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Sample records for acute lung function

  1. Acute Lung Function Response to Dust in Street Sweepers

    OpenAIRE

    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.

  2. Lung function evaluation in acute postradiation pneumonitis

    International Nuclear Information System (INIS)

    Jassem, E.; Zandwijk, N. van; Jassem, J.; Badzio, A.

    1997-01-01

    The aim of this study was pulmonary function evaluation in patients with radiation pneumonitis (rp). Study group included 18 patients with symptomatic rp (8 with breast cancer, 6 with Hodgkin's disease and 4 with lung cancer) treated at the Netherland s Cancer inst. In Amsterdam between 1988 and 1994. The lung function tests were performed at the time of rp presentation and monthly thereafter and consisted of a standard spirometry: forced expiratory volume in 1 sec. (FEV1), vital capacity (VC) and diffusing capacity for carbon monoxide (DLCO) performed with the use of a single breath technique. The mean values of DLCO, VC, FEV1 and TLC at the time of rp presentation were 72.2%, 91.0% and 85.8% of predicted value (pv), respectively. The results of the a bone tests at the last examination (66.4%, 85.6%, 77.2% and 76.2% of pv), respectively, were lower than those registered at the time of rp presentation. The highest degree of functional deterioration included diffusion capacity; the mean of the lowest values of DLCO was 56.4% of pv. Usually the lowest value of DLCO accompanied the exacerbation of clinical symptoms. The results of this study demonstrated pulmonary function deterioration in patients with rp. (author)

  3. Acute lung function response to dust in street sweepers.

    Science.gov (United States)

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

    2013-10-01

    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. The aim of this study was to determine the acute lung function changes in sweepers exposed to dust generated from street sweeping. This study was conducted in central Karnataka, India, on 25 female sweepers and 25 healthy female control subjects who were comparable in age, height and weight. The pulmonary function test was performed in controls, sweepers before and after sweeping, by using RMS medspiror and results were compared by Student's unpaired 't' test. 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. 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.

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

    Science.gov (United States)

    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.

  5. Prolonged recruitment manoeuvre improves lung function with less ultrastructural damage in experimental mild acute lung injury.

    Science.gov (United States)

    Rzezinski, Andréia F; Oliveira, Gisele P; Santiago, Viviane R; Santos, Raquel S; Ornellas, Debora S; Morales, Marcelo M; Capelozzi, Vera L; Amato, Marcelo B P; Conde, Marcus B; Pelosi, Paolo; Rocco, Patricia R M

    2009-12-31

    The effects of prolonged recruitment manoeuvre (PRM) were compared with sustained inflation (SI) in paraquat-induced mild acute lung injury (ALI) in rats. Twenty-four hours after ALI induction, rats were anesthetized and mechanically ventilated with VT=6 ml/kg and positive end-expiratory pressure (PEEP)=5 cmH(2)O for 1h. SI was performed with an instantaneous pressure increase of 40 cmH(2)O that was sustained for 40s, while PRM was done by a step-wise increase in positive inspiratory pressure (PIP) of 15-20-25 cmH(2)O above a PEEP of 15 cm H(2)O (maximal PIP=40 cmH(2)O), with interposed periods of PIP=10 cmH(2)O above a PEEP=15 cmH(2)O. Lung static elastance and the amount of alveolar collapse were more reduced with PRM than SI, yielding improved oxygenation. Additionally, tumour necrosis factor-alpha, interleukin-6, interferon-gamma, and type III procollagen mRNA expressions in lung tissue and lung epithelial cell apoptosis decreased more in PRM. In conclusion, PRM improved lung function, with less damage to alveolar epithelium, resulting in reduced pulmonary injury.

  6. Acute Exacerbations and Lung Function Loss in Smokers with and without Chronic Obstructive Pulmonary Disease.

    Science.gov (United States)

    Dransfield, Mark T; Kunisaki, Ken M; Strand, Matthew J; Anzueto, Antonio; Bhatt, Surya P; Bowler, Russell P; Criner, Gerard J; Curtis, Jeffrey L; Hanania, Nicola A; Nath, Hrudaya; Putcha, Nirupama; Roark, Sarah E; Wan, Emily S; Washko, George R; Wells, J Michael; Wendt, Christine H; Make, Barry J

    2017-02-01

    Acute exacerbations of chronic obstructive pulmonary disease (COPD) increase the risk of death and drive healthcare costs, but whether they accelerate loss of lung function remains controversial. Whether exacerbations in subjects with mild COPD or similar acute respiratory events in smokers without airflow obstruction affect lung function decline is unknown. To determine the association between acute exacerbations of COPD (and acute respiratory events in smokers without COPD) and the change in lung function over 5 years of follow-up. We examined data on the first 2,000 subjects who returned for a second COPDGene visit 5 years after enrollment. Baseline data included demographics, smoking history, and computed tomography emphysema. We defined exacerbations (and acute respiratory events in those without established COPD) as acute respiratory symptoms requiring either antibiotics or systemic steroids, and severe events by the need for hospitalization. Throughout the 5-year follow-up period, we collected self-reported acute respiratory event data at 6-month intervals. We used linear mixed models to fit FEV 1 decline based on reported exacerbations or acute respiratory events. In subjects with COPD, exacerbations were associated with excess FEV 1 decline, with the greatest effect in Global Initiative for Chronic Obstructive Lung Disease stage 1, where each exacerbation was associated with an additional 23 ml/yr decline (95% confidence interval, 2-44; P = 0.03), and each severe exacerbation with an additional 87 ml/yr decline (95% confidence interval, 23-151; P = 0.008); statistically significant but smaller effects were observed in Global Initiative for Chronic Obstructive Lung Disease stage 2 and 3 subjects. In subjects without airflow obstruction, acute respiratory events were not associated with additional FEV 1 decline. Exacerbations are associated with accelerated lung function loss in subjects with established COPD, particularly those with mild disease

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

    Science.gov (United States)

    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.

  8. Pediatric acute lung injury

    NARCIS (Netherlands)

    Dahlem, P.; van Aalderen, W. M. C.; Bos, A. P.

    2007-01-01

    Among ventilated children, the incidence of acute lung injury (ALI) was 9%; of that latter group 80% developed the acute respiratory distress syndrome (ARDS). The population-based prevalence of pediatric ARDS was 5.5 cases/100.000 inhabitants. Underlying diseases in children were septic shock (34%),

  9. Lung function

    International Nuclear Information System (INIS)

    Sorichter, S.

    2009-01-01

    The term lung function is often restricted to the assessment of volume time curves measured at the mouth. Spirometry includes the assessment of lung volumes which can be mobilised with the corresponding flow-volume curves. In addition, lung volumes that can not be mobilised, such as the residual volume, or only partially as FRC and TLC can be measured by body plethysmography combined with the determination of the airway resistance. Body plethysmography allows the correct positioning of forced breathing manoeuvres on the volume-axis, e.g. before and after pharmacotherapy. Adding the CO single breath transfer factor (T LCO ), which includes the measurement of the ventilated lung volume using He, enables a clear diagnosis of different obstructive, restrictive or mixed ventilatory defects with and without trapped air. Tests of reversibility and provocation, as well as the assessment of inspiratory mouth pressures (PI max , P 0.1 ) help to classify the underlying disorder and to clarify treatment strategies. For further information and to complete the diagnostic of disturbances of the ventilation, diffusion and/or perfusion (capillar-)arterial bloodgases at rest and under physical strain sometimes amended by ergospirometry are recommended. Ideally, lung function measurements are amended by radiological and nuclear medicine techniques. (orig.) [de

  10. Extravascular Lung Water and Acute Lung Injury

    Directory of Open Access Journals (Sweden)

    Ritesh Maharaj

    2012-01-01

    Full Text Available Acute lung injury carries a high burden of morbidity and mortality and is characterised by nonhydrostatic pulmonary oedema. The aim of this paper is to highlight the role of accurate quantification of extravascular lung water in diagnosis, management, and prognosis in “acute lung injury” and “acute respiratory distress syndrome”. Several studies have verified the accuracy of both the single and the double transpulmonary thermal indicator techniques. Both experimental and clinical studies were searched in PUBMED using the term “extravascular lung water” and “acute lung injury”. Extravascular lung water measurement offers information not otherwise available by other methods such as chest radiography, arterial blood gas, and chest auscultation at the bedside. Recent data have highlighted the role of extravascular lung water in response to treatment to guide fluid therapy and ventilator strategies. The quantification of extravascular lung water may predict mortality and multiorgan dysfunction. The limitations of the dilution method are also discussed.

  11. Exposure to Cooking Fumes and Acute Reversible Decrement in Lung Functional Capacity

    Directory of Open Access Journals (Sweden)

    Masoud Neghab

    2017-10-01

    Full Text Available Background: Being exposed to cooking fumes, kitchen workers are occupationally at risk of multiple respiratory hazards. No conclusive evidence exists as to whether occupational exposure to these fumes is associated with acute and chronic pulmonary effects and symptoms of respiratory diseases. Objective: To quantify the exposure levels and evaluate possible chronic and acute pulmonary effects associated with exposure to cooking fumes. Methods: In this cross-sectional study, 60 kitchen workers exposed to cooking fumes and 60 unexposed employees were investigated. The prevalence of respiratory symptoms among these groups was determined through completion of a standard questionnaire. Pulmonary function parameters were also measured before and after participants' work shift. Moreover, air samples were collected and analyzed to quantify their aldehyde, particle, and volatile organic contents. Results: The mean airborne concentrations of formaldehyde, acetaldehyde, and acrolein was 0.45 (SD 0.41, 0.13 (0.1, and 1.56 (0.41 mg/m3, respectively. The mean atmospheric concentrations of PM1, PM2.5, PM7, PM10, and total volatile organic compounds (TVOCs was 3.31 (2.6, 12.21 (5.9, 44.16 (16.6, 57 (21.55 μg/m3, and 1.31 (1.11 mg/m3, respectively. All respiratory symptoms were significantly (p<0.05 more prevalent in exposed group. No significant difference was noted between the pre-shift mean of spirometry parameters of exposed and unexposed group. However, exposed workers showed cross-shift decrease in most spirometry parameters, significantly lower than the pre-shift values and those of the comparison group. Conclusion: Exposure to cooking fumes is associated with a significant increase in the prevalence of respiratory symptoms as well as acute reversible decrease in lung functional capacity.

