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Sample records for acute lung disease

  1. Acute exacerbations of fibrotic interstitial lung disease.

    PubMed

    Churg, Andrew; Wright, Joanne L; Tazelaar, Henry D

    2011-03-01

    An acute exacerbation is the development of acute lung injury, usually resulting in acute respiratory distress syndrome, in a patient with a pre-existing fibrosing interstitial pneumonia. By definition, acute exacerbations are not caused by infection, heart failure, aspiration or drug reaction. Most patients with acute exacerbations have underlying usual interstitial pneumonia, either idiopathic or in association with a connective tissue disease, but the same process has been reported in patients with fibrotic non-specific interstitial pneumonia, fibrotic hypersensitivity pneumonitis, desquamative interstitial pneumonia and asbestosis. Occasionally an acute exacerbation is the initial manifestation of underlying interstitial lung disease. On biopsy, acute exacerbations appear as diffuse alveolar damage or bronchiolitis obliterans organizing pneumonia (BOOP) superimposed upon the fibrosing interstitial pneumonia. Biopsies may be extremely confusing, because the acute injury pattern can completely obscure the underlying disease; a useful clue is that diffuse alveolar damage and organizing pneumonia should not be associated with old dense fibrosis and peripheral honeycomb change. Consultation with radiology can also be extremely helpful, because the fibrosing disease may be evident on old or concurrent computed tomography scans. The aetiology of acute exacerbations is unknown, and the prognosis is poor; however, some patients survive with high-dose steroid therapy. PMID:20854464

  2. Protection from acute and chronic lung diseases by curcumin.

    PubMed

    Venkatesan, Narayanan; Punithavathi, Durairaj; Babu, Mary

    2007-01-01

    The aim of this review has been to describe the current state of the therapeutic potential of curcumin in acute and chronic lung injuries. Occupational and environmental exposures to mineral dusts, airborne pollutants, cigarette smoke, chemotherapy, and radiotherapy injure the lungs, resulting in acute and chronic inflammatory lung diseases. Despite major advances in treating lung diseases, until now disease-modifying efficacy has not been demonstrated for any of the existing drugs. Current medical therapy offers only marginal benefit; therefore, there is an essential need to develop new drugs that might be of effective benefit in clinical settings. Over the years, there has been increasing evidence that curcumin, a phytochemical present in turmeric (Curcuma longa), has a wide spectrum of therapeutic properties and a remarkable range of protective effects in various diseases. Several experimental animal models have tested curcumin on lung fibrosis and these studies demonstrate that curcumin attenuates lung injury and fibrosis caused by radiation, chemotherapeutic drugs, and toxicants. The growing amount of data from pharmacological and animal studies also supports the notion that curcumin plays a protective role in chronic obstructive pulmonary disease, acute lung injury, acute respiratory distress syndrome, and allergic asthma, its therapeutic action being on the prevention or modulation of inflammation and oxidative stress. These findings give substance to the possibility of testing curcumin in patients with lung diseases. PMID:17569221

  3. Metabolomics and Its Application to Acute Lung Diseases.

    PubMed

    Stringer, Kathleen A; McKay, Ryan T; Karnovsky, Alla; Quémerais, Bernadette; Lacy, Paige

    2016-01-01

    Metabolomics is a rapidly expanding field of systems biology that is gaining significant attention in many areas of biomedical research. Also known as metabonomics, it comprises the analysis of all small molecules or metabolites that are present within an organism or a specific compartment of the body. Metabolite detection and quantification provide a valuable addition to genomics and proteomics and give unique insights into metabolic changes that occur in tangent to alterations in gene and protein activity that are associated with disease. As a novel approach to understanding disease, metabolomics provides a "snapshot" in time of all metabolites present in a biological sample such as whole blood, plasma, serum, urine, and many other specimens that may be obtained from either patients or experimental models. In this article, we review the burgeoning field of metabolomics in its application to acute lung diseases, specifically pneumonia and acute respiratory disease syndrome (ARDS). We also discuss the potential applications of metabolomics for monitoring exposure to aerosolized environmental toxins. Recent reports have suggested that metabolomics analysis using nuclear magnetic resonance (NMR) and mass spectrometry (MS) approaches may provide clinicians with the opportunity to identify new biomarkers that may predict progression to more severe disease, such as sepsis, which kills many patients each year. In addition, metabolomics may provide more detailed phenotyping of patient heterogeneity, which is needed to achieve the goal of precision medicine. However, although several experimental and clinical metabolomics studies have been conducted assessing the application of the science to acute lung diseases, only incremental progress has been made. Specifically, little is known about the metabolic phenotypes of these illnesses. These data are needed to substantiate metabolomics biomarker credentials so that clinicians can employ them for clinical decision-making and investigators can use them to design clinical trials. PMID:26973643

  4. Metabolomics and Its Application to Acute Lung Diseases

    PubMed Central

    Stringer, Kathleen A.; McKay, Ryan T.; Karnovsky, Alla; Quémerais, Bernadette; Lacy, Paige

    2016-01-01

    Metabolomics is a rapidly expanding field of systems biology that is gaining significant attention in many areas of biomedical research. Also known as metabonomics, it comprises the analysis of all small molecules or metabolites that are present within an organism or a specific compartment of the body. Metabolite detection and quantification provide a valuable addition to genomics and proteomics and give unique insights into metabolic changes that occur in tangent to alterations in gene and protein activity that are associated with disease. As a novel approach to understanding disease, metabolomics provides a “snapshot” in time of all metabolites present in a biological sample such as whole blood, plasma, serum, urine, and many other specimens that may be obtained from either patients or experimental models. In this article, we review the burgeoning field of metabolomics in its application to acute lung diseases, specifically pneumonia and acute respiratory disease syndrome (ARDS). We also discuss the potential applications of metabolomics for monitoring exposure to aerosolized environmental toxins. Recent reports have suggested that metabolomics analysis using nuclear magnetic resonance (NMR) and mass spectrometry (MS) approaches may provide clinicians with the opportunity to identify new biomarkers that may predict progression to more severe disease, such as sepsis, which kills many patients each year. In addition, metabolomics may provide more detailed phenotyping of patient heterogeneity, which is needed to achieve the goal of precision medicine. However, although several experimental and clinical metabolomics studies have been conducted assessing the application of the science to acute lung diseases, only incremental progress has been made. Specifically, little is known about the metabolic phenotypes of these illnesses. These data are needed to substantiate metabolomics biomarker credentials so that clinicians can employ them for clinical decision-making and investigators can use them to design clinical trials. PMID:26973643

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

    PubMed Central

    de Abreu, Krasnalhia Lívia Soares; da Silva Junior, Geraldo Bezerra; Muniz, Thalita Diógenes; Barreto, Adller Gonçalves Costa; Lima, Rafael Siqueira Athayde; Holanda, Marcelo Alcântara; Pereira, Eanes Delgado Barros; Libório, Alexandre Braga; Daher, Elizabeth de Francesco

    2013-01-01

    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. PMID:23917978

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

    PubMed Central

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

    2011-01-01

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

  7. Acute Lung Failure

    PubMed Central

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

    2013-01-01

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

  8. [Acute respiratory distress syndrome caused by tropical eosinophilic lung disease: a case in Gabon].

    PubMed

    Chani, M; Iken, M; Eljahiri, Y; Nzenze, J R; Mion, G

    2011-04-01

    The purpose of this report is to describe the case of a 28-year-old woman in whom acute respiratory distress syndrome (ARDS) following cholecystectomy led to the discovery of eosinophilic lung disease. Outcome was favorable after oxygenotherapy and medical treatment using ivermectin and corticosteroids. The case shows that hypereosinophilic syndrome can be the underlying cause of ARDS. PMID:21695880

  9. Lung disease

    MedlinePlus

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

  10. Biomarkers in acute lung injury.

    PubMed

    Mokra, Daniela; Kosutova, Petra

    2015-04-01

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

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

    PubMed Central

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

    2014-01-01

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

  12. 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 ...

  13. Bedside Lung Ultrasound During Acute Chest Syndrome in Sickle Cell Disease.

    PubMed

    Razazi, Keyvan; Deux, Jean-Franois; de Prost, Nicolas; Boissier, Florence; Cuquemelle, Elise; Galactros, Frdric; Rahmouni, Alain; Matre, Bernard; Brun-Buisson, Christian; Mekontso Dessap, Armand

    2016-02-01

    Lung ultrasound (LU) is increasingly used to assess pleural and lung disease in intensive care unit (ICU) and emergency unit at the bedside. We assessed the performance of bedside chest radiograph (CR) and LU during severe acute chest syndrome (ACS), using computed tomography (CT) as the reference standard.We prospectively explored 44 ACS episodes (in 41 patients) admitted to the medical ICU. Three imaging findings were evaluated (consolidation, ground-glass opacities, and pleural effusion). A score was used to quantify and compare loss of lung aeration with each technique and assess its association with outcome.A total number of 496, 507, and 519 lung regions could be assessed by CT scan, bedside CR, and bedside LU, respectively. Consolidations were the most common pattern and prevailed in lung bases (especially postero-inferior regions). The agreement with CT scan patterns was significantly higher for LU as compared to CR (? coefficients of 0.45??0.03 vs 0.30??0.03, P?

  14. Lung disease - resources

    MedlinePlus

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

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

    SciTech Connect

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

    2013-10-15

    Sex-specific differences in pulmonary morbidity in humans are well documented. Hyperoxia contributes to lung injury in experimental animals and humans. The mechanisms responsible for sex differences in the susceptibility towards hyperoxic lung injury remain largely unknown. In this investigation, we tested the hypothesis that mice will display sex-specific differences in hyperoxic lung injury. Eight week-old male and female mice (C57BL/6J) were exposed to 72 h of hyperoxia (FiO{sub 2} > 0.95). After exposure to hyperoxia, lung injury, levels of 8-iso-prostaglandin F{sub 2} alpha (8-iso-PGF 2α) (LC–MS/MS), apoptosis (TUNEL) and inflammatory markers (suspension bead array) were determined. Cytochrome P450 (CYP)1A expression in the lung was assessed using immunohistochemistry and western blotting. After exposure to hyperoxia, males showed greater lung injury, neutrophil infiltration and apoptosis, compared to air-breathing controls than females. Pulmonary 8-iso-PGF 2α levels were higher in males than females after hyperoxia exposure. Sexually dimorphic increases in levels of IL-6 (F > M) and VEGF (M > F) in the lungs were also observed. CYP1A1 expression in the lung was higher in female mice compared to males under hyperoxic conditions. Overall, our results support the hypothesis that male mice are more susceptible than females to hyperoxic lung injury and that differences in inflammatory and oxidative stress markers contribute to these sex-specific dimorphic effects. In conclusion, this paper describes the establishment of an animal model that shows sex differences in hyperoxic lung injury in a temporal manner and thus has important implications for lung diseases mediated by hyperoxia in humans. - Highlights: • Male mice were more susceptible to hyperoxic lung injury than females. • Sex differences in inflammatory markers were observed. • CYP1A expression was higher in females after hyperoxia exposure.

  16. Rheumatoid lung disease

    MedlinePlus

    Lung disease - rheumatoid arthritis; Rheumatoid nodules; Rheumatoid lung ... Lung problems are common in rheumatoid arthritis. They often cause no symptoms. The cause of lung disease associated with rheumatoid arthritis is unknown. Sometimes, the medicines used to ...

  17. Severe acute interstitial lung disease in a patient with anaplastic lymphoma kinase rearrangement-positive non-small cell lung cancer treated with alectinib.

    PubMed

    Yamamoto, Yuzo; Okamoto, Isamu; Otsubo, Kohei; Iwama, Eiji; Hamada, Naoki; Harada, Taishi; Takayama, Koichi; Nakanishi, Yoichi

    2015-10-01

    Alectinib, the second generation anaplastic lymphoma kinase (ALK) inhibitor, has significant potency in patients with ALK rearrangement positive non-small cell lung cancer (NSCLC), and its toxicity is generally well tolerable. We report a patient who developed severe acute interstitial lung disease after alectinib treatment. An 86-year-old woman with stage IV lung adenocarcinoma positive for rearrangement of ALK gene was treated with alectinib. On the 215th day after initiation of alectinib administration, she was admitted to our hospital with the symptom of progressive dyspnea. Computed tomography (CT) revealed diffuse ground glass opacities and consolidations in both lungs, and analysis of bronchoalveolar lavage fluid revealed pronounced lymphocytosis. There was no evidence of infection or other specific causes of her condition, and she was therefore diagnosed with interstitial lung disease induced by alectinib. Her CT findings and respiratory condition improved after steroid pulse therapy. As far as we are aware, this is the first reported case of alectinib-induced severe interstitial lung disease (ILD). We should be aware of the possibility of such a severe adverse event and should therefore carefully monitor patients treated with this drug. PMID:26334220

  18. Interstitial Lung Disease

    MedlinePlus

    ... MD 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 ...

  19. Kidney-lung connections in acute and chronic diseases: current perspectives.

    PubMed

    Visconti, Luca; Santoro, Domenico; Cernaro, Valeria; Buemi, Michele; Lacquaniti, Antonio

    2016-06-01

    Lung and kidney functions are intimately related in both health and disease. The regulation of acid-base equilibrium, modification of partial pressure of carbon dioxide and bicarbonate concentration, and the control of blood pressure and fluid homeostasis all closely depend on renal and pulmonary activities. These interactions begin in fetal age and are often responsible for the genesis and progression of diseases. In gestational age, urine is a fundamental component of the amniotic fluid, acting on pulmonary maturation and growth. Moreover, in the first trimester of pregnancy, kidney is the main source of proline, contributing to collagen synthesis and lung parenchyma maturation. Pathologically speaking, the kidneys could become damaged by mediators of inflammation or immuno-mediated factors related to a primary lung pathology or, on the contrary, it could be the renal disease that determines a consecutive pulmonary damage. Furthermore, non immunological mechanisms are frequently involved in renal and pulmonary diseases, as observed in chronic pathologies such as sleep apnea syndrome, pulmonary hypertension, progressive renal disease and hemodialysis. Kidney damage has also been related to mechanical ventilation. The aim of this review is to describe pulmonary-renal interactions and their related pathologies, underscoring the need for a close collaboration between intensivists, pneumologists and nephrologists. PMID:26940339

  20. Hyperoxic Acute Lung Injury

    PubMed Central

    Kallet, Richard H; Matthay, Michael A

    2013-01-01

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

  1. Lung Disease

    MedlinePlus

    ... and taking birth control pills or menopausal hormone therapy . Pulmonary emboli can affect blood flow in the lungs and can reduce oxygen flow into the blood. Very large emboli can cause sudden death. Pulmonary hypertension. This is high blood pressure in the arteries that bring blood ...

  2. Particles causing lung disease.

    PubMed Central

    Kilburn, K H

    1984-01-01

    The lung has a limited number of patterns of reaction to inhaled particles. The disease observed depends upon the location: conducting airways, terminal bronchioles and alveoli, and upon the nature of inflammation induced: acute, subacute or chronic. Many different agents cause narrowing of conducting airways (asthma) and some of these cause permanent distortion or obliteration of airways as well. Terminal bronchioles appear to be particularly susceptible to particles which cause goblet cell metaplasia, mucous plugging and ultimately peribronchiolar fibrosis. Cancer is the last outcome at the bronchial level and appears to depend upon continuous exposure to or retention of an agent in the airway and failure of the affected cells to be exfoliated which may be due to squamous metaplasia. Alveoli are populated by endothelial cells, Type I or pavement epithelial cells and metabolically active cuboidal Type II cells that produce the lungs specific surfactant, dipalmytol lecithin. Disturbances of surfactant lead to edema in distal lung while laryngeal edema due to anaphylaxis or fumes may produce asphyxia. Physical retention of indigestible particles or retention by immune memory responses may provoke hyaline membranes, stimulate alveolar lipoproteinosis and finally fibrosis. This later exuberant deposition of connective tissue has been best studied in the occupational pneumoconioses especially silicosis and asbestosis. In contrast emphysema a catabolic response, appears frequently to result from leakage or release of lysosomal proteases into the lung during processing of cigarette smoke particles. The insidious and probably most important human lung disease due to particles is bronchiolar obstruction and obliteration, producing progressive impairment of air flow. The responsible particle is the complex combination of poorly digestive lipids and complex carbohydrates with active chemicals which we call cigarette smoke. More research is needed to perfect, correct and quantify our preliminary picture of the pathogenesis of lung disease by particles, but a useful start has been made. Images FIGURE 1. PMID:6376114

  3. Resolution of Acute Inflammation In The Lung

    PubMed Central

    Levy, Bruce D.; Serhan, Charles N.

    2015-01-01

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

  4. Lung Diseases

    MedlinePlus

    ... on Carcinogens: Captafol A Human Health Perspective on Climate Change (Full Report) (4MB) Certain Glass Wool Fibers (Inhalable) ( ... Environmental Public Health (PEPH) (1MB) Programs and Initiatives: Climate Change and Human Health Respiratory Disease and the Environment ( ...

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

    PubMed Central

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

    2014-01-01

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

  6. Interstitial Lung Diseases

    MedlinePlus

    ... to get enough oxygen. The scarring is called pulmonary fibrosis. Breathing in dust or other particles in the air is responsible for some types of interstitial lung diseases. Specific types include Black lung disease among ...

  7. Lung ultrasonography as a direct measure of evolving respiratory dysfunction and disease severity in patients with acute pancreatitis

    PubMed Central

    Skouras, Christos; Davis, Zoe A.; Sharkey, Joanne; Parks, Rowan W.; Garden, O. James; Murchison, John T.; Mole, Damian J.

    2015-01-01

    Background The value of lung ultrasonography in the diagnosis of respiratory dysfunction and severity stratification in patients with acute pancreatitis (AP) was investigated. Methods Over a 3-month period, 41 patients (median age: 59.1 years; 21 males) presenting with a diagnosis of potential AP were prospectively recruited. Each participant underwent lung ultrasonography and the number of comet tails was linked with contemporaneous clinical data. Group comparisons, areas under the curve (AUC) and respective measures of diagnostic accuracy were investigated. Results A greater number of comet tails were evident in patients with respiratory dysfunction (P = 0.021), those with severe disease (P < 0.001) and when contemporaneous and maximum CRP exceeded 100 mg/L (P = 0.048 and P = 0.003 respectively). Receiver-operator characteristic plot area under the curve (AUC) was greater when examining upper lung quadrants, using respiratory dysfunction and AP severity as variables of interest (AUC = 0.783, 95% C.I.: 0.544–0.962, and AUC = 0.996, 95% C.I.: 0.982–1.000, respectively). Examining all lung quadrants except for the lower lateral resulted in greater AUCs for contemporaneous and maximum CRP (AUC = 0.708, 95% C.I.: 0.510–0.883, and AUC = 0.800, 95% C.I.: 0.640–0.929). Discussion Ultrasonography of non-dependent lung parenchyma can reliably detect evolving respiratory dysfunction in AP. This simple bedside technique shows promise as an adjunct to severity stratification. PMID:26902135

  8. Particles causing lung disease

    SciTech Connect

    Kilburn, K.H.

    1984-04-01

    The lung has a limited number of patterns of reaction to inhaled particles. The disease observed depends upon the location: conducting airways, terminal bronchioles and alveoli, and upon the nature of inflammation induced: acute, subacute or chronic. Many different agents cause narrowing of conducting airways (asthma) and some of these cause permanent distortion or obliteration of airways as well. Terminal bronchioles appear to be particularly susceptible to particles which cause goblet cell metaplasia, mucous plugging and ultimately peribronchiolar fibrosis. Cancer is the last outcome at the bronchial level and appears to depend upon continuous exposure to or retention of an agent in the airway and failure of the affected cells to be exfoliated which may be due to squamous metaplasia. Alveoli are populated by endothelial cells, Type I or pavement epithelial cells and metabolically active cuboidal Type II cells that produce the lungs specific surfactant, dipalmytol lecithin. Disturbances of surfactant lead to edema in distal lung while laryngeal edema due to anaphylaxis or fumes may produce asphyxia. Physical retention of indigestible particles or retention by immune memory responses may provoke hyaline membranes, stimulate alveolar lipoproteinosis and finally fibrosis. This later exuberant deposition of connective tissue has been best studied in the occupational pneumoconioses especially silicosis and asbestosis. In contrast emphysema a catabolic response appears frequently to result from leakage or release of lysosomal proteases into the lung during processing of cigarette smoke particles. 164 references, 1 figure, 2 tables.

  9. 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 ...

  10. [Granulomatous lung and systemic diseases].

    PubMed

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

    2013-04-01

    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

  11. Lung Disease and Hypertension

    PubMed Central

    Imaizumi, Yuki; Eguchi, Kazuo; Kario, Kazuomi

    2014-01-01

    Chronic obstructive pulmonary disease (COPD) patients are at a high risk of developing cardiovascular diseases. Airflow limitation is a predictor of future risks of hypertension and cardiovascular events. COPD is now understood as a systemic inflammatory disease, with the focus on inflammation of the lungs. An association between inflammation and sympathetic overactivity has also been reported. In this article, we review the association between chronic lung disease and the risks of hypertension, cardiovascular morbidity, the underlying mechanisms, and the therapeutic approach to hypertension and cardiovascular diseases in patients with lung diseases. PMID:26587450

  12. Interstitial lung disease

    MedlinePlus

    ... a known cause. This is called idiopathic ILD. Idiopathic pulmonary fibrosis (IPF) is the most common disease of this ... pressure in the blood vessels of their lungs. Idiopathic pulmonary fibrosis has a poor outlook.

  13. Childhood Interstitial Lung Disease

    MedlinePlus

    ... forms, such as hypersensitivity pneumonitis (noo-mo-NI-tis), immunodeficiency-associated lung disease, and bronchiolitis (brong-ke-o-LI-tis) obliterans. However, research shows that the course and ...

  14. Obesity and Acute Lung Injury

    PubMed Central

    McCallister, Jennifer W.; Adkins, Eric J.; O’Brien, James M.

    2009-01-01

    Synopsis Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) are common indications for intensive care unit (ICU) admission and mechanical ventilation. ALI/ARDS also consumes significant health care resources and is a common cause of death in ICU patients. Obesity produces changes in respiratory system physiology that could affect outcomes for ALI/ARDS patients and their response to treatment. Additionally, the biochemical alterations seen in obese patients, such as increased inflammation and altered metabolism, could affect the risk of developing ALI/ARDS in patients with another risk factor (e.g. sepsis). The few studies which have examined the influence of obesity on the outcomes from ALI/ARDS are inconclusive. Furthermore, observed results could be biased by disparities in provided care. PMID:19700048

  15. NOD-Like Receptors in Lung Diseases

    PubMed Central

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

    2013-01-01

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

  16. Mitochondria in Lung Diseases

    PubMed Central

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

    2014-01-01

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

  17. Heme oxygenase-1 in lung disease.

    PubMed

    Raval, Chintan M; Lee, Patty J

    2010-12-01

    The lungs are a major target for various inflammatory, oxidative, carcinogenic or infectious stressors, which result in a range of lung diseases. Induction of heme oxygenase-1 (HO-1) during acute and chronic lung processes is a crucial defense mechanism. HO-1 catalyzes the degradation of free cellular heme to iron, carbon monoxide (CO) and biliverdin which is eventually converted to bilirubin by biliverdin reductase. In addition to the degradation of free heme, a pro-oxidant, HO-1 exerts anti-oxidant, anti-inflammatory and anti-apoptotic properties via its reaction products. This review summarizes the regulation and protective roles of HO-1 and its reaction products in several in vitro and in vivo lung disease models, including acute lung injury, ischemia-reperfusion (IR)-induced lung injury, cigarette smoke and chronic obstructive pulmonary disease (COPD), pulmonary arterial hypertension (PAH), lung cancer and asthma. The therapeutic applications of HO-1 in the lung as well as potential complications of excessive HO-1 induction are also covered. In summary, the HO-1 system is a powerful endogenous defense strategy with immense therapeutic potential against a range of lung diseases if optimal levels and tissue targeting can be achieved. PMID:20704548

  18. Occupational lung disease. Part 2. Discovering the cause of diffuse parenchymal lung disease.

    PubMed

    Kuschner, Ware G; Stark, Paul

    2003-04-01

    Diffuse parenchymal lung disease (also known as interstitial lung disease) and acute irritant reactions are much less commonly managed by primary care physicians than asthma. Acute irritant reactions are typically readily recognized because of the immediate exposure-response relationship. As with asthma, a diagnosis of diffuse parenchymal lung disease should prompt a careful review of the patient's work history. Findings from history taking and radiography provide most of the data needed to establish a diagnosis of asbestosis or silicosis. A pulmonologist should be consulted about lung disease that eludes diagnosis. In cases in which a link between work and illness is strongly suspected, an occupational medicine specialist may be consulted for assistance with preparing reports for a workers' compensation claim as well as characterizing and quantifying impairment. Various government agencies provide extensive information about specific toxic exposures and occupational lung diseases by telephone and on the World Wide Web. PMID:12718237

  19. Subclinical Interstitial Lung Disease

    PubMed Central

    Doyle, Tracy J.; Hunninghake, Gary M.

    2012-01-01

    The widespread use of high-resolution computed tomography in clinical and research settings has increased the detection of interstitial lung abnormalities (ILA) in asymptomatic and undiagnosed individuals. We reported that in smokers, ILA were present in about 1 of every 12 high-resolution computed tomographic scans; however, the long-term significance of these subclinical changes remains unclear. Studies in families affected with pulmonary fibrosis, smokers with chronic obstructive pulmonary disease, and patients with inflammatory lung disease have shown that asymptomatic and undiagnosed individuals with ILA have reductions in lung volume, functional limitations, increased pulmonary symptoms, histopathologic changes, and molecular profiles similar to those observed in patients with clinically significant interstitial lung disease (ILD). These findings suggest that, in select at-risk populations, ILA may represent early stages of pulmonary fibrosis or subclinical ILD. The growing interest surrounding this topic is motivated by our poor understanding of the inciting events and natural history of ILD, coupled with a lack of effective therapies. In this perspective, we outline past and current research focused on validating radiologic, physiological, and molecular methods to detect subclinical ILD. We discuss the limitations of the available cross-sectional studies and the need for future longitudinal studies to determine the prognostic and therapeutic implications of subclinical ILD in populations at risk of developing clinically significant ILD. PMID:22366047

  20. Reproducibility of the six-minute walk test and Glittre ADL-test in patients hospitalized for acute and exacerbated chronic lung disease

    PubMed Central

    José, Anderson; Dal Corso, Simone

    2015-01-01

    Background: The 6-minute walk test (6MWT) and the Glittre ADL-test (GT) are used to assess functional capacity and exercise tolerance; however, the reproducibility of these tests needs further study in patients with acute lung diseases. Objectives: The aim of this study was to investigate the reproducibility of the 6MWT and GT performed in patients hospitalized for acute and exacerbated chronic lung diseases. Method: 48 h after hospitalization, 81 patients (50 males, age: 52±18 years, FEV1: 58±20% of the predicted value) performed two 6MWTs and two GTs in random order on different days. Results: There was no difference between the first and second 6MWT (median 349 m [284-419] and 363 m [288-432], respectively) (ICC: 0.97; P<0.0001). A difference between the first and second tests was found in GT (median 286 s [220-378] and 244 s [197-323] respectively; P<0.001) (ICC: 0.91; P<0.0001). Conclusion: Although both the 6MWT and GT were reproducible, the best results occurred in the second test, demonstrating a learning effect. These results indicate that at least two tests are necessary to obtain reliable assessments. PMID:26039036

  1. Breathomics in lung disease.

    PubMed

    van der Schee, Marc Philippe; Paff, Tamara; Brinkman, Paul; van Aalderen, Willem Marinus Christiaan; Haarman, Eric Gerardus; Sterk, Peter Jan

    2015-01-01

    Volatile organic compounds (VOCs) are produced by virtually all metabolic processes of the body. As such, they have potential to serve as noninvasive metabolic biomarkers. Since exhaled VOCs are either derived from the respiratory tract itself or have passed the lungs from the circulation, they are candidate biomarkers in the diagnosis and monitoring of pulmonary diseases in particular. Good examples of the possibilities of exhaled volatiles in pulmonary medicine are provided by the potential use of VOCs to discriminate between patients with lung cancer and healthy control subjects and to noninvasively diagnose infectious diseases and the association between VOCs and markers of disease activity that has been established in obstructive lung diseases. Several steps are, however, required prior to implementation of breath-based diagnostics in daily clinical practice. First, VOCs should be studied in the intention-to-diagnose population, because biomarkers are likely to be affected by multiple (comorbid) conditions. Second, breath collection and analysis procedures need to be standardized to allow pooling of data. Finally, apart from probabilistic analysis for diagnostic purposes, detailed examination of the nature of volatile biomarkers not only will improve our understanding of the pathophysiologic origins of these markers and the nature of potential confounders but also can enable the development of sensors that exhibit maximum sensitivity and specificity toward specific applications. By adhering to such an approach, exhaled biomarkers can be validated in the diagnosis, monitoring, and treatment of patients in pulmonary medicine and contribute to the development of personalized medicine. PMID:25560860

  2. Lung Disease at High Altitude

    PubMed Central

    Stream, JO; Luks, AM; Grissom, CK

    2016-01-01

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

  3. Intravascular laser therapy in different forms of lung diseases

    NASA Astrophysics Data System (ADS)

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

    1993-06-01

    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.

  4. Asbestos-related lung disease

    SciTech Connect

    Westerfield, B.T. )

    1992-06-01

    Asbestos is a versatile fibrous mineral that can cause lung disease and death. Asbestosis, benign pleural disease, lung cancer, and mesothelioma can all result from inhaling asbestos. The history of disease and exposure risks are discussed. The difficult assessment of risk and the long latency period for development of disease demand evaluation and regular surveillance of asbestos-exposed workers.22 references.

  5. Therapeutic lymphangiogenesis ameliorates established acute lung allograft rejection.

    PubMed

    Cui, Ye; Liu, Kaifeng; Monzon-Medina, Maria E; Padera, Robert F; Wang, Hao; George, Gautam; Toprak, Demet; Abdelnour, Elie; D'Agostino, Emmanuel; Goldberg, Hilary J; Perrella, Mark A; Forteza, Rosanna Malbran; Rosas, Ivan O; Visner, Gary; El-Chemaly, Souheil

    2015-11-01

    Lung transplantation is the only viable option for patients suffering from otherwise incurable end-stage pulmonary diseases such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. Despite aggressive immunosuppression, acute rejection of the lung allograft occurs in over half of transplant recipients, and the factors that promote lung acceptance are poorly understood. The contribution of lymphatic vessels to transplant pathophysiology remains controversial, and data that directly address the exact roles of lymphatic vessels in lung allograft function and survival are limited. Here, we have shown that there is a marked decline in the density of lymphatic vessels, accompanied by accumulation of low-MW hyaluronan (HA) in mouse orthotopic allografts undergoing rejection. We found that stimulation of lymphangiogenesis with VEGF-C156S, a mutant form of VEGF-C with selective VEGFR-3 binding, alleviates an established rejection response and improves clearance of HA from the lung allograft. Longitudinal analysis of transbronchial biopsies from human lung transplant recipients demonstrated an association between resolution of acute lung rejection and decreased HA in the graft tissue. Taken together, these results indicate that lymphatic vessel formation after lung transplantation mediates HA drainage and suggest that treatments to stimulate lymphangiogenesis have promise for improving graft outcomes. PMID:26485284

  6. Types of Childhood Interstitial Lung Disease

    MedlinePlus

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

  7. How Is Childhood Interstitial Lung Disease Treated?

    MedlinePlus

    ... the NHLBI on Twitter. How Is Childhood Interstitial Lung Disease Treated? Childhood interstitial lung disease (chILD) is ... prevent acid reflux, which can lead to aspiration. Lung Transplant A lung transplant may be an option ...

  8. Animal models of acute lung injury

    PubMed Central

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

    2008-01-01

    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. PMID:18621912

  9. MicroRNAs: Novel regulatory molecules in acute lung injury/acute respiratory distress syndrome

    PubMed Central

    CAO, YONGMEI; LYU, YI; TANG, JIAHUA; LI, YINGCHUAN

    2016-01-01

    Acute lung injury (ALI) and the more severe acute respiratory distress syndrome (ARDS) are common and complex inflammatory lung diseases. MicroRNAs (miRNAs), a type of non-coding RNA molecule that regulate gene expression at the post-transcriptional level, have emerged as a novel class of gene regulators, which have critical roles in a wide range of human disorders and diseases, including ALI. Certain types of miRNAs are abnormally expressed in response to lung injury. miRNAs can regulate inflammation pathways by targeting specific molecules and modulate immune response in the process of lung injury and repair. The regulation of miRNA can relieve injury response and promote the recovery of ALI/ARDS. Therefore, miRNAs may serve as novel therapeutic targets in ALI/ARDS.

  10. Occupational and environmental lung disease.

    PubMed

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

    2015-06-01

    Occupational and environmental lung disease remains a major cause of respiratory impairment worldwide. Despite regulations, increasing rates of coal worker's pneumoconiosis and progressive massive fibrosis are being reported in the United States. Dust exposures are occurring in new industries, for instance, silica in hydraulic fracking. Nonoccupational environmental lung disease contributes to major respiratory disease, asthma, and COPD. Knowledge of the imaging patterns of occupational and environmental lung disease is critical in diagnosing patients with occult exposures and managing patients with suspected or known exposures. PMID:26024603

  11. Surfactant for Pediatric Acute Lung Injury

    PubMed Central

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

    2008-01-01

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

  12. Diverse macrophage populations mediate acute lung inflammation and resolution

    PubMed Central

    King, Landon S.; D'Alessio, Franco R.

    2014-01-01

    Acute respiratory distress syndrome (ARDS) is a devastating disease with distinct pathological stages. Fundamental to ARDS is the acute onset of lung inflammation as a part of the body's immune response to a variety of local and systemic stimuli. In patients surviving the inflammatory and subsequent fibroproliferative stages, transition from injury to resolution and recovery is an active process dependent on a series of highly coordinated events regulated by the immune system. Experimental animal models of acute lung injury (ALI) reproduce key components of the injury and resolution phases of human ARDS and provide a methodology to explore mechanisms and potential new therapies. Macrophages are essential to innate immunity and host defense, playing a featured role in the lung and alveolar space. Key aspects of their biological response, including differentiation, phenotype, function, and cellular interactions, are determined in large part by the presence, severity, and chronicity of local inflammation. Studies support the importance of macrophages to initiate and maintain the inflammatory response, as well as a determinant of resolution of lung inflammation and repair. We will discuss distinct roles for lung macrophages during early inflammatory and late resolution phases of ARDS using experimental animal models. In addition, each section will highlight human studies that relate to the diverse role of macrophages in initiation and resolution of ALI and ARDS. PMID:24508730

  13. Management of interstitial lung disease associated with connective tissue disease.

    PubMed

    Mathai, Stephen C; Danoff, Sonye K

    2016-01-01

    The lung is a common site of complications of systemic connective tissue disease (CTD), and lung involvement can present in several ways. Interstitial lung disease (ILD) and pulmonary hypertension are the most common lung manifestations in CTD. Although it is generally thought that interstitial lung disease develops later on in CTD it is often the initial presentation ("lung dominant" CTD). ILD can be present in most types of CTD, including rheumatoid arthritis, scleroderma, systemic lupus erythematosus, polymyositis or dermatomyositis, Sjögren's syndrome, and mixed connective tissue disease. Despite similarities in clinical and pathologic presentation, the prognosis and treatment of CTD associated ILD (CTD-ILD) can differ greatly from that of other forms of ILD, such as idiopathic pulmonary fibrosis. Pulmonary hypertension (PH) can present as a primary vasculopathy in pulmonary arterial hypertension or in association with ILD (PH-ILD). Therefore, detailed history, physical examination, targeted serologic testing, and, occasionally, lung biopsy are needed to diagnose CTD-ILD, whereas both non-invasive and invasive assessments of pulmonary hemodynamics are needed to diagnose pulmonary hypertension. Immunosuppression is the mainstay of treatment for ILD, although data from randomized controlled trials (RCTs) to support specific treatments are lacking. Furthermore, treatment strategies vary according to the clinical situation-for example, the treatment of a patient newly diagnosed as having CTD-ILD differs from that of someone with an acute exacerbation of the disease. Immunosuppression is indicated only in select cases of pulmonary arterial hypertension related to CTD; more commonly, selective pulmonary vasodilators are used. For both diseases, comorbidities such as sleep disordered breathing, symptoms of dyspnea, and cough should be evaluated and treated. Lung transplantation should be considered in patients with advanced disease but is not always feasible because of other manifestations of CTD and comorbidities. Clinical trials of novel therapies including immunosuppressive therapies are needed to inform best treatment strategies. PMID:26912511

  14. Dasatinib Reduces Lung Inflammation and Fibrosis in Acute Experimental Silicosis

    PubMed Central

    Cruz, Fernanda Ferreira; Horta, Lucas Felipe Bastos; Maia, Lígia de Albuquerque; Lopes-Pacheco, Miquéias; da Silva, André Benedito; Morales, Marcelo Marco; Gonçalves-de-Albuquerque, Cassiano Felippe; Takiya, Christina Maeda; de Castro-Faria-Neto, Hugo Caire; Rocco, Patricia Rieken Macedo

    2016-01-01

    Silicosis is an occupational lung disease with no effective treatment. We hypothesized that dasatinib, a tyrosine kinase inhibitor, might exhibit therapeutic efficacy in silica-induced pulmonary fibrosis. Silicosis was induced in C57BL/6 mice by a single intratracheal administration of silica particles, whereas the control group received saline. After 14 days, when the disease was already established, animals were randomly assigned to receive DMSO or dasatinib (1 mg/kg) by oral gavage, twice daily, for 14 days. On day 28, lung morphofunction, inflammation, and remodeling were investigated. RAW 264.7 cells (a macrophage cell line) were incubated with silica particles, followed by treatment or not with dasatinib, and evaluated for macrophage polarization. On day 28, dasatinib improved lung mechanics, increased M2 macrophage counts in lung parenchyma and granuloma, and was associated with reduction of fraction area of granuloma, fraction area of collapsed alveoli, protein levels of tumor necrosis factor-α, interleukin-1β, transforming growth factor-β, and reduced neutrophils, M1 macrophages, and collagen fiber content in lung tissue and granuloma in silicotic animals. Additionally, dasatinib reduced expression of iNOS and increased expression of arginase and metalloproteinase-9 in silicotic macrophages. Dasatinib was effective at inducing macrophage polarization toward the M2 phenotype and reducing lung inflammation and fibrosis, thus improving lung mechanics in a murine model of acute silicosis. PMID:26789403

  15. Dasatinib Reduces Lung Inflammation and Fibrosis in Acute Experimental Silicosis.

    PubMed

    Cruz, Fernanda Ferreira; Horta, Lucas Felipe Bastos; Maia, Lgia de Albuquerque; Lopes-Pacheco, Miquias; Silva, Andr Benedito da; Morales, Marcelo Marco; Gonalves-de-Albuquerque, Cassiano Felippe; Takiya, Christina Maeda; de Castro-Faria-Neto, Hugo Caire; Rocco, Patricia Rieken Macedo

    2016-01-01

    Silicosis is an occupational lung disease with no effective treatment. We hypothesized that dasatinib, a tyrosine kinase inhibitor, might exhibit therapeutic efficacy in silica-induced pulmonary fibrosis. Silicosis was induced in C57BL/6 mice by a single intratracheal administration of silica particles, whereas the control group received saline. After 14 days, when the disease was already established, animals were randomly assigned to receive DMSO or dasatinib (1 mg/kg) by oral gavage, twice daily, for 14 days. On day 28, lung morphofunction, inflammation, and remodeling were investigated. RAW 264.7 cells (a macrophage cell line) were incubated with silica particles, followed by treatment or not with dasatinib, and evaluated for macrophage polarization. On day 28, dasatinib improved lung mechanics, increased M2 macrophage counts in lung parenchyma and granuloma, and was associated with reduction of fraction area of granuloma, fraction area of collapsed alveoli, protein levels of tumor necrosis factor-?, interleukin-1?, transforming growth factor-?, and reduced neutrophils, M1 macrophages, and collagen fiber content in lung tissue and granuloma in silicotic animals. Additionally, dasatinib reduced expression of iNOS and increased expression of arginase and metalloproteinase-9 in silicotic macrophages. Dasatinib was effective at inducing macrophage polarization toward the M2 phenotype and reducing lung inflammation and fibrosis, thus improving lung mechanics in a murine model of acute silicosis. PMID:26789403

  16. Flavorings-Related Lung Disease

    MedlinePlus

    ... message, please visit this page: About CDC.gov . Workplace Safety & Health Topics Flavorings-Related Lung Disease Exposures to ... Clothing and Ensembles NIOSH Homepage NIOSH A-Z Workplace Safety & Health Topics Publications and Products Programs Contact NIOSH ...

  17. Acute Respiratory Distress Syndrome: Role of Oleic Acid-Triggered Lung Injury and Inflammation

    PubMed Central

    Gonçalves-de-Albuquerque, Cassiano Felippe; Silva, Adriana Ribeiro; Burth, Patrícia; Castro-Faria, Mauro Velho; Castro-Faria-Neto, Hugo Caire

    2015-01-01

    Lung injury especially acute respiratory distress syndrome (ARDS) can be triggered by diverse stimuli, including fatty acids and microbes. ARDS affects thousands of people worldwide each year, presenting high mortality rate and having an economic impact. One of the hallmarks of lung injury is edema formation with alveoli flooding. Animal models are used to study lung injury. Oleic acid-induced lung injury is a widely used model resembling the human disease. The oleic acid has been linked to metabolic and inflammatory diseases; here we focus on lung injury. Firstly, we briefly discuss ARDS and secondly we address the mechanisms by which oleic acid triggers lung injury and inflammation. PMID:26640323

  18. Agricultural lung diseases.

    PubMed Central

    Kirkhorn, S R; Garry, V F

    2000-01-01

    Agriculture is considered one of the most hazardous occupations. Organic dusts and toxic gases constitute some of the most common and potentially disabling occupational and environmental hazards. The changing patterns of agriculture have paradoxically contributed to both improved working conditions and increased exposure to respiratory hazards. Animal confinement operations with increasing animal density, particularly swine confinement, have contributed significantly to increased intensity and duration of exposure to indoor air toxins. Ongoing research has implicated bacterial endotoxins, fungal spores, and the inherent toxicity of grain dusts as causes of upper and lower airway inflammation and as immunologic agents in both grain and animal production. Animal confinement gases, particularly ammonia and hydrogen sulfide, have been implicated as additional sources of respiratory irritants. It has become evident that a significant percentage of agricultural workers have clinical symptoms associated with long-term exposure to organic dusts and animal confinement gases. Respiratory diseases and syndromes, including hypersensitivity pneumonitis, organic dust toxic syndrome, chronic bronchitis, mucous membrane inflammation syndrome, and asthmalike syndrome, result from ongoing acute and chronic exposures. In this review we focus upon the emerging respiratory health issues in a changing agricultural economic and technologic environment. Environmental and occupational hazards and exposures will be emphasized rather than clinical diagnosis and treatment. Methods of prevention, from both engineering controls and personal respiratory perspectives, are also addressed. PMID:10931789

  19. Scintigraphic perfusion patterns in patients with diffuse lung disease

    SciTech Connect

    Newman, G.E.; Sullivan, D.C.; Gottschalk, A.; Putman, C.E.

    1982-04-01

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

  20. Drug Induced Interstitial Lung Disease

    PubMed Central

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

    2012-01-01

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

  1. Pressure Controlled Ventilation to Induce Acute Lung Injury in Mice

    PubMed Central

    Koeppen, Michael; Eckle, Tobias; Eltzschig, Holger K.

    2011-01-01

    Murine models are extensively used to investigate acute injuries of different organs systems (1-34). Acute lung injury (ALI), which occurs with prolonged mechanical ventilation, contributes to morbidity and mortality of critical illness, and studies on novel genetic or pharmacological targets are areas of intense investigation (1-3, 5, 8, 26, 30, 33-36). ALI is defined by the acute onset of the disease, which leads to non-cardiac pulmonary edema and subsequent impairment of pulmonary gas exchange (36). We have developed a murine model of ALI by using a pressure-controlled ventilation to induce ventilator-induced lung injury (2). For this purpose, C57BL/6 mice are anesthetized and a tracheotomy is performed followed by induction of ALI via mechanical ventilation. Mice are ventilated in a pressure-controlled setting with an inspiratory peak pressure of 45 mbar over 1 - 3 hours. As outcome parameters, pulmonary edema (wet-to-dry ratio), bronchoalveolar fluid albumin content, bronchoalveolar fluid and pulmonary tissue myeloperoxidase content and pulmonary gas exchange are assessed (2). Using this technique we could show that it sufficiently induces acute lung inflammation and can distinguish between different treatment groups or genotypes (1-3, 5). Therefore this technique may be helpful for researchers who pursue molecular mechanisms involved in ALI using a genetic approach in mice with gene-targeted deletion. PMID:21587159

  2. [Lung problems in acute to subacute exposure to medium altitudes].

    PubMed

    Marugg, D

    1995-10-01

    The hypobaric hypoxia of moderate altitude elicits various mechanisms of acute to subacute physiologic adaptations of the healthy lung: First of all it causes a hyperventilation, which increases the diminished arterial pO2. Because of hypoxemia-induced vasoconstriction, pulmonary arterial hypertension develops. The adrenergic stimulation of the cardiac output also increases the pulmonary perfusion. Most likely because of the diminished density of ambient air there is a measurable increase of exspiratory bronchial flow or, respectively, a diminution of the peripheral airway resistance. In higher altitudes, limitation of oxygen-diffusion under physical exertion is observed. The consequences of acute hypobaric hypoxia for diseased lungs depend on preexisting ventilation/perfusion mismatch or diffusion impairment. Arterial hypoxemia and hence also pulmonary arterial hypertension are increased. In the presence of normal chemoreceptor sensitivity (type pink puffer), a hyperventilation, which is often perceived as dyspnea by the patient, is induced. Mostly patients with chronic obstructive pulmonary disease adapt, however, surprisingly well to moderate altitude. Bronchial asthma improves frequently because allergen concentrations are low and air density is diminished. On the other hand, physical exertion in dry and cold ambient air may also elicit acute asthmatic exacerbations. The assessment of moderate altitude tolerance by patients with chronic lung diseases and prophylactic precautions before the ascent are discussed. The only altitude-specific disease of the healthy lung is the so-called high-altitude pulmonary edema. The major pathogenetic factor for its development is an inadequate or overshooting response to hypobaric hypoxia (nonuniform pulmonary arterial vasoconstriction, diminished hypoxic ventilatory drive, retention of fluid, centralization of blood volume and capillary leak). Prophylactic and therapeutic implications are discussed. PMID:7481316

  3. Sleep in patients with restrictive lung disease.

    PubMed

    Won, Christine H J; Kryger, Meir

    2014-09-01

    Restrictive lung disease leads to ventilatory defects and diffusion impairments. These changes may contribute to abnormal nocturnal pathophysiology, including sleep architecture disruption and impaired ventilation and oxygenation. Patients with restrictive lung disease may suffer significant daytime fatigue and dysfunction. Hypercarbia and hypoxemia during sleep may impact progression of lung disease and related symptoms. Little is known about the impact of treatment of sleep disruption on sleep quality and overall prognosis in restrictive lung disease. This review discusses the pathophysiology of sleep and comorbid sleep disorders in restrictive lung diseases including interstitial lung disease, neuromuscular disease, and obesity hypoventilation syndrome. PMID:25156766

  4. Cilia Dysfunction in Lung Disease

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Land, Walter G.

    2013-01-01

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

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

    PubMed

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

    2015-10-01

    The concept of Childhood Interstitial Lung Disease (ChILD) is relatively young. There has been tremendous progress in this field in the last decade. The key advance has been the recognition of interstitial lung diseases that are often distinct and occur mainly in infants. Diagnosis is challenging because the incidence is low and no single center in the world has enough cases to promote experience and clinical skills. This has led to formation of international groups of people interested in the field and the "Children's interstitial and diffuse lung disease research network" (ChILDRN) is one such group which contributed to the progress of this field. Clinically, these disorders overlap with those of other common respiratory disorders. Hence, clinical practice guidelines emphasize the additional role of chest imaging, genetic testing and lung biopsy in the diagnostic evaluation. Genetic testing, in particular, has shown tremendous progress in this field. Being noninvasive, it has the potential to help early recognition in a vast majority. Despite progress, definitive therapeutic modalities are still lacking and supportive care is still the backbone of management in the majority. Early recognition of the definitive diagnosis helps in the management, even if, in a significant number, it helps in avoiding unnecessary therapy. Also discussed in this article, is the pulmonary manifestation of rheumatic diseases in children. The incidence and spectrum of pulmonary involvement in rheumatic conditions vary and can be result of the primary disease or its management or due to an concurrent infection. PMID:26286176

  7. Psychiatric aspects of heart and lung disease in critical care.

    PubMed

    Shapiro, Peter A; Fedoronko, David A; Epstein, Lucy A; Mirasol, Elsa G E; Desai, Chirag V

    2008-10-01

    Psychiatric issues are important in the management of patients with heart and lung disease in acute, intensive, and critical care. Adjustment disorders, anxiety disorders, depression, and delirium, sometimes in association with substance abuse and withdrawal problems, are the most common issues, and may affect risk and prognosis of the associated general medical conditions and management in the acute care setting. In children with lung and heart diseases requiring critical care, appreciation of cognitive and social-psychologic developmental milestones is necessary to provide adequate care. PMID:18929947

  8. Psychiatric aspects of heart and lung disease in critical care.

    PubMed

    Shapiro, Peter A; Fedoronko, David A; Epstein, Lucy A; Mirasol, Elsa G E; Desai, Chirag V

    2011-01-01

    Psychiatric issues are important in the management of patients with heart and lung disease in acute, intensive, and critical care. Adjustment disorders, anxiety disorders, depression, and delirium, sometimes in association with substance abuse and withdrawal problems, are the most common issues, and may affect risk and prognosis of the associated general medical conditions and management in the acute care setting. In children with lung and heart diseases requiring critical care, appreciation of cognitive and social-psychologic developmental milestones is necessary to provide adequate care. PMID:21109214

  9. Critical care in the ED: potentially fatal asthma and acute lung injury syndrome

    PubMed Central

    Hodder, Rick

    2012-01-01

    Emergency department clinicians are frequently called upon to assess, diagnose, and stabilize patients who present with acute respiratory failure. This review describes a rapid initial approach to acute respiratory failure in adults, illustrated by two common examples: (1) an airway diseaseacute potentially fatal asthma, and (2) a pulmonary parenchymal diseaseacute lung injury/acute respiratory distress syndrome. As such patients are usually admitted to hospital, discussion will be focused on those initial management aspects most relevant to the emergency department clinician. PMID:27147862

  10. It's all about sex: gender, lung development and lung disease.

    PubMed

    Carey, Michelle A; Card, Jeffrey W; Voltz, James W; Arbes, Samuel J; Germolec, Dori R; Korach, Kenneth S; Zeldin, Darryl C

    2007-10-01

    Accumulating evidence suggests that gender affects the incidence, susceptibility and severity of several lung diseases. Gender also influences lung development and physiology. Data from both human and animal studies indicate that sex hormones might contribute to disease pathogenesis or serve as protective factors, depending on the disease involved. In this review, the influence of gender and sex hormones on lung development and pathology will be discussed, with specific emphasis on pulmonary fibrosis, asthma and cancer. PMID:17764971

  11. Genetically manipulated mouse models of lung disease: potential and pitfalls

    PubMed Central

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

    2012-01-01

    Gene targeting in mice (transgenic and knockout) has provided investigators with an unparalleled armamentarium in recent decades to dissect the cellular and molecular basis of critical pathophysiological states. Fruitful information has been derived from studies using these genetically engineered mice with significant impact on our understanding, not only of specific biological processes spanning cell proliferation to cell death, but also of critical molecular events involved in the pathogenesis of human disease. This review will focus on the use of gene-targeted mice to study various models of lung disease including airways diseases such as asthma and chronic obstructive pulmonary disease, and parenchymal lung diseases including idiopathic pulmonary fibrosis, pulmonary hypertension, pneumonia, and acute lung injury. We will attempt to review the current technological approaches of generating gene-targeted mice and the enormous dataset derived from these studies, providing a template for lung investigators. PMID:22198907

  12. Alveolar Edema Fluid Clearance and Acute Lung Injury

    PubMed Central

    Berthiaume, Yves; Matthay, Michael A.

