscopy are technologies that require further evaluation to better define their respective roles in the diagnostic algorithms of pleural diseases in lung cancer. PMID:21697244

See, Kay Choong; Lee, Pyng

2011-12-01

281

N-acetylcysteine attenuates the acute lung injury caused by phorbol myristate acetate in isolated rat lungs  

Microsoft Academic Search

Acute lung injury (ALI) caused by phorbol myristate acetate (PMA) is characterized by pulmonary edema and inflammatory cells infiltration. PMA-activated neutrophils in vivo and in vitro to release free radicals, pro-inflammatory cytokines, nitric oxide (NO) and other mediators. These mediators may be the causes of pulmonary hypertension and increased microvascular permeability. In the present study, we used isolated perfused rat

I Chun Chuang; Demeral David Liu; Shang Jyh Kao; Hsing I Chen

2007-01-01

282

Dosimetric correlations of acute esophagitis in lung cancer patients treated with radiotherapy  

SciTech Connect

Purpose: To evaluate the factors associated with acute esophagitis in lung cancer patients treated with thoracic radiotherapy. Methods and Materials: We examined 35 patients with non-small-cell lung cancer (n = 27, 77%) and small-cell lung cancer (n = 8, 23%) treated with thoracic radiotherapy between February 2003 and November 2004. The median patient age was 70 years (range, 50-83 years). The disease stage was Stage I in 2 patients (6%), Stage II in 1 (3%), Stage IIIa in 10 (28%), Stage IIIb in 9 (26%), and Stage IV in 9 (26%); 4 patients (11%) had recurrent disease after surgery. A median dose of 60 Gy (range, 50-67 Gy) was given to the isocenter and delivered in single daily fractions of 1.8 or 2 Gy. With heterogeneity corrections, the median given dose to the isocenter was 60.3 Gy (range, 49.9-67.2 Gy). Of the 35 patients, 30 (86%) received concurrent chemotherapy consisting of a platinum agent, cisplatin or carboplatin, combined with paclitaxel in 18 patients (52%), irinotecan hydrochloride in 7 (20%), vincristine sulfate and etoposide in 2 (5%), vinorelbine ditartrate in 1 (3%), etoposide in 1 (3%), and docetaxel in 1 patient (3%). Three of these patients underwent induction therapy with cisplatin and irinotecan hydrochloride, administered before thoracic radiotherapy, and concurrent chemotherapy. Esophageal toxicity was graded according to the Radiation Therapy Oncology Group criteria. The following factors were analyzed with respect to their association with Grade 1 or worse esophagitis by univariate and multivariate analyses: age, gender, concurrent chemotherapy, chemotherapeutic agents, maximal esophageal dose, mean esophageal dose, and percentage of esophageal volume receiving >10 to >65 Gy in 5-Gy increments. Results: Of the 35 patients, 25 (71%) developed acute esophagitis, with Grade 1 in 20 (57%) and Grade 2 in 5 (14%). None of the patients had Grade 3 or worse toxicity. The most significant correlation was between esophagitis and percentage of esophageal volume receiving >35 Gy on univariate (p = 0.002) and multivariate (p = 0.018) analyses. Conclusion: The percentage of esophageal volume receiving >35 Gy was the most statistically significant factor associated with mild acute esophagitis.

Takeda, Ken [Department of Radiology, National Hospital Organization Sendai Medical Center, Sendai (Japan)]. E-mail: takedak41@yahoo.co.jp; Nemoto, Kenji [Department of Radiation Oncology, Tohoku University School of Medicine, Sendai (Japan); Saito, Haruo [Department of Radiology, National Hospital Organization Sendai Medical Center, Sendai (Japan); Ogawa, Yoshihiro [Department of Radiation Oncology, Tohoku University School of Medicine, Sendai (Japan); Takai, Yoshihiro [Department of Radiation Oncology, Tohoku University School of Medicine, Sendai (Japan); Yamada, Shogo [Department of Radiation Oncology, Tohoku University School of Medicine, Sendai (Japan)

2005-07-01

283

Mycoplasma pneumonia-associated acute hepatitis in an adult patient without lung infection.  

PubMed

Mycoplasma pneumonia is a major cause of respiratory infections in school-aged children. Most M. pneumonia infections in adults involve the respiratory tract. Extrapulmonary manifestations of M. pneumonia infection may be found in the skin, cardiovascular, neurologic and hematologic systems. Concomitant liver disease is rare in adults. Here, we report an unusual case of a patient who presented with fever and abdominal pain, but without pulmonary manifestations. The laboratory work-up demonstrated a hepatocellular pattern of acute hepatitis caused by M. pneumonia infection. Symptoms subsided and laboratory parameters improved with antibiotics treatment. Thus, this case can help raise clinicians' awareness of the possibility of M. pneumonia infection, with or without lung involvement, as a part of the evaluation of undetermined hepatitis. PMID:19372077

Lee, Shou-Wu; Yang, Sheng-Shun; Chang, Chi-Sen; Yeh, Hong-Jeh; Chow, Wai-Keung

2009-04-01

284

[Diffuse lung disease--advances in patient management].  

PubMed

Diffuse lung diseases (DLD), known as interstitial lung diseases or diffuse parenchymal lung diseases, are a large group of disorders of diverse etiology and causes, however, sharing similar clinical, radiological and pathophysiological characteristics. In the last fifteen years, DLD have attracted considerable interest of medical society. During that period, a consensus of the British Thoracic Society on the Diffuse Parenchymal Lung Disease and Statement of the American Thoracic Society (ATS) and European Respiratory Society (ERS) on idiopathic pulmonary fibrosis, idiopathic interstitial pneumonias and sarcoidosis have helped precisely define certain phenotypes. The newly developed technique of high resolution computed tomography, which can show finest details of lung parenchyma, has also helped precisely define diverse entities, which have aroused interest among molecular biologists and genetic researchers with a goal to define the etiology, pathogenesis and progression of these diseases. The renaissance of interest in this scientific field has also stimulated pharmaceutical industry to enhance its activity, which has resulted in intensified research of potentially new drugs, especially for fibrotic lung processes such as idiopathic pulmonary fibrosis. The disease outcome is very difficult to estimate in these, most often chronic diseases; however, it is very important to achieve the best possible if not the same quality of life as before the disease onset. Different questionnaires have been used and the results were not always as expected; for instance, worsened lung function tests were not most important in defining the quality of life. These vivacious activities have stimulated us to present to the patient and diligent reader recent advances in the management of DLD patient; the article is mostly dedicated to recent advances made in diagnostic procedures, hoping for a comparable success to be achieved in therapeutic approach. PMID:19205419

Peros-Golubici?, Tatjana

2008-10-01

285

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

286

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

287

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.

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

1996-01-01

288

Pulmonary vascular-bronchial interactions: acute reduction in pulmonary blood flow alters lung mechanics  

PubMed Central

BACKGROUND—Postoperative pulmonary hypertension in children after congenital heart surgery is a risk factor for death and is associated with severe acute changes in both pulmonary vascular resistance and lung mechanics.?OBJECTIVE—To examine the impact of changes in pulmonary blood flow on lung mechanics in preoperative children with congenital heart disease, in order to assess the cause-effect relation of pulmonary vascular-bronchial interactions.?DESIGN—Prospective, cross sectional study.?SETTING—Cardiac catheterisation laboratory, general anaesthesia with mechanical ventilation.?INTERVENTIONS—Variation of pulmonary blood flow (Qp) by either balloon occlusion of an atrial septal defect before interventional closure, or by complete occlusion of the pulmonary artery during balloon pulmonary valvuloplasty for pulmonary valve stenosis.?MAIN OUTCOME MEASURES—Ventilatory tidal volume (Vt), dynamic respiratory system compliance (Cdyn), respiratory system resistance (Rrs).?RESULTS—28 occlusions were examined in nine patients with atrial septal defect (median age 9.5 years) and 22 in eight patients with pulmonary stenosis (median age 1.2 years). Normalisation of Qp during balloon occlusion of atrial septal defect caused no significant change in airway pressures and Rrs, but there was a small decrease in Vt (mean (SD): 9.61 (0.85) to 9.52 (0.97) ml/kg; p < 0.05) and Cdyn (0.64 (0.11) to 0.59 (0.10) ml/cm H2O*kg; p < 0.01). These changes were more pronounced when there was complete cessation of Qp during balloon valvuloplasty in pulmonary stenosis, with a fall in Vt (9.71 (2.95) to 9.32 (2.84) ml/kg; p < 0.05) and Cdyn (0.72 (0.29) to 0.64 (0.26) ml/cm H2O*kg; p < 0.001), and there was also an increase in Rrs (25.1 (1.7) to 28.8 (1.6) cm H2O/litre*s; p < 0.01). All these changes exceeded the variability of the baseline measurements more than threefold.?CONCLUSIONS—Acute changes in pulmonary blood flow are associated with simultaneous changes in lung mechanics. While these changes are small they may represent a valid model to explain the pathophysiological impact of spontaneous changes in pulmonary blood flow in clinically more critical situations in children with congenital heart disease.???Keywords: pulmonary blood flow; lung mechanics; catheter intervention; cardiopulmonary interaction

Schulze-Neick, I; Penny, D; Derrick, G; Dhillon, R; Rigby, M; Kelleher, A; Bush, A; Redington, A

2000-01-01

289

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.

2013-01-01

290

Effect of Ergothioneine on Acute Lung Injury and Inflammation in Cytokine Insufflated Rats  

PubMed Central

Objective The Acute Respiratory Distress Syndrome (ARDS), the most severe form of Acute Lung Injury (ALI), is a highly-fatal, diffuse non-cardiogenic edematous lung disorder. The pathogenesis of ARDS is unknown but lung inflammation and lung oxidative stress are likely contributing factors. Since no specific pharmacologic intervention exists for ARDS, our objective was to determine the effect of treatment with ergothioneine---a safe agent with multiple anti-inflammatory and antioxidant properties on the development of lung injury and inflammation in rats insufflated with cytokines found in lung lavages of ARDS patients. Method Sprague-Dawley rats (3-10/group) were given 15 mg/kg or 150 mg/kg L-ergothioneine intravenously 1 hour before or 18 hours after cytokine (IL-1 and IFN?) insufflation. Lung injury (lavage LDH levels) and lung inflammation (lavage neutrophil numbers) were measured 24 hours after cytokine insufflation. Results Ergothioneine pre- and post- treatment generally decreased lung injury and lung inflammation in cytokine insufflated rats. Conclusion Ergothioneine should be considered for additional testing as a potential therapy for treating and preventing ARDS.

Repine, John E.; Elkins, Nancy D.

2012-01-01

291

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

PubMed

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

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

2014-01-01

292

Increased T cell glucose uptake reflects acute rejection in lung grafts.  

PubMed

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

Chen, D L; Wang, X; Yamamoto, S; Carpenter, D; Engle, J T; Li, W; Lin, X; Kreisel, D; Krupnick, A S; Huang, H J; Gelman, A E

2013-10-01

293

Mesenchymal stem cell therapy and lung diseases.  