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

    International Nuclear Information System (INIS)

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

    1987-01-01

    To investigate the acute physiological and structural changes after lung irradiation, the effects of whole-lung irradiation were investigated in fourteen sheep. Ten sheep were prepared with vascular and chronic lung lymph catheters, then a week later were given 1,500 rad whole-lung radiation and monitored for 2 days. Four sheep were given the same dose of radiation and were killed 4 h later for structural studies. Lung lymph flow increased at 3 h after radiation (14.6 +/- 2.1 ml/h) to twice the base-line flow rate (7.5 +/- 1.3), with a high lymph-to-plasma protein concentration. Pulmonary arterial pressure increased twofold from base line (18 +/- 1.6 cmH2O) at 2 h after radiation (33 +/- 3.8). Cardiac output and systemic pressure in the aorta did not change after lung radiation. Arterial O 2 tension decreased from 85 +/- 3 to 59 +/- 4 Torr at 1 day after radiation. Lymphocyte counts in both blood and lung lymph decreased to a nadir by 4 h and remained low. Thromboxane B2 concentration in lung lymph increased from base line (0.07 +/- 0.03 ng/ml) to peak at 3 h after radiation (8.2 +/- 3.7 ng/ml). The structural studies showed numerous damaged lymphocytes in the peripheral lung and bronchial associated lymphoid tissue. Quantitative analysis of the number of granulocytes in peripheral lung showed no significant change (base line 6.2 +/- 0.8 granulocytes/100 alveoli, 4 h = 10.3 +/- 2.3). The most striking change involved lung airways. The epithelial lining of the majority of airways from intrapulmonary bronchus to respiratory bronchiolus revealed damage with the appearance of intracellular and intercellular cell fragments and granules. This new large animal model of acute radiation lung injury can be used to monitor physiological, biochemical, and morphological changes after lung radiation. It is relevant to the investigation of diffuse oxidant lung injury as well as to radiobiology per se

  13. Probability of treatment following acute decline in lung function in children with cystic fibrosis is related to baseline pulmonary function.

    Science.gov (United States)

    Morgan, Wayne J; Wagener, Jeffrey S; Yegin, Ashley; Pasta, David J; Millar, Stefanie J; Konstan, Michael W

    2013-10-01

    To determine whether the association between high forced expiratory volume in 1 second (FEV1) and increased rate of decline in FEV1 in children with cystic fibrosis could be due to less frequent intervention after acute declines (sudden decline events) in FEV1. Patients with cystic fibrosis aged 6-17 years enrolled in the Epidemiologic Study of Cystic Fibrosis were assessed for a sudden decline event, defined as a 10% relative decline in FEV1% predicted from an average of 3 consecutive stable baseline spirometries. The likelihood of therapeutic intervention within 14 days before and 56 days after this event was then related to their baseline FEV1% predicted age-specific decile using a logistic regression adjusting for age group (6-12 years, 13-17 years) and presence of Pseudomonas aeruginosa on respiratory culture. A total of 10 888 patients had at least 1 sudden decline event in FEV1. Patients in the highest FEV1 decile were significantly less likely than those in the lowest decile to receive intravenous antibiotics (OR, 0.14; 95% CI, 0.11-0.18; P < .001) or be hospitalized (OR, 0.18; 95% CI, 0.14-0.23; P < .001) following decline. Children and adolescents with high baseline lung function are less likely to receive a therapeutic intervention following an acute decline in FEV1, which may explain their greater rate of FEV1 decline. Copyright © 2013 Mosby, Inc. All rights reserved.

  14. [Study on the function of osteopontin in hyperoxia-induced acute lung injury and its mechanism].

    Science.gov (United States)

    Zhang, Xiang-feng; Foda, Hussein D

    2006-06-01

    To examine the role of osteopontin (OPN) in hyperoxia-induced acute lung injury (ALI) and its relationships with matrix metalloproteinases (MMP). Seventy-two OPN gene wild type (OPN(+/+)) mice were divided into normal control group (WN group), hyperoxia for 24 hours group (WO(1) group), hyperoxia for 48 hours group (WO(2) group) and hyperoxia for 72 hours group (WO(3) group) randomly, 18 mice in each group; another seventy-two OPN gene knock-out (OPN(-/-)) mice were also divided into normal control group (DN group), hyperoxia for 24 hours group (DO(1) group), hyperoxia for 48 hours group (DO(2) group) and hyperoxia for 72 hours group (DO(3) group) randomly. The hyperoxia group mice were exposed in sealed cages > 95% oxygen, and their matched background control were put outside of sealed cages and breath room air. Severity of lung injury was assessed and the survival curve was calculated. Cell count and differentials in bronchoalveolar lavage fluid (BALF) in every group were performed, while another 40 OPN(-/-) mice and their matched OPN(+/+) mice were used for survival study. Samples obtained from BALF at the end of the experiment (24, 48 and 72 h) and control animals were used for the measurement of MMP-2, MMP-9 by gelatin zymography, and reverse transcript-polymerase chain reaction (RT-PCR) was used for the semiquantitative assay of mRNA coding for OPN, MMP-2, MMP-9, tissue-inhibitors of metalloproteinase-1, 2 (TIMP-1, TIMP-2). DO(3) group mice developed more severe ALI than WO(3) group mice and the survival times of OPN(-/-) mice were shorter than their matched OPN(+/+) mice (P < 0.01). The total cell count in BALF from DO(3) group mice was higher than WO(3) group mice [(72.2 +/- 22.3) x 10(4)/L, (39.7 +/- 10.4) x 10(4)/L, P < 0.05], the count of polymorphonuclear cells in BALF from DO(3) group mice was almost 8 folds higher than WO(3) group mice [(207.54 +/- 36.45) x 10(3)/L, (25.33 +/- 6.43) x 10(3)/L, P < 0.01]. Gelatin zymography showed that the level of

  15. Microparticles and acute lung injury.

    Science.gov (United States)

    McVey, Mark; Tabuchi, Arata; Kuebler, Wolfgang M

    2012-09-01

    The pathophysiology of acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), is characterized by increased vascular and epithelial permeability, hypercoagulation and hypofibrinolysis, inflammation, and immune modulation. These detrimental changes are orchestrated by cross talk between a complex network of cells, mediators, and signaling pathways. A rapidly growing number of studies have reported the appearance of distinct populations of microparticles (MPs) in both the vascular and alveolar compartments in animal models of ALI/ARDS or respective patient populations, where they may serve as diagnostic and prognostic biomarkers. MPs are small cytosolic vesicles with an intact lipid bilayer that can be released by a variety of vascular, parenchymal, or blood cells and that contain membrane and cytosolic proteins, organelles, lipids, and RNA supplied from and characteristic for their respective parental cells. Owing to this endowment, MPs can effectively interact with other cell types via fusion, receptor-mediated interaction, uptake, or mediator release, thereby acting as intrinsic stimulators, modulators, or even attenuators in a variety of disease processes. This review summarizes current knowledge on the formation and potential functional role of different MPs in inflammatory diseases with a specific focus on ALI/ARDS. ALI has been associated with the formation of MPs from such diverse cellular origins as platelets, neutrophils, monocytes, lymphocytes, red blood cells, and endothelial and epithelial cells. Because of their considerable heterogeneity in terms of origin and functional properties, MPs may contribute via both harmful and beneficial effects to the characteristic pathological features of ALI/ARDS. A better understanding of the formation, function, and relevance of MPs may give rise to new promising therapeutic strategies to modulate coagulation, inflammation, endothelial function, and permeability either through

  16. Nonrespiratory lung function

    International Nuclear Information System (INIS)

    Isawa, Toyoharu

    1994-01-01

    The function of the lungs is primarily the function as a gas exchanger: the venous blood returning to the lungs is arterialized with oxygen in the lungs and the arterialized blood is sent back again to the peripheral tissues of the whole body to be utilized for metabolic oxygenation. Besides the gas exchanging function which we call ''respiratory lung function'' the lungs have functions that have little to do with gas exchange itself. We categorically call the latter function of the lungs as ''nonrespiratory lung function''. The lungs consist of the conductive airways, the gas exchanging units like the alveoli, and the interstitial space that surrounds the former two compartments. The interstitial space contains the blood and lymphatic capillaries, collagen and elastic fibers and cement substances. The conductive airways and the gas exchanging units are directly exposed to the atmosphere that contains various toxic and nontoxic gases, fume and biological or nonbiological particles. Because the conductive airways are equipped with defense mechanisms like mucociliary clearance or coughs to get rid of these toxic gases, particles or locally produced biological debris, we are usually free from being succumbed to ill effects of inhaled materials. By use of nuclear medicine techniques, we can now evaluate mucociliary clearance function, and other nonrespiratory lung functions as well in vivo

  17. Low tidal volume protects pulmonary vasomotor function from “second-hit” injury in acute lung injury rats

    Directory of Open Access Journals (Sweden)

    Pan Chun

    2012-09-01

    Full Text Available Abstract Background Sepsis could induce indirect acute lung injury(ALI, and pulmonary vasomotor dysfunction. While low tidal volume is advocated for treatment of ALI patients. However, there is no evidence for low tidal volume that it could mitigate pulmonary vasomotor dysfunction in indirect ALI. Our study is to evaluate whether low tidal volume ventilation could protect the pulmonary vascular function in indirect lipopolysaccharide (LPS induced acute lung injury rats. Methods An indirect ALI rat model was induced by intravenous infusion of LPS. Thirty rats (n = 6 in each group were randomly divided into (1Control group; (2 ALI group; (3 LV group (tidal volume of 6mL/kg; (4 MV group (tidal volume of 12mL/kg; (5VLV group (tidal volume of 3mL/kg. Mean arterial pressure and blood gas analysis were monitored every 2 hours throughout the experiment. Lung tissues and pulmonary artery rings were immediately harvested after the rats were bled to be killed to detect the contents of endothelin-1 (ET-1, endothelial nitric oxide synthase (eNOS and TNF-α. Acetylcholine (Ache-induced endothelium-dependent and sodium nitroprusside (SNP-induced endothelium-independent relaxation of isolated pulmonary artery rings were measured by tensiometry. Results There was no difference within groups concerning blood pressure, PaCO2 and SNP-induced endothelium-independent relaxation of pulmonary artery rings. Compared with MV group, LV group significantly reduced LPS-induced expression of ET-1 level (113.79 ± 7.33pg/mL vs. 152.52 ± 12.75pg/mL, P P P -7mol/L-10-4mol/L-induced vasodilatation was ameliorated 30% more in LV group than in MV group. Conclusions Low tidal volume could protect the pulmonary vasodilative function during indirect ALI by decreasing vasoconstrictor factors, increasing expressions of vasodilator factors in pulmonary endothelial cells, and inhibiting inflammation injuries.

