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Sample records for acute lung disease

  1. 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

  2. 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

  3. 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

  4. Impact of Preexisting Interstitial Lung Disease on Acute, Extensive Radiation Pneumonitis: Retrospective Analysis of Patients with Lung Cancer

    PubMed Central

    Ozawa, Yuichi; Abe, Takefumi; Omae, Minako; Matsui, Takashi; Kato, Masato; Hasegawa, Hirotsugu; Enomoto, Yasunori; Ishihara, Takeaki; Inui, Naoki; Yamada, Kazunari; Yokomura, Koshi; Suda, Takafumi

    2015-01-01

    Introduction This study investigated the clinical characteristics and predictive factors for developing acute extended radiation pneumonitis with a focus on the presence and radiological characteristics of preexisting interstitial lung disease. Methods Of 1429 irradiations for lung cancer from May 2006 to August 2013, we reviewed 651 irradiations involving the lung field. The presence, compatibility with usual interstitial pneumonia, and occupying area of preexisting interstitial lung disease were retrospectively evaluated by pretreatment computed tomography. Cases of non-infectious, non-cardiogenic, acute respiratory failure with an extended bilateral shadow developing within 30 days after the last irradiation were defined as acute extended radiation pneumonitis. Results Nine (1.4%) patients developed acute extended radiation pneumonitis a mean of 6.7 days after the last irradiation. Although preexisting interstitial lung disease was found in 13% of patients (84 patients), 78% of patients (7 patients) with acute extended radiation pneumonitis cases had preexisting interstitial lung disease, which resulted in incidences of acute extended radiation pneumonitis of 0.35 and 8.3% in patients without and with preexisting interstitial lung disease, respectively. Multivariate logistic analysis indicated that the presence of preexisting interstitial lung disease (odds ratio = 22.6; 95% confidence interval = 5.29155; p < 0.001) and performance status (?2; odds ratio = 4.22; 95% confidence interval = 1.0620.8; p = 0.049) were significant predictive factors. Further analysis of the 84 patients with preexisting interstitial lung disease revealed that involvement of more than 10% of the lung field was the only independent predictive factor associated with the risk of acute extended radiation pneumonitis (odds ratio = 6.14; 95% confidence interval = 1.037.4); p = 0.038). Conclusions Pretreatment computed tomography evaluations of the presence of and area size occupied by preexisting interstitial lung disease should be assessed for safer irradiation of areas involving the lung field. PMID:26460792

  5. 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, Gyrgy; 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?=?1.010?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

  6. 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

  7. [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

  8. 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 ...

  9. 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

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

    PubMed Central

    Dias, Olvia Meira; Pereira, Daniel Antunes Silva; Baldi, Bruno Guedes; Costa, Andr 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

  11. Lung Diseases

    MedlinePLUS

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

  12. 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?

  13. Acute Respiratory Failure in Critically Ill Patients with Interstitial Lung Disease

    PubMed Central

    Zafrani, Lara; Lemiale, Virginie; Lapidus, Nathanael; Lorillon, Gwenael; Schlemmer, Benot; Azoulay, Elie

    2014-01-01

    Background Patients with chronic known or unknown interstitial lung disease (ILD) may present with severe respiratory flares that require intensive management. Outcome data in these patients are scarce. Patients and Methods Clinical and radiological features were collected in 83 patients with ILD-associated acute respiratory failure (ARF). Determinants of hospital mortality and response to corticosteroid therapy were identified by logistic regression. Results Hospital and 1-year mortality rates were 41% and 54% respectively. Pulmonary hypertension, computed tomography (CT) fibrosis and acute kidney injury were independently associated with mortality (odds ratio (OR) 4.55; 95% confidence interval (95%CI) (1.2017.33); OR, 7.68; (1.7833.22) and OR 10.60; (2.2549.97) respectively). Response to steroids was higher in patients with shorter time from hospital admission to corticosteroid therapy. Patients with fibrosis on CT had lower response to steroids (OR, 0.03; (0.0050.21)). In mechanically ventilated patients, overdistension induced by high PEEP settings was associated with CT fibrosis and hospital mortality. Conclusion Mortality is high in ILD-associated ARF. CT and echocardiography are valuable prognostic tools. Prompt corticosteroid therapy may improve survival. PMID:25115557

  14. 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.

  15. Incidence and risk factors for acute lung injury after open thoracotomy for thoracic diseases

    PubMed Central

    Yao, Shihua; Mao, Teng; Xu, Meiying; Chen, Wenhu

    2013-01-01

    Background Acute lung injury (ALI) is a major cause of morbidity and mortality after open thoracotomy. The purpose of the study was to identify the incidence and risk factors for ALI so as to prevent its occurrence and improve surgical results. Methods A prospective controlled study was carried out in 364 patients undergone open thoracotomy. Fifty-eight high risk elderly patients and 56 young patients as matched controls were prospectively entered into the study. The two groups were compared to identify the possible risk factors for ALI. Results ALI occurred exclusively in elderly patients, accounted for 2.7% of the whole series (10/364) and 7.9% of elderly patients (10/127). The mortality for patients with ALI was 30%, significantly higher than those without (1.0%, P=0.001). Upon univariate analysis, increased age, obesity, chronic obstructive pulmonary disease (COPD), poor spirometry, and positive fluid balance on postoperative day 1 were associated with increased risk of developing ALI. Upon multivariate analysis, only poor spirometry and excessive positive fluid balance on postoperative day 1 were revealed as independent risk factors for ALI. Conclusions ALI after open thoracotomy has a high mortality. COPD and excessive positive fluid balance on the first postoperative day are significant predictors, suggesting stringent patient selection and timely conservative fluid management may be helpful in reducing this extremely devastating complication. PMID:23991302

  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. Genetic polymorphisms associated with acute lung injury

    PubMed Central

    Reddy, Anita J; Kleeberger, Steven R

    2009-01-01

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

  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. Interstitial Lung Disease

    MedlinePLUS

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

  20. Lung Disease

    MedlinePLUS

    ... airways overreact to things like smoke, air pollution, mold, and many chemical sprays. They also can be ... that can be caused by bacteria , viruses , and fungi. Fluid builds up in the lungs and may ...

  1. Interstitial Lung Diseases

    MedlinePLUS

    Interstitial lung disease is the name for a large group of diseases that inflame or scar the lungs. The inflammation and scarring make it hard to ... air is responsible for some types of interstitial lung diseases. Specific types include Black lung disease among ...

  2. 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

  3. Interstitial lung disease

    MedlinePLUS

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

  4. 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

  5. Lung Diseases

    MedlinePLUS

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

  6. 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.

  7. 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 ...

  8. [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

  9. 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

  10. Lung disease - resources

    MedlinePLUS

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

  11. Efferocytosis and Lung Disease

    PubMed Central

    McCubbrey, Alexandra L.

    2013-01-01

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

  12. Gene therapy for acute lung injury.

    PubMed

    Brigham, K L; Stecenko, A A

    2000-01-01

    The remarkable transition of biological science into the age of molecular biology held great promise for development of new therapies for treatment of human disease. The fact that the technology exists for analyzing genetic material in exquisite detail and constructing DNA in virtually any desired form was the basis for promising rapid translation into clinical medicine and the final cure for genetically determined diseases; cystic fibrosis is the prime example of such a lung disease. The promise was not kept, at least not in a time frame which was expected. That result is neither because the rationale was faulty nor because the tools of molecular biology were wanting. The devil was and is in the details. How do you deliver DNA to the desired cell targets in amounts sufficient to accomplish the desired effect? Viral vectors have received the most attention, but viral vectors have proven to have both theoretical and practical problems. In the lungs, these vectors have not fulfilled their original promise. Non-viral based strategies work in a general sense, but efficiency of gene delivery in vivo has been a limitation. In addition, the experimental end points in both clinical and preclinical investigation have been most often designed to demonstrate phenomenology rather than potential efficacy. And, why limit the potential of gene therapy to inherited disease? In fact, treatment of acquired diseases by increasing or decreasing expression of a given gene in the lungs that would hasten recovery from an acquired disease might be easier than treating inherited disease because the requirements for duration of transgene expression would be less stringent. Over the past two decades, we have learned enough about the pathogenesis of acute lung injury to predict that increased (or decreased) production of certain biologically active mediators should be beneficial. Genes encoding some of these mediators have been cloned and constructs made which express the genes. It is now possible using either viral or non-viral strategies to deliver expression constructs to the lungs and, since acute lung injury has a dismal prognosis and no effective drugs have been identified, this seems a good clinical target for gene therapy. In preclinical studies, we have shown that increased expression of the gene encoding the constitutive form of the cyclooxygenase gene (COX-1) results in increased production of prostacyclin and PGE2 by the lungs and inhibits endotoxin induced pulmonary hypertension and edema. Additional studies demonstrate that increased expression of the alpha-1 antitrypsin gene in human respiratory epithelium in culture and in vivo has anti-viral and anti-inflammatory effects that are not predicted by extracellular concentrations of the transgene product. Thus, acute lung injury is a reasonable target for gene therapy, and evidence to date indicates that current technology is sufficiently robust to pursue this novel area for treatment of this devastating disease. PMID:10786968

  13. 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

  14. The inflammasome in lung diseases

    PubMed Central

    dos Santos, Gimena; Kutuzov, Mikhail A.

    2012-01-01

    Inflammation, the process aimed at restoring homeostasis after an insult, can be more damaging than the insult itself if uncontrolled, excessive, or prolonged. The inflammasome is an intracellular multimeric protein complex that regulates the maturation and release of proinflammatory cytokines of the IL-1 family in response to pathogens and endogenous danger signals. Growing evidence indicates that the inflammasome plays a key role in the pathogenesis of acute and chronic respiratory diseases. The inflammasome can be activated by the pathogens that account for the most prevalent infectious diseases of the respiratory tract, such as influenza A virus, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Mycobacterium tuberculosis. The inflammasome also plays a role in the chronic inflammation of the airways of patients with asthma and chronic obstructive pulmonary disease, as well as in the initiation and progression of the inflammatory process in pulmonary fibrosis. The aim of this review is to summarize the most relevant points of inflammasome activation in lung diseases. PMID:22904168

  15. Flavorings-Related Lung Disease

    MedlinePLUS

    ... Publications and Products Programs Contact NIOSH FLAVORINGS-RELATED LUNG DISEASE Recommend on Facebook Tweet Share Compartir On ... practices that place workers at risk. Flavorings-Related Lung Disease Microwave popcorn plant and flavoring plant workers ...

  16. 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

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

    PubMed Central

    Jos, 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: 5218 years, FEV1: 5820% 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

  18. 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

  19. 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

  20. 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.

  1. Interstitial Lung Disease (ILD): Treatment

    MedlinePLUS

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

  2. 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.

  3. 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

  4. Rapid evaluation by lung-cardiac-inferior vena cava (LCI) integrated ultrasound for differentiating heart failure from pulmonary disease as the cause of acute dyspnea in the emergency setting

    PubMed Central

    2012-01-01

    Background Rapid and accurate diagnosis and management can be lifesaving for patients with acute dyspnea. However, making a differential diagnosis and selecting early treatment for patients with acute dyspnea in the emergency setting is a clinical challenge that requires complex decision-making in order to achieve hemodynamic balance, improve functional capacity, and decrease mortality. In the present study, we examined the screening potential of rapid evaluation by lung-cardiac-inferior vena cava (LCI) integrated ultrasound for differentiating acute heart failure syndromes (AHFS) from primary pulmonary disease in patients with acute dyspnea in the emergency setting. Methods Between March 2011 and March 2012, 90 consecutive patients (45 women, 78.1??9.9?years) admitted to the emergency room of our hospital for acute dyspnea were enrolled. Within 30?minutes of admission, all patients underwent conventional physical examination, rapid ultrasound (lung-cardiac-inferior vena cava [LCI] integrated ultrasound) examination with a hand-held device, routine laboratory tests, measurement of brain natriuretic peptide, and chest X-ray in the emergency room. Results The final diagnosis was acute dyspnea due to AHFS in 53 patients, acute dyspnea due to pulmonary disease despite a history of heart failure in 18 patients, and acute dyspnea due to pulmonary disease in 19 patients. Lung ultrasound alone showed a sensitivity, specificity, negative predictive value, and positive predictive value of 96.2, 54.0, 90.9, and 75.0%, respectively, for differentiating AHFS from pulmonary disease. On the other hand, LCI integrated ultrasound had a sensitivity, specificity, negative predictive value, and positive predictive value of 94.3, 91.9, 91.9, and 94.3%, respectively. Conclusions Our study demonstrated that rapid evaluation by LCI integrated ultrasound is extremely accurate for differentiating acute dyspnea due to AHFS from that caused by primary pulmonary disease in the emergency setting. PMID:23210515

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

    PubMed Central

    Singh, Sonal

    2013-01-01

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

  6. What Are Asbestos-Related Lung Diseases?

    MedlinePLUS

    ... the NHLBI on Twitter. What Are Asbestos-Related Lung Diseases? Asbestos-related lung diseases are diseases caused ... peritoneum (PER-ih-to-NE-um). Asbestos-Related Lung Diseases Figure A shows the location of the ...

  7. 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 ...

  8. 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 ...

  9. Acute exacerbation of chronic obstructive pulmonary disease: cardiovascular links.

    PubMed

    Laratta, Cheryl R; van Eeden, Stephan

    2014-01-01

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

  10. Acute Exacerbation of Chronic Obstructive Pulmonary Disease: Cardiovascular Links

    PubMed Central

    Laratta, Cheryl R.; van Eeden, Stephan

    2014-01-01

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

  11. 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

  12. 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

  13. TOLL LIKE RECEPTORS IN DISEASES OF THE LUNG

    PubMed Central

    Kovach, Melissa A.; Standiford, Theodore J.

    2013-01-01

    The lung is in continuous contact with a diverse array of infectious agents, foreign antigens, and host-derived danger signals. To sample this expansive internal and external milieu, both resident myeloid and stromal/structure cells of the lung express a full complement of toll like receptors (TLRs) which recognize pathogen-associated molecular patterns (PAMPs) and endogenous danger-associated molecular patterns (DAMPs). TLRs play a vital role in immune host defense against bacterial, mycobacterial, fungal, and viral pathogens of the lung. Additionally, TLRs contribute to disease pathogenesis in non-infectious pulmonary disorders, including airways disease, acute lung injury, and interstitial lung disease. In this review, TLR biology in the context of experimental infectious and non-infectious lung disease is discussed, and correlates to human lung disease, including therapeutic implications of these findings, are defined. PMID:21624505

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. Cerebrovascular and ventilatory responses to acute isocapnic hypoxia in healthy aging and lung disease: effect of vitamin C.

    PubMed

    Hartmann, Sara E; Waltz, Xavier; Kissel, Christine K; Szabo, Lian; Walker, Brandie L; Leigh, Richard; Anderson, Todd J; Poulin, Marc J

    2015-08-15

    Acute hypoxia increases cerebral blood flow (CBF) and ventilation (V?e). It is unknown if these responses are impacted with normal aging, or in patients with enhanced oxidative stress, such as (COPD). The purpose of the study was to 1) investigate the effects of aging and COPD on the cerebrovascular and ventilatory responses to acute hypoxia, and 2) to assess the effect of vitamin C on these responses during hypoxia. In 12 Younger, 14 Older, and 12 COPD, we measured peak cerebral blood flow velocity (V?p; index of CBF), and V?e during two 5-min periods of acute isocapnic hypoxia, under conditions of 1) saline-sham; and 2) intravenous vitamin C. Antioxidants [vitamin C, superoxide dismutase (SOD), glutathione peroxidase, and catalase], oxidative stress [malondialdehyde (MDA) and advanced protein oxidation product], and nitric oxide metabolism end products (NOx) were measured in plasma. Following the administration of vitamin C, vitamin C, SOD, catalase, and MDA increased, while NOx decreased. V?p and V?e sensitivity to hypoxia was reduced in Older by ?60% (P < 0.02). COPD patients exhibited similar V?p and V?e responses to Older (P > 0.05). Vitamin C did not have an effect on the hypoxic V?e response but selectively decreased the V?p sensitivity in Younger only. These findings suggest a reduced integrative reflex (i.e., cerebrovascular and ventilatory) during acute hypoxemia in healthy older adults. Vitamin C does not appear to have a large influence on the cerebrovascular or ventilatory responses during acute hypoxia. PMID:26089546

  2. Military service and lung disease.

    PubMed

    Rose, Cecile S

    2012-12-01

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

  3. 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.

  4. Drug Induced Interstitial Lung Disease

    PubMed Central

    Schwaiblmair, Martin; Behr, Werner; Haeckel, Thomas; Mrkl, 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

  5. Aspiration-related lung diseases.

    PubMed

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

    2014-09-01

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

  6. 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

  7. Molecular diagnosis in lung diseases.

    PubMed

    Calabrese, Fiorella; Lunardi, Francesca; Popper, Helmut

    2015-01-01

    The development of different molecular biology techniques in the past decade has led to an explosion of new research in molecular pathology with consequent important applications to diagnosis, prognosis, and therapeutics, as well as a clearer concept of the disease pathogenesis. Many methods used in molecular pathology are now validated and used in several areas of pathological diagnosis, particularly on infectious and neoplastic diseases. The spectrum of infectious diseases, especially lung infective diseases, is now broadening and modifying, thus the pathologist is increasingly involved in the diagnosis of these pathologies. The precise tissue characterization of lung infections has an important impact on specific therapeutic treatment. Increased knowledge of significant alterations in lung cancer has led today to a better understanding of the pathogenic substrate underlying the development, progression and metastasis of neoplastic processes. Molecular tests are now routinely performed in different lung tumors allowing a more precise patient stratification in terms of prognosis and therapy. This review focuses on molecular pathology of the principal infective lung diseases and tumors. PMID:25553471

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

    PubMed

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

    2015-02-01

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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. Cough in interstitial lung disease.

    PubMed

    Garner, Justin; George, Peter M; Renzoni, Elisabetta

    2015-12-01

    Cough in the context of interstitial lung disease (ILD) has not been the focus of many studies. However, chronic cough has a major impact on quality of life in a significant proportion of patients with ILD. For the purpose of this review, we have chosen to highlight some of the more frequently encountered diffuse lung diseases including idiopathic pulmonary fibrosis, sarcoidosis, hypersensitivity pneumonitis and systemic sclerosis associated ILD. Many of the underlying mechanisms remain speculative and further research is now required to elucidate the complex pathways involved in the pathogenesis of chronic cough in ILD. This will hopefully pave the way for the identification of new therapeutic agents to alleviate this distressing and often intractable symptom. PMID:26545874

  15. Preemptive mechanical ventilation can block progressive acute lung injury.

    PubMed

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

    2016-02-01

    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

  16. 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

  17. [Imaging findings in intersitial lung diseases].

    PubMed

    Brauner, Michel; Ben Romdhane, Habib; Brillet, Pierre-Yves; Freynet, Olivia; Dion, Genevive; Valeyre, Dominique

    2010-01-01

    Subacute and chronic diffuse interstitial lung diseases Computed tomography (CT) plays an important role in all stages of management: positive diagnosis, etiological diagnosis, evaluation of lesions, ongoing monitoring, screening for complications, and prognosis. The etiological diagnosis is based on the imaging and analysis of patterns or groups of basic lesions often characteristics of a disease. Assessment of the images, the patient history, and the epidemiologic, clinical, laboratory, functional and cytologic data generally make it possible to reach a diagnosis. A pulmonary biopsy is rarely necessary. Acute diffuse interstitial lung diseases In the absence of an obvious clinical direction, CT, electrocardiography, and echocardiography are the first-line examinations to identify or rule out cardiogenic edema. CT can be used to guide bronchoalveolar lavage (BAL), widely used when the patient's respiratory condition permits. BAL can provide a diagnosis of diverse infections or help determine the cytologic type of alveolitis. CT also makes it possible to evaluate the lesions and plays a role in assessing severity. It makes it possible to choose the best sampling method and in principle directs sampling towards the most useful areas. It allows monitoring of disease course, screening of some complications, and precise localizing of tubes, drains, and catheters. Finally, it is used to assess the sequelae. PMID:19926247

  18. 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

  19. 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

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

    PubMed

    Sanderson, Michael J

    2011-10-01

    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

  1. Acute caprine fasciolosis: a case with unusual migration to lung.

    PubMed

    Hashemnia, Mohammad; Rezaei, Farid; Nikousefat, Zahra; Ghashghaii, Ali

    2015-09-01

    Fasciolosis is an important parasitic disease of domestic ruminants and occurs worldwide as a result of infection with liver fluke species. This report describes the macroscopic and microscopic characteristics of acute fasciolosis in a goat with unusual migration to lung. A 10-month-old goat was presented with history of weakness and acute recumbency from 12h ago. The clinicians didn't report clinical evidence of systemic disease. Hematological analysis showed no significant changes in blood parameters except a mild reduction in lymphocyte population and about 6% eosinophilia and also normocytic normochromic anemia. A noticeable increase in the level of serum ALP, AST and also GLDH were observed. Moreover, total protein and albumin showed a slight decrease in value comparing to reference intervals. In macroscopic examination numerous short vermiform cords were noted on the liver surface and the surface had an uneven appearance. A large number of immature, wandering flukes were seen on the cut surface. Histopathologically, a wide range of hepatic lesions was found. The most important lesions were moderate to severe perihepatitis and haemorrhagic tracts on the hepatic surface. These lesions corresponded to migratory tunnels filled with blood, fibrin and cellular debris. However histopathological findings of lung revealed chronic suppurative bronchopneumonia, but this lesion is not only associated with larval migration. PMID:26345062

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

    PubMed

    Htten, Matthias C; Kramer, Boris W

    2014-05-01

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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. New perspectives on basic mechanisms in lung disease. 6. Proteinase imbalance: its role in lung disease.