PubMed

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

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

2013-01-01

294

Triptolide ameliorates lipopolysaccharide-induced acute lung injury in rats  

PubMed Central

Background Acute lung injury (ALI) is a serious clinical syndrome with a high rate of mortality. In this study, the effects of triptolide on lipopolysaccharide (LPS)-induced ALI in rats were investigated. Methods Sixty-five male Sprague Dawley rats(approved by ethics committee of the First Affiliated Hospital of Soochow University) were randomly divided into five groups. The control group was injected with 2.5 mL saline/kg body weight via the tail vein and intraperitoneally with 1% dimethyl sulfoxide (DMSO) (n?=?5). The L group was administered with 0.2% LPS dissolved in saline (5 mg/kg) to induce ALI via the tail vein (n?=?15). The TP1, TP2, and TP3 groups were treated as rats in the L group and then intraperitoneally injected with 25, 50, and 100 ?g triptolide/kg body weight, respectively (15 rats per group). Blood samples from the left heart artery were taken for blood gas analysis at 1 hour before injection and at 1, 3, 6, and 12 hours after saline and DMSO administration in the control group, LPS injection in the L group, and triptolide injection in the TP1, TP2, and TP3 groups. Lung wet-to-dry weight (W/D) ratio, diffuse alveolar damage (DAD) score, TNF-? levels, and mRNA and protein expression of toll-like receptor 4 (TLR4) were analyzed. Results Compared with the control group, the arterial partial pressure of oxygen (PaO2) declined (P <0.05), the W/D ratio and DAD score increased (P <0.05), and TNF-? levels in serum and bronchoalveolar lavage fluid (BALF) and mRNA and protein expression of TLR4 were significantly increased in the L group (P <0.05). Compared with the L group, PaO2 significantly increased in the TP2 and TP3 groups (P <0.05), while the W/D ratio and DAD score were significantly decreased in the TP2 and TP3 groups (P <0.05). TNF-? levels and mRNA and protein expression of TLR4 were significantly decreased in the TP2 and TP3 groups compared with the L group (P <0.05). Conclusions Triptolide can ameliorate LPS-induced ALI by reducing the release of the inflammatory mediator TNF-? and inhibiting TLR4 expression.

2013-01-01

295

Molecular mechanisms of paraquat-induced acute lung injury: a current review.  

PubMed

Paraquat is an organic heterocyclic herbicide that is widely used in agriculture, especially in Asian countries. The prevalence of paraquat poisonings has increased dramatically in the past two decades in China. Nearly all paraquat poisonings resulted from intentional or accidental oral administration leading to acute lung injury and, ultimately, acute respiratory distress syndrome. The mortality rate has been reported to be greater than 90%. However, the exact toxic mechanism remains unclear. Herein, we reviewed and summarized the most recent publications related to the molecular mechanisms of paraquat-induced acute lung injury. PMID:24392656

Xu, Lingjie; Xu, Jun; Wang, Zhong

2014-04-01

296

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.

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

2014-01-01

297

Alcohol Worsens Acute Lung Injury by Inhibiting Alveolar Sodium Transport through the Adenosine A1 Receptor  

PubMed Central

Objective Alcohol intake increases the risk of acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) and is associated with poor outcomes in patients who develop these syndromes. No specific therapies are currently available to treat or decrease the risk of ARDS in patients with alcoholism. We have recently shown increased levels of lung adenosine inhibit alveolar fluid clearance, an important predictor of outcome in patients with ARDS. We hypothesized that alcohol might worsen lung injury by increasing lung adenosine levels, resulting in impaired active Na+ transport in the lung. Methods We treated wild-type mice with alcohol administered i.p. to achieve blood alcohol levels associated with moderate to severe intoxication and measured the rate of alveolar fluid clearance and Na,K-ATPase expression in peripheral lung tissue and assessed the effect of alcohol on survival during exposure to hyperoxia. We used primary rat alveolar type II cells to investigate the mechanisms by which alcohol regulates alveolar Na+ transport. Results Exposure to alcohol reduced alveolar fluid clearance, downregulated Na,K-ATPase in the lung tissue and worsened hyperoxia-induced lung injury. Alcohol caused an increase in BAL fluid adenosine levels. A similar increase in lung adenosine levels was observed after exposure to hyperoxia. In primary rat alveolar type II cells alcohol and adenosine decreased the abundance of the Na,K-ATPase at the basolateral membrane via a mechanism that required activation of the AMPK. Conclusions Alcohol decreases alveolar fluid clearance and impairs survival from acute lung injury. Alcohol induced increases in lung adenosine levels may be responsible for reduction in alveolar fluid clearance and associated worsening of lung injury.

Urich, Daniela; Soberanes, Saul; Manghi, Tomas S.; Chiarella, Sergio E.; Chandel, Navdeep S.; Budinger, G. R. Scott; Mutlu, Gokhan M.

2012-01-01

298

Genetic Predisposition to Respiratory Diseases: Infiltrative Lung Diseases  

PubMed Central

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 is determined by genetic factors. Sarcoidosis represents a complex disease with racial and ethnic differences in disease prevalence, and evidence of familial clustering. Familial aggregation of sarcoidosis from ‘A Case-Control Etiologic Study of Sarcoidosis’ (ACCESS) reveals a familial odds ratio (OR) of sarcoidosis of 5.8 (95% CI 2.1–15.9) for sibs and 3.8 (95% CI 1.2–11.3) for parents. Several HLA class II alleles have been associated with either increased or decreased risk of sarcoidosis, and results vary depending on study populations of different ethnicity. Genome-wide screening has conclusively identified linkage to chromosome 5q11and the development of sarcoidosis, and HLA genes and BTNL2 are susceptibility genes located in this region. Familial aggregation of idiopathic interstitial pneumonia (IIP) has been established by several groups, and a large US-based study suggests autosomal dominant inheritance with reduced penetrance; furthermore, cigarette smoking was associated with affection status among siblings (OR = 3.6, 95% CI 1.3–9.8, p = 0.01). Families demonstrate more than one type of IIP, suggesting various subtypes of IIP may share a common pathogenesis. Genome-wide linkage scans in familial interstitial pneumonia demonstrate linkage to chromosomes 4, 5 and 11. Candidate gene studies indicate that surfactant protein C and telomerase are susceptibility genes for the development of pulmonary fibrosis. Future challenges include determining how multiple susceptibility alleles interact with each other and environmental factors resulting in disease risk and multiple phenotypes, and determining the mechanism of action and cellular pathways involving susceptibility alleles. Further insight into these areas may lead to new therapeutic interventions.

Steele, Mark P.; Brown, Kevin K.

2010-01-01

299

MAINTENANCE OF IKK? ACTIVITY IS NECESSARY TO PROTECT LUNG GRAFTS FROM ACUTE INJURY  

PubMed Central

Background Signaling pathways that target I-?B kinase ? (IKK?) activation stimulate the expression of NF-?B-dependent genes and are thus thought to primarily promote inflammation and injury in solid organ grafts. Methods We examined the role of IKK? in a mouse model of lung transplantation-mediated ischemia-reperfusion injury using NF-?B essential modulator (NEMO)-binding domain (NBD) peptide to pharmacologically inhibit IKK activation. As myeloid cells are primarily responsible for the production of acute inflammatory mediators following lung transplantation, we also investigated the effects of myeloid cell-specific IKK? gene deletion on acute lung graft injury by transplanting mutant mice. Results When NBD was administered at a dose that partially inhibits IKK? activation, we observed attenuated lung graft injury and blunted expression of intragraft pro-inflammatory mediators. Surprisingly, when the dose of NBD was increased to a level that completely ablates intragraft IKK? activation, graft inflammation and injury were significantly worse compared to recipients treated with control peptide. Similar to lung recipients with pharmacologically ablated IKK? activity, donor-recipient transplant combinations with a myeloid cell-specific IKK? gene deletion had marked intragraft inflammation and poor lung function. Conclusions Our data show maintenance of IKK? activity is critical for the return of lung graft homeostasis with important implications for targeting NF-?B-dependent signaling pathways for treating acute lung injury.

Huang, Howard J.; Sugimoto, Seiichiro; Lai, Jiaming; Okazaki, Mikio; Yamamoto, Sumiharu; Krupnick, Alexander S.; Kreisel, Daniel; Gelman, Andrew E.

2014-01-01

300

Sivelestat, a specific neutrophil elastase inhibitor, prevented phorbol myristate acetate-induced acute lung injury in conscious rabbits  

Microsoft Academic Search

The in vivo contribution of neutrophil elastase (NE) in phorbol myristate acetate (PMA)-induced acute lung injury has so far been unclear. This study examined the role of NE in PMA-induced acute lung injury in conscious rabbits, using a specific NE inhibitor, sivelestat sodium hydrate (Sivelestat). A single bolus injection of PMA (40?g\\/kg) caused acute lung injury as indicated by an

T. Hagio; S. Matsumoto; S. Nakao; S. Matsuoka; K. Kawabata

2005-01-01

301

Acute lung injury and the coagulation pathway: potential role of gene polymorphisms in the protein C and fibrinolytic pathways  

Microsoft Academic Search

There is evidence that dysregulation of coagulation and fibrinolysis may \\u000aparticipate in the pathogenesis of acute lung injury (ALI) and the acute \\u000arespiratory distress syndrome (ARDS). Altered concentrations of several \\u000aproteins of the coagulation and fibrinolytic pathways in plasma and \\u000apulmonary edema fluid from patients with acute lung injury have been related \\u000ato the severity of lung injury and clinical

Anil Sapru; Joseph L. Wiemels; John S. Witte; Lorraine B. Ware; Michael A. Matthay

2006-01-01

302

[Occupational lung diseases other than asbestos- and indium-related disease].  

PubMed

In our country, pneumoconiosis used to hold an overwhelmingly majority in respiratory occupational lung diseases. Although the number of pneumoconiosis cases has been decreasing certainly, new cases have been arising even today. In addition, in place of pneumoconiosis or asbestos-related diseases, occupational asthma has become the most common forms of occupational lung disease in many industrialized countries. Occupational asthma has been implicated in 9 to 15% of adult asthma in the United States. Although the environmental causes of occupational lung disease are clear, the mechanisms of the diseases are not fully understood and need to be further elucidated. PMID:24605527

Kimura, Kiyonobu; Nakano, Ikuo; Ohtsuka, Yosinori; Igarashi, Takeshi; Okamoto, Kenzo

2014-02-01

303

Depressive Symptoms and Impaired Physical Function after Acute Lung Injury  

PubMed Central

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

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

2012-01-01

304

Lung cancer in never smokers: disease characteristics and risk factors.  

PubMed

It is estimated that approximately 25% of all lung cancer cases are observed in never-smokers and its incidence is expected to increase due to smoking prevention programs. Risk factors for the development of lung cancer described include second-hand smoking, radon exposure, occupational exposure to carcinogens and to cooking oil fumes and indoor coal burning. Other factors reported are infections (HPV and Mycobacterium tuberculosis), hormonal and diatery factors and diabetes mellitus. Having an affected relative also increases the risk for lung cancer while recent studies have identified several single nucleotide polymorphisms associated with increased risk for lung cancer development in never smokers. Distinct clinical, pathology and molecular characteristics are observed in lung cancer in never smokers; more frequently is observed in females and adenocarcinoma is the predominant histology while it has a different pattern of molecular alterations. The purpose of this review is to summarize our current knowledge of this disease. PMID:23921082

Pallis, Athanasios G; Syrigos, Konstantinos N

2013-12-01

305

Airbag lung: an unusual case of sarcoid-like granulomatous lung disease after a rollover motor vehicle accident.  