  18. Lung Function in Wheezing Infants after Acute Lower Respiratory Tract Infection and Its Association with Respiratory Outcome

    Directory of Open Access Journals (Sweden)

    Yuan-Yuan Qi

    2017-01-01

    Conclusions: Impaired lung function was present in wheezing infants with ALRTI and the deficits persisted. In addition, the lower level of TPTEF/TE and VPTEF/VE was a risk factor for poor respiratory outcome.

  19. Pediatric Acute Respiratory Distress Syndrome : Consensus Recommendations From the Pediatric Acute Lung Injury Consensus Conference

    NARCIS (Netherlands)

    Jouvet, Philippe; Thomas, Neal J.; Willson, Douglas F.; Erickson, Simon; Khemani, Robinder; Smith, Lincoln; Zimmerman, Jerry; Dahmer, Mary; Flori, Heidi; Quasney, Michael; Sapru, Anil; Cheifetz, Ira M.; Rimensberger, Peter C.; Kneyber, Martin; Tamburro, Robert F.; Curley, Martha A. Q.; Nadkarni, Vinay; Valentine, Stacey; Emeriaud, Guillaume; Newth, Christopher; Carroll, Christopher L.; Essouri, Sandrine; Dalton, Heidi; Macrae, Duncan; Lopez-Cruces, Yolanda; Quasney, Michael; Santschi, Miriam; Watson, R. Scott; Bembea, Melania

    Objective: To describe the final recommendations of the Pediatric Acute Lung Injury Consensus Conference. Design: Consensus conference of experts in pediatric acute lung injury. Setting: Not applicable. Subjects: PICU patients with evidence of acute lung injury or acute respiratory distress

  20. Receptor for advanced glycation end-products and World Trade Center particulate induced lung function loss: A case-cohort study and murine model of acute particulate exposure.

    Science.gov (United States)

    Caraher, Erin J; Kwon, Sophia; Haider, Syed H; Crowley, George; Lee, Audrey; Ebrahim, Minah; Zhang, Liqun; Chen, Lung-Chi; Gordon, Terry; Liu, Mengling; Prezant, David J; Schmidt, Ann Marie; Nolan, Anna

    2017-01-01

    World Trade Center-particulate matter(WTC-PM) exposure and metabolic-risk are associated with WTC-Lung Injury(WTC-LI). The receptor for advanced glycation end-products (RAGE) is most highly expressed in the lung, mediates metabolic risk, and single-nucleotide polymorphisms at the AGER-locus predict forced expiratory volume(FEV). Our objectives were to test the hypotheses that RAGE is a biomarker of WTC-LI in the FDNY-cohort and that loss of RAGE in a murine model would protect against acute PM-induced lung disease. We know from previous work that early intense exposure at the time of the WTC collapse was most predictive of WTC-LI therefore we utilized a murine model of intense acute PM-exposure to determine if loss of RAGE is protective and to identify signaling/cytokine intermediates. This study builds on a continuing effort to identify serum biomarkers that predict the development of WTC-LI. A case-cohort design was used to analyze a focused cohort of male never-smokers with normal pre-9/11 lung function. Odds of developing WTC-LI increased by 1.2, 1.8 and 1.0 in firefighters with soluble RAGE (sRAGE)≥97pg/mL, CRP≥2.4mg/L, and MMP-9≤397ng/mL, respectively, assessed in a multivariate logistic regression model (ROCAUC of 0.72). Wild type(WT) and RAGE-deficient(Ager-/-) mice were exposed to PM or PBS-control by oropharyngeal aspiration. Lung function, airway hyperreactivity, bronchoalveolar lavage, histology, transcription factors and plasma/BAL cytokines were quantified. WT-PM mice had decreased FEV and compliance, and increased airway resistance and methacholine reactivity after 24-hours. Decreased IFN-γ and increased LPA were observed in WT-PM mice; similar findings have been reported for firefighters who eventually develop WTC-LI. In the murine model, lack of RAGE was protective from loss of lung function and airway hyperreactivity and was associated with modulation of MAP kinases. We conclude that in a multivariate adjusted model increased sRAGE is

  1. Receptor for advanced glycation end-products and World Trade Center particulate induced lung function loss: A case-cohort study and murine model of acute particulate exposure.

    Directory of Open Access Journals (Sweden)

    Erin J Caraher

    Full Text Available World Trade Center-particulate matter(WTC-PM exposure and metabolic-risk are associated with WTC-Lung Injury(WTC-LI. The receptor for advanced glycation end-products (RAGE is most highly expressed in the lung, mediates metabolic risk, and single-nucleotide polymorphisms at the AGER-locus predict forced expiratory volume(FEV. Our objectives were to test the hypotheses that RAGE is a biomarker of WTC-LI in the FDNY-cohort and that loss of RAGE in a murine model would protect against acute PM-induced lung disease. We know from previous work that early intense exposure at the time of the WTC collapse was most predictive of WTC-LI therefore we utilized a murine model of intense acute PM-exposure to determine if loss of RAGE is protective and to identify signaling/cytokine intermediates. This study builds on a continuing effort to identify serum biomarkers that predict the development of WTC-LI. A case-cohort design was used to analyze a focused cohort of male never-smokers with normal pre-9/11 lung function. Odds of developing WTC-LI increased by 1.2, 1.8 and 1.0 in firefighters with soluble RAGE (sRAGE≥97pg/mL, CRP≥2.4mg/L, and MMP-9≤397ng/mL, respectively, assessed in a multivariate logistic regression model (ROCAUC of 0.72. Wild type(WT and RAGE-deficient(Ager-/- mice were exposed to PM or PBS-control by oropharyngeal aspiration. Lung function, airway hyperreactivity, bronchoalveolar lavage, histology, transcription factors and plasma/BAL cytokines were quantified. WT-PM mice had decreased FEV and compliance, and increased airway resistance and methacholine reactivity after 24-hours. Decreased IFN-γ and increased LPA were observed in WT-PM mice; similar findings have been reported for firefighters who eventually develop WTC-LI. In the murine model, lack of RAGE was protective from loss of lung function and airway hyperreactivity and was associated with modulation of MAP kinases. We conclude that in a multivariate adjusted model increased s

  2. Icam-1 and acute pancreatitis complicated by acute lung injury.

    Science.gov (United States)

    Zhang, XiPing; Wu, Dijiong; Jiang, Xinge

    2009-01-08

    One of the most common complications of acute pancreatitis is acute lung injury, during which intercellular adhesion molecule-1 (ICAM-1) plays an important role by participating in leukocyte adhesion and activation as well as by inducing the "cascade effect" of inflammatory mediators, pulmonary microcirculation dysfunction and even acute respiratory distress syndrome, multiple organ failure or death. Although it is generally believed that the modulatory mechanism of ICAM-1 during this process is associated with the activation of nuclear transcription factor kappa B which is mediated by IL-1, IL-6, IL-18 and oxygen free radical, etc., further studies are still required to clarify it. Since the upregulation of ICAM-1 expression in the lung during acute lung injury is one of main pathogeneses, the early detection of the ICAM-1 expression level may contribute to the prevention and treatment of acute lung injury. Moreover, reducing pulmonary ICAM-1 expression levels through treatment with anti-ICAM-1 monoclonal antibody (aICAM-1) and antagonists of the neurokinin 1 receptor, etc., should have a positive effect on protecting the lungs during acute pancreatitis. This review aims to further clarify the relationship between ICAM-1 and acute pancreatitis complicated by acute lung injury, and therefore provides a theoretical basis for the formulation of corresponding therapeutic measures in clinical practice for acute pancreatitis.

  3. Measurement of lung function in awake 2-4-year-old asthmatic children during methacholine challenge and acute asthma

    DEFF Research Database (Denmark)

    Klug, B; Bisgaard, H

    1996-01-01

    sensitive than Rint and Rrs5; the sensitivity of tcPo2, Rint, and Rrs5 was not significantly different. Measurements in eight of the subjects performed during an episode of acute asthma yielded comparable results in regard to the sensitivity of the techniques. Measurements improved significantly after...... bronchodilator administration; however, the response to bronchodilator tended to be less during acute asthma and was best demonstrated by a deterioration of tcPo2. All the evaluated techniques reliably reflect short-term changes in respiratory function and can provide clinically useful estimates of airway...

  4. Acute respiratory distress syndrome in a neonate due to possible transfusion-related acute lung injury

    Directory of Open Access Journals (Sweden)

    Arti Maria

    2017-01-01

    Full Text Available Transfusion-related acute lung injury (TRALI is a potentially life-threatening complication of blood component transfusion. It is relatively underdiagnosed entity in neonates with scant literature. We report a case of TRALI in a preterm neonate developing acute respiratory distress within 6 h of blood product transfusion in the absence of preexisting lung disease. Prompt ventilator and supportive management were instituted. The baby showed clinical and radiological improvement within 12 h; however, he succumbed to death due to acute massive pulmonary hemorrhage 36 h later. Possibility of TRALI should be kept if there is sudden deterioration of lung function after blood transfusion.