    2009-01-01

    Although lung-protective ventilation strategies have substantially reduced mortality of acute lung injury patients there is still a need for new therapies that can further decrease mortality in patients with acute lung injury. Studies of epithelial ion and fluid transport across the distal pulmonary epithelia have provided important new concepts regarding potential new therapies for acute lung injury. Overall, there is convincing evidence that the alveolar epithelium is not only a tight epithelial barrier that resists the movement of edema fluid into the alveoli, but it is also actively involved in the transport of ions and solutes, a process that is essential for edema fluid clearance and the resolution of acute lung injury. The objective of this article is to consider some areas of recent progress in the field of alveolar fluid transport under normal and pathologic conditions. Vectorial ion transport across the alveolar and distal airway epithelia is the primary determinant of alveolar fluid clearance. The general paradigm is that active Na+ and Cl? transport drives net alveolar fluid clearance, as demonstrated in several different species, including the human lung. Although these transport processes can be impaired in severe lung injury, multiple experimental studies suggest that upregulation of Na+ and Cl? transport might be an effective therapy in acute lung injury. We will review mechanisms involved in pharmacological modulation of ion transport in lung injury with a special focus on the use of ?-adrenergic agonists which has generated considerable interest and is a promising therapy for clinical acute lung injury. PMID:17604701

  13. [Lung diseases in pregnancy].

    PubMed

    Biedermann, K J; Kuhn, M

    1999-10-01

    Pulmonary diseases play a particular role during pregnancy. First, the adaptive hyperventilation of the mother implies sufficient pulmonary reserves, and second, and increasing oxygen consumption of the fetus during pregnancy might be compromised by maternal hypoxemia and could be followed by fetal growth retardation and fetal hypoxemia. Asthma bronchiale is the leading pulmonary disease in pregnancy and is not associated with higher risk for pregnancy and fetus when sufficiently threatened. First line medicaments are beta-2-agonists and steroids. Pneumonia however is a serious menace to the pregnant women, especially when not early diagnosed and correctly treated. Respecting the leading germs, macrolids or wide-spectrum penicillins are used. Tuberculosis has no deleterious effect on pregnancy with early diagnosis and treatment, which follows the usual guidelines during pregnancy with isoniacid, rifampicin and ethambutol. Cystic Fibrosis is not a strict contraindication for a pregnancy, especially for mild clinical forms. However, preconceptional counseling and regular clinical controls before and during pregnancy are indispensible. Deep vein thrombosis and pulmonary embolism are more frequent during pregnancy; the search for risk factors, prophylaxis and treatment are essential to avoid these complications. Heparin is the ideal prophylaxis and treatment in pregnancy, while oral anticoagulants should be avoided because of their effect on the fetus. PMID:10549231

  14. Preemptive mechanical ventilation can block progressive acute lung injury

    PubMed Central

    Sadowitz, Benjamin; Jain, Sumeet; Kollisch-Singule, Michaela; Satalin, Joshua; Andrews, Penny; Habashi, Nader; Gatto, Louis A; Nieman, Gary

    2016-01-01

    Mortality from acute respiratory distress syndrome (ARDS) remains unacceptable, approaching 45% in certain high-risk patient populations. Treating fulminant ARDS is currently relegated to supportive care measures only. Thus, the best treatment for ARDS may lie with preventing this syndrome from ever occurring. Clinical studies were examined to determine why ARDS has remained resistant to treatment over the past several decades. In addition, both basic science and clinical studies were examined to determine the impact that early, protective mechanical ventilation may have on preventing the development of ARDS in at-risk patients. Fulminant ARDS is highly resistant to both pharmacologic treatment and methods of mechanical ventilation. However, ARDS is a progressive disease with an early treatment window that can be exploited. In particular, protective mechanical ventilation initiated before the onset of lung injury can prevent the progression to ARDS. Airway pressure release ventilation (APRV) is a novel mechanical ventilation strategy for delivering a protective breath that has been shown to block progressive acute lung injury (ALI) and prevent ALI from progressing to ARDS. ARDS mortality currently remains as high as 45% in some studies. As ARDS is a progressive disease, the key to treatment lies with preventing the disease from ever occurring while it remains subclinical. Early protective mechanical ventilation with APRV appears to offer substantial benefit in this regard and may be the prophylactic treatment of choice for preventing ARDS. PMID:26855896

  15. FXR Protects Lung from Lipopolysaccharide-Induced Acute Injury

    PubMed Central

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

    2012-01-01

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

  16. Exploring lung physiology in health and disease with lung slices

    PubMed Central

    Sanderson, Michael J.

    2011-01-01

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

  17. Interstitial lung disease in children

    PubMed Central

    Kuo, Christin S.; Young, Lisa R.

    2014-01-01

    Purpose of review There has been tremendous progress in the approach to childhood interstitial lung diseases (ILD), with particular recognition that ILD in infants is often distinct from forms that occur in older children and adults. Diagnosis is challenging due to the rarity of ILD and the fact that presenting symptoms of ILD often overlap those of common respiratory disorders. This review summarizes newly published recommendations for diagnosis and management and highlights recent scientific advances in several specific forms of childhood ILD. Recent findings Clinical practice guidelines emphasize the role for chest CT, genetic testing, and lung biopsy in the diagnostic evaluation of children with suspected ILD. Recent studies have better defined the characteristics and molecular understanding of several different forms of ILD, including Neuroendocrine cell Hyperplasia of Infancy (NEHI) and ILD due to mutations in genes affecting surfactant production and metabolism. Despite significant progress, definitive therapies are often lacking. Summary Childhood ILD encompasses a collection of rare, diffuse lung diseases. Timely recognition of children with suspected ILD and initiation of appropriate diagnostic evaluations will facilitate medical management. Systematic approaches to clinical care and further study are needed to improve the outcomes of children with these rare disorders. PMID:24752172

  18. Fatal obstructive lung disease after haploidentical sibling cord blood transplantation.

    PubMed

    Ohnuma, K; Toyoda, Y; Ishida, Y; Honda, K; Nagao, T; Ijiri, R; Tanaka, Y; Goto, K; Hiroki, K; Kigasawa, H; Nishihira, H

    1998-05-01

    We report the case of a patient with fatal obstructive lung disease after an HLA-haploidentical sibling cord blood transplant (CBT), with severe acute GVHD. A 2-year-old girl developed expiratory air trapping gradually with acute and chronic GVHD after CBT for the treatment of ALL. Anti-CMV and immunosuppressive therapy were ineffective, and the patient died of progressive respiratory acidosis. Necropsy of the lung revealed severe bronchiolitis obliterans with cytomegalic inclusion cells in the granulation tissues of the bronchiolitis. Thus, immunologic and GVHD problems can occur even in CBT. PMID:9613788

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

    PubMed Central

    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

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

  20. Prevention of chronic lung disease

    PubMed Central

    Laughon, Matthew M.; Smith, P. Brian; Bose, Carl

    2010-01-01

    Considerable effort has been devoted to the development of strategies to reduce the incidence of chronic lung disease, including use of medications, nutritional therapies, and respiratory care practices. Unfortunately, most of these strategies have not been successful. To date, the only two treatments developed specifically to prevent CLD whose efficacy is supported by evidence from randomized, controlled trials are the parenteral administration of vitamin A and corticosteroids. Two other therapies, the use of caffeine for the treatment of apnea of prematurity and aggressive phototherapy for the treatment of hyperbilirubinemia were evaluated for the improvement of other outcomes and found to reduce CLD. Cohort studies suggest that the use of CPAP as a strategy for avoiding mechanical ventilation might also be beneficial. Other therapies reduce lung injury in animal models but do not appear to reduce CLD in humans. The benefits of the efficacious therapies have been modest, with an absolute risk reduction in the 7–11% range. Further preventive strategies are needed to reduce the burden of this disease. However, each will need to be tested in randomized, controlled trials, and the expectations of new therapies should be modest reductions of the incidence of the disease. PMID:19736053

  1. Interstitial lung diseases in children

    PubMed Central

    2010-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  3. Diffuse Cystic Lung Disease. Part I.

    PubMed

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

    2015-06-15

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

  4. Targeting maladaptive glutathione responses in lung disease

    PubMed Central

    Gould, Neal S.; Day, Brian J

    2010-01-01

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

  5. Mechanisms and mediators of lung injury after acute kidney injury.

    PubMed

    Faubel, Sarah; Edelstein, Charles L

    2016-01-01

    Acute kidney injury (AKI) is a common complication in hospitalized patients, associated with >50% mortality in those in intensive care who require renal replacement therapy. Data suggest that AKI is a systemic disease that adversely affects the immune system and organ function, and in this way contributes to the high mortality observed in affected patients. Data from patients and animal models indicate that AKI adversely affects the lungs. Respiratory complications are common in patients with AKI and include pulmonary oedema, respiratory failure requiring mechanical ventilation, prolonged duration of mechanical ventilation, and prolonged weaning from mechanical ventilation. The development of respiratory failure in patients with AKI greatly increases the risk of death. Data from animal models support the notion that cardiogenic pulmonary oedema (from volume overload) and non-cardiogenic pulmonary oedema (from endothelial injury due to inflammation and apoptosis) can occur in AKI. In this Review we discuss the clinical, epidemiologic, and animal data that provide insights into the mechanisms by which AKI can lead to lung injury and respiratory complications. Elucidation of the mechanisms of lung injury and respiratory complications after AKI is essential to develop effective therapies and reduce the high mortality associated with AKI and respiratory failure. PMID:26434402

  6. Antibiotic treatment for nontuberculous mycobacterial lung disease.

    PubMed

    Kang, Young Ae; Koh, Won-Jung

    2016-05-01

    Pulmonary infections are the most frequent diseases caused by nontuberculous mycobacteria (NTM). Common causative organisms of pulmonary infection are slowly growing mycobacteria including Mycobacterium avium complex and Mycobacterium kansasii, and rapidly growing mycobacteria including Mycobacterium abscessus complex. Clinical concern has been raised over the increasing incidence of NTM lung disease combined with the poor treatment outcomes of these chronic infectious diseases. Since treatment guidelines of the American Thoracic Society/Infectious Disease Society of America were published in 2007 there have been continuous efforts to improve the outcomes of NTM lung disease, albeit slowly and with limitations. Here, we focus on recent advances in the antibiotic treatment of NTM lung disease. PMID:26967761

  7. Sex steroid signaling: implications for lung diseases.

    PubMed

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

    2015-06-01

    There is increasing recognition that sex hormones (estrogen, progesterone, and testosterone) have biological and pathophysiological actions in peripheral, non-reproductive organs, including the lung. Clinically, sex differences in the incidence, morbidity and mortality of lung diseases such as asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, lung cancer and pulmonary hypertension have been noted, although intrinsic sex differences vs. the roles of sex steroids are still not well-understood. Accordingly, it becomes important to ask the following questions: 1) Which sex steroids are involved? 2) How do they affect different components of the lung under normal circumstances? 3) How does sex steroid signaling change in or contribute to lung disease, and in this regard, are sex steroids detrimental or beneficial? As our understanding of sex steroid signaling in the lung improves, it is important to consider whether such information can be used to develop new therapeutic strategies to target lung diseases, perhaps in both sexes or in a sex-specific manner. In this review, we focus on the basics of sex steroid signaling, and the current state of knowledge regarding how they influence structure and function of specific lung components across the life span and in the context of some important lung diseases. We then summarize the potential for sex steroids as useful biomarkers and therapeutic targets in these lung diseases as a basis for future translational research in the area of gender and individualized medicine. PMID:25595323

  8. Chronic exposure to ozone causes restrictive lung disease

    SciTech Connect

    Grose, E.C.; Costa, D.L.; Hatch, G.E.; Miller, F.J.; Graham, J.A.

    1989-01-01

    A chronic study to determine the progression and/or reversibility of ozone-induced lung disease was conducted. Male rats were exposed to a diurnal pattern of ozone (O{sub 3}) for 1 week, 3 weeks, 3 months, 12 months, or 18 months. The occurrence of chronic lung disease was determined by structural and functional endpoints. Structurally, a biphasic response was observed with an initial acute inflammatory response after 1 week of exposure, a reduced acute response after 3 weeks of exposure, and an epithelial and interstitial response observed after 3 months which persisted or increased in intensity up to 18 months of exposure. Functional studies showed a persistence of decreased total lung capacity and residual volumes at 3, 12, and 18 months of exposure, a response indicative of restrictive lung disease. Biochemical changes in antioxidant metabolism were also observed after 12 and 18 months of exposure. Most significant changes were resolved after the clean-air recovery period. The study has shown that chronic exposure to O{sub 3} causes restrictive lung disease as characterized by the development of focal interstitial fibrosis.

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

    PubMed Central

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

    2014-01-01

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

  10. Lung Disease Including Asthma and Adult Vaccination

    MedlinePlus

    ... Vaccine Finder . Lung Disease including Asthma and Adult Vaccination Recommend on Facebook Tweet Share Compartir Vaccines are ... have immunity to this disease Learn about adult vaccination and other health conditions Asplenia Diabetes Type 1 ...

  11. Oxidative stress and lung diseases.

    PubMed

    Maselli, R; Grembiale, R D; Pelaia, G; Cuda, G

    2002-01-01

    Several different lung diseases are characterized by an oxidant/antioxidant imbalance, which is a major cause of cell damage. Oxidative stress activates a complex network of intracellular signal transduction pathways involved in the regulation of transcription factors such as nuclear factor kappa B (NF-kappa B) and activator protein-1 (AP-1). Within this context, a key role is played by mitogen-activated protein kinases (MAPK), which are highly expressed by pulmonary endothelial and airway epithelial cells. By exposing these cell lines to oxidant agents, our group has shown that oxidative stress leads to a significant MAPK activation, which can be effectively inhibited by corticosteroids. We believe that studies such as ours may contribute to further elucidate the molecular events underlying the therapeutic action of these drugs in many respiratory disorders caused by oxidative/proinflammatory pathogenic mechanisms. In addition, our findings may help to unveil new anti-oxidant treatments based on MAPK modulation. PMID:12619379

  12. Neurotrophins in lung health and disease

    PubMed Central

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

    2010-01-01

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

  13. Krypton-81m ventilation scanning: acute respiratory disease

    SciTech Connect

    Lavender, J.P.; Irving, H.; Armstrong, J.D. II

    1981-02-01

    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.

  14. Histopathology of lung disease in the connective tissue diseases.

    PubMed

    Vivero, Marina; Padera, Robert F

    2015-05-01

    The pathologic correlates of interstitial lung disease (ILD) secondary to connective tissue disease (CTD) comprise a diverse group of histologic patterns. Lung biopsies in patients with CTD-associated ILD tend to demonstrate simultaneous involvement of multiple anatomic compartments of the lung. Certain histologic patterns tend to predominate in each defined CTD, and it is possible in many cases to confirm connective tissue-associated lung disease and guide patient management using surgical lung biopsy. This article will cover the pulmonary pathologies seen in rheumatoid arthritis, systemic sclerosis, myositis, systemic lupus erythematosus, Sjögren syndrome, and mixed CTD. PMID:25836637

  15. Acute fibrinous and organising pneumonia: a rare histopathological variant of chemotherapy-induced lung injury.

    PubMed

    Gupta, Arjun; Sen, Shiraj; Naina, Harris

    2016-01-01

    Bleomycin-induced lung injury is the most common chemotherapy-associated lung disease, and is linked with several histopathological patterns. Acute fibrinous and organising pneumonia (AFOP) is a relatively new and rare histological pattern of diffuse lung injury. We report the first known case of bleomycin-induced AFOP. A 36-year-old man with metastatic testicular cancer received three cycles of bleomycin, etoposide and cisplatin, before being transitioned to paclitaxel, ifosfamide and cisplatin. He subsequently presented with exertional dyspnoea, cough and pleuritic chest pain. CT of the chest demonstrated bilateral ground glass opacities with peribronchovascular distribution and pulmonary function tests demonstrated a restrictive pattern of lung disease with impaired diffusion. Transbronchial biopsy revealed intra-alveolar fibrin deposits with organising pneumonia, consisting of intraluminal loose connective tissue consistent with AFOP. The patient received high-dose corticosteroids with symptomatic and radiographic improvement. AFOP should be recognised as a histopathological variant of bleomycin-induced lung injury. PMID:27053543

  16. A Reconsideration of Acute Beryllium Disease

    PubMed Central

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

    2009-01-01

    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 μg/m3, and most were < 10 μg/m3, lower than usually described. In both cases, lung biopsy about 18 months after acute illness revealed noncaseating granulomas. Years after first exposure, the workers left employment because of CBD. Discussion Contrary to common understanding, these cases suggest that ABD and CBD represent a continuum of disease, and both involve hypersensitivity reactions to beryllium. Differences in disease presentation and progression are likely influenced by the solubility of the beryllium compound involved. Relevance to Practice ABD may occur after exposures lower than the high concentrations commonly described. Prudence dictates limitation of further beryllium exposure in both ABD and CBD. PMID:19672405

  17. Acute Werdnig-Hoffmann disease

    PubMed Central

    Pearn, J. H.; Wilson, J.

    1973-01-01

    76 cases of acute Werdnig-Hoffmann disease (acute infantile spinal muscular atrophy) have been reviewed. The cases comprise an unselected consecutive series in which rigid diagnostic criteria have been applied. The natural history of the disease has been investigated. In at least one-third of cases the disease is manifest before or at delivery. All cases have shown delayed milestones by 5 months of age: 95% are dead by 18 months. Cumulative frequency curves for age at onset and age at death figures are presented for use both as prognostic guidelines and as aids in the management of sibs of index cases. Diagnosis, management, and genetic implications are discussed. ImagesFIG. 1 PMID:4712772

  18. Lung VITAL: Rationale, design, and baseline characteristics of an ancillary study evaluating the effects of vitamin D and/or marine omega-3 fatty acid supplements on acute exacerbations of chronic respiratory disease, asthma control, pneumonia and lung function in adults.

    PubMed

    Gold, Diane R; Litonjua, Augusto A; Carey, Vincent J; Manson, JoAnn E; Buring, Julie E; Lee, I-Min; Gordon, David; Walter, Joseph; Friedenberg, Georgina; Hankinson, John L; Copeland, Trisha; Luttmann-Gibson, Heike

    2016-03-01

    Laboratory and observational research studies suggest that vitamin D and marine omega-3 fatty acids may reduce risk for pneumonia, acute exacerbations of respiratory diseases including chronic obstructive lung disease (COPD) or asthma, and decline of lung function, but prevention trials with adequate dosing, adequate power, and adequate time to follow-up are lacking. The ongoing Lung VITAL study is taking advantage of a large clinical trial-the VITamin D and OmegA-3 TriaL (VITAL)-to conduct the first major evaluation of the influences of vitamin D and marine omega-3 fatty acid supplementation on pneumonia risk, respiratory exacerbation episodes, asthma control and lung function in adults. VITAL is a 5-yearU.S.-wide randomized, double-blind, placebo-controlled, 2×2 factorial trial of supplementation with vitamin D3 ([cholecalciferol], 2000IU/day) and marine omega-3 FA (Omacor® fish oil, eicosapentaenoic acid [EPA]+docosahexaenoic acid [DHA], 1g/day) for primary prevention of CVD and cancer among men and women, at baseline aged ≥50 and ≥55, respectively, with 5107 African Americans. In a subset of 1973 participants from 11 urban U.S. centers, lung function is measured before and two years after randomization. Yearly follow-up questionnaires assess incident pneumonia in the entire randomized population, and exacerbations of respiratory disease, asthma control and dyspnea in a subpopulation of 4314 randomized participants enriched, as shown in presentation of baseline characteristics, for respiratory disease, respiratory symptoms, and history of cigarette smoking. Self-reported pneumonia hospitalization will be confirmed by medical record review, and exacerbations will be confirmed by Center for Medicare and Medicaid Services data review. PMID:26784651

  19. Imaging of occupational and environmental lung diseases

    SciTech Connect

    Akira, M.

    2008-03-15

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

  20. Asbestos-induced lung disease.

    PubMed Central

    Brody, A R

    1993-01-01

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

  1. Imaging of Childhood Interstitial Lung Disease

    PubMed Central

    2010-01-01

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

  2. Hypercapnic acidosis attenuates endotoxin-induced acute lung injury.

    PubMed

    Laffey, John G; Honan, Dave; Hopkins, Natalie; Hyvelin, Jean-Marc; Boylan, John F; McLoughlin, Paul

    2004-01-01

    Deliberate induction of prophylactic hypercapnic acidosis protects against lung injury after in vivo ischemia-reperfusion and ventilation-induced lung injury. However, the efficacy of hypercapnic acidosis in sepsis, the commonest cause of clinical acute respiratory distress syndrome, is not known. We investigated whether hypercapnic acidosis--induced by adding CO2 to inspired gas--would be protective against endotoxin-induced lung injury in an in vivo rat model. Prophylactic institution of hypercapnic acidosis (i.e., induction before endotoxin instillation) attenuated the decrement in arterial oxygenation, improved lung compliance, and attenuated alveolar neutrophil infiltration compared with control conditions. Therapeutic institution of hypercapnic acidosis, that is, induction after endotoxin instillation, attenuated the decrement in oxygenation, improved lung compliance, and reduced alveolar neutrophil infiltration and histologic indices of lung injury. Therapeutic hypercapnic acidosis attenuated the endotoxin-induced increase in the higher oxides of nitrogen and nitrosothiols in the lung tissue and epithelial lining fluid. Lung epithelial lining fluid nitrotyrosine concentrations were increased with hypercapnic acidosis. We conclude that hypercapnic acidosis attenuates acute endotoxin-induced lung injury, and is efficacious both prophylactically and therapeutically. The beneficial actions of hypercapnic acidosis were not mediated by inhibition of peroxynitrite-induced nitration within proteins. PMID:12958048

  3. Lung ultrasound-guided management of acute breathlessness during pregnancy.

    PubMed

    Zieleskiewicz, L; Lagier, D; Contargyris, C; Bourgoin, A; Gavage, L; Martin, C; Leone, M

    2013-01-01

    Lung ultrasonography is a standard tool in the intensive care unit and in emergency medicine, but has not been described in the particular setting of the labour ward. During pregnancy, acute respiratory failure and pulmonary oedema are not uncommon life-threatening events. We present two case reports outlining the potential of lung ultrasonography in parturients. In case 1, lung ultrasonography allowed early diagnosis and treatment of acute dyspnoea in a parturient admitted for suspected asthma exacerbation. Lung ultrasonography revealed a 'B-pattern' of vertical lines radiating into the lung tissue, indicating severe pulmonary oedema complicating previously undiagnosed pre-eclampsia. In case 2, a pre-eclamptic patient was managed with combined transthoracic echocardiography and lung ultrasonography. The accuracy of lung ultrasonography in detecting interstitial oedema at a pre-clinical stage allowed adequate fluid resuscitation in this patient who had a high risk of alveolar pulmonary oedema. We believe that these cases strongly support the prospective validation of lung ultrasound for management of lung disorders in pregnant women. PMID:23088788

  4. NMDA Receptor Antagonist Attenuates Bleomycin-Induced Acute Lung Injury

    PubMed Central

    Li, Yang; Liu, Yong; Peng, XiangPing; Liu, Wei; Zhao, FeiYan; Feng, DanDan; Han, JianZhong; Huang, YanHong; Luo, SiWei; Li, Lian; Yue, Shao Jie; Cheng, QingMei; Huang, XiaoTing; Luo, ZiQiang

    2015-01-01

    Background Glutamate is a major neurotransmitter in the central nervous system (CNS). Large amount of glutamate can overstimulate N-methyl-D-aspartate receptor (NMDAR), causing neuronal injury and death. Recently, NMDAR has been reported to be found in the lungs. The aim of this study is to examine the effects of memantine, a NMDAR channel blocker, on bleomycin-induced lung injury mice. Methods C57BL/6 mice were intratracheally injected with bleomycin (BLM) to induce lung injury. Mice were randomized to receive saline, memantine (Me), BLM, BLM plus Me. Lungs and BALF were harvested on day 3 or 7 for further evaluation. Results BLM caused leukocyte infiltration, pulmonary edema and increase in cytokines, and imposed significant oxidative stress (MDA as a marker) in lungs. Memantine significantly mitigated the oxidative stress, lung inflammatory response and acute lung injury caused by BLM. Moreover, activation of NMDAR enhances CD11b expression on neutrophils. Conclusions Memantine mitigates oxidative stress, lung inflammatory response and acute lung injury in BLM challenged mice. PMID:25942563

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

    PubMed Central

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

    2009-01-01

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

  6. Acute lung injury during antithymocyte globulin therapy for aplastic anemia

    PubMed Central

    Goligher, Ewan Christopher; Cserti-Gazdewich, Christine; Balter, Meyer; Gupta, Vikas; Brandwein, Joseph E

    2009-01-01

    The case of a 33-year-old man with aplastic anemia who experienced recurrent episodes of hypoxemia and pulmonary infiltrates during infusions of antithymocyte globulin (ATG) is described. With the use of high-dose corticosteroids, the patient’s original episodes resolved, and were subsequently prevented before additional administrations of ATG. Rare reports of an association between ATG and acute lung injury are found in the literature, but this is the first report of successful steroid-supported re-exposure. Although the mechanism of ATG-related acute lung injury remains uncertain, it may be parallel to the mechanism of transfusion-related acute lung injury because the pathogenesis of the latter relies, in part, on antileukocyte antibodies. ATG-related toxicity should be included in the differential diagnosis of new, infusion-associated pulmonary infiltrates, and corticosteroids may be a useful therapeutic consideration in the management. PMID:19399304

  7. Autophagy and Obesity-Related Lung Disease.

    PubMed

    Pabon, Maria A; Ma, Kevin C; Choi, Augustine M K

    2016-05-01

    Obesity-related disease is a significant source of premature death and economic burden globally. It is also a common comorbidity in patients suffering from lung disease, affecting both severity and treatment success. However, this complex association between obesity and the lung is poorly understood. Autophagy is a self-recycling homeostatic process that has been linked to beneficial or deleterious effects, depending on the specific lung disease. Obesity affects autophagy in a tissue-specific manner, activating autophagy in adipocytes and impairing autophagy in hepatocytes, immune cells, and pancreatic β-cells, among others. Obesity is also characterized by chronic low-grade inflammation that can be modulated by the pro- and antiinflammatory effects of the autophagic machinery. Scant evidence exists regarding the impact of autophagy in obesity-related lung diseases, but there are communal pathways that could be related to disease pathogenesis. Important signaling molecules in obesity, including IL-17, leptin, adiponectin, NLRP3 inflammasome, and TLR-4, have been implicated in the pathogenesis of lung disease. These mediators are known to be modulated by autophagy activity. In this perspective, we highlight the recent advances in the understanding of autophagy in obesity-related conditions, as well as the potential mechanisms that can link autophagy and obesity in the pathogenesis of lung disease. PMID:26900794

  8. What Are Asbestos-Related Lung Diseases?

    MedlinePlus

    ... have asbestos-related lung diseases now because the mineral is no longer widely used. The use of ... in those countries are still exposed to the mineral. Outlook The outlook for people who have asbestos- ...

  9. Aeroparticles, Composition, and Lung Diseases

    PubMed Central

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

    2016-01-01

    Urban air pollution is a serious worldwide problem due to its impact on human health. In the past 60 years, growing evidence established a correlation between exposure to air pollutants and the developing of severe respiratory diseases. Recently particulate matter (PM) is drawing more public attention to various aspects including historical backgrounds, physicochemical characteristics, and its pathological role. Therefore, this review is focused on these aspects. The most famous air pollution disaster happened in London on December 1952; it has been calculated that more than 4,000 deaths occurred during this event. Air pollution is a complex mix of gases and particles. Gaseous pollutants disseminate deeply into the alveoli, allowing its diffusion through the blood–air barrier to several organs. Meanwhile, PM is a mix of solid or liquid particles suspended in the air. PM is deposited at different levels of the respiratory tract, depending on its size: coarse particles (PM10) in upper airways and fine particles (PM2.5) can be accumulated in the lung parenchyma, inducing several respiratory diseases. Additionally to size, the composition of PM has been associated with different toxicological outcomes on clinical and epidemiological, as well as in vivo and in vitro animal and human studies. PM can be constituted by organic, inorganic, and biological compounds. All these compounds are capable of modifying several biological activities, including alterations in cytokine production, coagulation factors balance, pulmonary function, respiratory symptoms, and cardiac function. It can also generate different modifications during its passage through the airways, like inflammatory cells recruitment, with the release of cytokines and reactive oxygen species (ROS). These inflammatory mediators can activate different pathways, such as MAP kinases, NF-κB, and Stat-1, or induce DNA adducts. All these alterations can mediate obstructive or restrictive respiratory diseases like asthma, COPD, pulmonary fibrosis, and even cancer. In 2013, outdoor air pollution was classified as Group 1 by IARC based on all research studies data about air pollution effects. Therefore, it is important to understand how PM composition can generate several pulmonary pathologies. PMID:26834745

  10. Aeroparticles, Composition, and Lung Diseases.

    PubMed

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

    2016-01-01

    Urban air pollution is a serious worldwide problem due to its impact on human health. In the past 60 years, growing evidence established a correlation between exposure to air pollutants and the developing of severe respiratory diseases. Recently particulate matter (PM) is drawing more public attention to various aspects including historical backgrounds, physicochemical characteristics, and its pathological role. Therefore, this review is focused on these aspects. The most famous air pollution disaster happened in London on December 1952; it has been calculated that more than 4,000 deaths occurred during this event. Air pollution is a complex mix of gases and particles. Gaseous pollutants disseminate deeply into the alveoli, allowing its diffusion through the blood-air barrier to several organs. Meanwhile, PM is a mix of solid or liquid particles suspended in the air. PM is deposited at different levels of the respiratory tract, depending on its size: coarse particles (PM10) in upper airways and fine particles (PM2.5) can be accumulated in the lung parenchyma, inducing several respiratory diseases. Additionally to size, the composition of PM has been associated with different toxicological outcomes on clinical and epidemiological, as well as in vivo and in vitro animal and human studies. PM can be constituted by organic, inorganic, and biological compounds. All these compounds are capable of modifying several biological activities, including alterations in cytokine production, coagulation factors balance, pulmonary function, respiratory symptoms, and cardiac function. It can also generate different modifications during its passage through the airways, like inflammatory cells recruitment, with the release of cytokines and reactive oxygen species (ROS). These inflammatory mediators can activate different pathways, such as MAP kinases, NF-κB, and Stat-1, or induce DNA adducts. All these alterations can mediate obstructive or restrictive respiratory diseases like asthma, COPD, pulmonary fibrosis, and even cancer. In 2013, outdoor air pollution was classified as Group 1 by IARC based on all research studies data about air pollution effects. Therefore, it is important to understand how PM composition can generate several pulmonary pathologies. PMID:26834745

  11. Autotaxin and Endotoxin-Induced Acute Lung Injury

    PubMed Central

    Oikonomou, Nikos; Katsifa, Aggeliki; Prestwich, Glenn D.; Kaffe, Eleanna; Aidinis, Vassilis

    2015-01-01

    Acute Lung Injury (ALI) is a life-threatening, diffuse heterogeneous lung injury characterized by acute onset, pulmonary edema and respiratory failure. Lipopolysaccharide (LPS) is a common cause of both direct and indirect lung injury and when administered to a mouse induces a lung phenotype exhibiting some of the clinical characteristics of human ALI. Here, we report that LPS inhalation in mice results in increased bronchoalveolar lavage fluid (BALF) levels of Autotaxin (ATX, Enpp2), a lysophospholipase D largely responsible for the conversion of lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA) in biological fluids and chronically inflamed sites. In agreement, gradual increases were also detected in BALF LPA levels, following inflammation and pulmonary edema. However, genetic or pharmacologic targeting of ATX had minor effects in ALI severity, suggesting no major involvement of the ATX/LPA axis in acute inflammation. Moreover, systemic, chronic exposure to increased ATX/LPA levels was shown to predispose to and/or to promote acute inflammation and ALI unlike chronic inflammatory pathophysiological situations, further suggesting a differential involvement of the ATX/LPA axis in acute versus chronic pulmonary inflammation. PMID:26196781

  12. Preclinical lung disease in early rheumatoid arthritis.

    PubMed

    Robles-Perez, Alejandro; Luburich, Patricio; Rodriguez-Sanchon, Benigno; Dorca, Jordi; Nolla, Joan Miquel; Molina-Molina, Maria; Narvaez-Garcia, Javier

    2016-02-01

    Early detection and treatment of lung disease in patients with rheumatoid arthritis (RA) may ameliorate disease progression. The objectives of this study were to investigate the frequency of asymptomatic lung abnormalities in early RA patients and the potential association of positive RA blood reactive biomolecules with lung involvement. A prospective observational study was performed in a cohort of patients with early RA (joint symptoms < 2 years) without respiratory symptoms, who were included in a screening program for lung disease with a baseline chest radiograph (CR) and complete pulmonary function tests (PFTs). In those patients with lung abnormalities on the CR or PFTs, a high-resolution chest computed tomography scan (HRCT) was performed. We included 40 patients (30 women). Altered PFTs were detected in 18 (45%) of these patients. These cases had a diffusion lung transfer capacity of carbon monoxide (DLCO) of <80% of predicted, without a significant reduction in the forced vital capacity. The HRCT detected abnormalities in 11 of the 18 patients. Diffuse bronchiectasis was the main finding. An inverse correlation between the anti-citrullinated peptide antibody (ACPA) levels and DLCO was found. Asymptomatic lung disease is present in up to 45% of early RA patients and can be determined by PFTs and ACPA levels. PMID:26846584

  13. Aggressive and acute periodontal diseases.

    PubMed

    Albandar, Jasim M

    2014-06-01

    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

  14. Resolvin D1 protects against inflammation in experimental acute pancreatitis and associated lung injury.

    PubMed

    Liu, Yong; Zhou, Dan; Long, Fei-Wu; Chen, Ke-Ling; Yang, Hong-Wei; Lv, Zhao-Yin; Zhou, Bin; Peng, Zhi-Hai; Sun, Xiao-Feng; Li, Yuan; Zhou, Zong-Guang

    2016-03-01

    Acute pancreatitis is an inflammatory condition that may lead to multisystemic organ failure with considerable mortality. Recently, resolvin D1 (RvD1) as an endogenous anti-inflammatory lipid mediator has been confirmed to protect against many inflammatory diseases. This study was designed to investigate the effects of RvD1 in acute pancreatitis and associated lung injury. Acute pancreatitis varying from mild to severe was induced by cerulein or cerulein combined with LPS, respectively. Mice were pretreated with RvD1 at a dose of 300 ng/mouse 30 min before the first injection of cerulein. Severity of AP was assessed by biochemical markers and histology. Serum cytokines and myeloperoxidase (MPO) levels in pancreas and lung were determined for assessing the extent of inflammatory response. NF-κB activation was determined by Western blotting. The injection of cerulein or cerulein combined with LPS resulted in local injury in the pancreas and corresponding systemic inflammatory changes with pronounced severity in the cerulein and LPS group. Pretreated RvD1 significantly reduced the degree of amylase, lipase, TNF-α, and IL-6 serum levels; the MPO activities in the pancreas and the lungs; the pancreatic NF-κB activation; and the severity of pancreatic injury and associated lung injury, especially in the severe acute pancreatitis model. These results suggest that RvD1 is capable of improving injury of pancreas and lung and exerting anti-inflammatory effects through the inhibition of NF-κB activation in experimental acute pancreatitis, with more notable protective effect in severe acute pancreatitis. These findings indicate that RvD1 may constitute a novel therapeutic strategy in the management of severe acute pancreatitis. PMID:26702138

  15. Acute lung injury: functional genomics and genetic susceptibility.

    PubMed

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

    2002-03-01

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

  16. [Diagnosis and treatment of acute abscesses of the lungs].

    PubMed

    Lamm, Ia E; Abisheva, A B; Kozachenko, N V; Tsaplina, I E

    1988-06-01

    Under study were results of clinical, immunological and bacteriological examinations of 130 patients with acute abscesses of the lungs. The complex treatment included antibacterial therapy taking into account the antibiotic sensitivity of the microflora, correction of disturbances of the protein and water-salt metabolism, desintoxication measures, immunotherapy and sanitation of purulent cavities and the tracheobronchial tree. PMID:3222852

  17. Sodium thiosulfate attenuates acute lung injury in mice

    PubMed Central

    Sakaguchi, Masahiro; Marutani, Eizo; Shin, Hae-sook; Chen, Wei; Hanaoka, Kenjiro; Xian, Ming; Ichinose, Fumito

    2014-01-01

    Background Acute lung injury (ALI) is characterized by neutrophilic inflammation and increased lung permeability. Thiosulfate is a stable metabolite of hydrogen sulfide, a gaseous mediator that exerts anti-inflammatory effects. While sodium thiosulfate (STS) has been used as an antidote, the effect of STS in ALI is unknown. We assessed the effects of STS in mice lung and vascular endothelial cells subjected to acute inflammation. Methods Lung injury was assessed in mice challenged with intratracheal lipopolysaccharide or subjected to cecal ligation and puncture with or without STS. Effects of STS on endothelial permeability, and the production of inflammatory cytokines and reactive oxygen species were examined in cultured endothelial cells incubated with lipopolysaccharide or tumor necrosis factor alpha (TNFα). Levels of sulfide and sulfane sulfur were measured using novel fluorescence probes. Results STS inhibited lipopolysaccharide-induced production of cytokines (Interleukin-6 (pg/ml); 313±164, lipopolysaccharide; 79±27, lipopolysaccharide + STS (n=10)), lung permeability, histological lung injury, and nuclear factor-κB activation in the lung. STS also prevented upregulation of Interleukin-6 in the mouse lung subjected to cecal ligation and puncture. In endothelial cells, STS increased intracellular levels of sulfide and sulfane sulfur, inhibited lipopolysaccharide or TNFα-induced production of cytokines and reactive oxygen species. The beneficial effects of STS were associated with attenuation of the lipopolysaccharide-induced nuclear factor-κB activation through the inhibition of TNF receptor-associated factor 6 ubiquitination. Conclusions STS exerts robust anti-inflammatory effects in mice lung and vascular endothelium. Our results suggest a therapeutic potential of STS in ALI. PMID:25260144

  18. Rheumatoid disease resembling lung neoplasia.

    PubMed

    García-Vicuña, R; Díaz-González, F; Castañeda, S; Arranz, M; López-Bote, J P

    1990-12-01

    We describe a 67-year-old man with severe rheumatoid arthritis of long duration. He developed a peculiar extraarticular rheumatoid complication consisting of localized lung consolidation with a pathological costal fracture, together with an abrupt systemic reaction that occurred in the course of immunosuppressive treatment. The diagnosis first proposed was lung cancer with costal metastases. However exhaustive studies performed in the search of malignancy were systematically negative and pathologic studies finally demonstrated bronchiolitis obliterans with organizing pneumonia (BOOP) as responsible for parenchymal lung consolidation with a rheumatoid nodule eroding bone at the level of the rib fracture. These findings, after long followup of the patient, attest to the rheumatoid origin of his bizarre manifestations and definitely rule out a neoplastic etiology. PMID:2084246

  19. Timolol-induced interstitial lung disease

    PubMed Central

    Patel, Hetain; Wilches, Lina Vanessa; Guerrero, Jorge

    2015-01-01

    Timolol maleate is a non-selective beta-adrenergic receptor blocking agent with demonstrated efficacy in the treatment of open-angle glaucoma. A 76 year old female who presented with productive cough, progressive dyspnea and hypoxia after starting timolol maleate opthalamic drops following glaucoma surgery. The patient was diagnosed with interstitial lung disease secondary to timolol treatment and after cessation of the offending agent along with corticosteroid treatment, symptoms improved drastically. Elimination of other possible causes of disease along with evolution of radiological and functional signs left us with a diagnosis of timolol-induced interstitial lung disease. To our knowledge, this is the second reported case of timolol-induced interstitial lung disease. PMID:26236595

  20. Racial and Ethnic Disparities in Mortality from Acute Lung Injury

    PubMed Central

    Erickson, Sara E.; Shlipak, Michael G.; Martin, Greg S.; Wheeler, Arthur P.; Ancukiewicz, Marek; Matthay, Michael A.; Eisner, Mark D.

    2009-01-01

    Objective: Little is known about the influence of race and ethnicity on mortality from acute lung injury. We sought to determine whether black race or Hispanic ethnicity are independently associated with mortality among patients with acute lung injury. Design: Retrospective cohort study of patients enrolled in the Acute Respiratory Distress Syndrome (ARDS) Network randomized controlled trials. Setting: Adult intensive care units participating in the ARDS Network trials. Patients: 2362 mechanically ventilated patients (1,715 white, 449 black and 198 Hispanic) with acute lung injury. Measurements and Main Results: The primary outcome was 60-day mortality. A secondary outcome was number of ventilator-free days. Crude mortality was 33% for both blacks and Hispanics compared with 27% for whites (p=0.02). After adjusting for demographic and clinical covariates, the association between race/ethnicity and mortality persisted (OR = 1.42; 95% CI 1.10-1.84 for blacks; OR=1.94; 95% CI, 1.36-2.77 for Hispanics; OR=1 for whites, reference). After adjustment for severity of illness (Acute Physiology Score), black race was no longer significantly associated with mortality (OR =1.25; 95% CI, 0.95-1.66), whereas the association with Hispanic ethnicity persisted (OR=2.00; 95% CI, 1.37-2.90). Hispanics had significantly fewer ventilator-free days compared with whites after adjustment for demographic and clinical covariates (mean difference in days = -2.3; 95% CI -3.9 to -0.7). Conclusions: Black and Hispanic patients with acute lung injury have a significantly higher risk of death compared to white patients. This increased risk appeared to be mediated by increased severity of illness at presentation for blacks, but was unexplained among Hispanics. PMID:19050621

  1. The bacterial microbiota in inflammatory lung diseases.

    PubMed

    Huffnagle, Gary B; Dickson, Robert P

    2015-08-01

    Numerous lines of evidence, ranging from recent studies back to those in the 1920s, have demonstrated that the lungs are NOT bacteria-free during health. We have recently proposed that the entire respiratory tract should be considered a single ecosystem extending from the nasal and oral cavities to the alveoli, which includes gradients and niches that modulate microbiome dispersion, retention, survival and proliferation. Bacterial exposure and colonization of the lungs during health is most likely constant and transient, respectively. Host microanatomy, cell biology and innate defenses are altered during chronic lung disease, which in turn, alters the dynamics of bacterial turnover in the lungs and can lead to longer term bacterial colonization, as well as blooms of well-recognized respiratory bacterial pathogens. A few new respiratory colonizers have been identified by culture-independent methods, such as Pseudomonas fluorescens; however, the role of these bacteria in respiratory disease remains to be determined. PMID:26122174

  2. Lung cancer and chronic obstructive pulmonary disease.

    PubMed

    Petty, T L

    1997-06-01

    The application of current knowledge and technology could dramatically improve the survival rate in both lung cancer and COPD, even before physicians and other health workers are finally able to convince the population that both personal and environmental tobacco smoke must be eliminated to begin to reduce the premature morbidity and mortality from lung cancer, airflow obstruction, and other smoking-related diseases such as heart attack and stroke. PMID:9209909

  3. Lung cancer and chronic obstructive pulmonary disease.

    PubMed

    Petty, T L

    1996-05-01

    The application of current knowledge and technology could dramatically improve the survival rate in both lung cancer and COPD, even before physicians and other health workers are finally able to convince the population that both personal and environmental smoke must be eliminated to begin to reduce the premature morbidity and mortality from lung cancer, airflow obstruction, and other smoking-related diseases such as heart attack and stroke. PMID:8637308

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

    PubMed Central

    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.

    2012-01-01

    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

  5. Focus on acute diarrhoeal disease

    PubMed Central

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

    2009-01-01

    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

  6. Acute Lung Function Response to Dust in Street Sweepers

    PubMed Central

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

    2013-01-01

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

  7. Science review: Searching for gene candidates in acute lung injury

    PubMed Central

    Grigoryev, Dmitry N; Finigan, James H; Hassoun, Paul; Garcia, Joe GN

    2004-01-01

    Acute lung injury (ALI) is a complex and devastating illness, often occurring within the setting of sepsis, and carries an annual mortality rate of 30–50%. Although the genetic basis of ALI has not been fully established, an increasing body of evidence suggests that genetic predisposition contributes to disease susceptibility and severity. Significant difficulty exists, however, in defining the exact nature of these genetic factors, including large phenotypic variance, incomplete penetrance, complex gene–environment interactions, and strong potential for locus heterogeneity. We utilized the candidate gene approach and an ortholog gene database to provide relevant gene ontologies and insights into the genetic basis of ALI. We employed a Medline search of selected basic and clinical studies in the English literature and studies sponsored by the HopGene National Institutes of Health sponsored Program in Genomic Applications. Extensive gene expression profiling studies in animal models of ALI (rat, murine, canine), as well as in humans, were performed to identify potential candidate genes . We identified a number of candidate genes for ALI, with blood coagulation and inflammation gene ontologies being the most highly represented. The candidate gene approach coupled with extensive gene profiling and novel bioinformatics approaches is a valuable way to identify genes that are involved in ALI. PMID:15566614

  8. Platelet-derived Wnt antagonist Dickkopf-1 is implicated in ICAM-1/VCAM-1-mediated neutrophilic acute lung inflammation.

    PubMed

    Guo, Yujie; Mishra, Amarjit; Howland, Emily; Zhao, Chunling; Shukla, Dhananjay; Weng, Tingting; Liu, Lin

    2015-11-01

    Neutrophil infiltration represents the early acute inflammatory response in acute lung injury. The recruitment of neutrophils from the peripheral blood across the endothelial-epithelial barrier into the alveolar airspace is highly regulated by the adhesion molecules on alveolar epithelial cells (AECs). Wnt/?-catenin signaling is involved in the progression of inflammatory lung diseases including asthma, emphysema, and pulmonary fibrosis. However, the function of Wnt/?-catenin signaling in acute lung inflammation is unknown. Here, we identified platelet-derived Dickkopf-1 (Dkk1) as the major Wnt antagonist contributing to the suppression of Wnt/?-catenin signaling in AECs during acute lung inflammation. Intratracheal administration of Wnt3a or an antibody capable of neutralizing Dkk1 inhibited neutrophil influx into the alveolar airspace of injured lungs. Activation of Wnt/?-catenin signaling in AECs attenuated intercellular adhesion molecule 1 (ICAM-1)/vascular cell adhesion molecule 1 (VCAM-1)-mediated adhesion of both macrophages and neutrophils to AECs. Our results suggest a role for Wnt/?-catenin signaling in modulating the inflammatory response, and a functional communication between platelets and AECs during acute lung inflammation. Targeting Wnt/?-catenin signaling and the communication between platelets and AECs therefore represents potential therapeutic strategies to limit the damage of acute pulmonary inflammation. PMID:26351298

  9. Lung Postmortem Autopsy Revealing Extramedullary Involvement in Multiple Myeloma Causing Acute Respiratory Distress Syndrome

    PubMed Central

    Ravinet, Aurélie; Perbet, Sébastien; Guièze, Romain; Guérin, Renaud; Gayraud, Guillaume; Aliane, Jugurtha; Tremblay, Aymeric; Pascal, Julien; Ledoux, Albane; Chaleteix, Carine; Dechelotte, Pierre; Bay, Jacques-Olivier; Bazin, Jean-Etienne; Constantin, Jean-Michel

    2014-01-01

    Pulmonary involvement with multiple myeloma is rare. We report the case of a 61-year-old man with past medical history of chronic respiratory failure with emphysema, and a known multiple myeloma (Durie and Salmon stage III B and t(4;14) translocation). Six months after diagnosis and first line of treatment, he presented acute dyspnea with interstitial lung disease. Computed tomography showed severe bullous emphysema and diffuse, patchy, multifocal infiltrations bilaterally with nodular character, small bilateral pleural effusions, mediastinal lymphadenopathy, and a known lytic lesion of the 12th vertebra. He was treated with piperacillin-tazobactam, amikacin, oseltamivir, and methylprednisolone. Finally, outcome was unfavourable. Postmortem analysis revealed diffuse and nodular infracentimetric infiltration of the lung parenchyma by neoplastic plasma cells. Physicians should be aware that acute respiratory distress syndrome not responding to treatment of common causes could be a manifestation of the disease, even with negative BAL or biopsy and could be promptly treated with salvage therapy. PMID:25165587

  10. Acute Aortic Dissection Extending Into the Lung.

    PubMed

    Makdisi, George; Said, Sameh M; Schaff, Hartzell V

    2015-07-01

    The radiologic manifestations of ruptured acute aortic dissection, Stanford type A aortic dissection, DeBakey type 1 can present in different radiographic scenarios with devastating outcomes. Here, we present a rare case of a 70-year-old man who presented to the emergency department with chest pain radiating to the back. A chest computed tomography scan showed a Stanford type A, DeBakey type 1, acute aortic dissection ruptured into the aortopulmonary window and stenosing the pulmonary trunk, both main pulmonary arteries, and dissecting the bronchovascular sheaths and flow into the pulmonary interstitium, causing pulmonary interstitial hemorrhage. The patient underwent emergent ascending aorta replacement with hemiarch replacement with circulatory arrest. The postoperative course was unremarkable. PMID:26140779

  11. Alveolar Epithelial A2B Adenosine Receptors in Pulmonary Protection during Acute Lung Injury.

    PubMed

    Hoegl, Sandra; Brodsky, Kelley S; Blackburn, Michael R; Karmouty-Quintana, Harry; Zwissler, Bernhard; Eltzschig, Holger K

    2015-08-15

    Acute lung injury (ALI) is an acute inflammatory lung disease that causes morbidity and mortality in critically ill patients. However, there are many instances where ALI resolves spontaneously through endogenous pathways that help to control excessive lung inflammation. Previous studies have implicated the extracellular signaling molecule adenosine and signaling events through the A2B adenosine receptor in lung protection. In this context, we hypothesized that tissue-specific expression of the A2B adenosine receptor is responsible for the previously described attenuation of ALI. To address this hypothesis, we exposed mice with tissue-specific deletion of Adora2b to ALI, utilizing a two-hit model where intratracheal LPS treatment is followed by injurious mechanical ventilation. Interestingly, a head-to-head comparison of mice with deletion of Adora2b in the myeloid lineage (Adora2b(loxP/loxP) LysM Cre(+)), endothelial cells (Adora2b(loxP/loxP) VE-cadherin Cre(+)), or alveolar epithelial cells (Adora2b(loxP/loxP) SPC Cre(+)) revealed a selective increase in disease susceptibility in Adora2b(loxP/loxP) SPC Cre(+) mice. More detailed analysis of Adora2b(loxP/loxP) SPC Cre(+) mice confirmed elevated lung inflammation and attenuated alveolar fluid clearance. To directly deliver an A2B adenosine receptor-specific agonist to alveolar epithelial cells, we subsequently performed studies with inhaled BAY 60-6583. Indeed, aerosolized BAY 60-6583 treatment was associated with attenuated pulmonary edema, improved histologic lung injury, and dampened lung inflammation. Collectively, these findings suggest that alveolar epithelial A2B adenosine receptor signaling contributes to lung protection, and they implicate inhaled A2B adenosine receptor agonists in ALI treatment. PMID:26188061

  12. How Are Asbestos-Related Lung Diseases Treated?

    MedlinePlus

    ... the NHLBI on Twitter. How Are Asbestos-Related Lung Diseases Treated? No treatments can reverse the effects ... then draw out the excess fluid. Treatments for Lung Cancer and Mesothelioma If you have lung cancer ...