PubMed

Sarcoid-like granulomatous lung disease (SLGLD) is a condition associated with the formation of noncaseating, nonnecrotizing granulomas. The final by-product of airbag deployment is alkaline silicates or glass. Silicates trapped and sequestered in the lung parenchyma are a potential mediator for immune system activation and development of sarcoid-like granulomatous lung disease. PMID:24974560

Waring, Thomas P; Hegde, Poornima; Foley, Raymond J

2014-05-01

306

The Role of the Bacterial Microbiome in Lung Disease  

PubMed Central

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

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

2014-01-01

307

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

308

Physical Therapy for Children with Chronic Lung Disease  

Microsoft Academic Search

Chronic lung disease is a major health problem among children. Estimates suggest that one child in six has a chronic respiratory condition. This article reviews three common chronic respiratory conditions occurring in childhood for which physical therapy is usually recommended. The cause, pathophysiology, and medical treatment are explained for asthma, respiratory complications of chronic neuromuscular disease, and cystic fibrosis. The

JAN STEPHEN TECKLIN

309

Scintigraphic studies of inflammation in diffuse lung disease  

SciTech Connect

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

Line, B.R. (Albany Medical College, New York (USA))

1991-09-01

310

Genome?wide analysis of DNA methylation in rat lungs with lipopolysaccharide?induced acute lung injury.  

PubMed

Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) are associated with high morbidity and mortality in patients, however, the precise pathogenesis of ALI/ARDS remains unknown. Lipopolysaccharide (LPS) exhibits a number of critical functions and may be associated with the DNA methylation of genes in the lungs. In the present study a genome?wide analysis of DNA methylation was performed in rat lungs with LPS?induced ALI/ARDS. Normal and LPS?induced lung tissues with ALI were analyzed using methylated DNA immunoprecipitation and a rat DNA methylation promoter plus CpG island microarray and the candidate genes were validated by quantitative reverse transcriptase polymerase chain reaction (qRT?PCR). Aberrant DNA methylation of the promoter regions of 1,721 genes and the CpG islands of 990 genes was identified when normal lung tissues and lung tissues with LPS?induced ALI/ARDS were compared. These genes were commonly located on chromosomes 1, 3, 5, 7 and 10 (P<0.01). Methylation level and CpG density were compared and it was found that genes associated with high CpG density promoters had a high ratio of methylation. Furthermore, we performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. In addition, three genes (Mapk3, Pak1 and Rac2) were validated in the control and lung tissues with ALI by RT?PCR. The results indicate that aberrant DNA methylation of lung tissues may be involved in the pathophysiology of LPS?induced ALI/ARDS. Future studies are required to evaluate the therapeutic and prognostic value of the current novel observations in ALI/ARDS. PMID:23546543

Zhang, Xiao-Qiang; Lv, Chang-Jun; Liu, Xiang-Yong; Hao, Dong; Qin, Jing; Tian, Huan-Huan; Li, Yan; Wang, Xiao-Zhi

2013-05-01

311

Assessing Pseudomonas aeruginosa Virulence and the Host Response Using Murine Models of Acute and Chronic Lung Infection.  

PubMed

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

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

2014-01-01

312

A unified approach for EIT imaging of regional overdistension and atelectasis in acute lung injury.  

PubMed

Patients with acute lung injury or acute respiratory distress syndrome (ALI/ARDS) are vulnerable to ventilator-induced lung injury. Although this syndrome affects the lung heterogeneously, mechanical ventilation is not guided by regional indicators of potential lung injury. We used electrical impedance tomography (EIT) to estimate the extent of regional lung overdistension and atelectasis during mechanical ventilation. Techniques for tidal breath detection, lung identification, and regional compliance estimation were combined with the Graz consensus on EIT lung imaging (GREIT) algorithm. Nine ALI/ARDS patients were monitored during stepwise increases and decreases in airway pressure. Our method detected individual breaths with 96.0% sensitivity and 97.6% specificity. The duration and volume of tidal breaths erred on average by 0.2 s and 5%, respectively. Respiratory system compliance from EIT and ventilator measurements had a correlation coefficient of 0.80. Stepwise increases in pressure could reverse atelectasis in 17% of the lung. At the highest pressures, 73% of the lung became overdistended. During stepwise decreases in pressure, previously-atelectatic regions remained open at sub-baseline pressures. We recommend that the proposed approach be used in collaborative research of EIT-guided ventilation strategies for ALI/ARDS. PMID:22249646

Gómez-Laberge, Camille; Arnold, John H; Wolf, Gerhard K

2012-03-01

313

Hard metal lung disease diagnosed on a transbronchial lung biopsy following recurrent contact dermatitis.  

PubMed

A 63-year-old man employed in a hard metal manufacturing company for 40 years presented with a chronic dry cough and exertional dyspnea 20 years after the onset of recurrent exanthemas. A chest radiograph revealed bilateral reticular shadows in the upper lung field. Pathological specimens in which tungsten was detected were obtained via a transbronchial lung biopsy. Patch tests were positive for cobalt and other metals. The patient was diagnosed with hard metal lung disease (HMLD) concurrent with contact dermatitis and treated with corticosteroids. This case suggests that allergies to metal may play a role in the onset of HMLD. PMID:24429455

Nakamura, Yasukiyo; Nishizaka, Yasuo; Ariyasu, Ryo; Okamoto, Natsumi; Yoshida, Masanori; Taki, Masato; Nagano, Hiroaki; Hanaoka, Kenji; Nakagawa, Kazuhiko; Yoshimura, Chie; Wakayama, Toshiaki; Amitani, Ryoichi

2014-01-01

314

THE 5-LIPOXYGENASE PATHWAY IS REQUIRED FOR ACUTE LUNG INJURY FOLLOWING HEMORRHAGIC SHOCK  

PubMed Central

The cellular and biochemical mechanisms leading to acute lung injury and subsequent multiple organ failure are only partially understood. In order to study the potential role of eicosanoids, particularly leukotrienes, as possible mediators of acute lung injury, we used a murine experimental model of acute lung injury induced by hemorrhagic shock after blood removal via cardiac puncture. Neutrophil sequestration as shown by immunofluorescence, and protein leakage into the alveolar space, were measured as markers of injury. We used liquid chromatography coupled to tandem mass spectrometry to unequivocally identify several eicosanoids in the bronchoalveolar lavage fluid of experimental animals. MK886, a specific inhibitor of the 5-lipoxygenase pathway, as well as transgenic mice deficient in 5-lipoxygenase, were used to determine the role of this enzymatic pathway in this model. Leukotriene B4 and leukotriene C4 were consistently elevated in shock-treated mice compared to sham-treated mice. MK886 attenuated neutrophil infiltration and protein extravasation induced by hemorrhagic shock. 5-lipoxygenase-deficient mice showed reduced neutrophil infiltration and protein extravasation after shock treatment, indicating greatly reduced lung injury. These results support the hypothesis that 5-lipoxygenase, most likely through the generation of leukotrienes, plays an important role in the pathogenesis of acute lung injury induced by hemorrhagic shock in mice. This pathway could represent a new target for pharmacological intervention to reduce lung damage following severe primary injury.

Eun, John C.; Moore, Ernest E.; Mauchley, David C.; Johnson, Chris A.; Meng, Xianzhong; Banerjee, Anirban; Wohlauer, Max V.; Zarini, Simona; Gijon, Miguel A.; Murphy, Robert C.

2012-01-01

315

Clinical review: The implications of experimental and clinical studies of recruitment maneuvers in acute lung injury  

PubMed Central

Mechanical ventilation can cause and perpetuate lung injury if alveolar overdistension, cyclic collapse, and reopening of alveolar units occur. The use of low tidal volume and limited airway pressure has improved survival in patients with acute lung injury or acute respiratory distress syndrome. The use of recruitment maneuvers has been proposed as an adjunct to mechanical ventilation to re-expand collapsed lung tissue. Many investigators have studied the benefits of recruitment maneuvers in healthy anesthetized patients and in patients ventilated with low positive end-expiratory pressure. However, it is unclear whether recruitment maneuvers are useful when patients with acute lung injury or acute respiratory distress syndrome are ventilated with high positive end-expiratory pressure, and in the presence of lung fibrosis or a stiff chest wall. Moreover, it is unclear whether the use of high airway pressures during recruitment maneuvers can cause bacterial translocation. This article reviews the intrinsic mechanisms of mechanical stress, the controversy regarding clinical use of recruitment maneuvers, and the interactions between lung infection and application of high intrathoracic pressures.

Piacentini, Enrique; Villagra, Ana; Lopez-Aguilar, Josefina; Blanch, Lluis

2004-01-01

316

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

PubMed Central

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

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

2008-01-01

317

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

318

THE RON RECEPTOR TYROSINE KINASE REGULATES ACUTE LUNG INJURY AND SUPPRESSES NUCLEAR FACTOR ?B ACTIVATION  

PubMed Central

Emerging information implies that the Ron receptor tyrosine kinase may play a role in the inflammatory response. However, the manner in which this receptor contributes to the response is not well understood. In the present studies, we investigated the role of the Ron receptor in the acute lung inflammatory response. Wild-type and mutant mice lacking the tyrosine kinase domain of Ron (Ron TK?/?) were subjected to acute lung injury induced by intranasal administration of bacterial lipopolysaccharide (LPS). Wild-type mice showed increased lung injury after LPS administration, as determined by the leakage of albumin into the lung and by histopathological changes. Ron TK?/? mice had more than twice the amount of albumin leak and much greater thickening of the alveolar septae. Lipopolysaccharide administration caused neutrophil recruitment into the lungs, as measured by myeloperoxidase. However, Ron TK?/? mice had much higher baseline levels of myeloperoxidase, which did not increase further after LPS. Lung injury in wild-type mice occurred with activation of the transcription factor, nuclear factor ?B (NF-?B), and subsequent increases in intrapulmonary generation of tumor necrosis factor ?. In TK?/? mice, there was far less I?B-? and I?B-? protein and greater activation of NF-?B. This was associated with substantially increased production of tumor necrosis factor ? and the nitric oxide (NO) by-product, nitrite. The data suggest that the Ron receptor tyrosine kinase plays an important regulatory role in acute inflammatory lung injury by suppressing signals leading to activation of NF-?B.

Lentsch, Alex B.; Pathrose, Peterson; Kader, Sarah; Kuboki, Satoshi; Collins, Margaret H.; Waltz, Susan E.

2014-01-01

319

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.

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

2011-01-01

320

Longitudinal Studies of Acute Respiratory Diseases in Children.  

National Technical Information Service (NTIS)

The purpose of this program is to develop infant and child populations in Chapel Hill for longitudinal observations of the incidence and etiology of acute respiratory diseases and for evaluation of methods for the prevention of these diseases. Three inter...

F. W. Denny W. A. Clyde W. P. Glezen

1967-01-01

321

CCAAT/Enhancer-Binding Protein ? Is a Critical Mediator of Lipopolysaccharide-Induced Acute Lung Injury  

PubMed Central

Although inflammation plays a central role in the pathogenesis of acute lung injury, the molecular mechanisms underlying inflammatory responses in acute lung injury are poorly understood, and therapeutic options remain limited. CCAAT/enhancer-binding proteins, C/EBP? and C/EBP?, are expressed in the lung and have been implicated in the regulation of inflammatory mediators. However, their functions in lung pathobiological characteristics are not well characterized. Herein, we show that C/EBP? and C/EBP? are activated in mouse lung after intrapulmonary deposition of lipopolysaccharide (LPS). Mice carrying a targeted deletion of the C/EBP? gene displayed significant attenuation of the lung permeability index (lung vascular leak of albumin), lung neutrophil accumulation (myeloperoxidase activity), and neutrophils in bronchial alveolar lavage fluids compared with wild-type mice. These phenotypes were consistent with morphological evaluation of lung, which showed reduced inflammatory cell influx and minimal intra-alveolar hemorrhage. Moreover, mutant mice expressed considerably less tumor necrosis factor-?, IL-6, and macrophage inflammatory protein-2 in bronchial alveolar lavage fluids in LPS-injured lung compared with wild-type mice. In contrast, C/EBP? deficiency had no effect on LPS-induced lung injury. By using small-interfering RNA–mediated knockdown for C/EBP?, we demonstrate, for the first time to our knowledge, that C/EBP? plays a critical role for the tumor necrosis factor-?, IL-6, and macrophage inflammatory protein-2 production in LPS-stimulated alveolar macrophages. These findings demonstrate that C/EBP?, but not C/EBP?, plays an important role in LPS-induced lung inflammatory responses and injury.