  5. Effects of Conventional Mechanical Ventilation Performed by Two Neonatal Ventilators on the Lung Functions of Rabbits with Meconium-Induced Acute Lung Injury

    Directory of Open Access Journals (Sweden)

    Mokra D

    2016-12-01

    Full Text Available Severe meconium aspiration syndrome (MAS in the neonates often requires a ventilatory support. As a method of choice, a conventional mechanical ventilation with small tidal volumes (VT<6 ml/kg and appropriate ventilatory pressures is used. The purpose of this study was to assess the short-term effects of the small-volume CMV performed by two neonatal ventilators: Aura V (Chirana Stara Tura a.s., Slovakia and SLE5000 (SLE Ltd., UK on the lung functions of rabbits with experimentally-induced MAS and to estimate whether the newly developed neonatal version of the ventilator Aura V is suitable for ventilation of the animals with MAS.

  6. Lung function; Lungenfunktion

    Energy Technology Data Exchange (ETDEWEB)

    Sorichter, S. [Universitaetsklinikum Freiburg, Abteilung Pneumologie, Freiburg (Germany)

    2009-08-15

    The term lung function is often restricted to the assessment of volume time curves measured at the mouth. Spirometry includes the assessment of lung volumes which can be mobilised with the corresponding flow-volume curves. In addition, lung volumes that can not be mobilised, such as the residual volume, or only partially as FRC and TLC can be measured by body plethysmography combined with the determination of the airway resistance. Body plethysmography allows the correct positioning of forced breathing manoeuvres on the volume-axis, e.g. before and after pharmacotherapy. Adding the CO single breath transfer factor (T{sub LCO}), which includes the measurement of the ventilated lung volume using He, enables a clear diagnosis of different obstructive, restrictive or mixed ventilatory defects with and without trapped air. Tests of reversibility and provocation, as well as the assessment of inspiratory mouth pressures (PI{sub max}, P{sub 0.1}) help to classify the underlying disorder and to clarify treatment strategies. For further information and to complete the diagnostic of disturbances of the ventilation, diffusion and/or perfusion (capillar-)arterial bloodgases at rest and under physical strain sometimes amended by ergospirometry are recommended. Ideally, lung function measurements are amended by radiological and nuclear medicine techniques. (orig.) [German] Unter dem Begriff Lungenfunktion wird die Bestimmung der Lungenvolumina am Mund verstanden. Dabei werden die mobilisierbaren Lungenvolumina mit den zugehoerigen Fluss-Volumen-Kurven mittels Spirometrie und Ganzkoerperplethysmographie (GKP) und die nicht (RV) und teilweise mobilisierbaren Lungenvolumina (FRC, TLC) einschliesslich der Atemwegswiderstaende bestimmt. Die GKP ermoeglicht zusaetzlich die korrekte (Volumenachsen-)Positionierung der forcierten Atemmanoever. Dieses erlaubt eine uebersichtlichere graphische Darstellung z. B. vor und nach der Applikation pharmakologisch wirksamer Substanzen. Wird die GKP

  7. Non-invasive ventilation used as an adjunct to airway clearance treatments improves lung function during an acute exacerbation of cystic fibrosis: a randomised trial

    Directory of Open Access Journals (Sweden)

    Tiffany J Dwyer

    2015-07-01

    Full Text Available Question: During an acute exacerbation of cystic fibrosis, is non-invasive ventilation beneficial as an adjunct to the airway clearance regimen? Design: Randomised controlled trial with concealed allocation and intention-to-treat analysis. Participants: Forty adults with moderate to severe cystic fibrosis lung disease and who were admitted to hospital for an acute exacerbation. Intervention: Comprehensive inpatient care (control group compared to the same care with the addition of non-invasive ventilation during airway clearance treatments from Day 2 of admission until discharge (experimental group. Outcome measures: Lung function and subjective symptom severity were measured daily. Fatigue was measured at admission and discharge on the Schwartz Fatigue Scale from 7 (no fatigue to 63 (worst fatigue points. Quality of life and exercise capacity were also measured at admission and discharge. Length of admission and time to next hospital admission were recorded. Results: Analysed as the primary outcome, the experimental group had a greater rate of improvement in forced expiratory volume in 1 second (FEV1 than the control group, but this was not statistically significant (MD 0.13% predicted per day, 95% CI –0.03 to 0.28. However, the experimental group had a significantly higher FEV1 at discharge than the control group (MD 4.2% predicted, 95% CI 0.1 to 8.3. The experimental group reported significantly lower levels of fatigue on the Schwartz fatigue scale at discharge than the control group (MD 6 points, 95% CI 1 to 11. There was no significant difference between the experimental and control groups in subjective symptom severity, quality of life, exercise capacity, length of hospital admission or time to next hospital admission. Conclusion: Among people hospitalised for an acute exacerbation of cystic fibrosis, the use of non-invasive ventilation as an adjunct to the airway clearance regimen significantly improves FEV1 and fatigue. Trial

  8. [Effect of Ginkgo biloba extract on the function of alveolar polymorphonuclear neutrophils in severe acute pancreatitis rats complicated with lung injury].

    Science.gov (United States)

    Xu, Xiao-Wu; Yang, Xiao-Min; Jin, Zhou-Xiang; Zhu, Shao-Jun

    2014-04-01

    To explore the effect of Ginkgo biloba extract (GBE) on the function of alveolar polymorphonuclear neutrophils (PMN) in severe acute pancreatitis (SAP) rats complicated with lung injury (LI). Forty-eight adult SD rats were randomly divided into three groups, i.e., the sham-operation group, the SAP group, and the GBE treatment group, 16 in each group. The SAP model was successfully induced by retrograde injection of 5% sodium taurocholate solution into the biliopancreatic duct. Rats in the sham-operation group only received flipping of the duodenum. Those in the GBE treatment group received GBE intervention based on SAP model. Equal volume of normal saline was given to rats in the sham-operation group and the SAP group. Rats were sacrificed at 6 and 12 h after operation respectively. The lung tissue was sampled to evaluate the LI score. The wet/dry ratio (W/D) of lung tissues was detected. The activity of myeloperoxidase (MPO) was measured. Alveolar PMN was harvested by bronchoalveolar lavage. The content of neutrophil elastase (NE) in bronchoalveolar lavage fluid (BALF) was measured by enzyme-linked immunoabsorbent assay (ELISA). The percentage of CD11b/CD18 double positive PMN was detected using flow cytometry. The expression of intercellular adhesion molecule-1 (ICAM-1) and NE protein in the lung tissue was detected by Western blot. Compared with the sham-operation group, significant pathologic lesion occurred in the lung tissue of rats in the SAP group; the pathologic LI score, lung tissue W/D ratio, MPO, and NE content in BALF significantly increased, the expression of ICAM-1 and NE in the lung tissue was obviously up-regulated, and the percentage of CD11b/CD18 double positive PMN significantly increased (P treatment group (P complicated with LI, resulting in the adherence of PMN to pulmonary vascular endothelial cells, and then activating PMN to release NE and aggravate LI. GBE could alleviate LI through down-regulating the expression ICAM-1 and CD11b/CD18

  9. Lung function measurements in children

    DEFF Research Database (Denmark)

    Poorisrisak, Porntiva

    2010-01-01

    was to expand normative sRaw values for non-asthmatic children in 5 centers. 105 healthy preschool children were recruited locally for sRaw measurements. Normative data was generated and was without significant difference between centers and independent of height, weight, age and gender. Furthermore...... and highlights the need for developing methods for verification of resistance measures to assure accuracy. Normative data were subsequently generated. Importantly other centers using such normative data should first consider proper calibration before applying reference values. Study II-III: Acute respiratory...... syncytial virus (RSV) bronchiolitis may occur in otherwise healthy infants. It is not known whether viral bronchiolitis is causatively related to asthma or simply identifies infants at risk for subsequent wheezing from an atopic predisposition or pre-existing abnormal lung function. First aim...

  10. A lung function information system

    NARCIS (Netherlands)

    A.F.M. Verbraak (Anton); E.J. Hoorn (Ewout); J. de Vries (Julius); J.M. Bogaard (Jan); A. Versprille (Adrian)

    1991-01-01

    markdownabstractAbstract A lung function information system (LFIS) was developed for the data analysis of pulmonary function tests at different locations. This system was connected to the hospital information system (HIS) for the retrieval of patient data and the storage of the lung function

  11. Contribution of neutrophils to acute lung injury.

    Science.gov (United States)

    Grommes, Jochen; Soehnlein, Oliver

    2011-01-01

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

  12. Impaired Nongas Exchange Functions of the Lung and Their Role in the Development of Acute Respiratory Distress Syndrome in Severe Brain Injury

    Directory of Open Access Journals (Sweden)

    Yu. A. Churlyaev

    2005-01-01

    Full Text Available The study was undertaken to examine the impact of the lung on the content of adrenaline, noradrenaline, serotonin, and lactic acid in systemic blood flow and to define their contribution to the development of acute respiratory distress syndrome (ARDS in severe brain injury (SBI. Forty victims with severe brain injury were examined. A study group comprised 26 patients. On admission, the patients were found to have ARDSj, later on 12 patients of them were observed to have its progression and to develop pneumonia in its presence. A control group included 14 victims. There were no postoperative complications. During 7 days after brain injury, the time course of changes were determined in the mixed venous (pulmonary arterial and arterial (femoral arterial levels of adrenaline and noradrenaline by fluorometry and in those of serotonin and lactic acid by the fluorescence technique [8] and enzymatic assay, respectively. The performed studies have indicated that in SBI, a significant activation of the sympathicoadrenal system results in a noticeable humoral reaction, by increasing the concentration of biologically active substances in the blood flowing to the lung, which leads to a load and subsequent decompensation of nongas exchange functions of the lung in the inactivation of serotonin, noradrenaline, their absorption of lactate, which in the presence of neurodystrophic changes has a great impact on the development of ARDS in victims with SBI. In this case, the clinical, X-ray, and biochemical signs of the development of ARDS appear 12—36 hours after the detected nongas exchange dysfunctions are detectable.