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

    MedlinePlus

    ... your doctor about lung carcinoid tumors? Treatment of lung carcinoid, by type and extent of disease The ... those that can’t be removed completely Resectable lung carcinoid tumors Resectable carcinoid tumors haven’t spread ...

  14. PRIMING DONOR LUNGS WITH THIOREDOXIN ATTENUATES ACUTE ALLOGRAFT INJURY IN A RAT MODEL OF LUNG TRANSPLANTATION

    PubMed Central

    Hu, Hanbo; Lu, Li; Mu, Wei; Johnson, Richard J.; Block, Edward R.; Patel, Jawaharlal M.

    2008-01-01

    Background Lung graft dysfunction and rejection remain a significant cause of morbidity and mortality in transplant recipients. Thioredoxin-1 (Trx), a redox-regulatory protein, has been known to function as an antioxidant against oxidative injury in multiple organs including lungs. We examined whether priming of the donor lungs with Trx prior to transplantation attenuates acute lung injury. Methods Orthotopic left lung transplantation was performed from Lewis (donor) to Sprague-Dawley (recipient) rats using the cuff technique. For Trx priming, the donor lungs were perfused and stored in Perfadex solution with or without the presence of purified Trx prior to transplantation. Changes in bronchoalveolar (BAL) fluid analysis, allograft oxygen exchange function, nuclear factor kappa B (NF-kB)/DNA binding, myeloperoxidase (MPO) activities, and immunohisotologic evaluation of neutrophils, macrophages and cytotoxic T-cells (CD8+) infiltration were examined in one and/or five day post-transplant allograft (left) and native (right) lungs. Results BAL cell differential analysis showed significant increases in macrophages and neutrophils in one day post-transplant whereas lymphocyte infiltration was significantly increased in both one and five days post transplant allografts. MPO and NF-kB/DNA binding activities were increased over basal activities one and five days post transplant. Immunohistology staining of one and five day post transplant allografts revealed increased infiltration of macrophages, neutrophils, and CD8+ T cell subsets. Priming of donor lungs with Trx prior to transplantation improved O2 exchange and attenuated NF-kB/DNA binding activity and infiltration of macrophages, neutrophils, and CD8+ T cell subsets in one and five day post transplant allografts. Conclusions Priming of donor lungs with Trx prior to transplantation attenuates acute allograft injury in a rat model of lung transplantation. This protection appears to be associated with Trxs antioxidant function that limits early I/R injury, NF-kB activation, and progressive infiltration of inflammatory and immune cells in allografts. PMID:18926407

  15. Transfusion-Related Acute Lung Injured (TRALI): Current Concepts

    PubMed Central

    Álvarez, P; Carrasco, R; Romero-Dapueto, C; Castillo, R.L

    2015-01-01

    Transfusion-related acute lung injury (TRALI) is a life-threatening intervention that develops within 6 hours of transfusion of one or more units of blood, and is an important cause of morbidity and mortality resulting from transfusion. It is necessary to dismiss other causes of acute lung injury (ALI), like sepsis, acute cardiogenic edema, acute respiratory distress syndrome (ARDS) or bacterial infection. There are two mechanisms that lead to the development of this syndrome: immune-mediated and no immune- mediated TRALI. A common theme among the experimental TRALI models is the central importance of neutrophils in mediating the early immune response, and lung vascular injury. Central clinical symptoms are dyspnea, tachypnea, tachycardia, cyanosis and pulmonary secretions, altogether with other hemodynamic alterations, such as hypotension and fever. Complementary to these clinical findings, long-term validated animal models for TRALI should allow the determination of the cellular targets for TRALI-inducing alloantibodies as well as delineation of the underlying pathogenic molecular mechanisms, and key molecular mediators of the pathology. Diagnostic criteria have been established and preventive measures have been implemented. These actions have contributed to the reduction in the overallnumber of fatalities. However, TRALI still remains a clinical problem. Any complication suspected of TRALI should immediately be reported. PMID:26312100

  16. Transfusion-Related Acute Lung Injured (TRALI): Current Concepts.

    PubMed

    Álvarez, P; Carrasco, R; Romero-Dapueto, C; Castillo, R L

    2015-01-01

    Transfusion-related acute lung injury (TRALI) is a life-threatening intervention that develops within 6 hours of transfusion of one or more units of blood, and is an important cause of morbidity and mortality resulting from transfusion. It is necessary to dismiss other causes of acute lung injury (ALI), like sepsis, acute cardiogenic edema, acute respiratory distress syndrome (ARDS) or bacterial infection. There are two mechanisms that lead to the development of this syndrome: immune-mediated and no immune- mediated TRALI. A common theme among the experimental TRALI models is the central importance of neutrophils in mediating the early immune response, and lung vascular injury. Central clinical symptoms are dyspnea, tachypnea, tachycardia, cyanosis and pulmonary secretions, altogether with other hemodynamic alterations, such as hypotension and fever. Complementary to these clinical findings, long-term validated animal models for TRALI should allow the determination of the cellular targets for TRALI-inducing alloantibodies as well as delineation of the underlying pathogenic molecular mechanisms, and key molecular mediators of the pathology. Diagnostic criteria have been established and preventive measures have been implemented. These actions have contributed to the reduction in the overallnumber of fatalities. However, TRALI still remains a clinical problem. Any complication suspected of TRALI should immediately be reported. PMID:26312100

  17. Pulmonary hypertension associated with acute or chronic lung diseases in the preterm and term neonate and infant. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK.

    PubMed

    Hilgendorff, Anne; Apitz, Christian; Bonnet, Damien; Hansmann, Georg

    2016-05-01

    Persistent pulmonary hypertension of the newborn (PPHN) is the most common neonatal form and mostly reversible after a few days with improvement of the underlying pulmonary condition. When pulmonary hypertension (PH) persists despite adequate treatment, the severity of parenchymal lung disease should be assessed by chest CT. Pulmonary vein stenosis may need to be ruled out by cardiac catheterisation and lung biopsy, and genetic workup is necessary when alveolar capillary dysplasia is suspected. In PPHN, optimisation of the cardiopulmonary situation including surfactant therapy should aim for preductal SpO2between 91% and 95% and severe cases without post-tricuspid-unrestrictive shunt may receive prostaglandin E1 to maintain ductal patency in right heart failure. Inhaled nitric oxide is indicated in mechanically ventilated infants to reduce the need for extracorporal membrane oxygenation (ECMO), and sildenafil can be considered when this therapy is not available. ECMO may be indicated according to the ELSO guidelines. In older preterm infant, where PH is mainly associated with bronchopulmonary dysplasia (BPD) or in term infants with developmental lung anomalies such as congenital diaphragmatic hernia or cardiac anomalies, left ventricular diastolic dysfunction/left atrial hypertension or pulmonary vein stenosis, can add to the complexity of the disease. Here, oral or intravenous sildenafil should be considered for PH treatment in BPD, the latter for critically ill patients. Furthermore, prostanoids, mineralcorticoid receptor antagonists, and diuretics can be beneficial. Infants with proven or suspected PH should receive close follow-up, including preductal/postductal SpO2measurements, echocardiography and laboratory work-up including NT-proBNP, guided by clinical improvement or lack thereof. PMID:27053698

  18. [Pathomorphological changes in lungs in acute periods of myocardial infarction].

    PubMed

    Hychka, S H

    2003-01-01

    With the aid of morphological methods of investigation, the structure of the lungs was studied in those deceased persons having been ill with myocardial infarction and also in rats simulated with acute coronary failure. Comparison of results of studies made in autopsy and experimental material has shown that in the lungs occur certain stereotype structural changes which reflect abnormalities of lipid metabolism and manifest itself by fat microembolism of vessels of the microcirculatory bed and by accumulation of unemulsified fats in the interalveolar septa and alveolar lumens. PMID:14618811

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

    PubMed Central

    2014-01-01

    Background Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common cause of morbidity and mortality. Traditional Chinese medicine (TCM) is used to treat AECOPD as adjunctive therapy. This study aimed to evaluate the efficacy and safety of the TCM formula Xuan Bai Cheng Qi as an adjuvant therapy for AECOPD patients with the syndrome type of phlegm-heat obstructing the lungs. Methods A multicenter, randomized, double-blind, placebo-controlled clinical trial was conducted. A total of 244 patients were divided into the intervention group (n = 122, treated with conventional medicine and Xuan Bai Cheng Qi) and the control group (n = 122, treated with conventional medicine and placebo). Total symptom scores (cough, phlegm, wheezing, chest congestion) before treatment and at 3, 5, 7, 10 days post-treatment were recorded. Lung function, arterial blood gas, serum inflammatory cytokines, oxidation/anti-oxidation index were observed before treatment and at the end of the 10-day treatment. Results A total of 242 patients completed the study. The full analysis set (FAS) population was 244 and the per-protocol analysis set (PPS) population was 229. After the 10-day treatment, symptom scores of the Xuan Bai Cheng Qi group were significantly lower over time compared with the control group (FAS: mean difference -1.84, 95% CI -2.66 to -1.03, P < .001; PPS: mean difference -1.87, 95% CI -2.71 to -1.03, P < .001). FEV1, FVC, and FEV1%pred were significantly higher over time in the Xuan Bai Cheng Qi group compared with those in the control group (day 10, FAS and PPS: P < .05). PaO2 and PaCO2 were significantly improved in the Xuan Bai Cheng Qi group (day 10, FAS and PPS: P < .05). Xuan Bai Cheng Qi was also found to ameliorate cytokine levels and oxidation/antioxidant index compared with placebo. There were no differences in safety variables and adverse events between the two groups. Conclusions Xuan Bai Cheng Qi formula appears to be a safe and beneficial treatment for AECOPD of phlegm-heat obstructing the lungs syndrome type. PMID:25014996

  20. Lung Compliance and Chronic Obstructive Pulmonary Disease

    PubMed Central

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

    2012-01-01

    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. PMID:23150821

  1. Epigenetic contributions to the developmental origins of adult lung disease.

    PubMed

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

    2015-04-01

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

  2. Infections in “Noninfectious” Lung Diseases

    PubMed Central

    Sethi, Sanjay; Daley, Charles L.; Ray, Prabir; Beck, James M.; Gingo, Matthew R.

    2014-01-01

    Many chronic pulmonary diseases, including those that are not primarily infectious in etiology, have some aspects of their pathogenesis that are influenced by infectious organisms. Microorganisms may contribute to chronic lung diseases, either directly (i.e., overt infection) or indirectly, via the amplification of inflammatory pathways that are critical to host defense. As techniques for detecting and characterizing microorganisms have advanced, investigations of both infecting and colonizing organisms have yielded new insights into mechanisms of pulmonary disease. In addition, changes in patterns of infection and microbial resistance have important implications for treatment. Examples of these infectious–pulmonary associations, including Haemophilus influenzae infection and chronic obstructive pulmonary disease, nontuberculous mycobacteria and bronchiectasis, and human immunodeficiency virus and obstructive lung disease, are reviewed. PMID:25148428

  3. Diffuse Cystic Lung Diseases: Diagnostic Considerations.

    PubMed

    Xu, Kai-Feng; Feng, Ruie; Cui, Han; Tian, Xinlun; Wang, Hanping; Zhao, Jing; Huang, Hui; Zhang, Weihong; Lo, Bee Hong

    2016-06-01

    Diffuse cystic lung disease (DCLD) is a group of heterogeneous diseases that present as diffuse cystic changes in the lung on computed tomography of the chest. Most DCLD diseases are rare, although they might resemble common diseases such as emphysema and bronchiectasis. Main causes of DCLD include lymphangioleiomyomatosis, Birt-Hogg-Dubé syndrome, pulmonary Langerhans cell histiocytosis, lymphoid interstitial pneumonia, amyloidosis, light-chain deposition disease, Sjögren syndrome, and primary or metastatic neoplasm. We discuss clinical factors that are helpful in the differential diagnosis of DCLDsuch as sex and age, symptoms and signs, extrapulmonary presentations, cigarette smoking, and family history. Investigations for DCLD include high-resolution computed tomography, biochemical and histopathological studies, genetic tests, pulmonary function tests, and bronchoscopic and video-assisted thoracoscopic biopsies. A proposed diagnostic algorithm would enhance ease of diagnosing most cases of DCLD. PMID:27231867

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

    PubMed

    Cruse, Glenn; Bradding, Peter

    2016-05-01

    Mast cells are major effector cells of inflammation and there is strong evidence that mast cells play a significant role in asthma pathophysiology. There is also a growing body of evidence that mast cells contribute to other inflammatory and fibrotic lung diseases such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. This review discusses the role that mast cells play in airway diseases and highlights how mast cell microlocalisation within specific lung compartments and their cellular interactions are likely to be critical for their effector function in disease. PMID:25959386

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

    PubMed

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

    2016-02-01

    This review is devoted to the distinct associations of inflammatory bowel diseases (IBD) and chronic liver disorders with chronic airway diseases, namely chronic obstructive pulmonary disease and bronchial asthma, and other chronic respiratory disorders in the adult population. While there is strong evidence for the association of chronic airway diseases with IBD, the data are much weaker for the interplay between lung and liver multimorbidities. The association of IBD, encompassing Crohn's disease and ulcerative colitis, with pulmonary disorders is underlined by their heterogeneous respiratory manifestations and impact on chronic airway diseases. The potential relationship between the two most prevalent liver-induced pulmonary vascular entities, i.e. portopulmonary hypertension and hepatopulmonary syndrome, and also between liver disease and other chronic respiratory diseases is also approached. Abnormal lung function tests in liver diseases are described and the role of increased serum bilirubin levels on chronic respiratory problems are considered. PMID:26797027

  6. Autophagy in lung disease pathogenesis and therapeutics.

    PubMed

    Ryter, Stefan W; Choi, Augustine M K

    2015-01-01

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

  7. Autophagy in lung disease pathogenesis and therapeutics

    PubMed Central

    Ryter, Stefan W.; Choi, Augustine M.K.

    2015-01-01

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

  8. Diarrheal Diseases - Acute and Chronic

    MedlinePlus

    ... greasy or very bad smelling stools. Causes – Acute Diarrhea Most cases of acute, watery diarrhea are caused ... a common cause of traveler’s diarrhea. Causes – Chronic Diarrhea Chronic diarrhea is classified as fatty or malabsorption, ...

  9. Transfusion-related acute lung injury; clinical perspectives.

    PubMed

    Kim, Jeongmin; Na, Sungwon

    2015-04-01

    Transfusion-related acute lung injury (TRALI) was introduced in 1983 to describe a clinical syndrome seen within 6 h of a plasma-containing blood products transfusion. TRALI is a rare transfusion complication; however, the FDA has suggested that TRALI is the leading cause of transfusion-related mortality. Understanding the pathogenesis of TRALI will facilitate adopting preventive strategies, such as deferring high plasma volume female product donors. This review outlines the clinical features, pathogenesis, treatment, and prevention of TRALI. PMID:25844126

  10. Presumptive acute lung injury following multiple surgeries in a cat

    PubMed Central

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

    2013-01-01

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

  11. Monitoring of Lung Involvement in Rheumatologic Disease.

    PubMed

    Paschalaki, Koralia E; Jacob, Joseph; Wells, Athol U

    2016-01-01

    The monitoring of lung involvement in patients with connective tissue diseases is central to optimal long-term management and is directed towards: (a) the detection of supervening lung involvement not present at presentation and (b) the identification of disease progression in established lung disease. For both goals, accurate surveillance requires multi-disciplinary evaluation with the integration of symptomatic change, serial pulmonary function trends and imaging data. Evaluated in isolation, each of these monitoring domains has significant limitations. Symptomatic change may be confounded by a wide variety of systemic factors. Pulmonary function tests provide the most reliable data, but are limited by measurement variability, the heterogeneity of functional patterns and the confounding effects of non-pulmonary factors. Chest radiography is insensitive to change but may provide rapid confirmation of major disease progression or alert the clinician to respiratory co-morbidities. Although high-resolution computed tomography has a central role in assessing disease severity, it should be used very selectively as a monitoring tool due to the associated radiation burden. Ancillary tests include echocardiography and exercise testing to proactively identify cases of pulmonary hypertension and worsening of oxygenation. In summary, a multi-disciplinary approach is essential for the identification of disease progression and prompt treatment of comorbidities that severely impact on the morbidity and mortality of disease. PMID:26735151

  12. Autophagy: Friend or Foe in Lung Disease?

    PubMed

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

    2016-03-01

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

  13. Zingerone attenuates lipopolysaccharide-induced acute lung injury in mice.

    PubMed

    Xie, Xianxing; Sun, Shicheng; Zhong, Weiting; Soromou, Lanan Wassy; Zhou, Xuan; Wei, Miaomiao; Ren, Yanling; Ding, Yu

    2014-03-01

    Zingerone, one of the active components of ginger, is a phenolic alkanone with antioxidant and anti-inflammatory properties. In the present study, we analyzed the role of zingerone against RAW 264.7 cells and acute lung injury induced by lipopolysaccharide (LPS) in mice. RAW cells or BALB/c mice were pretreated with zingerone one hour before stimulated with LPS. We found that zingerone significantly inhibited the production of LPS-induced proinflammatory cytokines in vitro and in vivo. When pretreated with zingerone, pulmonary histopathologic changes, as well as alveolar hemorrhage and neutrophil infiltration were substantially suppressed in lung tissues, with evidence of reduced myeloperoxidase (MPO) activity in murine acute lung injury model. The lung wet-to-dry weight (W/D) ratios, as the index of pulmonary edema, were markedly decreased by zingerone pretreatment. Furthermore, we demonstrated that zingerone attenuates the mitogen-activated protein kinases (MAPK) and nuclear factor-kappaB (NF-?B) signaling pathways through blocking the phosphorylation of ERK, p38/MAPK and I?B?, NF-?B/P65. These results suggest that zingerone may provide protective effects against LPS-induced ALI. PMID:24412620

  14. Lung disease and brain development.

    PubMed

    Huppi, Petra; Sizonenko, Stephane; Amato, Maurizio

    2006-01-01

    With the technical progress made in fetal and neonatal intensive care, perinatal mortality has decreased by 25% over the last decade and has expanded the surviving premature population. Prematurity drastically changes the environment of the developing organism. Striking evidence from a number of disciplines has focused attention on the interplay between the developing organism and the circumstances in which it finds itself. The environmental event during a sensitive period in development, induces injury and/or biological adaptations that lead to altered differentiation of tissues. The organism can express specific adaptive responses to its environment which include short-term changes in physiology as well as long-term adjustments. This review addresses these short-term as well as longer-term changes occurring in lung and brain tissue and illustrates how these changes can be studied using advanced imaging techniques such as magnetic resonance imaging PMID:16770068

  15. Mucin overproduction in chronic inflammatory lung disease

    PubMed Central

    Hauber, Hans-Peter; Foley, Susan C; Hamid, Qutayba

    2006-01-01

    Mucus overproduction and hypersecretion are commonly observed in chronic inflammatory lung disease. Mucins are gel-forming glycoproteins that can be stimulated by a variety of mediators. The present review addresses the mechanisms involved in the upregulation of secreted mucins. Mucin induction by neutrophil elastase, bacteria, cytokines, growth factors, smoke and cystic fibrosis transmembrane conductance regulator malfunction are also discussed. PMID:16983448

  16. The therapeutic effects of tuberostemonine against cigarette smoke-induced acute lung inflammation in mice.

    PubMed

    Jung, Kyung-Hwa; Beak, Hyunjung; Park, Soojin; Shin, Dasom; Jung, Jaehoon; Park, Sangwon; Kim, Jinju; Bae, Hyunsu

    2016-03-01

    Chronic obstructive pulmonary disease (COPD) is mainly caused by cigarette smoking and is characterized by the destruction of lung parenchyma, structural alterations of the small airways, and systemic inflammation. Tuberostemonine (TS) is an alkaloid-type phytochemical from Stemona tuberosa. In the present study, we evaluated the anti-inflammatory effect of TS in a cigarette smoke (CS)-induced mouse model of acute lung inflammation. The mice were whole-body exposed to CS or fresh air for 7 days. TS was administered by an intraperitoneal (i.p.) injection 1h before exposure to CS. To test the effects of TS, the numbers of total cells, neutrophils, macrophages and lymphocytes in the bronchoalveolar lavage (BAL) fluid were counted. Furthermore, we measured the levels of several chemokines, such as GCP-2, MIP-3?, MCP-1 and KC, in the lung tissue. The cellular profiles and histopathological analysis demonstrated that the infiltration of peribronchial and perivascular inflammatory cells significantly decreased in the TS-treated groups compared with the CS-exposure group. The TS treatment significantly ameliorated the airway epithelial thickness induced by CS exposure and caused a significant decrement in the production of chemokines in the lung. These results suggest that TS has anti-inflammatory effects against CS-induced acute lung inflammation. PMID:26849941

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

    PubMed

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

    2016-04-01

    Pulmonary hypertension commonly complicates chronic obstructive pulmonary disease and interstitial lung disease. The association of chronic lung disease and pulmonary hypertension portends a worse prognosis. The pathophysiology of pulmonary hypertension differs in the presence or absence of lung disease. We describe the physiological determinants of the normal pulmonary circulation to better understand the pathophysiological factors implicated in chronic parenchymal lung disease-associated pulmonary hypertension. This review will focus on the pathophysiology of 3 forms of chronic lung disease-associated pulmonary hypertension: idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, and sarcoidosis. PMID:26706386

  18. Reversing disability of irreversible lung disease.

    PubMed Central

    Tiep, B. L.

    1991-01-01

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

  19. Extracellular matrix mechanics in lung parenchymal diseases

    PubMed Central

    Suki, Béla; Bates, Jason H.T.

    2008-01-01

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

  20. Antioxidant vitamins and prevention of lung disease

    SciTech Connect

    Menzel, D.B. )

    1992-09-30

    Although the evidence for oxidative stress for air pollution in the human lung is fragmentary, the hypothesis that oxidative stress is an important, if not the sole, mechanism of toxicity of oxidizing air pollutants and tobacco smoke is compelling and growing. First, biochemical mechanisms have been worked out for oxidation of lung lipids by the gas phase of cigarette smoke, NO[sub 2] and O[sub 3]. The oxidation of lung lipids can be prevented by both vitamins C and E. Vitamin C is more effective in preventing oxidation by NO[sub 2], and vitamin E is more effective against O[sub 3]. Second, multiple species of experimental animals develop lung disease similar to human bronchitis and emphysema from exposure to NO[sub 2] and O[sub 3], respectively. The development of these diseases occurs over a near lifetime exposure when the levels of NO[sub 2] or O[sub 3] are at near ambient air pollution values. Third, isolated human cells are protected against oxidative damage from NO[sub 2] and O[sub 3] by both vitamins C and E. Fourth, the vitamin C level in the lung either declines on exposure to NO[sub 2] for short-term exposures or increases on chronic cigarette smoke exposure. The effects of cigarette smoking on serum vitamin C is apparently complex and may be related to the daily intake of vitamin C as well as smoking. Serum vitamin C levels may be poor indicators of lung demands when daily vitamin C intakes are above 100 mg/day. Fifth, vitamin C supplementation protects against the effects of ambient levels of air pollution in adults as measured by histamine challenge. An augmented response to histamine challenge may represent increased lung permeability brought about by air pollution. In experimental animal and human experiments, the amount of vitamin C or E that afforded protection was in excess of the current recommended dietary allowance.

  1. Acute lung injury following lung resection: is one lung anaesthesia to blame?

    PubMed Central

    Williams, E. A.; Evans, T. W.; Goldstraw, P.

    1996-01-01

    Further examination of the parameters of oxidative stress, perioperative changes in the vasoregulatory mechanisms of the pulmonary circulation, and characterisation of the endothelial insult that probably occurs in all patients undergoing lung resection is necessary if the operative conditions under which lung surgery is carried out are to be optimised. Perhaps, then, more insight might be gained into how to improve preservation of lungs for transplantation and how to protect the lung from significant injury following resection. PMID:8711638

  2. Thaliporphine derivative improves acute lung injury after traumatic brain injury.

    PubMed

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

    2015-01-01

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

  3. RNAi Therapeutic Platforms for Lung Diseases

    PubMed Central

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

    2013-01-01

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

  4. Translational models of lung disease.

    PubMed

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

    2015-02-01

    The 2nd Cross Company Respiratory Symposium (CCRS), held in Horsham, U.K. in 2012, brought together representatives from across the pharmaceutical industry with expert academics, in the common interest of improving the design and translational predictiveness of in vivo models of respiratory disease. Organized by the respiratory representatives of the European Federation of Pharmaceutical Industries and Federations (EFPIA) group of companies involved in the EU-funded project (U-BIOPRED), the aim of the symposium was to identify state-of-the-art improvements in the utility and design of models of respiratory disease, with a view to improving their translational potential and reducing wasteful animal usage. The respiratory research and development community is responding to the challenge of improving translation in several ways: greater collaboration and open sharing of data, careful selection of the species, complexity and chronicity of the models, improved practices in preclinical research, continued refinement in models of respiratory diseases and their sub-types, greater understanding of the biology underlying human respiratory diseases and their sub-types, and finally greater use of human (and especially disease-relevant) cells, tissues and explants. The present review highlights these initiatives, combining lessons from the symposium and papers published in Clinical Science arising from the symposium, with critiques of the models currently used in the settings of asthma, idiopathic pulmonary fibrosis and COPD. The ultimate hope is that this will contribute to a more rational, efficient and sustainable development of a range of new treatments for respiratory diseases that continue to cause substantial morbidity and mortality across the world. PMID:25328010

  5. Risk factors for lung diseases after renal transplantation

    PubMed Central

    Pencheva, Ventsislava P.; Petrova, Daniela S.; Genov, Diyan K.; Georgiev, Ognian B.

    2015-01-01

    Background: Lung diseases are one of the major causes of morbidity and mortality after renal transplantation. The aim of the study is to define the risk factors for infectious and noninfectious pulmonary complications in kidney transplant patients. Materials and Methods: We prospectively studied 267 patients after renal transplantation. The kidney recipients were followed-up for the development of pulmonary complications for a period of 7 years. Different noninvasive and invasive diagnostic tests were used in cases suspected of lung disease. Results: The risk factors associated with the development of pulmonary complications were diabetes mellitus (odds ratio [OR] = 4.60; P = 0.001), arterial hypertension (OR = 1.95; P = 0.015), living related donor (OR = 2.69; P = 0.004), therapy for acute graft rejection (OR = 2.06; P = 0.038), immunosuppressive regimens that includes mycophenolate (OR = 2.40; P = 0.011), azathioprine (OR = 2.25; P = 0.023), and tacrolimus (OR = 1.83; P = 0.041). The only factor associated with the lower risk of complications was a positive serology test for Cytomegalovirus of the recipient before transplantation (OR = 0.1412; P = 0.001). Conclusion: The risk factors can be used to identify patients at increased risk for posttransplant lung diseases. Monitoring of higher-risk patients allow timely diagnosis and early adequate treatment and can reduce the morbidity and mortality after renal transplantation. PMID:26958045

  6. Procoagulant alveolar microparticles in the lungs of patients with acute respiratory distress syndrome.

    PubMed

    Bastarache, Julie A; Fremont, Richard D; Kropski, Jonathan A; Bossert, Frederick R; Ware, Lorraine B

    2009-12-01

    Coagulation and fibrinolysis abnormalities are observed in acute lung injury (ALI) in both human disease and animal models and may contribute to ongoing inflammation in the lung. Tissue factor (TF), the main initiator of the coagulation cascade, is upregulated in the lungs of patients with ALI/acute respiratory distress syndrome (ARDS) and likely contributes to fibrin deposition in the air space. The mechanisms that govern TF upregulation and activation in the lung are not well understood. In the vascular space, TF-bearing microparticles (MPs) are central to clot formation and propagation. We hypothesized that TF-bearing MPs in the lungs of patients with ARDS contribute to the procoagulant phenotype in the air space during acute injury and that the alveolar epithelium is one potential source of TF MPs. We studied pulmonary edema fluid collected from patients with ARDS compared with a control group of patients with hydrostatic pulmonary edema. Patients with ARDS have higher concentrations of MPs in the lung compared with patients with hydrostatic edema (25.5 IQR 21.3-46.9 vs. 7.8 IQR 2.3-27.5 micromol/l, P = 0.009 by Mann-Whitney U-test). These MPs are enriched for TF, have procoagulant activity, and likely originate from the alveolar epithelium [as measured by elevated levels of RAGE (receptor for advanced glycation end products) in ARDS MPs compared with hydrostatic MPs]. Furthermore, alveolar epithelial cells in culture release procoagulant TF MPs in response to a proinflammatory stimulus. These findings suggest that alveolar epithelial-derived MPs are one potential source of TF procoagulant activity in the air space in ARDS and that epithelial MP formation and release may represent a unique therapeutic target in ARDS. PMID:19700643

  7. [Effects of oxygen and nikethamide on central drive, ventilation and blood gases of patients with obstructive lung disease in acute exacerbation of respiratory failure].

    PubMed

    Ren, X H; Ding, D J; Chen, E Z

    1993-12-01

    Twelve subjects with COPD in acute exacerbation of respiratory failure were studied. The experiment of each subject was divided into three steps: room air breathing, 35% O2 inhalation for one hour, and then intravenous drip of nikethamide (1.875g) for two hours with 35% oxygen inhalation at the same time. At the end of each step, mouth occlusion pressure (P0.1), VT, VE, VA, VCO2, VD and PaO2, PaCO2 were measured respectively. The results showed that, when breathing air, all the patients presented significant higher P0.1 than normal subjects, indicated higher central drive. After oxygen inhalation, P0.1 decreased markedly, but still higher than normal. No correlation was found between delta P0.1 and delta PaO2. VE declined with the drop of P0.1, but this was due to a decrease of respiratory frequency, while VA remained unchanged (P > 0.05). The increase of PaCO2 was unremarkable. Neither correlation was found between delta VA and delta P0.1, nor between delta VA and delta PaCO2. However, a close correlation existed between delta VCO2/VCO2 and delta VE/VE. The result of our study is not consistent with the postulation, the removal of the hypoxic stimulate after oxygen administration results in a decrease of ventilation and CO2 retention. After nikethamide administration, P0.1 increased as well as VE while VA and PaCO2 remained unchanged. The increase of VE was caused by the increase of respiratory rate. Furthermore, PaO2 decreased in some patients. All of the changes demonstrated that nothing is worthwhile with the treatment of nikethamide, but a side effect from increasing work of breathing and consumption of oxygen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8033228

  8. Noninvasive In Vivo Quantification of Neutrophil Elastase Activity in Acute Experimental Mouse Lung Injury

    PubMed Central

    Kossodo, Sylvie; Zhang, Jun; Groves, Kevin; Cuneo, Garry J.; Handy, Emma; Morin, Jeff; Delaney, Jeannine; Yared, Wael; Rajopadhye, Milind; Peterson, Jeffrey D.

    2011-01-01

    We developed a neutrophil elastase-specific near-infrared fluorescence imaging agent, which, combined with fluorescence molecular tomographic imaging, allowed us to detect and quantify neutrophil elastase activity in vivo, in real time, and noninvasively in an acute model of lung injury (ALI). Significantly higher fluorescent signal was quantified in mice with LPS/fMLP-induced ALI as compared to healthy controls, correlating with increases in the number of bronchoalveolar lavage cells, neutrophils, and elastase activity. The agent was significantly activated ex vivo in lung sections from ALI but not from control mice, and this activation was ablated by the specific inhibitor sivelestat. Treatment with the specific inhibitor sivelestat significantly reduced lung signal in mice with ALI. These results underscore the unique ability of fluorescence molecular imaging to quantify specific molecular processes in vivo, crucial for understanding the mechanisms underlying disease progression and for assessing and monitoring novel pharmacological interventions. PMID:21941648

  9. Does aluminum smelting cause lung disease

    SciTech Connect

    Abramson, M.J.; Wlodarczyk, J.H.; Saunders, N.A.; Hensley, M.J.

    1989-04-01

    The evidence concerning a relationship between work in the aluminum industry and lung disease has been reviewed using epidemiologic criteria. Adequate data on environmental exposure are rarely presented. Case series on aluminum potroom workers over the past 50 years have identified an asthmalike syndrome that appears to be due to an irritant rather than an allergic mechanism. These studies have been supported by evidence of within shift variability of measures of lung function. However, to date, there is inadequate evidence to resolve the question of whether potroom exposure initiates asthma or merely precipitates asthmalike symptoms in a predisposed individual. Cross-sectional studies have demonstrated evidence of reduced lung function, consistent with chronic airflow limitation. In exposed aluminum smelter workers compared to unexposed control subjects. Cigarette smoking, the major potential confounding variable, has been measured and accounted for in multivariate analyses. To date, evidence is lacking from longitudinal studies about the development of disabling chronic obstructive lung disease. Exposure to coal tar pitch volatiles in the production and consumption of anodes has biologic plausibility for an association of lung cancer with work in an aluminum smelter. Although retrospective mortality studies have failed to account for the probable high prevalence of smoking in blue collar workers, the relative risk of lung cancer is very low if present at all. Pulmonary fibrosis has not been shown to be a significant problem in aluminum smelter workers. Future research in the aluminum industry needs to concentrate on longitudinal studies, preferably with an inception cohort for the investigation of potroom asthma. 92 references.

  10. Does aluminum smelting cause lung disease?

    PubMed

    Abramson, M J; Wlodarczyk, J H; Saunders, N A; Hensley, M J

    1989-04-01

    The evidence concerning a relationship between work in the aluminum industry and lung disease has been reviewed using epidemiologic criteria. Adequate data on environmental exposure are rarely presented. Case series on aluminum potroom workers over the past 50 years have identified an asthmalike syndrome that appears to be due to an irritant rather than an allergic mechanism. These studies have been supported by evidence of within shift variability of measures of lung function. However, to date, there is inadequate evidence to resolve the question of whether potroom exposure initiates asthma or merely precipitates asthmalike symptoms in a predisposed individual. Cross-sectional studies have demonstrated evidence of reduced lung function, consistent with chronic airflow limitation. In exposed aluminum smelter workers compared to unexposed control subjects. Cigarette smoking, the major potential confounding variable, has been measured and accounted for in multivariate analyses. To date, evidence is lacking from longitudinal studies about the development of disabling chronic obstructive lung disease. Exposure to coal tar pitch volatiles in the production and consumption of anodes has biologic plausibility for an association of lung cancer with work in an aluminum smelter. Although retrospective mortality studies have failed to account for the probable high prevalence of smoking in blue collar workers, the relative risk of lung cancer is very low if present at all. Pulmonary fibrosis has not been shown to be a significant problem in aluminum smelter workers. Future research in the aluminum industry needs to concentrate on longitudinal studies, preferably with an inception cohort for the investigation of potroom asthma. PMID:2648910

  11. Clinical features of rheumatoid arthritis-associated interstitial lung disease.

    PubMed

    Wang, Ting; Zheng, Xing-Ju; Liang, Bin-Miao; Liang, Zong-An

    2015-01-01

    Interstitial lung disease (ILD) is the most common extra-articular manifestations of rheumatoid arthritis (RA) in the lung. This study aimed to identify clinical features of RA-associated ILD (RA-ILD). Patients with RA were retrospectively enrolled and sub-classified as RA-ILD or RA without ILD based on high-resolution computed tomography imaging. Pulmonary function testing parameters and levels of RA-related biomarkers, tumour markers, and acute-phase proteins were compared between the two groups. Logistic regression model was used to assess the strength of association between RA-ILD and clinical features of interest. Receiver operating characteristic analysis was performed to assess potential predictive value of clinical features for detecting RA-ILD. Comparison analysis indicated that the percentage of predicted value of total lung capacity, inspiratory capacity, and diffusion capacity of the lung for carbon monoxide (DLCO) were reduced in patients with RA-ILD. Tumour markers CA15-3 and CA125 were increased in patients with RA-ILD. Logistic regression analysis revealed that decreased DLCO was related to the increased likelihood of RA-ILD (OR = 0.94, 95%CI = [0.91, 0.98]). The cut-off point at 52.95 percent of predicted value could sensitively discriminate RA patients with or without ILD. Our study suggested that DLCO value could be a useful tool for detecting ILD in patients with RA. PMID:26443305

  12. Therapeutic Effect of the Tuber of Alisma orientale on Lipopolysaccharide-Induced Acute Lung Injury

    PubMed Central

    Kwun, Min Jung; Choi, Jun-Yong; Ahn, Kyung-Seop; Oh, Sei-Ryang; Lee, Yong Gyu; Christman, John W.; Sadikot, Ruxana T.

    2013-01-01

    Although Alisma orientale, an ethnic herb, has been prescribed for treating various diseases in Asian traditional medicine, experimental evidence to support its therapeutic effects is lacking. Here, we sought to determine whether A. orientale has a therapeutic effect on acute lung injury (ALI). Ethanol extract of the tuber of A. orientale (EEAO) was prepared and fingerprinted by HPLC for its constituents. Mice received an intraperitoneal (i.p.) injection of lipopolysaccharide (LPS) for the induction of ALI. At 2 h after LPS treatment, mice received an intratracheal (i.t.) spraying of various amounts of EEAO to the lung. Bioluminescence imaging of transgenic NF-κB/luciferase reporter mice shows that i.t. EEAO posttreatment suppressed lung inflammation. In similar experiments with C57BL/6 mice, EEAO posttreatment significantly improved lung inflammation, as assessed by H&E staining of lung sections, counting of neutrophils in bronchoalveolar lavage fluid, and semiquantitative RT-PCR analyses of proinflammatory cytokines and Nrf2-dependent genes in the inflamed lungs. Furthermore, EEAO posttreatment enhanced the survival of mice that received a lethal dose of LPS. Together, our results provide evidence that A. orientale has a therapeutic effect on ALI induced by sepsis. PMID:23983806

  13. OXIDANTS AND THE PATHOGENESIS OF LUNG DISEASES

    PubMed Central

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

    2009-01-01

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

  14. Does detoxification reverse the acute lung injury of crack smokers?

    PubMed

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

    1996-11-01

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

  15. Posttransplant Lymphoproliferative Disease after Lung Transplantation

    PubMed Central

    Neuringer, Isabel P.

    2013-01-01

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

  16. Nilotinib ameliorates lipopolysaccharide-induced acute lung injury in rats

    SciTech Connect

    El-Agamy, Dina S.

    2011-06-01

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

  17. The Heat Shock Response and Acute Lung Injury

    PubMed Central

    Wheeler, Derek S.; Wong, Hector R.

    2006-01-01

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

  18. Protective effects of erythropoietin against acute lung injury in a rat model of acute necrotizing pancreatitis

    PubMed Central

    Tascilar, Oge; Cakmak, Gldeniz Karadeniz; Tekin, Ishak Ozel; Emre, Ali Ugur; Ucan, Bulent Hamdi; Bahadir, Burak; Acikgoz, Serefden; Irkorucu, Oktay; Karakaya, Kemal; Balbaloglu, Hakan; Kertis, Grkan; Ankarali, Handan; Comert, Mustafa

    2007-01-01

    AIM: To investigate the effect of exogenous erythro-poietin (EPO) administration on acute lung injury (ALI) in an experimental model of sodium taurodeoxycholate-induced acute necrotizing pancreatitis (ANP). METHODS: Forty-seven male Wistar albino rats were randomly divided into 7 groups: sham group (n = 5), 3 ANP groups (n = 7 each) and 3 EPO groups (n = 7 each). ANP was induced by retrograde infusion of 5% sodium taurodeoxycholate into the common bile duct. Rats in EPO groups received 1000 U/kg intramuscular EPO immediately after induction of ANP. Rats in ANP groups were given 1 mL normal saline instead. All animals were sacrificed at postoperative 24 h, 48 h and 72 h. Serum amilase, IL-2, IL-6 and lung tissue malondialdehyde (MDA) were measured. Pleural effusion volume and lung/body weight (LW/BW) ratios were calculated. Tissue levels of TNF-?, IL-2 and IL-6 were screened immunohistochemically. Additionally, ox-LDL accumulation was assessed with immune-fluorescent staining. Histopathological alterations in the lungs were also scored. RESULTS: The mean pleural effusion volume, calculated LW/BW ratio, serum IL-6 and lung tissue MDA levels were significantly lower in EPO groups than in ANP groups. No statistically significant difference was observed in either serum or tissue values of IL-2 among the groups. The level of tumor necrosis factor-? (TNF-?) and IL-6 and accumulation of ox-LDL were evident in the lung tissues of ANP groups when compared to EPO groups, particularly at 72 h. Histopathological evaluation confirmed the improvement in lung injury parameters after exogenous EPO administration, particularly at 48 h and 72 h. CONCLUSION: EPO administration leads to a significant decrease in ALI parameters by inhibiting polymorphonuclear leukocyte (PMNL) accumulation, decreasing the levels of proinflammatory cytokines in circulation, preserving microvascular endothelial cell integrity and reducing oxidative stress-associated lipid peroxidation and therefore, can be regarded as a cytoprotective agent in ANP-induced ALI. PMID:18069756

  19. Pulmonary hypertension in chronic lung diseases.

    PubMed

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

    2013-12-24

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

  20. [Pulmonary hypertension in chronic lung diseases].

    PubMed

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

    2014-10-01

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

  1. Evaluation and Diagnosis of HIV-Associated Lung Disease.

    PubMed

    Maximous, Stephanie; Huang, Laurence; Morris, Alison

    2016-04-01

    There are myriad pulmonary conditions associated with HIV, ranging from acute infections to chronic noncommunicable diseases. The epidemiology of these diseases has changed significantly in the era of widespread antiretroviral therapy. Evaluation of the HIV-infected patient involves assessment of the severity of illness and a thorough yet efficient pursuit of definitive diagnosis, which may involve multiple etiologies simultaneously. Important clues to a diagnosis include medical and social history, demographic details such as travel and geography of residence, substance use, sexual practices, and domiciliary and incarceration status. CD4 cell count is a tremendously useful measure of immune function and risk for HIV-related diseases, and helps narrow down the differential. Careful history of current symptoms and physical examination with particular attention to extrapulmonary signs are crucial early steps. Many adjunctive laboratory studies can suggest or rule out particular diagnoses. Pulmonary function testing (PFT) may aid in characterization of several chronic noninfectious illnesses accelerated by HIV. Chest radiograph and computed tomography (CT) scan allow for classification of diseases by pathognomonic imaging patterns, although many infectious conditions present atypically, particularly with lower CD4 counts. Ultimately, definitive diagnosis with sputum, bronchoscopy with bronchoalveolar lavage, or lung tissue is often needed. It is of utmost importance to maintain a high degree of suspicion for HIV in otherwise undiagnosed patients, as the first presentation of HIV may be via an acute pulmonary illness. PMID:26974298

  2. Imbalance of Th17/Tregs in rats with smoke inhalation-induced acute lung injury

    PubMed Central

    Zhang, Fan; Li, Mian-yang; Lan, Ya-ting; Wang, Cheng-bin

    2016-01-01

    T helper (Th) 17 cells and CD4+ CD25+ regulatory T (Treg) cells are supposed to be critically involved in regulating autoimmune and inflammatory diseases. The aim of this study was to investigate the Th17/Treg pattern in rats with gunpowder smog-induced acute lung injury. Wistar rats were equally randomized to three groups: normal control group, ALI 6 h group (smoke inhalation for 6 h) and ALI 24 h group (smoke inhalation for 24 h). We observed changes in cell counting in bronchoalveolar lavage fluid (BALF), alveolar-capillary membrane permeability and lung tissue pathology. Moreover, rats in ALI 6 h and ALI 24 h group showed increased expression of Th17 cell and related cytokines (IL-17 A, IL-6, TGF-β and IL-23). Meanwhile, Treg prevalence and related cytokines (IL-10, IL-2 and IL-35) were decreased. Consequently, the ratio of Th17/Treg was higher after smoke inhalation. Additionally, Th1 cell decreased while Th2 cell increased at 6 h and 24 h after smoke inhalation. In conclusion, Th17/Treg imbalance exists in rats with smoke inhalation-induced acute lung injury, suggesting its potential role in the pathogenesis of this disease. PMID:26884314

  3. Imbalance of Th17/Tregs in rats with smoke inhalation-induced acute lung injury.

    PubMed

    Zhang, Fan; Li, Mian-Yang; Lan, Ya-Ting; Wang, Cheng-Bin

    2016-01-01

    T helper (Th) 17 cells and CD4(+) CD25(+) regulatory T (Treg) cells are supposed to be critically involved in regulating autoimmune and inflammatory diseases. The aim of this study was to investigate the Th17/Treg pattern in rats with gunpowder smog-induced acute lung injury. Wistar rats were equally randomized to three groups: normal control group, ALI 6 h group (smoke inhalation for 6 h) and ALI 24 h group (smoke inhalation for 24 h). We observed changes in cell counting in bronchoalveolar lavage fluid (BALF), alveolar-capillary membrane permeability and lung tissue pathology. Moreover, rats in ALI 6 h and ALI 24 h group showed increased expression of Th17 cell and related cytokines (IL-17 A, IL-6, TGF-β and IL-23). Meanwhile, Treg prevalence and related cytokines (IL-10, IL-2 and IL-35) were decreased. Consequently, the ratio of Th17/Treg was higher after smoke inhalation. Additionally, Th1 cell decreased while Th2 cell increased at 6 h and 24 h after smoke inhalation. In conclusion, Th17/Treg imbalance exists in rats with smoke inhalation-induced acute lung injury, suggesting its potential role in the pathogenesis of this disease. PMID:26884314

  4. Autoimmune-Featured Interstitial Lung Disease

    PubMed Central

    Vij, Rekha; Strek, Mary E.