Yan, Chunguang; Johnson, Peter F.; Tang, Huifang; Ye, Yan; Wu, Min; Gao, Hongwei

2014-01-01

322

Atopic disease and childhood acute lymphoblastic leukemia.  

PubMed

Our objective was to test the hypothesis that the risk of childhood leukemia is associated with allergies or a family history of allergy. We used a German population-based case-control study with self-reported information on allergies of the children and their first-degree relatives. Our study included a total of 1,130 cases of acute lymphoblastic leukemia (ALL), 164 cases of acute myeloid leukemia (AML) and 2,957 controls. A major finding of our study is that hay fever, neurodermatitis and contact eczema are underrepresented within the group of children with ALL, with respective odds ratios (OR) of 0.45 (95% confidence interval [CI] 0.31-0.66) for hay fever, of 0.49 (CI 0.34-0.71) for neurodermatitis and of 0.62 (CI 0.39-0.99) for eczema, respectively. Atopic diseases, comprising hay fever, neurodermatitis and asthma, are much stronger related with a reduced risk of ALL than other allergies (OR 0.52, CI 0.40-0.67 vs. OR 0.89, CI 0.66-1.21). The strongest association is seen with an atopy in the index child; however, ALL risk is also reduced if one of the parents or a sibling had an atopic disease. No such consistent pattern is seen for AML. Our data suggest that atopy or a family history of atopy are associated with a reduced risk of childhood ALL. Recall bias remains a concern, but sensitivity analysis provided some evidence that the protective effect is unlikely to be attributable to this bias in its entirety. PMID:12673688

Schüz, Joachim; Morgan, Gareth; Böhler, Eva; Kaatsch, Peter; Michaelis, Jörg

2003-06-10

323

Investigation of the child with interstitial lung disease  

Microsoft Academic Search

Many disorders can affect the pulmonary interstitium in children. Although individual interstitial lung diseases are rare,\\u000a the range of conditions encountered is wide. Interstitial disease is also seen increasingly as a consequence of the treatment\\u000a of children having other primary problems including cancer, immunodeficiency and haemotological diseases, as well as in recipients\\u000a of solid organ and bone marrow transplants. The

David Spencer; Andrew Fall

2000-01-01

324

[Interstitial lung diseases--problem of ageing societies].  

PubMed

Chronic lung diseases are on increase mainly in developed countries that are characteristic by ageing societies. Despite this, interstitial lung diseases, together with lung fibrosis, seemed to be forgotten by researchers and clinicians till last years. Sufficient epidemiological data are lacking (especially little is known on the environmental and occupational causative factors). No effective treatment is available so far - diagnostic and therapeutic options available nowadays are characterized by high costs (e.g. lung transplantation) and low effectiveness. The average age of patients first diagnosed with lung fibrosis is 61 +/- 0,7 years, which poses a rising public health problem of ageing societies, especially those in Europe, USA and Japan. The average duration of life after the diagnosis is only 3 years. Facing these facts, a new approach to this group of diseases is urgently needed. A first step should include thorough epidemiological studies aimed at identification of causes and risk factors of these diseases. Results of such research should be subsequently transferred into health policy. Especially needed are sensitive screening programs and development of effective treatment that would substantially improve life expectancy and quality of life of the affected people. PMID:18293853

Golec, Marcin; W?adysiuk-Blicharz, Magdalena; Spiewak, Rados?aw

2007-10-01

325

Gene therapy for cystic fibrosis lung disease  

Microsoft Academic Search

\\u000a Cystic fibrosis (CF) is characterised by respiratory and pancreatic deficiencies that stem from the loss of fully functional\\u000a CFTR (CF transmembrane conductance regulator) at the membrane of epithelial cells. Current treatment modalities aim to delay\\u000a the deterioration in lung function, Which is mostly responsible for the relatively short life expectancy of CF sufferers;\\u000a however none have so far successfully dealt

Stephanie G. Sumner-Jones; Deborah R. Gill; Stephen C. Hyde

326

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.

2013-01-01

327

Exhaled nitric oxide in interstitial lung diseases.  

PubMed

Nitric oxide (NO) is a biomarker of nitrosative stress, which is involved in the pathogenesis of idiopathic interstitial pneumonias (IIP). This study evaluates exhaled NO levels in IIP patients and relates alveolar concentrations of NO (CalvNO) to pulmonary function test (PFT) and 6-minute walking test (6MWT) parameters. We measured fractional exhaled nitric oxide (FeNO), CalvNO and maximum conducting airway wall flux (J'awNO) in 30 healthy subjects and 30 patients with IIP (22 idiopathic pulmonary fibrosis and 8 idiopathic non-specific interstitial pneumonias). IIP patients had higher FeNO at flow rates of 50-100-150 ml/s and higher CalvNO levels than healthy controls (p<0.0001). CalvNO was significantly correlated with 6-minute walking distance (p<0.0001), recovery time (p<0.0005), TLC (p<0.001), FVC (p=0.01) and TLCO (p<0.01). IIP patients showed abnormal nitric oxide production, probably due to lung fibrosis and oxidative-mediated lung injury. CalvNO was correlated with PFT and 6MWT parameters and is proposed as a potential biomarker of lung fibrosis and exercise tolerance. PMID:24703971

Cameli, P; Bargagli, E; Refini, R M; Pieroni, M G; Bennett, D; Rottoli, P

2014-06-15

328

Acute Demyelinating Disease after Oral Therapy with Herbal Extracts  

PubMed Central

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

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

2011-01-01

329

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

330

Defect in early lung defense against Pseudomonas aeruginosa in DBA/2 mice is associated with acute inflammatory lung injury and reduced bactericidal activity in na?ve macrophages  

PubMed Central

Pseudomonas aeruginosa is an opportunistic pathogen that causes serious respiratory disease in the immune compromised host. Using an aerosol infection model, eleven inbred mouse strains (129/Sv, A/J, BALB/c, C3H/HeN, C57BL/6, DBA/2, FVB, B10.D2/oSnJ, B10.D2/nSnJ, AKR/J and SWR/J) were tested for increased susceptibility to P. aeruginosa lung colonizations. DBA/2 was the only mouse strain that had increased bacterial counts in the lung within 6h post infection. This deficiency incited a marked inflammatory response with reduced bacterial lung clearance and a mortality rate of 96.7%. DBA/2 displayed progressive deterioration of lung pathology with extensive alveolar exudate and edema formation at 48-72h post infection. The neutrophil-specific myeloperoxidase activity remained elevated throughout infection, suggesting that the increased leukocyte infiltrations into alveoli caused acute inflammatory lung injury. DBA/2 lacks the hemolytic complement; however, three additional mouse strains (AKR/J, SWR/J and A/J) with the same defect effectively cleared the infection, indicating other host factors are involved in the defense. Bone marrow derived macrophages of DBA/2 showed an initial increase in phagocytosis, while their bactericidal activity was reduced compared to that of C57BL/6 macrophages. Comparison of pulmonary cytokine profiles of DBA/2 vs. C57BL/6 or C3H/HeN indicated DBA/2 had a similar increase in TNF?, KC, and IL-1a as C3H/HeN but showed specific induction of IL-17, MCP-1, and VEGF. Together, DBA/2 mice have a defect in the initial lung defense against P. aeruginosa colonization, which causes the host to produce a greater, but damaging, inflammatory response. Such a response may originate from the reduced antimicrobial activity of DBA/2 macrophages.

Wilson, Kari R.; Napper, Jennifer M.; Denvir, James; Sollars, Vincent E.; Yu, Hongwei D.

2007-01-01

331

Airway pressure release ventilation in morbidly obese surgical patients with acute lung injury and acute respiratory distress syndrome.  

PubMed

Morbidly obese patients with body mass index greater than 40 kg/m(2) and respiratory failure requiring critical care services are increasingly seen in trauma and acute care surgical centers. Baseline respiratory pathophysiology including decreased pulmonary compliance with dependent atelectasis and abnormal ventilation-perfusion relationships predisposes these patients to acute lung injury (ALI) and adult respiratory distress syndrome (ARDS) as well as prolonged stays in the intensive care unit. Airway pressure release ventilation (APRV) is an increasingly used alternative mode for salvage therapy in patients with hypoxemic respiratory failure that also provides lung protection from ventilator-induced lung injury. APRV provides the conceptual advantage of an "open lung" approach to ventilation that may be extended to the morbidly obese patient population with ALI and ARDS. We discuss the theoretical benefits and a recent clinical experience of APRV ventilation in the morbidly obese patient with respiratory failure at a Level I trauma, surgical critical care, and acute care surgery center. PMID:23461947

Testerman, George M; Breitman, Igal; Hensley, Sarah

2013-03-01

332

Synchrotron microradiography study on acute lung injury of mouse caused by PM 2.5 aerosols  

Microsoft Academic Search

In order to investigate FeSO4, ZnSO4 (the two of main metal compositions of Shanghai PM2.5 (particle matter with those aerodynamical diameter <2.5?m)) effects on acute lung injury, six solutions contained PM2.5 aerosol particles, FeSO4, ZnSO4 and their mixtures were instilled intratracheally into mouse lungs for experiment. By 2 days after instillation, the live mice were checked in vivo by synchrotron

Yongpeng Tong; Guilin Zhang; Yan Li; Mingguan Tan; Wei Wang; Jianmin Chen; Yeukuang Hwu; Pei-Chebg Hsu; Jung Ho Je; Giorgio Margaritondo; Weiming Song; Rongfang Jiang; Zhihai Jiang

2006-01-01

333

Transfusion related acute lung injury with massive pulmonary secretion during cardiac surgery. A case report.  