  13. MODERN INSIGHTS INTO THE ROLE OF HEMORHEOLOGICAL DEVIATIONS AND FUNCTIONAL STATUS OF THE ENDOTHELIAL TISSUE IN THE PATHOGENESIS OF ACUTE INFLAMMATORY LUNG AND BRONCHIAL DISEASES AMONG CHILDREN

    Directory of Open Access Journals (Sweden)

    A.V. Mozhaev

    2007-01-01

    Full Text Available Disorders of the endothelial tissue and hemorheology function build up one of the pathogenic bases to form the acute inflammatory abnormality of the respiratory tract among children. The overview highlights the information on the role and disorders of the erythrocyte clumping and plasticity, blood viscosity and function of the endothelial tissue as a response to the acute respiratory infections among children.Key words: endothelial dysfunction, hemorheology, hemorheological deviations, acute respiratory infections, acute bronchopulmonary diseases, children.

  14. Effect of dobutamine on extravascular lung water index, ventilator function, and perfusion parameters in acute respiratory distress syndrome associated with septic shock.

    Science.gov (United States)

    Zhou, Min; Dai, Ji; Du, Min; Wang, Wei; Guo, Changxing; Wang, Yi; Tang, Rui; Xu, Fengling; Rao, Zhuqing; Sun, Gengyun

    2016-08-01

    The role of dobutamine in the relief of pulmonary edema during septic shock-induced acute respiratory distress syndrome (ARDS) remains undetermined, due to a lack of controllable and quantitative clinical studies. Our objective was to assess the potential effects of dobutamine on extravascular lung water index (ELWI) in septic shock-induced ARDS, reflecting its importance in pulmonary edema. At the same time, ventilator function and perfusion parameters were evaluated. We designed a prospective, non-randomized, non-blinded, controlled study to compare the differences in PiCCO parameters after 6 h of constant dobutamine infusion (15 μg/kg/min), in the baseline parameters in 26 septic shock-related ARDS patients with cardiac index ≥ 2.5I/min/m(2) and hyperlactatemia. These patients (12 survivors/14 non-survivors) were monitored using the PiCCO catheter system within 48 h of onset of septic shock. The dynamic changes in ELWI, which is typically used for quantifying the extent of pulmonary edema, were evaluated, and the corresponding ventilator function and tissue perfusion parameters were also measured. Decreasing ELWI (p = 0.0376) was accompanied by significantly decreased SVRI (p septic shock-induced ARDS, dobutamine treatment demonstrated a beneficial effect by relieving pulmonary edema in patients, without a negative elevation in preload or hemodynamics, which might account for the improvements in ventilator function and tissue hypoperfusion.

  15. Acute and subacute chemical-induced lung injuries: HRCT findings

    Energy Technology Data Exchange (ETDEWEB)

    Akira, Masanori, E-mail: Akira@kch.hosp.go.jp [Department of Radiology, National Hospital Organization Kinki-Chuo Chest Medical Center, 1180 Nagasone-cho, Kita-ku, Sakai City, Osaka 591-8555 (Japan); Suganuma, Narufumi [Department of Environmental Medicine, Kochi Medical School (Japan)

    2014-08-15

    Lung injury caused by chemicals includes bronchitis, bronchiolitis, chemical pneumonitis, pulmonary edema, acute respiratory distress syndrome, organizing pneumonia, hypersensitivity pneumonitis, acute eosinophilic pneumonia, and sarcoid-like granulomatous lung disease. Each chemical induces variable pathophysiology and the situation resembles to the drug induced lung disease. The HRCT features are variable and nonspecific, however HRCT may be useful in the evaluation of the lung injuries and so we should know about HRCT features of lung parenchymal abnormalities caused by chemicals.

  16. Human models of acute lung injury

    Directory of Open Access Journals (Sweden)

    Alastair G. Proudfoot

    2011-03-01

    Full Text Available Acute lung injury (ALI is a syndrome that is characterised by acute inflammation and tissue injury that affects normal gas exchange in the lungs. Hallmarks of ALI include dysfunction of the alveolar-capillary membrane resulting in increased vascular permeability, an influx of inflammatory cells into the lung and a local pro-coagulant state. Patients with ALI present with severe hypoxaemia and radiological evidence of bilateral pulmonary oedema. The syndrome has a mortality rate of approximately 35% and usually requires invasive mechanical ventilation. ALI can follow direct pulmonary insults, such as pneumonia, or occur indirectly as a result of blood-borne insults, commonly severe bacterial sepsis. Although animal models of ALI have been developed, none of them fully recapitulate the human disease. The differences between the human syndrome and the phenotype observed in animal models might, in part, explain why interventions that are successful in models have failed to translate into novel therapies. Improved animal models and the development of human in vivo and ex vivo models are therefore required. In this article, we consider the clinical features of ALI, discuss the limitations of current animal models and highlight how emerging human models of ALI might help to answer outstanding questions about this syndrome.

  17. LUNG FUNCTION TESTING IN CHILDREN

    Directory of Open Access Journals (Sweden)

    Matjaž Fležar

    2004-03-01

    Full Text Available Background. Lung function testing in children above five years old is standardised similarly as is in adult population (1. Nevertheless bronchial provocation testing can be more hazardous since the calibre and reactivity of childhood airway is different. We analysed the frequency of different lung function testing procedures and addressed the safety issues of bronchial provocation testing in children.Methods. We analysed lung function testing results in 517 children, older than 5 years, tested in our laboratory in threeyear period. Spirometry was done in every patient, metacholine provocation test was used as a part of diagnostic work-up in suspected asthma. In case of airway obstruction, bronchodilator test with salbutamol was used instead of a metacholine provocation test.Results. The most common procedure in children was spirometry with bronchial provocation test as a part of diagnostic work-up of obstructive syndrome (mostly asthma. 291 children required metacholine test and 153 tests were interpreted as positive. The decline in expiratory flows (forced expiratory flow in first second – FEV1 in positive tests was greater than in adult population as was the dose of metacholine, needed to induce bronchoconstriction. The compliance of children was better than in adults.Conclusions. Lung function testing in children is reliable and safe and can be done in a well-standardised laboratory that follows the regulations of such testing in adults.

  18. Acute lung injury induces cardiovascular dysfunction

    DEFF Research Database (Denmark)

    Suda, Koichi; Tsuruta, Masashi; Eom, Jihyoun

    2011-01-01

    Acute lung injury (ALI) is associated with systemic inflammation and cardiovascular dysfunction. IL-6 is a biomarker of this systemic response and a predictor of cardiovascular events, but its possible causal role is uncertain. Inhaled corticosteroids and long-acting β2 agonists (ICS/LABA) down......-regulate the systemic expression of IL-6, but whether they can ameliorate the cardiovascular dysfunction related to ALI is uncertain. We sought to determine whether IL-6 contributes to the cardiovascular dysfunction related to ALI, and whether budesonide/formoterol ameliorates this process. Wild-type mice were...... the rise in the systemic expression of IL-6 (P cardiovascular dysfunction related to LPS, and pretreatment with budesonide/formoterol reduces the systemic expression of IL-6 and improves cardiovascular dysfunction. ICS/LABA may reduce acute cardiovascular...

  19. Allicin Protects against Lipopolysaccharide-Induced Acute Lung ...

    African Journals Online (AJOL)

    Purpose: To investigate the effect of allicin, an active component of garlic, on lipopolysaccharide (LPS)- induced acute lung injury. Methods: Wistar rats were subjected to LPS intravenous injection with or without allicin treatment to induce acute lung injury (ALI) model. Also, A549 cells were stimulated with LPS in the ...

  20. Early detection of acute lung injury uncoupled to hypoxemia in pigs using ultrasound lung comets.

    Science.gov (United States)

    Gargani, Luna; Lionetti, Vincenzo; Di Cristofano, Claudio; Bevilacqua, Generoso; Recchia, Fabio A; Picano, Eugenio

    2007-12-01

    Oleic acid-induced lung injury is an established experimental model of acute lung injury in pigs and is considered to reproduce the early exudative phase of acute respiratory distress syndrome. Ultrasound lung comets are an echographic sign of extravascular lung water, originating from thickened interlobular septa. The objective of this study was to evaluate the timing and relationship between the number of ultrasound lung comets, the Pao2/Fio2 ratio, and the static respiratory compliance in an experimental model of oleic acid-induced lung injury in pigs. Laboratory experiment. Research institute. Ten anesthetized pigs. Acute lung injury was induced by injection of oleic acid (0.1 mL/kg, intravenously). Ultrasound lung comets, Pao2/Fio2, and static respiratory compliance were measured at baseline and at 15, 30, 60, and 90 mins after the injection of oleic acid. We evaluated ultrasound lung comets by transthoracic echography (7.5-MHz vascular probe), scanning on right and left hemithoraxes at 12 predefined scanning sites. Acute lung injury/acute respiratory distress syndrome was present in all pigs at 90 mins. The number of ultrasound lung comets increased over time and was consistently earlier than the decrease in Pao2/Fio2. At 15 mins, ultrasound lung comets were markedly increased, but no significant changes in Pao2/Fio2 were observed. Accordingly, static respiratory compliance was dramatically reduced at 15 mins compared with baseline (17.04 +/- 1.82 vs. 34.84 +/- 2.62 mL/cm H2O, p comets, assessed by transthoracic echography, detected extravascular lung water accumulation very early in the course of the oleic acid lung injury in pigs, in the presence of a normal Pao2/Fio2. These results suggest that ultrasound lung comets could be a very early, noninvasive, and simple method to detect and quantify pulmonary edema in acute lung injury.

  1. Lung injury in acute pancreatitis: mechanisms, prevention, and therapy.

    LENUS (Irish Health Repository)

    Shields, Conor J

    2012-02-03

    Lung injury is the most pertinent manifestation of extra-abdominal organ dysfunction in pancreatitis. The propensity of this retroperitoneal inflammatory condition to engender a diffuse and life-threatening lung injury is significant. Approximately one third of patients will develop acute lung injury and acute respiratory distress syndrome, which account for 60% of all deaths within the first week. The variability in the clinical course of pancreatitis renders it a vexing entity and makes demonstration of the efficacy of any specific intervention difficult. The distinct pathologic entity of pancreatitis-associated lung injury is reviewed with a focus on etiology and potential therapeutic maneuvers.