    2011-01-01

    Background: Patients with interstitial lung disease (ILD) may have features of an autoimmune disorder that do not meet the diagnostic criteria for connective tissue diseases. We determined the prevalence and characteristics of autoimmune-featured ILD (AIF-ILD) and compared these with those of idiopathic pulmonary fibrosis (IPF) and known connective tissue disease-related ILD (CTD-ILD). Methods: Patients with ILD who did not meet the criteria for a connective tissue disease were defined as having AIF-ILD if they had a sign or symptom suggestive of a connective tissue disease and a serologic test reflective of an autoimmune process. Clinical characteristics, high-resolution CT images, and lung biopsy specimens were analyzed and compared with those of patients with IPF and CTD-ILD. Survival was evaluated using a Kaplan-Meier curve. Results: Two hundred subjects completed the questionnaire and serologic testing. AIF-ILD was identified in 32%, IPF in 29%, and CTD-ILD in 19%. Gender, age, and race differed among groups (P < .01). Sixty-two percent of patients with AIF-ILD had a typical usual interstitial pneumonia (UIP) pattern on CT images. In 31 patients with AIF-ILD, lung biopsy specimens showed UIP in 81% and nonspecific interstitial pneumonia in 6%. Patients with AIF-ILD and IPF had similar survival, worse than those with CTD-ILD (P < .01). Antinuclear antibody (ANA) titers ≥ 1:1280 were associated with improved survival in patients with AIF-ILD (P = .02). Conclusions: Systematic evaluation of symptoms and serologic tests in ILD can identify AIF-ILD. A UIP pattern on CT images and histopathology is common in AIF-ILD. Although survival for patients with AIF-ILD is poor, ANA titers ≥ 1:1280 are associated with improved survival. PMID:21565966

  5. Microsatellite DNA instability in benign lung diseases.

    PubMed

    Samara, Katerina; Zervou, Maria; Siafakas, Nikolaos M; Tzortzaki, Eleni G

    2006-02-01

    Recently DNA mismatch repair system (MMR) has been extensively investigated in molecular medicine. Microsatellite (MS) DNA alterations are considered as indicating an ineffective MMR system. MS loss of heterozygosity (LOH) and microsatellite instability (MSI) have been reported in a number of human malignancies. LOH and MSI have recently been detected in benign diseases, such as actinic keratosis, pterygium and atherosclerosis. In addition, MSI and LOH have been detected in asthma, chronic obstructive pulmonary disease, sarcoidosis and idiopathic pulmonary fibrosis. This is a review of MSI in benign lung diseases. It is concluded that detecting genetic alterations at the MS DNA level could be a useful technique to identify locus of potential altered genes that may play a key role in the pathogenesis of these diseases. In addition, MSI and LOH could be used as a genetic screening tool in molecular epidemiology. PMID:16005622

  6. Diagnosis and Treatment of Nontuberculous Mycobacterial Lung Disease.

    PubMed

    Kwon, Yong-Soo; Koh, Won-Jung

    2016-05-01

    Nontuberculous mycobacteria (NTM) are ubiquitous organisms; their isolation from clinical specimens does not always indicate clinical disease. The incidence of NTM lung diseases has been increasing worldwide. Although the geographic diversity of NTM species is well known, Mycobacterium avium complex (MAC), M. abscessus complex (MABC), and M. kansasii are the most commonly encountered and important etiologic organisms. Two distinct types of NTM lung diseases have been reported, namely fibrocavitary and nodular bronchiectatic forms. For laboratory diagnosis of NTM lung diseases, both liquid and solid media cultures and species-level identification are strongly recommended to enhance growth detection and determine the clinical relevance of isolates. Treatment for NTM lung diseases consists of a multidrug regimen and a long course of therapy, lasting more than 12 months after negative sputum conversion. For MAC lung disease, several new macrolide-based regimens are now recommended. For nodular bronchiectatic forms of MAC lung diseases, an intermittent three-time-weekly regimen produces outcomes similar to those of daily therapy. Treatment of MABC lung disease is very difficult, requiring long-term use of parenteral agents in combination with new macrolides. Treatment outcomes are much better for M. massiliense lung disease than for M. abscessus lung disease. Thus, precise identification of species in MABC infection is needed for the prediction of antibiotic response. Likewise, increased efforts to improve treatment outcomes and develop new agents for NTM lung disease are needed. PMID:27134484

  7. Diagnosis and Treatment of Nontuberculous Mycobacterial Lung Disease

    PubMed Central

    2016-01-01

    Nontuberculous mycobacteria (NTM) are ubiquitous organisms; their isolation from clinical specimens does not always indicate clinical disease. The incidence of NTM lung diseases has been increasing worldwide. Although the geographic diversity of NTM species is well known, Mycobacterium avium complex (MAC), M. abscessus complex (MABC), and M. kansasii are the most commonly encountered and important etiologic organisms. Two distinct types of NTM lung diseases have been reported, namely fibrocavitary and nodular bronchiectatic forms. For laboratory diagnosis of NTM lung diseases, both liquid and solid media cultures and species-level identification are strongly recommended to enhance growth detection and determine the clinical relevance of isolates. Treatment for NTM lung diseases consists of a multidrug regimen and a long course of therapy, lasting more than 12 months after negative sputum conversion. For MAC lung disease, several new macrolide-based regimens are now recommended. For nodular bronchiectatic forms of MAC lung diseases, an intermittent three-time-weekly regimen produces outcomes similar to those of daily therapy. Treatment of MABC lung disease is very difficult, requiring long-term use of parenteral agents in combination with new macrolides. Treatment outcomes are much better for M. massiliense lung disease than for M. abscessus lung disease. Thus, precise identification of species in MABC infection is needed for the prediction of antibiotic response. Likewise, increased efforts to improve treatment outcomes and develop new agents for NTM lung disease are needed. PMID:27134484

  8. Rare lung diseases II: Pulmonary alveolar proteinosis

    PubMed Central

    Juvet, Stephen C; Hwang, David; Waddell, Thomas K; Downey, Gregory P

    2008-01-01

    The present article is the second in a series on rare lung diseases. It focuses on pulmonary alveolar proteinosis (PAP), a disorder in which lipoproteinaceous material accumulates in the alveolar space. PAP was first described in 1958, and for many years the nature of the material accumulating in the lungs was unknown. Major insights into PAP have been made in the past decade, and these have led to the notion that PAP is an autoimmume disorder in which autoantibodies interfere with signalling through the granulocyte-macrophage colony-stimulating factor receptor, leading to macrophage and neutrophil dysfunction. This has spurred new therapeutic approaches to this disorder. The discussion of PAP will begin with a case report, then will highlight the classification of PAP and review recent insights into the pathogenesis of PAP. The approach to therapy and the prognosis of PAP will also be discussed. PMID:18551202

  9. Unclassifiable interstitial lung disease: A review.

    PubMed

    Skolnik, Kate; Ryerson, Christopher J

    2016-01-01

    Accurate classification of interstitial lung disease (ILD) requires a multidisciplinary approach that incorporates input from an experienced respirologist, chest radiologist and lung pathologist. Despite a thorough multidisciplinary evaluation, up to 15% of ILD patients have unclassifiable ILD and cannot be given a specific diagnosis. The objectives of this review are to discuss the definition and features of unclassifiable ILD, identify the barriers to ILD classification and outline an approach to management of unclassifiable ILD. Several recent studies have described the characteristics of these patients; however, there are inconsistencies in the definition and terminology of unclassifiable ILD due to limited research in this population. Additional studies are required to determine the appropriate evaluation and management of patients with unclassifiable ILD. PMID:26059704

  10. Differential diagnosis of acute pelvic inflammatory disease.

    PubMed

    Jacobson, L

    1980-12-01

    Laparoscopic investigations have shown that clinical symptoms and signs in cases of acute pelvic inflammatory disease (acute salpingitis) show considerable variation and seem to a great extent to be nonspecific. Diagnosis based on clinical criteria alone is, therefore, unacceptably unreliable. Different intrapelvic disorders and acute infections limited to the lower genital tract (LGTI) represent substantial differential diagnostic problems. The routine use of laparoscopy is currently the best method for solving these problems but its broader application is restricted by several factors. Determination of specific genital isoamylases obtained at vaginal puncture of the cul-de-sac seems to represent a promising and specific laboratory test for differentiating between acute PID and LGTI that simulates acute PID. PMID:6451174

  11. Arctigenin attenuates lipopolysaccharide-induced acute lung injury in rats.

    PubMed

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

    2015-04-01

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

  12. Extracorporeal lung assist for sepsis and acute respiratory distress syndrome.

    PubMed

    Iwashita, Yoshiaki; Imai, Hiroshi

    2015-01-01

    Acute respiratory distress syndrome (ARDS) is one of the major causes of ICU deaths. Extracorporeal lung assist (ECLA) has been used as a rescue therapy for most severe form of ARDS. However, its survival benefit had not been shown until CESAR trial in 2009. This has been because the concept of lung protective ventilation strategy had not yet known. Since CESAR trial, the clinical application of ECLA for ARDS as a method to achieve lung rest has wide spread. The effectiveness is further appreciated during the 2009 H1N1 influenza pandemic. The succeeded countries achieved building the transportation systems to collect ECLA patients. With the accumulating evidences of survival benefit, the long-term outcome such as pulmonary function and quality of life are in concern. PumplessECLA which is a newly developed form of ECLA is also reviewed. In this essay we will firstly review the basics of ARDS and ECLA. Then the historical development of ECLA evidences for ARDS are reviewed. PMID:25567336

  13. [Role of computed tomography in the diagnosis of acute lung injury/acute respiratory distress syndrome].

    PubMed

    Mazzei, Maria Antonietta; Guerrini, Susanna; Cioffi Squitieri, Nevada; Franchi, Federico; Volterrani, Luca; Genovese, Eugenio Annibale; Macarini, Luca

    2012-11-01

    Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a complex pulmonary pathology with high mortality rates, manifesting over a wide range of severity. Clinical diagnosis relies on the following 4 criteria stated by the American-European Consensus Conference: acute onset of impaired gas exchange, severe hypoxemia defined as a PaO2 to FiO2 ratio <300 (PaO2 in mmHg), bilateral diffuse infiltration on chest X-ray; pulmonary artery wedge pressure of ≤18 mmHg to rule out cardiogenic causes of pulmonary edema. The aim of this study was to determine the usefulness of CT in the diagnosis and management of this condition. PMID:23096732

  14. Cardiovascular biomarkers in acute Kawasaki disease

    PubMed Central

    Sato, Yuichiro Z.; Molkara, Delaram P.; Daniels, Lori B.; Tremoulet, Adriana H.; Shimizu, Chisato; Kanegaye, John T.; Best, Brookie M.; Snider, James V.; Frazer, Jeffrey R.; Maisel, Alan; Burns, Jane C.

    2011-01-01

    Background Endomycocardial biopsies have demonstrated that subclinical myocarditis is a universal feature of acute Kawasaki disease (KD). Methods We investigated biochemical evidence of myocardial strain, oxidative stress, and cardiomyocyte injury in 55 acute KD subjects (30 with paired convalescent samples), 54 febrile control (FC), and 50 healthy control (HC) children by measuring concentrations of cardiovascular biomarkers. Results Levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and soluble ST2 (sST2) were elevated in acute vs. convalescent KD, FC, and HC (p≤0.0002), while γ-glutamyl transferase and alanine amino transferase as measures of oxidative stress were increased in acute vs. FC (p≤0.0008). Cardiac troponin I (cTnI) levels, using a highly sensitive assay, were elevated in 30% and 40% of paired acute and convalescent KD subjects, respectively, and normalized within two years of disease onset. NT-proBNP and sST2 negatively correlated with measures of diastolic function (MV E:A ratio and deceleration time), but only NT-proBNP positively correlated with the coronary artery Z score. Conclusions NT-proBNP and sST2 were elevated in acute KD subjects and correlated with impaired myocardial relaxation. These findings, combined with elevated levels of cTnI, suggest that both cardiomyocyte stress and cell death are associated with myocardial inflammation in acute KD. PMID:21777987

  15. Enhanced Resolution of Hyperoxic Acute Lung Injury as a result of Aspirin Triggered Resolvin D1 Treatment.

    PubMed

    Cox, Ruan; Phillips, Oluwakemi; Fukumoto, Jutaro; Fukumoto, Itsuko; Parthasarathy, Prasanna Tamarapu; Arias, Stephen; Cho, Young; Lockey, Richard F; Kolliputi, Narasaiah

    2015-09-01

    Acute lung injury (ALI), which presents as acute respiratory failure, is a major clinical problem that requires aggressive care, and patients who require prolonged oxygen exposure are at risk of developing this disease. Although molecular determinants of ALI have been reported, the molecules involved in disease catabasis associated with oxygen toxicity have not been well studied. It has been reported that lung mucosa is rich in omega-3 fatty acid dicosahexanoic acid (DHA), which has antiinflammatory properties. Aspirin-triggered resolvin D1 (AT-RvD1) is a potent proresolution metabolite of DHA that can curb the inflammatory effects in various acute injuries, yet the effect of AT-RvD1 on hyperoxic acute lung injury (HALI) or in the oxygen toxicity setting in general has not been investigated. The effects of AT-RvD1 on HALI were determined for the first time in 8- to 10-week-old C57BL/6 mice that were exposed to hyperoxia (≥95% O2) for 48 hours. Mice were given AT-RvD1 (100 ng) in saline or a saline vehicle for 24 hours in normoxic (≈21% O2) conditions after hyperoxia. Lung tissue and bronchoalveolar lavage (BAL) fluid were collected for analysis associated with proinflammatory signaling and lung inflammation. AT-RvD1 treatment resulted in reduced oxidative stress, increased glutathione production, and significantly decreased tissue inflammation. AT-RvD1 treatment also significantly reduced the lung wet/dry ratio, protein in BAL fluid, and decreased apoptotic and NF-κB signaling. These results show that AT-RvD1 curbs oxygen-induced lung edema, permeability, inflammation, and apoptosis and is thus an effective therapy for prolonged hyperoxia exposure in this murine model. PMID:25647402

  16. Genetic testing in diffuse parenchymal lung disease

    PubMed Central

    2012-01-01

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

  17. Myeloid tissue factor does not modulate lung inflammation or permeability during experimental acute lung injury.

    PubMed

    Shaver, Ciara M; Grove, Brandon S; Clune, Jennifer K; Mackman, Nigel; Ware, Lorraine B; Bastarache, Julie A

    2016-01-01

    Tissue factor (TF) is a critical mediator of direct acute lung injury (ALI) with global TF deficiency resulting in increased airspace inflammation, alveolar-capillary permeability, and alveolar hemorrhage after intra-tracheal lipopolysaccharide (LPS). In the lung, TF is expressed diffusely on the lung epithelium and intensely on cells of the myeloid lineage. We recently reported that TF on the lung epithelium, but not on myeloid cells, was the major source of TF during intra-tracheal LPS-induced ALI. Because of a growing body of literature demonstrating important pathophysiologic differences between ALI caused by different etiologies, we hypothesized that TF on myeloid cells may have distinct contributions to airspace inflammation and permeability between direct and indirect causes of ALI. To test this, we compared mice lacking TF on myeloid cells (TF(∆mye), LysM.Cre(+/-)TF(flox/flox)) to littermate controls during direct (bacterial pneumonia, ventilator-induced ALI, bleomycin-induced ALI) and indirect ALI (systemic LPS, cecal ligation and puncture). ALI was quantified by weight loss, bronchoalveolar lavage (BAL) inflammatory cell number, cytokine concentration, protein concentration, and BAL procoagulant activity. There was no significant contribution of TF on myeloid cells in multiple models of experimental ALI, leading to the conclusion that TF in myeloid cells is not a major contributor to experimental ALI. PMID:26924425

  18. Myeloid tissue factor does not modulate lung inflammation or permeability during experimental acute lung injury

    PubMed Central

    Shaver, Ciara M.; Grove, Brandon S.; Clune, Jennifer K.; Mackman, Nigel; Ware, Lorraine B.; Bastarache, Julie A.

    2016-01-01

    Tissue factor (TF) is a critical mediator of direct acute lung injury (ALI) with global TF deficiency resulting in increased airspace inflammation, alveolar-capillary permeability, and alveolar hemorrhage after intra-tracheal lipopolysaccharide (LPS). In the lung, TF is expressed diffusely on the lung epithelium and intensely on cells of the myeloid lineage. We recently reported that TF on the lung epithelium, but not on myeloid cells, was the major source of TF during intra-tracheal LPS-induced ALI. Because of a growing body of literature demonstrating important pathophysiologic differences between ALI caused by different etiologies, we hypothesized that TF on myeloid cells may have distinct contributions to airspace inflammation and permeability between direct and indirect causes of ALI. To test this, we compared mice lacking TF on myeloid cells (TF∆mye, LysM.Cre+/−TFflox/flox) to littermate controls during direct (bacterial pneumonia, ventilator-induced ALI, bleomycin-induced ALI) and indirect ALI (systemic LPS, cecal ligation and puncture). ALI was quantified by weight loss, bronchoalveolar lavage (BAL) inflammatory cell number, cytokine concentration, protein concentration, and BAL procoagulant activity. There was no significant contribution of TF on myeloid cells in multiple models of experimental ALI, leading to the conclusion that TF in myeloid cells is not a major contributor to experimental ALI. PMID:26924425

  19. [CYSTIC FIBROSIS: CARE OF THE LUNG DISEASE].

    PubMed

    Hubert, Dominique

    2015-10-01

    (Rh-DNase) and/or hydration (hypertonic saline) nebulisations, Moreover, treatment with inhaled antibiotics is indicated (tobramycin, colistine or aztreonam lysine) for chronic lung infection with Pseudomonas aeruginosa (PA). The treatment regimen also includes bronchodilators for bronchospasms and azithromycin. Regular physical activity is recommended. A treatment potentiating the CFTR protein, ivacaftor, is now indicated for patients with a class 3 mutation. Initial bronchial infection with PA must be treated as soon as possible in order to eradicate the pathogen. Pulmonary exacerbations require antibiotic courses, either orally or intravenously for PA infection. Complications require hospitalisation, with thoracic chest tube placement for a pneumothorax or bronchial artery embolisation for massive hemoptysis. Oxygen therapy and non-invasive ventilation with a nasal mask become necessary when respiratory insufficiency progresses, justifying the initiation of the lung transplant process. Lung disease affects the prognosis of cystic fibrosis, therefore its management in cystic fibrosis centres is of utmost importance. Maintenance treatment mainly relies on daily chest physiotherapy, which can be facilitated by mucolytic PMID:26749716

  20. MSC Microvesicles for the Treatment of Lung Disease: A New Paradigm for Cell-Free Therapy

    PubMed Central

    Sdrimas, Konstantinos

    2014-01-01

    Abstract Significance: Bronchopulmonary dysplasia (BPD), also known as chronic lung disease of infancy, is a major complication of preterm birth that, despite improvements in neonatal respiratory support and perinatal care, remains an important cause of morbidity and mortality, often with severe adverse neurodevelopmental sequelae. Even with major advances in our understanding of the pathogenesis of this disease, BPD remains essentially without adequate treatment. Recent Advances: Cell-based therapies arose as a promising treatment for acute and chronic lung injury in many experimental models of disease. Currently, more than 3000 human clinical trials employing cell therapy for the treatment of diverse diseases, including cardiac, neurologic, immune, and respiratory conditions, are ongoing or completed. Among the treatments, mesenchymal stem cells (MSCs) are the most studied and have been extensively tested in experimental models of BPD, pulmonary hypertension, pulmonary fibrosis, and acute lung injury. Critical Issues: Despite the promising potential, MSC therapy for human lung disease still remains at an experimental stage and optimal transplantation conditions need to be determined. Although the mechanism of MSC action can be manifold, accumulating evidence suggests a predominant paracrine, immunomodulatory, and cytoprotective effect. Future Directions: The current review summarizes the effect of MSC treatment in models of lung injury, including BPD, and focuses on the MSC secretome and, specifically, MSC-derived microvesicles as potential key mediators of therapeutic action that can be the focus of future therapies. Antioxid. Redox Signal. 21, 1905–1915. PMID:24382303

  1. Resveratrol potentiates the effect of dexamethasone in rat model of acute lung inflammation.

    PubMed

    Sadarani, Bhakti N; Majumdar, Anuradha S

    2015-09-01

    Cigarette smoking is considered to be the main etiological factor in Chronic Obstructive Pulmonary Disease (COPD). In this study, we explored the potential of resveratrol, to reinstate the effectiveness of dexamethasone when administered as an adjunct in acute lung inflammation induced by cigarette smoke (CS) and lipopolysaccharide (LPS). CS and LPS instillation produced acute inflammatory response exhibited by increased leukocyte count, particularly neutrophils, total protein, MMP-9 activity, cytokines like TNF-α, IL-8 in bronchoalveolar lavage fluid (BALF) as well as elevated myeloperoxidase activity, and lipid peroxidation in lung. These alterations were not abated by dexamethasone (2.5mg/kg & 10mg/kg) and resveratrol (50mg/kg) alone. Combination of resveratrol (50mg/kg) and dexamethasone (2.5mg/kg) significantly reduced all inflammatory parameters. The protective effect of the combination was abolished when co-administered with sirtinol, a SIRT1 inhibitor. The results indicate that the combination therapy may serve as a potential approach for treating lung inflammatory conditions like COPD. PMID:26283591

  2. Enforced expression of miR-125b attenuates LPS-induced acute lung injury.

    PubMed

    Guo, Zhongliang; Gu, Yutong; Wang, Chunhong; Zhang, Jie; Shan, Shan; Gu, Xia; Wang, Kailing; Han, Yang; Ren, Tao

    2014-11-01

    The acute respiratory distress syndrome (ARDS), a severe form of acute lung injury (ALI) in humans, is a leading cause of morbidity and mortality in critically ill patients. Despite decades of research, few therapeutic strategies for clinical ARDS have emerged. Recent evidence implicated a potential role of miR-125b in development of ALI. Here we evaluated the miR-125b-based strategy in treatment of ARDS using the murine model of lipopolysaccharide (LPS)-induced ALI. We found that up-regulation of miR-125b expression maintained the body weight and survival of ALI mice, and significantly reduced LPS-induced pulmonary inflammation as reflected by reductions in total cell and neutrophil counts, proinflammatory cytokines, as well as chemokines in BAL fluid. Further, enforced expression of miR-125b resulted in remarkable reversal of LPS-induced increases in lung permeability as assessed by reductions in total protein, albumin and IgM in BAL fluid, and ameliorated the histopathology changes of lung in LPS-induced ALI mice. Of interest, serum miR-125b expression was also decreased and inversely correlated with the disease severity in patients with ARDS. Our findings strongly demonstrated that enforced expression of miR-125b could effectively ameliorate the LPS-induced ALI, suggesting a potential application for miR-125b-based therapy to treat clinical ARDS. PMID:25004393

  3. Farmer's lung

    PubMed Central

    Hapke, E. J.; Seal, R. M. E.; Thomas, G. O.; Hayes, M.; Meek, J. C.

    1968-01-01

    In assessing patients suffering from farmer's lung, the acute stage must be distinguished from the chronic stage of the disease. The conspicuous radiographic signs in the acute farmer's lung episode and the often dramatic clearing make an important contribution to the diagnosis. The radiographic changes in chronic farmer's lung are not specific and cover a wide range of appearances. Even minor nodular changes are significant. Farmer's lung, acute and chronic, is not a disease predominantly characterized by a defect in gas exchange. During the acute illness the reduction in diffusing capacity is often accompanied by a decrease in lung volumes; the pulmonary function profile of the chronic stage is variable. In only a relatively small proportion of chronic farmer's lung patients does a defect in gas exchange predominate, and in some it may be manifest only during exercise. Airway obstruction is a feature of chronic farmer's lung. In chronic farmer's lung patients discrepancies between the severity of complaints and results of pulmonary function tests are not infrequent. In some patients with considerable disability conventional pulmonary function studies may demonstrate little or no impairment of the functions measured. In patients suffering from an acute farmer's lung episode, serological tests should be positive, possibly in high titre. In the chronic stage of the disease the chance of finding positive serology in a patient diminishes with the length of time elapsed since the last acute episode. The period of serological transition appears to be the third year. Images PMID:4971361

  4. Effect of dobutamine on lung aquaporin 5 in endotoxine shock-induced acute lung injury rabbit

    PubMed Central

    Sun, Cai-Zhi; Shen, Hua; He, Xiao-Wei; Bao, Lei; Song, Yang

    2015-01-01

    Background Dobutamine, a commonly used vasoactive drug, has been reported to reduce pulmonary edema and protect against acute lung injury (ALI) by up-regulating aquaporin 5 (AQP5) expressions. However, the underlying mechanism is still elusive. Methods ALI was induced by intravenous injection of LPS. Seventy male New Zealand white rabbits were randomly divided into seven groups: sham group, ALI group, dobutamine low-dose group [group ALI + Dob (L)], dobutamine medium-dose group [group ALI + Dob (M)], dobutamine high-dose group [group ALI + Dob (H)], ALI + Dob (H) + ICI group and sham + ICI group. ICI 118,551, a potent and specific beta-2 antagonist, could block the effect of dobutamine. The animals were sacrificed at 3 h after endotoxic shock and lungs were removed. The arterial blood gas was analyzed. The lung wet to dry (W/D) ratio was determined. The level of cyclic AMP (cAMP) in lung tissue was assessed by ELISA. The expression of AQP5 protein was determined by western blotting and immunohistochemistry. The pathological alteration in lung tissue was evaluated by optical microscopy and electron microscope, and lung injury score was assessed. Results Dobutamine increased AQP5 protein expression and cAMP level in a dose-dependent manner. Meanwhile, the degree of lung pathological and ultrastructural lesion was ameliorated and arterial blood gas was improved obviously. Additionally, W/D ratio and histological scores decreased significantly. However, the AQP5 protein expression and cAMP level were significantly decreased in group ALI + Dob (H) + ICI than that in group ALI + Dob (H), the degree of lung pathological and ultrastructural lesion was more serious in group ALI + Dob (H) + ICI than that in group ALI + Dob (H) and the arterial blood gas was not obviously improved. Conclusions These results suggested that protective effect of dobutamine against endotoxin shock-induced ALI may be due to its ability of up-regulating AQP5 protein expression via increasing intracellular cAMP concentration. PMID:26380773

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2004-01-01

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

  7. Environmental and occupational lung diseases in Indonesia.

    PubMed

    Mangunnegoro, H; Sutoyo, D K

    1996-06-01

    Indonesia as a developing country has air pollution which is mainly caused by motor vehicle emissions and industrial smoke. The most important indoor air pollution is cigarette smoke. The prevalence of smoking among Indonesian men is 45.7%. Of the population, 10.8% are ex-smokers and 43.5% are non-smokers. Among the female population, only 1.8% smoke. There are some important factors that influence the air pollution in Indonesia; this paper identifies the real problems and their impact. The paper reviews various studies that have been carried out in Indonesia which were related to ambient air quality, industrial air pollutants levels (SO2, NOx, Ox, Pb, CO, HC) in large cities in Indonesia have exceeded the acceptable level, especially in industrial trade and heavy traffic areas. The more cigarettes inhaled and the deeper the inhalation, especially the kretek cigarettes, the risk of ling function abnormality becomes greater. Smoking high dose kretek cigarettes, that is > or = 116 cigarettes/day x years, the risk of abnormal lung function is 13-fold that of a non-smoker; if added with the deep inhalation of smoke, the risk becomes 20-fold. Smoking increases the risk of occupational lung disease. The level of dust in some industrial areas exceeded the standard level and correlated with respiratory problems. The existence of industry caused by air pollution in the environment increased the incidence of obstructive airway diseases. We conclude that the main cause of air pollution in Indonesia is motor vehicle emissions, followed by industrial smoke. Cigarette smoke is also related to abnormal lung function. PMID:9434323

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

    PubMed

    Takada, Toshinori; Moriyama, Hiroshi; Suzuki, Eiichi

    2014-01-01

    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

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

    PubMed Central

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

    2013-01-01

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

  10. Protein-based Therapies for Acute Lung Injury: Targeting Neutrophil Extracellular Traps

    PubMed Central

    Bosmann, Markus; Ward, Peter A.

    2014-01-01

    Introduction Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the acute onset of non-cardiac respiratory insufficiency associated with bilateral lung infiltrations. During the past decade, mechanical ventilation strategies using low tidal volumes have reduced the mortality of ALI/ARDS to around 20-40%. However, ALI/ARDS continues to be a major factor in global burden of diseases, with no pharmacologic agents currently available. Areas covered In this review we discuss several inflammatory proteins involved in the molecular pathogenesis of ALI/ARDS. The complement cleavage product, C5a, is a peptide acting as a potent anaphylatoxin. C5a may trigger the formation of neutrophil extracellular traps (NETs) and release of histone proteins to the extracellular compartment during ALI/ARDS.NETs may activate platelets to release TGFβ which is involved in tissue remodeling during the later phases of ALI/ARDS. Interception of C5a signaling or blockade of extracellular histones has recently shown promising beneficial effects in small animal models of ALI/ARDS. Expert opinion Novel protein-based strategies for the treatment of ALI/ARDS may inspire the hopes of scientists, clinicians and patients. While neutralization of extracellular histones / NETs, C5a and TGFβ is effective in experimental models of ALI/ARDS, controlled clinical trials will be necessary for further evaluation in future. PMID:24670033

  11. The role of C5a in acute lung injury induced by highly pathogenic viral infections

    PubMed Central

    Wang, Renxi; Xiao, He; Guo, Renfeng; Li, Yan; Shen, Beifen

    2015-01-01

    The complement system, an important part of innate immunity, plays a critical role in pathogen clearance. Unregulated complement activation is likely to play a crucial role in the pathogenesis of acute lung injury (ALI) induced by highly pathogenic virus including influenza A viruses H5N1, H7N9, and severe acute respiratory syndrome (SARS) coronavirus. In highly pathogenic virus-induced acute lung diseases, high levels of chemotactic and anaphylatoxic C5a were produced as a result of excessive complement activaiton. Overproduced C5a displays powerful biological activities in activation of phagocytic cells, generation of oxidants, and inflammatory sequelae named “cytokine storm”, and so on. Blockade of C5a signaling have been implicated in the treatment of ALI induced by highly pathogenic virus. Herein, we review the literature that links C5a and ALI, and review our understanding of the mechanisms by which C5a affects ALI during highly pathogenic viral infection. In particular, we discuss the potential of the blockade of C5a signaling to treat ALI induced by highly pathogenic viruses. PMID:26060601

  12. Biomarkers in Acute Lung Injury – Marking Forward Progress

    PubMed Central

    Barnett, Nicolas; Ware, Lorraine B.

    2011-01-01

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

  13. Microcirculation in Acute and Chronic Kidney Diseases.

    PubMed

    Zafrani, Lara; Ince, Can

    2015-12-01

    The renal microvasculature is emerging as a key player in acute and chronic kidney diseases. Renal microvascular disease involves alterations in endothelial barrier permeability, exaggerated inflammation, impairment of endothelium-dependent vasorelaxation involving the nitric oxide system, increased oxidative stress, and loss of angiogenic factors. Moreover, evidence suggests that there is a microvascular component to the pathogenesis of renal scarring. New technology is being developed to explore renal microcirculation in vivo in experimental models and humans. This technology will provide a better understanding of the pathogenesis of kidney diseases and will help guide specific therapeutic strategies aimed at restoring the renal microcirculation. This article reviews the cellular and molecular mechanisms of renal microvascular dysfunction in acute and chronic kidney diseases and the potential diagnostic and therapeutic implications of these findings. Recent developments in the monitoring of renal microcirculation are described with respect to their advantages and limitations, and future directions are outlined. PMID:26231789

  14. Lung Neutrophilia in Myeloperoxidase Deficient Mice during the Course of Acute Pulmonary Inflammation

    PubMed Central

    Kremserova, Silvie; Perecko, Tomas; Soucek, Karel; Klinke, Anna; Baldus, Stephan; Eiserich, Jason P.; Kubala, Lukas

    2016-01-01

    Systemic inflammation accompanying diseases such as sepsis affects primarily lungs and induces their failure. This remains the most common cause of sepsis induced mortality. While neutrophils play a key role in pulmonary failure, the mechanisms remain incompletely characterized. We report that myeloperoxidase (MPO), abundant enzyme in neutrophil granules, modulates the course of acute pulmonary inflammatory responses induced by intranasal application of lipopolysaccharide. MPO deficient mice had significantly increased numbers of airway infiltrated neutrophils compared to wild-type mice during the whole course of lung inflammation. This was accompanied by higher levels of RANTES in bronchoalveolar lavage fluid from the MPO deficient mice. Other markers of lung injury and inflammation, which contribute to recruitment of neutrophils into the inflamed lungs, including total protein and other selected proinflammatory cytokines did not significantly differ in bronchoalveolar lavage fluid from the wild-type and the MPO deficient mice. Interestingly, MPO deficient neutrophils revealed a decreased rate of cell death characterized by phosphatidylserine surface expression. Collectively, the importance of MPO in regulation of pulmonary inflammation, independent of its putative microbicidal functions, can be potentially linked to MPO ability to modulate the life span of neutrophils and to affect accumulation of chemotactic factors at the inflammatory site. PMID:26998194

  15. Effects of ischemic acute kidney injury on lung water balance: nephrogenic pulmonary edema?

    PubMed

    Basu, Rajit K; Wheeler, Derek

    2011-01-01

    Pulmonary edema worsens the morbidity and increases the mortality of critically ill patients. Mechanistically, edema formation in the lung is a result of net flow across the alveolar capillary membrane, dependent on the relationship of hydrostatic and oncotic pressures. Traditionally, the contribution of acute kidney injury (AKI) to the formation of pulmonary edema has been attributed to bulk fluid accumulation, increasing capillary hydrostatic pressure and the gradient favoring net flow into the alveolar spaces. Recent research has revealed more subtle, and distant, effects of AKI. In this review we discuss the concept of nephrogenic pulmonary edema. Pro-inflammatory gene upregulation, chemokine over-expression, altered biochemical channel function, and apoptotic dysregulation manifest in the lung are now understood as "extra-renal" and pulmonary effects of AKI. AKI should be counted as a disease process that alters the endothelial integrity of the alveolar capillary barrier and has the potential to overpower the ability of the lung to regulate fluid balance. Nephrogenic pulmonary edema, therefore, is the net effect of fluid accumulation in the lung as a result of both the macroscopic and microscopic effects of AKI. PMID:21660235

  16. Effects of Ischemic Acute Kidney Injury on Lung Water Balance: Nephrogenic Pulmonary Edema?

    PubMed Central

    Basu, Rajit K.; Wheeler, Derek

    2011-01-01

    Pulmonary edema worsens the morbidity and increases the mortality of critically ill patients. Mechanistically, edema formation in the lung is a result of net flow across the alveolar capillary membrane, dependent on the relationship of hydrostatic and oncotic pressures. Traditionally, the contribution of acute kidney injury (AKI) to the formation of pulmonary edema has been attributed to bulk fluid accumulation, increasing capillary hydrostatic pressure and the gradient favoring net flow into the alveolar spaces. Recent research has revealed more subtle, and distant, effects of AKI. In this review we discuss the concept of nephrogenic pulmonary edema. Pro-inflammatory gene upregulation, chemokine over-expression, altered biochemical channel function, and apoptotic dysregulation manifest in the lung are now understood as extra-renal and pulmonary effects of AKI. AKI should be counted as a disease process that alters the endothelial integrity of the alveolar capillary barrier and has the potential to overpower the ability of the lung to regulate fluid balance. Nephrogenic pulmonary edema, therefore, is the net effect of fluid accumulation in the lung as a result of both the macroscopic and microscopic effects of AKI. PMID:21660235

  17. Impact of mechanical ventilation on the pathophysiology of progressive acute lung injury.

    PubMed

    Nieman, Gary F; Gatto, Louis A; Habashi, Nader M

    2015-12-01

    The earliest description of what is now known as the acute respiratory distress syndrome (ARDS) was a highly lethal double pneumonia. Ashbaugh and colleagues (Ashbaugh DG, Bigelow DB, Petty TL, Levine BE Lancet 2: 319-323, 1967) correctly identified the disease as ARDS in 1967. Their initial study showing the positive effect of mechanical ventilation with positive end-expiratory pressure (PEEP) on ARDS mortality was dampened when it was discovered that improperly used mechanical ventilation can cause a secondary ventilator-induced lung injury (VILI), thereby greatly exacerbating ARDS mortality. This Synthesis Report will review the pathophysiology of ARDS and VILI from a mechanical stress-strain perspective. Although inflammation is also an important component of VILI pathology, it is secondary to the mechanical damage caused by excessive strain. The mechanical breath will be deconstructed to show that multiple parameters that comprise the breath-airway pressure, flows, volumes, and the duration during which they are applied to each breath-are critical to lung injury and protection. Specifically, the mechanisms by which a properly set mechanical breath can reduce the development of excessive fluid flux and pulmonary edema, which are a hallmark of ARDS pathology, are reviewed. Using our knowledge of how multiple parameters in the mechanical breath affect lung physiology, the optimal combination of pressures, volumes, flows, and durations that should offer maximum lung protection are postulated. PMID:26472873

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

    PubMed

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

    1983-06-01

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

  19. Inhibition of lipopolysaccharide induced acute inflammation in lung by chlorination.

    PubMed

    Zhang, Jinshan; Xue, Jinling; Xu, Bi; Xie, Jiani; Qiao, Juan; Lu, Yun

    2016-02-13

    Lipopolysaccharide (LPS, also called endotoxin) is a pro-inflammatory constituent of gram negative bacteria and cyanobacteria, which causes a potential health risk in the process of routine urban application of reclaimed water, such as car wash, irrigation, scenic water refilling, etc. Previous studies indicated that the common disinfection treatment, chlorination, has little effect on endotoxin activity removal measured by Limulus amebocyte lysate (LAL) assay. However, in this study, significant decrease of acute inflammatory effects was observed in mouse lung, while LAL assay still presented a moderate increase of endotoxin activity. To explore the possible mechanisms, the nuclear magnetic resonance (NMR) results showed the chlorination happened in alkyl chain of LPS molecules, which could affect the interaction between LPS and LPS-binding protein. Also the size of LPS aggregates was found to drop significantly after treatment, which could be another results of chlorination caused polarity change. In conclusion, our observation demonstrated that chlorination is effective to reduce the LPS induced inflammation in lung, and it is recommended to use health effect-based methods to assess risk removal of water treatment technologies. PMID:26530889

  20. Strain Echocardiography in Acute Cardiovascular Diseases

    PubMed Central

    Favot, Mark; Courage, Cheryl; Ehrman, Robert; Khait, Lyudmila; Levy, Phillip

    2016-01-01

    Echocardiography has become a critical tool in the evaluation of patients presenting to the emergency department (ED) with acute cardiovascular diseases and undifferentiated cardiopulmonary symptoms. New technological advances allow clinicians to accurately measure left ventricular (LV) strain, a superior marker of LV systolic function compared to traditional measures such as ejection fraction, but most emergency physicians (EPs) are unfamiliar with this method of echocardiographic assessment. This article discusses the application of LV longitudinal strain in the ED and reviews how it has been used in various disease states including acute heart failure, acute coronary syndromes (ACS) and pulmonary embolism. It is important for EPs to understand the utility of technological and software advances in ultrasound and how new methods can build on traditional two-dimensional and Doppler techniques of standard echocardiography. The next step in competency development for EP-performed focused echocardiography is to adopt novel approaches such as strain using speckle-tracking software in the management of patients with acute cardiovascular disease. With the advent of speckle tracking, strain image acquisition and interpretation has become semi-automated making it something that could be routinely added to the sonographic evaluation of patients presenting to the ED with cardiovascular disease. Once strain imaging is adopted by skilled EPs, focused echocardiography can be expanded and more direct, phenotype-driven care may be achievable for ED patients with a variety of conditions including heart failure, ACS and shock. PMID:26823931

  1. Strain Echocardiography in Acute Cardiovascular Diseases.

    PubMed

    Favot, Mark; Courage, Cheryl; Ehrman, Robert; Khait, Lyudmila; Levy, Phillip

    2016-01-01

    Echocardiography has become a critical tool in the evaluation of patients presenting to the emergency department (ED) with acute cardiovascular diseases and undifferentiated cardiopulmonary symptoms. New technological advances allow clinicians to accurately measure left ventricular (LV) strain, a superior marker of LV systolic function compared to traditional measures such as ejection fraction, but most emergency physicians (EPs) are unfamiliar with this method of echocardiographic assessment. This article discusses the application of LV longitudinal strain in the ED and reviews how it has been used in various disease states including acute heart failure, acute coronary syndromes (ACS) and pulmonary embolism. It is important for EPs to understand the utility of technological and software advances in ultrasound and how new methods can build on traditional two-dimensional and Doppler techniques of standard echocardiography. The next step in competency development for EP-performed focused echocardiography is to adopt novel approaches such as strain using speckle-tracking software in the management of patients with acute cardiovascular disease. With the advent of speckle tracking, strain image acquisition and interpretation has become semi-automated making it something that could be routinely added to the sonographic evaluation of patients presenting to the ED with cardiovascular disease. Once strain imaging is adopted by skilled EPs, focused echocardiography can be expanded and more direct, phenotype-driven care may be achievable for ED patients with a variety of conditions including heart failure, ACS and shock. PMID:26823931

  2. IL-17 response mediates acute lung injury induced by the 2009 pandemic influenza A (H1N1) virus.

    PubMed

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

    2012-03-01

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

  3. Upregulation of PIAS1 protects against sodium taurocholate-induced severe acute pancreatitis associated with acute lung injury.

    PubMed

    Chen, Ping; Huang, Liya; Sun, Yunwei; Yuan, Yaozong

    2011-06-01

    The regulator of cytokine signaling known as protein inhibitor of activated STAT-1 (PIAS1) is increasingly understood to have diverse regulatory functions for inflammation, but its effect in inflammatory conditions such as severe acute pancreatitis (SAP) has not previously been reported. The aim of this study was to investigate the effect of upregulation of PIAS1 on SAP associated with acute lung injury (ALI), and its subsequent effect on disease severity. Sprague-Dawley rats were given an IV injection of adenovirus serotype 5 (Ad5)/F35-PIAS1, Ad5/F35-vector or saline before induction of SAP. The control group received only a sham operation. Lung and pancreas samples were harvested 16h after induction. The protein levels of PIAS1 in tissue were investigated. The severity of pancreatic injury was determined by a histological score of pancreatic injury, serum amylase, and pancreatic water content. The lung injury was evaluated by measurement of pulmonary microvascular permeability, lung myeloperoxidase activity and malondialdehyde levels. The survival rates of rats were also analyzed. The results found that in Ad5/F35-PIAS1 treated rats, serum tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 levels were decreased but showed no influence on the levels of IL-10, and the severity of pancreatic tissue injury was less compared with either untreated SAP or Ad5/F35-vector treated rats (P<0.01). The administration of Ad5/F35-PIAS1 in SAP-induced rats downregulated the activity of the signal transducer and activator of transcription-1 (STAT1) pathway and the expressions of matrix metalloproteinase-9 (MMP-9) and intercellular adhesion molecule (ICAM)-1 protein in lung. Thus, compared with the untreated SAP rats, the inflammatory response and the severity of ALI decreased, and the survival rates increased (P<0.01). These findings suggest that PIAS1 could augment anti-inflammatory activity by inhibiting STAT1, thus attenuating the severity of SAP associated with ALI. PMID:21419645

  4. Allograft inflammatory factor-1 in the pathogenesis of bleomycin-induced acute lung injury.

    PubMed

    Nagahara, Hidetake; Yamamoto, Aihiro; Seno, Takahiro; Obayashi, Hiroshi; Kida, Takashi; Nakabayashi, Amane; Kukida, Yuji; Fujioka, Kazuki; Fujii, Wataru; Murakami, Ken; Kohno, Masataka; Kawahito, Yutaka

    2016-03-10

    Allograft inflammatory factor-1 (AIF-1) is a protein expressed by macrophages infiltrating the area around the coronary arteries of rats with an ectopic cardiac allograft. Some studies have shown that expression of AIF-1 increased in a mouse model of trinitrobenzene sulfonic acid-induced acute colitis and in acute cellular rejection of human cardiac allografts. These results suggest that AIF-1 is related to acute inflammation. The current study used bleomycin-induced acute lung injury to analyze the expression of AIF-1 and to examine its function in acute lung injury. Results showed that AIF-1 was significantly expressed in lung macrophages and increased in bronchoalveolar lavage fluid from mice with bleomycin-induced acute lung injury in comparison to control mice. Recombinant AIF-1 increased the production of IL-6 and TNF-α from RAW264.7 (a mouse macrophage cell line) and primary lung fibroblasts, and it also increased the production of KC (CXCL1) from lung fibroblasts. These results suggest that AIF-1 plays an important role in the mechanism underlying acute lung injury. PMID:26911661

  5. Underlying host risk factors for nontuberculous mycobacterial lung disease.

    PubMed

    Chan, Edward D; Iseman, Michael D

    2013-02-01

    Nontuberculous mycobacteria (NTM) are environmental microbes that cause a variety of human diseases, particularly chronic lung infections. Despite the fact that NTM are widespread in the environment, relatively few people develop NTM lung disease, suggesting intrinsic vulnerability in some individuals. This paper reviews the evidence that underlying disorders predispose to NTM lung disease, in particular primary conditions that result in bronchiectasis, chronic obstructive pulmonary disease, α-1-antitrypsin anomalies, pneumoconiosis, pulmonary alveolar proteinosis, and frank immunosuppressive states such as that associated with the use of anti-tumor necrosis factor-α biologics, posttransplantation immunosuppression, and HIV infection. Over the past several decades, NTM lung disease has been increasingly identified in postmenopausal women with slender body habitus. Thus we will also review the clinical and experimental evidence which supports the observation that such individuals are predisposed to NTM lung disease. PMID:23460011

  6. Fas and Fas Ligand Are Up-Regulated in Pulmonary Edema Fluid and Lung Tissue of Patients with Acute Lung Injury and the Acute Respiratory Distress Syndrome

    PubMed Central

    Albertine, Kurt H.; Soulier, Matthew F.; Wang, Zhengming; Ishizaka, Akitoshi; Hashimoto, Satoru; Zimmerman, Guy A.; Matthay, Michael A.; Ware, Lorraine B.

    2002-01-01

    Apoptosis mediated by Fas/Fas ligand (FasL) interaction has been implicated in human disease processes, including pulmonary disorders. However, the role of the Fas/FasL system in acute lung injury (ALI) and in the acute respiratory distress syndrome (ARDS) is poorly defined. Accordingly, we investigated both the soluble and cellular expression of the Fas/FasL system in patients with ALI or ARDS. The major findings are summarized as follows. First, the soluble expression of the Fas/FasL system was assessed in undiluted pulmonary edema fluid and simultaneous plasma. Pulmonary edema fluid obtained from patients with ALI or ARDS (n = 51) had significantly higher concentrations of both soluble Fas (27 ng/ml; median; P < 0.05) and soluble FasL (0.125 ng/ml; P < 0.05) compared to control patients with hydrostatic pulmonary edema (n = 40; soluble Fas, 12 ng/ml; soluble FasL, 0.080 ng/ml). In addition, the concentrations of both soluble Fas and soluble FasL were significantly higher in the pulmonary edema fluid of the patients with ALI or ARDS compared to simultaneous plasma samples (soluble Fas, 16 ng/ml; soluble FasL, 0.058 ng/ml; P < 0.05), indicating local release in the lung. Higher soluble Fas concentrations were associated with worse clinical outcomes. Second, cellular expression of the Fas/FasL system was assessed by semiquantitative immunofluorescence microscopy in lung tissue obtained at autopsy from a different set of patients. Both Fas and FasL were immunolocalized to a greater extent in the patients who died with ALI or ARDS (n = 10) than in the patients who died without pulmonary disease (n = 10). Both proteins were co-expressed by epithelial cells that lined the alveolar walls, as well as by inflammatory cells and sloughed epithelial cells that were located in the air spaces. Semiquantitative immunohistochemistry showed that markers of apoptosis (terminal dUTP nick-end labeling, caspase-3, Bax, and p53) were more prevalent in alveolar wall cells from the patients who died with ALI or ARDS compared to the patients who died without pulmonary disease. These findings indicate that alveolar epithelial injury in humans with ALI or ARDS is in part associated with local up-regulation of the Fas/FasL system and activation of the apoptotic cascade in the epithelial cells that line the alveolar air spaces. PMID:12414525

  7. Invasive Aspergillus infections in hospitalized patients with chronic lung disease

    PubMed Central

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

    2013-01-01

    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. PMID:23761976

  8. [Lung resection for patients with lung cancer and chronic obstructive pulmonary disease].

    PubMed

    Nishikawa, S; Chihara, K

    2012-07-01

    The number of lung resection for patients with lung cancer has been increasing lineally for last two decades in Japan. It reached more than 30,000 in 2009. Subsequently those combined with chronic obstructive pulmonary disease (COPD) also have increased. As pulmonary vascular bed has already been lost to some extent due to chronic alveolar destruction, a careful preoperative physiologic assessment according to a guideline by American College of Chest Physicians (ACCP) or European Respiratory Society( ERS)/European Society of Thoracic Surgeons( ESTS) is important to select patients to be underwent lung resection within acceptable risk. The process to evaluate the risk of lung resection for a lung cancer patient has three steps structured by forced expiratory volume in 1 sec( FEV1), diffusion capacitiy for carbon monoxide (DLco), and exercise capacity. We suggested that it would be more practical to add global initiative for obstructive lung disease( GOLD) staging of each patient and distribution of emphysematous lung obtained by functional imaging modarities to the pathway of flow chart of the guideline. Some patients with very low FEV1 demonstrate increase in FEV1 after lung resection by so called lung volume reduction effect. To utilize lots of findings and experiences obtained from lung volume reduction surgery( LVRS) contributes to select patients with lung cancer and COPD and to perform lung resection and perioperative care properly. PMID:22868433

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

    PubMed Central

    2014-01-01

    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

  10. Blue Journal Conference. Aging and Susceptibility to Lung Disease

    PubMed Central

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

    2015-01-01

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

  11. CHRONIC EXPOSURE TO OZONE CAUSES RESTRICTIVE LUNG DISEASE

    EPA Science Inventory

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

  12. Smart Technology in Lung Disease Clinical Trials.

    PubMed

    Geller, Nancy L; Kim, Dong-Yun; Tian, Xin

    2016-01-01

    This article describes the use of smart technology by investigators and patients to facilitate lung disease clinical trials and make them less costly and more efficient. By "smart technology" we include various electronic media, such as computer databases, the Internet, and mobile devices. We first describe the use of electronic health records for identifying potential subjects and then discuss electronic informed consent. We give several examples of using the Internet and mobile technology in clinical trials. Interventions have been delivered via the World Wide Web or via mobile devices, and both have been used to collect outcome data. We discuss examples of new electronic devices that recently have been introduced to collect health data. While use of smart technology in clinical trials is an exciting development, comparison with similar interventions applied in a conventional manner is still in its infancy. We discuss advantages and disadvantages of using this omnipresent, powerful tool in clinical trials, as well as directions for future research. PMID:26135330

  13. Total ginsenosides synergize with ulinastatin against septic acute lung injury and acute respiratory distress syndrome.

    PubMed

    Sun, Rongju; Li, Yana; Chen, Wei; Zhang, Fei; Li, Tanshi

    2015-01-01

    Total ginsenosides synergize with ulinastatin (UTI) against septic acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). We randomly divided 80 cases of severe sepsis-induced ALI and ARDS into a UTI group and a ginsenosides (GS)+UTI group. Continuous electrocardiac monitoring of pulse, respiratory rate, blood pressure, and heart rate; invasive hemodynamic monitoring; ventilator-assisted breathing and circulation support; and anti-infection as well as UTI treatment were given in the UTI group with GS treatment added for 7 consecutive days in the GS+UTI group. The indicators of pulmonary vascular permeability, pulmonary circulation, blood gases, and hemodynamics as well as APACHE II and ALI scores were detected on days 1, 3, and 7. The ALI score in the GS+UTI group was significantly decreased (P < 0.05) compared with that of the UTI group, and the indicators of pulmonary capillary permeability such as pulmonary vascular permeability index, extravascular lung water index, and oxygenation index, in the GS+UTI group improved significantly more than that of the UTI group. The indicators of hemodynamics and pulmonary circulation such as cardiac index, intrathoracic blood volume index, and central venous pressure improved significantly (P < 0.05), and the APACHE II score in the GS+UTI group was lower than that of the UTI group. GS can effectively collaborate with UTI against ALI and/or ARDS. PMID:26261640

  14. Lung diseases in the tropics. Part 2: Common tropical lung diseases: diagnosis and management.

    PubMed

    Sharma, O P; Maheshwari, A

    1993-12-01

    This is the second of the two articles discussing clinical features, radiographic abnormalities, laboratory tests, pathogenesis and therapy of common tropical disorders affecting the lungs. We have arbitrarily selected the diseases, which are worldwide in distribution and demand urgency in addressing the problems of morbidity and mortality. The tropical physician is often reduced to administering pills, capsules or liquids. Our aim is to provide succinct and clear descriptions combining scientific information with common sense clinical wisdom. PMID:8136488

  15. Gastroesophageal Reflux Disease and Graft Failure Following Lung Transplantation

    PubMed Central

    Mohammed, Aminu; Neujahr, David C.