PubMed

A Indo-Caribbean patient undergoing cardiac surgery developed Transfusion Related Acute Lung Injury (TRALI) with massive endobronchial secretion of clear fluid mimicking severe pulmonary edema. Hypoxemia and lung stiffness were so severe that didn't allow closure of the sternum on completion of surgery. The patient was treated with invasive ventilation, high positive pressure and % FiO2 and aggressive endotracheal suction. After several hours, secretions reduced spontaneously and the patient made an uneventful recovery. PMID:24694086

Teodori, Julien; Rampersad, Kamal; Teodori, Giovanni; Roopchand, Roland; Angelini, Gianni Davide

2014-01-01

334

Chronic kidney disease in acute coronary syndromes  

PubMed Central

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

Marenzi, Giancarlo; Cabiati, Angelo; Assanelli, Emilio

2012-01-01

335

Mitogen-activated Protein Kinase Kinase Kinase 1 Protects against Nickel-induced Acute Lung Injury  

PubMed Central

Nickel compounds are environmental and occupational hazards that pose serious health problems and are causative factors of acute lung injury. The c-jun N-terminal kinases (JNKs) are regulated through a mitogen-activated protein (MAP) 3 kinase-MAP2 kinase cascade and have been implicated in nickel toxicity. In this study, we used genetically modified cells and mice to investigate the involvement of two upstream MAP3Ks, MAP3K1 and 2, in nickel-induced JNK activation and acute lung injury. In mouse embryonic fibroblasts, levels of JNK activation and cytotoxicity induced by nickel were similar in the Map3k2-null and wild-type cells but were much lower in the Map3k1/Map3k2 double-null cells. Conversely, the levels of JNK activation and cytotoxicity were unexpectedly much higher in the Map3k1-null cells. In adult mouse tissue, MAP3K1 was widely distributed but was abundantly expressed in the bronchiole epithelium of the lung. Accordingly, MAP3K1 ablation in mice resulted in severe nickel-induced acute lung injury and reduced survival. Based on these findings, we propose a role for MAP3K1 in reducing JNK activation and protecting the mice from nickel-induced acute lung injury.

Mongan, Maureen; Tan, Zongqing; Chen, Liang; Peng, Zhimin; Dietsch, Maggie; Su, Bing; Leikauf, George; Xia, Ying

2008-01-01

336

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

PubMed

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

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

2014-03-01

337

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

PubMed Central

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

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

2014-01-01

338

Three-Dimensional Mapping of Ozone-Induced Acute Cytotoxicity in Tracheobronchial Airways of Isolated Perfused Rat Lung  

Microsoft Academic Search

Acute lung injury induced by reactive oxygen gases such as ozone (O 3 ) is focal and site-selective. To de- fine patterns of acute epithelial injury along intrapulmonary airways, we developed a new analytic ap- proach incorporating labeling of permeable cells, airway microdissection, and laser scanning confocal mi- croscopy, and applied it to isolated perfused rat lungs where ventilation and

Edward M. Postlethwait; Jessie P. Joad; Dallas M. Hyde; Edward S. Schelegle; John M. Bric; Alison J. Weir; Leialoha F. Putney; Viviana J. Wong; Leonard W. Velsor; Charles G. Plopper

339

17?-Estradiol Protects the Lung against Acute Injury: Possible Mediation by Vasoactive Intestinal Polypeptide  

PubMed Central

Beyond their classical role as a class of female sex hormones, estrogens (e.g. 17?-estradiol) exert important biological actions, both protective and undesirable. We have investigated the ability of estradiol to protect the lung in three models of acute injury induced by 1) oxidant stress due to the herbicide paraquat; 2) excitotoxicity, caused by glutamate agonist N-methyl-d-aspartate; and 3) acute alveolar anoxia. We also assessed the role of estrogen receptors (ER) ER? and ER? and the neuropeptide vasoactive intestinal peptide (VIP) in mediating this protection. Isolated guinea pig or rat lungs were perfused in situ at constant flow and mechanically ventilated. The onset and severity of lung injury were monitored by increases in pulmonary arterial and airway pressures, wet/dry lung weight ratio, and bronchoalveolar lavage fluid protein content. Estradiol was infused into the pulmonary circulation, beginning 10 min before induction of injury and continued for 60–90 min. Lung injury was marked by significant increases in the above measurements, with paraquat producing the most severe, and excitotoxicity the least severe, injury. Estradiol significantly attenuated the injury in each model. Both ER were constitutively expressed and immunohistochemically demonstrable in normal lung, and their selective agonists reduced anoxic injury, the only model in which they were tested. As it protected against injury, estradiol rapidly and significantly stimulated VIP mRNA expression in rat lung. Estradiol attenuated acute lung injury in three experimental models while stimulating VIP gene expression, a known mechanism of lung protection. The up-regulated VIP expression could have partially mediated the protection by estrogen.

Hamidi, Sayyed A.; Dickman, Kathleen G.; Berisha, Hasan

2011-01-01

340

17?-estradiol protects the lung against acute injury: possible mediation by vasoactive intestinal polypeptide.  

PubMed

Beyond their classical role as a class of female sex hormones, estrogens (e.g. 17?-estradiol) exert important biological actions, both protective and undesirable. We have investigated the ability of estradiol to protect the lung in three models of acute injury induced by 1) oxidant stress due to the herbicide paraquat; 2) excitotoxicity, caused by glutamate agonist N-methyl-d-aspartate; and 3) acute alveolar anoxia. We also assessed the role of estrogen receptors (ER) ER? and ER? and the neuropeptide vasoactive intestinal peptide (VIP) in mediating this protection. Isolated guinea pig or rat lungs were perfused in situ at constant flow and mechanically ventilated. The onset and severity of lung injury were monitored by increases in pulmonary arterial and airway pressures, wet/dry lung weight ratio, and bronchoalveolar lavage fluid protein content. Estradiol was infused into the pulmonary circulation, beginning 10 min before induction of injury and continued for 60-90 min. Lung injury was marked by significant increases in the above measurements, with paraquat producing the most severe, and excitotoxicity the least severe, injury. Estradiol significantly attenuated the injury in each model. Both ER were constitutively expressed and immunohistochemically demonstrable in normal lung, and their selective agonists reduced anoxic injury, the only model in which they were tested. As it protected against injury, estradiol rapidly and significantly stimulated VIP mRNA expression in rat lung. Estradiol attenuated acute lung injury in three experimental models while stimulating VIP gene expression, a known mechanism of lung protection. The up-regulated VIP expression could have partially mediated the protection by estrogen. PMID:22009726

Hamidi, Sayyed A; Dickman, Kathleen G; Berisha, Hasan; Said, Sami I

2011-12-01

341

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

Microsoft Academic Search

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

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

342

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

Microsoft Academic Search

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

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

343

Effects of Sivelestat Sodium Hydrate for Acute Lung Injury Complicated by Stroke  

Microsoft Academic Search

Sivelestat sodium hydrate(SSH) a selective neutrophil elastase inhibitor is effective in treating acute lung injury(ALI)or acute respiratory distress syndrome(ARDS)associated with systemic inflammatory response syndrome(SIRS) .?SSH was administered to 1 4 patients (11 males and 3 femal es ranging from 3 4 to 87 years of age)who were admitted between 2 0 0 2 and 2 0 0 8 due to

Naoki WAKUTA; Mitsutoshi IWAASA; Tooru INOUE; Taisuke KITAMURA; Hiroyasu ISHIKURA

2009-01-01

344

Effector T cells control lung inflammation during acute influenza virus infection by producing IL10  

Microsoft Academic Search

Activated antigen-specific T cells produce a variety of effector molecules for clearing infection but also contribute to inflammation and tissue injury. Here we report an anti-inflammatory property of antiviral CD8+ and CD4+ effector T cells (Teff cells) in the infected periphery during acute virus infection. We find that, during acute influenza infection, interleukin-10 (IL-10) is produced in the infected lungs

Jie Sun; Rajat Madan; Christopher L Karp; Thomas J Braciale

2009-01-01

345

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.

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

2014-01-01

346

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

PubMed

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

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

2014-01-01

347

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

348

Indoor air pollution from solid fuel use, chronic lung diseases and lung cancer in Harbin, Northeast China  

Microsoft Academic Search

In some areas of China, indoor air pollution (IAP) originating principally from the combustion of solid fuels has a relevant role in lung cancer. Most previous studies focused on the female population and only a few on both the sexes. We analyzed the relationship between IAP from solid fuel use and selected chronic lung diseases and lung cancer risk in

Carlotta Galeone; Claudio Pelucchi; Carlo La Vecchia; Eva Negri; Cristina Bosetti; Jinfu Hu

2008-01-01

349

Endothelial MKK3 is a critical mediator of lethal murine endotoxemia and acute lung injury  

PubMed Central

Sepsis is a leading cause of intensive care unit admissions with high mortality and morbidity. Although outcomes have improved with better supportive care, specific therapies are limited. Endothelial activation and oxidant injury are key events in the pathogenesis of sepsis-induced lung injury. The signaling pathways leading to these events remain poorly defined and need to be studied. We sought to determine the role of MAP kinase kinase 3 (MKK3), a kinase of the p38 group in the pathogenesis of sepsis. We used a murine intraperitoneal lipopolysaccharide (LPS) model of systemic inflammation to mimic sepsis. Lung injury parameters were assessed in lung tissue and bronchoalveolar lavage. Primary lung endothelial cells were cultured and assessed for mediators of inflammation and injury such as ICAM-1, AP-1, NF-?B and mitochondrial ROS. Our studies demonstrate that MKK3 deficiency confers virtually complete protection against organ injury after intraperitoneal LPS. Specifically, MKK3 ?/? mice were protected against acute lung injury, as assessed by reduced inflammation, mitochondrial reactive oxygen species (ROS) generation, endothelial injury and ICAM-1 expression after LPS. Our results show that endothelial MKK3 is required for inflammatory cell recruitment to the lungs, mitochondrial oxidant-mediated AP-1, NF-?B activation and ICAM-1 expression during LPS challenge. Collectively, these studies identify a novel role for MKK3 in lethal LPS responses and provide new therapeutic targets against sepsis and acute lung injury.

Mannam, Praveen; Zhang, Xuchen; Shan, Peiying; Zhang, Yi; Shinn, Amanda S.; Zhang, Yitao; Lee, Patty J.

2012-01-01

350

Peripheral Leukocytapheresis Attenuates Acute Lung Injury Induced by Lipopolysaccharide In Vivo  

PubMed Central

The mortality of acute lung injury and acute respiratory distress syndrome (ALI/ARDS) remains high and efforts for prevention and treatments have shown little improvement over the past decades. The present study investigated the efficacy and mechanism of leukocytapheresis (LCAP) to partially eliminate peripheral neutrophils and attenuate lipopolysaccharide (LPS)-induced lung injury in dogs. A total of 24 healthy male mongrel dogs were enrolled and randomly divided into LPS, LCAP and LCAP-sham groups. All animals were injected with LPS to induce endotoxemia. The serum levels of leucocytes, neutrophil elastase, arterial blood gas, nuclear factor-kappa B (NF-?B) subunit p65 in lung tissues were measured. The histopathology and parenchyma apoptosis of lung tissues were examined. We found that 7, 3, and 7 animals in the LPS, LCAP, and sham-LCAP groups, respectively, developed ALI 36?h after LPS infusion. The levels of NF-?B p65 in lung tissue, neutrophils and elastase in blood, decreased significantly following LCAP. LCAP also alleviated apoptosis, and NF-?B p65 in lung tissues. Collectively, our results show that partial removal of leucocytes from peripheral blood decreases elastase level in serum. This, in turn, attenuates lung injuries and may potentially decrease the incidence of ALI.

He, Zhi-Gao; Huang, Jian; Zhou, Shun-Gang; He, Jing; Chen, Fang-Xiang; Huang, Xian-Kai

2012-01-01

351

Occupational lung diseases and the mining industry in Mongolia  

SciTech Connect

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

Lkhasuren, O.; Takahashi, K.; Dash-Onolt, L. [Health Science University of Mongolia, Ulaanbaatar (Mongolia)

2007-04-15

352

[Tumor-like tracheal and lung diseases in biopsy samples].  