  2. Lung function measurements in children

    DEFF Research Database (Denmark)

    Poorisrisak, Porntiva

    2010-01-01

    The Ph.D. thesis is based on studies conducted at 6 pediatric departments in following hospitals: Naestved, Gentofte, Kolding, Skejby, Hvidovre and Rigshospitalet. Study I: Specific airway resistance (sRaw) measured by wholebody plethysmography in preschool children is increasingly used in research......, there was no effect of the child's history of atopy, parental atopy or smoking. We subsequently pooled these normative data (105 children) with previous data from 121 healthy young children; mean sRaw (SD) 1.27 kPa*s (0.25). Conclusion: Control using biological standards revealed errors in factory setting...... function and bronchial responsiveness. We found no differences within MZ twin pairs with respect to pulmonary function, fractional exhaled nitric oxide, asthma prevalence, asthma medication use, or sensitization. Secondary aim was to compare prospectively the baseline lung function and bronchial...

  3. Transfusion-related acute lung injury (TRALI – acase report

    Directory of Open Access Journals (Sweden)

    Anna Łata

    2016-03-01

    Full Text Available Transfusion-related acute lung injury is defined as acute respiratory failure which develops during or within 6 hours after transfusion of a blood component in a patient with no risk factors for respiratory insufficiency. Transfusion-related acute lung injury is diagnosed based on clinical manifestation and by excluding other causes of acute lung injury. Unambiguous diagnosis is difficult. Looking for anti-HLA and/or anti-HNA antibodies in donors and sometimes in recipients plays an important role in lab tests. Negative antibody findings, either in a donor or in a recipient, do not exclude transfusion-related acute lung injury, which, however, does not exempt from performing leukocyte antibody tests since they are extremely important for transfusion-related acute lung injury prophylaxis. The ways to prevent this reaction include: disqualifying donors with anti-HLA/HNA antibodies, screening for antibodies in multiparous women and in individuals after transfusion, modifying the way blood components are prepared and limiting blood transfusion in clinical practice. The paper presents a case of a 38-year-old woman with acute myeloid leukaemia, hospitalised at the Department of Internal Diseases and Haematology of the Military Institute of Medicine for subsequent courses of chemotherapy. During treatment, the patient had red cells and platelets concentrates transfused several times with no transfusion-related reactions. Eight days after the last chemotherapy infusion, the patient developed high temperature and her platelet count was 14 × 103 /mL. Therefore, the patient received a platelet concentrate again. About 1 hour after transfusion, the patient complained about chest pain and dyspnoea. She needed oxygen therapy. Chest X-ray revealed lung oedema with no signs of left ventricular failure. Once other causes of acute lung injury were excluded, transfusion-related acute lung injury was diagnosed.

  4. Role of TNF-α in lung tight junction alteration in mouse model of acute lung inflammation

    Directory of Open Access Journals (Sweden)

    Cuzzocrea Salvatore

    2007-10-01

    Full Text Available Abstract In the present study, we used tumor necrosis factor-R1 knock out mice (TNF-αR1KO to understand the roles of TNF-α on epithelial function in models of carrageenan-induced acute lung inflammation. In order to elucidate whether the observed anti-inflammatory status is related to the inhibition of TNF-α, we also investigated the effect of etanercept, a TNF-α soluble receptor construct, on lung TJ function. Pharmacological and genetic TNF-α inhibition significantly reduced the degree of (1 TNF-α production in pleural exudates and in the lung tissues, (2 the inflammatory cell infiltration in the pleural cavity as well as in the lung tissues (evaluated by MPO activity, (3 the alteration of ZO-1, Claudin-2, Claudin-4, Claudin-5 and β-catenin (immunohistochemistry and (4 apoptosis (TUNEL staining, Bax, Bcl-2 expression. Taken together, our results demonstrate that inhibition of TNF-α reduces the tight junction permeability in the lung tissues associated with acute lung inflammation, suggesting a possible role of TNF-α on lung barrier dysfunction.

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

    OpenAIRE

    Gilliss, Brian M.; Looney, Mark R.

    2011-01-01

    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 approache...

  6. An acute adrenal insufficiency revealing pituitary metastases of lung ...

    African Journals Online (AJOL)

    An acute adrenal insufficiency revealing pituitary metastases of lung cancer in an elderly patient. ... The hypothalamic-pituitary MRI showed a pituitary hypertrophy, a nodular thickening of the pituitary stalk. The chest X Rays ... Hence we concluded to a lung cancer with multiple pituitary and adrenal gland metastases.

  7. Transfusion related acute lung injury presenting with acute dyspnoea: a case report

    Directory of Open Access Journals (Sweden)

    Haji Altaf

    2008-10-01

    Full Text Available Abstract Introduction Transfusion-related acute lung injury is emerging as a common cause of transfusion-related adverse events. However, awareness about this entity in the medical fraternity is low and it, consequently, remains a very under-reported and often an under-diagnosed complication of transfusion therapy. Case presentation We report a case of a 46-year old woman who developed acute respiratory and hemodynamic instability following a single unit blood transfusion in the postoperative period. Investigation results were non-specific and a diagnosis of transfusion-related acute lung injury was made after excluding other possible causes of acute lung injury. She responded to symptomatic management with ventilatory and vasopressor support and recovered completely over the next 72 hours. Conclusion The diagnosis of transfusion-related acute lung injury relies on excluding other causes of acute pulmonary edema following transfusion, such as sepsis, volume overload, and cardiogenic pulmonary edema. All plasma containing blood products have been implicated in transfusion-related acute lung injury, with the majority being linked to whole blood, packed red blood cells, platelets, and fresh-frozen plasma. The pathogenesis of transfusion-related acute lung injury may be explained by a "two-hit" hypothesis, involving priming of the inflammatory machinery and then activation of this primed mechanism. Treatment is supportive, with prognosis being substantially better than for most other causes of acute lung injury.

  8. Exhaled CO, a predictor of lung function?

    DEFF Research Database (Denmark)

    Fabricius, Peder; Scharling, Henrik; Løkke, Anders

    2007-01-01

    and whether CO could provide additional information to usual measures of smoking regarding prediction of present lung function and decline in lung function over an extended period of time. METHOD: Cigarette smokers from the Copenhagen City Heart Study with valid measures of lung function and exhaled CO.......001). Increasing CO levels were correlated to a lower FEV(1)%pred and to an accelerated decline in lung function. However, in multiple linear regression analyses these correlations were not significant. CONCLUSION: Inhalation and type of cigarette affects exhaled CO levels. CO measures have no predictive value...

  9. DISTINCT PHENOTYPES OF INFILTRATING CELLS DURING ACUTE AND CHRONIC LUNG REJECTION IN HUMAN HEART-LUNG TRANSPLANTS

    NARCIS (Netherlands)

    WINTER, JB; CLELLAND, C; GOUW, ASH; PROP, J

    1995-01-01

    To differentiate between acute and chronic lung rejection in an early stage, phenotypes of infiltrating inflammatory cells were analyzed in 34 transbronchial biopsies (TBBs) of 24 patients after heart-lung transplantation. TBBs were taken during during acute lung rejection and chronic lung

  10. Multiple image x-radiography for functional lung imaging

    Science.gov (United States)

    Aulakh, G. K.; Mann, A.; Belev, G.; Wiebe, S.; Kuebler, W. M.; Singh, B.; Chapman, D.

    2018-01-01

    Detection and visualization of lung tissue structures is impaired by predominance of air. However, by using synchrotron x-rays, refraction of x-rays at the interface of tissue and air can be utilized to generate contrast which may in turn enable quantification of lung optical properties. We utilized multiple image radiography, a variant of diffraction enhanced imaging, at the Canadian light source to quantify changes in unique x-ray optical properties of lungs, namely attenuation, refraction and ultra small-angle scatter (USAXS or width) contrast ratios as a function of lung orientation in free-breathing or respiratory-gated mice before and after intra-nasal bacterial endotoxin (lipopolysaccharide) instillation. The lung ultra small-angle scatter and attenuation contrast ratios were significantly higher 9 h post lipopolysaccharide instillation compared to saline treatment whereas the refraction contrast decreased in magnitude. In ventilated mice, end-expiratory pressures result in an increase in ultra small-angle scatter contrast ratio when compared to end-inspiratory pressures. There were no detectable changes in lung attenuation or refraction contrast ratio with change in lung pressure alone. In effect, multiple image radiography can be applied towards following optical properties of lung air-tissue barrier over time during pathologies such as acute lung injury.

  11. Adaptive Support Ventilation May Deliver Unwanted Respiratory Rate-Tidal Volume Combinations in Patients with Acute Lung Injury Ventilated According to an Open Lung Concept

    NARCIS (Netherlands)

    Dongelmans, Dave A.; Paulus, Frederique; Veelo, Denise P.; Binnekade, Jan M.; Vroom, Margreeth B.; Schultz, Marcus J.

    2011-01-01

    Background: With adaptive support ventilation, respiratory rate and tidal volume (V(T)) are a function of the Otis least work of breathing formula. We hypothesized that adaptive support ventilation in an open lung ventilator strategy would deliver higher V(T)s to patients with acute lung injury.

  12. Platelets induce neutrophil extracellular traps in transfusion-related acute lung injury.

    Science.gov (United States)

    Caudrillier, Axelle; Kessenbrock, Kai; Gilliss, Brian M; Nguyen, John X; Marques, Marisa B; Monestier, Marc; Toy, Pearl; Werb, Zena; Looney, Mark R

    2012-07-01

    There is emerging evidence that platelets are major contributors to inflammatory processes through intimate associations with innate immune cells. Here, we report that activated platelets induce the formation of neutrophil extracellular traps (NETs) in transfusion-related acute lung injury (TRALI), which is the leading cause of death after transfusion therapy. NETs are composed of decondensed chromatin decorated with granular proteins that function to trap extracellular pathogens; their formation requires the activation of neutrophils and release of their DNA in a process that may or may not result in neutrophil death. In a mouse model of TRALI that is neutrophil and platelet dependent, NETs appeared in the lung microvasculature and NET components increased in the plasma. We detected NETs in the lungs and plasma of human TRALI and in the plasma of patients with acute lung injury. In the experimental TRALI model, targeting platelet activation with either aspirin or a glycoprotein IIb/IIIa inhibitor decreased NET formation and lung injury. We then directly targeted NET components with a histone blocking antibody and DNase1, both of which protected mice from TRALI. These data suggest that NETs contribute to lung endothelial injury and that targeting NET formation may be a promising new direction for the treatment of acute lung injury.