    2010-01-01

    In spite of advances in the field of lung transplantation, the median survival following lung transplant remains below 5 years, an outcome which is significantly worse than other solid organ transplants. Efforts to understand the unique hurdles faced in lung transplant have revealed gastroesophageal reflux disease (GERD) as a risk factor for ultimate graft failure. The link between GERD and chronic lung rejection parallels the association between GERD and other forms of lung disease such as idiopathic pulmonary fibrosis. Understanding how GERD predisposes to graft failure is an important issue as it may lead to therapies such as surgical correction which aim to lessen the exposure of the pulmonary epithelium to gastric contents. Here we review the link between GERD and lung disease and discuss the preclinical and clinical studies which are starting to elucidate a mechanism for this association. PMID:20153957

  16. Malfolded Protein Structure and Proteostasis in Lung Diseases

    PubMed Central

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

    2014-01-01

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

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

    SciTech Connect

    De Ruyck, Kim; Sabbe, Nick; Oberije, Cary; Vandecasteele, Katrien; Thas, Olivier; De Ruysscher, Dirk; Lambin, Phillipe; Van Meerbeeck, Jan; De Neve, Wilfried; Thierens, Hubert

    2011-10-01

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

  18. Acute exacerbations of chronic obstructive pulmonary disease: causes and impacts.

    PubMed

    Chhabra, Sunil K; Dash, Devi Jyoti

    2014-01-01

    Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are recognised clinically as episodes of increased breathlessness and productive cough requiring a more intensive treatment. A subset of patients with this disease is especially prone to such exacerbations. These patients are labelled as 'frequent exacerbators'. Though yet poorly characterised in terms of host characteristics, including any genetic basis, these patients are believed to represent a distinct phenotype as they have a different natural history with a more progressive disease and a poorer prognosis than those who get exacerbations infrequently. Most exacerbations appear to be associated with infective triggers, either bacterial or viral, although 'non-infective' agents, such as air pollution and other irritants may also be important. Susceptibility to exacerbations is determined by multiple factors. Several risk factors have been identified, some of which are modifiable. Chronic obstructive pulmonary disease (COPD) exacerbations are major drivers of health status and patient-centered outcomes, and are a major reason for health care utilisation including hospitalisations and intensive care admissions. These are associated with considerable morbidity and mortality, both immediate and long-term. These episodes have a negative impact on the patient and the disease including high economic burden, increased mortality, worsening of health status, limitation of activity, and aggravation of comorbidities including cardiovascular disease, osteoporosis and neuro-psychiatric complications. Exacerbations also increase the rate of progression of disease, increasing the annual decline in lung function and leading to a poorer prognosis. Evaluation of risk of exacerbations is now included as a major component of the initial assessment of a patient with COPD in addition to the traditionally used lung function parameter, forced expiratory volume in one second (FEV1). Decreasing the risk of exacerbations and their prevention is a major therapeutic goal of management in COPD. PMID:25230550

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

    PubMed Central

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

    2013-01-01

    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. PMID:24204926

  20. Lung Transcriptomics during Protective Ventilatory Support in Sepsis-Induced Acute Lung Injury

    PubMed Central

    Acosta-Herrera, Marialbert; Lorenzo-Diaz, Fabian; Pino-Yanes, Maria; Corrales, Almudena; Valladares, Francisco; Klassert, Tilman E.; Valladares, Basilio; Slevogt, Hortense; Ma, Shwu-Fan

    2015-01-01

    Acute lung injury (ALI) is a severe inflammatory process of the lung. The only proven life-saving support is mechanical ventilation (MV) using low tidal volumes (LVT) plus moderate to high levels of positive end-expiratory pressure (PEEP). However, it is currently unknown how they exert the protective effects. To identify the molecular mechanisms modulated by protective MV, this study reports transcriptomic analyses based on microarray and microRNA sequencing in lung tissues from a clinically relevant animal model of sepsis-induced ALI. Sepsis was induced by cecal ligation and puncture (CLP) in male Sprague-Dawley rats. At 24 hours post-CLP, septic animals were randomized to three ventilatory strategies: spontaneous breathing, LVT (6 ml/kg) plus 10 cmH2O PEEP and high tidal volume (HVT, 20 ml/kg) plus 2 cmH2O PEEP. Healthy, non-septic, non-ventilated animals served as controls. After 4 hours of ventilation, lung samples were obtained for histological examination and gene expression analysis using microarray and microRNA sequencing. Validations were assessed using parallel analyses on existing publicly available genome-wide association study findings and transcriptomic human data. The catalogue of deregulated processes differed among experimental groups. The ‘response to microorganisms’ was the most prominent biological process in septic, non-ventilated and in HVT animals. Unexpectedly, the ‘neuron projection morphogenesis’ process was one of the most significantly deregulated in LVT. Further support for the key role of the latter process was obtained by microRNA studies, as four species targeting many of its genes (Mir-27a, Mir-103, Mir-17-5p and Mir-130a) were found deregulated. Additional analyses revealed 'VEGF signaling' as a central underlying response mechanism to all the septic groups (spontaneously breathing or mechanically ventilated). Based on this data, we conclude that a co-deregulation of 'VEGF signaling' along with 'neuron projection morphogenesis', which have been never anticipated in ALI pathogenesis, promotes lung-protective effects of LVT with high levels of PEEP. PMID:26147972

  1. Acute recurrent pancreatitis: An autoimmune disease?

    PubMed Central

    Pezzilli, Raffaele

    2008-01-01

    In this review article, we will briefly describe the main characteristics of autoimmune pancreatitis and then we will concentrate on our aim, namely, evaluating the clinical characteristics of patients having recurrence of pain from the disease. In fact, the open question is to evaluate the possible presence of autoimmune pancreatitis in patients with an undefined etiology of acute pancreatitis and for this reason we carried out a search in the literature in order to explore this issue. In cases of recurrent attacks of pain in patients with “diopathic”pancreatitis, we need to keep in mind the possibility that our patients may have autoimmune pancreatitis. Even though the frequency of this disease seems to be quite low, we believe that in the future, by increasing our knowledge on the subject, we will be able to diagnose an ever-increasing number of patients having acute recurrence of pain from autoimmune pancreatitis. PMID:18286678

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

    PubMed Central

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

    2015-01-01

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

  3. Inflammatory Lung Disease in Rett Syndrome

    PubMed Central

    De Felice, Claudio; Rossi, Marcello; Chisci, Glauco; Lonetti, Giuseppina; Vannuccini, Laura; Spina, Donatella; Iacona, Ingrid; Cortelazzo, Alessio; Ciccoli, Lucia; Pizzorusso, Tommaso; Hayek, Joussef

    2014-01-01

    Rett syndrome (RTT) is a pervasive neurodevelopmental disorder mainly linked to mutations in the gene encoding the methyl-CpG-binding protein 2 (MeCP2). Respiratory dysfunction, historically credited to brainstem immaturity, represents a major challenge in RTT. Our aim was to characterize the relationships between pulmonary gas exchange abnormality (GEA), upper airway obstruction, and redox status in patients with typical RTT (n = 228) and to examine lung histology in a Mecp2-null mouse model of the disease. GEA was detectable in ~80% (184/228) of patients versus ~18% of healthy controls, with “high” (39.8%) and “low” (34.8%) patterns dominating over “mixed” (19.6%) and “simple mismatch” (5.9%) types. Increased plasma levels of non-protein-bound iron (NPBI), F2-isoprostanes (F2-IsoPs), intraerythrocyte NPBI (IE-NPBI), and reduced and oxidized glutathione (i.e., GSH and GSSG) were evidenced in RTT with consequently decreased GSH/GSSG ratios. Apnea frequency/severity was positively correlated with IE-NPBI, F2-IsoPs, and GSSG and negatively with GSH/GSSG ratio. A diffuse inflammatory infiltrate of the terminal bronchioles and alveoli was evidenced in half of the examined Mecp2-mutant mice, well fitting with the radiological findings previously observed in RTT patients. Our findings indicate that GEA is a key feature of RTT and that terminal bronchioles are a likely major target of the disease. PMID:24757286

  4. Alternatives to resectional surgery for infectious disease of the lung: from embolization to thoracoplasty.

    PubMed

    Alifano, Marco; Gaucher, Sonia; Rabbat, Antoine; Brandolini, Jury; Guinet, Claude; Damotte, Diane; Regnard, Jean-François

    2012-08-01

    Surgical treatment of lung diseases is based on removal of the affected lung tissue, achieved by atypical or anatomic lung resection. Infectious lung diseases are generally treated by medical therapy, including medications, chest physiotherapy, bronchoscopic toilet, and respiratory rehabilitation. Surgical management of infectious disease of the lung is integrated in the multispecialty care. This article focuses exclusively on nonresectional surgery and other alternatives to lung resection and addresses bacterial infection and fungal disease of the lung. PMID:22789603

  5. VEGF-D promotes pulmonary oedema in hyperoxic acute lung injury.

    PubMed

    Sato, Teruhiko; Paquet-Fifield, Sophie; Harris, Nicole C; Roufail, Sally; Turner, Debra J; Yuan, Yinan; Zhang, You-Fang; Fox, Stephen B; Hibbs, Margaret L; Wilkinson-Berka, Jennifer L; Williams, Richard A; Stacker, Steven A; Sly, Peter D; Achen, Marc G

    2016-06-01

    Leakage of fluid from blood vessels, leading to oedema, is a key feature of many diseases including hyperoxic acute lung injury (HALI), which can occur when patients are ventilated with high concentrations of oxygen (hyperoxia). The molecular mechanisms driving vascular leak and oedema in HALI are poorly understood. VEGF-D is a protein that promotes blood vessel leak and oedema when overexpressed in tissues, but the role of endogenous VEGF-D in pathological oedema was unknown. To address these issues, we exposed Vegfd-deficient mice to hyperoxia. The resulting pulmonary oedema in Vegfd-deficient mice was substantially reduced compared to wild-type, as was the protein content of bronchoalveolar lavage fluid, consistent with reduced vascular leak. Vegf-d and its receptor Vegfr-3 were more highly expressed in lungs of hyperoxic, versus normoxic, wild-type mice, indicating that components of the Vegf-d signalling pathway are up-regulated in hyperoxia. Importantly, VEGF-D and its receptors were co-localized on blood vessels in clinical samples of human lungs exposed to hyperoxia; hence, VEGF-D may act directly on blood vessels to promote fluid leak. Our studies show that Vegf-d promotes oedema in response to hyperoxia in mice and support the hypothesis that VEGF-D signalling promotes vascular leak in human HALI. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. PMID:26924464

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

    PubMed Central

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

    2014-01-01

    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-α (TNF-α), whereas knockdown of PRDX1 led to downregulated expression of cytokines induced by LPS. In conclusion, our findings provide a global alteration in the proteome of lung tissues in the ALI rat model and indicate that PRDX1 may play a critical role in the pathogenesis of ARDS by promoting inflammation and represent a novel strategy for the development of new therapies against ALI. PMID:25024510

  7. Regulation of alveolar procoagulant activity and permeability in direct acute lung injury by lung epithelial tissue factor.

    PubMed

    Shaver, Ciara M; Grove, Brandon S; Putz, Nathan D; Clune, Jennifer K; Lawson, William E; Carnahan, Robert H; Mackman, Nigel; Ware, Lorraine B; Bastarache, Julie A

    2015-11-01

    Tissue factor (TF) initiates the extrinsic coagulation cascade in response to tissue injury, leading to local fibrin deposition. Low levels of TF in mice are associated with increased severity of acute lung injury (ALI) after intratracheal LPS administration. However, the cellular sources of the TF required for protection from LPS-induced ALI remain unknown. In the current study, transgenic mice with cell-specific deletions of TF in the lung epithelium or myeloid cells were treated with intratracheal LPS to determine the cellular sources of TF important in direct ALI. Cell-specific deletion of TF in the lung epithelium reduced total lung TF expression to 39% of wild-type (WT) levels at baseline and to 29% of WT levels after intratracheal LPS. In contrast, there was no reduction of TF with myeloid cell TF deletion. Mice lacking myeloid cell TF did not differ from WT mice in coagulation, inflammation, permeability, or hemorrhage. However, mice lacking lung epithelial TF had increased tissue injury, impaired activation of coagulation in the airspace, disrupted alveolar permeability, and increased alveolar hemorrhage after intratracheal LPS. Deletion of epithelial TF did not affect alveolar permeability in an indirect model of ALI caused by systemic LPS infusion. These studies demonstrate that the lung epithelium is the primary source of TF in the lung, contributing 60-70% of total lung TF, and that lung epithelial, but not myeloid, TF may be protective in direct ALI. PMID:25884207

  8. Significance of the microbiome in obstructive lung disease.

    PubMed

    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

    2012-05-01

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

  9. Acute Kawasaki Disease: Not Just for Kids

    PubMed Central

    Wolff, Anne E.; Hansen, Karen E.

    2007-01-01

    Kawasaki Disease is a small-to-medium-vessel vasculitis that preferentially affects children. Kawasaki Disease can occur in adults, but the presentation may differ from that observed in children. Typical findings in both adults and children include fever, conjunctivitis, pharyngitis, and skin erythema progressing to a desquamating rash on the palms and soles. Adults more frequently present with cervical adenopathy (93% of adults vs. 15% of children), hepatitis (65% vs. 10%), and arthralgia (61% vs. 24–38%). In contrast, adults are less frequently affected by meningitis (10% vs. 34%), thrombocytosis (55% vs. 100%), and coronary artery aneurysms (5% vs. 18–25%). We report a case of acute Kawasaki Disease in a 24-year-old man who presented with rash, fever, and arthritis. He was successfully treated with high-dose aspirin and intravenous immunoglobulin (IVIG). Our case highlights the importance of considering Kawasaki Disease in adults presenting with symptoms commonly encountered in a general medical practice. PMID:17443379

  10. Fisetin Alleviates Lipopolysaccharide-Induced Acute Lung Injury via TLR4-Mediated NF-κB Signaling Pathway in Rats.

    PubMed

    Feng, Guang; Jiang, Ze-Yu; Sun, Bo; Fu, Jie; Li, Tian-Zuo

    2016-02-01

    Acute lung injury (ALI), a common component of systemic inflammatory disease, is a life-threatening condition without many effective treatments. Fisetin, a natural flavonoid from fruits and vegetables, was reported to have wide pharmacological properties such as anti-inflammatory, antioxidant, and anticancer activities. The aim of this study was to detect the effects of fisetin on lipopolysaccharide (LPS)-induced acute lung injury and investigate the potential mechanism. Fisetin was injected (1, 2, and 4 mg/kg, i.v.) 30 min before LPS administration (5 mg/kg, i.v.). Our results showed that fisetin effectively reduced the inflammatory cytokine release and total protein in bronchoalveolar lavage fluids (BALF), decreased the lung wet/dry ratios, and obviously improved the pulmonary histology in LPS-induced ALI. Furthermore, fisetin inhibited LPS-induced increases of neutrophils and macrophage infiltration and attenuated MPO activity in lung tissues. Additionally, fisetin could significantly inhibit the Toll-like receptor 4 (TLR4) expression and the activation of NF-κB in lung tissues. Our data indicates that fisetin has a protective effect against LPS-induced ALI via suppression of TLR4-mediated NF-κB signaling pathways, and fisetin may be a promising candidate for LPS-induced ALI treatment. PMID:26272311

  11. Sex Differences and Sex Steroids in Lung Health and Disease

    PubMed Central

    Townsend, Elizabeth A.; Miller, Virginia M.

    2012-01-01

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

  12. Interleukin-6 mediates lung injury following ischemic acute kidney injury or bilateral nephrectomy.

    PubMed

    Klein, Christina L; Hoke, Tom S; Fang, Wen-Feng; Altmann, Christopher J; Douglas, Ivor S; Faubel, Sarah

    2008-10-01

    Patients with acute kidney injury frequently have pulmonary complications. Similarly ischemic acute kidney injury or bilateral nephrectomy in rodents causes lung injury characterized by pulmonary edema, increased pulmonary capillary leak and interstitial leukocyte infiltration. Interleukin-6 is a pro-inflammatory cytokine that is increased in the serum of patients with acute kidney injury and predicts mortality. Here we found that lung neutrophil infiltration, myeloperoxidase activity, the neutrophil chemokines KC and MIP-2 and capillary leak all increased within 4 h following acute kidney injury in wild-type mice. These pathologic factors were reduced in interleukin-6-deficient mice following acute kidney injury or bilateral nephrectomy. The lungs of mutant mice had reduced KC but MIP-2 was similar to that of wild type mice. Wild-type mice, treated with an interleukin-6 inactivating antibody, had decreased lung myeloperoxidase activity and KC levels following acute kidney injury. Our study shows that interleukin-6 contributes to lung injury following acute kidney injury. PMID:18596724

  13. Abdominal Mondor disease mimicking acute appendicitis

    PubMed Central

    Schuppisser, Myriam; Khallouf, Joe; Abbassi, Ziad; Erne, Michel; Vettorel, Denise; Paroz, Alexandre; Naiken, Surennaidoo P.

    2016-01-01

    Introduction Mondor disease (MD), a superficial thrombophlebitis of the thoraco-epigastric veins and their confluents is rarely reported in the literature. The superior epigastric vein is the most affected vessel but involvement of the inferior epigastric vessels or their branches have also been described. There is no universal consensus on treatment in the literature but most authors suggest symptomatic treatment with non-steroid anti-inflammatory drugs (NSAIDs). Case report We report the case of a marathon runner who presented with right iliac fossa pain mimicking the clinical symptomatology of an acute appendicitis. The history and the calculated Alvarado score were not in favor of an acute appendicitis. This situation motivated multiple investigations and we finally arrived at the diagnosis of MD. Discussion Acute appendicitis (AA) is the most common cause of surgical emergencies and one of the most frequent indications for an urgent abdominal surgical procedure around the world. In some cases, right lower quadrant pain remains unclear in spite of US, CT scan, and exclusion of urological and gynecological causes, thus we need to think of some rare pathologies like MD. Conclusion MD is often mentioned in the differential diagnosis of breast pathologies but rarely in abdominal pain assessment. It should be mentioned in the differential diagnosis of the right lower quadrant pain when the clinical presentation is unclear and when acute appendicitis has been excluded. Awareness of MD can avoid misdiagnosis and decrease extra costs by sparing unnecessary imaging. PMID:26803533

  14. Pulmonary hypertension associated with lung diseases and hypoxemia.

    PubMed

    Cuttica, Michael J

    2016-05-01

    Pulmonary hypertension that develops in the setting of underlying lung diseases such as COPD or idiopathic pulmonary fibrosis (IPF) is associated with decreased functional status, worsening hypoxemia and quality of life, and increased mortality. This complication of lung disease is complex in its origin and carries a unique set of diagnostic and therapeutic issues. This review attempts to provide an overview of mechanisms associated with the onset of pulmonary hypertension in COPD and IPF, touches on appropriate evaluation, and reviews the state of knowledge on treating pulmonary hypertension related to underlying lung disease. PMID:27086030

  15. CXCR4 Receptor Overexpression in Mesenchymal Stem Cells Facilitates Treatment of Acute Lung Injury in Rats*

    PubMed Central

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

    2015-01-01

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

  16. Clinical potentials of human pluripotent stem cells in lung diseases.

    PubMed

    Quan, Yuan; Wang, Dachun

    2014-01-01

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

  17. Oxygen therapy in acute exacerbations of chronic obstructive pulmonary disease

    PubMed Central

    Brill, Simon E; Wedzicha, Jadwiga A

    2014-01-01

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

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

    PubMed Central

    Silveyra, Patricia; Floros, Joanna

    2013-01-01

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

  19. Is Previous Respiratory Disease a Risk Factor for Lung Cancer?

    PubMed Central

    Denholm, Rachel; Schüz, Joachim; Straif, Kurt; Stücker, Isabelle; Jöckel, Karl-Heinz; Brenner, Darren R.; De Matteis, Sara; Boffetta, Paolo; Guida, Florence; Brüske, Irene; Wichmann, Heinz-Erich; Landi, Maria Teresa; Caporaso, Neil; Siemiatycki, Jack; Ahrens, Wolfgang; Pohlabeln, Hermann; Zaridze, David; Field, John K.; McLaughlin, John; Demers, Paul; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Dumitru, Rodica Stanescu; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Kendzia, Benjamin; Peters, Susan; Behrens, Thomas; Vermeulen, Roel; Brüning, Thomas; Kromhout, Hans

    2014-01-01

    Rationale: Previous respiratory diseases have been associated with increased risk of lung cancer. Respiratory conditions often co-occur and few studies have investigated multiple conditions simultaneously. Objectives: Investigate lung cancer risk associated with chronic bronchitis, emphysema, tuberculosis, pneumonia, and asthma. Methods: The SYNERGY project pooled information on previous respiratory diseases from 12,739 case subjects and 14,945 control subjects from 7 case–control studies conducted in Europe and Canada. Multivariate logistic regression models were used to investigate the relationship between individual diseases adjusting for co-occurring conditions, and patterns of respiratory disease diagnoses and lung cancer. Analyses were stratified by sex, and adjusted for age, center, ever-employed in a high-risk occupation, education, smoking status, cigarette pack-years, and time since quitting smoking. Measurements and Main Results: Chronic bronchitis and emphysema were positively associated with lung cancer, after accounting for other respiratory diseases and smoking (e.g., in men: odds ratio [OR], 1.33; 95% confidence interval [CI], 1.20–1.48 and OR, 1.50; 95% CI, 1.21–1.87, respectively). A positive relationship was observed between lung cancer and pneumonia diagnosed 2 years or less before lung cancer (OR, 3.31; 95% CI, 2.33–4.70 for men), but not longer. Co-occurrence of chronic bronchitis and emphysema and/or pneumonia had a stronger positive association with lung cancer than chronic bronchitis “only.” Asthma had an inverse association with lung cancer, the association being stronger with an asthma diagnosis 5 years or more before lung cancer compared with shorter. Conclusions: Findings from this large international case–control consortium indicate that after accounting for co-occurring respiratory diseases, chronic bronchitis and emphysema continue to have a positive association with lung cancer. PMID:25054566

  20. Lung cancer screening in patients with chronic obstructive pulmonary disease

    PubMed Central

    Gonzalez, Jessica; Marín, Marta; Sánchez-Salcedo, Pablo

    2016-01-01

    Lung cancer and chronic obstructive pulmonary disease (COPD) are two intimately related diseases, with great impact on public health. Annual screening using low-dose computed tomography (LDCT) of the chest significantly reduces mortality due to lung cancer, and several scientific societies now recommend this technique. COPD, defined by the presence of airflow obstruction [forced expiratory volume and forced vital capacity (FVC) ratio less than 0.70], and their clinical phenotypes, namely emphysema and chronic bronchitis, have been associated with increased lung cancer risk. Several epidemiological studies, including lung cancer screening trials, have found a 2- to 4-fold increase in lung cancer risk in patients with COPD when compared to individuals without airflow obstruction. Part of the risk attributed to airflow obstruction appears to be derived from the presence of radiographic emphysema. The latter has proven to be an important lung cancer risk factor in smokers without airflow obstruction and even in never smokers. This evidence supports the idea of including patients with COPD and/or emphysema in lung cancer screening programs. There is evidence that lung cancer screening in this population is effective and can potentially reduce mortality. Specific lung cancer risk scores have been developed for patients with COPD [COPD lung cancer screening score (LUCSS) and COPD-LUCSS-diffusing capacity for carbon monoxide (DLCO)] to identify those at high risk. A multidisciplinary approach for an adequate patient selection, especially of patients with severe disease, is key to maximize benefits and reduce harms from lung cancer screening in this population. Patients with COPD included in lung cancer screening programs could also benefit from other interventions, such as smoking cessation and adequate treatment. PMID:27195278

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

    PubMed Central

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

    2015-01-01

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

  2. New insights into mechanisms controlling the NLRP3 inflammasome and its role in lung disease.

    PubMed

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

    2014-01-01

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

  3. [Basic lung ultrasound. Part 2. Parenchymal diseases].

    PubMed

    de la Quintana Gordon, F B; Nacarino Alcorta, B; Fajardo Pérez, M

    2015-01-01

    In this second part, an analysis is made of the pathology of lung parenchyma. This text is structured into different sections, including the study of atelectasias, pneumonia and abscess, interstitial/alveolar or Blines patterns, and finally an analysis is made of pulmonary embolism. With this second part, the basic knowledge to develop lung ultrasound in the anesthesia department has been presented. PMID:25708093

  4. CT in the diagnosis of interstitial lung disease

    SciTech Connect

    Bergin, C.J.; Mueller, N.L.

    1985-09-01

    The computed tomographic (CT) appearance of interstitial lung disease was assessed in 23 patients with known interstitial disease. These included seven patients with fibrosing alveolitis, six with silicosis, two with hypersensitivity pneumonitis, three with lymphangitic spread of tumor, two with sarcoidosis, one with rheumatoid lung disease, and two with neurofibromatosis. The CT appearance of the interstitial changes in the different disease entities was assessed. Nodules were a prominent CT feature in silicosis, sarcoidosis, and lymphangitic spread of malignancy. Distribution of nodules and associated interlobular septal thickening provided further distinguishing features in these diseases. Reticular densities were the predominant CT change in fibrosing alveolitis, rheumatoid lung disease, and extrinsic allergic alveolitis. CT can be useful in the investigation of selected instances of interstitial pulmonary disease.

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

    SciTech Connect

    Jain, D.; Lahiri, A.; Raftery, E.B. )

    1990-01-15

    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.

  6. Pathogenesis and risk factors for nontuberculous mycobacterial lung disease.

    PubMed

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

    2015-03-01

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

  7. Lung volume reduction surgery after lung transplantation for emphysema-chronic obstructive pulmonary disease.

    PubMed

    Arango, E; Espinosa, D; Illana, J; Carrasco, G; Moreno, P; Algar, F J; Alvarez, A; Cerezo, F; Baamonde, C; Requejo, A; Redel, J; Vaquero, J; Santos, F; Salvatierra, A

    2012-09-01

    Lung Volume Reduction Surgery (LVRS) has become a palliative treatment for patients with advanced emphysema and disabling dyspnea. After single lung transplantation in chronic obstructive pulmonary disease, LVRS may be indicated to improve graft dysfunction caused by native lung hyperinflation compressing the grafted lung. This common complication is the subject of our study, which showed LVRS to be helpful to manage this situation. We performed an observational retrospective and descriptive study using the data of 293 patients transplanted in our center between January 1996 and October 2011. Some of the patients who underwent a single lung transplantation developed native lung hyperinflation years after the transplantation, interfering with respiratory function due to graft compression. PMID:22974928

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    Schluger, Neil W; Koppaka, Ram

    2014-03-01

    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

  10. CXCR4+ granulocytes reflect fungal cystic fibrosis lung disease.

    PubMed

    Carevic, Melanie; Singh, Anurag; Rieber, Nikolaus; Eickmeier, Olaf; Griese, Matthias; Hector, Andreas; Hartl, Dominik

    2015-08-01

    Cystic fibrosis airways are frequently colonised with fungi. However, the interaction of these fungi with immune cells and the clinical relevance in cystic fibrosis lung disease are incompletely understood.We characterised granulocytes in airway fluids and peripheral blood from cystic fibrosis patients with and without fungal colonisation, non-cystic fibrosis disease controls and healthy control subjects cross-sectionally and longitudinally and correlated these findings with lung function parameters.Cystic fibrosis patients with chronic fungal colonisation by Aspergillus fumigatus were characterised by an accumulation of a distinct granulocyte subset, expressing the HIV coreceptor CXCR4. Percentages of airway CXCR4(+) granulocytes correlated with lung disease severity in patients with cystic fibrosis.These studies demonstrate that chronic fungal colonisation with A. fumigatus in cystic fibrosis patients is associated with CXCR4(+) airway granulocytes, which may serve as a potential biomarker and therapeutic target in fungal cystic fibrosis lung disease. PMID:25929952

  11. Depressive Symptoms and Impaired Physical Function after Acute Lung Injury

    PubMed Central

    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

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

  12. General anxiety symptoms after acute lung injury: Predictors and correlates

    PubMed Central

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

    2014-01-01

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

  13. Quercetin protects against lipopolysaccharide-induced acute lung injury in rats through suppression of inflammation and oxidative stress

    PubMed Central

    Huang, Risheng; Wu, Hao

    2015-01-01

    Introduction Acute lung injury (ALI) is an acute inflammatory disease characterized by excess production of inflammatory factors in lung tissue. Quercetin, a herbal flavonoid, exhibits anti-inflammatory and anti-oxidative properties. This study was performed to assess the effects of quercetin on lipopolysaccharide (LPS)-induced ALI. Material and methods Sprague-Dawley rats were randomly divided into 3 groups: the control group (saline alone), the LPS group challenged with LPS (Escherichia coli 026:B6; 100 µg/kg), and the quercetin group pretreated with quercetin (50 mg/kg, by gavage) 1 h before LPS challenge. Bronchoalveolar lavage fluid (BALF) samples and lung tissues were collected 6 h after LPS administration. Histopathological and biochemical parameters were measured. Results The LPS treatment led to increased alveolar wall thickening and cellular infiltration in the lung, which was markedly prevented by quercetin pretreatment. Moreover, quercetin significantly (p < 0.05) attenuated the increase in the BALF protein level and neutrophil count and lung wet/dry weight ratio and myeloperoxidase activity in LPS-challenged rats. The LPS exposure evoked a 4- to 5-fold rise in BALF levels of tumor necrosis factor-α and interleukin-6, which was significantly (p < 0.05) counteracted by quercetin pretreatment. Additionally, quercetin significantly (p < 0.05) suppressed the malondialdehyde level and increased the activities of superoxide dismutase, catalase, and glutathione peroxidase in the lung of LPS-treated rats. Conclusions Quercetin pretreatment effectively ameliorates LPS-induced ALI, largely through suppression of inflammation and oxidative stress, and may thus have therapeutic potential in the prevention of this disease. PMID:25995762

  14. Asbestos lung burden and disease patterns in man

    SciTech Connect

    Churg, A.

    1993-12-31

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

  15. Diagnosis and management of drug-associated interstitial lung disease

    PubMed Central

    Müller, N L; White, D A; Jiang, H; Gemma, A

    2004-01-01

    Symptoms of drug-associated interstitial lung disease (ILD) are nonspecific and can be difficult to distinguish from a number of illnesses that commonly occur in patients with non-small-cell lung cancer (NSCLC) on therapy. Identification of drug involvement and differentiation from other illnesses is problematic, although radiological manifestations and clinical tests enable many of the alternative causes of symptoms in advanced NSCLC to be excluded. In lung cancer patients, high-resolution computed tomography (HRCT) is more sensitive than a chest radiograph in evaluating the severity and progression of parenchymal lung disease. Indeed, the use of HRCT imaging has led to the recognition of many distinct patterns of lung involvement and, along with clinical signs and symptoms, helps to predict both outcome and response to treatment. This manuscript outlines the radiology of drug-associated ILD and its differential diagnosis in NSCLC. An algorithm that uses clinical tests to exclude alternative diagnoses is also described. PMID:15340375

  16. Asbestos-related lung disease: a pictorial review.

    PubMed

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

    2015-01-01

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

  17. Endoscopic lung volume reduction effectively treats acute respiratory failure secondary to bullous emphysema.

    PubMed

    Sexton, Paul; Garrett, Jeffrey E; Rankin, Nigel; Anderson, Graeme

    2010-10-01

    Emphysema often affects the lungs in a heterogeneous fashion, and collapse or removal of severely hyperinflated portions of lung can improve overall lung function and symptoms. The role of lung volume reduction (LVR) surgery in selected patients is well established, but that of non-surgical LVR is still being defined. In particular, use of endobronchial LVR is still under development. This case report describes a 48-year-old non-smoker with severe bullous emphysema complicated by acute hypercapnic respiratory failure, who was successfully treated by endobronchial valve placement while intubated in an intensive care unit. PMID:20723138

  18. The role of leukocytes in the pathogenesis of fibrin deposition in bovine acute lung injury.

    PubMed Central

    Car, B. D.; Suyemoto, M. M.; Neilsen, N. R.; Slauson, D. O.

    1991-01-01

    The peculiarly fibrinous nature of bovine acute lung injury due to infection with Pasteurella haemolytica A1 suggests an imbalance between leukocyte-directed procoagulant and profibrinolytic influences in the inflamed bovine lung. Calves with experimental pneumonia produced by intratracheal inoculation with P. haemolytica A1 developed acute locally extensive cranioventral fibrinopurulent bronchopneumonia. Pulmonary alveolar macrophages (PAM) recovered by segmental lavage from affected lung lobes were 30 times more procoagulant than PAM obtained from unaffected lung lobes and 37-fold more procoagulant than PAM from control calf lungs. Unlike the enhancement of procoagulant activity, profibrinolytic activity (plasminogen activator amidolysis) of total lung leukocytes (PAM and plasminogen activator neutrophils [PMN]) was decreased 23 times in cells obtained from affected lung lobes and also was decreased four times in cells obtained from unaffected lobes of infected animals. This marked imbalance in cellular procoagulant and fibrinolytic activity probably contributes significantly to enhanced fibrin deposition and retarded fibrin removal. In addition, PAM from inflamed lungs were strongly positive for bovine tissue factor antigen as demonstrated by immunocytochemistry. Intensely tissue factor-positive PAM enmeshed in fibrinocellular exudates and positive alveolar walls were situated such that they were likely to have, in concert, initiated extrinsic activation of coagulation in the acutely inflamed lung. These data collectively suggest that enhanced PAM-directed procoagulant activity and diminished PAM- and PMN-directed profibrinolytic activity represent important modifications of local leukocyte function in bovine acute lung injury that are central to the pathogenesis of lesion development with extensive fibrin deposition and retarded fibrin removal. Images Figure 2 Figure 3 PMID:2024707

  19. Diagnosis and Treatment of Nontuberculous Mycobacterial Lung Disease: Clinicians' Perspectives

    PubMed Central

    Ryu, Yon Ju; Koh, Won-Jung

    2016-01-01

    Nontuberculous mycobacteria (NTM) are emerging pathogens that affect both immunocompromised and immunocompetent patients. The incidence and prevalence of NTM lung disease are increasing worldwide and rapidly becoming a major public health problem. For the diagnosis of NTM lung disease, patients suspected to have NTM lung disease are required to meet all clinical and microbiologic criteria. The development of molecular methods allows the characterization of new species and NTM identification at a subspecies level. Even after the identification of NTM species from respiratory specimens, clinicians should consider the clinical significance of such findings. Besides the limited options, treatment is lengthy and varies by species, and therefore a challenge. Treatment may be complicated by potential toxicity with discouraging outcomes. The decision to start treatment for NTM lung disease is not easy and requires careful individualized analysis of risks and benefits. Clinicians should be alert to those unique aspects of NTM lung disease concerning diagnosis with advanced molecular methods and treatment with limited options. Current recommendations and recent advances for diagnosis and treatment of NTM lung disease are summarized in this article. PMID:27066084

  20. Diagnosis and Treatment of Nontuberculous Mycobacterial Lung Disease: Clinicians' Perspectives.

    PubMed

    Ryu, Yon Ju; Koh, Won-Jung; Daley, Charles L

    2016-04-01

    Nontuberculous mycobacteria (NTM) are emerging pathogens that affect both immunocompromised and immunocompetent patients. The incidence and prevalence of NTM lung disease are increasing worldwide and rapidly becoming a major public health problem. For the diagnosis of NTM lung disease, patients suspected to have NTM lung disease are required to meet all clinical and microbiologic criteria. The development of molecular methods allows the characterization of new species and NTM identification at a subspecies level. Even after the identification of NTM species from respiratory specimens, clinicians should consider the clinical significance of such findings. Besides the limited options, treatment is lengthy and varies by species, and therefore a challenge. Treatment may be complicated by potential toxicity with discouraging outcomes. The decision to start treatment for NTM lung disease is not easy and requires careful individualized analysis of risks and benefits. Clinicians should be alert to those unique aspects of NTM lung disease concerning diagnosis with advanced molecular methods and treatment with limited options. Current recommendations and recent advances for diagnosis and treatment of NTM lung disease are summarized in this article. PMID:27066084

  1. Integrin α3 Mutations with Kidney, Lung, and Skin Disease

    PubMed Central

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

    2012-01-01

    SUMMARY Integrin α3 is a transmembrane integrin receptor subunit that mediates signals between the cells and their microenvironment. We identified three patients with homozygous mutations in the integrin α3 gene that were associated with disrupted basement-membrane structures and compromised barrier functions in kidney, lung, and skin. The patients had a multiorgan disorder that included congenital nephrotic syndrome, interstitial lung disease, and epidermolysis bullosa. The renal and respiratory features predominated, and the lung involvement accounted for the lethal course of the disease. Although skin fragility was mild, it provided clues to the diagnosis. PMID:22512483

  2. Inducible expression of indoleamine 2,3-dioxygenase attenuates acute rejection of tissue-engineered lung allografts in rats.

    PubMed

    Ebrahimi, Ammar; Kardar, Gholam Ali; Toolabi, LadanTeimoori; Ghanbari, Hossein; Sadroddiny, Esmaeil

    2016-01-15

    Lung disease remains one of the principal causes of death worldwide and the incidence of pulmonary diseases is increasing. Complexity in treatments and shortage of donors leads us to develop new ways for lung disease treatment. One promising strategy is preparing engineered lung for transplantation. In this context, employing new immunosuppression strategies which suppresses immune system locally rather than systemic improves transplant survival. This tends to reduce the difficulties in transplant rejection and the systemic impact of the use of immunosuppressive drugs which causes side effects such as serious infections and malignancies. In our study examining the immunosuppressive effects of IDO expression, we produced rat lung tissues with the help of decellularized tissue, differentiating medium and rat mesenchymal stem cells. Transduction of these cells by IDO expressing lentiviruses provided inducible and local expression of this gene. To examine immunosuppressive properties of IDO expression by these tissues, we transplanted these allografts into rats and, subsequently, evaluated cytokine expression and histopathological properties. Expression of inflammatory cytokines IFNγ and TNFα were significantly downregulated in IDO expressing allograft. Moreover, acute rejection score of this experimental group was also lower comparing other two groups and mRNA levels of FOXP3, a regulatory T cell marker, upregulated in IDO expressing group. However, infiltrating lymphocyte counting did not show significant difference between groups. This study demonstrates that IDO gene transfer into engineered lung allograft tissues significantly attenuates acute allograft damage suggesting local therapy with IDO as a strategy to reduce the need for systemic immunosuppression and, thereby, its side effects. PMID:26506443

  3. Understanding Exercise, Diet and Lung Disease

    MedlinePlus

    ... mucus and beats in a rhythmic fashion to clean the lungs. The airways are also surrounded by ... on a path to better health. Exercise Increases • Energy level • Endurance (Cardiopulmonary) • Muscle strength • Bone density • Ability ...

  4. Angiotensin II is related to the acute aortic dissection complicated with lung injury through mediating the release of MMP9 from macrophages

    PubMed Central

    Wu, Zhiyong; Ruan, Yongle; Chang, Jinxing; Li, Bowen; Ren, Wei

    2016-01-01

    Background: Acute aortic dissection (AAD) patients usually show concurrent lung injury mainly featured by hyoxemia. To date, no effective treatment method has been established for the AAD complicated with acute lung injury (ALI). Matrix metalloproteinases (MMPs), especially MMP2 and MMP9, have been considered to be closely related to the onset of aortic disease including AAD. To investigate the roles of MMP in the pathogenesis of AAD complicated with ALI, we determined the expression of MMP2 and MMP9 in serum and lung tissues of AAD patients. In addition, a new rat model of AAD complicated with ALI was established to investigate the pathogenesis of such complicated conditions. Methods and results: Angiotensin II (Ang II) and MMP9 were up-regulated in the AAD complicated with ALI patients compared to those of the AAD without ALI patients, normal individuals and the patients with non-ruptured aneurysm. Besides, massive macrophages with MMP9 expression was noticed in the lung tissues in the AAD complicated with ALI patients. On this basis, AAD complicated with ALI rat model was established based on BAPN feeding and infusion of Ang II. Obvious lung injury was observed in the BAPN+Ang II group compared to that of the BAPN group, together with macrophage accumulation in lung tissues, as well as over-expression of MMP9 in lung tissues. After interference of MMP antagonist, a large number of macrophages were still accumulated in the lung tissues, but the lung injury was obviously attenuated. After the interference of AT1 receptor, the number of macrophages in the lung tissues was obviously decreased and the lung injury was obviously relieved. Conclusions: Ang II is closely related to the lung injury at the early stage of AAD through mediating the release of MMP9 in the macrophages in the lung tissues. PMID:27186269

  5. Design, synthesis and biological evaluation of paralleled Aza resveratrol-chalcone compounds as potential anti-inflammatory agents for the treatment of acute lung injury.

    PubMed

    Chen, Wenbo; Ge, Xiangting; Xu, Fengli; Zhang, Yali; Liu, Zhiguo; Pan, Jialing; Song, Jiao; Dai, Yuanrong; Zhou, Jianmin; Feng, Jianpeng; Liang, Guang

    2015-08-01

    Acute lung injury (ALI) is a major cause of acute respiratory failure in critically-ill patients. It has been reported that both resveratrol and chalcone derivatives could ameliorate lung injury induced by inflammation. A series of paralleled Aza resveratrol-chalcone compounds (5a-5m, 6a-6i) were designed, synthesized and screened for anti-inflammatory activity. A majority showed potent inhibition on the IL-6 and TNF-α expression-stimulated by LPS in macrophages, of which compound 6b is the most potent analog by inhibition of LPS-induced IL-6 release in a dose-dependent manner. Moreover, 6b exhibited protection against LPS-induced acute lung injury in vivo. These results offer further insight into the use of Aza resveratrol-chalcone compounds for the treatment of inflammatory diseases, and the use of compound 6b as a lead compound for the development of anti-ALI agents. PMID:26048788

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

    PubMed

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

    2014-10-01

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

  7. Minimal Residual Disease in Acute Myeloid Leukemia

    PubMed Central

    Hourigan, Christopher S.; Karp, Judith E.

    2014-01-01

    Technological advances in the laboratory have lead to substantial improvements in clinical decision-making by the use of pre-treatment prognostic risk stratification factors in acute myeloid leukemia (AML). Unfortunately similar progress has not been made in treatment response criteria, with the definition of “complete remission” in AML largely unchanged for over half a century. Several recent clinical trials have demonstrated that higher sensitivity measurements of residual disease burden during or after treatment can be performed, that results are predictive for clinical outcome and can be used to improve outcomes by guiding additional therapeutic intervention to patients in clinical complete remission but at increased relapse risk. We review here these recent trials, the characteristics and challenges of the modalities currently used to detect minimal residual disease (MRD), and outline opportunities to both refine detection and better clinically utilize MRD measurements. MRD measurement is already the standard of care in other myeloid malignancies such as chronic myelogenous leukemia (CML) and acute promyelocytic leukemia (APL). It is our belief that response criteria for non-APL AML should be updated to include assessment for molecular complete remission (mCR) and that recommendations for post-consolidation surveillance should include regular monitoring for molecular relapse as a standard of care. PMID:23799371

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

    PubMed Central

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

    2012-01-01

    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. PMID:22392149

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

    PubMed Central

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

    2014-01-01

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

  10. Interactive effects of hypoxia, carbon monoxide and acute lung injury on oxygen transport and aerobic capacity.

    PubMed

    Crocker, George H; Jones, James H

    2016-05-01

    This study determined how breathing hypoxic gas, reducing circulatory capacitance for O2 by breathing CO, and impairing pulmonary gas exchange by acutely injuring the lungs interact to limit cardiopulmonary O2 delivery, O2 extraction and maximal aerobic capacity (VO2max). Five goats ran on a treadmill at VO2max following oleic-acid induced acute lung injury that impaired pulmonary gas exchange, after partial recovery or with no acute lung injury. Goats breathed normoxic or hypoxic inspired gas fractions (FIO2 0.21 or 0.12) with and without small amounts of CO to maintain carboxyhemoglobin fractions (FHbCO) of 0.02 or 0.30. With the exception of elevated FHbCO with acute lung injury (P=0.08), all combinations of hypoxia, elevated FHbCO and acute lung injury attenuated the reduction in VO2max by 15-27% compared to the sum of each treatment's individual reduction in VO2max when administered separately. Simultaneous administration of two treatments attenuated the reduction in VO2max by attenuating the decrease in cardiopulmonary O2 delivery, not synergistically increasing O2 extraction. PMID:26845454

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

    PubMed Central

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

    2013-01-01

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

  12. Animal models of beryllium-induced lung disease

    SciTech Connect

    Finch, G.L.; Hoover, M.D.; Hahn, F.F.

    1996-10-01

    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.

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

    PubMed Central

    2013-01-01

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

  14. Impact of diabetes, chronic heart failure, congenital heart disease and chronic obstructive pulmonary disease on acute and chronic exercise responses

    PubMed Central

    Brassard, Patrice; Ferland, Annie; Marquis, Karine; Maltais, François; Jobin, Jean; Poirier, Paul

    2007-01-01

    Several chronic diseases are known to negatively affect the ability of an individual to perform exercise. However, the altered exercise capacity observed in these patients is not solely associated with the heart and lungs dysfunction. Exercise has also been shown to play an important role in the management of several pathologies encountered in the fields of cardiology and pneumology. Studies conducted in our institution regarding the influence of diabetes, chronic heart failure, congenital heart disease and chronic pulmonary obstructive disease on the acute and chronic exercise responses, along with the beneficial effects of exercise training in these populations, are reviewed. PMID:17932595

  15. Magnetic resonance imaging of cystic fibrosis lung disease.

    PubMed

    Wielptz, Mark O; Eichinger, Monika; Puderbach, Michael

    2013-05-01

    Lung involvement in cystic fibrosis (CF) disease continues to be a major life-limiting factor of this autosomal recessive genetic disorder. Efforts made toward early diagnosis and advances in therapy have led to sustained survival of affected patients, and many are now of adult age. Because imaging provides detailed information on regional distribution of CF lung disease, repetitive imaging is required for severity assessment and therapy monitoring not only in clinical routine but also for interventional trials. Computed tomography has long succeeded chest radiograph because it provides the highest morphologic detail of airway and parenchymal changes. This is inseparably accompanied by an increase in radiation exposure to CF individuals, who are critically susceptible to, and may accumulate, relevant doses during their lifetime. Magnetic resonance imaging (MRI) as an ionizing radiation-free cross-sectional imaging modality is capable of depicting anatomic hallmarks of CF lung disease at lower spatial resolution but with enhanced tissue characterization. Comprehensive functional lung imaging (imaging of respiratory mechanics, ventilation, and lung perfusion) provides valuable additional information that cannot or can hardly be obtained by any other single diagnostic procedure. The present review article strives to present the current state of lung MRI in CF, as well as its future perspectives. Functional MRI of the CF lung is at the threshold of being considered a routine application, which, supporting early diagnosis, may help to further improve the survival of CF patients. PMID:23545948

  16. FLUID BALANCE IN CRITICALLY ILL CHILDREN WITH ACUTE LUNG INJURY

    PubMed Central

    Valentine, Stacey L.; Sapru, Anil; Higgerson, Renee A.; Spinella, Phillip C.; Flori, Heidi R.; Graham, Dionne A.; Brett, Molly; Convery, Maureen; Christie, LeeAnn M.; Karamessinis, Laurie; Randolph, Adrienne G.

    2012-01-01

    Objective In the Fluid and Catheter Treatment Trial (FACTT)(NCT00281268), adults with acute lung injury (ALI) randomized to a conservative versus liberal fluid management protocol had increased days alive and free of mechanical ventilator support (ventilator-free days). Recruiting sufficient children with ALI into a pediatric trial is challenging. A Bayesian statistical approach relies on the adult trial for the a priori effect estimate, requiring fewer patients. Preparing for a Bayesian pediatric trial mirroring FACTT, we aimed to: a.)Identify an inverse association between fluid balance and VFDs; and b.)Determine if fluid balance over time is more similar to adults in the FACTT liberal or conservative arms. Design Multi-centered retrospective cohort study. Setting Five pediatric intensive care units. Patients Mechanically ventilated children (age ≥1 month to <18 years) with ALI admitted 2007–2010. Interventions None. Measurements and Main Results Fluid intake, output and net fluid balance were collected days 1–7 in 168 children with ALI (median age 3 years, median PaO2/FiO2 138) and weight-adjusted (ml/kg). Using multivariable linear regression to adjust for age, gender, race, admission day illness severity, PaO2/FiO2 and vasopressor use, increasing cumulative fluid balance (ml/kg) at day 3 was associated with fewer VFDs (p=0.02). Adjusted for weight, daily fluid balance on days 1–3 and cumulative fluid balance on days 1–7 were higher in these children compared to adults in the FACTT conservative arm (p<0.001, each day) and was similar to adults in the liberal arm. Conclusions Increasing fluid balance at day three in children with ALI at these centers is independently associated with fewer VFDs. Our findings and the similarity of fluid balance patterns in our cohort to adults in the FACTT liberal arm demonstrate the need to determine whether a conservative fluid management strategy improves clinical outcomes in children with ALI and support a Bayesian trial mirroring the FACTT trial. PMID:22824936

  17. Leukocyte-specific protein 1 regulates neutrophil recruitment in acute lung inflammation.

    PubMed

    Le, Nguyen Phuong Khanh; Channabasappa, Shankaramurthy; Hossain, Mokarram; Liu, Lixin; Singh, Baljit

    2015-11-01

    The mechanisms of excessive migration of activated neutrophils into inflamed lungs, credited with tissue damage, are not fully understood. We explored the hitherto unknown expression of leukocyte-specific protein 1 (LSP1) in human and mouse lungs and neutrophils and examined its role in neutrophil migration in acute lung inflammation. Autopsied septic human lungs showed increased LSP1 labeling in epithelium, endothelium, and leukocytes, including in their nuclei compared with normal lungs. We induced acute lung inflammation through intranasal administration of E. coli lipopolysaccharide (LPS) (80 μg) in LSP1-deficient (Lsp1(-/-)) and wild-type (WT) 129/SvJ mice. Immunocytochemistry and Western blots showed increased expression of LSP1 and phosphorylated LSP1 in lungs of LPS-treated WT mice. Histology showed more congestion, inflammation, and Gr-1(+) neutrophils in lung of WT mice than Lsp1(-/-) mice. LPS-treated WT mice had significantly more neutrophils in bronchoalveolar lavage (BAL) and myeloperoxidase levels in lungs compared with Lsp1(-/-) mice. However, there were no differences in lung tissue and BAL concentrations of keratinocyte-derived chemokine, monocyte chemoattractant protein-1, macrophage inflammatory protein-1α and -1β, vascular permeability, and phosphorylated p38 MAPK between LPS-treated WT and Lsp1(-/-) mice, whereas TNF-α concentration was higher in BAL fluid from LPS-treated WT. Immunoelectron microscopy showed increased LSP1 in the nuclei of LPS-treated neutrophils. We also found increased levels of phosphorylated LSP1 associated with plasma membrane, nucleus, and cytosol at various times after LPS treatment of murine bone marrow-derived neutrophils, suggesting its role in modulation of neutrophil cytoskeleton and the membrane. These data collectively show increased expression of LSP1 in inflamed mouse and human lungs and its role in neutrophil recruitment and lung inflammation. PMID:26320151

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-05-01

    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

  20. NLRP3 deletion protects from hyperoxia-induced acute lung injury

    PubMed Central

    Fukumoto, Jutaro; Fukumoto, Itsuko; Parthasarathy, Prasanna Tamarapu; Cox, Ruan; Huynh, Bao; Ramanathan, Gurukumar Kollongod; Venugopal, Rajan Babu; Allen-Gipson, Diane S.; Lockey, Richard F.

    2013-01-01

    Inspiration of a high concentration of oxygen, a therapy for acute lung injury (ALI), could unexpectedly lead to reactive oxygen species (ROS) production and hyperoxia-induced acute lung injury (HALI). Nucleotide-binding domain and leucine-rich repeat PYD-containing protein 3 (NLRP3) senses the ROS, triggering inflammasome activation and interleukin-1β (IL-1β) production and secretion. However, the role of NLRP3 inflammasome in HALI is unclear. The main aim of this study is to determine the effect of NLRP3 gene deletion on inflammatory response and lung epithelial cell death. Wild-type (WT) and NLRP3−/− mice were exposed to 100% O2 for 48–72 h. Bronchoalveolar lavage fluid and lung tissues were examined for proinflammatory cytokine production and lung inflammation. Hyperoxia-induced lung pathological score was suppressed in NLRP3−/− mice compared with WT mice. Hyperoxia-induced recruitment of inflammatory cells and elevation of IL-1β, TNFα, macrophage inflammatory protein-2, and monocyte chemoattractant protein-1 were attenuated in NLRP3−/− mice. NLRP3 deletion decreased lung epithelial cell death and caspase-3 levels and a suppressed NF-κB levels compared with WT controls. Taken together, this research demonstrates for the first time that NLRP3-deficient mice have suppressed inflammatory response and blunted lung epithelial cell apoptosis to HALI. PMID:23636457

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

    SciTech Connect

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

    1988-11-01

    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.