    PubMed Central

    Tetley, T D

    1993-01-01

    The hypothesis, some 30 years ago, that NE was the sole proteolytic agent responsible for the development of emphysema seems naive in retrospect. The availability of technology to measure NE facilitated the early research into the relationship between NE and lung disease. Despite an abundance of information on the activity of NE in the lung, it will probably require prospective studies in man with specific NE inhibitors or control at the gene level to establish a causal relationship between NE and lung disease. Parallel research has resulted in the isolation and characterisation of NE inhibitors other than PI and, indeed, alternative proteolytic enzymes that might contribute to lung disease. It is perhaps impossible now to think that a single proteinase, however omnipotent it may be, causes lung diseases as diverse as emphysema and fibrosis. An important aspect that is emerging is the interrelationship between proteolytic enzymes produced by different, or sometimes the same, cells that could potentiate tissue proteolysis. The evidence suggests that there is likely to be coordinated action between neutrophils, macrophages, and possibly mesenchymal proteinases which can activate or inactivate each other. In addition, one class of proteinases often appears able to proteolytically inactivate inhibitors of the opposite class, which presumably could amplify proteolysis if it occurred in vivo. Although the work on this aspect of proteinase activity is in its infancy, one suspects that part of the normal regulation of proteinase activity might include compartmentalisation. For example, the neutrophil stores proteinases before appropriate release and can inactivate PI to enable proteolytic action pericellularly, whereas degradation of extracellular matrix by macrophages requires interaction between the cell and matrix which is facilitated by cell receptor bound uPA. Disintegration of these "compartments" due to oedema, proteolysis, or for mechanical reasons could, firstly, expose further extracellular matrix substrates to inflammatory and damaged cell proteinases but, secondly, might enhance proteinase potential by the cooperative action of these enzymes. It seems increasingly likely that, where proteinases play a part, there is a cocktail of proteinases that is characteristic of the injury that develops (fig). What remains unclear is why only a proportion of those susceptible, such as smokers or those with acute lung injury, develop irreversible lung disease. This suggests that there are other factors acquired or inherited that need to be considered. Images PMID:8322246

  9. Pulmonary nuclear medicine: Techniques in diagnosis of lung disease

    SciTech Connect

    Atkins, H.L.

    1984-01-01

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

  10. 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

  11. 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

  12. 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.

  13. Genomic insights into acute inflammatory lung injury.

    PubMed

    Garcia, Joe G N; Moreno Vinasco, Liliana

    2006-12-01

    Acute lung injury (ALI) is a devastating syndrome (usually associated with sepsis) that represents a major healthcare burden in the United States. We have focused our studies on unraveling the genetic underpinnings of this syndrome utilizing a candidate gene approach to identify novel genes for ALI susceptibility. Two novel genes identified by this approach include pre-B cell colony-enhancing factor (PBEF) and the gene for myosin light chain kinase (MLCK). PBEF protein levels were elevated in human bronchoalveolar lavage and serum samples from patients with ALI, and DNA sequencing identified two single nucleotide polymorphisms in the PBEF promoter (T-1001G, C-1543T) that were overrepresented in patients with sepsis-induced ALI. More recently, we found MLCK single polymorphisms and haplotypes to be associated with human ALI with unique variants observed in African-Americans with ALI. Thus genomic and genetic approaches represent powerful strategies in the identification of novel candidate genes and potential targets for ALI therapies. PMID:16877634

  14. 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

  15. Pleuroparenchymal fibroelastosis: a rare interstitial lung disease

    PubMed Central

    English, John C; Mayo, John R; Levy, Robert; Yee, John; Leslie, Kevin O

    2015-01-01

    Pleuroparenchymal fibroelastosis (PPFE) is a newly described form of interstitial lung disease that originates in the upper lung zones and typically progresses to involve the entire lung. The disease may be idiopathic but is often associated with other pre- or coexisting conditions. Pneumothorax is a common complication and can occur at presentation or at other times during the course of the disease. Pathologically, interstitial fibrosis takes the form of a dense consolidation with some preservation of alveolar septal outlines and demonstrates a distinctly abrupt interface with residual normal lung. Unrecognized cases of PPFE may be incorrectly diagnosed as sarcoidosis, atypical idiopathic pulmonary fibrosis, or other unclassifiable interstitial pneumonias. PMID:26090119

  16. 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 ...

  17. 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

  18. 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.

  19. 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

  20. 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.

  1. 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

  2. Acute graft versus host disease

    PubMed Central

    Jacobsohn, David A; Vogelsang, Georgia B

    2007-01-01

    Acute graft-versus-host disease (GVHD) occurs after allogeneic hematopoietic stem cell transplant and is a reaction of donor immune cells against host tissues. Activated donor T cells damage host epithelial cells after an inflammatory cascade that begins with the preparative regimen. About 35%50% of hematopoietic stem cell transplant (HSCT) recipients will develop acute GVHD. The exact risk is dependent on the stem cell source, age of the patient, conditioning, and GVHD prophylaxis used. Given the number of transplants performed, we can expect about 5500 patients/year to develop acute GVHD. Patients can have involvement of three organs: skin (rash/dermatitis), liver (hepatitis/jaundice), and gastrointestinal tract (abdominal pain/diarrhea). One or more organs may be involved. GVHD is a clinical diagnosis that may be supported with appropriate biopsies. The reason to pursue a tissue biopsy is to help differentiate from other diagnoses which may mimic GVHD, such as viral infection (hepatitis, colitis) or drug reaction (causing skin rash). Acute GVHD is staged and graded (grade 0-IV) by the number and extent of organ involvement. Patients with grade III/IV acute GVHD tend to have a poor outcome. Generally the patient is treated by optimizing their immunosuppression and adding methylprednisolone. About 50% of patients will have a solid response to methylprednisolone. If patients progress after 3 days or are not improved after 7 days, they will get salvage (second-line) immunosuppressive therapy for which there is currently no standard-of-care. Well-organized clinical trials are imperative to better define second-line therapies for this disease. Additional management issues are attention to wound infections in skin GVHD and fluid/nutrition management in gastrointestinal GVHD. About 50% of patients with acute GVHD will eventually have manifestations of chronic GVHD. PMID:17784964

  3. 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

  4. ?-Catenin in the Fibroproliferative Response to Acute Lung Injury

    PubMed Central

    Douglas, Ivor S.; del Valle, Fernando Diaz; Winn, Robert A.; Voelkel, Norbert F.

    2006-01-01

    Resolution of alveolar epithelial/capillary membrane damage after acute lung injury requires coordinated and effective tissue repair to reestablish a functional alveolar epithelial/capillary membrane barrier. We hypothesized that signaling pathways important in lung alveolar bud ontogeny are activated in the recovery and remodeling phases after profound oxidant stress lung injury in a murine model. To test this, we characterized the expression of noncanonical ?-catenin pathway proteins E-cadherin, integrin-linked kinase1, and ?-catenin in mice undergoing normoxic recovery after exposure to butylated hydroxytoluene (BHT, ionol) and concomitant sublethal (75% O2) hyperoxia. Mice developed early acute lung injury with subsequent inflammation, collagen deposition, interstitial cellular proliferation, and lung architectural distortion. Reduced E-cadherin expression after 6 d of BHT and hyperoxia was accompanied by enhanced expression and nuclear localization of ?-catenin and increased integrin-linked kinase-1 expression during subsequent normoxic recovery. This resulted in increased expression of the cotranscriptional regulators TCF-1 and -3 and cyclin D1. Proliferation of murine lung epithelial-12 cells in vitro after 8 h of treatment with BHT quinone-methide and hyperoxia and 48 h of normoxic recovery was enhanced 2.7-fold compared with vehicle-treated control mice at the same time point. BHT/hyperoxia-exposed mice treated with the pan-caspase inhibitor z-ASP had increased acute lung injury and reduced survival despite the presence of TUNEL-positive cells, suggesting enhanced lung cell necrosis. ?-Catenin expression was reduced in z-ASPco-treated lungs after BHT/hyperoxia. The noncanonical cadherin?-catenin axis is associated with fibroproliferative repair after BHT/hyperoxia exposure and may regulate epithelial proliferation and lung matrix remodeling and repair in response to lung injury. PMID:16272459

  5. ACUTE CONSTRICTIVE PERICARDITIS FOLLOWING LUNG TRANSPLANTATION FOR LYMPHANGIOLEIOMYOMATOSIS: A CASE REPORT

    PubMed Central

    Billings, Martha E.; Mulligan, Michael; Raghu, Ganesh

    2009-01-01

    Lymphangioleiomyomatosis (LAM) is a rare cystic progressive lung disease with many extra-pulmonary manifestations which may complicate allograft function after transplantation. We present a LAM patient, one-year status-post bilateral lung transplant, with new dyspnea and declining spirometry without rejection, infection or recurrence. Investigation revealed acute constrictive pericarditis which has not previously been reported in LAM lung transplant patients. This represents a novel complication likely due to progression of extra-pulmonary LAM that should be considered in LAM transplant patients with dyspnea. PMID:19134542

  6. Life-threatening acute pneumonitis in mixed connective tissue disease: a case report and literature review.

    PubMed

    Rath, Eva; Zandieh, Shahin; Lckinger, Alexander; Hirschl, Mirko; Klaushofer, Klaus; Zwerina, Jochen

    2015-10-01

    Mixed connective tissue disease (MCTD) is a rare connective tissue disease frequently involving the lungs. The main characteristic is a systemic sclerosis-like picture of slowly progressing interstitial lung disease consistent with lung fibrosis, while pulmonary arterial hypertension is rare. Herein, we present a case of a newly diagnosed MCTD patient developing life-threatening acute pneumonitis similar to lupus pneumonitis. Previous literature on this exceptionally rare complication of MCTD is reviewed and differential diagnosis and management discussed. PMID:26142172

  7. 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

  8. 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

  9. 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

  10. Molecular imaging of folate receptor ?-positive macrophages during acute lung inflammation.

    PubMed

    Han, Wei; Zaynagetdinov, Rinat; Yull, Fiona E; Polosukhin, Vasiliy V; Gleaves, Linda A; Tanjore, Harikrishna; Young, Lisa R; Peterson, Todd E; Manning, H Charles; Prince, Lawrence S; Blackwell, Timothy S

    2015-07-01

    Characterization of markers that identify activated macrophages could advance understanding of inflammatory lung diseases and facilitate development of novel methodologies for monitoring disease activity. We investigated whether folate receptor ? (FR?) expression could be used to identify and quantify activated macrophages in the lungs during acute inflammation induced by Escherichia coli LPS. We found that FR? expression was markedly increased in lung macrophages at 48 hours after intratracheal LPS. In vivo molecular imaging with a fluorescent probe (cyanine 5 polyethylene glycol folate) showed that the fluorescence signal over the chest peaked at 48 hours after intratracheal LPS and was markedly attenuated after depletion of macrophages. Using flow cytometry, we identified the cells responsible for uptake of cyanine 5-conjugated folate as FR?(+) interstitial macrophages and pulmonary monocytes, which coexpressed markers associated with an M1 proinflammatory macrophage phenotype. These findings were confirmed using a second model of acute lung inflammation generated by inducible transgenic expression of an NF-?B activator in airway epithelium. Using CC chemokine receptor 2-deficient mice, we found that FR?(+) macrophage/monocyte recruitment was dependent on the monocyte chemotactic protein-1/CC chemokine receptor 2 pathway. Together, our results demonstrate that folate-based molecular imaging can be used as a noninvasive approach to detect classically activated monocytes/macrophages recruited to the lungs during acute inflammation. PMID:25375039

  11. 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-Lefvre 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

  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. 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

  14. Interstitial Lung Disease in Idiopathic Inflammatory Myopathy

    PubMed Central

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

    2011-01-01

    The lung is one of the most common extra-muscular targets in idiopathic inflammatory myopathies (IIM) and interstitial lung disease (ILD) is a prevalent and often devastating manifestation of IIM. IIM-associated ILD (IIM-ILD) contributes to nearly 80% of the mortality in IIM with a reported prevalence of 65% of newly diagnosed IIM cases. Although ILD frequently accompanies clinical and laboratory findings of myositis, overt signs of muscle disease may be absent in the setting of significant lung disease. Understanding the varied scope of presentation of these diseases is essential to providing optimal patient care. This review will provide an in depth examination of ILD in IIM both from a rheumatologic and pulmonary perspective and will discuss the scope of disease, presenting features, genetic associations, pathogenesis, diagnosis, radiographic and histopathologic findings, along with biomarker assessment and a rationale for therapeutic intervention. PMID:21941374

  15. [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

  16. 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

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

    PubMed Central

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

    2015-01-01

    Background. Paraquat (PQ) poisoning is a lethal toxicological challenge that served as a disease model of acute lung injury and pulmonary fibrosis, but the mechanism is undetermined and no effective treatment has been discovered. Methods and Findings. We demonstrated that PQ injures mitochondria and leads to mtDNA release. The mtDNA mediated PBMC recruitment and stimulated the alveolar epithelial cell production of TGF-?1 in vitro. The levels of mtDNA in circulation and bronchial alveolar lavage fluid (BALF) were elevated in a mouse of PQ-induced lung injury. DNaseI could protect PQ-induced lung injury and significantly improved survival. Acute lung injury markers, such as TNF?, IL-1?, and IL-6, and marker of fibrosis, collagen I, were downregulated in parallel with the elimination of mtDNA by DNaseI. These data indicate a possible mechanism for PQ-induced, mtDNA-mediated lung injury, which may be shared by other causes of lung injury, as suggested by the same protective effect of DNaseI in bleomycin-induced lung injury model. Interestingly, increased mtDNA in the BALF of patients with amyopathic dermatomyositis-interstitial lung disease can be appreciated. Conclusions. DNaseI targeting mtDNA may be a promising approach for the treatment of PQ-induced acute lung injury and pulmonary fibrosis that merits fast tracking through clinical trials. PMID:25759818

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

    PubMed

    Bo?tsova, E V; Beliashova, M A; Ovsiannikov, D Iu

    2015-01-01

    Interstitial lung diseases (ILD, diffuse lung diseases) are a heterogeneous group of diseases in which a pathological process primarily involved alveoli and perialveolar interstitium, resulting in impaired gas exchange, restrictive changes of lung ventilation function and diffuse interstitial changes detectable by X-ray. Children's interstitial lung diseases is an topical problem ofpediatricpulmonoogy. The article presents current information about classification, epidemiology, clinical presentation, diagnostics, treatment and prognosis of these rare diseases. The article describes the differences in the structure, pathogenesis, detection of various histological changes in children's ILD compared with adult patients with ILD. Authors cite an instance of registers pediatric patients with ILD. The clinical semiotics of ILD, the possible results of objective research, the frequency of symptoms, the features of medical history, the changes detected on chest X-rays, CT semiotics described in detail. Particular attention was paid to interstitial lung diseases, occurring mainly in newborns and children during the first two years of life, such as congenital deficiencies of surfactant proteins, neuroendocrine cell hyperplasia of infancy, pulmonary interstitial glycogenosis. The diagnostic program for children's ILD, therapy options are presented in this article. PMID:26234096

  19. Uncommon causes of occupational interstitial lung diseases.

    PubMed

    Gong, H

    1996-09-01

    Uncommon causes of occupational interstitial lung disease, or pneumoconiosis, are being increasingly recognized and diagnosed. The fibrogenic potential of numerous types of respirable inorganic particles remains poorly understood but is significantly determined by lung deposition and clearance, the agent's size and solubility, host susceptibility, and other factors. Microanalytic techniques have improved the identification of uncommon or unusual biopersistent particles or elements in fibrotic lung tissue. Recent findings in workers exposed to manmade vitreous fibers, silicon carbide, talc, titanium, cerium, and polyvinyl chloride provide new clinical insights into not only their specific fibrogenic capabilities but also in the broader appreciation that many cases of unexplained interstitial lung disease may be caused by occupational exposures to one or more uncommon airborne substances. PMID:9363175

  20. [Pathomorphological changes in the lung in acute posthemorrhagic anemia].

    PubMed

    Pigolkin, Iu I; Dolzhanski?, O V; Borlakova, B U

    2008-01-01

    Lung tissue was histologically studied in 30 cadavers of those who had died from acute hemorrhage. When death occurred, several minutes after blood were marked by emphysema without alveolar edema and lymph-macrophageal infiltration of interalveolar septa whereas 1.5-2 hours after blood loss, emphysematous changes in lung tissues were accompanied with significant lymph-macrophageal infiltration of interalveolar septa and intraalveolar edema and with the signs of micro disseminated intravascular coagulation in the lung. Desquamation and necrotic changes of alveocytes were observed. At death, 24 hours or more following blood loss, there was, along with alveocytic necrotic changes in lung tissue, type 2 pneumocytic proliferation, as well as alveolar hemorrhages, vascular thrombosis in the microcirculatory bed, fibrin lumps and threads in the alveolar lumen. PMID:18807527

  1. 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

  2. Metallothionein-induced zinc partitioning exacerbates hyperoxic acute lung injury

    PubMed Central

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

    2013-01-01

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

  3. 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 Students 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

  4. 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

  5. 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 ...

  6. 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

  7. Lung postmortem autopsy revealing extramedullary involvement in multiple myeloma causing acute respiratory distress syndrome.

    PubMed

    Ravinet, Aurlie; Perbet, Sbastien; Guize, Romain; Lemal, Richard; Gurin, 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

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

    PubMed Central

    Ravinet, Aurlie; Perbet, Sbastien; Guize, Romain; Gurin, 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

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

    PubMed

    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 (10mg/kg) by oral gavage twice daily for 1week prior to exposure to aerosolized LPS. At 24h 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(2)(-)/NO(3)(-)) levels were measured in lung tissues. The expression of inflammatory cytokines, tumor necrosis factor-? (TNF-?), transforming growth factor-?(1) (TGF-?(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(2)(-)/NO(3)(-) levels. Importantly, nilotinib caused down-regulation of the inflammatory cytokines TNF-?, TGF-?(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. PMID:21473879

  15. 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

  16. 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

  17. 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

  18. 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

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

    PubMed Central

    Gilliss, Brian M.; Looney, Mark R.

    2010-01-01

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

  20. 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

  1. 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

  2. ncRNA-regulated immune response and its role in inflammatory lung diseases.

    PubMed

    Xie, Na; Liu, Gang

    2015-11-15

    Despite the greatly expanded knowledge on the regulation of immune response by protein molecules, there is increasing understanding that noncoding RNAs (ncRNAs) are also an integral component of this regulatory network. Abnormal immune response serves a central role in the initiation, progression, and exacerbation of inflammatory lung diseases, such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, and acute respiratory distress syndrome/acute lung injury. Dysregulation of ncRNAs has been linked to various immunopathologies. In this review, we highlighted the role of ncRNAs in the regulation of innate and adaptive immunity and summarized recent findings that ncRNAs participate in the pathogenesis of inflammatory lung diseases via their regulation of pulmonary immunity. We also discussed therapeutic potentials for targeting ncRNAs to treat these lung disorders. PMID:26432871

  3. 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

  4. Genetic polymorphisms and susceptibility to lung disease

    PubMed Central

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

    2006-01-01

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

  5. 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

  6. Extracellular matrix mechanics in lung parenchymal diseases

    PubMed Central

    Suki, Bla; 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

  7. 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

  8. 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.