  13. Obesity-Induced Endoplasmic Reticulum Stress Causes Lung Endothelial Dysfunction and Promotes Acute Lung Injury.

    Science.gov (United States)

    Shah, Dilip; Romero, Freddy; Guo, Zhi; Sun, Jianxin; Li, Jonathan; Kallen, Caleb B; Naik, Ulhas P; Summer, Ross

    2017-08-01

    Obesity is a significant risk factor for acute respiratory distress syndrome. The mechanisms underlying this association are unknown. We recently showed that diet-induced obese mice exhibit pulmonary vascular endothelial dysfunction, which is associated with enhanced susceptibility to LPS-induced acute lung injury. Here, we demonstrate that lung endothelial dysfunction in diet-induced obese mice coincides with increased endoplasmic reticulum (ER) stress. Specifically, we observed enhanced expression of the major sensors of misfolded proteins, including protein kinase R-like ER kinase, inositol-requiring enzyme α, and activating transcription factor 6, in whole lung and in primary lung endothelial cells isolated from diet-induced obese mice. Furthermore, we found that primary lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of diet-induced obese mice, including an increase in expression of endothelial adhesion molecules and a decrease in expression of endothelial cell-cell junctional proteins. Similar changes were observed in lung endothelial cells and in whole-lung tissue after exposure to tunicamycin, a compound that causes ER stress by blocking N-linked glycosylation, indicating that ER stress causes endothelial dysfunction in the lung. Treatment with 4-phenylbutyric acid, a chemical protein chaperone that reduces ER stress, restored vascular endothelial cell expression of adhesion molecules and protected against LPS-induced acute lung injury in diet-induced obese mice. Our work indicates that fatty acids in obese serum induce ER stress in the pulmonary endothelium, leading to pulmonary endothelial cell dysfunction. Our work suggests that reducing protein load in the ER of pulmonary endothelial cells might protect against acute respiratory distress syndrome in obese

  14. Mechanisms of decreased intestinal epithelial proliferation and increased apoptosis in murine acute lung injury.

    Science.gov (United States)

    Husain, Kareem D; Stromberg, Paul E; Woolsey, Cheryl A; Turnbull, Isaiah R; Dunne, W Michael; Javadi, Pardis; Buchman, Timothy G; Karl, Irene E; Hotchkiss, Richard S; Coopersmith, Craig M

    2005-10-01

    The aim of this study was to determine the effects of acute lung injury on the gut epithelium and examine mechanisms underlying changes in crypt proliferation and apoptosis. The relationship between severity and timing of lung injury to intestinal pathology was also examined. Randomized, controlled study. University research laboratory. Genetically inbred mice. Following induction of acute lung injury, gut epithelial proliferation and apoptosis were assessed in a) C3H/HeN wild-type and C3H/HeJ mice, which lack functional Toll-like receptor 4 (n = 17); b) C57Bl/6 mice that received monoclonal anti-tumor necrosis factor-alpha or control antibody (n = 22); and c) C57Bl/6 wild-type and transgenic mice that overexpress Bcl-2 in their gut epithelium (n = 21). Intestinal epithelial proliferation and death were also examined in animals with differing degrees of lung inflammation (n = 24) as well as in a time course analysis following a fixed injury (n = 18). Acute lung injury caused decreased proliferation and increased apoptosis in crypt epithelial cells in all animals studied. C3H/HeJ mice had higher levels of proliferation than C3H/HeN animals without additional changes in apoptosis. Anti-tumor necrosis factor-alpha antibody had no effect on gut epithelial proliferation or death. Overexpression of Bcl-2 did not change proliferation despite decreasing gut apoptosis. Proliferation and apoptosis were not correlated to severity of lung injury, as gut alterations were lost in mice with more severe acute lung injury. Changes in both gut epithelial proliferation and death were apparent within 12 hrs, but proliferation was decreased 36 hrs following acute lung injury while apoptosis returned to normal. Acute lung injury causes disparate effects on crypt proliferation and apoptosis, which occur, at least in part, through differing mechanisms involving Toll-like receptor 4 and Bcl-2. Severity of lung injury does not correlate with perturbations in proliferation or death in the

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

    Science.gov (United States)

    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

  16. Electrical impedance tomography (EIT) for quantification of pulmonary edema in acute lung injury.

    Science.gov (United States)

    Trepte, Constantin J C; Phillips, Charles R; Solà, Josep; Adler, Andy; Haas, Sebastian A; Rapin, Michael; Böhm, Stephan H; Reuter, Daniel A

    2016-01-22

    Assessment of pulmonary edema is a key factor in monitoring and guidance of therapy in critically ill patients. To date, methods available at the bedside for estimating the physiologic correlate of pulmonary edema, extravascular lung water, often are unreliable or require invasive measurements. The aim of the present study was to develop a novel approach to reliably assess extravascular lung water by making use of the functional imaging capabilities of electrical impedance tomography. Thirty domestic pigs were anesthetized and randomized to three different groups. Group 1 was a sham group with no lung injury. Group 2 had acute lung injury induced by saline lavage. Group 3 had vascular lung injury induced by intravenous injection of oleic acid. A novel, noninvasive technique using changes in thoracic electrical impedance with lateral body rotation was used to measure a new metric, the lung water ratioEIT, which reflects total extravascular lung water. The lung water ratioEIT was compared with postmortem gravimetric lung water analysis and transcardiopulmonary thermodilution measurements. A significant correlation was found between extravascular lung water as measured by postmortem gravimetric analysis and electrical impedance tomography (r = 0.80; p pulmonary edema.

  17. Autotaxin and Endotoxin-Induced Acute Lung Injury

    Science.gov (United States)

    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

  18. Autotaxin and Endotoxin-Induced Acute Lung Injury.

    Directory of Open Access Journals (Sweden)

    Marios-Angelos Mouratis

    Full Text Available 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.

  19. Role of macrophage inflammatory protein-1 alpha (MIP-1 alpha) in acute lung injury in rats

    DEFF Research Database (Denmark)

    Shanley, T P; Schmal, H; Friedl, H P

    1995-01-01

    The role of macrophage inflammatory protein-1 alpha (MIP-1 alpha) in the pathogenesis of acute lung injury in rats after intrapulmonary deposition of IgG immune complexes or intratracheal administration of LPS has been assessed. Critical to these studies was the cloning and functional expression...

  20. Transfusion Related Acute Lung Injury -A Case Report

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    Anamika

    2008-01-01

    Full Text Available Transfusion related acute lung injury (TRALI is a rare but life threatening complication of blood transfusion which is being increasingly recognized. It is caused by cross reaction between donor antibodies and host leucocytes or between donor leucocytes with host antibodies. TRALI usually presents as an Acute Lung Injury (ALI resulting in pulmonary congestion and edema, often leading to Acute Respiratory Distress Syndrome (ARDS. We report a case of TRALI in a patient who underwent laparotomy for ruptured corpus luteal cyst requiring blood transfusion. She presented with acute pulmonary edema about an hour after commencing a blood transfusion .This was managed conservatively with oxygen, steroids and diuretics. Patient improved rapidly and later discharged without any residual complications.

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

    Science.gov (United States)

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

    2016-03-01

    Laboratory and observational research studies suggest that vitamin D and marine omega-3 fatty acids may reduce risk for pneumonia, acute exacerbations of respiratory diseases including chronic obstructive lung disease (COPD) or asthma, and decline of lung function, but prevention trials with adequate dosing, adequate power, and adequate time to follow-up are lacking. The ongoing Lung VITAL study is taking advantage of a large clinical trial-the VITamin D and OmegA-3 TriaL (VITAL)--to conduct the first major evaluation of the influences of vitamin D and marine omega-3 fatty acid supplementation on pneumonia risk, respiratory exacerbation episodes, asthma control and lung function in adults. VITAL is a 5-year U.S.-wide randomized, double-blind, placebo-controlled, 2 × 2 factorial trial of supplementation with vitamin D3 ([cholecalciferol], 2000 IU/day) and marine omega-3 FA (Omacor® fish oil, eicosapentaenoic acid [EPA]+docosahexaenoic acid [DHA], 1g/day) for primary prevention of CVD and cancer among men and women, at baseline aged ≥50 and ≥55, respectively, with 5107 African Americans. In a subset of 1973 participants from 11 urban U.S. centers, lung function is measured before and two years after randomization. Yearly follow-up questionnaires assess incident pneumonia in the entire randomized population, and exacerbations of respiratory disease, asthma control and dyspnea in a subpopulation of 4314 randomized participants enriched, as shown in presentation of baseline characteristics, for respiratory disease, respiratory symptoms, and history of cigarette smoking. Self-reported pneumonia hospitalization will be confirmed by medical record review, and exacerbations will be confirmed by Center for Medicare and Medicaid Services data review. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. CHANGES IN LUNG FUNCTION IN THE TREATMENT OF PATIENTS WITH EXOGENOUS ALLERGIC ALVEOLITIS

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    V. B. Nefedov

    2014-01-01

    Full Text Available Total lung capacity (TLC, lung capacity (LC, forced LC (FLC, intrathoracic volume (ITV, pulmonary residual volume (PRV, forced expiratory volume in one second (FEV1 , (FEV1 /LC%, peak expiratory flow (PEF, maximum expiratory flow rate (MEFR25, MEFR50, MEFR75, Raw, Rin, Rex, DLCO-SB, DLCO-SB/VА, РаО2 , and РаСО2 were determined in 43 patients with exogenous allergic alveolitis (EAA before, during, and after treatment with glucocorticosteroids, hemapheresis, ambroxol, and fluimucil. Lung function became better in more than half (53.5% of the patients and worse in one fourth (25.6%; a combination of positive and negative functional changes was detected in 14.0%. Improved lung function was noted in 75.0, 50.0, and 38.5% of the patients with acute, subacute, and chronic EAA, respectively. Deterioration of lung function was determined in 46.2, 22.2, and 8.3% of the patients with chronic, subacute, and acute alveolitis, respectively. Better lung function manifested itself mainly as positive changes in lung volumes and capacities and pulmonary gas exchange function, less frequently as improved bronchial patency in the patients with acute and subacute EAA whereas the rate of positive functional changes in lung volumes and capacities, bronchial patency, and pulmonary gas exchange function was equal in those with chronic EAA. Poorer lung function appeared as negative changes in lung volumes and capacities in the patients with acute EAA, as worse pulmonary gas exchange function and negative changes in lung volumes and capacities and deteriorated bronchial patency in those with subacute and chronic EAA.