  2. Acute lung injury after inhalation of water-proofing spray while smoking a cigarette.

    PubMed

    Jinn, Y; Akizuki, N; Ohkouchi, M; Inase, N; Ichioka, M; Marumo, F

    1998-01-01

    A 34-year-old Japanese woman developed acute lung injury soon after inhaling a water-proofing spray which she applied onto her ski suit while smoking a cigarette at the same time. She initially demonstrated arterial hypoxemia (PaO2 = 59 mm Hg) and ground-glass opacities in both lung fields on the CT scan, which both returned to normal without any medication. Several water-proofing sprays, which are easily obtainable in Japan, contain 1,1,1-trichloroethane, liquefied petroleum gas and fluoride resin. Although these components have not been reported to be toxic to the lung yet, high concentrations of these components and/or the pyrolytic products of fluoride resin may have caused acute lung injury in this case. PMID:9817966

  3. The Role of the Bacterial Microbiome in Lung Disease

    PubMed Central

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

    2014-01-01

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

  4. Inflammatory Diseases of the Lung Induced by Conventional Cigarette Smoke: A Review.

    PubMed

    Crotty Alexander, Laura E; Shin, Stephanie; Hwang, John H

    2015-11-01

    Smoking-induced lung diseases were extremely rare prior to the 20th century. With commercialization and introduction of machine-made cigarettes, worldwide use skyrocketed and several new pulmonary diseases have been recognized. The majority of pulmonary diseases caused by cigarette smoke (CS) are inflammatory in origin. Airway epithelial cells and alveolar macrophages have altered inflammatory signaling in response to CS, which leads to recruitment of lymphocytes, eosinophils, neutrophils, and mast cells to the lungs-depending on the signaling pathway (nuclear factor-κB, adenosine monophosphate-activated protein kinase, c-Jun N-terminal kinase, p38, and signal transducer and activator of transcription 3) activated. Multiple proteins are upregulated and secreted in response to CS exposure, and many of these have immunomodulatory activities that contribute to disease pathogenesis. In particular, metalloproteases 9 and 12, surfactant protein D, antimicrobial peptides (LL-37 and human β defensin 2), and IL-1, IL-6, IL-8, and IL-17 have been found in higher quantities in the lungs of smokers with ongoing inflammation. However, many underlying mechanisms of smoking-induced inflammatory diseases are not yet known. We review here the known cellular and molecular mechanisms of CS-induced diseases, including COPD, respiratory bronchiolitis-interstitial lung disease, desquamative interstitial pneumonia, acute eosinophilic pneumonia, chronic rhinosinusitis, pulmonary Langerhans cell histiocytosis, and chronic bacterial infections. We also discuss inflammation induced by secondhand and thirdhand smoke exposure and the pulmonary diseases that result. New targeted antiinflammatory therapeutic options are currently under investigation and hopefully will yield promising results for the treatment of these highly prevalent smoking-induced diseases. PMID:26135024

  5. Acute rheumatic fever and rheumatic heart disease.

    PubMed

    Carapetis, Jonathan R; Beaton, Andrea; Cunningham, Madeleine W; Guilherme, Luiza; Karthikeyan, Ganesan; Mayosi, Bongani M; Sable, Craig; Steer, Andrew; Wilson, Nigel; Wyber, Rosemary; Zühlke, Liesl

    2016-01-01

    Acute rheumatic fever (ARF) is the result of an autoimmune response to pharyngitis caused by infection with group A Streptococcus. The long-term damage to cardiac valves caused by ARF, which can result from a single severe episode or from multiple recurrent episodes of the illness, is known as rheumatic heart disease (RHD) and is a notable cause of morbidity and mortality in resource-poor settings around the world. Although our understanding of disease pathogenesis has advanced in recent years, this has not led to dramatic improvements in diagnostic approaches, which are still reliant on clinical features using the Jones Criteria, or treatment practices. Indeed, penicillin has been the mainstay of treatment for decades and there is no other treatment that has been proven to alter the likelihood or the severity of RHD after an episode of ARF. Recent advances - including the use of echocardiographic diagnosis in those with ARF and in screening for early detection of RHD, progress in developing group A streptococcal vaccines and an increased focus on the lived experience of those with RHD and the need to improve quality of life - give cause for optimism that progress will be made in coming years against this neglected disease that affects populations around the world, but is a particular issue for those living in poverty. PMID:27188830

  6. Clinical Trials for Rare Lung Diseases: Lessons from Lymphangioleiomyomatosis

    PubMed Central

    McCormack, Francis X.

    2010-01-01

    Abstract Lymphangioleiomyomatosis (LAM) is a rare, slowly progressive neoplasm that causes gradual but often life-threatening cystic destruction of the lung. Advances in our understanding of the molecular and cellular pathogenesis have LAM have identified a number of promising targets for testing in therapeutic trials. However, the design, prioritization, organization, and implementation of clinical trials in rare lung diseases poses unique challenges, including geographically disperse populations, sluggish enrollment, off- label drug use, burdensome regulations, and paucity of validated surrogate endpoints. PMID:20235889

  7. [Acute bacterial meningitis as an occupational disease].

    PubMed

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

    2014-01-01

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

  8. Fatal Acute Chagas Disease in a Chimpanzee

    PubMed Central

    Bommineni, Yugendar R.; Dick, Edward J.; Estep, J. Scot; Van de Berg, John L.; Hubbard, Gene B.

    2009-01-01

    Background Chagas disease (CD) or American trypanosomiasis is caused by a hemoflagellate protozoan, Trypanosoma cruzi (TC). This organism has been isolated from more than 100 mammalian species and several insect vectors demonstrating a wide host distribution and low host specificity. Methods A 23 year old male chimpanzee died acutely and a complete necropsy was performed to evaluate gross and microscopic pathologic changes. After observation of trypanosomal amastigotes in the myocardium, PCR and immunohistochemistry was employed to confirm the diagnosis of TC. Results Gross findings were consistent with mild congestive heart failure. Microscopic findings included multifocal myocardial necrosis associated with severe lymphocytic to mixed inflammatory infiltrates, edema, and mild chronic interstitial fibrosis. Multifocal intracytoplasmic amastigotes morphologically consistent with TC were observed in cardiac myofibers. TC was confirmed by PCR and immunohistochemistry. Conclusion We report, to the best of our knowledge, the first fatal spontaneous case of TC infection in a chimpanzee. PMID:19281482

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

    PubMed Central

    2012-01-01

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

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

    PubMed Central

    Levitt, Joseph E; Matthay, Michael A

    2011-01-01

    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. PMID:21128753

  11. Transfusion-related acute lung injury following coronary artery bypass graft surgery.

    PubMed

    Bitargil, M; Arslan, C; Başbuğ, H S; Göçer, H; Günerhan, Y; Bekov, Y Y

    2015-11-01

    Blood transfusion is sometimes a necessary procedure during or following coronary artery bypass graft (CABG) surgery. However, transfusion-related acute lung injury (TRALI)/possible TRALI is a rare and fatal complication and characterized by acute hypoxemia and non-cardiogenic pulmonary edema that occurs within 6 hours following a transfusion. Anti-leukocyte antibodies or, possibly, other bioactive substances cause inflammation and capillary endothelial destruction in susceptible recipients' lungs. Prompt diagnosis and mechanical ventilatory support are important. A successful treatment of two male patients following CABG surgery, compatible with TRALI/possible TRALI, is presented here. PMID:25575703

  12. Perfusatory recovery of the grafted lung during convalescence from acute rejection.

    PubMed

    Yamamoto, H; Okada, M; Tobe, S; Tsuji, F; Ohbo, H; Yamashita, C

    2000-01-01

    The aim of this study was to evaluate whether or not perfusatory recovery of the grafted lung occurs is the early stage of convalesce from acute rejection following a single lung transplantation. Eight adult mongrel dogs underwent an allotransplantation of the left lung with treatment of 10 mg/kg cyclosporine and 4 mg/kg azathioprine. Doppler flow probes were placed to the ascending aorta and the left pulmonary artery. Immunosuppressant therapy was discontinued to induce rejection after postoperative day 14. When the left pulmonary artery flow rate (l-PAFR) decreased to less than 20%, methylprednisolone (20 mg/kg) was administered for 3 days along with a resumption of cyclosporine and azathioprine. Pulmonary circulation and chest roentgenograms were evaluated every day through the rejection episode. An open lung biopsy was also performed in each dog to obtain specimens of the grafts and native lungs for histologic examination. When l-PAFR decreased to less than 20%, mild acute rejection was found in all dogs. l-PAFR increased significantly on the third day after methylprednisolone treatment. Thereafter, a histologic examination revealed minimal acute rejection in one dog and no abnormality in seven dogs. The perfusatory recovery of the grafted lung was thought to reflect the histological change in the course of convalescence. PMID:10664339

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

    PubMed Central

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

    2004-01-01

    Acute lung injury (ALI) and the acute respiratory distress syndrome are complex syndromes because both inflammatory and coagulation cascades cause lung injury. Transport of salt and water, repair and remodeling of the lung, apoptosis, and necrosis are additional important mechanisms of injury. Alveolar edema is cleared by active transport of salt and water from the alveoli into the lung interstitium by complex cellular mechanisms. Beta-2 agonists act on the cellular mechanisms of pulmonary edema clearance as well as other pathways relevant to repair in ALI. Numerous studies suggest that the beneficial effects of beta-2 agonists in ALI include at least enhanced fluid clearance from the alveolar space, anti-inflammatory actions, and bronchodilation. The purposes of the present review are to consider the effects of beta agonists on three mechanisms of improvement of lung injury: edema clearance, anti-inflammatory effects, and bronchodilation. This update reviews specifically the evidence on the effects of beta-2 agonists in human ALI and in models of ALI. The available evidence suggests that beta-2 agonists may be efficacious therapy in ALI. Further randomized controlled trials of beta agonists in pulmonary edema and in acute lung injury are necessary. PMID:15312205

  14. 17β-estradiol protects the lung against acute injury: possible mediation by vasoactive intestinal polypeptide.

    PubMed

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

    2011-12-01

    Beyond their classical role as a class of female sex hormones, estrogens (e.g. 17β-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) ERα and ERβ 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

  15. 17β-Estradiol Protects the Lung against Acute Injury: Possible Mediation by Vasoactive Intestinal Polypeptide

    PubMed Central

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

    2011-01-01

    Beyond their classical role as a class of female sex hormones, estrogens (e.g. 17β-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) ERα and ERβ 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

  16. CT of chronic infiltrative lung disease: Prevalence of mediastinal lymphadenopathy

    SciTech Connect

    Niimi, Hiroshi; Kang, Eun-Young; Kwong, S.

    1996-03-01

    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.

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

    PubMed

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

    2014-03-01

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

  18. The pathology of the acute and chronic stages of farmer's lung

    PubMed Central

    Seal, R. M. E.; Hapke, E. J.; Thomas, G. O.; Meek, J. C.; Hayes, M.

    1968-01-01

    The pathology of five patients who had a biopsy in the acute stage is described; interstitial pneumonia, sarcoid-like granulomata, bronchiolitis, and vasculitis were found. Three of these patients progressed to the chronic stage, when the one with the most extensive bronchiolar involvement had lung function findings of airway obstruction. One progressed to the chronic stage with lung function findings of a transfer defect, and another had radiographic evidence of pulmonary fibrosis with normal lung function tests at rest. The pathology of the chronic stage is described in six patients, with necropsy findings in five. Interstitial pulmonary fibrosis, cystic change, and pulmonary hypertensive changes were the principal findings. Images PMID:5680234

  19. Connective tissue diseases, multimorbidity and the ageing lung.

    PubMed

    Spagnolo, Paolo; Cordier, Jean-François; Cottin, Vincent

    2016-05-01

    Connective tissue diseases encompass a wide range of heterogeneous disorders characterised by immune-mediated chronic inflammation often leading to tissue damage, collagen deposition and possible loss of function of the target organ. Lung involvement is a common complication of connective tissue diseases. Depending on the underlying disease, various thoracic compartments can be involved but interstitial lung disease is a major contributor to morbidity and mortality. Interstitial lung disease, pulmonary hypertension or both are found most commonly in systemic sclerosis. In the elderly, the prevalence of connective tissue diseases continues to rise due to both longer life expectancy and more effective and better-tolerated treatments. In the geriatric population, connective tissue diseases are almost invariably accompanied by age-related comorbidities, and disease- and treatment-related complications, which contribute to the significant morbidity and mortality associated with these conditions, and complicate treatment decision-making. Connective tissue diseases in the elderly represent a growing concern for healthcare providers and an increasing burden of global health resources worldwide. A better understanding of the mechanisms involved in the regulation of the immune functions in the elderly and evidence-based guidelines specifically designed for this patient population are instrumental to improving the management of connective tissue diseases in elderly patients. PMID:26917611

  20. Protective Role of Proton-Sensing TDAG8 in Lipopolysaccharide-Induced Acute Lung Injury

    PubMed Central

    Tsurumaki, Hiroaki; Mogi, Chihiro; Aoki-Saito, Haruka; Tobo, Masayuki; Kamide, Yosuke; Yatomi, Masakiyo; Sato, Koichi; Dobashi, Kunio; Ishizuka, Tamotsu; Hisada, Takeshi; Yamada, Masanobu; Okajima, Fumikazu

    2015-01-01

    Acute lung injury is characterized by the infiltration of neutrophils into lungs and the subsequent impairment of lung function. Here we explored the role of TDAG8 in lung injury induced by lipopolysaccharide (LPS) administrated intratracheally. In this model, cytokines and chemokines released from resident macrophages are shown to cause neutrophilic inflammation in the lungs. We found that LPS treatment increased TDAG8 expression in the lungs and confirmed its expression in resident macrophages in bronchoalveolar lavage (BAL) fluids. LPS administration remarkably increased neutrophil accumulation without appreciable change in the resident macrophages, which was associated with increased penetration of blood proteins into BAL fluids, interstitial accumulation of inflammatory cells, and damage of the alveolar architecture. The LPS-induced neutrophil accumulation and the associated lung damage were enhanced in TDAG8-deficient mice as compared with those in wild-type mice. LPS also increased several mRNA and protein expressions of inflammatory cytokines and chemokines in the lungs or BAL fluids. Among these inflammatory mediators, mRNA and protein expression of KC (also known as CXCL1), a chemokine of neutrophils, were significantly enhanced by TDAG8 deficiency. We conclude that TDAG8 is a negative regulator for lung neutrophilic inflammation and injury, in part, through the inhibition of chemokine production. PMID:26690120

  1. Oxidative Stress and Therapeutic Development in Lung Diseases

    PubMed Central

    Villegas, Leah; Stidham, Timothy; Nozik-Grayck, Eva

    2016-01-01

    Oxidative stress has many implications in the pathogenesis of lung diseases. In this review, we provide an overview of Reactive Oxygen Species (ROS) and nitrogen (RNS) species and antioxidants, how they relate to normal physiological function and the pathophysiology of different lung diseases, and therapeutic strategies. The production of ROS/RNS from endogenous and exogenous sources is first discussed, followed by antioxidant systems that restore oxidative balance and cellular homeostasis. The contribution of oxidant/antioxidant imbalance in lung disease pathogenesis is also discussed. An overview of therapeutic strategies is provided, such as augmenting NO bioactivity, blocking the production of ROS/RNS and replacement of deficient antioxidants. The limitations of current strategies and failures of clinical trials are then addressed, followed by discussion of novel experimental approaches for the development of improved antioxidant therapies.

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

    PubMed

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

    2014-01-01

    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

  3. Human mesenchymal stromal cells reduce influenza A H5N1-associated acute lung injury in vitro and in vivo.

    PubMed

    Chan, Michael C W; Kuok, Denise I T; Leung, Connie Y H; Hui, Kenrie P Y; Valkenburg, Sophie A; Lau, Eric H Y; Nicholls, John M; Fang, Xiaohui; Guan, Yi; Lee, Jae W; Chan, Renee W Y; Webster, Robert G; Matthay, Michael A; Peiris, J S Malik

    2016-03-29

    Influenza can cause acute lung injury. Because immune responses often play a role, antivirals may not ensure a successful outcome. To identify pathogenic mechanisms and potential adjunctive therapeutic options, we compared the extent to which avian influenza A/H5N1 virus and seasonal influenza A/H1N1 virus impair alveolar fluid clearance and protein permeability in an in vitro model of acute lung injury, defined the role of virus-induced soluble mediators in these injury effects, and demonstrated that the effects are prevented or reduced by bone marrow-derived multipotent mesenchymal stromal cells. We verified the in vivo relevance of these findings in mice experimentally infected with influenza A/H5N1. We found that, in vitro, the alveolar epithelium's protein permeability and fluid clearance were dysregulated by soluble immune mediators released upon infection with avian (A/Hong Kong/483/97, H5N1) but not seasonal (A/Hong Kong/54/98, H1N1) influenza virus. The reduced alveolar fluid transport associated with down-regulation of sodium and chloride transporters was prevented or reduced by coculture with mesenchymal stromal cells. In vivo, treatment of aged H5N1-infected mice with mesenchymal stromal cells increased their likelihood of survival. We conclude that mesenchymal stromal cells significantly reduce the impairment of alveolar fluid clearance induced by A/H5N1 infection in vitro and prevent or reduce A/H5N1-associated acute lung injury in vivo. This potential adjunctive therapy for severe influenza-induced lung disease warrants rapid clinical investigation. PMID:26976597

  4. Human mesenchymal stromal cells reduce influenza A H5N1-associated acute lung injury in vitro and in vivo

    PubMed Central

    Chan, Michael C. W.; Kuok, Denise I. T.; Leung, Connie Y. H.; Hui, Kenrie P. Y.; Valkenburg, Sophie A.; Lau, Eric H. Y.; Nicholls, John M.; Fang, Xiaohui; Guan, Yi; Lee, Jae W.; Chan, Renee W. Y.; Webster, Robert G.; Matthay, Michael A.; Peiris, J. S. Malik

    2016-01-01

    Influenza can cause acute lung injury. Because immune responses often play a role, antivirals may not ensure a successful outcome. To identify pathogenic mechanisms and potential adjunctive therapeutic options, we compared the extent to which avian influenza A/H5N1 virus and seasonal influenza A/H1N1 virus impair alveolar fluid clearance and protein permeability in an in vitro model of acute lung injury, defined the role of virus-induced soluble mediators in these injury effects, and demonstrated that the effects are prevented or reduced by bone marrow-derived multipotent mesenchymal stromal cells. We verified the in vivo relevance of these findings in mice experimentally infected with influenza A/H5N1. We found that, in vitro, the alveolar epithelium’s protein permeability and fluid clearance were dysregulated by soluble immune mediators released upon infection with avian (A/Hong Kong/483/97, H5N1) but not seasonal (A/Hong Kong/54/98, H1N1) influenza virus. The reduced alveolar fluid transport associated with down-regulation of sodium and chloride transporters was prevented or reduced by coculture with mesenchymal stromal cells. In vivo, treatment of aged H5N1-infected mice with mesenchymal stromal cells increased their likelihood of survival. We conclude that mesenchymal stromal cells significantly reduce the impairment of alveolar fluid clearance induced by A/H5N1 infection in vitro and prevent or reduce A/H5N1-associated acute lung injury in vivo. This potential adjunctive therapy for severe influenza-induced lung disease warrants rapid clinical investigation. PMID:26976597

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

    SciTech Connect

    Infante, P.F.; Wagoner, J.K.; Sprince, N.L.

    1980-02-01

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

  6. Unusual progression and subsequent improvement in cystic lung disease in a child with radiation-induced lung injury.

    PubMed

    Wolf, Michael S; Chadha, Ashley D; Carroll, Clinton M; Borinstein, Scott C; Young, Lisa R

    2015-07-01

    Radiation-induced lung disease is a known complication of therapeutic lung irradiation, but the features have not been well described in children. We report the clinical, radiologic and histologic features of interstitial lung disease (ILD) in a 4-year-old child who had previously received lung irradiation as part of successful treatment for metastatic Wilms tumor. Her radiologic abnormalities and clinical symptoms developed in an indolent manner. Clinical improvement gradually occurred with corticosteroid therapy. However, the observed radiologic progression from interstitial and reticulonodular opacities to diffuse cystic lung disease, with subsequent improvement, is striking and has not been previously described in children. PMID:25434733

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-03-01

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

  9. Exhaled nitric oxide as biomarker of acute lung injury: an unfulfilled promise?

    PubMed

    Boshier, Piers R; Hanna, George B; Marczin, Nandor

    2013-03-01

    The discovery of nitric oxide (NO) as a signalling and regulatory molecule and its subsequent detection in the exhaled breath has not only yielded new mechanistic insights but also diagnostic opportunities and therapeutic targets in several important medical conditions. In diseases involving chronic pulmonary inflammation such as asthma that affects millions worldwide, exhaled NO has achieved spectacular successes with patients currently owning handheld devices and monitoring inflammatory aspects of their conditions in their own homes. This has been facilitated by recognition by regulatory bodies, scientific and clinical societies and insurance companies. While characteristic changes in exhaled NO have also been observed in acute lung injury (ALI), the promise of exhaled NO as a surrogate biomarker of this life-threatening disease has not been achieved. In this work, we have analysed factors contributing to successes of exhaled NO in the asthma field and contrasted these on the ALI field. We provide a snapshot of current status of exhaled NO field in ALI and propose a framework for definite evaluation of exhaled NO as a clinically useful biomarker. PMID:23445570

  10. αKlotho deficiency in acute kidney injury contributes to lung damage.

    PubMed

    Ravikumar, Priya; Li, Liping; Ye, Jianfeng; Shi, Mingjun; Taniguchi, Masatomo; Zhang, Jianning; Kuro-O, Makoto; Hu, Ming Chang; Moe, Orson W; Hsia, Connie C W

    2016-04-01

    αKlotho is a circulating protein that originates predominantly from the kidney and exerts cytoprotective effects in distant sites. We previously showed in rodents that the lung is particularly vulnerable to αKlotho deficiency. Because acute lung injury is a common and serious complication of acute kidney injury (AKI), we hypothesized that αKlotho deficiency in AKI contributes to lung injury. To test the hypothesis, we created AKI by renal artery ischemia-reperfusion in rats and observed the development of alveolar interstitial edema and increased pulmonary oxidative damage to DNA, protein, and lipids. Administration of αKlotho-containing conditioned media 6 h post-AKI did not alter plasma creatinine but improved recovery of endogenous αKlotho production 3 days post-AKI, reduced lung edema and oxidative damage, and increased endogenous antioxidative capacity in the lung. Intravenously injected αKlotho rapidly exits alveolar capillaries as a macromolecule, suggesting transcytosis and direct access to the epithelium. To explore the epithelial action of αKlotho, we simulated oxidative stress in vitro by adding hydrogen peroxide to cultured A549 lung epithelial cells. Purified recombinant αKlotho directly protected cells at 20 pM with half-maximal effects at 40-50 pM, which is compatible with circulating αKlotho levels. Addition of recombinant αKlotho activated an antioxidant response element reporter and increased the levels of target proteins of the nuclear factor erythroid-derived 2 related factor system. In summary, αKlotho deficiency in AKI contributes to acute lung injury by reducing endogenous antioxidative capacity and increasing oxidative damage in the lung. αKlotho replacement partially reversed these abnormalities and mitigated pulmonary complications in AKI. PMID:26718784

  11. Enteropathogens associated with acute diarrhoeal diseases.

    PubMed

    Niyogi, S K; Saha, M R; De, S P

    1994-01-01

    Five types of Escherichia coli are responsible for as much as 25% of all diarrheal diseases in developing countries. They tend to be transmitted via contaminated foods, particularly weaning foods, and water. They include enterotoxigenic, enteropathogenic, enteroadherent, enteroinvasive, and enterohemorrhagic E. coli. Shigella species are responsible for 10-15% of acute diarrheas in children less than 5 years old and the most common etiologic agents of childhood dysentery. Shigellosis is common in the warm season. An outbreak of shigella dysentery in West Bengal, India, had a high attack rate in children less than 5 years old and was resistant to many drugs. Nontyphoid Salmonella species cause watery diarrhea with nausea, cramps, and fever. Worldwide, various Salmonella strains exhibit resistance to ampicillin, chloramphenicol, and co-trimoxazole. Campylobacter jejuni produces watery diarrhea which, in 33% of cases and 1-2 days after onset, contains blood and mucus. Many normal healthy children in developing countries are carriers of C. jejuni. Vibrio cholerae O1 is endemic in parts of Africa and Asia (e.g., 5-10% of hospitalized diarrhea patients). The ElTor cholera biotype is responsible for the 7th pandemic. Other bacterial enteropathogens are Aeromonas species, Bacteroides fragilis, and Providencia alcalifaciens. Rotavirus is a major cause of sporadic and epidemic diarrhea among 6-23 month olds. Its incidence peaks in cold or dry seasons. Other viral enteropathogens are Norwalk virus, adenoviruses, astroviruses, and coronaviruses. In India, the prevalence of Entamoeba histolytica varies from 3.6% to 47.4%. It occurs equally in high and low socioeconomic classes. Giardia lamblia usually infects 1-5 year old children. Its transmission routes are food, water, and the fecal-oral route. Cryptosporidia produce acute watery diarrhea, especially in children less than 2 years old. Cryptosporidia diarrhea is common among AIDS patients. Oral rehydration therapy and proper feeding during and after diarrhea reduces deaths from diarrhea. PMID:7835992

  12. Bone Marrow Stromal Cells Attenuate Lung Injury in a Murine Model of Neonatal Chronic Lung Disease

    PubMed Central

    Aslam, Muhammad; Baveja, Rajiv; Liang, Olin D.; Fernandez-Gonzalez, Angeles; Lee, Changjin; Mitsialis, S. Alex; Kourembanas, Stella

    2009-01-01

    Rationale: Neonatal chronic lung disease, known as bronchopulmonary dysplasia (BPD), remains a serious complication of prematurity despite advances in the treatment of extremely low birth weight infants. Objectives: Given the reported protective actions of bone marrow stromal cells (BMSCs; mesenchymal stem cells) in models of lung and cardiovascular injury, we tested their therapeutic potential in a murine model of BPD. Methods: Neonatal mice exposed to hyperoxia (75% O2) were injected intravenously on Day 4 with either BMSCs or BMSC-conditioned media (CM) and assessed on Day 14 for lung morphometry, vascular changes associated with pulmonary hypertension, and lung cytokine profile. Measurements and Main Results: Injection of BMSCs but not pulmonary artery smooth muscle cells (PASMCs) reduced alveolar loss and lung inflammation, and prevented pulmonary hypertension. Although more donor BMSCs engrafted in hyperoxic lungs compared with normoxic controls, the overall low numbers suggest protective mechanisms other than direct tissue repair. Injection of BMSC-CM had a more pronounced effect than BMSCs, preventing both vessel remodeling and alveolar injury. Treated animals had normal alveolar numbers at Day 14 of hyperoxia and a drastically reduced lung neutrophil and macrophage accumulation compared with PASMC–CM-treated controls. Macrophage stimulating factor 1 and osteopontin, both present at high levels in BMSC-CM, may be involved in this immunomodulation. Conclusions: BMSCs act in a paracrine manner via the release of immunomodulatory factors to ameliorate the parenchymal and vascular injury of BPD in vivo. Our study suggests that BMSCs and factor(s) they secrete offer new therapeutic approaches for lung diseases currently lacking effective treatment. PMID:19713447

  13. NLRP3, a Double-edged Sword in Lung Injury Diseases.

    PubMed

    Wu, Jun-Xu; Shi, Kai-Hu

    2015-10-01

    Nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) plays a key role in lung injury diseases regulation, and its expression is increased in lung injury diseases. NLRP3 may be a good therapeutic target for lung injury diseases. The molecular mechanisms of NLRP3 in lung injury diseases remain unclear. It is a key to study the potential mechanism of NLRP3 during lung injury diseases, so that to exploit it as a good target for lung injury diseases therapy. PMID:25899804

  14. Rationale and emerging approaches for targeting lung repair and regeneration in the treatment of chronic obstructive pulmonary disease.

    PubMed

    Rennard, Stephen I; Wachenfeldt, Karin von

    2011-08-01

    Lung repair and regeneration are appropriate therapeutic targets for the treatment of chronic obstructive pulmonary disease (COPD). Abnormal repair results if fibrosis of the airways is a major contributor to fixed airflow limitation in airway disease. Inadequate repair in the face of tissue injury can contribute to the development of emphysema. With respect to the latter, acute exposure to cigarette smoke can impair repair responses of several cell types in the lung. Fibroblasts cultured from the lungs of patients with emphysema have persistent defects in repair that include modulation of extracellular matrix as well as production of growth factors that modulate other lung parenchymal cells. Some of the deficient repair functions appear to result from insensitivity to TGF-β and overproduction of prostaglandin E. Pharmacologic interventions targeting these pathways have the potential to at least partially reverse the abnormal repair. Alternate strategies that could modulate lung repair and regeneration could target resident or circulating stem/progenitor cells or potentially involve transplantation of new stem cells. Therapy directed at lung repair has the potential to restore lost lung function. In contrast to therapy designed to slow the progression of COPD, it may be much easier and less expensive to demonstrate efficacy for a therapy that restores lung function. PMID:21816994

  15. Perinatal Factors in Neonatal and Pediatric Lung Diseases

    PubMed Central

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

    2014-01-01

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

  16. A genetic variant of cortactin linked to acute lung injury impairs lamellipodia dynamics and endothelial wound healing.

    PubMed

    Choi, Sangwook; Camp, Sara M; Dan, Arkaprava; Garcia, Joe G N; Dudek, Steven M; Leckband, Deborah E

    2015-11-01

    Inflammatory mediators released in acute lung injury (ALI) trigger the disruption of interendothelial junctions, leading to loss of vascular barrier function, protein-rich pulmonary edema, and severe hypoxemia. Genetic signatures that predict patient recovery or disease progression are poorly defined, but recent genetic screening of ALI patients has identified an association between lung inflammatory disease and a single nucleotide polymorphism (SNP) in the gene for the actin-binding and barrier-regulatory protein cortactin. This study investigated the impact of this disease-linked cortactin variant on wound healing processes that may contribute to endothelial barrier restoration. A microfabricated platform was used to quantify wound healing in terms of gap closure speed, lamellipodia dynamics, and cell velocity. Overexpression of wild-type cortactin in endothelial cells (ECs) improved directional cell motility and enhanced lamellipodial protrusion length, resulting in enhanced gap closure rates. By contrast, the cortactin SNP impaired wound closure and cell locomotion, consistent with the observed reduction in lamellipodial protrusion length and persistence. Overexpression of the cortactin SNP in lung ECs mitigated the barrier-enhancing activity of sphingosine 1-phosphate. These findings suggest that this common cortactin variant may functionally contribute to ALI predisposition by impeding endothelial wound healing. PMID:26361873

  17. Clinical review: Exogenous surfactant therapy for acute lung injury/acute respiratory distress syndrome--where do we go from here?

    PubMed

    Dushianthan, Ahilanandan; Cusack, Rebecca; Goss, Victoria; Postle, Anthony D; Grocott, Mike P W

    2012-01-01

    Acute lung injury and acute respiratory distress syndrome (ARDS) are characterised by severe hypoxemic respiratory failure and poor lung compliance. Despite advances in clinical management, morbidity and mortality remains high. Supportive measures including protective lung ventilation confer a survival advantage in patients with ARDS, but management is otherwise limited by the lack of effective pharmacological therapies. Surfactant dysfunction with quantitative and qualitative abnormalities of both phospholipids and proteins are characteristic of patients with ARDS. Exogenous surfactant replacement in animal models of ARDS and neonatal respiratory distress syndrome shows consistent improvements in gas exchange and survival. However, whilst some adult studies have shown improved oxygenation, no survival benefit has been demonstrated to date. This lack of clinical efficacy may be related to disease heterogeneity (where treatment responders may be obscured by nonresponders), limited understanding of surfactant biology in patients or an absence of therapeutic effect in this population. Crucially, the mechanism of lung injury in neonates is different from that in ARDS: surfactant inhibition by plasma constituents is a typical feature of ARDS, whereas the primary pathology in neonates is the deficiency of surfactant material due to reduced synthesis. Absence of phenotypic characterisation of patients, the lack of an ideal natural surfactant material with adequate surfactant proteins, coupled with uncertainty about optimal timing, dosing and delivery method are some of the limitations of published surfactant replacement clinical trials. Recent advances in stable isotope labelling of surfactant phospholipids coupled with analytical methods using electrospray ionisation mass spectrometry enable highly specific molecular assessment of phospholipid subclasses and synthetic rates that can be utilised for phenotypic characterisation and individualisation of exogenous surfactant replacement therapy. Exploring the clinical benefit of such an approach should be a priority for future ARDS research. PMID:23171712

  18. 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 ...

  19. 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 ...

  20. [Chronic interstitial lung disease in children: Diagnostic approach and management].

    PubMed

    Fuger, M; Clair, M-P; El Ayoun Ibrahim, N; L'Excellent, S; Nizery, L; O'Neill, C; Tabone, L; Truffinet, O; Yakovleff, C; de Blic, J

    2016-05-01

    Chronic interstitial lung disease (ILD) in children is a heterogeneous group of rare lung disorders characterized by an inflammatory process of the alveolar wall and the pulmonary interstitium that induces gas exchange disorders. The diagnostic approach to an ILD involves three essential steps: recognizing the ILD, appreciating the impact, and identifying the cause. The spectrum of clinical findings depends to a large extent on age. In the newborn, the beginning is often abrupt (neonatal respiratory distress), whereas there is a more gradual onset in infants (failure to thrive, tachypnea, indrawing of the respiratory muscles). In older children, the onset is insidious and the diagnosis can only be made at an advanced stage of the disease. The diagnosis is based on noninvasive methods (clinical history, respiratory function tests, chest X-ray, and high-resolution CT scan) and invasive techniques (bronchoalveolar lavage, transbronchial biopsy, video-assisted thoracoscopic biopsy, and open lung biopsy). The treatment of interstitial lung disease in children depends on the nature of the underlying pathology. The most common therapeutic approach involves the use of corticosteroids and immunosuppressive agents for their anti-inflammatory and antifibrotic effects. Children with ILD also need support therapy (oxygen therapy, nutritional support, treatment of pulmonary arterial hypertension, vaccination). Lung transplantation is discussed in patients with severe respiratory failure. PMID:27021883

  1. Drug induced lung disease--amiodarone in focus.

    PubMed

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

    2014-01-01

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

  2. Clinical application of lung ultrasound in patients with acute dyspnea: differential diagnosis between cardiogenic and pulmonary causes.

    PubMed

    Cardinale, L; Volpicelli, G; Binello, F; Garofalo, G; Priola, S M; Veltri, A; Fava, C

    2009-10-01

    This review discusses the usefulness of bedside lung ultrasound in the diagnostic distinction between the various causes of acute dyspnoea in the emergency department, with special attention to the differential diagnosis of pulmonary oedema and exacerbation of chronic obstructive pulmonary disease (COPD). This is made possible by using mid- to low-end scanners and simple acquisition techniques accessible to both radiologists and clinicians. Major advantages include ready availability at the bedside, the absence of ionising radiation, high reproducibility and cost efficiency. The technique is based on the recognition and analysis of sonographic artefacts rather than direct visualisation of the pulmonary structures. These artefacts are caused by the interaction of water-rich structures and air, called comet tails or B-lines. When such artefacts are widely detected on anterolateral transthoracic lung scans, diffuse alveolar-interstitial syndrome can be diagnosed, which is often a sign of acute pulmonary oedema. This condition rules out exacerbation of COPD as the main cause of acute dyspnoea. PMID:19697100

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

    PubMed Central

    2010-01-01

    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-1β, 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. PMID:20546573

  4. Modifications of lung clearance mechanisms by acute influenza A infection

    SciTech Connect

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

    1985-10-01

    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.

  5. [Clinical study on development of nontuberculous mycobacterial lung disease].

    PubMed

    Kurashima, Atsuyuki

    2004-12-01

    DEVELOPEMENT OF MAC LUNG DISEASE: An increase of nodular bronchiectatic type of MAC lung disease becomes a problem among respiratory physician today. The reason is still unknown, but it seems to be globally recognized that this type of MAC disease is developing particularly in middle-aged woman. Some papers mentioned the existence of such type of MAC lung disease already early in the 70s, in Japan. Yamamoto described that 17 cases of middle lobe type lung disease out of 154 non-photochoromogen cases, and 76.5% were female, in 1970. Shimoide also pointed such type of 39 cases out of 240 MAC lung disease and 84.6% were female, in 1980. Prince reported MAC lung disease seen in old and middle age female of 21 cases including lethality example of 4 cases without a precedent disease in 1989. After his report, the international consensus of this peculiar type of MAC lung disease seems to be spread. In 1989, we compared 72 cases of nodular bronchiectatic type of MAC lung disease and 56 cases of diffuse panbronchiolitis (DPB) that was a most typical chronic airway disease at that time in Japan. The average age of disease onset of DPB group was 37.0 +/- 16.3 years old and that of MAC group was 54.5 +/- 16.3 years old. The percentage of female was 32% in DPB group and 87.5% in MAC group. It was highly possible that two groups belong different parent population. We could grasp that nodular bronchiectatic type of MAC lung disease patients is a unique group. We observed the serial films of 21 cases of nodular bronchiectatic MAC lung disease, and divide the progression of the disease to sequential 7 steps as Fig. 1. Small nodules progress to cavities in mean about 10 years. However, why is MAC which is opportunistic pathogen with weak virulence, able to form a lesion at unimpaired lung parenchyma? Is there really normal site? Why dose it start from lingula? Why is MAC seen a lot in woman? While it is extremely pathognomonic clinical picture, and, is an extremely interesting problem, most are still unidentified. STUDY OF MAC LUNG DISEASE TREATMENT: It was known that Mycobacterium kansasii lung disease is healed with a chemotherapy like analog of anti-tuberculosis chemotherapy, already in those days. However, the results of MAC lung disease chemotherapy were extremely poor. We tried to express a physicians experience quantitatively as follows, in 1987. The results of 8 weeks sputum culture on Ogawa egg medium were converted semi-quantitatively to CFU numbers based on "Japanese standard guideline of Mycobacterium tuberculosis inspection". We exhibit the ratio of post-treatment consecutive 6 months culture yield to pre-treatment culture yield as response rate, about 110 pulmonary MAC cases. Through this study, we clarify the followings. The results of chemotherapy do not correlate susceptibility test for Mycobacterium tuberculosis. Multidrug regimen is more useful. Small extent of lesion is more responsive. Combination with aminoglycoside chemotherapy is more effective. These conclusions were almost same as the ATS guideline of 1990. New drugs such as, new macrolides and new quinolones appeared for pulmonary MAC treatment through the feedback from systemic MAC complicated AIDS treatments from the latter half of 90's. We measured the sensitive strain ratio at 2 mcg/ml of OFLX, CPFX, LVFX about 990 clinical isolates and could expect availability for M. kansasii or M. fortuitum, but these new quinolones are not enough effective for MAC. Also we examined MIC for various antimycobacterial agent by 50 MAC clinical isolates, and we could expect a certain availability of SPFX, GFLX, CPFX, CAM for MAC. The availability of clarithromycin (CAM) has been established through many randomized clinical trials for disseminated MAC complicated AIDS, but for pulmonary MAC, complete cure is still difficult if we use CAM including regimen. We performed surgical treatment for relatively young patients with localized lesions. We carry out the adaptation reference such as Table, now. The localization of the lesions become a problem at surgical resection. Through the study of our 55 surgical treatment cases, 8 cases (67%) relapsed out of 12 cases which had destructive airway structure in unresected lung field. On the other, only 1 case relapsed (10%) relapsed out of 10 cases without airway destruction in unresected lung. Therefore, even if there is a little dispersal focus without airway destruction in the other pulmonary lobe except purpose focus of resection, it seems that control is possible by post operational chemotherapy. LONG SURVIVAL: As overall consequence, we calculate the survival curves of 201 pulmonary MAC patients visited Tokyo National Hospital from 1953. The survival medium value was 7332 days. The prognosis of nodular bronchiectatic type was better than that of post-tuberculosis type. Extent of disease measured by chest X-ray examination at the time of first visit may be a most affecting factor to the survival rate. PMID:15782619

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

    PubMed

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

    2013-01-01

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

  7. OPTICAL IMAGING OF LIPOPOLYSACCHARIDE-INDUCED OXIDATIVE STRESS IN ACUTE LUNG INJURY FROM HYPEROXIA AND SEPSIS

    PubMed Central

    SEPEHR, REYHANEH; AUDI, SAID H.; MALEKI, SEPIDEH; STANISZEWSKI, KEVIN; EIS, ANNIE L.; KONDURI, GIRIJA G.; RANJI, MAHSA

    2014-01-01

    Reactive oxygen species (ROS) have been implicated in the pathogenesis of many acute and chronic pulmonary disorders such as acute lung injury (ALI) in adults and bronchopulmonary dysplasia (BPD) in premature infants. Bacterial infection and oxygen toxicity, which result in pulmonary vascular endothelial injury, contribute to impaired vascular growth and alveolar simplification seen in the lungs of premature infants with BPD. Hyperoxia induces ALI, reduces cell proliferation, causes DNA damage and promotes cell death by causing mitochondrial dysfunction. The objective of this study was to use an optical imaging technique to evaluate the variations in fluorescence intensities of the auto-fluorescent mitochondrial metabolic coenzymes, NADH and FAD in four different groups of rats. The ratio of these fluorescence signals (NADH/FAD), referred to as NADH redox ratio (NADH RR) has been used as an indicator of tissue metabolism in injuries. Here, we investigated whether the changes in metabolic state can be used as a marker of oxidative stress caused by hyperoxia and bacterial lipopolysaccharide (LPS) exposure in neonatal rat lungs. We examined the tissue redox states of lungs from four groups of rat pups: normoxic (21% O2) pups, hyperoxic (90% O2) pups, pups treated with LPS (normoxic + LPS), and pups treated with LPS and hyperoxia (hyperoxic + LPS). Our results show that hyperoxia oxidized the respiratory chain as reflected by a ~31% decrease in lung tissue NADH RR as compared to that for normoxic lungs. LPS treatment alone or with hyperoxia had no significant effect on lung tissue NADH RR as compared to that for normoxic or hyperoxic lungs, respectively. Thus, NADH RR serves as a quantitative marker of oxidative stress level in lung injury caused by two clinically important conditions: hyperoxia and LPS exposure. PMID:24672581

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

    PubMed

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

    1988-12-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-11-01

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

  10. RAGE/NF-κB signaling mediates lipopolysaccharide induced acute lung injury in neonate rat model.

    PubMed

    Li, Yuhong; Wu, Rong; Tian, Yian; Yu, Min; Tang, Yun; Cheng, Huaipin; Tian, Zhaofang

    2015-01-01

    Lipopolysaccharide (LPS) is known to induce acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Accumulating data suggest the crucial role of RAGE in the pathogenesis of ALI/ARDS. However, the mechanism by which RAGE mediates inflammatory lung injury in the neonates remains elusive. In this study we established LPS-induced ALI model in neonate rats, and investigated the role of RAGE/NF-κB signaling in mediating ALI. We found that RAGE antibody or bortezomib reduced LPS-induced histopathological abnormalities in the lung and lung damage score. RAGE antibody or bortezomib also reduced TNF-α level in both serum and BALF of the rats. Furthermore, RAGE antibody or bortezomib significantly reduced LPS-induced upregulation of RAGE and NF-κB expression in the lung. In conclusion, we established ALI model in neonate rats to demonstrate that LPS induced inflammatory lung injury via RAGE/NF-κB signaling. Interference with RAGE/NF-κB signaling is a potential approach to prevent and treat sepsis-related ALI/ARDS. PMID:26550268

  11. The Design of Future Pediatric Mechanical Ventilation Trials for Acute Lung Injury

    PubMed Central

    Khemani, Robinder G.; Newth, Christopher J. L.

    2010-01-01

    Pediatric practitioners face unique challenges when attempting to translate or adapt adult-derived evidence regarding ventilation practices for acute lung injury or acute respiratory distress syndrome into pediatric practice. Fortunately or unfortunately, there appears to be selective adoption of adult practices for pediatric mechanical ventilation, many of which pose considerable challenges or uncertainty when translated to pediatrics. These differences, combined with heterogeneous management strategies within pediatric critical care, can complicate clinical practice and make designing robust clinical trials in pediatric acute respiratory failure particularly difficult. These issues surround the lack of explicit ventilator protocols in pediatrics, either computer or paper based; differences in modes of conventional ventilation and perceived marked differences in the approach to high-frequency oscillatory ventilation; challenges with patient recruitment; the shortcomings of the definition of acute lung injury and acute respiratory distress syndrome; the more reliable yet still somewhat unpredictable relationship between lung injury severity and outcome; and the reliance on potentially biased surrogate outcome measures, such as ventilator-free days, for all pediatric trials. The purpose of this review is to highlight these challenges, discuss pertinent work that has begun to address them, and propose potential solutions or future investigations that may help facilitate comprehensive trials on pediatric mechanical ventilation and define clinical practice standards. PMID:20732987

  12. Interstitial Lung Disease: NHLBI Workshop on the Primary Prevention of Chronic Lung Diseases

    PubMed Central

    Rosas, Ivan O.; Dellaripa, Paul F.; Lederer, David J.; Khanna, Dinesh; Young, Lisa R.

    2014-01-01

    Population-based, longitudinal studies spanning decades linking risk factors in childhood, adolescence and early adulthood to incident clinical interstitial lung disease (ILD) events in late adulthood have not been performed. In addition, no observational or randomized clinical trials have been conducted; therefore, there is presently no evidence to support the notion that reduction of risk factor levels in early life prevents ILD events in adult life. Primary prevention strategies are host-directed interventions designed to modify adverse risk factors (i.e., smoking) with the goal of preventing the development of ILD, whereas primordial prevention for ILD can be defined as the elimination of external risk factors (i.e., environmental pollutants). As no ILD primary prevention studies have been previously conducted, we propose that research studies that promote implementation of primary prevention strategies could, over time, make a subset of ILD preventable. Herein, we provide a number of initial steps required for the future implementation of prevention strategies; this statement discusses the rationale and available evidence that support potential opportunities for primordial and primary prevention, as well as fertile areas for future research of preventive intervention in ILD. PMID:24754826

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

    PubMed Central

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

    2014-01-01

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

  14. Metabolomics Investigation Reveals Metabolite Mediators Associated with Acute Lung Injury and Repair in a Murine Model of Influenza Pneumonia.

    PubMed

    Cui, Liang; Zheng, Dahai; Lee, Yie Hou; Chan, Tze Khee; Kumar, Yadunanda; Ho, Wanxing Eugene; Chen, Jian Zhu; Tannenbaum, Steven R; Ong, Choon Nam

    2016-01-01

    Influenza virus infection (IVI) can cause primary viral pneumonia, which may progress to acute lung injury (ALI) and respiratory failure with a potentially fatal outcome. At present, the interactions between host and influenza virus at molecular levels and the underlying mechanisms that give rise to IVI-induced ALI are poorly understood. We conducted a comprehensive mass spectrometry-based metabolic profiling of serum, lung tissue and bronchoalveolar lavage fluid (BALF) from a non-lethal mouse model with influenza A virus at 0, 6, 10, 14, 21 and 28 days post infection (dpi), representing the major stages of IVI. Distinct metabolite signatures were observed in mice sera, lung tissues and BALF, indicating the molecular differences between systematic and localized host responses to IVI. More than 100 differential metabolites were captured in mice sera, lung tissues and BALF, including purines, pyrimidines, acylcarnitines, fatty acids, amino acids, glucocorticoids, sphingolipids, phospholipids, etc. Many of these metabolites belonged to pulmonary surfactants, indicating IVI-induced aberrations of the pulmonary surfactant system might play an important role in the etiology of respiratory failure and repair. Our findings revealed dynamic host responses to IVI and various metabolic pathways linked to disease progression, and provided mechanistic insights into IVI-induced ALI and repair process. PMID:27188343

  15. Minimal residual disease in acute lymphoblastic leukemia.

    PubMed

    Campana, Dario

    2009-01-01

    In patients with acute lymphoblastic leukemia (ALL), monitoring of minimal residual disease (MRD) offers a way to precisely assess early treatment response and detect relapse. Established methods to study MRD are flow cytometric detection of abnormal immunophenotypes, polymerase chain reaction (PCR) amplification of antigen-receptor genes, and PCR amplification of fusion transcripts. The strong correlation between MRD levels and risk of relapse in childhood ALL is well demonstrated; studies in adult patients also support its prognostic value. Hence, results of MRD studies can be used to select treatment intensity and duration, and to estimate the optimal timing for hematopoietic stem cell transplantation. Practical issues in the implementation of MRD assays in clinical studies include determining the most informative time point to study MRD and the levels of MRD that will trigger changes in treatment intensity, as well as the relative cost and informative power of different methodologies. The identification of new markers of leukemia and the use of increasingly refined assays should further facilitate routine monitoring of MRD and help to clarify the cellular and biologic features of leukemic cells that resist chemotherapy in vivo. PMID:19100372

  16. Review of Elephant Endotheliotropic Herpesviruses and Acute Hemorrhagic Disease.

    PubMed

    Long, Simon Y; Latimer, Erin M; Hayward, Gary S

    2016-02-24

    More than 100 young captive and wild Asian elephants are known to have died from a rapid-onset, acute hemorrhagic disease caused primarily by multiple distinct strains of two closely related chimeric variants of a novel herpesvirus species designated elephant endotheliotropic herpesvirus (EEHV1A and EEHV1B). These and two other species of Probosciviruses (EEHV4 and EEHV5) are evidently ancient and likely nearly ubiquitous asymptomatic infections of adult Asian elephants worldwide that are occasionally shed in trunk wash secretions. Although only a handful of similar cases have been observed in African elephants, they also have proved to harbor their own multiple and distinct species of Probosciviruses-EEHV2, EEHV3, EEHV6, and EEHV7-found in lung and skin nodules or saliva. For reasons that are not yet understood, approximately 20% of Asian elephant calves appear to be susceptible to the disease when primary infections are not controlled by normal innate cellular and humoral immune responses. Sensitive specific polymerase chain reaction (PCR) DNA blood tests have been developed, routine monitoring has been established, the complete large DNA genomes of each of the four Asian EEHV species have now been sequenced, and PCR gene subtyping has provided unambiguous evidence that this is a sporadic rather than epidemic disease that it is not being spread among zoos or other elephant housing facilities. Nevertheless, researchers have not yet been able to propagate EEHV in cell culture, determine whether or not human antiherpesvirus drugs are effective inhibitors, or develop serology assays that can distinguish between antibodies against the multiple different EEHV species. PMID:26912715

  17. Occupational lung diseases and the mining industry in Mongolia

    SciTech Connect

    Lkhasuren, O.; Takahashi, K.; Dash-Onolt, L.

    2007-04-15

    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.

  18. Fibrocytes in chronic lung disease--facts and controversies.

    PubMed

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

    2012-08-01

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

  19. Observations on a model of proliferative lung disease

    PubMed Central

    Strauss, B.; Caldwell, P. R. B.; Fritts, H. W.