  9. 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

  10. 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

  11. Long-Term Control Medications for Lung Diseases

    MedlinePLUS

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

  12. Long-Term Control Medications for Lung Diseases

    MedlinePLUS

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

  13. Respiratory disease and respiratory physiology: putting lung function into perspective interstitial lung disease.

    PubMed

    Berend, Norbert

    2014-10-01

    The interstitial lung diseases pathologically involve the pulmonary interstitium but may also involve the airways, pleura and pulmonary circulation. They may be idiopathic, be part of other conditions, or be related to drug or environmental exposures. This review will focus on diagnostic and prognostic information provided by lung function tests in the idiopathic interstitial pneumonias, particularly idiopathic pulmonary fibrosis and non-specific interstitial pneumonia. These disorders are characterized by small stiff lungs with impaired gas exchange. Lung function tests, particularly lung volumes and gas transfer, used initially on patient presentation and then repeatedly on follow up, together with high-resolution computed tomography scans, can generate predictive formulae which are superior to single tests and can be used to provide useful information to assess the natural history of the disease or guide therapy. The concomitant presence of emphysema may mask the degree of restriction and may have adverse prognostic implications when accompanied by pulmonary hypertension. PMID:25039623

  14. Thaliporphine Derivative Improves Acute Lung Injury after Traumatic Brain Injury

    PubMed Central

    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

  15. 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

  16. 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

  17. Mechanisms of acute exacerbation of respiratory symptoms in chronic obstructive pulmonary disease.

    PubMed

    Roca, Mihai; Verduri, Alessia; Corbetta, Lorenzo; Clini, Enrico; Fabbri, Leonardo M; Begh, Bianca

    2013-05-01

    Exacerbations of chronic obstructive respiratory disease (ECOPD) are acute events characterized by worsening of the patient's respiratory symptoms, particularly dyspnoea, leading to change in medical treatment and/or hospitalisation. AECOP are considered respiratory diseases, with reference to the respiratory nature of symptoms and to the involvement of airways and lung. Indeed respiratory infections and/or air pollution are the main causes of ECOPD. They cause an acute inflammation of the airways and the lung on top of the chronic inflammation that is associated with COPD. This acute inflammation is responsible of the development of acute respiratory symptoms (in these cases the term ECOPD is appropriate). However, the acute inflammation caused by infections/pollutants is almost associated with systemic inflammation, that may cause acute respiratory symptoms through decompensation of concomitant chronic diseases (eg acute heart failure, thromboembolism, etc) almost invariably associated with COPD. Most concomitant chronic diseases share with COPD not only the underlying chronic inflammation of the target organs (i.e. lungs, myocardium, vessels, adipose tissue), but also clinical manifestations like fatigue and dyspnoea. For this reason, in patients with multi-morbidity (eg COPD with chronic heart failure and hypertension, etc), the exacerbation of respiratory symptoms may be particularly difficult to investigate, as it may be caused by exacerbation of COPD and/or ? comorbidity, (e.g. decompensated heart failure, arrhythmias, thromboembolisms) without necessarily involving the airways and lung. In these cases the term ECOPD is inappropriate and misleading. PMID:23489139

  18. The role of toll-like receptors in acute and chronic lung inflammation

    PubMed Central

    2010-01-01

    By virtue of its direct contact with the environment, the lung is constantly challenged by infectious and non-infectious stimuli that necessitate a robust yet highly controlled host response coordinated by the innate and adaptive arms of the immune system. Mammalian Toll-like receptors (TLRs) function as crucial sentinels of microbial and non-infectious antigens throughout the respiratory tract and mediate host innate immunity. Selective induction of inflammatory responses to harmful environmental exposures and tolerance to innocuous antigens are required to maintain tissue homeostasis and integrity. Conversely, dysregulated innate immune responses manifest as sustained and self-perpetuating tissue damage rather than controlled tissue repair. In this article we review aspects of Toll-like receptor function that are relevant to the development of acute lung injury and chronic obstructive lung diseases as well as resistance to frequently associated microbial infections. PMID:21108806

  19. Searching for candidate genes in acute lung injury: SNPs, Chips and PBEF.

    PubMed

    Garcia, Joe G N

    2005-01-01

    Acute lung injury (ALI) is a devastating illness, occurring in the setting of sepsis, with genetic variations contributing to ALI susceptibility and severity. We utilized the "candidate gene approach" with extensive expression profiling in animal and human ALI models to identify novel candidate genes. We noted significant expression of pre-B-cell colony enhancing factor (PBEF), a gene not previously associated with lung pathophysiology. This finding was validated by molecular, biochemical and immunohistochemical approaches with increased levels of PBEF also detected in human BAL and serum. DNA sequencing identified two single nucleotide polymorphisms (SNPs) in the PBEF promoter (T-1001G, C-1543T), which were genotyped in a Caucasian cohort of sepsis-associated ALI patients. Carriers of the GC haplotype exhibited a 5.7-fold relative ALI risk compared to controls associated with increased PBEF promoter activity. These studies demonstrate the successful application of genomic technologies in the identification of novel candidate genes in complex lung disease. PMID:16555615

  20. 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

  1. 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.

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

    PubMed Central

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

    2009-01-01

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

  3. 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

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

    PubMed Central

    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 CA153 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

  5. Niacinamide mitigated the acute lung injury induced by phorbol myristate acetate in isolated rat's lungs

    PubMed Central

    2012-01-01

    Background Phorbol myristate acetate (PMA) is a strong neutrophil activator and has been used to induce acute lung injury (ALI). Niacinamide (NAC) is a compound of B complex. It exerts protective effects on the ALI caused by various challenges. The purpose was to evaluate the protective effects of niacinamide (NAC) on the PMA-induced ALI and associated changes. Methods The rat's lungs were isolated in situ and perfused with constant flow. A total of 60 isolated lungs were randomized into 6 groups to received Vehicle (DMSO 100 ?g/g), PMA 4 ?g/g (lung weight), cotreated with NAC 0, 100, 200 and 400 mg/g (lung weight). There were 10 isolated lungs in each group. We measured the lung weight and parameters related to ALI. The pulmonary arterial pressure and capillary filtration coefficient (Kfc) were determined in isolated lungs. ATP (adenotriphosphate) and PARP [poly(adenosine diphophate-ribose) polymerase] contents in lung tissues were detected. Real-time PCR was employed to display the expression of inducible and endothelial NO synthases (iNOS and eNOS). The neutrophil-derived mediators in lung perfusate were determined. Results PMA caused increases in lung weight parameters. This agent produced pulmonary hypertension and increased microvascular permeability. It resulted in decrease in ATP and increase in PARP. The expression of iNOS and eNOS was upregulated following PMA. PMA increased the neutrophil-derived mediators. Pathological examination revealed lung edema and hemorrhage with inflammatory cell infiltration. Immunohistochemical stain disclosed the presence of iNOS-positive cells in macrophages and endothelial cells. These pathophysiological and biochemical changes were diminished by NAC treatment. The NAC effects were dose-dependent. Conclusions Our results suggest that neutrophil activation and release of neutrophil-derived mediators by PMA cause ALI and associated changes. NO production through the iNOS-producing cells plays a detrimental role in the PMA-induced lung injury. ATP is beneficial, while PARP plays a deteriorative effect on the PMA-induced ALI. NAC exerts protective effects on the inflammatory cascade leading to pulmonary injury. This B complex compound may be applied for clinical usage and therapeutic regimen. PMID:22375599

  6. Primary Severe Acute Respiratory Syndrome Coronavirus Infection Limits Replication but Not Lung Inflammation upon Homologous Rechallenge

    PubMed Central

    Clay, Candice; Donart, Nathan; Fomukong, Ndingsa; Knight, Jennifer B.; Lei, Wanli; Price, Lance; Hahn, Fletcher; Van Westrienen, Jesse

    2012-01-01

    Our knowledge regarding immune-protective and immunopathogenic events in severe acute respiratory syndrome coronavirus (SARS-CoV) infection is limited, and little is known about the dynamics of the immune response at the primary site of disease. Here, an African green monkey (AGM) model was used to elucidate immune mechanisms that facilitate viral clearance but may also contribute to persistent lung inflammation following SARS-CoV infection. During primary infection, SARS-CoV replicated in the AGM lung for up to 10 days. Interestingly, lung inflammation was more prevalent following viral clearance, as leukocyte numbers peaked at 14 days postinfection (dpi) and remained elevated at 28 dpi compared to those of mock-infected controls. Lung macrophages but not dendritic cells were rapidly activated, and both cell types had high activation marker expression at late infection time points. Lung proinflammatory cytokines were induced at 1 to 14 dpi, but most returned to baseline by 28 dpi except interleukin 12 (IL-12) and gamma interferon. In SARS-CoV homologous rechallenge studies, 11 of the 12 animals were free of replicating virus at day 5 after rechallenge. However, incidence and severity of lung inflammation was not reduced despite the limited viral replication upon rechallenge. Evaluating the role of antibodies in immune protection or potentiation revealed a progressive increase in anti-SARS-CoV antibodies in lung and serum that did not correlate temporally or spatially with enhanced viral replication. This study represents one of the first comprehensive analyses of lung immunity, including changes in leukocyte populations, lung-specific cytokines, and antibody responses following SARS-CoV rechallenge in AGMs. PMID:22345460

  7. 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

  8. 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

  9. Acute renal failure in typical Kawasaki disease.

    PubMed

    Bonany, Pablo J; Bilkis, Manuel D; Gallo, Guillermo; Lago, Nstor; Dennehy, Mara V; Sosa del Valle, Juan M; Vallejo, Graciela; Cnepa, Carlos

    2002-05-01

    Few cases of Kawasaki disease with acute renal failure have been described and only three articles report histological findings. We present an 8-year-old boy with typical Kawasaki disease and acute renal failure who did not require dialysis and had a complete recovery. Pathological findings in percutaneous biopsy included tubulointerstitial nephropathy with mild mesangial expansion, without vessel involvement or deposits in basal membrane. These findings were similar to those previously reported. We also detected apoptotic bodies in tubules. PMID:12042888

  10. 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.

  11. 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

  12. Apocynin ameliorates endotoxin-induced acute lung injury in rats.

    PubMed

    Abdelmageed, Marwa E; El-Awady, Mohammed S; Suddek, Ghada M

    2016-01-01

    Acute lung injury (ALI) is a serious clinical syndrome with a high rate of mortality. In this study, the effects of apocynin, a NADPH-oxidase (NOX) inhibitor on lipopolysaccharide (LPS)-induced ALI in rats were investigated. Male Sprague-Dawley rats were treated with apocynin (10mg/kg) intraperitoneally (i.p.) 1h before LPS injection (10mg/kg, i.p.). The results revealed that apocynin attenuated LPS-induced ALI as it decreased total protein content, lactate dehydrogenase (LDH) activity and the accumulation of the inflammatory cells in the bronchoalveolar lavage fluid (BALF), In addition, apocynin significantly increased superoxide dismutase (SOD) and reduced glutathione (GSH) activities with significant decrease in the lung malondialdehyde (MDA) content as compared to LPS group in lung tissue and decreased pulmonary artery contraction induced by LPS. It also upregulated mRNA expression of inhibitory protein kappaB-alpha (NF?Bia) and downregulated mRNA expression of Toll-Like receptor 4 (TLR4) and decreased inflammation observed in lung tissues. Collectively, these results demonstrate the protective effects of apocynin against the LPS-induced ALI in rats through its antioxidant and antiinflammatory effect that may be attributed to the decrease in mRNA expression of TLR4 and increasing that of NF?Bia. PMID:26687059

  13. 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

  14. 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

  15. [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

  16. Obstructive lung disease models: what is valid?

    PubMed

    Ferdinands, Jill M; Mannino, David M

    2008-12-01

    Use of disease simulation models has led to scrutiny of model methods and demand for evidence that models credibly simulate health outcomes. We sought to describe recent obstructive lung disease simulation models and their validation. Medline and EMBASE were used to identify obstructive lung disease simulation models published from January 2000 to June 2006. Publications were reviewed to assess model attributes and four types of validation: first-order (verification/debugging), second-order (comparison with studies used in model development), third-order (comparison with studies not used in model development), and predictive validity. Six asthma and seven chronic obstructive pulmonary disease models were identified. Seven (54%) models included second-order validation, typically by comparing observed outcomes to simulations of source study cohorts. Seven (54%) models included third-order validation, in which modeled outcomes were usually compared qualitatively for agreement with studies independent of the model. Validation endpoints included disease prevalence, exacerbation, and all-cause mortality. Validation was typically described as acceptable, despite near-universal absence of criteria for judging adequacy of validation. Although over half of recent obstructive lung disease simulation models report validation, inconsistencies in validation methods and lack of detailed reporting make assessing adequacy of validation difficult. For simulation modeling to be accepted as a tool for evaluating clinical and public health programs, models must be validated to credibly simulate health outcomes of interest. Defining the required level of validation and providing guidance for quantitative assessment and reporting of validation are important future steps in promoting simulation models as practical decision tools. PMID:19353353

  17. Neurtrophil degranulation in cadmium-chloride-induced acute lung inflammation.

    PubMed Central

    Yamada, H.; Damiano, V. V.; Tsang, A. L.; Meranze, D. R.; Glasgow, J.; Abrams, W. R.; Weinbaum, G.

    1982-01-01

    Lobar intrabronchial instillation of cadmium chloride (200 micrograms/ml) in saline causes a reproducible acute pulmonary inflammation in dogs. The influx of inflammatory neutrophils from the circulation into the alveolar spaces reaches a maximum approximately 16 hours after the cadmium chloride treatment in the treated lobe, while the controlateral lung appears normal. Morphometric quantitation of peroxidase-positive (azurophilic) granules in the inflammatory neutrophils shows a 74% loss of these granules, with little or no loss of the peroxidase-negative (specific) granules. These data are in good agreement with the measured loss of intracellular elastase, an enzyme known to be localized in the azurophilic granules. The results suggest that degranulation of azurophilic granules may occur selectively during this chemically induced acute inflammation. Images Figure 3 Figure 4 Figure 5 Figure 6 PMID:6923702

  18. Management of connective tissue disease-associated interstitial lung disease.

    PubMed

    Chartrand, Sandra; Fischer, Aryeh

    2015-05-01

    A thorough, often multidisciplinary assessment to determine extrathoracic versus intrathoracic disease activity and degrees of impairment is needed to optimize the management of connective tissue disease (CTD)-associated interstitial lung disease (ILD). Pharmacologic intervention with immunosuppression is the mainstay of therapy for all forms of CTD-ILD, but should be reserved for those that show clinically significant and/or progressive disease. The management of CTD-ILD is not yet evidence based and there is a need for controlled trials across the spectrum of CTD-ILD. Nonpharmacologic management strategies and addressing comorbidities or aggravating factors should be included in the comprehensive treatment plan for CTD-ILD. PMID:25836643

  19. Neuraminidase reprograms lung tissue and potentiates lipopolysaccharide-induced acute lung injury in mice.

    PubMed

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

    2013-11-01

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

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

    PubMed Central

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

    2013-01-01

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

  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. Apios americana Medik Extract Alleviates Lung Inflammation in Influenza Virus H1N1- and Endotoxin-Induced Acute Lung Injury.

    PubMed

    Sohn, Sung-Hwa; Lee, Sang-Yeon; Cui, Jun; Jang, Ho Hee; Kang, Tae-Hoon; Kim, Jong-Keun; Kim, In-Kyoung; Lee, Deuk-Ki; Choi, Seulgi; Yoon, Il-Sub; Chung, Ji-Woo; Nam, Jae-Hwan

    2015-12-28

    Apios americana Medik (hereinafter Apios) has been reported to treat diseases, including cancer, hypertension, obesity, and diabetes. The therapeutic effect of Apios is likely to be associated with its anti-inflammatory activity. This study was conducted to evaluate the protective effects of Apios in animal models of acute lung injury induced by lipopolysaccharide (LPS) or pandemic H1N1 2009 influenza A virus (H1N1). Mice were exposed to LPS or H1N1 for 2-4 days to induce acute lung injury. The treatment groups were administered Apios extracts via oral injection for 8 weeks before LPS treatment or H1N1 infection. To investigate the effects of Apios, we assessed the mice for in vivo effects of Apios on immune cell infiltration and the level of pro-inflammatory cytokines in the bronchoalveolar lavage (BAL) fluid, and histopathological changes in the lung. After induction of acute lung injury, the numbers of neutrophils and total cells were lower in the Apios-treated groups than in the non-Apios-treated LPS and H1N1 groups. The Apios groups tended to have lower levels of tumor necrosis factor-a and interleukin-6 in BAL fluid. In addition, the histopathological changes in the lungs were markedly reduced in the Apios-treated groups. These data suggest that Apios treatment reduces LPS- and H1N1-induced lung inflammation. These protective effects of Apios suggest that it may have therapeutic potential in acute lung injury. PMID:26323273

  5. 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

  6. Acute lung injury in preterm fetuses and neonates: mechanisms and molecular pathways.

    PubMed

    Iliodromiti, Zoe; Zygouris, Dimitrios; Sifakis, Stavros; Pappa, Kalliopi I; Tsikouras, Panagiotis; Salakos, Nikolaos; Daniilidis, Angelos; Siristatidis, Charalambos; Vrachnis, Nikolaos

    2013-11-01

    Acute lung injury (ALI) results in high morbidity and mortality among preterm neonates and efforts have therefore been devoted to both antenatal and postnatal prevention of the disease. ALI is the result of an inflammatory response which is triggered by a variety of different mechanisms. It mostly affects the fetal lung and, in particular, causes damage to the integrity of the lung's alveolar-capillary unit while weakening its cellular linings. Chemotactic activity and inflammatory products, such as proinflammatory cytokines TNF-?, IL-1, IL-6, IL-11, VEGF,TGF-? and TGF-?, provoke serious damage to the capillary endothelium and the alveolar epithelium, resulting in hyaline membrane formation and leakage of protein-rich edema fluid into the alveoli. Chorioamnionitis plays a major part in triggering fetal lung inflammation, while mechanical ventilation, the application of which is frequently necessary in preterm neonates, also causes ALI by inducing proinflammatory cytokines. Many different ventilation-strategies have been developed in order to reduce potential lung injury. Furthermore, tissue injury may occur as a result of injurious oxygen by-products (Reactive Oxygen Species, ROS), secondary to hyperoxia. Knowledge of the inflammatory pathways that connect intra-amniotic inflammation and ALI can lead to the formulation of novel interventional procedures. Future research should concentrate on the pathophysiology of ALI in preterm neonates and ?n possible pharmaceutical interventions targeting prevention and/or resolution of ALI. PMID:23611524

  7. Acute lung injury: what have we learned from animal models?

    PubMed

    Windsor, A C; Mullen, P G; Fowler, A A

    1993-08-01

    In 1950, Carl John Wiggers, philosopher and physiologist, wrote, "Reactions to definite types of stimulation may be observed or recorded, and concealed phenomena may be revealed by the use of apparatus that transforms them into forms that are recognizable by human senses. But complete understanding of physiological reactions often necessitates extensive operative procedures and sometimes the ultimate sacrifice of life. For this reason experimentation on animals is indispensable." Acute lung injury is still a significant cause of death in the developed world, and modern pharmacology and intensive care have failed to alter the clinical course of this complex condition. In the past decade, there was an explosion in understanding of the pathophysiology of acute lung injury, and with this has come the development of a new generation of agents that may provide a tool with which to combat this disorder. Use of animal model systems led to this greater understanding and is currently at the heart of evaluating the new therapeutic agents. This review briefly addresses the contribution animal model systems have made to what appear to be a watershed in attempts to obviate the effects of this mortal condition. PMID:8362891

  8. Diarrheal Diseases - Acute and Chronic

    MedlinePLUS

    ... to inflammatory bowel disease (IBD), which is ulcerative colitis or Crohn's disease. Other less common causes include ... and renal insufficiency, and albumin to assess your nutritional status. A stool sample may help define the type ...

  9. 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

  10. 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

  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-?), interleukin-1? (IL-1?), and interleukin-1 (IL-6) in the bronchoalveolar lavage fluid. Furthermore, ATG downregulated the expression of nuclear factor kappa B (NF-?B) p65, promoted the phosphorylation of inhibitor of nuclear factor-?B-? (I?B?) and activated the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK?) in the lung tissues. Our results suggested that ATG attenuates the LPS-induced ALI via activation of AMPK and suppression of NF-?B signaling pathway. PMID:25008149

  12. Escin attenuates acute lung injury induced by endotoxin in mice.

    PubMed

    Xin, Wenyu; Zhang, Leiming; Fan, Huaying; Jiang, Na; Wang, Tian; Fu, Fenghua

    2011-01-18

    Endotoxin causes multiple organ dysfunctions, including acute lung injury (ALI). The current therapeutic strategies for endotoxemia are designed to neutralize one or more of the inflammatory mediators. Accumulating experimental evidence suggests that escin exerts anti-inflammatory and anti-edematous effects. The aim of this study was to evaluate the effect of escin on ALI induced by endotoxin in mice. ALI was induced by injection of lipopolysaccharide (LPS) intravenously. The mice were given dexamethasone or escin before injection of LPS. The mortality rate was recorded. Tumor necrosis factor-? (TNF-?), interleukin 1? (IL-1?) and nitric oxide (NO) were measured. Pulmonary superoxide dismutase (SOD), glutathione peroxidase (GPx) activity, glutathione (GSH), malondialdehyde (MDA) contents, and myeloperoxidase (MPO) activity were also determined. The expression of glucocorticoid receptor (GR) level was detected by Western blotting. Pretreatment with escin could decrease the mortality rate, attenuate lung injury resulted from LPS, down-regulate the level of the inflammation mediators, including NO, TNF-?, and IL-1?, enhance the endogenous antioxidant capacity, and up-regulating the GR expression in lung. The results suggest that escin may have potent protective effect on the LPS-induced ALI by inhibiting of the inflammatory response, and its mechanism involves in up-regulating the GR and enhancing the endogenous antioxidant capacity. PMID:21040784

  13. Efferent vagal nerve stimulation attenuates acute lung injury following burn: The importance of the gut-lung axis

    PubMed Central

    Krzyzaniak, Michael J.; Peterson, Carrie Y.; Cheadle, Gerald; Loomis, William; Wolf, Paul; Kennedy, Vince; Putnam, James G.; Bansal, Vishal; Eliceiri, Brian; Baird, Andrew; Coimbra, Raul

    2014-01-01

    Background The purpose of this study was to assess acute lung injury when protection to the gut mucosal barrier offered by vagus nerve stimulation is eliminated by an abdominal vagotomy. Methods Male balb/c mice were subjected to 30% total body surface area steam burn with and without electrical stimulation to the right cervical vagus nerve. A cohort of animals were subjected to abdominal vagotomy. Lung histology, myeloperoxidase and ICAM-1 immune staining, myeloperoxidase enzymatic assay, and tissue KC levels were analyzed 24 hours after burn. Additionally, lung IkB-?, NF-kB immunoblots, and NF-kB-DNA binding measured by photon emission analysis using NF-kB-luc transgenic mice were performed. Results Six hours post burn, phosphorylation of both NF-kB p65 and IkB-? were observed. Increased photon emission signal was seen in the lungs of NF-kB-luc transgenic animals. Vagal nerve stimulation blunted NF-kB activation similar to sham animals whereas abdominal vagotomy eliminated the anti-inflammatory effect. After burn, MPO positive cells and ICAM-1 expression in the lung endothelium was increased, and lung histology demonstrated significant injury at 24 hours. Vagal nerve stimulation markedly decreased neutrophil infiltration as demonstrated by MPO immune staining and enzyme activity. Vagal stimulation also markedly attenuated acute lung injury at 24 hours. The protective effects of vagal nerve stimulation were reversed by performing an abdominal vagotomy. Conclusion Vagal nerve stimulation is an effective strategy to protect against acute lung injury following burn. Moreover, the protective effects of vagal nerve stimulation in the prevention of acute lung injury are eliminated by performing an abdominal vagotomy. These results establish the importance of the gut-lung axis after burn in the genesis of acute lung injury. PMID:21783215

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

    PubMed Central

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

    2010-01-01

    Family history (FH) of lung cancer is an established risk factor for lung cancer, but the modifying effect of smoking in relatives has been rarely examined. Also, the role of FH of non-malignant lung diseases on lung cancer risk is not well known. We examined the role of FH of cancer and FH of non-malignant lung diseases in lung cancer risk, overall, and by personal smoking, FH of smoking, and histology in 1,946 cases and 2,116 population-based controls within the Environment And Genetics in Lung cancer Etiology (EAGLE) study. Odds ratios (ORs) and 95% CI from logistic regression were calculated adjusting for age, gender, residence, education, and cigarette smoking. FH of lung cancer in any family member was associated with increased lung cancer risk (OR = 1.57, 95% CI = 1.251.98). The odds associated with fathers, mothers and siblings history of lung cancer were 1.41, 2.14, and 1.53, respectively. The associations were generally stronger in never smokers, younger subjects, and for the adenocarcinoma and squamous cell carcinoma subtypes. FH of chronic bronchitis and pneumonia were associated with increased (OR =1.49, 95% CI = 1.231.80) and decreased (OR = 0.73, 95% CI = 0.610.87) lung cancer risk, respectively. FH of lung cancer and FH of non-malignant lung diseases affected lung cancer risk independently, and did not appear to be modified by FH of smoking. PMID:19350630

  16. Genetic Susceptibility and Interstitial Lung Diseases

    PubMed Central

    Mathai, Susan K.; Schwartz, David A.; Warg, Laura A.