PubMed

Tumor like miscellaneous lung diseases are rare conditions. They can be confused with benign and malignant tumors. We describe the clinicopathological features some of this conditions i.e.: two cases of osteoplastic tracheopathy, one inflammatory tracheal polyp, two cases of tumor mimicking foreign body aspiration, and one case of tracheobronchial amyloidosis. PMID:11915189

Vajda, Katalin; Mészáros, Imre; Mórócz, Eva; Strausz, János

2002-02-10

353

DOES CHRONIC OZONE EXPOSURE LEAD TO LUNG DISEASE?  

EPA Science Inventory

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

354

Mycophenolate mofetil for interstitial lung disease in dermatomyositis  

PubMed Central

Objective To report our experience using mycophenolate mofetil as first-line treatment for dermatomyositis-associated interstitial lung disease. Methods We examined the medical records of all 16 dermatomyositis patients with interstitial lung disease seen in our outpatient university hospital dermatology clinic between May 26, 2006 and May 25, 2009. In this retrospective case series, we describe the clinical course of the four patients with definitive evidence of interstitial lung disease on radiologic imaging who were treated with mycophenolate mofetil and had pulmonary data available to document their outcome. All patients also received prednisone. Results All three patients with at least one year of follow-up on mycophenolate mofetil experienced complete normalization of pulmonary function tests (including diffusing capacity for carbon monoxide) and resolution of dyspnea. They were also able to reduce their prednisone doses. The only patient with pre- and post-treatment chest computed tomography imaging had total resolution of her interstitial opacities. The patient with only five months of post-treatment follow-up experienced an improvement in diffusing capacity for carbon monoxide from 44 to 77% predicted but no change in dyspnea. Conclusion These promising data indicate that mycophenolate mofetil may be a useful therapy for interstitial lung disease in dermatomyositis patients, but larger studies are needed to more definitively evaluate this medication’s role in therapy.

Morganroth, Pamela A.; Kreider, Mary Elizabeth; Werth, Victoria P.

2011-01-01

355

Role of Ureaplasma urealyticum in lung disease of prematurity  

Microsoft Academic Search

AIMTo examine the role of Ureaplasma urealyticum colonisation or infection in neonatal lung disease.METHODSEndotracheal aspirates from ventilated infants less than 28 weeks of gestation were cultured for U urealyticum and outcomes compared in infants with positive and negative cultures.RESULTSU urealyticum was isolated from aspirates of 39 of 143 (27%) infants. Respiratory distress syndrome (RDS) occurred significantly less often in colonised,

Kirsty Hannaford; David A Todd; Heather Jeffery; Elizabeth John; Karen Blyth; Gwendolyn L Gilbert

1999-01-01

356

Hot tub lung mimicking classic acute and chronic hypersensitivity pneumonitis: Two case reports  

PubMed Central

Pulmonary disease in otherwise healthy patients can occur by secondary exposure to nontuberculous mycobacteria from hot tubs. The pathology of hot tub lung may be related to an infection, a hypersensitivity reaction or both. Previous reports of hot tub lung have highlighted distinct pathological features that have distinguished this entity from classic hypersensitivity pneumonitis. Two cases of hot tub lung in Ontario, which presented at very different time points in their disease course, are reported; one patient presented more fulminantly with a clinical picture resembling subacute hypersensitivity pneumonitis, and the other presented with chronic disease. Both cases exhibited clinical, radiological and pathological findings closely mimicking classic subacute and chronic hypersensitivity pneumonitis.

Verma, Geetika; Jamieson, Frances; Chedore, Pamela; Hwang, David; Boerner, Scott; Geddie, William R; Chapman, Kenneth R; Marras, Theodore K

2007-01-01

357

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

358

OXIDATIVE STRESS RELATED APOPTOSIS IN SMOKERS AND CHRONIC LUNG DISEASES  

Microsoft Academic Search

Cigarette smoke contains various carcinogens, reactive oxygen species (ROS) and reactive nitrogen species (RNS). It has been found that cigarette smoking causes several chronic lung diseases including chronic obstructive pulmonary diseases (COPD). There are mul- tiple markers used for oxidative damage\\/stress in smokers such as urinary 8- hydroxydeoxyguanosine (8-OHdG), serum hydrogen peroxide (H2O2), interleukin-8 (IL-8) and H2O2 in breath condensate.

Ratana Banjerdpongchai

2006-01-01

359

Smoking-Related Small Airways and Interstitial Lung Disease  

Microsoft Academic Search

The consequences of airways and interstitial inflammation caused by cigarette smoking are many and varied. In addition to\\u000a well-recognized smoking-related disorders, including chronic bronchitis and emphysema, there is increasing appreciation of\\u000a the complex relationship between small airways and interstitial damage, typified by respiratory bronchiolitis interstitial\\u000a lung disease. Individual diseases ascribable to cigarette smoking and their relationship to each other are

David M. Hansell; Athol U. Wells

360

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

PubMed Central

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

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

2012-01-01

361

The systemic nature of chronic lung disease.  

PubMed

The systemic effects and comorbidities of chronic respiratory disease such as COPD contribute substantially to its burden. Symptoms in COPD do not solely arise from the degree of airflow obstruction as exercise limitation is compounded by the specific secondary manifestations of the disease including skeletal muscle impairment, osteoporosis, mood disturbance, anemia, and hormonal imbalance. Pulmonary rehabilitation targets the systemic manifestations of COPD, the causes of which include inactivity, systemic inflammation, hypoxia and corticosteroid treatment. Comorbidities are common, including cardiac disease, obesity, and metabolic syndrome and should not preclude pulmonary rehabilitation as they may also benefit from similar approaches. PMID:24874124

Evans, Rachael A; Morgan, Michael D L

2014-06-01

362

Isoforskolin pretreatment attenuates lipopolysaccharide-induced acute lung injury in animal models.  

PubMed

Isoforskolin was isolated from Coleus forskohlii native to Yunnan in China. We hypothesize that isoforskolin pretreatment attenuates acute lung injury induced by lipopolysaccharide (endotoxin). Three acute lung injury models were used: situ perfused rat lung, rat and mouse models of endotoxic shock. Additionally, lipopolysaccharide stimulated proinflammatory cytokine production was evaluated in human mononuclear leukocyte. In situ perfused rat lungs, pre-perfusion with isoforskolin (100, and 200 ?M) and dexamethasone (65 ?M, positive control) inhibited lipopolysaccharide (10 mg/L) induced increases in lung neutrophil adhesion rate, myeloperoxidase activity, lung weight Wet/Dry ratio, permeability-surface area product value, and tumor necrosis factor (TNF)-? levels. In rats, pretreatments with isoforskolin (5, 10, and 20 mg/kg, i.p.) and dexamethasone (5mg/kg, i.p.) markedly reduced lipopolysaccharide (6 mg/kg i.v.) induced increases of karyocyte, neutrophil counts and protein content in bronchoalveolar lavage fluid, and plasma myeloperoxidase activity. Lung histopathology showed that morphologic changes induced by lipopolysaccharide were less pronounced in the isoforskolin and dexamethasone pretreated rats. In mice, 5 mg/kg isoforskolin and dexamethasone caused 100% and 80% survival, respectively, after administration of lipopolysaccharide (62.5mg/kg, i.v., 40% survival if untreated). In human mononuclear leukocyte, isoforskolin (50, 100, and 200 ?M) and dexamethasone (10 ?M) pre-incubation lowered lipopolysaccharide (2 ?g/mL) induced secretion of the cytokine TNF-?, and interleukins (IL)-1?, IL-6, and IL-8. In conclusion, pretreatment with isoforskolin attenuates lipopolysaccharide-induced acute lung injury in several models, and it is involved in down-regulation of inflammatory responses and proinflammatory cytokines TNF-?, IL-1?, IL-6, and IL-8. PMID:21272678

Yang, Weimin; Qiang, Dongjin; Zhang, Min; Ma, Limei; Zhang, Yonghui; Qing, Chen; Xu, Yunlong; Zhen, Chunlan; Liu, Jikai; Chen, Yan-Hua

2011-06-01

363

BPIFB1 IS A LUNG-SPECIFIC AUTOANTIGEN ASSOCIATED WITH INTERSTITIAL LUNG DISEASE**  

PubMed Central

Interstitial lung disease (ILD) is a complex and heterogeneous disorder that is often associated with autoimmune syndromes (1). Despite the connection between ILD and autoimmunity, it remains unclear whether ILD can develop from an autoimmune response that specifically targets the lung parenchyma. Here, we utilized a severe form of autoimmune disease, Autoimmune Polyglandular Syndrome Type 1 (APS1), to establish a strong link between an autoimmune response to the lung-specific protein BPIFB1 and clinical ILD. Screening of a large cohort of APS1 patients revealed autoantibodies to BPIFB1 in 9.6% of APS1 subjects overall and in 100% of APS1 subjects with ILD. Further investigation of ILD outside the APS1 disorder revealed BPIFB1 autoantibodies specifically present in 14.6% of patients with connective tissue disease-associated ILD and in 12.0% of patients with idiopathic ILD. Utilizing the animal model for APS1 to examine the mechanism of ILD pathogenesis, we found that Aire?/? mice harbor autoantibodies to a similar lung antigen named BPIFB9 that are a marker for ILD, and determined that a defect in thymic tolerance is responsible for the production of BPIFB9 autoantibodies and the development of ILD. Importantly, we also found that immunoreactivity targeting BPIFB1 independent of a defect in Aire also leads to ILD, consistent with our discovery of BPIFB1 autoantibodies in non-APS1 patients. Overall, our results demonstrate that autoimmunity targeting the lung-specific antigen BPIFB1 may be important to the pathogenesis of ILD in patients with APS1 and in subsets of patients with non-APS1 ILD, demonstrating the role of lung-specific autoimmunity in the genesis of ILD.

Shum, Anthony K.; Alimohammadi, Mohammad; Tan, Catherine L.; Cheng, Mickie H.; Metzger, Todd C.; Law, Christopher S.; Lwin, Wint; Perheentupa, Jaakko; Carel, Jean Claude; Husebye, Eystein S.; De Luca, Filippo; Janson, Christer; Sargur, Ravishankar; Dubois, Noemie; Kajosaari, Merja; Wolters, Paul J.; Chapman, Harold A.; Kampe, Olle; Anderson, Mark S.

2013-01-01

364

BPIFB1 is a lung-specific autoantigen associated with interstitial lung disease.  