    1970-01-01

    Intravenous injections of complete Freund's adjuvant, used by others to stimulate the reticuloendothelial system of small laboratory animals, produced granulomas resembling sarcoid in the lung of the dog. At the height of the disease, when granulomas occupied more than half of the alveolar tissues, transpulmonary arteriovenous (A-[unk]V) differences of lactate, pyruvate, and glucose were measured. When the diseased dogs breathed room air, the A-[unk]V differences of lactate and pyruvate were greater than normal; and when the dogs breathed an hypoxic mixture, the differences increased further. Hence the model affords the opportunity for studying the in vivo metabolism of diseased lungs. It may also prove useful for studying other aspects of granulomatous disease which cannot be easily approached in man. PMID:5432367

  20. Pulmonary functional magnetic resonance imaging for paediatric lung disease.

    PubMed

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

    2013-09-01

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

  1. Epigenetic targets for novel therapies of lung diseases

    PubMed Central

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

    2014-01-01

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

  2. Recent Advances and Future Needs in Interstitial Lung Diseases.

    PubMed

    Jones, Mark G; Richeldi, Luca

    2016-06-01

    Interstitial lung diseases (ILDs) are a diverse range of conditions affecting the lung interstitium. The prototypic ILD, idiopathic pulmonary fibrosis (IPF), is a chronic progressive fibrotic lung disease with a median survival of only 3 years from the time of diagnosis. Recently significant progress has been made in both our understanding of the pathogenesis and of the therapeutic targeting of IPF. This culminated in the worldwide approval of the first antifibrotic therapies nintedanib and pirfenidone. While an important first step, patients continue to progress and better therapies are urgently required. The aim of this article is to highlight some of the recent advances that have been made in our understanding of genetics, disease classification, clinical trial design, and novel antifibrotic therapy in IPF. It discusses future priorities if we are to continue to increase the length and quality of life of patients with IPF, and considers possible approaches to translate the progress made in IPF to other progressive fibrotic lung diseases where our understanding remains limited. PMID:27231869

  3. 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...

  4. Work of breathing in children with diffuse parenchymal lung disease.

    PubMed

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

    2015-01-15

    Respiratory mechanics have been poorly studied in children with chronic diffuse parenchymal lung disease (DPLD). The aim of the study was to assess the usefulness of respiratory mechanics to monitor lung function alteration in children with DPLD. Respiratory mechanics, total (WOBt), elastic (WOBe) and resistive (WOBr) work of breathing, gas exchange, lung function and respiratory muscle strength were measured in 10 children, aged 1.8-18.4 years old, who were followed in our national reference centre. Mean tidal volume (Vt) was normal (114mL/kg) but respiratory rate (fr, 3219breaths/min), fr/Vt (11875breaths/min/L) and total lung resistance (10.24.8cmH2OL(-1)s) were increased. Mean WOBt was increased mainly due to WOBe. Dynamic lung compliance (Cldyn) was severely reduced (2624mL/cmH2O). Cldyn and the oesophageal pressure-time product strongly correlated with vital capacity and functional residual capacity. Respiratory muscle strength was within the normal range. In conclusion, lung mechanics may be considered as useful complementary or alternative markers of functional abnormalities in children with DPLD. PMID:25445729

  5. Interstitial lung disease induced by alectinib (CH5424802/RO5424802).

    PubMed

    Ikeda, Satoshi; Yoshioka, Hiroshige; Arita, Machiko; Sakai, Takahiro; Sone, Naoyuki; Nishiyama, Akihiro; Niwa, Takashi; Hotta, Machiko; Tanaka, Tomohiro; Ishida, Tadashi

    2015-02-01

    A 75-year-old woman with anaplastic lymphoma kinase (ALK)-rearranged Stage IV lung adenocarcinoma was administered the selective anaplastic lymphoma kinase inhibitor, alectinib, as a third-line treatment in a Phase 1-2 study. On the 102nd day, chest computed tomography showed diffuse ground glass opacities. Laboratory data revealed high serum levels of KL-6, SP-D and lactate dehydrogenase without any clinical symptoms. There was no evidence of infection. Marked lymphocytosis was seen in bronchoalveolar lavage fluid analysis, and transbronchial lung biopsy showed mild thickening of alveolar septa and lymphocyte infiltration. Interstitial lung disease was judged to be related to alectinib based on improvements in imaging findings and serum biomarkers after discontinuation of alectinib. To our knowledge, this is the first reported case of alectinib-induced interstitial lung disease. Alectinib is a promising drug for ALK-rearranged non-small cell lung cancer. Clinical trials of this selective anaplastic lymphoma kinase inhibitor will facilitate the meticulous elucidation of its long-term safety profile. PMID:25398579

  6. Protein misfolding and endoplasmic reticulum stress in chronic lung disease.

    PubMed

    Wei, James; Rahman, Sadaf; Ayaub, Ehab A; Dickhout, Jeffrey G; Ask, Kjetil

    2013-04-01

    The pathogenesis of chronic lung disorders is poorly understood but is often thought to arise because of repeated injuries derived from exposure to exogenous or endogenous stress factors. Protein-misfolding events have been observed in a variety of genetic and nongenetic chronic lung disorders and may contribute to both the initiation and the progression of lung disease through endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR). Evidence indicates that exposure to common lung irritants such as cigarette smoke, environmental pollutants, and infectious viral or bacterial agents can induce ER stress and protein misfolding. Although the UPR is thought to be a molecular mechanism involved in the repair and restoration of protein homeostasis or "proteostasis," prolonged activation of the UPR may lead to compromised cellular functions, cellular transformation, or cell death. Here, we review literature that associates protein-misfolding events with ER stress and UPR activation and discuss how this basic molecular repair mechanism may contribute to the initiation and progression of various genetic and nongenetic chronic lung diseases. PMID:23546482

  7. Acute ischemic optic neuropathy with extended prone position ventilation in a lung transplant recipient.

    PubMed

    Panchabhai, Tanmay S; Bandyopadhyay, Debabrata; Kapoor, Aanchal; Akindipe, Olufemi; Lane, Charles; Krishnan, Sudhir

    2016-01-01

    Prone position ventilation (PPV) improves mortality in severe acute respiratory distress syndrome (ARDS), but outcomes following its use in lung transplant recipients are not known. We report the case of a 42-year-old Caucasian man who presented with severe ARDS from Bordetella pertussis, 5 years after bilateral sequential lung transplant for cystic fibrosis. He was managed with PPV for 22 days and had a prolonged ICU stay complicated by hypoxic ischemic optic neuropathy leading to blindness. Since his discharge from the ICU 6 months ago, his FEV1 has recovered to 47% predicted compared to his pre-ICU peak FEV1 of 85% predicted, suggesting recovery of lung function. This is the first report of optic nerve damage and vision loss in patients undergoing PPV. Our report also suggests that, in appropriately selected lung transplant recipients, severe hypoxemia could potentially be managed with prone ventilation. PMID:27051622

  8. Acute ischemic optic neuropathy with extended prone position ventilation in a lung transplant recipient

    PubMed Central

    Panchabhai, Tanmay S; Bandyopadhyay, Debabrata; Kapoor, Aanchal; Akindipe, Olufemi; Lane, Charles; Krishnan, Sudhir

    2016-01-01

    Prone position ventilation (PPV) improves mortality in severe acute respiratory distress syndrome (ARDS), but outcomes following its use in lung transplant recipients are not known. We report the case of a 42-year-old Caucasian man who presented with severe ARDS from Bordetella pertussis, 5 years after bilateral sequential lung transplant for cystic fibrosis. He was managed with PPV for 22 days and had a prolonged ICU stay complicated by hypoxic ischemic optic neuropathy leading to blindness. Since his discharge from the ICU 6 months ago, his FEV1 has recovered to 47% predicted compared to his pre-ICU peak FEV1 of 85% predicted, suggesting recovery of lung function. This is the first report of optic nerve damage and vision loss in patients undergoing PPV. Our report also suggests that, in appropriately selected lung transplant recipients, severe hypoxemia could potentially be managed with prone ventilation.

  9. ROLE OF TACHYKININS IN OZONE-INDUCED ACUTE LUNG INJURY

    EPA Science Inventory

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

  10. Computational modeling of the obstructive lung diseases asthma and COPD.

    PubMed

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

    2014-11-28

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

  11. Computational modeling of the obstructive lung diseases asthma and COPD

    PubMed Central

    2014-01-01

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

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

    PubMed Central

    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, Noémie; Kajosaari, Merja; Wolters, Paul J.; Chapman, Harold A.; Kämpe, Olle; Anderson, Mark S.

    2013-01-01

    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. PMID:24107778

  13. Occupational lung disease. Part 1. Identifying work-related asthma and other disorders.

    PubMed

    Kuschner, Ware G; Stark, Paul

    2003-04-01

    Lung disease is prevalent among workers. Occupational toxicant exposures have an important role in many cases of lung disease seen in workers. Most occupational lung diseases can be grouped into one of four categories that include asthma and the diffuse parenchymal lung diseases (also known as interstitial lung disease). Asthma is especially prevalent among workers, and occupational factors should be explored in all adults with asthma. A worker's visit to a primary care physician often represents the first opportunity to establish a link between lung disease and the workplace. Therefore, it is important to maintain a high level of suspicion about the potential etiologic role of workplace exposures, especially in new cases of lung disease among workers. Although accumulating absolute proof of work-relatedness may not be possible, a brief occupational history and physical evaluation can provide substantial evidence to effectively rule out, or begin to rule in, a link between work and lung disease. PMID:12718236

  14. Effects on rat lung immunity by acute lung exposure to benzo(a)pyrene

    SciTech Connect

    Schnizlein, C.T.; Bice, D.E.; Mitchell, C.E.; Hahn, F.F.

    1982-07-01

    This study describes the effects of intratracheal instillation of benzo(a)pyrene (BaP) on immunological responses in the lung-associated lymph nodes, cervical lymph nodes, and spleen after deposition of 10/sup 8/ sheep red blood cells (SRBC) in the lung or peritoneal cavity of rats. An increased number of anti-SRBC antibody-forming cells was observed in the lung-associated lymph nodes when rats were immunized simultaneously with BaP instillation. A suppression in the number of anti-SRBC antibody-forming cells occurred when SRBC were given intratracheally 4 or 7 days after BaP. The effects of the BaP appeared to be on the function of the cells in the lung-associated lymph nodes rather than due to changes in the exposed lung. BaP-induced changes in antigen handling or in regulatory populations of immune cells in the lung-associated lymph nodes may be responsible for the immune alterations observed.

  15. Effects on rat lung immunity by acute lung exposure to benzo(a)pyrene

    SciTech Connect

    Schnizlein, C.T.; Bice, D.E.; Mitchell, C.E.; Hahn, F.F.

    1982-07-01

    This study describes the effect of intratracheal instillation of benzo(a)pyrene (BaP) on immunological responses in the lung-associated lymph nodes, cervical lymph nodes, and spleen after deposition of 10/sup 8/ sheep red blood cells (SRCB) in the lung or peritoneal cavity of rats. An increased number of anti-SRBC antibody-forming cells was observed in the lung-assoicated lymph nodes when rats were immunized simultaneously with BaP instillation. A suppression in the number of anti-SRBC antibody-forming cells occurred when SRBC were given intratracheally 4 or 7 days after BaP. The effects of the BaP appeared to be on the function of the cells in the lung-associated lymph nodes rather than due to changes in the exposed lung. BaP-induced changes in antigen handling or in regulatory populations of immune cells in the lung-associated lymph nodes may be responsible for the immune alterations observed.

  16. Blood transfusion for the treatment of acute anaemia in inflammatory bowel disease and other digestive diseases

    PubMed Central

    García-Erce, José Antonio; Gomollón, Fernando; Muñoz, Manuel

    2009-01-01

    Allogeneic blood transfusion (ABT) is frequently used as the first therapeutic option for the treatment of acute anaemia in patients with inflammatory bowel disease (IBD), especially when it developed due to gastrointestinal or perioperative blood loss, but is not risk-free. Adverse effects of ABT include, but are not limited to, acute hemolytic reaction (wrong blood or wrong patient), febrile non-hemolytic transfusional reaction, bacterial contamination, transfusion-related acute lung injury, transfusion associated circulatory overload, transfusion-related immuno-modulation, and transmission of almost all infectious diseases (bacteria, virus, protozoa and prion), which might result in increased risk of morbidity and mortality. Unfortunately, the main physiological goal of ABT, i.e. to increase oxygen consumption by the hypoxic tissues, has not been well documented. In contrast, the ABT is usually misused only to increase the haemoglobin level within a fixed protocol [mostly two by two packed red blood cell (PRC) units] independently of the patient’s tolerance to normovolemic anaemia or his clinical response to the transfusion of PRC units according to a “one-by-one” administration schedule. Evidence-based clinical guidelines may promote best transfusion practices by implementing restrictive transfusion protocols, thus reducing variability and minimizing the avoidable risks of transfusion, and the use of autologous blood and pharmacologic alternatives. In this regard, preoperative autologous blood donation (PABD) consistently diminished the frequency of ABT, although its contribution to ABT avoidance is reduced when performed under a transfusion protocol. In addition, interpretation of utility of PABD in surgical IBD patients is hampered by scarcity of published data. However, the role of autologous red blood cells as drug carriers is promising. Finally, it must be stressed that a combination of methods used within well-constructed protocols will offer better prospects for blood conservation in selected IBD patients undergoing elective surgery. PMID:19787832

  17. Errors in the measurement of total lung capacity in chronic obstructive lung disease.

    PubMed

    Paré, P D; Wiggs, B J; Coppin, C A

    1983-06-01

    The standard plethysmographic method of measuring total lung capacity (TLC) has been reported to result in spuriously high estimates in patients with severe airway obstruction. The helium-dilution method is known to underestimate TLC in the same patients. To determine the magnitude of these possible errors we measured TLC by four methods in 20 patients with varying degrees of chronic obstructive lung disease and in 11 normal subjects. TLC was measured by (1) helium dilution (TLCHe); (2) a volume-displacement body plethysmograph, box volume being plotted against mouth pressure (TLCm); (3) the same body plethysmograph with volume plotted against pressure measured with an oesophageal balloon (TLCes); and (4) a radiological technique (TLCxr). In normal subjects there was no difference between TCLm (6.57 +/- 1.20) and TLCes (6.51 +/- 1.24). In the patients with chronic obstructive lung disease TLCm gave results significantly higher than those of any other method. If TLCes is taken as the closest estimate of true TLC, TLCm consistently overestimates and TLCHe underestimates TLC. There was no relationship between the degree of airway obstruction and (TLCm - TLCes) but there was between (TLCes - TLCHe) and severity of airway obstruction. We conclude that using mouth pressure in the plethysmographic measurement of TLC in patients with chronic obstructive lung disease results in consistent but slight overestimation of TLC. PMID:6879500

  18. Severe right heart failure in a patient with chronic obstructive lung disease: a diagnostic challenge.

    PubMed

    Meysman, M; Pipeleers-Marichal, M; Geers, C; Ilsen, B; Vincken, W

    2013-01-01

    A 55-year-old male was admitted for evaluation of severe dyspnoea and hypoxaemia. Physical examination upon admission showed elevated jugular venous pressure and an accentuated second heart sound. Chest radiograph showed cardiomegaly with increased bibasilar markings. Arterial blood gas analysis while breathing room air showed marked hypoxaemia. High resolution computed tomography angiography of the chest showed modestly enlarged mediastinal lymph nodes with discrete diffuse ground-glass attenuation especially at the lower lung zones. Positron emission tomography using 18F labelled 2-deoxy-D-glucose (FDG) demonstrated the mediastinal lymph nodes were FDG-avid. Transthoracic echocardiography showed dilated hypokinetic right heart chambers with bulging of the interventricular septum to the left, compatible with acute cor-pulmonale. From the tricuspid regurgitation jet measurement a systolic pulmonary artery pressure (PAP) of 48 mmHg was estimated. Patent foramen ovale was suspected on bubble test. Right heart catheterisation confirmed pulmonary arterial hypertension: mPAP 47 mmHg, pulmonary artery occlusion pressure 5 mmHg, cardiac index 1.1 L/min/m2, pulmonary vascular resistance (PVR) 959 dyne.sec.cm(-5). Pulmonary function tests showed a marked diffusing capacity for carbon monoxide (DLCO) decrease of 32% predicted but no obstructive lung deficit. Before an open lung biopsy could be scheduled the patient developed acute cardiogenic shock. At autopsy pulmonary veno-occlusive disease with marked pulmonary hypertension was diagnosed. PMID:24380224

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

    PubMed Central

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

    2015-01-01

    Immune-complexes play an important role in the inflammatory diseases of the lung. Neutrophil activation mediates immune-complex (IC) deposition-induced acute lung injury (ALI). Components of gamma amino butyric acid (GABA) signaling, including GABA B receptor 2 (GABABR2), GAD65/67 and the GABA transporter, are present in the lungs and in the neutrophils. However, the role of pulmonary GABABR activation in the context of neutrophil-mediated ALI has not been determined. Thus, the objective of the current study was to determine whether administration of a GABABR agonist, baclofen would ameliorate or exacerbate ALI. We hypothesized that baclofen would regulate IC-induced ALI by preserving pulmonary GABABR expression. Rats were subjected to sham injury or IC-induced ALI and two hours later rats were treated intratracheally with saline or 1 mg/kg baclofen for 2 additional hours and sacrificed. ALI was assessed by vascular leakage, histology, TUNEL, and lung caspase-3 cleavage. ALI increased total protein, tumor necrosis factor α (TNF-α and interleukin-1 receptor associated protein (IL-1R AcP), in the bronchoalveolar lavage fluid (BALF). Moreover, ALI decreased lung GABABR2 expression, increased phospho-p38 MAPK, promoted IκB degradation and increased neutrophil influx in the lung. Administration of baclofen, after initiation of ALI, restored GABABR expression, which was inhibited in the presence of a GABABR antagonist, CGP52432. Baclofen administration activated pulmonary phospho-ERK and inhibited p38 MAPK phosphorylation and IκB degradation. Additionally, baclofen significantly inhibited pro-inflammatory TNF-α and IL-1βAcP release and promoted BAL neutrophil apoptosis. Protective effects of baclofen treatment on ALI were possibly mediated by inhibition of TNF-α- and IL-1β-mediated inflammatory signaling. Interestingly, GABABR2 expression was regulated in the type II pneumocytes in lung tissue sections from lung injured patients, further suggesting a physiological role for GABABR2 in the repair process of lung damage. GABABR2 agonists may play a potential therapeutic role in ALI. PMID:25848767

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

    PubMed Central

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

    2013-01-01

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

  1. Role of transcriptional factor Nrf2 in the acute lung injury of mice

    PubMed Central

    Kong, Minghao; Mao, Jing; Luo, Bijun; Qin, Zonghao

    2015-01-01

    Objective: This study aimed to investigate the expression and role of Nrf2 in the acute lung injury (ALI) of mice. Methods: A total of 60 BABL/c mice were randomly divided into 2 groups: ALI group and control group. In ALI group, ALI was introduced by injection of LPS. Immunohistochemistry was performed to detect Nrf2 expression in the lung; Western blot assay was employed to detect the expression of Nrf2 in the lung homogenate; ELISA was conducted to detect the expression of Nrf2 in the lung homogenate and BALF. Results: As compared to control group, ALI mice had a high Nrf2 expression in the lung as shown in immunohistochemistry, and the Nrf2 expression in the lung homogenate and BALF also increased markedly (P<0.05). Conclusion: The Nrf2 expression increases in the lung and BALF of ALI mice, suggesting that Nrf2 is involved in the inflammation during ALI and may serve as a new target in the therapy of ALI. PMID:26617809

  2. Activation of PPARα by Wy-14643 ameliorates systemic lipopolysaccharide-induced acute lung injury

    SciTech Connect

    Yoo, Seong Ho; Abdelmegeed, Mohamed A.; Song, Byoung-Joon

    2013-07-05

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

  3. Ventilator-Induced Lung Injury (VILI) in Acute Respiratory Distress Syndrome (ARDS): Volutrauma and Molecular Effects

    PubMed Central

    Carrasco Loza, R; Villamizar Rodríguez, G; Medel Fernández, N

    2015-01-01

    Acute Respiratory Distress Syndrome (ARDS) is a clinical condition secondary to a variety of insults leading to a severe acute respiratory failure and high mortality in critically ill patients. Patients with ARDS generally require mechanical ventilation, which is another important factor that may increase the ALI (acute lung injury) by a series of pathophysiological mechanisms, whose common element is the initial volutrauma in the alveolar units, and forming part of an entity known clinically as ventilator-induced lung injury (VILI). Injured lungs can be partially protected by optimal settings and ventilation modes, using low tidal volume (VT) values and high positive-end expiratory pressure (PEEP). The benefits in ARDS outcomes caused by these interventions have been confirmed by several prospective randomized controlled trials (RCTs) and are attributed to reduction in volutrauma. The purpose of this article is to present an approach to VILI pathophysiology focused on the effects of volutrauma that lead to lung injury and the ‘mechanotransduction’ mechanism. A more complete understanding about the molecular effects that physical forces could have, is essential for a better assessment of existing strategies as well as the development of new therapeutic strategies to reduce the damage resulting from VILI, and thereby contribute to reducing mortality in ARDS. PMID:26312103

  4. Towards the prevention of acute lung injury: a population based cohort study protocol

    PubMed Central

    2010-01-01

    Background Acute lung injury (ALI) is an example of a critical care syndrome with limited treatment options once the condition is fully established. Despite improved understanding of pathophysiology of ALI, the clinical impact has been limited to improvements in supportive treatment. On the other hand, little has been done on the prevention of ALI. Olmsted County, MN, geographically isolated from other urban areas offers the opportunity to study clinical pathogenesis of ALI in a search for potential prevention targets. Methods/Design In this population-based observational cohort study, the investigators identify patients at high risk of ALI using the prediction model applied within the first six hours of hospital admission. Using a validated system-wide electronic surveillance, Olmsted County patients at risk are followed until ALI, death or hospital discharge. Detailed in-hospital (second hit) exposures and meaningful short and long term outcomes (quality-adjusted survival) are compared between ALI cases and high risk controls matched by age, gender and probability of developing ALI. Time sensitive biospecimens are collected for collaborative research studies. Nested case control comparison of 500 patients who developed ALI with 500 matched controls will provide an adequate power to determine significant differences in common hospital exposures and outcomes between the two groups. Discussion This population-based observational cohort study will identify patients at high risk early in the course of disease, the burden of ALI in the community, and the potential targets for future prevention trials. PMID:20420711

  5. Bifunctional lipocalin ameliorates murine immune complex-induced acute lung injury.

    PubMed

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

    2013-06-28

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

  6. Transfusion of Human Platelets Treated with Mirasol Pathogen Reduction Technology Does Not Induce Acute Lung Injury in Mice.

    PubMed

    Caudrillier, Axelle; Mallavia, Beñat; Rouse, Lindsay; Marschner, Susanne; Looney, Mark R

    2015-01-01

    Pathogen reduction technology (PRT) has been developed in an effort to make the blood supply safer, but there is controversy as to whether it may induce structural or functional changes to platelets that could lead to acute lung injury after transfusion. In this study, we used a commercial PRT system to treat human platelets that were then transfused into immunodeficient mice, and the development of acute lung injury was determined. P-selectin expression was higher in the Mirasol PRT-treated platelets compared to control platelets on storage day 5, but not storage day 1. Transfusion of control vs. Mirasol PRT-treated platelets (day 5 of storage, 109 platelets per mouse) into NOD/SCID mice did not result in lung injury, however transfusion of storage day 5 platelets treated with thrombin receptor-activating peptide increased both extravascular lung water and lung vascular permeability. Transfusion of day 1 platelets did not produce lung injury in any group, and LPS priming 24 hours before transfusion had no effect on lung injury. In a model of transfusion-related acute lung injury, NOD/SCID mice were susceptible to acute lung injury when challenged with H-2Kd monoclonal antibody vs. isotype control antibody. Using lung intravital microscopy, we did not detect a difference in the dynamic retention of platelets in the lung circulation in control vs. Mirasol PRT-treated groups. In conclusion, Mirasol PRT produced an increase in P-selectin expression that is storage-dependent, but transfusion of human platelets treated with Mirasol PRT into immunodeficient mice did not result in greater platelet retention in the lungs or the development of acute lung injury. PMID:26176623

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

    PubMed

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

    2015-06-01

    Inhalation of coal mine dust results in a spectrum of symptoms, dysfunction, and pathological changes in the respiratory tract that collectively have been labeled coal mine dust lung disease. Recent reports from periodic health surveillance among underground and surface coal miners in the United States have demonstrated an increasing prevalence and severity of dust diseases, and have also documented that some miners experience rapid disease progression. The coal macule is an inflammatory lesion associated with deposited dust, and occurs in the region of the most distal conducting airways and proximal respiratory bronchioles. Inflammatory changes in the small airways have long been recognized as the signature lung pathology among coal miners. Human and laboratory studies have suggested oxidant injury, and increased recruitment and activity of macrophages play important roles in dust-induced lung injury. However, the functional importance of the small airway changes was debated for many years. We reviewed published literature that documents a pervasive occurrence of both physiologic and structural abnormalities in small airways among coal miners and other workers exposed to airborne particulates. There is increasing evidence supporting an important association of abnormalities in the small peripheral airways with the development of respiratory symptoms, deficits in spirometry values, and accelerated declines in ventilatory lung function. Pathologic changes associated with mineral dust deposition in the small airways may be of particular importance in contemporary miners with rapidly progressive respiratory impairment. PMID:26024344

  8. [Current approaches to the treatment of severe hypoxic respiratory insufficiency (acute lung injury; acute respiratory distress syndrome)].

    PubMed

    Kluge, S; Müller, T; Pfeifer, M

    2011-02-01

    Lung-protective ventilation with a low tidal volume, plateau pressure < 30 cm H(2)O. oxygen saturation > 90% and permissive hypercapnia results in reduction of the mortality rate in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). The level of the positive end-expiratory pressure (PEEP) must be chosen in relation to oxygen requirement. High frequency oscillatory ventilation and neurally adjusted ventilatory assist are promising methods. However, further studies with firm end-points have to be awaited before a final judgment is possible. Veno-venous extracorporeal membrane oxygenation (ECMO) can ensure life-sustaining gas exchange in patients with severe vitally compromised pulmonary failure, to provide time for lung tissue to heal and reduce ventilatory stress. The latest guidelines for analgesia and sedation in intensive care medicine demand consistent monitoring of the level of sedation and the intensity of pain. The sedation should be interrupted daily, with phases of awakenings and, if possible, spontaneous breathing. Methods of supportive treatment: Positional treatment (prone position) and inhalation of vasodilators can improve ventilation/perfusion mismatch and thus oxygenation. However, administration of surfactant is currently not advised in adult respiratory failure. PMID:21271478

  9. Melatonin reduces acute lung inflammation, edema, and hemorrhage in heatstroke rats

    PubMed Central

    Wu, Wen-shiann; Chou, Ming-ting; Chao, Chien-ming; Chang, Chen-kuei; Lin, Mao-tsun; Chang, Ching-ping

    2012-01-01

    Aim: To assess the therapeutic effect of melatonin on heat-induced acute lung inflammation and injury in rats. Methods: Heatstroke was induced by exposing anesthetized rats to heat stress (36 °C, 100 min). Rats were treated with vehicle or melatonin (0.2, 1, 5 mg/kg) by intravenous administration 100 min after the initiatioin of heatstroke and were allowed to recover at room temperature (26 °C). The acute lung injury was quantified by morphological examination and by determination of the volume of pleural exudates, the number of polymorphonuclear (PMN) cells, and the myeloperoxidase (MPO) activity. The concentrations of tumor necrosis factor, interleukin (IL)-1β, IL-6, and IL-10 in bronchoalveolar fluid (BALF) were measured by ELISA. Nitric oxide (NO) level was determined by Griess method. The levels of glutamate and lactate-to-pyruvate ratio were analyzed by CMA600 microdialysis analyzer. The concentrations of hydroxyl radicals were measured by a procedure based on the hydroxylation of sodium salicylates leading to the production of 2,3-dihydroxybenzoic acid (DHBA). Results: Melatonin (1 and 5 mg/kg) significantly (i) prolonged the survival time of heartstroke rats (117 and 186 min vs 59 min); (ii) attenuated heatstroke-induced hyperthermia and hypotension; (iii) attenuated acute lung injury, including edema, neutrophil infiltration, and hemorrhage scores; (iv) down-regulated exudate volume, BALF PMN cell number, and MPO activity; (v) decreased the BALF levels of lung inflammation response cytokines like TNF-alpha, interleukin (IL)-1β, and IL-6 but further increased the level of an anti-inflammatory cytokine IL-10; (vi) reduced BALF levels of glutamate, lactate-to-pyruvate ratio, NO, 2,3-DHBA, and lactate dehydrogenase. Conclusion: Melatonin may improve the outcome of heatstroke in rats by attenuating acute lung inflammation and injury. PMID:22609835

  10. Autophagy: a potential therapeutic target in lung diseases

    PubMed Central

    Nakahira, Kiichi

    2013-01-01

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

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    2004-08-01

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

  13. Activation of AMPK attenuates neutrophil proinflammatory activity and decreases the severity of acute lung injury.

    PubMed

    Zhao, Xia; Zmijewski, Jaroslaw W; Lorne, Emmanuel; Liu, Gang; Park, Young-Jun; Tsuruta, Yuko; Abraham, Edward

    2008-09-01

    AMP-activated protein kinase (AMPK) is activated by increases in the intracellular AMP-to-ATP ratio and plays a central role in cellular responses to metabolic stress. Although activation of AMPK has been shown to have anti-inflammatory effects, there is little information concerning the role that AMPK may play in modulating neutrophil function and neutrophil-dependent inflammatory events, such as acute lung injury. To examine these issues, we determined the effects of pharmacological activators of AMPK, 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) and barberine, on Toll-like receptor 4 (TLR4)-induced neutrophil activation. AICAR and barberine dose-dependently activated AMPK in murine bone marrow neutrophils. Exposure of LPS-stimulated neutrophils to AICAR or barberine inhibited release of TNF-alpha and IL-6, as well as degradation of IkappaBalpha and nuclear translocation of NF-kappaB, compared with findings in neutrophil cultures that contained LPS without AICAR or barberine. Administration of AICAR to mice resulted in activation of AMPK in the lungs and was associated with decreased severity of LPS-induced lung injury, as determined by diminished neutrophil accumulation in the lungs, reduced interstitial pulmonary edema, and diminished levels of TNF-alpha and IL-6 in bronchoalveolar lavage fluid. These results suggest that AMPK activation reduces TLR4-induced neutrophil activation and diminishes the severity of neutrophil-driven proinflammatory processes, including acute lung injury. PMID:18586954

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

    PubMed

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

    2014-06-01

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

  15. Inhaled hydrogen sulfide protects against lipopolysaccharide-induced acute lung injury in mice

    PubMed Central

    2012-01-01

    Background Local pulmonary and systemic infections can lead to acute lung injury (ALI). The resulting lung damage can evoke lung failure and multiple organ dysfunction associated with increased mortality. Hydrogen sulfide (H2S) appears to represent a new therapeutic approach to ALI. The gas has been shown to mediate potent anti-inflammatory and organ protective effects in vivo. This study was designed to define its potentially protective role in sepsis-induced lung injury. Methods C57BL/6 N mice received lipopolysaccharide (LPS) intranasally in the absence or presence of 80 parts per million H2S. After 6 h, acute lung injury was determined by comparative histology. Bronchoalveolar lavage (BAL) fluid was analyzed for total protein content and differential cell counting. BAL and serum were further analyzed for interleukin-1β, macrophage inflammatory protein-2, and/or myeloperoxidase glycoprotein levels by enzyme-linked immunosorbent assays. Differences between groups were analyzed by one way analysis of variance. Results Histological analysis revealed that LPS instillation led to increased alveolar wall thickening, cellular infiltration, and to an elevated ALI score. In the presence of H2S these changes were not observed despite LPS treatment. Moreover, neutrophil influx, and pro-inflammatory cytokine release were enhanced in BAL fluid of LPS-treated mice, but comparable to control levels in H2S treated mice. In addition, myeloperoxidase levels were increased in serum after LPS challenge and this was prevented by H2S inhalation. Conclusion Inhalation of hydrogen sulfide protects against LPS-induced acute lung injury by attenuating pro-inflammatory responses. PMID:23025523

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

    NASA Astrophysics Data System (ADS)

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

    2008-03-01

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

  17. Growth arrest-specific protein 6 attenuates neutrophil migration and acute lung injury in sepsis.

    PubMed

    Giangola, Matthew D; Yang, Weng-Lang; Rajayer, Salil R; Nicastro, Jeffrey; Coppa, Gene F; Wang, Ping

    2013-12-01

    Sepsis is an acute inflammatory condition that can result in multiple organ failure and acute lung injury. Growth arrest-specific protein 6 (Gas6) is a broad regulator of the innate immune response involved with the nuclear factor ?B signaling pathway. We hypothesized that Gas6 could have a protective role in attenuating the severity of acute lung injury and sepsis. Male mice were subjected to sepsis by cecal ligation and puncture (CLP) after which recombinant murine Gas6 (rmGas6; 5 ?g/mouse) or normal saline (vehicle) was administered intravenously. Blood and lung tissues were collected at 20 h after CLP for various measurements. Treatment with rmGas6 significantly reduced serum levels of the injury markers aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase, as well as proinflammatory cytokines interleukin 6 (IL-6) and IL-17, compared with the vehicle group (P < 0.05). The parenchyma of the lungs damaged by CLP was attenuated by rmGas6 treatment. Lung mRNA levels of tumor necrosis factor ?, IL-1?, IL-6, IL-17, and macrophage inflammatory protein 2 (MIP-2) were decreased by 60%, 86%, 82%, 93%, and 82%, respectively, with rmGas6 treatment as determined by real-time reverse transcriptase-polymerase chain reaction (P < 0.05). The degradation of I?B-? induced by CLP in the lungs was inhibited by rmGas6 treatment. The number of neutrophils and myeloperoxidase activity in the lungs were significantly reduced in the rmGas6 group. Moreover, rmGas6 reduced the in vitro migration of differentiated human promyelocytic HL60 cells by 64%. Finally, the 10-day survival rate of mice subjected to CLP was increased from 31% in the vehicle group to 67% in the rmGas6 group (P < 0.05). Thus, Gas6 has potential to be developed as a novel therapeutic agent to treat patients with sepsis and acute lung injury. PMID:23881260

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

    PubMed Central

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

    2014-01-01

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

  19. [Mechanical ventilation and fluid management in acute lung injury. Effects on gas exchange and hemodynamics].

    PubMed

    Bercker, S; Busch, T; Donaubauer, B; Schreiter, D; Kaisers, U

    2009-04-01

    Basic therapy of acute lung injury (ALI) covers a pressure-limited lung protective mechanical ventilation with low tidal volumes (6-8 ml/kg ideal body weight), adequate positive end-expiratory pressure (PEEP) combined with early recruitment maneuvers and a restrictive fluid management (in hypoproteinemic patients preferably with albumin and diuretics). These measures aim at providing sufficient oxygenation while simultaneously minimizing airway pressure, atelectasis and edema formation. The main hemodynamic effects are a decrease in cardiac output and in systemic arterial pressure potentially reducing organ perfusion. However, successful therapy reduces hypoxic pulmonary vasoconstriction and hypercapnia, thus lowering pulmonary artery pressure, unloading the right ventricle, and stabilising hemodynamics. PMID:19326053

  20. [Acute pancreatitis with hypertriglyceridemia--an underestimated disease?].

    PubMed

    Wild, Wolfgang; Tajjiou, Morad; Ferschke, Melanie; Bormann, Fabian; Dörr, Pius; Schwarzbach, Matthias

    2016-01-01

    Hypertriglyceridemia is a rare, but since a long time well known etiology for acute pancreatitis. It could occure alone or coactive with other triggers like alcohlic excess. Nevertheless it found no approach to the current classifications and parameters of prognosis of the acute pancreatitis. We refer about two patients with hypertriglyceridemia and acute pancreatitis, whose initial disease was limited on the tail of the pancreas with just a circumscripted or--in the other case--no necrosis. However, in both cases and although a consequent treatment started immediately, a serious process developed including a life-threatening acute respiratory distress syndrome in one case, which necessitated an extracorporal membrane oxygenation. PMID:26710203

  1. Acute Demyelinating Disease after Oral Therapy with Herbal Extracts

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

    Lippmann, M

    1990-01-01

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

  3. Cigarette Smoke Disrupted Lung Endothelial Barrier Integrity and Increased Susceptibility to Acute Lung Injury via Histone Deacetylase 6.

    PubMed

    Borgas, Diana; Chambers, Eboni; Newton, Julie; Ko, Junsuk; Rivera, Stephanie; Rounds, Sharon; Lu, Qing

    2016-05-01

    Epidemiologic evidence indicates that cigarette smoke (CS) is associated with the development of acute lung injury (ALI). We have previously shown that brief CS exposure exacerbates lipopolysaccharide (LPS)-induced ALI in vivo and endothelial barrier dysfunction in vitro. In this study, we found that CS also exacerbated Pseudomonas-induced ALI in mice. We demonstrated that lung microvascular endothelial cells (ECs) isolated from mice exposed to CS had a greater permeability or incomplete recovery after challenges by LPS and thrombin. Histone deacetylase (HDAC) 6 deacetylates proteins essential for maintenance of endothelial barrier function. We found that HDAC6 phosphorylation at serine-22 was increased in lung tissues of mice exposed to CS and in lung ECs exposed to cigarette smoke extract (CSE). Inhibition of HDAC6 attenuated CSE-induced increases in EC permeability and CS priming of ALI. Similar barrier protection was provided by the microtubule stabilizer taxol, which preserved α-tubulin acetylation. CSE decreased α-tubulin acetylation and caused microtubule depolymerization. In coordination with increased HDAC6 phosphorylation, CSE inhibited Akt and activated glycogen synthase kinase (GSK)-3β; these effects were ameliorated by the antioxidant N-acetyl cysteine. Our results suggest that CS increases lung EC permeability, thereby enhancing susceptibility to ALI, likely through oxidative stress-induced Akt inactivation and subsequent GSK-3β activation. Activated GSK-3β may activate HDAC6 via phosphorylation of serine-22, leading to α-tubulin deacetylation and microtubule disassembly. Inhibition of HDAC6 may be a novel therapeutic option for ALI in cigarette smokers. PMID:26452072

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

    PubMed Central

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

    2011-01-01

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

  5. Mycobacterial Lung Disease Complicating HIV Infection.

    PubMed

    Haas, Michelle K; Daley, Charles L

    2016-04-01

    Mycobacterial infections have caused enormous morbidity and mortality in people living with human immunodeficiency virus (HIV) infection. Of these, the most devastating has been tuberculosis (TB), the leading cause of death among HIV-positive persons globally. TB has killed more people living with HIV than any other infection. Diagnosis of latent TB infection (LTBI) is critical as treatment can prevent emergence of TB disease. Bacteriologic confirmation of TB disease should be sought whenever possible as well as drug susceptibility testing. When detected early, drug susceptible TB is curable. Similar to TB, nontuberculous mycobacteria (NTM) can also produce pulmonary and extrapulmonary infections including disseminated disease that can be fatal. Diagnosis through accurate identification of the pathogenic organism will greatly inform treatment. Depending on the NTM identified, treatment may not be curable. Ultimately, preventive strategies such as initiation of antiretroviral drugs and treatment of LTBI are interventions expected to have significant impacts on control of TB and NTM in the setting of HIV. This chapter will review the impact of pulmonary mycobacterial infections on HIV-positive individuals. PMID:26974300

  6. Segmentation of interstitial lung disease patterns in HRCT images

    NASA Astrophysics Data System (ADS)

    Dash, Jatindra K.; Madhavi, Vaddepalli; Mukhopadhyay, Sudipta; Khandelwal, Niranjan; Kumar, Prafulla

    2015-03-01

    Automated segmentation of pathological bearing region is the first step towards the development of lung CAD. Most of the work reported in the literature related to automated analysis of lung tissue aims towards classification of fixed sized block into one of the classes. This block level classification of lung tissues in the image never results in accurate or smooth boundaries between different regions. In this work, effort is taken to investigate the performance of three automated image segmentation algorithms those results in smooth boundaries among lung tissue patterns commonly encountered in HRCT images of the thorax. A public database that consists of HRCT images taken from patients affected with Interstitial Lung Diseases (ILDs) is used for the evaluation. The algorithms considered are Markov Random Field (MRF), Gaussian Mixture Model (GMM) and Mean Shift (MS). 2-fold cross validation approach is followed for the selection of the best parameter value for individual algorithm as well as to evaluate the performance of all the algorithms. Mean shift algorithm is observed as the best performer in terms of Jaccard Index, Modified Hausdorff Distance, accuracy, Dice Similarity Coefficient and execution speed.

  7. Lung transplantation for chronic obstructive pulmonary disease: special considerations.

    PubMed

    Diamond, Joshua; Kotloff, Robert M

    2010-04-01

    Since the introduction of lung transplantation nearly half a century ago, more procedures have been performed for chronic obstructive pulmonary disease (COPD) than for any other single indication. Because COPD tends to progress slowly and long-term survival is possible even in the advanced stages, the time at which transplantation should be offered remains unclear. Current recommendations rely on use of the BODE index to provide guidance on listing. Although both single lung transplantation (SLT) and bilateral lung transplantation (BLT) are suitable procedures for the COPD population, BLT has become the preferred procedure, particularly for patients under age 60, for whom it appears to offer superior survival and functional benefits. Whether lung transplantation truly extends survival for patients with COPD is uncertain. Preliminary answers have come from use of survivorship models that suggest a subset of COPD patients do derive a survival benefit, and that the size of this subgroup can be enhanced by selecting patients with extremely severe airflow obstruction and preferentially utilizing BLT. Those undergoing SLT are uniquely at risk for complications related to the remaining native lung-bronchogenic carcinoma and progressive hyperinflation-which are fortunately rare. PMID:20354925

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

    PubMed Central

    Vallyathan, V; Shi, X

    1997-01-01

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

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

    PubMed

    Vallyathan, V; Shi, X

    1997-02-01

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

  10. Crosstalk between ACE2 and PLGF regulates vascular permeability during acute lung injury

    PubMed Central

    Wang, Lantao; Li, Yong; Qin, Hao; Xing, Dong; Su, Jie; Hu, Zhenjie

    2016-01-01

    Angiotensin converting enzyme 2 (ACE2) treatment suppresses the severity of acute lung injury (ALI), through antagonizing hydrolyzing angiotensin II (AngII) and the ALI-induced apoptosis of pulmonary endothelial cells. Nevertheless, the effects of ACE2 on vessel permeability and its relationship with placental growth factor (PLGF) remain ill-defined. In the current study, we examined the relationship between ACE2 and PLGF in ALI model in mice. We used a previously published bleomycin method to induce ALI in mice, and treated the mice with ACE2. We analyzed the levels of PLGF in these mice. The mouse lung vessel permeability was determined by a fluorescence pharmacokinetic assay following i.v. injection of 62.5 µg/kg Visudyne. PLGF pump or soluble Flt-1 (sFlt-1) pump was given to augment or suppress PLGF effects, respectively. The long-term effects on lung function were determined by measurement of lung resistance using methacholine. We found that ACE2 treatment did not alter PLGF levels in lung, but antagonized the effects of PLGF on increases of lung vessel permeability. Ectogenic PLGF abolished the antagonizing effects of ACE2 on the vessel permeability against PLGF. On the other hand, suppression of PLGF signaling mimicked the effects of ACE2 on the vessel permeability against PLGF. The suppression of vessel permeability resulted in improvement of lung function after ALI. Thus, ACE2 may antagonize the PLGF-mediated increases in lung vessel permeability during ALI, resulting in improvement of lung function after ALI.

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

    PubMed Central

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

    2015-01-01

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

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

    SciTech Connect

    Lee, Ye-Ji; Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, Seoul ; Lee, Seung-Hae; Youn, Young-So; Choi, Ji-Yeon; Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, Seoul ; Song, Keung-Sub; Cho, Min-Sun; Kang, Jihee Lee

    2012-08-15

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

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

    PubMed

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

    1990-06-01

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

  14. Antimicrobial Peptides and Innate Lung Defenses: Role in Infectious and Noninfectious Lung Diseases and Therapeutic Applications.

    PubMed

    Hiemstra, Pieter S; Amatngalim, Gimano D; van der Does, Anne M; Taube, Christian

    2016-02-01

    Respiratory infections are a major clinical problem, and treatment is increasingly complicated by the emergence of microbial antibiotic resistance. Development of new antibiotics is notoriously costly and slow; therefore, alternative strategies are needed. Antimicrobial peptides, central effector molecules of the immune system, are being considered as alternatives to conventional antibiotics. These peptides display a range of activities, including not only direct antimicrobial activity, but also immunomodulation and wound repair. In the lung, airway epithelial cells and neutrophils in particular contribute to their synthesis. The relevance of antimicrobial peptides for host defense against infection has been demonstrated in animal models and is supported by observations in patient studies, showing altered expression and/or unfavorable circumstances for their action in a variety of lung diseases. Importantly, antimicrobial peptides are active against microorganisms that are resistant against conventional antibiotics, including multidrug-resistant bacteria. Several strategies have been proposed to use these peptides in the treatment of infections, including direct administration of antimicrobial peptides, enhancement of their local production, and creation of more favorable circumstances for their action. In this review, recent developments in antimicrobial peptides research in the lung and clinical applications for novel therapies of lung diseases are discussed. PMID:26502035

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

    PubMed Central

    Meyer, Keith C; Nathanson, Ian; Angel, Luis; Bhorade, Sangeeta M; Chan, Kevin M; Culver, Daniel; Harrod, Christopher G; Hayney, Mary S; Highland, Kristen B; Limper, Andrew H; Patrick, Herbert; Strange, Charlie; Whelan, Timothy

    2012-01-01

    Objectives: Immunosuppressive pharmacologic agents prescribed to patients with diffuse interstitial and inflammatory lung disease and lung transplant recipients are associated with potential risks for adverse reactions. Strategies for minimizing such risks include administering these drugs according to established, safe protocols; monitoring to detect manifestations of toxicity; and patient education. Hence, an evidence-based guideline for physicians can improve safety and optimize the likelihood of a successful outcome. To maximize the likelihood that these agents will be used safely, the American College of Chest Physicians established a committee to examine the clinical evidence for the administration and monitoring of immunosuppressive drugs (with the exception of corticosteroids) to identify associated toxicities associated with each drug and appropriate protocols for monitoring these agents. Methods: Committee members developed and refined a series of questions about toxicities of immunosuppressives and current approaches to administration and monitoring. A systematic review was carried out by the American College of Chest Physicians. Committee members were supplied with this information and created this evidence-based guideline. Conclusions: It is hoped that these guidelines will improve patient safety when immunosuppressive drugs are given to lung transplant recipients and to patients with diffuse interstitial lung disease. PMID:23131960

  16. Levels of interleukin-6, superoxide dismutase and malondialdehyde in the lung tissue of a rat model of hypoxia-induced acute pulmonary edema

    PubMed Central

    GAO, HENGBO; TIAN, YINGPING; WANG, WEI; YAO, DONGQI; ZHENG, TUOKANG; MENG, QINGBING

    2016-01-01

    The present study aimed to investigate the levels of malondialdehyde (MDA), superoxide dismutase (SOD) and interleukin (IL)-6 in the lung tissue of a rat model of acute pulmonary edema induced by acute hypoxia, and its pathophysiological significance. A total of 48 adult Wistar rats were randomly divided into group A, a normal group; group B, a model of acute pulmonary edema induced by hypoxia for 24 h; group C, a model of acute pulmonary edema induced by hypoxia for 48 h; and group D, a model of acute pulmonary edema induced by hypoxia for 72 h. The rats in groups B-D were intraperitoneally injected with 6% ammonium chloride to establish the model of acute pulmonary edema, and were subsequently sacrificed following successful modeling for 24, 48 and 72 h. The plasma of rats was isolated and the lungs of the rats were removed. Subsequently, a 10% lung homogenate was prepared and the contents and the activities of MDA, SOD and IL-6 in the lung tissue and IL-6 in the plasma were detected by enzyme-linked immunosorbent assay. MDA and IL-6 expression levels increased and SOD activity decreased in the lung tissue in group B as compared with group A; however the difference did not reach significance (P>0.05). MDA, IL-6 and SOD levels in the lung tissue of rats were significantly altered following the increased duration of pulmonary edema in groups C and D, as compared group A (P<0.05). The plasma IL-6 levels of the rats in groups B-D significantly increased, as compared with those in group A (P<0.05). In conclusion, the results of the present study demonstrated that the incidence of acute pulmonary edema may be associated with oxidative stress. Furthermore, decreased antioxidant capacity and increased free radical levels may be associated with pulmonary edema, as in the present study the levels of IL-6, SOD and MDA in the lung tissue were observed to be associated with the pathological changes of the disease. PMID:26998026

  17. Organoids as a model system for studying human lung development and disease.

    PubMed

    Nadkarni, Rohan R; Abed, Soumeya; Draper, Jonathan S

    2016-05-01

    The lung is a complex organ comprising multiple cell types that perform a variety of vital processes, including immune defense and gas exchange. Diseases of the lung, such as chronic obstructive pulmonary disease, asthma and lung cancer, together represent one of the largest causes of patient suffering and mortality. Logistical barriers that hamper access to embryonic, normal adult or diseased lung tissue currently hinder the study of lung disease. In vitro lung modeling represents an attractive and accessible avenue for investigating lung development, function and disease pathology, but accurately modeling the lung in vitro requires a system that recapitulates the structural features of the native lung. Organoids are stem cell-derived three-dimensional structures that are supported by an extracellular matrix and contain multiple cell types whose spatial arrangement and interactions mimic those of the native organ. Recently, organoids representative of the respiratory system have been generated from adult lung stem cells and human pluripotent stem cells. Ongoing studies are showing that organoids may be used to model human lung development, and can serve as a platform for interrogating the function of lung-related genes and signalling pathways. In a therapeutic context, organoids may be used for modeling lung diseases, and as a platform for screening for drugs that alleviate respiratory disease. Here, we summarize the organoid-forming capacity of respiratory cells, current lung organoid technologies and their potential use in future therapeutic applications. PMID:26721435

  18. Standardized Combination Antibiotic Treatment of Mycobacterium avium Complex Lung Disease

    PubMed Central

    Sim, Yun Su; Park, Hye Yun; Jeon, Kyeongman; Suh, Gee Young; Kwon, O Jung

    2010-01-01

    Purpose The optimal treatment regimen for Mycobacterium avium complex (MAC) lung disease has not yet been fully established. We evaluated the efficacy of standardized combination antibiotic therapy and the factors that might affect unfavorable microbiologic responses in patients with MAC pulmonary disease. Materials and Methods This retrospective study reviewed data from 96 patients (56 females; median age 59 years) treated with newly diagnosed MAC lung disease between January 2003 and December 2006. Results All patients received standardized combination antibiotic therapy, consisting of clarithromycin, rifampicin, and ethambutol. Streptomycin was additionally given in 72 patients (75%) for a median duration of 4.5 months. The overall favorable microbiologic response rate was 79% (76/96); 20 patients (21%) had unfavorable microbiologic responses, including failure to sputum conversion (n = 13), relapse (n = 3), and MAC-related death (n = 4). A positive sputum acid-fast bacillus smear at the start of treatment was an independent predictor of an unfavorable microbiologic response. Conclusion Standardized combination antibiotic therapy consisting of clarithromycin, rifampicin, and ethambutol with or without initial use of streptomycin is effective in treating patients with newly diagnosed MAC lung disease. PMID:20879056

  19. [Chronic nonspecific lung diseases in the Estonian SSR (author's transl)].