    2015-01-01

    Purpose of Review Recent genetic findings have identified new targets of investigation in the field of interstitial lung diseases and have the potential to change clinical care. Recent Findings These findings implicate abnormalities in (1) host defense, (2) cell-cell adhesion, and (3) aging and senescence in the pathophysiology of pulmonary fibrosis. At least one common genetic variant strongly associated with pulmonary fibrosis appears to have prognostic implications for patients. Summary The inherited risk for pulmonary fibrosis is substantial, and recent data suggests that genetic risk for familial and sporadic forms of the disease are similar. Further characterization of the genetic risk will influence clinical practice in terms of categorization, diagnosis, and screening of individuals for this disease. PMID:25022318

  17. 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

  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. 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

  20. [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

  1. Prognostic Factors for Myositis-Associated Interstitial Lung Disease

    PubMed Central

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

    2014-01-01

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

  2. 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

  3. 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

  4. 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

  5. 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

  6. [Chronic obstructive pulmonary disease--acute bacterial exacerbations].

    PubMed

    Kask, Viktor

    2004-04-01

    COPD (Chronic obstructive pulmonary disease) belongs to leading causes of morbidity and mortality worldwide and results in substantial and everincreasing medical, social and economic burden. The same applies to the Czech Republic as well. To combat the disease the Global Initiative for Obstructive Lung Disease (GOLD) has been founded in collaboration with the World Health Organization (WHO). GOLD guideline was published in April 2001 and its Czech version appeared in November 2001. The prevention and management of acute exacerbations of COPD forms one of the basic chapters of the document. A COPD exacerbation is defined as sustained worsening of the patient's condition compared to the stable state and beyond normal day-to-day variations that is acute in onset and may warrant additional treatment in a patient with known COPD. COPD exacerbations can be triggered by both an acute infection (viral or bacterial) and noninfectious cause (air pollution events, cold weather, interruption of regular treatment). Accurate diagnosis and assessment of the severity of COPD exacrbation, adequate therapy including rational application of antibiotics, accurate indication for hospitalization and timely admission to an intensive care unit decrease the COPD -associated mortality. PMID:15146384

  7. 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

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

    PubMed

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

    2015-05-01

    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

  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. Stem Cells and Regenerative Medicine in Lung Biology and Diseases

    PubMed Central

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

    2012-01-01

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

  12. Acute lung injury after allogeneic stem cell transplantation: from the clinic, to the bench and back again.

    PubMed

    Cooke, Kenneth R

    2005-12-01

    Allogeneic hematopoietic stem cell transplantation (SCT) is the only curative therapeutic option for a number of malignant and non-malignant conditions, but the success of this treatment strategy is limited by several side effects. Diffuse lung injury is a major complication of SCT that responds poorly to standard treatment and significantly contributes to transplant related morbidity and mortality. Lung injury occurs in both acute and chronic forms and can be either infectious or non-infectious in nature. Acute, non-infectious lung injury following SCT has been defined as idiopathic pneumonia syndrome (IPS). This review will outline the clinical spectrum, risk factors, and pathogeneses of IPS and discuss how current approaches to therapy are being influenced by insights generated using animal models of disease. PMID:16305615

  13. Hesperetin attenuates ventilator-induced acute lung injury through inhibition of NF-?B-mediated inflammation.

    PubMed

    Ma, Hongzhong; Feng, Xiaoli; Ding, Suchun

    2015-12-15

    Hesperetin, a major bioflavonoid in sweet oranges and lemons, has been reported to have anti-inflammatory properties. However, the effect of hesperetin on ventilator-induced acute lung injury has not been studied. In present study, we investigated the protective effect of hesperetin on ventilator-induced acute lung injury in rats. Rats were orally administered hesperetin (10, 20, or 40mg/kg) two hour before acute lung injury was induced by mechanical ventilation. Rats were then randomly divided into six groups: the lung protective ventilation group (n=20, LV group), injurious ventilation group (n=20, HV group), vehicle-treated injurious ventilation group (n=20, LV+vehicle group), hesperetin (10mg/kg)-treated acute lung injury group (n=20, HV+Hsp (10mg)), hesperetin (20mg/kg)-treated acute lung injury group (n=20, HV+Hsp (20mg)), and hesperetin (40mg/kg)-treated acute lung injury group (n=20, HV+Hsp (40mg)). The lung tissues and bronchoalveolar lavage fluid were isolated for subsequent measurements. Treatment with hesperetin dramatically improved the histology of lung tissue, and reduced the wet/dry ratio, myeloperoxidase activity, protein concentration, and production of tumor necrosis factor (TNF)-?, interleukin (IL)-6, IL-1?, and MIP-2 in the bronchoalveolar lavage fluid of rats with ventilator-induced acute lung injury. Additionally, our study indicated that this protective effect of hesperetin results from its ability to increase the expression of peroxisome proliferator-activated receptor (PPAR)-? and inhibit the activation of the nuclear factor (NF)-?B pathway. These results suggest that hesperetin may be a potential novel therapeutic candidate for protection against ventilator-induced acute lung injury. PMID:26610718

  14. 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

  15. 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

  16. First case of atypical takotsubo cardiomyopathy in a bilateral lung-transplanted patient due to acute respiratory failure.

    PubMed

    Ghadri, Jelena R; Bataisou, Roxana D; Diekmann, Johanna; Lscher, Thomas F; Templin, Christian

    2015-10-01

    Takotsubo cardiomyopathy which is characterised by a transient left ventricular wall motion abnormality was first described in 1990. The disease is still not well known, and as such it is suggested that an emotional trigger is mandatory in this disease. We present the case of a 51-year old female patient seven years after bilateral lung transplantation, who developed acute respiratory distress syndrome and subsequently suffered from atypical takotsubo cardiomyopathy with transient severe reduction of ejection fraction and haemodynamic instability needing acute intensive care treatment. Acute respiratory failure has emerged as an important physical trigger factor in takotsubo cardiomyopathy. Little is known about the association of hypoxia and takotsubo cardiomyopathy which can elicit a life-threatening condition requiring acute intensive care. Therefore, experimental studies are needed to investigate the role of hypoxia in takotsubo cardiomyopathy. PMID:24627332

  17. 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

  18. 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

  19. 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

  20. 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

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

    PubMed Central

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

    2014-01-01

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

  2. 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

  3. 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

  4. 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

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

    PubMed Central

    2013-01-01

    Over the past 30years 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

  6. 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

  7. 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)-?, interleukin (IL)-1? 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

  8. 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

  9. Genetics of acute lung injury: past, present and future.

    PubMed

    Flores, C; Pino-Yanes, M M; Casula, M; Villar, J

    2010-10-01

    Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are major health problems worldwide. Critical care physicians have long recognized that there are patients who progress poorly despite therapy while others do unexpectedly better than it might be predicted. It is now well accepted that these responses might be related to variations in the genome. However, little is known about the genes that are responsible for susceptibility and outcome in ALI and ARDS. The search for genetic variants determining susceptibility and predicting outcome is still a developing field. The identification of important associations between genotype and clinical outcomes will have an impact on the development of more efficient genotype- or phenotype-guided therapies for patients with ALI/ARDS. Using this point of view, we will discuss some of the advances in genetic association studies in relation to the occurrence and severity of ALI/ARDS. In addition, we will also discuss the strategic and medical implications of using genetic testing to detect or predict the occurrence and prognosis of ALI/ARDS. PMID:20935622

  10. Therapeutic targeting of acute lung injury and acute respiratory distress syndrome.

    PubMed

    Standiford, Theodore J; Ward, Peter A

    2016-01-01

    There is no Food and Drug Administration-approved treatment for acute respiratory distress syndrome (ARDS), in spite of the relatively large number of patients with the diagnosis. In this report, we provide an overview of preclinical studies and a description of completed and future clinical trials in humans with ARDS. Preclinical studies dealing with acute lung injury have suggested roles for complement and complement receptors, as well as the evolving role of histones, but details of these pathways are inadequately understood. Anti-inflammatory interventions have not been convincingly effective. Various cell growth factors are being considered for clinical study. Interventions to block complement activation or its products are under consideration. Stem cell therapies have shown efficacy in preclinical studies, which have motivated phase I/II trials in humans with ARDS. PMID:26003524

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

    PubMed Central

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

    2003-01-01

    Background Intravenous injection of contrast material is routinely performed in order to differentiate nonaerated lung parenchyma from pleural effusion in critically ill patients undergoing thoracic computed tomography (CT). The aim of the present study was to evaluate the effects of contrast material on CT measurement of lung volumes in 14 patients with acute lung injury. Method A spiral thoracic CT scan, consisting of contiguous axial sections of 10 mm thickness, was performed from the apex to the diaphragm at end-expiration both before and 30 s (group 1; n = 7) or 15 min (group 2; n = 7) after injection of 80 ml contrast material. Volumes of gas and tissue, and volumic distribution of CT attenuations were measured before and after injection using specially designed software (Lungview; Institut National des Tlcommunications, Evry, France). The maximal artifactual increase in lung tissue resulting from a hypothetical leakage within the lung of the 80 ml contrast material was calculated. Results Injection of contrast material significantly increased the apparent volume of lung tissue by 83 57 ml in group 1 and 102 80 ml in group 2, whereas the corresponding maximal artifactual increases in lung tissue were 42 52 ml and 31 18 ml. Conclusion Because systematic injection of contrast material increases the amount of extravascular lung water in patients with acute lung injury, it seems prudent to avoid this procedure in critically ill patients undergoing a thoracic CT scan and to reserve its use for specific indications. PMID:12617742

  12. 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

  13. 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

  14. [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

  15. 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

  16. Lung Disease Caused by Mycobacterium malmoense in an Immunocompetent Patient

    PubMed Central

    Jeon, Min Kyung; Yoon, Jung A; Kim, Junhwan; Yi, Sangyoung; Sung, Heungsup; Shim, Tae Sun

    2015-01-01

    Mycobacterium malmoense is a very rare cause of lung disease in South Korea. We reported the first case of lung disease caused by M. malmoense in an immunocompetent patient. The patient was successfully treated with a 14-month course of antibiotics. PMID:26175789

  17. 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...

  18. Clinical and biological heterogeneity in acute respiratory distress syndrome: direct versus indirect lung injury.

    PubMed

    Shaver, Ciara M; Bastarache, Julie A

    2014-12-01

    The acute respiratory distress syndrome (ARDS) is a heterogeneous group of illnesses affecting the pulmonary parenchyma with acute onset bilateral inflammatory pulmonary infiltrates with associated hypoxemia. ARDS occurs after 2 major types of pulmonary injury: direct lung injury affecting the lung epithelium or indirect lung injury disrupting the vascular endothelium. Greater understanding of the differences between direct and indirect lung injury may refine the classification of patients with ARDS and lead to development of new therapeutics targeted at specific subpopulations of patients with ARDS. PMID:25453415

  19. 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

  20. Aerosol Therapy for Obstructive Lung Diseases

    PubMed Central

    2011-01-01

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

  1. 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

  2. Keratinocyte growth factor-2 is protective in lipopolysaccharide-induced acute lung injury in rats.

    PubMed

    Tong, Lin; Bi, Jing; Zhu, Xiaodan; Wang, Guifang; Liu, Jie; Rong, Linyi; Wang, Qin; Xu, Nuo; Zhong, Ming; Zhu, Duming; Song, Yuanlin; Bai, Chunxue

    2014-09-15

    Keratinocyte growth factor-2 (KGF-2) plays a key role in lung development, but its role in acute lung injury has not been well characterized. Lipopolysaccharide instillation caused acute lung injury, which significantly elevated lung wet-to-dry weight ratio, protein and neutrophils in bronchoalveolar lavage fluid (BALF), inhibited surfactant protein A and C expression in lung tissue, and increased pathological injury. Pretreatment with KGF-2 improved the above lung injury parameters, partially restored surfactant protein A and C expression, and KGF-2 given 2-3 days before LPS challenge showed maximum lung injury improvement. Pretreatment with KGF-2 also markedly reduced the levels of TNF-?, MIP-2, IL-1? and IL-6 in BALF and the levels of IL-1? and IL-6 in lung tissue. Histological analysis showed there was increased proliferation of alveolar type II epithelial cells in lung parenchyma, which reached maximal 2 days after KGF-2 instillation. Intratracheal administration of KGF-2 attenuates lung injury induced by LPS, suggesting KGF-2 may be potent in the intervention of acute lung injury. PMID:24973472

  3. Acute chest syndrome in children with sickle cell disease.

    PubMed

    Srair, H A; Owa, J A; Aman, H A; Madan, M A

    1995-01-01

    Acute chest syndrome (ACS) is an acute pulmonic process in patients with sickle cell disease. We prospectively studied 50 patients with ACS admitted to the Pediatric Medical Ward during one year period (Jan. 1993 through Dec. 1993). Twenty eight of them were males and twenty two were females giving a male: female ratio of 1.2:1. The age ranged between one and 12 years. Twelve (24%) of the patients had chest pain on presentation. Twenty seven (54%) patients had significant temperature (> 38 degrees C). The x-ray findings showed that the right lung was involved in 30 patients, the left in 10 patients and both lungs in 10 patients. Three patients had pleural effusion that required chest tube insertion. Laboratory profiles showed that the erythrocyte sedimentation rate ranged between 15 and 90 mm/h, and their hemoglobin ranged between 4.2 gm and 12 gm/dl. Seven (14%) patients had significantly positive mycoplasma pneumoniae titer. None of the blood cultures was positive. All of our patient received antibiotic, usually either Cefuroxime or Ceftriaxone with Erythromycin in addition to other supportive measures such as blood transfusion, oxygen therapy and hydration therapy. PMID:10829868

  4. 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

  5. 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

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

    PubMed Central

    Tager, I B

    2000-01-01

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

  7. 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

  8. Lung disease with chronic obstruction in opium smokers in Singapore

    PubMed Central

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

    1971-01-01

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

  9. 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.

  10. 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

  11. Sensitivity of Lung Clearance Index and chest computed tomography in early CF lung disease.

    PubMed

    Ellemunter, Helmut; Fuchs, Susanne I; Unsinn, Karin M; Freund, Martin C; Waltner-Romen, Maria; Steinkamp, Gratiana; Gappa, Monika

    2010-12-01

    It is widely accepted that CF lung disease starts before clinical symptoms become apparent or spirometry deteriorates. Computed chest tomography (CT) is the reference method for identifying structural changes in CF; however, radiation exposure limits its use as a monitoring tool. It has been suggested that the Lung Clearance Index (LCI) measured by Multiple Breath Washout (MBW) for assessing ventilation inhomogeneity is a more sensitive surrogate marker than spirometry allowing non-invasive monitoring of CF lung disease. The aim of this study was to prospectively investigate the diagnostic accuracy of the LCI in comparison to CT in CF patients with early lung disease and normal FEV(1) (>80% pred.). MBW and ultra-low-dose CT were performed in 34 patients (6-26 years). LCI was abnormal in 76.5% subjects. LCI and CT correlated significantly in 82.3%. LCI was related to presence and extent of structural lung changes observed on CT with a sensitivity of 88%. Diagnostic accuracy of the LCI for detecting CF lung disease in patients with normal FEV(1) was good when compared to CT. Results indicate that structural changes are unlikely if a normal LCI is measured. We speculate that serial measurements of the LCI for assessing ventilation inhomogeneity may help to identify early structural lung disease and help to reduce the individual cumulative radiation dose. The LCI may be a suitable surrogate marker for monitoring progression of CF lung disease and effect of treatment in both, clinical care and research settings. PMID:20637585

  12. 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

  13. 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

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

    PubMed

    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

  15. CT appearance of acute radiation-induced injury in the lung

    SciTech Connect

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

    1988-04-01

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

  16. 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

  17. TREM-2 promotes macrophage survival and lung disease after respiratory viral infection

    PubMed Central

    Wu, Kangyun; Byers, Derek E.; Jin, Xiaohua; Agapov, Eugene; Alexander-Brett, Jennifer; Patel, Anand C.; Cella, Marina; Gilfilan, Susan; Colonna, Marco; Kober, Daniel L.; Brett, Tom J.

    2015-01-01

    Viral infections and type 2 immune responses are thought to be critical for the development of chronic respiratory disease, but the link between these events needs to be better defined. Here, we study a mouse model in which infection with a mouse parainfluenza virus known as Sendai virus (SeV) leads to long-term activation of innate immune cells that drive IL-13dependent lung disease. We find that chronic postviral disease (signified by formation of excess airway mucus and accumulation of M2-differentiating lung macrophages) requires macrophage expression of triggering receptor expressed on myeloid cells-2 (TREM-2). Analysis of mechanism shows that viral replication increases lung macrophage levels of intracellular and cell surface TREM-2, and this action prevents macrophage apoptosis that would otherwise occur during the acute illness (512 d after inoculation). However, the largest increases in TREM-2 levels are found as the soluble form (sTREM-2) long after clearance of infection (49 d after inoculation). At this time, IL-13 and the adapter protein DAP12 promote TREM-2 cleavage to sTREM-2 that is unexpectedly active in preventing macrophage apoptosis. The results thereby define an unprecedented mechanism for a feed-forward expansion of lung macrophages (with IL-13 production and consequent M2 differentiation) that further explains how acute infection leads to chronic inflammatory disease. PMID:25897174

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

    SciTech Connect

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

    1988-01-01

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

  19. 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

  20. Chronic or high dose acute caffeine treatment protects mice against oleic acid-induced acute lung injury via an adenosine A2A receptor-independent mechanism.

    PubMed

    Li, Jun; Li, Gongbo; Hu, Jian-Lin; Fu, Xiao-Hong; Zeng, Yi-Jun; Zhou, Yuan-Guo; Xiong, Gang; Yang, Nan; Dai, Shuang-Shuang; He, Feng-Tian

    2011-03-11

    The antagonism or genetic deletion of adenosine A(2A) receptors has been shown to exacerbate tissue damage in acute lung injury. Caffeine, a widely consumed behavioral drug, acts as a non-selective antagonist of A(2A) receptor and also has additional pharmacological effects. Thus, the protective vs. deleterious effects of caffeine in acute lung injury should be evaluated. In a murine oleic acid-induced model of acute lung injury, we found that chronic caffeine treatment by drinking water (0.1g/l or 0.25g/l for 2 weeks before acute lung injury) or acute caffeine treatment at high dose (i.p. 50mg/kg, injection, 30min before acute lung injury) significantly attenuated the lung edema, hemorrhage, neutrophil recruitment as well as the inflammatory cytokine tumor necrosis factor-? (TNF-?) and interleukin-1 (IL-1) expressions in both of the wild type (WT) and A(2A) receptor knockout (KO) mice. This profile was accompanied by increased cAMP levels and up-regulation of A2B receptor mRNAs in the lungs. In contrast, acute caffeine treatment at low dose (i.p. 5mg/kg or 15mg/kg, injection, 30min before acute lung injury) enhanced the inflammation and lung damage in WT mice with decreasing cAMP but not in A(2A) receptor KO mice. These results indicate that caffeine either enhances lung damage by antagonizing A(2A) receptor or exerts protection against lung damage via A(2A) receptor-independent mechanisms, depending on the timing of exposure (chronic vs. acute) and dose of administration (low vs. high). These findings provide new insight of caffeine in acute lung injury and highlight the potential benefit and strategy of caffeine intake or administration for preventing acute lung injury. PMID:21238452

  1. 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

  2. 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

  3. Fisetin Alleviates Lipopolysaccharide-Induced Acute Lung Injury via TLR4-Mediated NF-?B 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 4mg/kg, i.v.) 30min before LPS administration (5mg/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-?B in lung tissues. Our data indicates that fisetin has a protective effect against LPS-induced ALI via suppression of TLR4-mediated NF-?B signaling pathways, and fisetin may be a promising candidate for LPS-induced ALI treatment. PMID:26272311

  4. Increased elastin production in experimental granulomatous lung disease.

    PubMed Central

    Mariani, T. J.; Crouch, E.; Roby, J. D.; Starcher, B.; Pierce, R. A.