PubMed

Interstitial lung disease (ILD) is a complex and heterogeneous disorder that is often associated with autoimmune syndromes. Despite the connection between ILD and autoimmunity, it remains unclear whether ILD can develop from an autoimmune response that specifically targets the lung parenchyma. We examined a severe form of autoimmune disease, autoimmune polyglandular syndrome type 1 (APS1), and established a strong link between an autoimmune response to the lung-specific protein BPIFB1 (bactericidal/permeability-increasing fold-containing B1) and clinical ILD. Screening of a large cohort of APS1 patients revealed autoantibodies to BPIFB1 in 9.6% of APS1 subjects overall and in 100% of APS1 subjects with ILD. Further investigation of ILD outside the APS1 disorder revealed BPIFB1 autoantibodies present in 14.6% of patients with connective tissue disease-associated ILD and in 12.0% of patients with idiopathic ILD. The animal model for APS1, Aire?/? mice, harbors autoantibodies to a similar lung antigen (BPIFB9); these autoantibodies are a marker for ILD. We found that a defect in thymic tolerance was responsible for the production of BPIFB9 autoantibodies and the development of ILD. We also found that immunoreactivity targeting BPIFB1 independent of a defect in Aire also led to ILD, consistent with our discovery of BPIFB1 autoantibodies in non-APS1 patients. Overall, our results demonstrate that autoimmunity targeting the lung-specific antigen BPIFB1 may contribute to the pathogenesis of ILD in patients with APS1 and in subsets of patients with non-APS1 ILD, demonstrating the role of lung-specific autoimmunity in the genesis of ILD. PMID:24107778

Shum, Anthony K; Alimohammadi, Mohammad; Tan, Catherine L; Cheng, Mickie H; Metzger, Todd C; Law, Christopher S; Lwin, Wint; Perheentupa, Jaakko; Bour-Jordan, Helene; Carel, Jean Claude; Husebye, Eystein S; De Luca, Filippo; Janson, Christer; Sargur, Ravishankar; Dubois, Noémie; Kajosaari, Merja; Wolters, Paul J; Chapman, Harold A; Kämpe, Olle; Anderson, Mark S

2013-10-01

365

IL1B Polymorphisms Modulate Cystic Fibrosis Lung Disease  

PubMed Central

Summary Rationale: Variability in pulmonary disease severity is found in patients with cystic fibrosis (CF) who have identical mutations in the CF transmembrane conductance regulator (CFTR) gene. We hypothesized that one factor accounting for heterogeneity in pulmonary disease severity is variation in the family of genes affecting the biology of interleukin-1 (IL-1), which impacts acquisition and maintenance of Pseudomonas aeruginosa infection in animal models of chronic infection. Methods: We genotyped 58 single nucleotide polymorphisms (SNPs) in the IL-1 gene cluster in 808 CF subjects from the University of North Carolina and Case Western Reserve University (UNC/CWRU) joint cohort. All were homozygous for ?F508, and categories of “severe” (cases) or “mild” (control subjects) lung disease were defined by the lowest or highest quartile of forced expired volume (FEV1) for age in the CF population. After adjustment for age and gender, genotypic data were tested for association with lung disease severity. Odds ratios (ORs) comparing severe versus mild CF were also calculated for each genotype (with the homozygote major allele as the reference group) for all 58 SNPs. From these analyses, nine SNPs with a moderate effect size, OR ? 0.5or > 1.5, were selected for further testing. To replicate the case-control study results, we genotyped the same nine SNPs in a second population of CF parent-offspring trios (recruited from Children’s Hospital Boston), in which the offspring had similar pulmonary phenotypes. For the trio analysis, both family-based and population-based associations were performed. Results: SNPs rs1143634 and rs1143639 in the IL1B gene demonstrated a consistent association with lung disease severity categories (P < 0.10) and longitudinal analysis of lung disease severity (P < 0.10) in CF in both the case-control and family-based studies. In females, there was a consistent association (false discovery rate adjusted joint P-value < 0.06 for both SNPs) in both the analysis of lung disease severity in the UNC/CWRU cohort and the family-based analysis of affection status. Conclusion: Our findings suggest that IL1? is a clinically relevant modulator of CF lung disease.

Levy, Hara; Murphy, Amy; Zou, Fei; Gerard, Craig; Klanderman, Barbara; Schuemann, Brooke; Lazarus, Ross; Garcia, K. Christopher; Celedon, Juan C.; Drumm, Mitch; Dahmer, Mary; Quasney, Michael; Schneck, Kaitlyn; Reske, Melissa; Knowles, Michael R.; Pier, Gerald B.; Lange, Christoph; Weiss, Scott T.

2013-01-01

366

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

PubMed

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

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

2014-08-01

367

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 ...

368

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 ...

369

Therapeutic Effect of Hyperoxygenated Solution on Acute Lung Injury Induced by Oleic Acid  

Microsoft Academic Search

Background\\/Aims: Hyperoxygenated solution (HOS) has been shown to protect the myocardium, spinal cord and brain from ischemic injury. In this study, we evaluated the effect of HOS on acute lung injury (ALI) induced by oleic acid in rabbits. Methods: 24 rabbits were randomized into four groups: control (C), oleic acid (OA), inhaled oxygen (OX), and HOS treatment (HOS). The ALI

R. F. Xu; T. T. Li; X. Y. Feng; H. Zhang; B. Song; C. R. Liu; L. X. Xu

2008-01-01

370

Hypervolemia induces and potentiates lung damage after recruitment maneuver in a model of sepsis-induced acute lung injury  

PubMed Central

Introduction Recruitment maneuvers (RMs) seem to be more effective in extrapulmonary acute lung injury (ALI), caused mainly by sepsis, than in pulmonary ALI. Nevertheless, the maintenance of adequate volemic status is particularly challenging in sepsis. Since the interaction between volemic status and RMs is not well established, we investigated the effects of RMs on lung and distal organs in the presence of hypovolemia, normovolemia, and hypervolemia in a model of extrapulmonary lung injury induced by sepsis. Methods ALI was induced by cecal ligation and puncture surgery in 66 Wistar rats. After 48 h, animals were anesthetized, mechanically ventilated and randomly assigned to 3 volemic status (n = 22/group): 1) hypovolemia induced by blood drainage at mean arterial pressure (MAP)?70 mmHg; 2) normovolemia (MAP?100 mmHg), and 3) hypervolemia with colloid administration to achieve a MAP?130 mmHg. In each group, animals were further randomized to be recruited (CPAP = 40 cm H2O for 40 s) or not (NR) (n = 11/group), followed by 1 h of protective mechanical ventilation. Echocardiography, arterial blood gases, static lung elastance (Est,L), histology (light and electron microscopy), lung wet-to-dry (W/D) ratio, interleukin (IL)-6, IL-1?, caspase-3, type III procollagen (PCIII), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) mRNA expressions in lung tissue, as well as lung and distal organ epithelial cell apoptosis were analyzed. Results We observed that: 1) hypervolemia increased lung W/D ratio with impairment of oxygenation and Est,L, and was associated with alveolar and endothelial cell damage and increased IL-6, VCAM-1, and ICAM-1 mRNA expressions; and 2) RM reduced alveolar collapse independent of volemic status. In hypervolemic animals, RM improved oxygenation above the levels observed with the use of positive-end expiratory pressure (PEEP), but increased lung injury and led to higher inflammatory and fibrogenetic responses. Conclusions Volemic status should be taken into account during RMs, since in this sepsis-induced ALI model hypervolemia promoted and potentiated lung injury compared to hypo- and normovolemia.

2010-01-01

371

Enhanced CXCL1 production and angiogenesis in adenosine-mediated lung disease  

Microsoft Academic Search

Angiogenesis is a feature of chronic lung diseases such as asthma and pulmonary fibrosis; how- ever, the pathways controlling pathological angiogene- sis during lung disease are not completely understood. Adenosine is a signaling molecule that has been impli- cated in the exacerbation of chronic lung disease and in the regulation of angiogenesis; however, the relation- ship between these factors has

Amir Mohsenin; Marie D. Burdick; Jose G. Molina; Michael P. Keane; Michael R. Blackburn

2007-01-01

372

[Management of hydatid disease of the lung].  

PubMed

Cystic echinococcosis is a worldwide zoonose which is not infectious from man to man occurring seldom in our country. The diagnosis and the treatment of a case of a 4-year-old girl with large left-sided lung cyst were presented. Diagnosis was based on history, clinical findings, imaging techniques (conventional X-ray examination, ultrasonography, computer tomography), eosinophilia (7-50%) in blood smear, leucocytosis (28,000), increased sedimentation of blood (85 mm/hour), significantly elevated antibody against of Echinococcus in immunodiagnostic test (passive haemagglutination) with high sensitivity and specificity, light microscopic radiological and scanning electronmicroscopic analysis of cyst content. Continuous thoracic drainage, twice percutan drainage under CT guidance and a new technique for treatment as Puncture-Aspiration-Injection-Respiration and lavage with hypertonic sodium chlorate, long-term chemotherapy with benzimidazole-carbamates (Vermox: 20 mg/kg/day, Zentel: 30-50 mg/kg/day) were reported. The cyst was grown down into a solid mass as large as 4 cm. The body-weight of this child has grown 6 kilograms and laboratory parameters were normalized. PMID:9451907

Bede, O; Gellén, B; Szénási, Z; Morvay, Z; Farkas, Z; Kövesdi, J

1998-01-11

373

Autophagy: a potential therapeutic target in lung diseases  

PubMed Central

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

Nakahira, Kiichi

2013-01-01

374

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

SciTech Connect

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

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

1986-07-01

375

Murine models of acute and chronic lung infection with cystic fibrosis pathogens.  

PubMed

Animal models of acute and chronic infection, along with mice genetically modified for the Cftr gene, are a key asset in cystic fibrosis (CF) research. Despite some limitations, these models provide valuable resources to mimic the initial and progressive bronchopulmonary infection typical of CF patients. The following review summarizes the strengths and weaknesses of different types of animal models with a major emphasis placed on the significant species differences between mice and humans. Murine models of acute and chronic lung infection with Pseudomonas aeruginosa, Burkholderia cenocepacia, Staphylococcus aureus, and Haemophilus influenzae have been used to study the molecular mechanisms underlying the pathogen virulence and host defense. In addition, they have provided insights in the potential of vaccination to restrict infectious exacerbations, the activity of antibiotics, and the effectiveness of anti-inflammatory therapy in reducing lung damage. Indeed, animal models of infection should allow the validation of future therapeutic interventions for lung infections in patients with CF. PMID:20951086

Bragonzi, Alessandra

2010-12-01

376

Pulmonary Administration of a Water-Soluble Curcumin Complex Reduces Severity of Acute Lung Injury  

PubMed Central

Local or systemic inflammation can result in acute lung injury (ALI), and is associated with capillary leakage, reduced lung compliance, and hypoxemia. Curcumin, a plant-derived polyphenolic compound, exhibits potent anti-inflammatory properties, but its poor solubility and limited oral bioavailability reduce its therapeutic potential. A novel curcumin formulation (CDC) was developed by complexing the compound with hydroxypropyl-?-cyclodextrin (CD). This results in greatly enhanced water solubility and stability that facilitate direct pulmonary delivery. In vitro studies demonstrated that CDC increased curcumin’s association with and transport across Calu-3 human airway epithelial cell monolayers, compared with uncomplexed curcumin solubilized using DMSO or ethanol. Importantly, Calu-3 cell monolayer integrity was preserved after CDC exposure, whereas it was disrupted by equivalent uncomplexed curcumin solutions. We then tested whether direct delivery of CDC to the lung would reduce severity of ALI in a murine model. Fluorescence microscopic examination revealed an association of curcumin with cells throughout the lung. The administration of CDC after LPS attenuated multiple markers of inflammation and injury, including pulmonary edema and neutrophils in bronchoalveolar lavage fluid and lung tissue. CDC also reduced oxidant stress in the lungs and activation of the proinflammatory transcription factor NF-?B. These results demonstrate the efficacy of CDC in a murine model of lung inflammation and injury, and support the feasibility of developing a lung-targeted, curcumin-based therapy for the treatment of patients with ALI.