    PubMed

    Kama, E K

    1977-02-01

    Report on chronic nonspecific lung diseases (CNLD) in the Estonian SSR basing on the data of the ministry of health. The statistical incidence of chronic nonspecific lung diseases has increased from 59.7 new cases per 10 000 inhabitants (1967) to 93.7 in 1974 (100.2 in males and 88.1 in females). This increase is resulting from a real increase of new cases but also from the improvement of diagnostics and better coverage in the degree as tuberculosis has diminished. Cases of tuberculosis among adults decreased to 1/8 and among children to 1/100 of that 20 years ago. Among CNLD the portion of chronic bronchitis amounted to 48%, of chronic bronchitis to 35.9% and bronchial asthma to 16.1%. CNLD is rather frequent among children. In persons older than 40 years CNLD becomes more common, more in males than in females. Not all persons notified with the diagnosis chronic lung disease need treatment. In epidemiological surveys 5.5 to 9.3% of the population corresponded to the definition of chronic airway disease. A systematic dispensary care of CNLD is going to be organised since 1969. It is the task of all therapeutists in the medical districts. More and more the tuberculosis clinics are integrated into this system. PMID:899047

  20. Update in Diffuse Parenchymal Lung Disease 2013

    PubMed Central

    Kaminski, Naftali

    2015-01-01

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

  1. Acquired Cell-Mediated Immunodepression in Acute Chagas' Disease

    PubMed Central

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

    1978-01-01

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

  2. Immunohistochemical demonstration of influenza A nucleoprotein in lungs of turkeys with natural and experimental influenza respiratory disease.

    PubMed

    Swayne, D E; Ficken, M D; Guy, J S

    1992-12-01

    Influenza A virus (H1N1) and several bacteria were recovered from lungs of turkey breeder hens during a respiratory disease outbreak. Influenza A nucleoprotein was detected in the pneumonic lung tissue within macrophages and, rarely, in atrial-lining epithelium. Inconsistent recovery of pathogenic bacteria suggested that death in some turkeys resulted from acute primary viral pneumonia. In an experimental study, the gross and histologic lesions confirmed the respiratory pathogenicity of the influenza virus. The presence of intranuclear and intracytoplasmic influenza A nucleoprotein within macrophages and atrial lining epithelium of the lung, respiratory epithelium of the trachea and hypertrophied epithelial cells of the airsacs verified influenza virus replication in the respiratory system. However, the absence of mortality may suggest that secondary factors, such as bacteria, may modify the disease in natural outbreaks. PMID:18670973

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

    PubMed Central

    Rao, Roshni; Nagarkatti, Prakash

    2014-01-01

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

  4. Detection of acute inhalation injury in fire victims by means of technetium-99m DTPA radioaerosol inhalation lung scintigraphy.

    PubMed

    Lin, W Y; Kao, C H; Wang, S J

    1997-02-01

    Mortality and morbidity in fire victims are largely a function of injury due to heat and smoke. While the degree and area of burn together constitute a reliable numerical measure of cutaneous injury due to heat, as yet no satisfactory measure of inhalation injury has been developed. In this study, we employed technetium-99m diethylene triamine penta-acetic acid (DTPA) radioaerosol lung scintigraphy (inhalation scan) to evaluate acute inhalation injury in fire victims. Ten normal controls and 17 survivors from a fire accident were enrolled in the study. All patients suffered from respiratory symptoms (dyspnoea and/or cough with sputum). 99mTc-DTPA aerosol inhalation lung scintigraphy was performed in all subjects, using a commercial lung aerosol delivery unit. The degree of lung damage was presented as the clearance rate (k; %/min) calculated from the time-activity curve over the right lungs. In addition, the distribution pattern of the radioactivity in the lungs was evaluated and classified into two groups: homogeneous distribution and inhomogeneous distribution. A plain chest radiograph (CxR) and pulmonary function test (PFT) were performed in the same group of patients. The results showed that 6/17 (35.3%) patients had inhomogeneous distribution of radioactivity in their inhalation scans, and 11/17 (64.7%) had homogeneous scans. Five of the six patients with inhomogeneous scans were admitted for further management, and all patients with homogeneous scans were discharged from the emergency department and needed no further intensive care. The clearance rates of the right lung were 0.73%+/-0.13%/min for normal controls and 1.54%+/-0.58%/min for fire victims. The difference was significant, with a P value of less than 0.01. Using a cut-off value of 0.9%/min (all normal subjects were below 0. 9%/min), 14 (82.4%) patients had abnormal clearance rates of 99mTc-DTPA from the lung. In contrast, only three (17.6%) patients had abnormal CxR and three (17.6%) had abnormal PFTs. We conclude that (1) conventional CxR and PFT are not good modalities for evaluating inhalation injury in fire victims because of their low sensitivity, and (2) 99mTc-DTPA radioaerosol inhalation scintigraphy can provide an objective evaluation of inhalation injury during a fire accident and may be useful in therapeutic decision-making and disease monitoring. PMID:9021108

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

    PubMed Central

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

    2015-01-01

    The effect of betanin on a rat paraquat-induced acute lung injury (ALI) model was investigated. Paraquat was injected intraperitoneally at a single dose of 20 mg/kg body weight, and betanin (25 and 100 mg/kg/d) was orally administered 3 days before and 2 days after paraquat administration. Rats were sacrificed 24 hours after the last betanin dosage, and lung tissue and bronchoalveolar lavage fluid (BALF) were collected. In rats treated only with paraquat, extensive lung injury characteristic of ALI was observed, including histological changes, elevation of lung : body weight ratio, increased lung permeability, increased lung neutrophilia infiltration, increased malondialdehyde (MDA) and myeloperoxidase (MPO) activity, reduced superoxide dismutase (SOD) activity, reduced claudin-4 and zonula occluden-1 protein levels, increased BALF interleukin (IL-1) and tumor necrosis factor (TNF)-α levels, reduced BALF IL-10 levels, and increased lung nuclear factor kappa (NF-κB) activity. In rats treated with betanin, paraquat-induced ALI was attenuated in a dose-dependent manner. In conclusion, our results indicate that betanin attenuates paraquat-induced ALI possibly via antioxidant and anti-inflammatory mechanisms. Thus, the potential for using betanin as an auxilliary therapy for ALI should be explored further. PMID:25861636

  6. HIF2α signaling inhibits adherens junctional disruption in acute lung injury

    PubMed Central

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

    2015-01-01

    Vascular endothelial barrier dysfunction underlies diseases such as acute respiratory distress syndrome (ARDS), characterized by edema and inflammatory cell infiltration. The transcription factor HIF2α is highly expressed in vascular endothelial cells (ECs) and may regulate endothelial barrier function. Here, we analyzed promoter sequences of genes encoding proteins that regulate adherens junction (AJ) integrity and determined that vascular endothelial protein tyrosine phosphatase (VE-PTP) is a HIF2α target. HIF2α-induced VE-PTP expression enhanced dephosphorylation of VE-cadherin, which reduced VE-cadherin endocytosis and thereby augmented AJ integrity and endothelial barrier function. Mice harboring an EC-specific deletion of Hif2a exhibited decreased VE-PTP expression and increased VE-cadherin phosphorylation, resulting in defective AJs. Mice lacking HIF2α in ECs had increased lung vascular permeability and water content, both of which were further exacerbated by endotoxin-mediated injury. Treatment of these mice with Fg4497, a prolyl hydroxylase domain 2 (PHD2) inhibitor, activated HIF2α-mediated transcription in a hypoxia-independent manner. HIF2α activation increased VE-PTP expression, decreased VE-cadherin phosphorylation, promoted AJ integrity, and prevented the loss of endothelial barrier function. These findings demonstrate that HIF2α enhances endothelial barrier integrity, in part through VE-PTP expression and the resultant VE-cadherin dephosphorylation-mediated assembly of AJs. Moreover, activation of HIF2α/VE-PTP signaling via PHD2 inhibition has the potential to prevent the formation of leaky vessels and edema in inflammatory diseases such as ARDS. PMID:25574837

  7. Mesenchymal stem cells in acute lung injury: are they ready for translational medicine?

    PubMed Central

    Xu, Feng; Hu, Yue; Zhou, Jiebai; Wang, Xiangdong

    2013-01-01

    Acute lung injury (ALI) is a severe clinical condition responsible for high mortality and the development of multiple organ dysfunctions, because of the lack of specific and effective therapies for ALI. Increasing evidence from pre-clinical studies supports preventive and therapeutic effects of mesenchymal stem cells (MSCs, also called mesenchymal stromal cells) in ALI/ARDS (acute respiratory distress syndrome). Therapeutic effects of MSCs were noticed in various delivery approaches (systemic, local, or other locations), multiple origins (bone marrow or other tissues), or different schedules of administrations (before or after the challenges). MSCs could reduce the over-production of inflammatory mediators, leucocyte infiltration, tissue injury and pulmonary failure, and produce a number of benefit factors through interaction with other cells in the process of lung tissue repair. Thus, it is necessary to establish guidelines, standard operating procedures and evaluation criteria for translating MSC-based therapies into clinical application for patients with ALI. PMID:23834470

  8. Acute lung injury after platelet transfusion in a patient with dengue fever.

    PubMed

    Karoli, Ritu; Bhat, Sanjay; Fatima, Jalees; Verma, Pankaj

    2014-07-01

    Transfusion-related acute lung injury (TRALI) is a serious clinical syndrome associated with the transfusion of plasmacontaining blood components. Recently, TRALI has come to be recognized as the leading cause of transfusion-related mortality. This complication typically presents as shortness of breath, hypoxemia, hypotension, fever, and non cardiogenic pulmonary edema, occurring within 6 h after transfusion. Although the mechanism of TRALI has not been exactly known, it has been associated with human leukocyte antigen antibodies and with biologically active mediators in stored cellular blood components. We, hereby, present a case of a patient with dengue fever who developed acute lung injury (ALI), presumably TRALI, after transfusion of platelet concentrates. He was treated with supportive measures and mechanical ventilation. Greater knowledge and increased awareness especially amongst the clinicians regarding TRALI is needed for prevention and treatment of this potentially severe complication of blood/component transfusion. PMID:25161356

  9. Acute Kidney Disease After Liver and Heart Transplantation.

    PubMed

    Rossi, Ana P; Vella, John P

    2016-03-01

    After transplantation of nonrenal solid organs, an acute decline in kidney function develops in the majority of patients. In addition, a significant number of nonrenal solid organ transplant recipients develop chronic kidney disease, and some develop end-stage renal disease, requiring renal replacement therapy. The incidence varies depending on the transplanted organ. Acute kidney injury after nonrenal solid organ transplantation is associated with prolonged length of stay, cost, increased risk of death, de novo chronic kidney disease, and end-stage renal disease. This overview focuses on the risk factors for posttransplant acute kidney injury after liver and heart transplantation, integrating discussion of proteinuria and chronic kidney disease with emphasis on pathogenesis, histopathology, and management including the use of mechanistic target of rapamycin inhibition and costimulatory blockade. PMID:26502368

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

    SciTech Connect

    Wang, Chaoyun; Huang, Qingxian; Wang, Chunhua; Zhu, Xiaoxi; Duan, Yunfeng; Yuan, Shuai; Bai, Xianyong

    2013-11-01

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

  11. Endothelial dysfunction and lung capillary injury in cardiovascular diseases.

    PubMed

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

    2015-01-01

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

  12. Genetic Susceptibility to Interstitial Lung Disease Associated with Systemic Sclerosis

    PubMed Central

    Tochimoto, Akiko; Kawaguchi, Yasushi; Yamanaka, Hisashi

    2015-01-01

    Systemic sclerosis (SSc) is a connective tissue disease that is characterized by tissue fibrosis, microvasculopathy, and autoimmunity. Interstitial lung disease (ILD) is a common complication of SSc and is one of the frequent causes of mortality in SSc. Although the exact etiology of SSc remains unknown, clinical and experimental investigations have suggested that genetic and environmental factors are relevant to the pathogenesis of SSc and SSc-ILD. More than 30 genes have been identified as susceptibility loci for SSc, most of which are involved in immune regulation and inflammation. It is thought that the key pathogenesis of SSc-ILD is caused by the release of profibrotic mediators such as transforming growth factor β1 and connective tissue growth factor from lung cells induced by a persistent damage. This review presents the genetic susceptibility to SSc-ILD, including human leukocyte antigen and non-human leukocyte antigen genes, especially focusing on connective tissue growth factor. PMID:26997879

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

    PubMed Central

    Foong, Rachel E.; Zosky, Graeme R.

    2013-01-01

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

  14. Apoptosis is a major pathway responsible for the resolution of type II pneumocytes in acute lung injury.

    PubMed Central

    Bardales, R. H.; Xie, S. S.; Schaefer, R. F.; Hsu, S. M.

    1996-01-01

    Proliferation of type II pneumocytes has been linked to a repair process during the early phase of acute lung injury, and it persists for a variable period. The mechanisms responsible for their dissolution and/or disappearance are not known, but we speculate that it may be partly due to apoptosis. Sections of lung tissue from patients with acute lung injury (n = 7) and chronic interstitial pneumonia (n = 14) were stained for detection of apoptotic cells via specific labeling of nuclear DNA fragmentation. Results were correlated with those of proliferating cell nuclear antigen (PCNA) staining for cell proliferation. Marked apoptosis of CD68-negative type II pneumocytes (30 to 80%) was detected in four of the seven (57%) cases of acute lung injury. In these cases, representing the resolution phase of acute lung injury, PCNA positivity in pneumocytes was extremely rare. In the 3 other cases in the acute/proliferative phase, apoptotic type II pneumocytes were rare whereas PCNA expression was quite evident in these cells. In chronic interstitial pneumonia, only rare type II pneumocytes (< 5%) exhibited apoptosis, and they showed variable staining for PCNA (up to 70%). We conclude that proliferation of type II pneumocytes occurs during the early phase of acute lung injury and is of variable extent and duration. In the resolution phase of acute lung injury, extensive apoptosis of type II pneumocytes is largely responsible for the disappearance of these cells. The time frame within which the apoptotic response occurs is variable and is likely to be dependent upon the specific etiology and extent of the injury. In chronic interstitial pneumonia, type II pneumocytes proliferate continuously, although to a much lesser degree than in the early phase of acute lung injury, and are minimally apoptotic. Images Figure 1 PMID:8780388

  15. Rapid acute onset of bronchiolitis obliterans syndrome in a lung transplant recipient after respiratory syncytial virus infection.

    PubMed

    Hayes, D; Mansour, H M; Kirkby, S; Phillips, A B

    2012-10-01

    Bronchiolitis obliterans syndrome (BOS) can have either an acute or chronic onset with an abrupt or insidious course. The diagnosis is typically achieved by physiological criteria with development of a sustained decline in expiratory flow rates for at least 3weeks. We review the rapid development of acute BOS and bronchiectasis after respiratory syncytial virus infection in a lung transplant recipient, who had been doing well with normal pulmonary function for 3years after lung transplantation. PMID:22650803

  16. Applications of hyperpolarized helium-3 gas magnetic resonance imaging in pediatric lung disease.

    PubMed

    Altes, Talissa A; de Lange, Eduard E

    2003-06-01

    Hyperpolarized gas magnetic resonance imaging (MRI) of the lung provides high temporal and spatial resolution images of the air spaces of the lung and can be used to elucidate both lung ventilation and morphology. Because no ionizing radiation is involved, hyperpolarized gas MRI is ideal for the evaluation of pediatric lung diseases. In the article, we describe briefly the basic principles of hyperpolarized gas MRI, review the literature of hyperpolarized gas MRI in two pediatric lung diseases (asthma and cystic fibrosis), and discuss possible future clinical applications of hyperpolarized gas imaging in pediatric lung disease. PMID:12973130

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

    PubMed Central

    Rom, William N.; Weiden, Michael D.

    2014-01-01

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

  18. Pulmonary rehabilitation improves sleep quality in chronic lung disease.

    PubMed

    Soler, Xavier; Diaz-Piedra, Carolina; Ries, Andrew L

    2013-04-01

    Sleep-related disorders are common in patients with chronic obstructive pulmonary disease (COPD) and, possibily, other lung disorders. Exercise has been shown to improve sleep disturbances. In patients with COPD, pulmonary rehabilitation (PR) produces important health benefits with improvement in symptoms, exercise tolerance, and quality of life. However, the effect of PR on sleep quality remains unknown. The aim of this observational study was to evaluate sleep quality in patients with chronic lung disease and the role of PR as a non-pharmacologic treatment to improve sleep. Sixty-four patients with chronic lung disease enrolled in an 8-week comprehensive PR program, and completed the study (48% male; obstructive [72%], restrictive [20%], mixed [8%]; 44% on supplemental oxygen). Baseline spirometry [mean (SD)]: FEV1% pred = 48.9 (17.4), FVC% pred = 72.5 (18.1), and FEV1/FVC% = 53.1 (18.9). Exercise tolerance and questionnaires related to symptoms, health-related quality of life (HRQL), and sleep quality using the Pittsburgh Sleep Quality Index (PSQI) were obtained before and after PR. 58% reported poor sleep quality (PSQI > 5) at baseline. Sleep quality improved by 19% (p = 0.017) after PR, along with significant improvements in dyspnea, exercise tolerance, self-efficacy, and HRQL. Sleep quality in patients with chronic lung disease was poor. In addition to expected improvements in symptoms, exercise tolerance, and HRQL after PR, the subgroup of patients with COPD had a significant improvement in sleep quality. These findings suggest that PR may be an effective, non-pharmacologic treatment option for sleep problems in patients with COPD. PMID:23514215

  19. [Intersticial lung disease as the sole manifestation of antisynthetase syndrome].

    PubMed

    Monteiro, Paulo; Coutinho, Margarida; Machado, Pedro; Garcia, Jorge; Salvador, Maria João; Inês, Luís; Silva, Jorge; Malcata, Armando

    2009-01-01

    The authors report a clinical case of a woman who had a 3 years diagnosis of hipersensitivity pneumonitis based on intersticial lung disease without other manifestations. The diagnosis of antisynthetase syndrome was made three years after the initial symptoms upon the onset of systemic manifestations with articular involvement, myositis and determination of anti-PL 7 antibodies. In this syndrome, the isolated pulmonary involvement is rare. PMID:19474779

  20. Childhood Interstitial Lung Diseases: An 18-year Retrospective Analysis

    PubMed Central

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

    2013-01-01

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

  1. Transfusion-related acute lung injury: transfusion, platelets and biological response modifiers.

    PubMed

    Tariket, Sofiane; Sut, Caroline; Hamzeh-Cognasse, Hind; Laradi, Sandrine; Pozzetto, Bruno; Garraud, Olivier; Cognasse, Fabrice

    2016-05-01

    Transfusion-related acute lung injury (TRALI) may be induced by plasma, platelet concentrates and red blood cell concentrates. The mechanism leading to TRALI is thought to involve two steps. The priming step consists of previous inflammatory pathological conditions or external factors attracting leukocytes to lung vessels and creating conditions favorable for the second step, in which anti-HLA or anti-HNA antibodies or biologically active lipids, usually in transfused blood products, stress leukocytes and inflame lung epithelia. Platelets may be involved in the pathogenesis of TRALI because of their secretory potential and capacity to interact with other immune cells. There is no drug based-prophylaxis, but transfusion strategies are used to mitigate the risk of TRALI. PMID:26855042

  2. Effects of GW274150, a novel and selective inhibitor of iNOS activity, in acute lung inflammation

    PubMed Central

    Dugo, Laura; Marzocco, Stefania; Mazzon, Emanuela; Paola, Rosanna Di; Genovese, Tiziana; Caputi, Achille P; Cuzzocrea, Salvatore

    2004-01-01

    The aim of this study was to investigate the effect of GW274150, a novel, potent and selective inhibitor of inducible nitric oxide synthase (iNOS) activity in a model of lung injury induced by carrageenan administration in the rats. Injection of carrageenan into the pleural cavity of rats elicited an acute inflammatory response characterized by: fluid accumulation in the pleural cavity which contained a large number of polymorphonuclear cells (PMNs) as well as an infiltration of PMNs in lung tissues and subsequent lipid peroxidation, and increased production of nitrite/nitrate (NOx), tumour necrosis factor α (TNF-α) and interleukin-1β (IL-1β). All parameters of inflammation were attenuated in a dose-dependent manner by GW274150 (2.5, 5 and 10 mg kg−1 injected i.p. 5 min before carrageenan). Carrageenan induced an upregulation of the intracellular adhesion molecules-1 (ICAM-1), as well as nitrotyrosine and poly (ADP-ribose) (PAR) as determined by immunohistochemical analysis of lung tissues. The degree of staining for the ICAM-1, nitrotyrosine and PAR was reduced by GW274150. These results clearly confirm that NO from iNOS plays a role in the development of the inflammatory response by altering key components of the inflammatory cascade. GW274150 may offer a novel therapeutic approach for the management of various inflammatory diseases where NO and related radicals have been postulated to play a role. PMID:14769784

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

    PubMed

    Shen, Yongbin; Sun, Zhanfeng; Guo, Xiaotong

    2015-01-15

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

  4. Right ventricular failure in acute lung injury and acute respiratory distress syndrome.

    PubMed

    Repessé, X; Charron, C; Vieillard-Baron, A

    2012-08-01

    Acute respiratory distress syndrome (ARDS) is a clinical entity involving not only alveolar lesions but also capillary lesions, both of which have deleterious effects on the pulmonary circulation, leading to constant pulmonary hypertension and to acute cor pulmonale (ACP) in 20-25% of patients ventilated with a limited plateau pressure (Pplat). Considering the poor prognosis of patients suffering from such acute right ventricular (RV) dysfunction, RV protection by appropriate ventilatory settings has become a crucial issue in ARDS management. The goal of this review is to emphasize the importance of analyzing RV function in ARDS, using echocardiography, in order to limit RV afterload. Any observed acute RV dysfunction should lead physicians to consider a strategy for RV protection, including strict limitation of Pplat, diminution of positive end-expiratory pressure (PEEP) and control of hypercapnia, all goals achieved by prone positioning. PMID:22672932

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

    PubMed Central

    Entezari, Maria; Javdan, Mohammad; Antoine, Daniel J.; Morrow, Dympna M.P.; Sitapara, Ravikumar A.; Patel, Vivek; Wang, Mao; Sharma, Lokesh; Gorasiya, Samir; Zur, Michelle; Wu, Wenjun; Li, JianHua; Yang, Huan; Ashby, Charles R.; Thomas, Douglas; Wang, Haichao; Mantell, Lin L.

    2014-01-01

    Prolonged exposure to hyperoxia results in acute lung injury (ALI), accompanied by a significant elevation in the levels of proinflammatory cytokines and leukocyte infiltration in the lungs. However, the mechanisms underlying hyperoxia-induced proinflammatory ALI remain to be elucidated. In this study, we investigated the role of the proinflammatory cytokine high mobility group box protein 1 (HMGB1) in hyperoxic inflammatory lung injury, using an adult mouse model. The exposure of C57BL/6 mice to ≥99% O2 (hyperoxia) significantly increased the accumulation of HMGB1 in the bronchoalveolar lavage fluids (BALF) prior to the onset of severe inflammatory lung injury. In the airways of hyperoxic mice, HMGB1 was hyperacetylated and existed in various redox forms. Intratracheal administration of recombinant HMGB1 (rHMGB1) caused a significant increase in leukocyte infiltration into the lungs compared to animal treated with a non-specific peptide. Neutralizing anti-HMGB1 antibodies, administrated before hyperoxia significantly attenuated pulmonary edema and inflammatory responses, as indicated by decreased total protein content, wet/dry weight ratio, and numbers of leukocytes in the airways. This protection was also observed when HMGB1 inhibitors were administered after the onset of the hyperoxic exposure. The aliphatic antioxidant, ethyl pyruvate (EP), inhibited HMGB1 secretion from hyperoxic macrophages and attenuated hyperoxic lung injury. Overall, our data suggest that HMGB1 plays a critical role in mediating hyperoxic ALI through the recruitment of leukocytes into the lungs. If these results can be translated to humans, they suggest that HMGB1 inhibitors provide treatment regimens for oxidative inflammatory lung injury in patients receiving hyperoxia through mechanical ventilation. PMID:24563849

  6. T cell immunohistochemistry refines lung transplant acute rejection diagnosis and grading

    PubMed Central

    2013-01-01

    Objective Lung transplant volume has been increasing. However, inaccurate and uncertain diagnosis for lung transplant rejection hurdles long-term outcome due to, in part, interobserver variability in rejection grading. Therefore, a more reliable method to facilitate diagnosing and grading rejection is warranted. Method Rat lung grafts were harvested on day 3, 7, 14 and 28 post transplant for histological and immunohistochemical assessment. No immunosuppressive treatment was administered. We explored the value of interstitial T lymphocytes quantification by immunohistochemistry and compared the role of T cell immunohistochemistry with H&E staining in diagnosing and grading lung transplant rejection. Results Typical acute rejection from grade A1 to A4 was found. Rejection severity was heterogeneously distributed in one-third transplanted lungs (14/40): lesions in apex and center were more augmented than in the base and periphery of the grafts, respectively. Immunohistochemistry showed profound difference in T lymphocyte infiltration among grade A1 to A4 rejections. The coincidence rate of H&E and immunohistochemistry was 77.5%. The amount of interstitial T lymphocyte infiltration increased gradually with the upgrading of rejection. The statistical analysis demonstrated that the difference in the amount of interstitial T lymphocytes between grade A2 and A3 was not obvious. However, T lymphocytes in lung tissue of grade A4 were significantly more abundant than in other grades. Conclusions Rejection severity was heterogeneously distributed within lung grafts. Immunohistochemistry improves the sensitivity and specificity of rejection diagnosis, and interstitial T lymphocyte quantitation has potential value in diagnosing and monitoring lung allograft rejection. Virtual slides The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1536075282108217. PMID:24330571

  7. Pulmonary Hypertension and Right Heart Dysfunction in Chronic Lung Disease

    PubMed Central

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

    2014-01-01

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

  8. Deletion of ASK1 Protects against Hyperoxia-Induced Acute Lung Injury.

    PubMed

    Fukumoto, Jutaro; Cox, Ruan; Fukumoto, Itsuko; Cho, Young; Parthasarathy, Prasanna Tamarapu; Galam, Lakshmi; Lockey, Richard F; Kolliputi, Narasaiah

    2016-01-01

    Apoptosis signal-regulating kinase 1 (ASK1), a member of the MAPK kinase kinase kinase (MAP3K) family, is activated by various stimuli, which include oxidative stress, endoplasmic reticulum (ER) stress, calcium influx, DNA damage-inducing agents and receptor-mediated signaling through tumor necrosis factor receptor (TNFR). Inspiration of a high concentration of oxygen is a palliative therapy which counteracts hypoxemia caused by acute lung injury (ALI)-induced pulmonary edema. However, animal experiments so far have shown that hyperoxia itself could exacerbate ALI through reactive oxygen species (ROS). Our previous data indicates that ASK1 plays a pivotal role in hyperoxia-induced acute lung injury (HALI). However, it is unclear whether or not deletion of ASK1 in vivo protects against HALI. In this study, we investigated whether ASK1 deletion would lead to attenuation of HALI. Our results show that ASK1 deletion in vivo significantly suppresses hyperoxia-induced elevation of inflammatory cytokines (i.e. IL-1? and TNF-?), cell apoptosis in the lung, and recruitment of immune cells. In summary, the results from the study suggest that deletion of ASK1 in mice significantly inhibits hyperoxic lung injury. PMID:26807721

  9. Kallistatin protects against sepsis-related acute lung injury via inhibiting inflammation and apoptosis

    PubMed Central

    Lin, Wei-Chieh; Chen, Chang-Wen; Huang, Yu-Wen; Chao, Lee; Chao, Julie; Lin, Yee-Shin; Lin, Chiou-Feng

    2015-01-01

    Kallistatin, an endogenous plasma protein, exhibits pleiotropic properties in inhibiting inflammation, oxidative stress and apoptosis, as evidenced in various animal models and cultured cells. Here, we demonstrate that kallistatin levels were positively correlated with the concentration of total protein in bronchoalveolar lavage fluids (BALF) from patients with sepsis-related acute respiratory distress syndrome (ARDS), indicating a compensatory mechanism. Lower ratio of kallistatin to total protein in BALF showed a significant trend toward elevated neutrophil counts (P = 0.002) in BALF and increased mortality (P = 0.046). In lipopolysaccharide (LPS)-treated mice, expression of human kallistatin in lung by gene transfer with human kallistatin-encoding plasmid ameliorated acute lung injury (ALI) and reduced cytokine/chemokine levels in BALF. These mice exhibited attenuated lung epithelial apoptosis and decreased Fas/FasL expression compared to the control mice. Mouse survival was improved by kallistatin gene transfer or recombinant human kallistatin treatment after LPS challenge. In LPS-stimulated A549 human lung epithelial cells, kallistatin attenuated apoptosis, down-regulated Fas/FasL signaling, suppressed intracellular reactive oxygen species (ROS) and inhibited ROS-mediated NF-κB activation and inflammation. Furthermore, LPS-induced apoptosis was blocked by antioxidant N-acetylcysteine or NF-κB inhibitor via down-regulating Fas expression. These findings suggest the therapeutic potential of kallistatin for sepsis-related ALI/ARDS. PMID:26198099

  10. Kallistatin protects against sepsis-related acute lung injury via inhibiting inflammation and apoptosis.

    PubMed

    Lin, Wei-Chieh; Chen, Chang-Wen; Huang, Yu-Wen; Chao, Lee; Chao, Julie; Lin, Yee-Shin; Lin, Chiou-Feng

    2015-01-01

    Kallistatin, an endogenous plasma protein, exhibits pleiotropic properties in inhibiting inflammation, oxidative stress and apoptosis, as evidenced in various animal models and cultured cells. Here, we demonstrate that kallistatin levels were positively correlated with the concentration of total protein in bronchoalveolar lavage fluids (BALF) from patients with sepsis-related acute respiratory distress syndrome (ARDS), indicating a compensatory mechanism. Lower ratio of kallistatin to total protein in BALF showed a significant trend toward elevated neutrophil counts (P = 0.002) in BALF and increased mortality (P = 0.046). In lipopolysaccharide (LPS)-treated mice, expression of human kallistatin in lung by gene transfer with human kallistatin-encoding plasmid ameliorated acute lung injury (ALI) and reduced cytokine/chemokine levels in BALF. These mice exhibited attenuated lung epithelial apoptosis and decreased Fas/FasL expression compared to the control mice. Mouse survival was improved by kallistatin gene transfer or recombinant human kallistatin treatment after LPS challenge. In LPS-stimulated A549 human lung epithelial cells, kallistatin attenuated apoptosis, down-regulated Fas/FasL signaling, suppressed intracellular reactive oxygen species (ROS) and inhibited ROS-mediated NF-κB activation and inflammation. Furthermore, LPS-induced apoptosis was blocked by antioxidant N-acetylcysteine or NF-κB inhibitor via down-regulating Fas expression. These findings suggest the therapeutic potential of kallistatin for sepsis-related ALI/ARDS. PMID:26198099

  11. Deletion of ASK1 Protects against Hyperoxia-Induced Acute Lung Injury

    PubMed Central

    Fukumoto, Jutaro; Cox, Ruan; Fukumoto, Itsuko; Cho, Young; Parthasarathy, Prasanna Tamarapu; Galam, Lakshmi; Lockey, Richard F.; Kolliputi, Narasaiah

    2016-01-01

    Apoptosis signal-regulating kinase 1 (ASK1), a member of the MAPK kinase kinase kinase (MAP3K) family, is activated by various stimuli, which include oxidative stress, endoplasmic reticulum (ER) stress, calcium influx, DNA damage-inducing agents and receptor-mediated signaling through tumor necrosis factor receptor (TNFR). Inspiration of a high concentration of oxygen is a palliative therapy which counteracts hypoxemia caused by acute lung injury (ALI)-induced pulmonary edema. However, animal experiments so far have shown that hyperoxia itself could exacerbate ALI through reactive oxygen species (ROS). Our previous data indicates that ASK1 plays a pivotal role in hyperoxia-induced acute lung injury (HALI). However, it is unclear whether or not deletion of ASK1 in vivo protects against HALI. In this study, we investigated whether ASK1 deletion would lead to attenuation of HALI. Our results show that ASK1 deletion in vivo significantly suppresses hyperoxia-induced elevation of inflammatory cytokines (i.e. IL-1? and TNF-?), cell apoptosis in the lung, and recruitment of immune cells. In summary, the results from the study suggest that deletion of ASK1 in mice significantly inhibits hyperoxic lung injury. PMID:26807721

  12. Lobeline improves acute lung injury via nuclear factor-κB-signaling pathway and oxidative stress.

    PubMed

    Li, Kun-Cheng; Ho, Yu-Ling; Chen, Cing-Yu; Hsieh, Wen-Tsong; Chang, Yuan-Shiun; Huang, Guan-Jhong

    2016-05-01

    Acute lung injury (ALI) is a severe, life-threatening medical condition whose pathogenesis is linked to neutrophil infiltration of the lung. Activation and recruitment of neutrophils to the lung is mostly attributed to the production of chemokines NO, IL-6, for instance. This study aims to investigate lobeline ability in reducing NO production, and nitric oxide synthase (iNOs) expression. Lobeline was tested by inhibiting phosphorylation of mitogen-activated protein kinases (MAPKs), NF-κB and IκBα in LPS-stimulated RAW 264.7 cells. When RAW 264.7 macrophages were given lobeline with LPS, a significant concentration-dependent inhibition of NO production was detected. In vivo tests, mice were either treated with normal saline, 10mg/kg dexmethasone or 5, 10, 20mg/kg lobeline intraperitoneally, and after an hour, the administration of 5mg/kg of LPS was given intratracheally. External performance, cytokines, MAPK pathways and antioxidative enzymes (AOEs) were also carried out to evaluate the effects of these drugs. This is the first investigation in which lobeline was found to effectively inhibit acute lung edema, which may provide a potential target for treating ALI. Lobeline may utilize MAPKs pathways as well as AOEs activity to attenuate LPS-induced nonspecific pulmonary inflammation. PMID:26702732

  13. Genome-wide association mapping of acute lung injury in neonatal inbred mice

    PubMed Central

    Nichols, Jennifer L.; Gladwell, Wesley; Verhein, Kirsten C.; Cho, Hye-Youn; Wess, Jürgen; Suzuki, Oscar; Wiltshire, Tim; Kleeberger, Steven R.

    2014-01-01

    Reactive oxygen species (ROS) contribute to the pathogenesis of many acute and chronic pulmonary disorders, including bronchopulmonary dysplasia (BPD), a respiratory condition that affects preterm infants. However, the mechanisms of susceptibility to oxidant stress in neonatal lungs are not completely understood. We evaluated the role of genetic background in response to oxidant stress in the neonatal lung by exposing mice from 36 inbred strains to hyperoxia (95% O2) for 72 h after birth. Hyperoxia-induced lung injury was evaluated by using bronchoalveolar lavage fluid (BALF) analysis and pathology. Statistically significant interstrain variation was found for BALF inflammatory cells and protein (heritability estimates range: 33.6–55.7%). Genome-wide association mapping using injury phenotypes identified quantitative trait loci (QTLs) on chromosomes 1, 2, 4, 6, and 7. Comparative mapping of the chromosome 6 QTLs identified Chrm2 (cholinergic receptor, muscarinic 2, cardiac) as a candidate susceptibility gene, and mouse strains with a nonsynonymous coding single-nucleotide polymorphism (SNP) in Chrm2 that causes an amino acid substitution (P265L) had significantly reduced hyperoxia-induced inflammation compared to strains without the SNP. Further, hyperoxia-induced lung injury was significantly reduced in neonatal mice with targeted deletion of Chrm2, relative to wild-type controls. This study has important implications for understanding the mechanisms of oxidative lung injury in neonates.—Nichols, J. L., Gladwell, W., Verhein, K. C., Cho, H.-Y., Wess, J., Suzuki, O., Wiltshire, T., Kleeberger, S. R. Genome-wide association mapping of acute lung injury in neonatal inbred mice. PMID:24571919

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

    PubMed

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

    2014-03-01

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

  15. Granulocyte depletion prevents tumor necrosis factor-mediated acute lung injury in guinea pigs.

    PubMed

    Stephens, K E; Ishizaka, A; Wu, Z H; Larrick, J W; Raffin, T A

    1988-11-01

    To examine the role of polymorphonuclear neutrophils (PMN) and other granulocytes in the pathogenesis of acute lung injury caused by tumor necrosis factor alpha (TNF), we compared the permeability edema and pulmonary histopathology in normal (granulocyte sufficient) guinea pigs and in granulocytopenic guinea pigs treated with TNF. Circulating granulocytes were depleted with cyclophosphamide. Two groups of normal animals were treated with either saline (PMN+/Control) or 1.4 x 10(6) U/kg recombinant human TNF (PMN+/TNF). Three granulocytopenic groups were treated with either saline (PMN-/Control), TNF (PMN-/TNF), or intravenous infusion of 2 x 10(9) E. coli strain J96 (PMN-/Sepsis). We measured the amount of 125I-labeled albumin in bronchoalveolar lavage (BAL) fluid and whole lung tissue and the wet/dry lung weight ratio to assess pulmonary transvascular protein flux and edema. We also quantified PMN in BAL fluid and fixed lung tissue. There were no statistically significant differences in any of these parameters between the PMN+/Control, PMN-/Control, or PMN-/TNF groups, except that the PMN+/Control predictably had more PMN/alveolus than the PMN- groups. However, both the PMN+/TNF and the PMN-/Sepsis groups had increased amounts of 125I-labeled albumin in BAL fluid and lung tissue (p less than 0.01) and increased wet/dry lung weight ratios (p less than 0.05), compared to all other groups. Histopathologically, capillary congestion and moderate inflammation were seen in the PMN+/TNF group, and acute inflammation and gross alveolar hemorrhage were seen in the PMN-/Sepsis group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3059892

  16. Integrative Assessment of Chlorine-Induced Acute Lung Injury in Mice

    PubMed Central

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

    2012-01-01

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

  17. Effect of lung damage by acute exposure to nitrogen dioxide on lung immunity in the rat

    SciTech Connect

    Schnizlein, C.T.; Bice, D.E.; Rebar, A.H.; Wolff, R.K.; Beethe, R.L.

    1980-12-01

    Exposure to nitrogen dioxide damages Type I alveolar epithelial cells and the epithelium of the terminal bronchiole. Because an intact epithelium may help control the number of inhaled particles that are cleared by the pulmonary lymphatics, damage to the alveolar epithelium could alter the antigen load to the lung-associated lymph nodes. To determine the effects of lung damage by NO/sub 2/ inhalation on lung immunity, we exposed adult, male rats to 26 ppM NO/sub 2/ for 24 h at various time intervals before and after intratracheal immunization with 10/sup 8/ sheep red blood cells. Seven days after immunization, we determined the number of anti-SRBC antibody-forming cells in the LALN, cervical lymph nodes, and spleen. The immunologic response to SRBC was limited to the LALN, with few or no AFC in either the cervical lymph nodes or spleen. A fivefold increase in the number of IgG anti-SRBC AFC/10/sup 6/ LALN cells was evident in rats immunized 1 day after NO/sub 2/ exposure. The increase was followed by a slight suppression of the IgG response when rats were immunized 3 days after exposure, returning to normal levels by 7 days after exposure. Histopathological examination of lung tissues showed a slight respiratory bronchiolitis which was followed by a bronchiolar epithelial cell hyperplasia and Type II cell hyperplasia in the adjacent alveoli. Based on these observations, it appears that the fluctuations observedin the LALN response may be the result of damage and subsequent repair of bronchiolar and alveolar epithelium following NO/sub 2/ inhalation.

  18. Cerebrospinal Fluid Proteome of Patients with Acute Lyme Disease

    SciTech Connect

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

    2012-10-05

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

  19. Cartography of Pathway Signal Perturbations Identifies Distinct Molecular Pathomechanisms in Malignant and Chronic Lung Diseases.

    PubMed

    Arakelyan, Arsen; Nersisyan, Lilit; Petrek, Martin; Löffler-Wirth, Henry; Binder, Hans

    2016-01-01

    Lung diseases are described by a wide variety of developmental mechanisms and clinical manifestations. Accurate classification and diagnosis of lung diseases are the bases for development of effective treatments. While extensive studies are conducted toward characterization of various lung diseases at molecular level, no systematic approach has been developed so far. Here we have applied a methodology for pathway-centered mining of high throughput gene expression data to describe a wide range of lung diseases in the light of shared and specific pathway activity profiles. We have applied an algorithm combining a Pathway Signal Flow (PSF) algorithm for estimation of pathway activity deregulation states in lung diseases and malignancies, and a Self Organizing Maps algorithm for classification and clustering of the pathway activity profiles. The analysis results allowed clearly distinguish between cancer and non-cancer lung diseases. Lung cancers were characterized by pathways implicated in cell proliferation, metabolism, while non-malignant lung diseases were characterized by deregulations in pathways involved in immune/inflammatory response and fibrotic tissue remodeling. In contrast to lung malignancies, chronic lung diseases had relatively heterogeneous pathway deregulation profiles. We identified three groups of interstitial lung diseases and showed that the development of characteristic pathological processes, such as fibrosis, can be initiated by deregulations in different signaling pathways. In conclusion, this paper describes the pathobiology of lung diseases from systems viewpoint using pathway centered high-dimensional data mining approach. Our results contribute largely to current understanding of pathological events in lung cancers and non-malignant lung diseases. Moreover, this paper provides new insight into molecular mechanisms of a number of interstitial lung diseases that have been studied to a lesser extent. PMID:27200087

  20. Cartography of Pathway Signal Perturbations Identifies Distinct Molecular Pathomechanisms in Malignant and Chronic Lung Diseases

    PubMed Central

    Arakelyan, Arsen; Nersisyan, Lilit; Petrek, Martin; Löffler-Wirth, Henry; Binder, Hans

    2016-01-01

    Lung diseases are described by a wide variety of developmental mechanisms and clinical manifestations. Accurate classification and diagnosis of lung diseases are the bases for development of effective treatments. While extensive studies are conducted toward characterization of various lung diseases at molecular level, no systematic approach has been developed so far. Here we have applied a methodology for pathway-centered mining of high throughput gene expression data to describe a wide range of lung diseases in the light of shared and specific pathway activity profiles. We have applied an algorithm combining a Pathway Signal Flow (PSF) algorithm for estimation of pathway activity deregulation states in lung diseases and malignancies, and a Self Organizing Maps algorithm for classification and clustering of the pathway activity profiles. The analysis results allowed clearly distinguish between cancer and non-cancer lung diseases. Lung cancers were characterized by pathways implicated in cell proliferation, metabolism, while non-malignant lung diseases were characterized by deregulations in pathways involved in immune/inflammatory response and fibrotic tissue remodeling. In contrast to lung malignancies, chronic lung diseases had relatively heterogeneous pathway deregulation profiles. We identified three groups of interstitial lung diseases and showed that the development of characteristic pathological processes, such as fibrosis, can be initiated by deregulations in different signaling pathways. In conclusion, this paper describes the pathobiology of lung diseases from systems viewpoint using pathway centered high-dimensional data mining approach. Our results contribute largely to current understanding of pathological events in lung cancers and non-malignant lung diseases. Moreover, this paper provides new insight into molecular mechanisms of a number of interstitial lung diseases that have been studied to a lesser extent. PMID:27200087

  1. Modeling human lung development and disease using pluripotent stem cells.

    PubMed

    Snoeck, Hans-Willem

    2015-01-01

    Directed differentiation of human pluripotent stem cells (hPSCs) into mature cells, tissues and organs holds major promise for the development of novel approaches in regenerative medicine, and provides a unique tool for disease modeling and drug discovery. Sometimes underappreciated is the fact that directed differentiation of hPSCs also provides a unique model for human development, with a number of important advantages over model organisms. Here, I discuss the importance of using human stem cell models for understanding human lung development and disease. PMID:25516965

  2. Cellular interactions in the pathogenesis of interstitial lung diseases.

    PubMed

    Bagnato, Gianluca; Harari, Sergio

    2015-03-01

    Interstitial lung disease (ILD) encompasses a large and diverse group of pathological conditions that share similar clinical, radiological and pathological manifestations, despite potentially having quite different aetiologies and comorbidities. Idiopathic pulmonary fibrosis (IPF) represents probably the most aggressive form of ILD and systemic sclerosis is a multiorgan fibrotic disease frequently associated with ILD. Although the aetiology of these disorders remains unknown, in this review we analyse the pathogenic mechanisms by cell of interest (fibroblast, fibrocyte, myofibroblast, endothelial and alveolar epithelial cells and immune competent cells). New insights into the complex cellular contributions and interactions will be provided, comparing the role of cell subsets in the pathogenesis of IPF and systemic sclerosis. PMID:25726561

  3. The Efficacy and Safety of Chemotherapy in Patients With Nonsmall Cell Lung Cancer and Interstitial Lung Disease

    PubMed Central

    Chen, Yu Jie; Chen, Ling Xiao; Han, Mei Xiang; Zhang, Tian Song; Zhou, Zhi Rui; Zhong, Dian Sheng

    2015-01-01

    Abstract Chemotherapy plays a critical and venturous role against the co-morbidity of nonsmall cell lung cancer and interstitial lung disease (NSCLC–ILD). We performed a Bayesian meta-analysis and systematic review to evaluate the safety and efficacy of the chemotherapy in NSCLC–ILD patients. EMBASE, PubMed, the Cochrane Central Register of Controlled Trials, and clinicaltrials.gov (up to January 2015). We included all study designs except case reports, all studies with NSCLC–ILD patients and all the possible chemotherapy regimens. Quality was assessed by a components approach. We derived summary estimates using Bayesian method through WinBUGS (version 1.4.3, MRC Biostatistics Unit, Cambridge, UK). Seven studies involving 251 patients with NSCLC–ILD were included in the meta-analysis. The treatment response (complete remission, 0; [partial remission, 39.1%; 95% credible interval [CrI], 32.6–45.7]; [stable disease, 36%; 95% CrI, 29.6–42.2]; [PD, 15.4%; 95% CrI, 11.3–19.8]; [nonevaluable, 6.4%; 95% CrI, 2.7–10.1]; [overall response rate, 41.3%; 95% CrI, 35.3–47.4]; [disease control rate, 77.7%; 95% CrI, 72.2–82.7]) were comparable to that of patients with NSCLC alone; the survival outcomes (median overall survival, median progression-free survival, and 1-year survival rate) were slightly worse, especially the lower 1-year survival rate. Platinum-based doublets as first-line chemotherapy may be related to higher incidence of acute exacerbation-ILD in first line chemotherapy (AE, 8.47%; 95% CrI, 5.04–12.6). The data selection bias and small patient number make the meta-analysis of treatment response and conclusions generated from these data inaccurate. The present meta-analysis suggests that chemotherapy might be an effective therapy for patients with NSCLC–ILD, but it might be associated with higher incidence of acute exacerbation. PMID:26356699

  4. Applying Biotechnology and Bioengineering to Pediatric Lung Disease: Emerging Paradigms and Platforms

    PubMed Central

    Colvin, Kelley L.; Yeager, Michael E.

    2015-01-01

    Pediatric lung diseases remain a costly worldwide health burden. For many children with end-stage lung disease, lung transplantation remains the only therapeutic option. Due to the limited number of lungs available for transplantation, alternatives to lung transplant are desperately needed. Recently, major improvements in tissue engineering have resulted in newer technology and methodology to develop viable bioengineered lungs. These include critical advances in lung cell biology, stem cell biology, lung extracellular matrix, microfabrication techniques, and orthotopic transplantation of bioartificial lungs. The goal of this short review is to engage the reader’s interest with regard to these emerging concepts and to stimulate their interest to learn more. We review the existing state of the art of lung tissue engineering, and point to emerging paradigms and platforms in the field. Finally, we summarize the challenges and unmet needs that remain to be overcome. PMID:26106589

  5. Does hydatid disease have protective effects against lung cancer?

    PubMed

    Karadayi, Sule; Arslan, Sulhattin; Sumer, Zeynep; Turan, Mustafa; Sumer, Haldun; Karadayi, Kursat

    2013-08-01

    We hypothesized that solid tumors rarely occur in patients with hydatid disease. We obtained the serum of 14 patients diagnosed with hydatid disease, the serum of 10 patients who did not have a history of hydatid disease, and the hydatid cyst fluid from six patients. These sera and fluid samples were added at different concentrations to NCI-H209/An1 human lung small cell carcinoma cells and L929 mouse fibroblasts as a control group. Sera of patients with hydatid diseases had cytotoxic effects on NCI-H209/An1 cells, but they did not have cytotoxic effects on fibroblast cells. Sera from healthy subjects did not have a cytotoxic effect on the tumor cell line or control fibroblasts. Cyst fluid, also, did not have toxic effects on the NCI-H209/An1 cell line, but was toxic to fibroblasts up to a 1:32 dilution. Sera from patients with hydatid disease had cytotoxic effects on human small cell lung cancer cells in vitro. PMID:23645038

  6. Will chronic e-cigarette use cause lung disease?

    PubMed

    Rowell, Temperance R; Tarran, Robert

    2015-12-15

    Chronic tobacco smoking is a major cause of preventable morbidity and mortality worldwide. In the lung, tobacco smoking increases the risk of lung cancer, and also causes chronic obstructive pulmonary disease (COPD), which encompasses both emphysema and chronic bronchitis. E-cigarettes (E-Cigs), or electronic nicotine delivery systems, were developed over a decade ago and are designed to deliver nicotine without combusting tobacco. Although tobacco smoking has declined since the 1950s, E-Cig usage has increased, attracting both former tobacco smokers and never smokers. E-Cig liquids (e-liquids) contain nicotine in a glycerol/propylene glycol vehicle with flavorings, which are vaporized and inhaled. To date, neither E-Cig devices, nor e-liquids, are regulated by the Food and Drug Administration (FDA). The FDA has proposed a deeming rule, which aims to initiate legislation to regulate E-Cigs, but the timeline to take effect is uncertain. Proponents of E-Cigs say that they are safe and should not be regulated. Opposition is varied, with some opponents proposing that E-Cig usage will introduce a new generation to nicotine addiction, reversing the decline seen with tobacco smoking, or that E-Cigs generally may not be safe and will trigger diseases like tobacco. In this review, we shall discuss what is known about the effects of E-Cigs on the mammalian lung and isolated lung cells in vitro. We hope that collating this data will help illustrate gaps in the knowledge of this burgeoning field, directing researchers toward answering whether or not E-Cigs are capable of causing disease. PMID:26408554

  7. P38. Extraesophageal reflux disease and lung cancer

    PubMed Central

    Pesek, Milos; Terezie, Turkova-Sedlackova; Radka, Bittenglova; Lucie, Fremundova

    2014-01-01

    Introduction Gastroesophageal reflux disease is recognised as a substantial risk factor of esophageal cancer, as well its extraesophageal form should be a risk factor of pharyngeal and laryngeal cancers. EER should