    1995-01-01

    In the normal, healthy lung, elastin production is restricted to periods of development and growth. However, elastin expression in the adult lung has been observed in some forms of pulmonary injury, including pulmonary fibrosis. Here, we report that elastin production is significantly increased within precise interstitial compartments of the lung in an experimental model of granulomatous lung disease. An increase in the number and volume of elastic fibers within the alveolar walls was apparent on histological examination of Verhoeff-van Gieson-stained sections of silicotic rat lungs. Quantitation of mature elastin cross-links indicated that silicosis was accompanied by a 17-fold increase in lung elastin content when compared with values from saline-treated controls. In situ hybridization for tropoelastin mRNA revealed that elastin production was absent from granulomatous lesions yet was prominent at nonfibrotic alveolar septal tips, where a high density of elastic fibers is seen in the normal lung. Immunohistochemistry indicated tropoelastin was being expressed by alpha-smooth muscle actin-containing cells. Transforming growth factor-beta was immunolocalized to granulomatous regions of the silicotic lung but was absent from regions showing increased tropoelastin expression. These data indicate that the reinitiation of tropoelastin gene expression is associated with granulomatous lung disease, and this expression leads to the aberrant accumulation of mature elastin in the lung. Images Figure 1 Figure 2 Figure 4 Figure 5 Figure 6 PMID:7573374

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

    PubMed Central

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

    2013-01-01

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

  6. 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

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

    PubMed Central

    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

  8. 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

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

    SciTech Connect

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

    1986-07-01

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

  10. 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

  11. [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

  12. Matrix metalloproteinases and protein tyrosine kinases: potential novel targets in acute lung injury and ARDS.

    PubMed

    Aschner, Yael; Zemans, Rachel L; Yamashita, Cory M; Downey, Gregory P

    2014-10-01

    Acute lung injury (ALI) and ARDS fall within a spectrum of pulmonary disease that is characterized by hypoxemia, noncardiogenic pulmonary edema, and dysregulated and excessive inflammation. While mortality rates have improved with the advent of specialized ICUs and lung protective mechanical ventilation strategies, few other therapies have proven effective in the management of ARDS, which remains a significant clinical problem. Further development of biomarkers of disease severity, response to therapy, and prognosis is urgently needed. Several novel pathways have been identified and studied with respect to the pathogenesis of ALI and ARDS that show promise in bridging some of these gaps. This review will focus on the roles of matrix metalloproteinases and protein tyrosine kinases in the pathobiology of ALI in humans, and in animal models and in vitro studies. These molecules can act independently, as well as coordinately, in a feed-forward manner via activation of tyrosine kinase-regulated pathways that are pivotal in the development of ARDS. Specific signaling events involving proteolytic processing by matrix metalloproteinases that contribute to ALI, including cytokine and chemokine activation and release, neutrophil recruitment, transmigration and activation, and disruption of the intact alveolar-capillary barrier, will be explored in the context of these novel molecular pathways. PMID:25287998

  13. 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.

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-10-01

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

  16. Sonic Hedgehog Signaling in the Lung. From Development to Disease

    PubMed Central

    Joyner, Alexandra L.; Loomis, Cynthia A.; Munger, John S.

    2015-01-01

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

  17. Emerging therapies for treatment of acute lung injury and acute respiratory distress syndrome.

    PubMed

    Bosma, Karen J; Lewis, James F

    2007-09-01

    Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a life-threatening form of respiratory failure that affects a heterogeneous population of critically ill patients. Although overall mortality appears to be decreasing in recent years due to improvements in supportive care, there are presently no proven, effective pharmacological therapies to treat ARDS and prevent its associated complications. The most common cause of death in ARDS is not hypoxemia or pulmonary failure, but rather multiple organ dysfunction syndrome (MODS), suggesting that improving survival in patients with ARDS may be linked to decreasing the incidence or severity of MODS. The key to developing novel treatments depends, in part, on identifying and understanding the mechanisms by which ARDS leads to MODS, although the heterogeneity and complexity of this disorder certainly poses a challenge to investigators. Novel therapies in development for treatment of ALI/ARDS include exogenous surfactant, therapies aimed at modulating neutrophil activity, such as prostaglandin and complement inhibitors, and treatments targeting earlier resolution of ARDS, such as beta-agonists and granulocyte macrophage colony-stimulating factor. From a clinical perspective, identifying subpopulations of patients most likely to benefit from a particular therapy and recognising the appropriate stage of illness in which to initiate treatment could potentially lead to better outcomes in the short term. PMID:17874973

  18. 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.

  19. Biomarkers of Rheumatoid ArthritisAssociated Interstitial Lung Disease

    PubMed Central

    Chen, Juan; Doyle, Tracy J.; Liu, Yongliang; Aggarwal, Rohit; Wang, Xiaoping; Shi, Yonghong; Ge, Sheng Xiang; Huang, Heqing; Lin, Qingyan; Liu, Wen; Cai, Yongjin; Koontz, Diane; Fuhrman, Carl R.; Golzarri, Maria F.; Liu, Yushi; Hatabu, Hiroto; Nishino, Mizuki; Araki, Tetsuro; Dellaripa, Paul F.; Oddis, Chester V.; Rosas, Ivan O.; Ascherman, Dana P.

    2015-01-01

    Objective Interstitial lung disease (ILD) is a relatively common extraarticular manifestation of rheumatoid arthritis (RA) that contributes significantly to disease burden and excess mortality. The purpose of this study was to identify peripheral blood markers of RA-associated ILD that can facilitate earlier diagnosis and provide insight regarding the pathogenesis of this potentially devastating disease complication. Methods Patients with RA who were enrolled in a well-characterized Chinese identification cohort or a US replication cohort were subclassified as having RAno ILD, RAmild ILD, or RAadvanced ILD, based on high-resolution computed tomography scans of the chest. Multiplex enzyme-linked immunosorbent assays (ELISAs) and Luminex xMAP technology were used to assess 36 cytokines/chemokines, matrix metalloproteinases (MMPs), and acute-phase proteins in the identification cohort. Unadjusted and adjusted logistic regression models were used to quantify the strength of association between RA-ILD and biomarkers of interest. Results MMP-7 and interferon-?inducible protein 10 (IP-10)/CXCL10 were identified by multiplex ELISA as potential biomarkers for RA-ILD in 133 RA patients comprising the Chinese identification cohort (50 RAno ILD, 41 RA-ILD, 42 RAindeterminate ILD). The findings were confirmed by standard solid-phase sandwich ELISA in the Chinese identification cohort as well as an independent cohort of US patients with RA and different stages of ILD (22 RAno ILD, 49 RA-ILD, 15 RAindeterminate ILD), with statistically significant associations in both unadjusted and adjusted logistic regression analyses. Conclusion Levels of MMP-7 and IP-10/CXCL10 are elevated in the serum of RA patients with ILD, whether mild or advanced, supporting their value as pathogenically relevant biomarkers that can contribute to noninvasive detection of this extraarticular disease complication. PMID:25302945

  20. 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

  1. Interstitial lung disease in children genetic background and associated phenotypes

    PubMed Central

    Hartl, Dominik; Griese, Matthias

    2005-01-01

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

  2. E-Cigarettes May Contain Chemicals Linked to Lung Disease

    MedlinePLUS

    ... nlm.nih.gov/medlineplus/news/fullstory_156113.html E-Cigarettes May Contain Chemicals Linked to Lung Disease Flavoring ... Health in Boston tested 51 types of flavored e-cigarettes and liquids. The investigators found that 47 (more ...

  3. Posttraumatic Stress Disorder in Survivors of Acute Lung Injury

    PubMed Central

    Williams, Jason B.; Yang, Andrew; Hopkins, Ramona O.; Needham, Dale M.

    2013-01-01

    Background: Survivors of acute lung injury (ALI) and other critical illnesses often experience substantial posttraumatic stress disorder (PTSD) symptoms. However, most questionnaires have not been validated against a PTSD diagnostic reference standard in this patient population. Hence, in the current study of survivors of ALI, we evaluated the Impact of Events Scale-Revised (IES-R), a questionnaire measure of PTSD symptoms, against the Clinician-Administered PTSD Scale (CAPS), the current state-of-the-art PTSD diagnostic reference standard, which also provides a quantitative assessment of PTSD symptoms. Methods: We evaluated the IES-R questionnaire vs the CAPS diagnostic interview in 60 of 77 consecutively recruited survivors of ALI from two prospective cohort studies of patients 1 to 5 years after ALI. Results: The IES-R total score (range: 0.0-3.2) and the CAPS total severity score (range: 0-70) were strongly related (Pearson r = 0.80, Spearman ? = 0.69). Using CAPS data, eight of the 60 patients (13%) had PTSD at the time of assessment, and an additional eight patients had partial PTSD (total prevalence, 27%). In a receiver operating characteristics curve analysis with CAPS PTSD or partial PTSD as criterion variables, the area under the curve ranged from 95% (95% CI, 88%-100%) to 97% (95% CI, 92%-100%). At an IES-R threshold of 1.6, with the same criterion variables, sensitivities ranged from 80% to 100%, specificities 85% to 91%, positive predictive values 50% to 75%, negative predictive values 93% to 100%, positive likelihood ratios 6.5 to 9.0, negative likelihood ratios 0.0 to 0.2, and efficiencies 87% to 90%. Conclusions: The IES-R appears to be an excellent brief PTSD symptom measure and screening tool in ALI survivors. PMID:23699588

  4. Lung cancer in Hodgkin's disease: association with previous radiotherapy

    SciTech Connect

    List, A.F.; Doll, D.C.; Greco, F.A.

    1985-02-01

    Seven cases of lung cancer were observed in patients with Hodgkin's disease (HD) since 1970. The risk ratio for the development of lung cancer among HD patients was 5.6 times that expected in the general population. The pertinent clinical data from these patients are described and compared to 28 additional patients reported from other institutions. Small-cell lung cancer represented the predominant histologic type of lung cancer encountered in both smoking and nonsmoking patients with HD, accounting for 42% of cases overall and greater than 55% of cases reported in reviews of second malignancies. Tobacco use was noted in only 53% of patients. Twenty-eight (94%) of 30 patients developing metachronous lung cancer received supradiaphragmatic irradiation as primary therapy for HD. Nineteen (68%) of these patients received subsequent chemotherapy salvage. The median age at diagnosis of HD and lung cancer was 39 and 45 years, respectively. The interval between diagnosis of HD and metachronous lung cancer averaged seven years but appeared to vary inversely with age. HD patients treated with supradiaphragmatic irradiation or combined modality therapy may be at increased risk for developing lung cancer. The high frequency of in-field malignancies that the authors observed and the prevalence of small-cell lung cancer in both smoking and nonsmoking patients suggests that chest irradiation may influence the development of metachronous lung cancer in these patients. The finding of a mean latent interval in excess of seven years emphasizes the need for close long-term observation.

  5. 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.

  6. 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

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

    PubMed

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

    2015-04-01

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

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

    PubMed

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

    2012-04-19

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

  9. Integrin ?3 Mutations with Kidney, Lung, and Skin Disease

    PubMed Central

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

  10. 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 IFN? and TNF? 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

  11. [The lung microbiome in 2015: a window on chronic lung diseases].

    PubMed

    Andrjak, Claire; Delhaes, Laurence

    2015-11-01

    Recent development of high-throughput sequencing methods has shown that the human respiratory tract (including lower airways) is not sterile as formerly thought, but composed of a previously unappreciated complex microbial community referred as the lung microbiome and composed of bacteria, viruses and fungi. However, many questions remain unresolved, especially in terms of lung microbiome role, its interactions with host but also with environmental pathogens. Although data are still limited, links have already been demonstrated between lung microbiome and chronic respiratory diseases (such as asthma, chronic obstructive pulmonary disease or cystic fibrosis). This lung microbiome appears to play an important role both in disease genesis and evolution, and consequently offers an emerging research field. PMID:26576604

  12. New insights into lung diseases using hyperpolarized gas MRI.

    PubMed

    Flors, L; Altes, T A; Mugler, J P; de Lange, E E; Miller, G W; Mata, J F; Ruset, I C; Hersman, F W

    2015-01-01

    Hyperpolarized (HP) gases are a new class of contrast agents that permit to obtain high temporal and spatial resolution magnetic resonance images (MRI) of the lung airspaces. HP gas MRI has become important research tool not only for morphological and functional evaluation of normal pulmonary physiology but also for regional quantification of pathologic changes occurring in several lung diseases. The purpose of this work is to provide an introduction to MRI using HP noble gases, describing both the basic principles of the technique and the new information about lung disease provided by clinical studies with this method. The applications of the technique in normal subjects, smoking related lung disease, asthma, and cystic fibrosis are reviewed. PMID:25747807

  13. [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

  14. 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

  15. 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

  16. 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.

  17. Heritability of Lung Disease Severity in Cystic Fibrosis

    PubMed Central

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

    2007-01-01

    Rationale: Obstructive lung disease, the major cause of mortality in cystic fibrosis (CF), is poorly correlated with mutations in the disease-causing gene, indicating that other factors determine severity of lung disease. Objectives: To quantify the contribution of modifier genes to variation in CF lung disease severity. Methods: Pulmonary function data from patients with CF living with their affected twin or sibling were converted into reference values based on both healthy and CF populations. The best measure of FEV1 within the last year was used for cross-sectional analysis. FEV1 measures collected over at least 4 years were used for longitudinal analysis. Genetic contribution to disease variation (i.e., heritability) was estimated in two ways: by comparing similarity of lung function in monozygous (MZ) twins (? 100% gene sharing) with that of dizygous (DZ) twins/siblings (? 50% gene sharing), and by comparing similarity of lung function measures for related siblings to similarity for all study subjects. Measurements and Main Results: Forty-seven MZ twin pairs, 10 DZ twin pairs, and 231 sibling pairs (of a total of 526 patients) with CF were studied. Correlations for all measures of lung function for MZ twins (0.820.91, p < 0.0001) were higher than for DZ twins and siblings (0.500.64, p < 0.001). Heritability estimates from both methods were consistent for each measure of lung function and ranged from 0.54 to 1.0. Heritability estimates generally increased after adjustment for differences in nutritional status (measured as body mass index z-score). Conclusions: Our heritability estimates indicate substantial genetic control of variation in CF lung disease severity, independent of CFTR genotype. PMID:17332481

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

    PubMed

    Ahrens, P; Weimer, B; Hofmann, D

    1999-07-01

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

  19. Wheezing, a significant clinical phenotype of COPD: experience from the Taiwan Obstructive Lung Disease Study

    PubMed Central

    Huang, Wan-Chun; Tsai, Ying-Huang; Wei, Yu-Feng; Kuo, Ping-Hung; Tao, Chi-Wei; Cheng, Shih-Lung; Lee, Chao-Hsien; Wu, Yao-Kuang; Chen, Ning-Hung; Hsu, Wu-Huei; Hsu, Jeng-Yuan; Wang, Chin-Chou; Lin, Ming-Shian

    2015-01-01

    Background COPD is an important public health challenge with significant heterogeneity of clinical presentation and disease progression. Clinicians have been trying to find phenotypes that may be linked to distinct prognoses and different therapeutic choices. Not all patients with COPD present with wheezing, a possible clinical phenotype that can help differentiate patient subgroups. Methods The Taiwan Obstructive Lung Disease study was a retrospective, multicenter research study to investigate the treatment patterns of COPD after the implementation of the Global Initiative for Chronic Obstructive Lung Disease 2011 guidelines. Between November 2012 and August 2013, medical records were retrieved from patients with COPD aged ?40 years; patients diagnosed with asthma were excluded. Demographic data, lung function, symptom scores, and acute exacerbation were recorded and analyzed, and the differences between patients with and without wheezing were evaluated. Results Of the 1,096 patients with COPD, 424 (38.7%) had the wheezing phenotype. The wheezing group had significantly higher COPD Assessment Test scores (12.47.8 versus 10.56.7, P<0.001), higher modified Medical Research Council grade (2.01.0 versus 1.70.9, P<0.001), and more acute exacerbations within the past year (0.91.3 versus 0.40.9, P<0.001) than the nonwheezing group. The postbronchodilator forced expiratory volume in 1 second was lower in wheezing patients (1.20.5 L versus 1.50.6 L, P<0.001). Even in patients with maintenance treatment fitting the Global Initiative for Chronic Obstructive Lung Disease 2011 guidelines, the wheezing group still had worse symptom scores and more exacerbations. Conclusion Wheezing is an important phenotype in patients with COPD. Patients with COPD having the wheezing phenotype are associated with worse symptoms, more exacerbations, and worse lung function. PMID:26504377

  20. 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

  1. 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

  2. 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

  3. 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 ?g) 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-1? and -1?, vascular permeability, and phosphorylated p38 MAPK between LPS-treated WT and Lsp1(-/-) mice, whereas TNF-? 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

  4. Lung sonography and recruitment in patients with early acute respiratory distress syndrome: A pilot study

    PubMed Central

    2011-01-01

    Introduction Bedside lung sonography is a useful imaging tool to assess lung aeration in critically ill patients. The purpose of this study was to evaluate the role of lung sonography in estimating the nonaerated area changes in the dependent lung regions during a positive end-expiratory pressure (PEEP) trial of patients with early acute respiratory distress syndrome (ARDS). Methods Ten patients (mean standard deviation (SD): age 64 7 years, Acute Physiology and Chronic Health Evaluation II (APACHE II) score 21 4) with early ARDS on mechanical ventilation were included in the study. Transthoracic sonography was performed in all patients to depict the nonaerated area in the dependent lung regions at different PEEP settings of 5, 10 and 15 cm H2O. Lung sonographic assessment of the nonaerated lung area and arterial blood gas analysis were performed simultaneously at the end of each period. A control group of five early ARDS patients matched for APACHE II score was also included in the study. Results The nonaerated areas in the dependent lung regions were significantly reduced during PEEP increases from 5 to 10 to 15 cm H2O (27 31 cm2 to 20 24 cm2 to 11 12 cm2, respectively; P < 0.01). These changes were associated with a significant increase in arterial oxygen partial pressure (74 15 mmHg to 90 19 mmHg to 102 26 mmHg; P < 0.001, respectively). No significant changes were observed in the nonaerated areas in the dependent lung regions in the control group. Conclusions In this study, we show that transthoracic lung sonography can detect the nonaerated lung area changes during a PEEP trial of patients with early ARDS. Thus, transthoracic lung sonography might be considered as a useful clinical tool in the management of ARDS patients. PMID:21816054

  5. Roles of CEACAM1 in cell communication and signaling of lung cancer and other diseases.

    PubMed

    Ling, Ye; Wang, Jian; Wang, Lingyan; Hou, Jiayun; Qian, Peiyu; Xiang-dong, Wang

    2015-06-01

    Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a broadly-expressed immunoglobulin-like cell adhesion molecule with a wide range of biological functions to regulate cell signaling. The present article mainly focuses on the role of CEACAM1 as a therapeutic target in lung diseases and discusses the potential of therapeutic strategies targeting CEACAM1. The article overviews the structure and its sub-types, biological function, and potential roles of CEACAM1 in lung diseases. Alterations of CEACAM1 expression and CEACAM1-S/CEACAM1-L ratio promote the growth and metastasis of non-small cell lung carcinoma (NSCLC). Moreover, CEACAM1 mediates bacterial adherence and transcellular transcytosis, resulting in the suppression of immune cell activities and inflammatory responses, which may trigger acute exacerbation of chronic obstructive pulmonary disease (AECOPD). CEACAM1 plays a critical role in the development of NSCLC and AECOPD and can be a diagnostic biomarker and therapeutic target in lung diseases. PMID:26081722

  6. 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

  7. 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

  8. 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.

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

    PubMed

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

    2012-05-01

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

  10. 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

  11. Acute diarrhoeal disease in less developed countries

    PubMed Central

    Gordon, John E.; Bhar, Moiss; Scrimshaw, Nevin S.

    1964-01-01

    The programme presented in this article for controlling the diarrhoeas and dysenteries of less developed countries is based on epidemiological principles applicable to acute undifferentiated diarrhoeal diseaseits specific as well as its non-specific elements. The dominant importance of weanling diarrhoea requires a main emphasis on maternal and child health procedures, with nutrition singled out for attention, along with public health education and medical care of patients: this in addition to the established worth of means for promoting environmental sanitation. The several features of the suggested programme are within four broad divisions: preventive measures; control of patients, contacts and the immediate environment; measures specifically useful in epidemics; and international measures conducive to broad restriction of the syndrome. PMID:14230891

  12. 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

  13. 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

  14. Divers' lung function: small airways disease?

    PubMed Central

    Thorsen, E; Segadal, K; Kambestad, B; Gulsvik, A

    1990-01-01

    Pulmonary function was measured in 152 professional saturation divers and in a matched control group of 106 subjects. Static lung volumes, dynamic lung volumes and flows, transfer factor for carbon monoxide (T1CO), transfer volume per unit alveolar volume (KCO), delta-N2, and closing volume (CV) were measured and compared with reference values from recent Scandinavian studies, British submariners, and the European Community for Coal and Steel (ECCS) recommended reference values. Diving exposure was assessed as years of diving experience, total number of days in saturation and depth, and as the product of days in saturation and mean depth. Divers had significantly lower values for forced expired volume in one second (FEV1), FEV1/forced vital capacity (FVC) ratio, FEF25-75%, FEF75-85%, FEF50%, FEF75%, T1CO, and KCO compared with the controls and a significantly higher CV. There was a positive correlation between diving exposure and CV, whereas the other variables had negative correlations with diving exposure. Values for the control group were not different from the predictive values of Scandinavian reference studies or British submariners, although the ECCS standard predicted significantly lower values for the lung function variables both in divers and the control group. The pattern of the differences in lung function variables between the divers and controls is consistent with small airways dysfunction and with the transient changes in lung function found immediately after a single saturation dive. The association between reduced pulmonary function and previous diving exposure further indicates the presence of cumulative long term effects of diving on pulmonary function. PMID:2393630

  15. Human CD56+ Cytotoxic Lung Lymphocytes Kill Autologous Lung Cells in Chronic Obstructive Pulmonary Disease

    PubMed Central

    Freeman, Christine M.; Stolberg, Valerie R.; Crudgington, Sean; Martinez, Fernando J.; Han, MeiLan K.; Chensue, Stephen W.; Arenberg, Douglas A.; Meldrum, Catherine A.; McCloskey, Lisa; Curtis, Jeffrey L.