Suresh, Madathilparambil V.; Wagner, Matthew C.; Rosania, Gus R.; Stringer, Kathleen A.; Min, Kyoung Ah; Risler, Linda; Shen, Danny D.; Georges, George E.; Reddy, Aravind T.; Parkkinen, Jaakko

2012-01-01

377

Fluid homeostasis in chronic obstructive lung disease  

Microsoft Academic Search

Chronic obstructive pulmonary disease (COPD) often leads to massive oedema and the development of what is usually called cor pulmonale. The mechanisms by which patients with COPD retain salt and water are not completely understood. Several abnormalities have been found including reduced renal blood flow with relatively preserved glomerular filtration rate and elevated levels of renin, aldosterone, arginine vasopressin and

P. W. de Leeuw; A. Dees

2003-01-01

378

Anti-inflammatory effects of ?2 adrenergic receptor agonists in experimental acute lung injury  

PubMed Central

These studies were undertaken to extend emerging evidence that ?2 adrenergic receptor (?2AR) agonists, in addition to their bronchorelaxing effects, may have broad anti-inflammatory effects in the lung following onset of experimental acute lung injury (ALI). Young male C57BL/6 mice (25 g) developed ALI following airway deposition of bacterial LPS or IgG immune complexes in the absence or presence of appropriate stereoisomers (enantiomers) of ?2AR agonists, albuterol or formoterol. Endpoints included albumin leak into lung and buildup of polymorphonuclear neutrophils and cytokines/chemokines in bronchoalveolar fluids. Both ?2AR agonists suppressed lung inflammatory parameters (IC50=10?7 M). Similar effects of ?2AR agonists on mediator release were found when mouse macrophages were stimulated in vitro with LPS. The protective effects were associated with reduced activation (phosphorylation) of JNK but not of other signaling proteins. Collectively, these data suggest that ?2AR agonists have broad anti-inflammatory effects in the setting of ALI. While ?2AR agonists suppress JNK activation, the extent to which this can explain the blunted lung inflammatory responses in the ALI models remains to be determined.—Bosmann, M., Grailer, J. J., Zhu, K., Matthay, M A., Vidya Sarma, J., Zetoune, F. S., Ward, P. A. Anti-inflammatory effects of ?2 adrenergic receptor agonists in experimental acute lung injury.

Bosmann, Markus; Grailer, Jamison J.; Zhu, Ketong; Matthay, Michael A.; Sarma, J. Vidya; Zetoune, Firas S.; Ward, Peter A.

2012-01-01

379

Protective effects of sialylated oligosaccharides in immune complex- induced acute lung injury  

PubMed Central

Using sialyl Lewisx (SLX) oligosaccharides derived from fucosyl transferase-expressing cells or generated synthetically, the ability of these compounds to protect against acute lung damage after deposition of immunoglobulin (Ig)G or IgA immune complexes has been determined. The synthetic compounds were tetra- and pentasaccharide derivates of SLX as well as the nonfucosylated forms of SLX as controls. In the IgG immune complex model of lung injury, which is E-selectin dependent, SLX preparations provided dose-dependent protective effects, as assessed by changes in lung vascular permeability and hemorrhage. Protective effects were associated with diminished tissue accumulation of neutrophils in lungs (as assessed by myeloperoxidase). Morphological assessment revealed reduced physical contact of neutrophils with the pulmonary vascular endothelium and reduced tissue accumulation of neutrophils. In the model of IgA immune complex-induced lung injury, which does not involve participation of neutrophils and is independent of the requirement for E-selectin, SLX preparations were not protective. These data suggest that, in neutrophil-mediated and E- selectin-dependent lung injury, SLX preparations provide significant, protective effects against inflammatory vascular injury. The ability to achieve antiinflammatory outcomes in vivo with appropriate oligosaccharides suggests a new approach to the blocking of acute inflammatory responses.

1993-01-01

380

Modifications of lung clearance mechanisms by acute influenza A infection  

SciTech Connect

Four volunteers with naturally acquired, culture-proved influenza A infection inhaled a radiolabeled aerosol to permit investigation of lung mucociliary clearance mechanisms during and after symptomatic illness. Mucus transport in the trachea was undetectable when monitored with an external multidetector probe within 48 hours of the onset of the illness, but was found at a normal velocity by 1 week in three of the four subjects. In two volunteers who coughed 23 to 48 times during the 4.5-hour observation period, whole lung clearance was as fast within the first 48 hours of illness as during health 3 months later in spite of the absence of measurable tracheal mucus transport. Conversely, in spite of the return 1 week later of mucus transport at velocities expected in the trachea, whole lung clearance for the 4.5-hour period was slowed in two volunteers who coughed less than once an hour. The data offer evidence that cough is important in maintaining lung clearance for at least several days after symptomatic influenza A infection when other mechanisms that depend on ciliary function are severely deficient.

Levandowski, R.A.; Gerrity, T.R.; Garrard, C.S.

1985-10-01

381

The role of neutrophil elastase in acute lung injury  

Microsoft Academic Search

Beside its physiological function as a powerful host defense, neutrophil elastase is also known as one of the most destructive enzymes in the body. Current notion holds that neutrophil elastase is able to escape from regulation by multiple protease inhibitors at inflammatory sites. Once unregulated, this enzyme disturbs the function of the lung permeability barrier and induces the release of

Kazuhito Kawabata; Tetsuya Hagio; Shozo Matsuoka

2002-01-01

382

Quantitative Lung Perfusion Scintigraphy in Patients with Congenital Heart Disease  

PubMed Central

The objectives of this article are to review different patterns and potential pitfalls of quantitative lung perfusion scintigraphy (LPS) in patients with congenital heart disease (CHD). The patterns of quantitative LPS in patients with CHD include normal symmetrical bilateral perfusion to both lungs, unilateral absent perfusion in one lung, unilateral decreased perfusion, and multiple segmental perfusion abnormalities that suggest pulmonary embolism. Knowledge of several potential pitfalls is very important to avoid false interpretations; common pitfalls are related to type of site of injection (upper versus lower extremities), right or left upper extremity in case of persistence of left superior vena cava and previous surgery. An important incidental finding that may prompt immediate attenuation is multiple segmental defect that suggests asymptomatic pulmonary embolism, which is relatively common in this population.

Fathala, Ahmed

2010-01-01

383

Effects of sivelestat treatment on acute lung injury in paraquat-intoxicated rats.  

PubMed

Lung injury is the main cause of death in acute paraquat (PQ) intoxication. Sivelestat (SV), a neutrophil elastase inhibitor, is effective in reducing inflammation in acute lung injury. The aim of this study was to examine the effect of SV on acute lung injury in PQ-intoxicated rats. Seven-week-old male Sprague-Dawley rats were randomly assigned to four groups: (1) control group (group N; n?=?5); (2) PQ?+?normal saline (group P; n?=?6); (3) normal saline?+?SV (group S; n?=?6) and (4) PQ?+?SV (group PS; n?=?6). SV treatment (intraperitoneally [i.p.], 20?mg/kg) was performed 30 minutes after PQ injection (i.p., 100?mg/kg), and injections were continued every hour for a total of five doses. One hour after the last treatment, blood samples were obtained for analysis of interleukin (IL)-6 and tumor necrosis factor alpha (TNF-?). Lung sections were stained with hematoxylin--eosin for light microscopic analysis. Neutrophil infiltration score of group PS was significantly lower than that of group P (p?acute lung injury in rats. In addition, systemic inflammation was partially suppressed with SV treatment, suppressing TNF-? production. These results suggest that SV reduces paraquat-induced lung injury, at least partially, by inhibiting neutrophil infiltration and TNF-? secretion. PMID:24111663

Park, Jung Soo; Park, Kyung Hye; Kim, Hoon; Choi, Song Yi

2014-01-01

384

Surfactant protein polymorphisms and neonatal lung disease.  

PubMed

Here, we describe the approach of defining the genetic contribution to disease and discuss the polymorphisms of some genes that are associated with respiratory disease. The common allelic variants of SP-A1, SP-A2, SP-B, SP-C, and SP-D genes are associated with respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), or respiratory syncytial virus (RSV) bronchiolitis. The main SP-A haplotype, interactively with SP-B Ile131Thr polymorphism and with constitutional and environmental factors, influences the risk of RDS. The polymorphisms of SP-A2 and SP-D are associated with the risk of severe RSV. The polymorphism may turn out to be important in susceptibility to influenza virus. The SP-B intron 4 deletion variant is the risk factor of BPD. Understanding the molecular mechanisms behind the hereditary risk may lead to new focused treatment strategies. PMID:17142161

Hallman, Mikko; Haataja, Ritva

2006-12-01

385

[Enigmatic lymphatic diseases involving the lung].  

PubMed

Lymphedema associated with other developmental malformations (Milroy syndrome, Hennekam syndrome, Noonan syndrome, Gorham-Stout syndrome, yellow nail syndrome) are unfrequent disease, but explorations led to the identification of genetic mutations that have then been validated in mouse models. However, lymphatic vessels complexity and its proximity with the venous system suggest the need for further researches, especially in the comprehension of pulmonary symptoms. PMID:23561737

Khen-Dunlop, N; Amiel, J; Delacourt, C; Révillon, Y

2013-10-01

386

Acute Respiratory Disease and Meningococcal Infection in Army Recruits.  

National Technical Information Service (NTIS)

The chronologic association of acute respiratory disease and meningococcal infection was examined in army recruits by weekly surveys of 17 basic training platoons. Nine platoons had received live, attenuated adenovirus vaccine, type 4, orally; the other e...

M. S. Artenstein J. H. Rust D. H. Hunter T. H. Lamson E. L. Buescher

1967-01-01

387

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

PubMed Central

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, particularly when the broad definition of ILD is used. In most patients with ILD a cause is not identified; nevertheless, among the established causes are a number of drug therapies and infections. Occupational causes are lessening in importance, while cigarette smoking is now an established risk factor. Radiation therapy for cancer is a well-established cause of ILD that usually, but not always, localises within the radiation portal and may occur later after completion of therapy. Similarly, exposure to drugs long after radiation therapy may be an aetiological factor for the development of ILD later in life, although the magnitude of this risk requires further epidemiological investigation. The possibility that ILD and lung cancer are associated has been recognised for >50 years, but it remains unclear whether ILD precedes lung cancer or vice versa. In this review, we examine the epidemiology of ILD and the basis for its association with lung cancer.

Raghu, G; Nyberg, F; Morgan, G

2004-01-01

388

Acute Exacerbations and Respiratory Failure in Chronic Obstructive Pulmonary Disease  

Microsoft Academic Search

and they account for significant consumption of health care resour- ces. Although bacterial infections are the most common causes of AECOPD, viral infections and environmental stresses are also impli- cated. AECOPD episodes can be triggered or complicated by other comorbidities, such as heart disease, other lung diseases (e.g., pul- monary emboli, aspiration, pneumothorax), or systemic processes. Pharmacologic management includes bronchodilators,

Neil MacIntyre; Yuh Chin Huang

2008-01-01

389

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

390

[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

391

Neu-164 and Neu-107, two novel antioxidant and anti-myeloperoxidase compounds, inhibit acute cigarette smoke-induced lung inflammation  

PubMed Central

Cigarette smoke is a profound proinflammatory stimulus that causes acute lung inflammation and chronic lung disease, including chronic obstructive pulmonary disease (COPD, emphysema, and chronic bronchitis), via a variety of mechanisms, including oxidative stress. Cigarette smoke contains high levels of free radicals, whereas inflammatory cells, including macrophages and neutrophils, express enzymes, including NADPH oxidase, nitric oxide synthase, and myeloperoxidase, that generate reactive oxygen species in situ and contribute to inflammation and tissue damage. Neu-164 and Neu-107 are small-molecule inhibitors of myeloperoxidase, as well as potent antioxidants. We hypothesized that Neu-164 and Neu-107 would inhibit acute cigarette smoke-induced inflammation. Adult C57BL/6J mice were exposed to mainstream cigarette smoke for 3 days to ind