    2014-01-01

    CD56+ natural killer (NK) and CD56+ T cells, from sputum or bronchoalveolar lavage of subjects with chronic obstructive pulmonary disease (COPD) are more cytotoxic to highly susceptible NK targets than those from control subjects. Whether the same is true in lung parenchyma, and if NK activity actually contributes to emphysema progression are unknown. To address these questions, we performed two types of experiments on lung tissue from clinically-indicated resections (n?=?60). First, we used flow cytometry on fresh single-cell suspension to measure expression of cell-surface molecules (CD56, CD16, CD8, NKG2D and NKp44) on lung lymphocytes and of the 6D4 epitope common to MICA and MICB on lung epithelial (CD326+) cells. Second, we sequentially isolated CD56+, CD8+ and CD4+ lung lymphocytes, co-cultured each with autologous lung target cells, then determined apoptosis of individual target cells using Annexin-V and 7-AAD staining. Lung NK cells (CD56+ CD3?) and CD56+ T cells (CD56+ CD3+) were present in a range of frequencies that did not differ significantly between smokers without COPD and subjects with COPD. Lung NK cells had a predominantly cytotoxic CD56+ CD16+ phenotype; their co-expression of CD8 was common, but the percentage expressing CD8 fell as FEV1 % predicted decreased. Greater expression by autologous lung epithelial cells of the NKG2D ligands, MICA/MICB, but not expression by lung CD56+ cells of the activating receptor NKG2D, correlated inversely with FEV1 % predicted. Lung CD56+ lymphocytes, but not CD4+ or CD8+ conventional lung T cells, rapidly killed autologous lung cells without additional stimulation. Such natural cytotoxicity was increased in subjects with severe COPD and was unexplained in multiple regression analysis by age or cancer as indication for surgery. These data show that as spirometry worsens in COPD, CD56+ lung lymphocytes exhibit spontaneous cytotoxicity of autologous structural lung cells, supporting their potential role in emphysema progression. Trial Registration ClinicalTrials.gov NCT00281229 PMID:25078269

  16. 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 (19801988). 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

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

    PubMed

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

    2000-09-01

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

  18. 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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-03-01

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

  1. Relevance of Lung Ultrasound in the Diagnosis of Acute Respiratory Failure*

    PubMed Central

    Mezire, Gilbert A.

    2008-01-01

    Background: This study assesses the potential of lung ultrasonography to diagnose acute respiratory failure. Methods: This observational study was conducted in university-affiliated teaching-hospital ICUs. We performed ultrasonography on consecutive patients admitted to the ICU with acute respiratory failure, comparing lung ultrasonography results on initial presentation with the final diagnosis by the ICU team. Uncertain diagnoses and rare causes (frequency < 2%) were excluded.Weincluded 260 dyspneic patients with a definite diagnosis. Three items were assessed: artifacts (horizontal A lines or vertical B lines indicating interstitial syndrome), lung sliding, and alveolar consolidation and/or pleural effusion. Combined with venous analysis, these items were grouped to assess ultrasound profiles. Results: Predominant A lines plus lung sliding indicated asthma (n = 34) or COPD (n = 49) with 89% sensitivity and 97% specificity. Multiple anterior diffuse B lines with lung sliding indicated pulmonary edema (n = 64) with 97% sensitivity and 95% specificity. A normal anterior profile plus deep venous thrombosis indicated pulmonary embolism (n = 21) with 81% sensitivity and 99% specificity. Anterior absent lung sliding plus A lines plus lung point indicated pneumothorax (n = 9) with 81% sensitivity and 100% specificity. Anterior alveolar consolidations, anterior diffuse B lines with abolished lung sliding, anterior asymmetric interstitial patterns, posterior consolidations or effusions without anterior diffuse B lines indicated pneumonia (n = 83) with 89% sensitivity and 94% specificity. The use of these profiles would have provided correct diagnoses in 90.5% of cases. Conclusions: Lung ultrasound can help the clinician make a rapid diagnosis in patients with acute respiratory failure, thus meeting the priority objective of saving time. PMID:18403664

  2. Acute cholangitis due to pancreatic metastasis from squamous cell lung carcinoma: a case report and review of literature

    PubMed Central

    2009-01-01

    Introduction The pancreas is a well-documented but relatively uncommon site of non-small-cell cancer metastases. However, at the time of diagnosis the disease is usually locoregionally advanced, therefore therapeutic management is mostly palliative and symptomatic. Case Presentation We report the case of a 77-year-old Caucasian male patient who presented initially with a clinical picture of acute cholangitis approximately 2 years after a left lower lobectomy for a low-grade squamous lung carcinoma. CT scan imaging of the abdomen and chest revealed an abnormal growth of the pancreatic head and distention of both the intra- and extra-hepatic billiary tree, whereas osteolytic abnormalities were observed of the 5th left rib, consistent with secondary deposits. Initially an endoscopic retrograde cholangio-pancreatography (ERCP) and sphincterectomy was performed and a plastic stent was placed in the common bile duct to decompress the biliary tree. Cytological examination of the aspirate collected by FNA of the pancreatic lession under EUS guidance revealed cells consistent with a low grade squamous lung carcinoma. Two months later an open cholecystectomy along with a gastrojejunostomy was performed to relieve the patient's gastric outlet obstruction symptoms. Following remission of the patient's attack of acute cholangitis and excessive vomiting he was released from the hospital and instructed to initiate chemotherapy with vinorelbine. The patient succumbed to disseminated disease almost 5 months later. Conclusion Symptomatic metastatic lesions of the pancreas from squamous cell carcinoma of the lung are infrequent. Typically, the patients remain asymptomatic until their disease reaches a fairly advanced stage and therapeutic options are limited to palliative measures. A high index of suspicion is the only way of early detection and potentially effective treatment for this rare localization of metastatic squamous lung carcinoma. PMID:20062690

  3. 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.

  4. A decremental PEEP trial for determining open-lung PEEP in a rabbit model of acute lung injury.

    PubMed

    Hua, Yi-Ming; Lien, Shao-Hung; Liu, Tao-Yuan; Lee, Chuen-Ming; Yuh, Yeong-Seng

    2008-04-01

    A positive end-expiratory pressure (PEEP) above the lower inflection point (LIP) of the pressure-volume curve has been thought necessary to maintain recruited lung volume in acute lung injury (ALI). We used a strategy to identify the level of open-lung PEEP (OLP) by detecting the maximum tidal compliance during a decremental PEEP trial (DPT). We performed a randomized controlled study to compare the effect of the OLP to PEEP above LIP and zero PEEP on pulmonary mechanics, gas exchange, hemodynamic change, and lung injury in 26 rabbits with ALI. After recruitment maneuver, the lavage-injured rabbits received DPTs to identify the OLP. Animals were randomized to receive volume controlled ventilation with either: (a) PEEP = 0 cm H2O (ZEEP); (b) PEEP = 2 cm H2O above OLP (OLP + 2); or (c) PEEP = 2 cm H2O above LIP (LIP + 2). Peak inspiratory pressure and mean airway pressure were recorded and arterial blood gases were analyzed every 30 min. Mean blood pressure and heart rate were monitored continuously. Lung injury severity was assessed by lung wet/dry weight ratio. Animals in OLP + 2 group had less lung injury as well as relatively better compliance, more stable pH, and less hypercapnia compared to the LIP + 2 and ZEEP groups. We concluded that setting PEEP according to the OLP identified by DPTs is an effective method to attenuate lung injury. This strategy could be used as an indicator for optimal PEEP. The approach is simple and noninvasive and may be of clinical interest. PMID:18293413

  5. 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

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

    PubMed Central

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

    2014-01-01

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

  7. 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.

  8. 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

  9. 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 declinesnot 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 individuals 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

  10. 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

  11. Lung injury in mice and rats acutely exposed to beryllium

    SciTech Connect

    Sendelbach, L.E. Jr.

    1985-01-01

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

  12. Nanotechnology approaches for inhalation treatment of lung diseases.

    PubMed

    Kuzmov, Andriy; Minko, Tamara

    2015-12-10

    Local administration of therapeutics by inhalation for treatment of lung diseases has the ability to deliver drugs, nucleic acids and peptides specifically to the site of their action and therefore enhance the efficacy of the treatment, limit the penetration of nebulized therapeutic agent(s) into the bloodstream and consequently decrease adverse systemic side effects of the treatment. Nanotechnology allows for a further enhancement of the treatment efficiency. The present review analyzes modern therapeutic approaches of inhaled nanoscale-based pharmaceutics for the detection and treatment of various lung diseases. PMID:26297206

  13. 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

  14. Nutritional state and lung disease in cystic fibrosis.

    PubMed

    Bakker, W

    1992-10-01

    The life expectancy of patients with cystic fibrosis (CF) is largely dependent on the severity and progress of the pulmonary involvement associated with the disease. Many data support the view that malnutrition and deterioration of lung function are closely interrelated and interdependent, with each affecting the other, leading to a spiral decline in both. The occurrence of malnutrition appears to be associated with poor lung function and poor survival, and conversely prevention of malnutrition appears to be associated with better lung function and improved survival. Nutritional intervention may lead to an improvement in body weight, lung function and exercise tolerance, provided that the intervention is combined with exercise training in order to increase both respiratory and other muscle mass. These improvements can be preserved when patients have the stamina to continue with a high-energy, high-fat diet and daily exercise training at home. PMID:1470283

  15. 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

  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. 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

  18. Update on scleroderma-associated interstitial lung disease

    PubMed Central

    Fan, Ming-Hui; Feghali-Bostwick, Carol A.; Silver, Richard M.

    2015-01-01

    Systemic sclerosis (SSc), or scleroderma, is a heterogeneous and complex autoimmune disease characterized by varying degrees of skin and organ fibrosis and obliterative vasculopathy. The disease results in significant morbidity and mortality and to date available treatments are limited. Lung involvement is currently the leading cause of death of patients with SSc. Over the past year, significant advances have been made in our understanding of SSc-associated lung disease and this review attempts to encapsulate these most recent findings and place them in context. We divide our discussion of the most recent literature into 1) clinical aspects of SSc lung management, including classification, imaging, biomarkers, and treatment; 2) promising new animal models that may improve our ability to accurately study this disease; and 3) studies that advance or change our understanding of lung disease pathogenesis, thereby raising the potential for new targets for therapeutic intervention. The goal of this review is to highlight and summarize the most significant studies of the past year and to bring clinicians and researchers alike in the field up to date. PMID:25191993

  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. 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 ...

  1. Lung Protective Ventilation (ARDSNet) versus APRV: Ventilatory Management in a Combined Model of Acute Lung and Brain Injury

    PubMed Central

    Davies, Stephen W.; Leonard, Kenji L.; Falls, Randall K.; Mageau, Ronald P.; Efird, Jimmy T.; Hollowell, Joseph P.; Trainor, Wayne E.; Kanaan, Hilal A.; Hickner, Robert C.; Sawyer, Robert G.; Poulin, Nathaniel R.; Waibel, Brett H.; Toschlog, Eric A.

    2014-01-01

    Background Concomitant lung/brain traumatic injury, results in significant morbidity and mortality. Lung protective ventilation (ARDSNet) has become the standard for managing acute respiratory distress syndrome (ARDS); however, the resulting permissive hypercapnea may compound traumatic brain injury (TBI). Airway pressure release ventilation (APRV) offers an alternative strategy for management of this patient population. APRV was hypothesized to retard the progression of acute lung/brain injury to a greater degree than ARDSNet in a swine model. Methods Yorkshire swine were randomized to ARDSNet, APRV, or sham. Ventilatory settings and pulmonary parameters, vitals, blood gases, quantitative histopathology, and cerebral microdialysis were compared between groups using chi-square, Fishers exact, Students t-test, Wilcoxon rank-sum, and mixed effects repeated measures modeling. Results 22 swine (17 male, 5 female), weighing 256.0kg, were randomized to APRV (n=9), ARDSNet (n=12), or sham (n=1). PaO2/FiO2 (P/F) ratio dropped significantly while intracranial pressure increased significantly for all three groups immediately following lung and brain injury. Over time, peak inspiratory pressure, mean airway pressure, and P/F ratio significantly increased, while total respiratory rate significantly decreased within the APRV group compared to the ARDSNet group. Histopathology did not show significant differences between groups in overall brain or lung tissue injury; however, cerebral microdialysis trends suggested increased ischemia within the APRV group compared to ARDSNet over time. Conclusion Previous studies have not evaluated the effects of APRV in this population. While our macroscopic parameters and histopathology did not observe a significant difference between groups, microdialysis data suggest a trend toward increased cerebral ischemia associated with APRV over time. Additional and future studies should focus on extending the time interval for observation to further delineate differences between groups. Level of Evidence II Study Type Therapeutic PMID:25757107

  2. [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

  3. 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.

  4. The effect of fibreoptic bronchoscopy in acute respiratory distress syndrome: experimental evidence from a lung model.

    PubMed

    Nay, M-A; Mankikian, J; Auvet, A; Dequin, P-F; Guillon, A

    2016-02-01

    Flexible bronchoscopy is essential for appropriate care during mechanical ventilation, but can significantly affect mechanical ventilation of the lungs, particularly for patients with acute respiratory distress syndrome. We aimed to describe the consequences of bronchoscopy during lung-protective ventilation in a bench study, and thereby to determine the optimal diameter of the bronchoscope for avoiding disruption of the protective-ventilation strategy during the procedure. Immediately following the insertion of the bronchoscope into the tracheal tube, either minute ventilation decreased significantly, or positive end-expiratory pressure increased substantially, according to the setting of the inspiratory pressure limit. The increase in end-expiratory pressure led to an equivalent increase in the plateau pressure, and lung-protective ventilation was significantly altered during the procedure. We showed that a bronchoscope with an external diameter of 4mm (or less) would allow safer bronchoscopic interventions in patients with severe acute respiratory distress syndrome. PMID:26559154

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

    PubMed Central

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

    2012-01-01

    Local or systemic inflammation can result in acute lung injury (ALI), and is associated with capillary leakage, reduced lung compliance, and hypoxemia. Curcumin, a plant-derived polyphenolic compound, exhibits potent anti-inflammatory properties, but its poor solubility and limited oral bioavailability reduce its therapeutic potential. A novel curcumin formulation (CDC) was developed by complexing the compound with hydroxypropyl-?-cyclodextrin (CD). This results in greatly enhanced water solubility and stability that facilitate direct pulmonary delivery. In vitro studies demonstrated that CDC increased curcumins association with and transport across Calu-3 human airway epithelial cell monolayers, compared with uncomplexed curcumin solubilized using DMSO or ethanol. Importantly, Calu-3 cell monolayer integrity was preserved after CDC exposure, whereas it was disrupted by equivalent uncomplexed curcumin solutions. We then tested whether direct delivery of CDC to the lung would reduce severity of ALI in a murine model. Fluorescence microscopic examination revealed an association of curcumin with cells throughout the lung. The administration of CDC after LPS attenuated multiple markers of inflammation and injury, including pulmonary edema and neutrophils in bronchoalveolar lavage fluid and lung tissue. CDC also reduced oxidant stress in the lungs and activation of the proinflammatory transcription factor NF-?B. These results demonstrate the efficacy of CDC in a murine model of lung inflammation and injury, and support the feasibility of developing a lung-targeted, curcumin-based therapy for the treatment of patients with ALI. PMID:22312018

  6. 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.

  7. Metastasis-Induced Acute Pancreatitis Successfully Treated with Chemotherapy and Radiotherapy in a Patient with Small Cell Lung Cancer

    PubMed Central

    Okutur, Kerem; Bozkurt, Mustafa; Korkmaz, Taner; Karaaslan, Ercan; Guner, Levent; Goksel, Suha; Demir, Gokhan

    2015-01-01

    Although involvement of pancreas is a common finding in small cell lung cancer (SCLC), metastasis-induced acute pancreatitis (MIAP) is very rare. A 50-year-old female with SCLC who had limited disease and achieved full response after treatment presented with acute pancreatitis during her follow-up. The radiologic studies revealed a small area causing obliteration of the pancreatic duct without mass in the pancreatic neck, and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) confirmed the metastasis of SCLC. The patient was treated successfully with systemic chemotherapy and radiotherapy delivered to pancreatic field. In SCLC, cases of MIAP can be encountered with conventional computed tomography with no mass image, and positron emission tomography and EUS-FNA can be useful for diagnosis of such cases. Aggressive systemic and local treatment can prolong survival, especially in patients with good performance status. PMID:26075124

  8. 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

  9. 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

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

    PubMed Central

    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-?B 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-? level in both serum and BALF of the rats. Furthermore, RAGE antibody or bortezomib significantly reduced LPS-induced upregulation of RAGE and NF-?B expression in the lung. In conclusion, we established ALI model in neonate rats to demonstrate that LPS induced inflammatory lung injury via RAGE/NF-?B signaling. Interference with RAGE/NF-?B signaling is a potential approach to prevent and treat sepsis-related ALI/ARDS. PMID:26550268

  11. 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 Ss; Kyjovska, Zdenka O; Halappanavar, Sabina; Yauk, Carole L; Wallin, Hkan; 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, 6:517531. doi: 10.1002/wnan.1279 PMID:24920450

  12. Cryoglobulins in acute and chronic liver diseases

    PubMed Central

    Florin-Christensen, A.; Roux, Mara E. B.; Arana, R. M.

    1974-01-01

    Cryoglobulins were detected in the sera of thirteen patients with acute viral hepatitis and of twelve with chronic hepatic diseases (active chronic hepatitis, primary biliary cirrhosis and cryptogenic cirrhosis). Their nature and antibody activity was studied. In both groups, most of them consisted of mixed cryoimmunoglobulins (IgM, IgG and/or IgA), but some were single-class immunoglobulins with one or both types of light chains. Unusual components were also found. ?1-fetoprotein was present in four cryoprecipitates: in two as the single constituent and in two associated to immunoglobulins; hepatitis-associated antigen co-existed in one of the latter. Some cryoglobulins showed antibody activity against human IgG, smooth muscle and mitochondrial antigens. In one case, the IgM-kappa of the cryoprecipitate had antibody activity against ?1-fetoprotein; this antigen was also present in the cryoprecipitate, suggesting immune-complex formation. Autoantibodies were also looked for in the sera of the twenty-five patients; apart from the most common ones, antibodies to ?1-fetoprotein were found in two patients. PMID:4143195

  13. Fitness to fly in patients with lung disease.

    PubMed

    Nicholson, Trevor T; Sznajder, Jacob I

    2014-12-01

    Patients with chronic lung disease may have mild hypoxemia at sea level. Some of these cases may go unrecognized, and even among those who are known to be hypoxemic, some do not use supplemental oxygen. During air travel in a hypobaric hypoxic environment, compensatory pulmonary mechanisms may be inadequate in patients with lung disease despite normal sea-level oxygen requirements. In addition, compensatory cardiovascular mechanisms may be less effective in some patients who are unable to increase cardiac output. Air travel also presents an increased risk of venous thromboembolism. Patients with cystic lung disease may also be at increased risk of pneumothorax. Although overall this risk appears to be relatively low, should a pneumothorax occur, it could present a significant challenge to the patient with chronic lung disease, particularly if hypoxemia is already present. As such, a thorough assessment of patients with chronic lung disease and cardiac disease who are contemplating air travel should be performed. The duration of the planned flight, the anticipated levels of activity, comorbid illnesses, and the presence of risk factors for venous thromboembolism are important considerations. Hypobaric hypoxic challenge testing reproduces an environment most similar to that encountered during actual air travel; however, it is not widely available. Assessment for hypoxia is otherwise best performed using a normobaric hypoxic challenge test. Patients in need of supplemental oxygen need to contact the airline and request this accommodation during flight. They should also be advised on arranging portable oxygen concentrators before air travel, and a discussion of the potential risks of travel should take place. PMID:25393882

  14. Pre-B-cell colony-enhancing factor as a potential novel biomarker in acute lung injury.

    PubMed

    Ye, Shui Q; Simon, Brett A; Maloney, James P; Zambelli-Weiner, April; Gao, Li; Grant, Audrey; Easley, R Blaine; McVerry, Bryan J; Tuder, Rubin M; Standiford, Theodore; Brower, Roy G; Barnes, Kathleen C; Garcia, Joe G N

    2005-02-15

    Although the pathogenic and genetic basis of acute lung injury (ALI) remains incompletely understood, the identification of novel ALI biomarkers holds promise for unique insights. Expression profiling in animal models of ALI (canine and murine) and human ALI detected significant expression of pre-B-cell colony-enhancing factor (PBEF), a gene not previously associated with lung pathophysiology. These results were validated by real-time polymerase chain reaction and immunohistochemistry studies, with PBEF protein levels significantly increased in both bronchoalveolar lavage fluid and serum of ALI models and in cytokine- or cyclic stretch-activated lung microvascular endothelium. We genotyped two PBEF single-nucleotide polymorphisms (SNPs) in a well characterized sample of white patients with sepsis-associated ALI, patients with severe sepsis, and healthy subjects and observed that carriers of the haplotype GC from SNPs T-1001G and C-1543T had a 7.7-fold higher risk of ALI (95% confidence interval 3.01-19.75, p < 0.001). The T variant from the SNP C-1543T resulted in a significant decrease in the transcription rate (1.8-fold; p < 0.01) by the reporter gene assay. Together, these results strongly indicate that PBEF is a potential novel biomarker in ALI and demonstrate the successful application of robust genomic technologies in the identification of candidate genes in complex lung disease. PMID:15579727

  15. 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

  16. 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.

  17. 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

  18. 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

  19. 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...

  20. 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

  1. Indications for manual lung hyperinflation (MHI) in the mechanically ventilated patient with chronic obstructive pulmonary disease.

    PubMed

    Ntoumenopoulos, G

    2005-01-01

    Manual lung hyperinflation (MHI) can enhance secretion clearance, improve total lung/thorax compliance and assist in the resolution of acute atelectasis. To enhance secretion clearance in the intubated patient, the evidence highlights the need to maximize expiratory flow. Chronic pulmonary diseases such as chronic obstructive pulmonary disease (COPD) have often been cited as potential precautions and/or contra-indications to the use of manual lung hyperinflation (MHI). There is an absence of evidence on the effects of MHI in the patient with COPD. Research on the effects of mechanical ventilation in the patient with COPD provides a useful clinical examination of the effect of positive pressure on cardiac and pulmonary function. The potential effects of MHI in the COPD patient group were extrapolated on the basis of the MHI and mechanical ventilation literature. There is the potential for MHI to have both detrimental and beneficial effects on cardiac and pulmonary function in patients with COPD. The potential detrimental effects of MHI may include either, increased intrinsic peep through inadequate time for expiration by the breath delivery rate, tidal volume delivered or through the removal of applied external PEEP thereby causing more dynamic airway compression compromising downward expiratory flow, which may also retard bronchial mucus transport. MHI may also increase right ventricular after load through raised intrathoracic pressures with lung hyperinflation, and may therefore impair right ventricular function in patients with evidence of cor pulmonale. There is the potential for beneficial effects from MHI in the intubated COPD patient group (i.e., secretion clearance), but further research is required, especially on the effect of MHI on inspiratory and expiratory flow rate profiles in this patient group. The more controlled delivery of lung hyperinflation through the use of the mechanical ventilator may be a more optimal means of providing lung hyperinflation and should be further investigated. PMID:16541603

  2. [Management of acute complications in sickle cell disease ].

    PubMed

    Gellen-Dautremer, Justine; Brousse, Valentine; Arlet, Jean-Benot

    2014-10-01

    Acute complications in sickle cell disease are a major and life-long cause for hospital referral. The most frequent events are painful acute vaso-occlusive crisis involving the limbs and back, and acute chest syndrome. Acute vaso-occlusive crisis is a therapeutic emergency because of the very high level of pain. Acute chest syndrome may be potentially fatal and must be adequately searched for and treated. Sickle cell patients are susceptible to pneumococcal infections notably, but any infection may favour vaso-occlusive crisis. Triggers of sickle cell vase occlusion must be tracked and corrected, if possible. Moderate crisis can be managed at home, but referral is necessary as soon as opiates are needed and/or if acute chest syndrome is suspected. Additional treatments besides opiates include co analgesics, oxygen, hydration, physiotherapy. Blood transfusion may be required but is not systematic. Acute spleen sequestration occurs in young children and requires immediate hospital referral for transfusion. PMID:25510139

  3. Piperine Ameliorates Lipopolysaccharide-Induced Acute Lung Injury via Modulating NF-?B Signaling Pathways.

    PubMed

    Lu, Ying; Liu, Jingyao; Li, Hongyan; Gu, Lina

    2016-02-01

    Piperine, one of the active components of black pepper, has been reported to have antioxidant and anti-inflammatory activities. However, the effects of piperine on lipolysaccharide (LPS)-induced acute lung injury (ALI) have not been reported. Thus, the protective effects of piperine against LPS-induced ALI were investigated in this study. LPS-induced lung injury was assessed by histological study, myeloperoxidase (MPO) activity, and inflammatory cytokine production. Our results demonstrated that piperine attenuated LPS-induced MPO activity, lung edema, and inflammatory cytokines TNF-?, IL-6, and IL-1? production. Histological studies showed that piperine obviously attenuated LPS-induced lung injury. In addition, piperine significantly inhibited LPS-induced NF-?B activation. In conclusion, our results demonstrated that piperine had a protective effect on LPS-induced ALI. The anti-inflammatory mechanism of piperine is through inhibition of NF-?B activation. Piperine may be a potential therapeutic agent for ALI. PMID:26410851

  4. 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

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

    PubMed

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

    2013-10-01

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

  6. 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

  7. 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. ...

  8. 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

  9. Giant bullous lung disease: evaluation, selection, techniques, and outcomes.

    PubMed

    Greenberg, Jacob A; Singhal, Sunil; Kaiser, Larry R

    2003-11-01

    Patient selection remains one of the most important aspects of successful surgery for bullous disease. Operation is indicated for patients who have incapacitating dyspnea with large bullae that fill more than 30% of the hemithorax and result in the compression of healthy adjacent lung tissue. Operation is also indicated for patients who have complications related to bullous disease such as infection or pneumothorax. Patients who have bullous disease in the presence of diffuse lung disease (emphysematous or nonemphysematous) should be evaluated on an individual basis and surgery should be performed on patients in whom even a small increase in pulmonary function might be of major benefit. Smoking cessation and outpatient pulmonary rehabilitation are required of all patients preoperatively. Patients should undergo PFTs including lung volumes by whole body plethysmography, spirometry, diffusion capacity, and arterial blood gas. CT remains the most important preoperative evaluation because it is useful assessing the extent of bullous disease and the quality of the surrounding lung tissue. The authors favor a minimally invasive technique through VATS whenever possible because it might allow for a quicker recovery and might be associated with less pain than is seen following thoracotomy. Modified Monaldi-type drainage procedures are also effective, especially in high-risk patients who cannot tolerate excisional procedures. Special care must be taken to avoid sacrifice of any potentially functional lung tissue. Lobectomies should be avoided whenever possible. The best results are seen in limited resections of large bullae that spare all surrounding functional pulmonary parenchyma. Postoperative complications are minimized through aggressive tracheobronchial toilet and vigorous chest physiotherapy. Adequate pain control in maintained throughout the postoperative period, initially by way of epidural infusion of morphine or fentanyl and later through oral opioids. Early ambulation and pulmonary rehabilitation also help minimize complications. PMID:14682599

  10. Wading into the genomic pool to unravel acute lung injury genetics.

    PubMed

    Meyer, Nuala J; Garcia, Joe G N

    2007-01-01

    Acute lung injury (ALI) is a common and often devastating illness characterized by acute hypoxemia, alveolar flooding, and an unacceptably high morbidity and mortality. Because only a fraction of the patients exposed to ALI-inciting events progress to development of the syndrome, there is significant interest in the identification of genetic factors potentially contributing to ALI susceptibility or prognosis. Two complementary strategies used to elucidate ALI genetics formulate the "candidate gene approach," whereby genes are identified by either global gene expression profiling in humans or animal models of ALI, often yielding highly conserved candidates across multiple species, or by related literature searches. Relevant variants or single nucleotide polymorphisms (single base pair substitutions) in these ALI candidate genes are tested for differences in allelic frequency for both ALI susceptibility and outcome between ALI cases and control patients at risk for ALI. This approach has yielded important variants in a number of genes (angiotensin converting enzyme, surfactant protein B, heat shock protein 70, pre-B-cell colony enhancing factor, myosin light chain kinase, and macrophage migration inhibitory factor) contributing toward an ALI phenotype. An alternative strategy not yet used in ALI genetic studies includes genomewide analyses to locate "hot" genomic segments harboring several hundred genes, with potential ALI candidate genes embedded within these segments. Overall, the detailing of specific ALI-associated polymorphisms will continue to provide new insights in the understanding of ALI pathogenesis, reveal novel molecular targets, and promote the development of individualized therapies to reduce morbidity and mortality from this devastating disease. PMID:17202294

  11. 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

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

    PubMed

    Thatcher, Thomas H; Hsiao, Hsi-Min; Pinner, Elhanan; Laudon, Moshe; Pollock, Stephen J; Sime, Patricia J; Phipps, Richard P

    2013-07-15

    Cigarette smoke is a profound proinflammatory stimulus that causes acute lung inflammation and chronic lung disease, including chronic obstructive pulmonary disease (COPD, emphysema, and chronic bronchitis), via a variety of mechanisms, including oxidative stress. Cigarette smoke contains high levels of free radicals, whereas inflammatory cells, including macrophages and neutrophils, express enzymes, including NADPH oxidase, nitric oxide synthase, and myeloperoxidase, that generate reactive oxygen species in situ and contribute to inflammation and tissue damage. Neu-164 and Neu-107 are small-molecule inhibitors of myeloperoxidase, as well as potent antioxidants. We hypothesized that Neu-164 and Neu-107 would inhibit acute cigarette smoke-induced inflammation. Adult C57BL/6J mice were exposed to mainstream cigarette smoke for 3 days to induce acute inflammation and were treated daily by inhalation with Neu-164, Neu-107, or dexamethasone as a control. Inflammatory cells and cytokines were assessed by bronchoalveolar lavage and histology. mRNA levels of endogenous antioxidant genes heme oxygenase-1 and glutamate-cysteine ligase modifier subunit were determined by qPCR. Cigarette smoke exposure induced acute lung inflammation with accumulation of neutrophils and upregulation of proinflammatory cytokines, including IL-6, macrophage inflammatory protein-2, and keratinocyte-derived cytokine. Both Neu-164 and Neu-107 significantly reduced the accumulation of inflammatory cells and the expression of inflammatory cytokines as effectively as dexamethasone. Upregulation of endogenous antioxidant genes was dampened. Neu-164 and Neu-107 inhibit acute cigarette smoke-induced inflammation by scavenging reactive oxygen species in cigarette smoke and by inhibiting further oxidative stress caused by inflammatory cells. These compounds may have promise in preventing or treating lung disease associated with chronic smoke exposure, including COPD. PMID:23686858

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

    PubMed Central

    Thatcher, Thomas H.; Hsiao, Hsi-Min; Pinner, Elhanan; Laudon, Moshe; Pollock, Stephen J.; Sime, Patricia J.

    2013-01-01

    Cigarette smoke is a profound proinflammatory stimulus that causes acute lung inflammation and chronic lung disease, including chronic obstructive pulmonary disease (COPD, emphysema, and chronic bronchitis), via a variety of mechanisms, including oxidative stress. Cigarette smoke contains high levels of free radicals, whereas inflammatory cells, including macrophages and neutrophils, express enzymes, including NADPH oxidase, nitric oxide synthase, and myeloperoxidase, that generate reactive oxygen species in situ and contribute to inflammation and tissue damage. Neu-164 and Neu-107 are small-molecule inhibitors of myeloperoxidase, as well as potent antioxidants. We hypothesized that Neu-164 and Neu-107 would inhibit acute cigarette smoke-induced inflammation. Adult C57BL/6J mice were exposed to mainstream cigarette smoke for 3 days to induce acute inflammation and were treated daily by inhalation with Neu-164, Neu-107, or dexamethasone as a control. Inflammatory cells and cytokines were assessed by bronchoalveolar lavage and histology. mRNA levels of endogenous antioxidant genes heme oxygenase-1 and glutamate-cysteine ligase modifier subunit were determined by qPCR. Cigarette smoke exposure induced acute lung inflammation with accumulation of neutrophils and upregulation of proinflammatory cytokines, including IL-6, macrophage inflammatory protein-2, and keratinocyte-derived cytokine. Both Neu-164 and Neu-107 significantly reduced the accumulation of inflammatory cells and the expression of inflammatory cytokines as effectively as dexamethasone. Upregulation of endogenous antioxidant genes was dampened. Neu-164 and Neu-107 inhibit acute cigarette smoke-induced inflammation by scavenging reactive oxygen species in cigarette smoke and by inhibiting further oxidative stress caused by inflammatory cells. These compounds may have promise in preventing or treating lung disease associated with chronic smoke exposure, including COPD. PMID:23686858

  14. 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

  15. 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

  16. Experimental study of Tong Xia purgative method in ameliorating lung injury in acute necrotizing pancreatitis

    PubMed Central

    Xia, Qing; Jiang, Jun-Ming; Gong, Xu; Chen, Guang-Yuan; Li, Lei; Huang, Zong-Wen

    2000-01-01

    AIM: To investigate the role of tumor necrosis factor (TNF) in lung injury during acute necrotizing pancreatitis (ANP), and the therapeutic ef fect of Tong Xia purgative method in minimizing the severity of lung injury. METHODS: Fourteen canines were randomly divided into 3 groups: the Tong Xia treatment group (n = 5) using Dachengqitang; saline control group (n = 5), and the sham operation group (n = 4). TNF activity in serum and in bronchoalveolar lavage fluid (BALF), the serum endotoxin levels were meas ured, and the severity of lung injury evaluated. RESULTS: Elevation of TNF activity was more prominent in BALF than in serum. TNF activity in serum at 6 and 12 h and in BALF was significantly decreased in the Tong Xia treatment group than in the saline control one (q = 21.11, q = 12.07, q = 9.03, respectively, P < 0.01) and the lung injury was significantly alleviated at 12 h as compared with that in the saline group, manifested as amelioration of the lung wet/dry weight ratio, decrease in protein concentration and neutrophils count in BALF, and improvement of pulmonary inflammatory changes. A positive correlation was demonstrated between serum TNF activity and endotoxin level. CONCLUSION: Hypersecretion of TNF is shown to be one of the majo r causes of lung injury during ANP; Tong Xia purgative method could allevia te the degree of lung injury mediated by TNF. PMID:11819536

  17. 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)-? levels, reduced BALF IL-10 levels, and increased lung nuclear factor kappa (NF-?B) activity. In rats treated with betanin, paraquat-induced ALI was attenuated in a dose-dependent manner. In conclusion, our results indicate that betanin attenuates paraquat-induced ALI possibly via antioxidant and anti-inflammatory mechanisms. Thus, the potential for using betanin as an auxilliary therapy for ALI should be explored further. PMID:25861636

  18. 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

  19. 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

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

  1. Ventilator-Induced Lung Injury (VILI) in Acute Respiratory Distress Syndrome (ARDS): Volutrauma and Molecular Effects

    PubMed Central

    Carrasco Loza, R; Villamizar Rodrguez, G; Medel Fernndez, 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 con?rmed 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

  2. 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

  3. Transfusion of Human Platelets Treated with Mirasol Pathogen Reduction Technology Does Not Induce Acute Lung Injury in Mice

    PubMed Central

    Caudrillier, Axelle; Mallavia, Beat; 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

  4. 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)-1?, 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)-1?, 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

  5. 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

  6. PPAR?: A Novel Molecular Target in Lung Disease

    PubMed Central

    Hart, C. Michael; Roman, Jesse; Reddy, Raju; Sime, Patricia J.

    2015-01-01

    Interest in peroxisome proliferatoractivated receptors (PPARs) has steadily increased over the past 15 years. The recognition that subclasses of this receptor played critical roles in regulation of metabolism led to the development of synthetic ligands and their widespread application in the treatment of type 2 diabetes. At the same time, emerging evidence demonstrated that the influence of PPARs extends well beyond metabolism and diabetes. A salient example of this can be seen in studies that explore the role of PPARs in lung cell biology. In fact, current literature suggests that PPAR receptors may well represent exciting new targets for treatment in a variety of lung disorders. In an attempt to keep the scientific and medical communities abreast of these developments, a symposium sponsored by the American Federation for Medical Research entitled PPAR?: A Novel Molecular Target in Lung Disease was convened on April 29, 2007, at the Experimental Biology Meeting in Washington, DC. During that symposium, 4 speakers reviewed the latest developments in basic and translational research as they relate to specific lung diseases. Jesse Roman, MD, professor and director of the Emory University Division of Pulmonary, Allergy, and Critical Care Medicine, reviewed the role of PPAR? in the pathogenesis of lung cancer and its implications for therapy. Raju Reddy, MD, assistant professor of Medicine at the University of Michigan, presented data regarding the immunomodula-tory role of PPAR? in alveolar macrophages. Patricia J. Sime, MD, associate professor of Medicine, Environmental Medicine, and Oncology at the University of Rochester School of Medicine, discussed the antifibrogenic potential of PPAR? ligands in pulmonary fibrosis. Finally, C. Michael Hart, MD, professor of Medicine at Emory University and chief of the Atlanta Veterans Affairs Medical Center Pulmonary Section, reviewed the role of PPAR? in pulmonary vascular disease. This brief introduction to the symposium will provide background information about PPARs to facilitate the general reader's appreciation of the more in-depth and disease-specific discussions that follow. PMID:18317433

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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.

  12. Pathogenesis of Interstitial Lung Disease in Children and Adults

    PubMed Central

    Glasser, Stephan W.; Hardie, William D.

    2010-01-01

    Interstitial lung diseases (ILDs) occur across the lifespan, from birth to advanced age. However, the causes, clinical manifestations, histopathology, and management of ILD differ greatly among infants, older children, and adults. The historical approach of classifying childhood ILD (chILD) using adult classification schemes may therefore have done more harm than good. Nevertheless, identification of novel forms of chILD in the past decade, such as surfactant metabolism dysfunction disorders and neuroendocrine cell hyperplasia of infancy (NEHI), as well as genomic analysis of adult ILDs, has taught us that identical genotypes may result in distinct phenotypes at different ages and developmental stages, and that lung developmental pathways and cellular phenotypes are often recapitulated in adult ILDs. Thus comparison of the pathophysiology of ILD in children and adults in the context of lung development is useful in understanding the pathogenesis of these disorders, and may lead to novel therapeutic interventions for ILDs at all ages. PMID:22087431

  13. Acute Demyelinating Disease after Oral Therapy with Herbal Extracts

    PubMed Central

    Kostianovsky, Alex; Maskin, Patricio; Noriega, Mara M.; Soler, Cristina; Bonelli, Ignacio; Riley, Claire S.; O'Connor, Kevin C.; Saubidet, Cristin Lpez; 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

  14. The future of surfactant therapy for patients with acute lung injury - new requirements and new surfactants.

    PubMed

    Spragg, Roger G

    2002-01-01

    New requirements must be considered when designing trials of new lung surfactants for patients with acute lung injury (ALI). Radiographic inclusion criteria must be carefully applied if they are to generate reproducible patient groups. Strategies for ventilation are now known to significantly affect outcome and also must be clearly defined and applied. Similar mortality rates in patients with different degrees of gas exchange and radiographic abnormalities suggest that prior clinical distinctions should be re-examined. Current trials of surfactant therapy for ALI are examining the efficacy of a natural surfactant, a surfactant containing recombinant SP-C and a surfactant based on an SP-B-like peptide. PMID:12011562

  15. 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

  16. 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

  17. 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

  18. Angiogenesis in the pathogenesis of inflammatory joint and lung diseases

    PubMed Central

    Walsh, David A; Pearson, Claire I

    2001-01-01

    This paper reviews hypotheses about roles of angiogenesis in the pathogenesis of inflammatory disease in two organs, the synovial joint and the lung. Neovascularisation is a fundamental process for growth and tissue repair after injury. Nevertheless, it may contribute to a variety of chronic inflammatory diseases, including rheumatoid arthritis, osteoarthritis, asthma, and pulmonary fibrosis. Inflammation can promote angiogenesis, and new vessels may enhance tissue inflammation. Angiogenesis in inflammatory disease may also contribute to tissue growth, disordered tissue perfusion, abnormal ossification, and enhanced responses to normal or pathological stimuli. Angiogenesis inhibitors may reduce inflammation and may also help to restore appropriate tissue structure and function. PMID:11299055

  19. 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

  20. 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

  1. 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.

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

    SciTech Connect

    Vallyathan, V.; Shi, Xianglin

    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. 147 refs., 1 fig.

  3. 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

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

    PubMed

    Luo, Sa; Pauluhn, Jrgen; Trbel, Hubert; Wang, Chen

    2014-08-17

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

  5. 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

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. Acquired cell-mediated immunodepression in acute Chagas' disease.

    PubMed

    Teixeira, A R; Teixeira, G; Macdo, V; Prata, A

    1978-12-01

    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. PMID:107195

  11. 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

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

    PubMed Central

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

    2015-01-01

    Introduction: Diagnostic criteria for acute lung injury (ALI) and Acute Respiratory Distress syndrome (ARDS) includes acute onset of disease, chest radiograph demonstrating bilateral pulmonary infiltrates, lack of significant left ventricular dysfunction and Pao2/Fio2 (PF) ratio ?300 for ALI or ?200 for ARDS. Recent criteria require invasive arterial sampling. The pulse oximetric saturation Spo2/Fio2 (SF) ratio may be a reliable non-invasive alternative to the PF ratio. Methods: In this cross-sectional study, we enrolled 70 patients with ALI or ARDS who were admitted in Tabriz childrens hospital pediatrics intensive care unit (PICU). Spo2, Fio2, Pao2, charted within 5 minutes of each other and calculated SF and PF were recorded to determine the relationship between SF and PF ratio. SF values were examined as a substitute of PF ratio for diagnosis ARDS and ALI. Results: The relationship between SF and PF ratio was described by the following regression equation: SF=57+0.61 PF (P<0.001). SF ratios of 181 and 235 corresponded of PF ratio 300 and 200. The SF cutoff of 235 had 57% sensitivity and 100% specificity for diagnosis of ALI. The SF cutoff of 181 had 71% sensitivity and 82% specificity for diagnosis of ARDS. Conclusion: SF ratio is a reliable noninvasive surrogate for PF ratio to identify children with ALI or ARDS with the advantage of replacing invasive arterial blood sampling by non-invasive pulse oximetry. PMID:25859313

  13. 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

  14. 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

  15. 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

  16. 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

  17. ABCA3 lung disease in an ex 27 week preterm infant responsive to systemic glucocorticosteroids.

    PubMed

    Tan, Jason Kg; Murray, Conor; Schultz, Andre

    2016-01-01

    We present a case of an infant born at almost 28 weeks gestation, found to be homozygous for a missense mutation of ABCA3, with diffuse lung disease that has continued throughout infancy. The patient's clinical course and chest imaging was highly suggestive of diffuse lung disease of infancy, and not of chronic lung disease of prematurity. The lung disease proved to be highly responsive to systemic corticosteroids. This is a case of ABCA3 lung disease that demonstrated improvement after systemic glucocorticosteroid administration. Pediatr Pulmonol. 2016;51:E1-E3. 2015 Wiley Periodicals, Inc. PMID:26222203

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. 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

  5. Acute lung injury and other serious complications of Plasmodium vivax malaria.

    PubMed

    Tan, Lionel K K; Yacoub, Sophie; Scott, Sarah; Bhagani, Sanjay; Jacobs, Michael

    2008-07-01

    Plasmodium vivax infection is classified among the so-called benign malarias, but it is increasingly recognised that serious and even life-threatening complications may occur. We present the case of a returning traveller with P vivax infection who developed acute lung injury 3 days into treatment, and discuss the serious complications of this infection. The case highlights the fact that P vivax infection is benign by name but not always by nature. PMID:18582837

  6. 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

  7. 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

  8. Method Of Treating Silicosis And Other Occupational Lung Diseases

    Cancer.gov

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

  9. 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

  10. Primary anaplastic large cell lymphoma of the lung presenting with acute atelectasis

    PubMed Central

    Han, Sang Hoon; Maeng, Young Hee; Kim, Young Sill; Jo, Jae Min; Kwon, Jung Mi; Kim, Woo Kun; Kim, Mi Ok

    2014-01-01

    Non-Hodgkin lymphoma only rarely occurs as a primary lung mass. We report a very rare case of primary pulmonary anaplastic large cell lymphoma presenting with acute atelectasis in a 55-year-old man. Chest computed tomography revealed a consolidated central mass in the left lung with obstructive pneumonia that had developed into total atelectasis. After a bronchoscopic examination failed to yield a definite diagnosis, supraclavicular lymph node biopsy was performed, revealing an anaplastic large cell lymphoma. This case illustrates the need for rapidly locating a possible biopsy site, other than the primary lung mass itself, and the value of empirical steroid treatment for avoiding devastating exacerbation when aggressive pulmonary lymphoma is suspected.

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

    PubMed

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

    2014-02-01

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

  12. Impact of TREM-2 gene silencing on inflammatory response of endotoxin-induced acute lung injury in mice.

    PubMed

    Liu, Dai; Dong, Yanting; Liu, Zhuola; Niu, Bo; Wang, Yaowei; Gao, Xiaoling

    2014-09-01

    Acute lung injury (ALI) is one of the critical clinical respiratory diseases, of which infection is the main cause and the first risk factor. This study investigated the impact of triggering receptor of myeloid cells expression (TREM)-2 gene silencing on inflammatory response of endotoxin-induced ALI in mice. Lentivirus-mediated TREM-2-shRNA was transfected into healthy male C57BL/6 mice, and the lipopolysaccharide-induced ALI model was established. The immunohistochemistry, immunofluorescence, fluorescence quantitative PCR, western blot, and ELISA were applied to detect the pathological changes of lung tissue and expressions of TREM-2, tumor necrosis factor-? (TNF-?), and interleukin 10 (IL-10) in bronchoalveolar lavage fluid. The lentivirus group, saline control group, ALI model group, blank control group, and negative control group were set up at the same time. Results found that, in lentivirus group, the pathological change of lung tissue was significantly lighter than ALI model group (P < 0.05), and the expression of TREM-2 was significantly reduced compared with all control groups (P < 0.05). The levels of TNF-? and IL-10 were significantly increased than all control groups (P < 0.05), while above indexes in negative control group and blank control group showed no significant difference with ALI group (P > 0.05). This study indicates that TREM-2 has a protective effect on inflammatory response of endotoxin-induced ALI in mice, which has provided new potential targets for prevention and treatment of ALI. PMID:24916365

  13. [Use of rifamethoprim in acute and chronic respiratory tract diseases].

    PubMed

    Orlov, V A; Sokolova, V I; Troshina, E V; Manu?lov, K K; Pozdniakova, V P; Berezovskaia, L N

    1992-01-01

    Rifamethoprim is a new formulation containing rifampicin and trimethoprim. Its efficacy was studied in the treatment of a group of patients with various nonspecific diseases of the lungs. It was shown to be highly active against a broad spectrum of pathogens. With inclusion of trimethoprim to the formulation it appeared possible to markedly lower the bacterial ability to develop resistance to rifampicin, which solved the problem of long-term antibiotic use. The unique pharmacokinetic properties of rifampicin such as its capacity to penetrating into the sputum, lung tissues and cells make rifamethoprim be the drug of optimal choice in the treatment of respiratory diseases. PMID:1530359

  14. Toxic inhalational injury-associated interstitial lung disease in children.

    PubMed

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

    2013-06-01

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

  15. 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

  16. 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

  17. 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

  18. Protection of LPS-Induced Murine Acute Lung Injury by Sphingosine-1-Phosphate Lyase Suppression

    PubMed Central

    Zhao, Yutong; Gorshkova, Irina A.; Berdyshev, Evgeny; He, Donghong; Fu, Panfeng; Ma, Wenli; Su, Yanlin; Usatyuk, Peter V.; Pendyala, Srikanth; Oskouian, Babak; Saba, Julie D.; Garcia, Joe G. N.; Natarajan, Viswanathan

    2011-01-01

    A defining feature of acute lung injury (ALI) is the increased lung vascular permeability and alveolar flooding, which leads to associated morbidity and mortality. Specific therapies to alleviate the unremitting vascular leak in ALI are not currently clinically available; however, our prior studies indicate a protective role for sphingosine-1-phosphate (S1P) in animal models of ALI with reductions in lung edema. As S1P levels are tightly regulated by synthesis and degradation, we tested the hypothesis that inhibition of S1P lyase (S1PL), the enzyme that irreversibly degrades S1P via cleavage, could ameliorate ALI. Intratracheal instillation of LPS to mice enhanced S1PL expression, decreased S1P levels in lung tissue, and induced lung inflammation and injury. LPS challenge of wild-type mice receiving 2-acetyl-4(5)-[1(R),2(S),3(R),4-tetrahydroxybutyl]-imidazole to inhibit S1PL or S1PL+/? mice resulted in increased S1P levels in lung tissue and bronchoalveolar lavage fluids and reduced lung injury and inflammation. Moreover, down-regulation of S1PL expression by short interfering RNA (siRNA) in primary human lung microvascular endothelial cells increased S1P levels, and attenuated LPS-mediated phosphorylation of p38 mitogen-activated protein kinase and I-?B, IL-6 secretion, and endothelial barrier disruption via Rac1 activation. These results identify a novel role for intracellularly generated S1P in protection against ALI and suggest S1PL as a potential therapeutic target. PMID:21148740

  19. 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

  20. 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

  1. 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

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

    PubMed

    Amirshahrokhi, Keyvan; Bohlooli, Shahab

    2013-10-01

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

  3. Lung ultrasound in acute respiratory failure an introduction to the BLUE-protocol.

    PubMed

    Lichtenstein, D

    2009-05-01

    Critical ultrasound, apparently a recent field, is in fact the outcome of a slow process, initiated since 1946. The lung was traditionally not considered as part of ultrasound, yet we considered its inclusion as a priority in our definition of critical ultrasound. Acute respiratory failure is one of the most distressing situations for the patient. An ultrasound approach of this disorder - the BLUE-protocol allows rapid diagnosis. Its main features will be described. Each kind of respiratory failure provides a particular ultrasound profile. In this difficult setting, initial mistakes are frequent. The BLUE-protocol proposes a step-by-step approach for making accurate diagnosis. By combining three signs with binary answer (anterior lung sliding, anterior lung-rockets), with venous analysis when required, seven profiles are generated, yielding a 90.5% accuracy. This rate is highly enhanced when simple clinical and laboratory data are considered. The BLUE-protocol can be achieved in three minutes, because the use of an intelligent machine, a universal probe, and standardized points allow major time-saving. Lung ultrasound in the critically ill was long available. In a domain where everything must be fast and accurate, the BLUE-protocol can play a major role in the diagnosis of an acute respiratory failure, usually answering immediately to questions where only sophisticated techniques were hitherto used. PMID:19412150

  4. 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

  5. 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-?B activation and inflammation. Furthermore, LPS-induced apoptosis was blocked by antioxidant N-acetylcysteine or NF-?B inhibitor via down-regulating Fas expression. These findings suggest the therapeutic potential of kallistatin for sepsis-related ALI/ARDS. PMID:26198099

  6. Transcriptome Profiling of the Newborn Mouse Lung Response to Acute Ozone Exposure

    PubMed Central

    Loader, Joan E.; White, Carl W.; Dakhama, Azzeddine

    2014-01-01

    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

  7. 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

  8. The impact of sodium aescinate on acute lung injury induced by oleic acid in rats.

    PubMed

    Wei, Tian; Tong, Wang; Wen-ping, Sun; Xiao-hui, Deng; Qiang, Xue; Tian-shui, Li; Zhi-fang, Chen; Hong-fang, Jin; Li, Ni; Bin, Zhao; Jun-bao, Du; Bao-ming, Ge

    2011-12-01

    Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are associated with high rates of morbidity and mortality. Currently, several surfactant or anti-inflammatory drugs are under test as treatments for ALI. Sodium aescinate (SA) has been shown to exert anti-inflammatory and antiedematous effects. In the present work, the authors explored the effects of SA and the possible mechanisms of SA action in rats with ALI induced by oleic acid (OA) administration. Eight groups of rats received infusions of normal saline (NS) or OA. Rats exposed to OA were pretreated with 1 mg/kg of SA, or posttreated with SA at low (1 mg/kg), medium (2 mg/kg), or high (6 mg/kg) dose; a positive-control group received methylprednisolone. The pressure of oxygen in arterial blood (P(O(2))) levels, the pulmonary wet/dry weight (W/D) ratios, and indices of quantitative assessment (IQA) of histological lung injury were obtained 2 or 6 hours after OA injection (0.1 mL/kg, intravenously). The levels of superoxide dismutase (SOD), malondialdehyde (MDA), matrix metalloproteinase gelatinase B (MMP-9), and tissue inhibitor of metalloproteinase (TIMP-1) in both plasma and lung tissue were also determined. Both pre- and posttreatment with SA improved OA-induced pulmonary injury, increased P(O(2)) and SOD values, lowered IQA scores, and decreased the lung W/D ratio and MDA and MMP-9 levels in plasma and lung tissue. SA appeared to abrogate OA-induced ALI by modulating the levels of SOD, MDA, and MMP-9 in plasma and lung tissue. PMID:22087513

  9. 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.

  10. Hyaluronate and type III procollagen peptide concentrations in bronchoalveolar lavage fluid as markers of disease activity in farmer's lung.

    PubMed Central

    Bjermer, L; Engstrm-Laurent, A; Lundgren, R; Rosenhall, L; Hllgren, R

    1987-01-01

    Ten patients were studied during an acute episode of farmer's lung. Prominent findings were an impaired diffusion capacity (on average only 51% of predicted) and substantially increased amounts of hyaluronate and type III procollagen peptide recovered during bronchoalveolar lavage; mean concentrations of these constituents in lavage fluid were 547 (range 137-1125) and 9.7 (2.8-19.4) micrograms/l, respectively. In bronchoalveolar lavage fluid from healthy controls (n = 21) hyaluronate concentrations were less than 15 micrograms/l and procollagen peptide concentrations less than 0.2 micrograms/l. Lavage fluid concentrations of these potential markers of fibroblast activation declined during the recovery phase of farmer's lung; four to 10 weeks after admission (n = 7) mean concentrations of hyaluronate and procollagen peptide were 154 (range 38-650) and 4.4 (0.6-15.8) micrograms/l, respectively. At clinical remission six to 14 months after admission concentrations of these markers had returned almost to normal, though slightly increased concentrations were still evident in about half the patients (n = 7). At that time lung volumes were normal but diffusion capacity remained slightly subnormal. It was concluded that in farmer's lung release of hyaluronate and type III procollagen peptide reflects activity of the disease. Increased synthesis of these connective tissue components continuing in a patient avoiding mouldy plant material may signal an increased risk of developing fibrotic lung disease. The abnormal accumulation of hyaluronate in the smaller airways in acute farmer's lung may be expected to immobilize water and thereby provide a possible mechanism of the interstitial inflammatory lung oedema with associated impaired gas diffusion. This hypothesis is supported by the relation found between hyaluronate in lavage fluid and reduced diffusion capacity. PMID:3119050

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. Inflammation in chronic obstructive pulmonary disease and its role in cardiovascular disease and lung cancer.

    PubMed

    King, Paul T

    2015-12-01

    Chronic obstructive pulmonary disease (COPD) is characterized by lung inflammation that persists after smoking cessation. This inflammation is heterogeneous but the key inflammatory cell types involved are macrophages, neutrophils and T cells. Other lung cells may also produce inflammatory mediators, particularly the epithelial cells. The main inflammatory mediators include tumor necrosis factor alpha, interleukin-1, interleukin-6, reactive oxygen species and proteases. COPD is also associated with systemic inflammation and there is a markedly increased risk of cardiovascular disease (particularly coronary artery disease) and lung cancer in patients with COPD. There is strong associative evidence that the inflammatory cells/mediators in COPD are also relevant to the development of cardiovascular disease and lung cancer. There are a large number of potential inhibitors of inflammation in COPD that may well have beneficial effects for these comorbidities. This is a not well-understood area and there is a requirement for more definitive clinical and mechanistic studies to define the relationship between the inflammatory process of COPD and cardiovascular disease and lung cancer. PMID:26220864

  18. Pathophysiology of coronary artery disease leading to acute coronary syndromes

    PubMed Central

    Singh, Manmeet

    2015-01-01

    Acute myocardial infarction (AMI) and sudden cardiac death (SCD) are among the most serious and catastrophic of acute cardiac disorders, accounting for hundreds of thousands of deaths each year worldwide. Although the incidence of AMI has been decreasing in the US according to the American Heart Association, heart disease is still the leading cause of mortality in adults. In most cases of AMI and in a majority of cases of SCD, the underlying pathology is acute intraluminal coronary thrombus formation within an epicardial coronary artery leading to total or near-total acute coronary occlusion. This article summarizes our current understanding of the pathophysiology of these acute coronary syndromes and briefly discusses new approaches currently being researched in an attempt to define and ultimately reduce their incidence. PMID:25705391

  19. Different Effects of Farrerol on an OVA-Induced Allergic Asthma and LPS-induced Acute Lung Injury

    PubMed Central

    Wei, Miaomiao; Yang, Xiaofeng; Cai, Qinren; Deng, Xuming

    2012-01-01

    Background Farrerol, isolated from rhododendron, has been shown to have the anti-bacterial activity, but no details on the anti-inflammatory activity. We further evaluated the effects of this compound in two experimental models of lung diseases. Methodology/Principal Findings For the asthma model, female BALB/c mice were challenged with ovalbumin (OVA), and then treated daily with farrerol (20 and 40 mg/kg, ip) as a therapeutic treatment from day 22 to day 26 post immunization. To induce acute lung injury, female BALB/c mice were injected intranasally with LPS and treated with farrerol (20 and 40 mg/kg, i.p.) 1 h prior to LPS stimulation. Inflammation in the two different models was determined using ELISA, histology, real-time PCR and western blot. Farrerol significantly regulated the phenotype challenged by OVA, like cell number, Th1 and Th2 cytokines levels in the BALF, the OVA-specific IgE level in the serum, goblet cell hyperplasia in the airway, airway hyperresponsiveness to inhaled methacholine and mRNA expression of chemokines and their receptors. Furthermore, farrerol markedly attenuated the activation of phosphorylation of Akt and nuclear factor-?B (NF-?B) subunit p65 both in vivo and in vitro. However, farrerol has no effect on the acute lung injury model. Conclusion/Significance Our finding demonstrates that the distinct anti-inflammatory effect of farrerol in the treatment of asthma acts by inhibiting the PI3K and NF-?B pathway. PMID:22563373

  20. 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 take an active part in the exacerbations of COPD, interstitial pulmonary processes and of extrinsic allergic alveolities. Those diseases are also associated with increased risk of lung cancer. Methods and patients We used commercial diagnostic test Pep test, we tested saliva or sputum. A detection limit of the method is 25 ng/mL. We performed investigations of pepsin levels in saliva/sputum in patients suffering from verified lung cancer. A method of estimation is described on Peptest, RD Biomed Limited, Hull UK, (www.peptest.co.uk). Results From June 2013 till August 2014 we received Peptest results from 44 patients suffering from verified lung cancer, there were 30 men and 14 women. Positive results were found in 31 patients (75.6%), positive results in the range of 59-250 ng/mL of pepsin concentration had 22 patients (24.4%), modestly positive results of range 25-57 ng/mL of pepsin were found in nine patients (21.6%l), in 10 patients (24.4%) the results were negative, in three patients we observed a failure of test due to abnormal suptum viscosity. Conclusions Extraesophageal reflux has been documented by detection of pepsin in saliva/sputum or other respiratory secretions. Pepsin should act as a cancerogen in upper or lower airways, or should be able to potentiate the cancerogenic effects of other chemical cancerogens, e.g., smoking related. Pepsin and bile acids contained in refluxate should be able to induce not solely the cancer growth, but also the exacerbations of other pulmonary diseases frequently associated with lung cancer, e.g., COPD, IPF, bronchiectasis and to bring some inflammatory complications of the course of treatment of lung cancer. Investigation of EER should be considered in lung cancer patients also in the time of preoperative investigation to prevent postoperative inflammatory complications.

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

    PubMed Central

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

    2014-01-01

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

  2. Technetium-99m glucoheptonate imaging in lung cancer and benign lung diseases: concise communication

    SciTech Connect

    Passamonte, P.M.; Seger, R.M.; Holmes, R.A.; Hurst, D.J.

    1983-11-01

    Technetium-99m glucoheptonate (Tc-GHA) uptake was prospectively studied in 58 patients with newly diagnosed lung cancer and in 20 patients with pulmonary inflammatory disease or metastatic carcinoma. Fifty-three (91%) primary tumors accumulated Tc-GHA: squamous cell 20/22, adenocarcinoma 7/7, large cell 10/11, and small cell 16/18. Intensity of tumor uptake was greatest in small-cell cancer. Supraclavicular metastases were detected in two patients. Fourteen patients with mediastinal evaluation by Tc-GHA imaging and trispiral tomography underwent mediastinoscopy or thoracotomy. Five of ten patients with negative mediastinum by tomography and Tc-GHA imaging showed metastases by biopsy (false- negative Tc-GHA). Less intense accumulation of Tc-GHA was observed in 18/20 cases of pulmonary inflammatory disease or pulmonary metastases. Although Tc-GHA accumulates by an unknown mechanism in primary lung cancer, we cannot recommend its use in detecting mediastinal spread of lung cancer due to its unacceptably high false-negative rate.

  3. Allergic Airway Inflammation Decreases Lung Bacterial Burden following Acute Klebsiella pneumoniae Infection in a Neutrophil- and CCL8-Dependent Manner

    PubMed Central

    Dulek, Daniel E.; Newcomb, Dawn C.; Goleniewska, Kasia; Cephus, Jaqueline; Zhou, Weisong; Reiss, Sara; Toki, Shinji; Ye, Fei; Zaynagetdinov, Rinat; Sherrill, Taylor P.; Blackwell, Timothy S.; Moore, Martin L.; Boyd, Kelli L.; Kolls, Jay K.

    2014-01-01

    The Th17 cytokines interleukin-17A (IL-17A), IL-17F, and IL-22 are critical for the lung immune response to a variety of bacterial pathogens, including Klebsiella pneumoniae. Th2 cytokine expression in the airways is a characteristic feature of asthma and allergic airway inflammation. The Th2 cytokines IL-4 and IL-13 diminish ex vivo and in vivo IL-17A protein expression by Th17 cells. To determine the effect of IL-4 and IL-13 on IL-17-dependent lung immune responses to acute bacterial infection, we developed a combined model in which allergic airway inflammation and lung IL-4 and IL-13 expression were induced by ovalbumin sensitization and challenge prior to acute lung infection with K. pneumoniae. We hypothesized that preexisting allergic airway inflammation decreases lung IL-17A expression and airway neutrophil recruitment in response to acute K. pneumoniae infection and thereb