  3. Methodology of the Pediatric Acute Lung Injury Consensus Conference.

    Science.gov (United States)

    Bembea, Melania M; Jouvet, Philippe; Willson, Douglas; Thomas, Neal J

    2015-06-01

    This article describes the methodology used for the Pediatric Acute Lung Injury Consensus Conference. Consensus conference of international experts in pediatric acute respiratory distress syndrome using the Research ANd Development/University of California, Los Angeles appropriateness method and an expert recommendations process developed by the French-speaking intensive care society. Topics related to pediatric acute respiratory distress syndrome were divided into nine subgroups with a review of the literature. A group of 27 experts met three times over the course of 2 years and collaborated in their respective subgroups to define pediatric acute respiratory distress syndrome and to make recommendations regarding treatment and future research priorities. The consensus conference resulted in summary of recommendations published in Pediatric Critical Care Medicine, the present Pediatric Acute Lung Injury Consensus Conference methodology article, articles on the nine pediatric acute respiratory distress syndrome subtopics, and a review of pediatric acute respiratory distress syndrome pathophysiology published in this supplement of Pediatric Critical Care Medicine. The methodology described involved experts from around the world and the use of modern information technology. This resulted in recommendations for pediatric acute respiratory distress syndrome management, the identification of current research gaps, and future priorities.

  4. Transfusion-related acute lung injury: a change of perspective

    NARCIS (Netherlands)

    Vlaar, A. P.; Schultz, M. J.; Juffermans, N. P.

    2009-01-01

    Two decades ago, transfusion-related acute lung injury (TRALI) was considered a rare complication of transfusion medicine. Nowadays, TRALI has emerged as the leading cause of transfusion-related mortality, presumably as a consequence of reaching international agreement on defining TRALI with

  5. Life-threatening acute lung injury after gamma butyrolactone ingestion

    NARCIS (Netherlands)

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

    We describe a case of a 44-year-old woman with a borderline personality disorder and chronic gamma-butyrolactone (GBL) use who presented with progressive dyspnoea and an altered mental status. A high anion gap metabolic acidosis and acute lung injury was diagnosed. We hypothesise this was caused by

  6. Efficacy and safety of lung recruitment in pediatric patients with acute lung injury.

    Science.gov (United States)

    Boriosi, Juan P; Sapru, Anil; Hanson, James H; Asselin, Jeanette; Gildengorin, Ginny; Newman, Vivienne; Sabato, Katie; Flori, Heidi R

    2011-07-01

    To assess the safety and efficacy of a recruitment maneuver, the Open Lung Tool, in pediatric patients with acute lung injury and acute respiratory distress syndrome. Prospective cohort study using a repeated-measures design. Pediatric intensive care unit at an urban tertiary children's hospital. Twenty-one ventilated pediatric patients with acute lung injury. Recruitment maneuver using incremental positive end-expiratory pressure. The ratio of partial pressure of arterial oxygen over fraction of inspired oxygen (Pao2/Fio2 ratio) increased 53% immediately after the recruitment maneuver. The median Pao2/Fio2 ratio increased from 111 (interquartile range, 73-266) prerecruitment maneuver to 170 (interquartile range, 102-341) immediately postrecruitment maneuver (p interquartile range, 116-257) 4 hrs postrecruitment maneuver (p interquartile range, 127-236) 12 hrs postrecruitment maneuver (p interquartile range, 44-60) prerecruitment maneuver compared with 48 torr (interquartile range, 43-50) immediately postrecruitment maneuver (p = .69), 45 torr (interquartile range, 41-50) at 4 hrs postrecruitment maneuver (p interquartile range, 38-51) at 12 hrs postrecruitment maneuver. Recruitment maneuvers were well tolerated except for significant increase in Paco2 in three patients. There were no serious adverse events related to the recruitment maneuver. Using the modified open lung tool recruitment maneuver, pediatric patients with acute lung injury may safely achieve improved oxygenation and ventilation with these benefits potentially lasting up to 12 hrs postrecruitment maneuver.

  7. Protective role of vascular endothelial growth factor in endotoxin-induced acute lung injury in mice

    Directory of Open Access Journals (Sweden)

    Adachi Yoshiyuki

    2007-08-01

    inflammatory stimuli and functions as a protective factor against acute lung injury.

  8. Mesenchymal Stem Cells Promoted Lung Wound Repair through Hox A9 during Endotoxemia-Induced Acute Lung Injury

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    Xi Xin

    2017-01-01

    Full Text Available Objectives. Acute lung injury (ALI is a common clinical critical disease. Stem cells transplantation is recognized as an effective way to repair injured lung tissues. The present study was designed to evaluate the effects of mesenchymal stem cells (MSCs on repair of lung and its mechanism. Methods. MSCs carrying GFP were administrated via trachea into wild-type SD rats 4 hours later after LPS administration. The lung histological pathology and the distribution of MSCs were determined by HE staining and fluorescence microscopy, respectively. Next, differentially expressed HOX genes were screened by using real-time PCR array and abnormal expression and function of Hox A9 were analyzed in the lung and the cells. Results. MSCs promoted survival rate of ALI animals. The expression levels of multiple HOX genes had obvious changes after MSCs administration and HOX A9 gene increased by 5.94-fold after MSCs administration into ALI animals. HOX A9 was distributed in endothelial cells and epithelial cells in animal models and overexpression of Hox A9 can promote proliferation and inhibit inflammatory adhesion of MSCs. Conclusion. HoxA9 overexpression induced by MSCs may be closely linked with lung repair after endotoxin shock.

  9. Hyperinsulinemia adversely affects lung structure and function

    DEFF Research Database (Denmark)

    Singh, Suchita; Bodas, Manish; Bhatraju, Naveen K

    2016-01-01

    , was observed in the lungs of insulin-treated mice and lung cells. Our data suggests that hyperinsulinemia may have adverse effects on airway structure and function. Insulin-induced activation of β-catenin in lung tissue and the contractile effects on ASM cells may be causally related to the development...... that insulin can adversely affect respiratory health. Insulin treatment (1 μg/ml) significantly (P cells and induced collagen release. Additionally, ASM cells showed a significant increase in calcium response and mitochondrial...

  10. Immune function in acute stress.

    Science.gov (United States)

    Segal, A B; Bruno, S; Forte, W C N

    2006-01-01

    The aim of this study was to evaluate immune function in acute stress in medical students before academic examinations. Twenty-five medical students were selected because they presented intense acute stress, evaluated by the presence of the following classic signs: cold hands, intense sudoresis in the extremities, generalized sudoresis, paleness, tachycardia, confused reasoning, nervous irritability, diarrhea, and sleep disorders in the hours preceding the examination (agitated sleep, insomnia). Immediately before the examination, peripheral blood was collected from the 25 students presenting acute stress to analyze T and B cells, CD4+ and CD8+ cells, immunoglobulins, and C3 and C4 complement components, as well as phagocytic activity in neutrophils and monocytes. These investigations were repeated in the same students in situations free of acute stress. The results of the two samples collected from each student were compared. The means and standard deviations showed no significant differences for any of the parameters analyzed (p> or =0.01). We conclude that acute stress did not cause changes in the lymphocyte subpopulations, phagocytic activity of neutrophils and monocytes, serum immunoglobulins, or C3 and C4 complement components in students participating in the present study. In conditions of basal chronic stress, acute stress may cause alterations in immune function.

  11. RAGE inhibition reduces acute lung injury in mice.

    Science.gov (United States)

    Blondonnet, Raiko; Audard, Jules; Belville, Corinne; Clairefond, Gael; Lutz, Jean; Bouvier, Damien; Roszyk, Laurence; Gross, Christelle; Lavergne, Marilyne; Fournet, Marianne; Blanchon, Loic; Vachias, Caroline; Damon-Soubeyrand, Christelle; Sapin, Vincent; Constantin, Jean-Michel; Jabaudon, Matthieu

    2017-08-03

    The receptor for advanced glycation end-products (RAGE) is involved in inflammatory response during acute respiratory distress syndrome (ARDS). Growing body of evidence support strategies of RAGE inhibition in experimental lung injury, but its modalities and effects remain underinvestigated. Anesthetised C57BL/6JRj mice were divided in four groups; three of them underwent orotracheal instillation of acid and were treated with anti-RAGE monoclonal antibody (mAb) or recombinant soluble RAGE (sRAGE), acting as a decoy receptor. The fourth group served as a control. Lung injury was assessed by the analysis of blood gases, alveolar permeability, histology, AFC, and cytokines. Lung expression and distribution epithelial channels ENaC, Na,K-ATPase, and aquaporin (AQP)-5 were assessed. Treatment with either anti-RAGE mAb or sRAGE improved lung injury, arterial oxygenation and decreased alveolar inflammation in acid-injured animals. Anti-RAGE therapies were associated with restored AFC and increased lung expression of AQP-5 in alveolar cell. Blocking RAGE had potential therapeutic effects in a translational mouse model of ARDS, possibly through a decrease in alveolar type 1 epithelial cell injury as shown by restored AFC and lung AQP-5 expression. Further mechanistic studies are warranted to describe intracellular pathways that may control such effects of RAGE on lung epithelial injury and repair.

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

    Science.gov (United States)

    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

    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. 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. 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 = 5.29-155; p acute extended radiation pneumonitis (odds ratio = 6.14; 95% confidence interval = 1.0-37.4); p = 0.038). 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.

  13. Independent lung ventilation in a newborn with asymmetric acute lung injury due to respiratory syncytial virus: a case report

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    Di Nardo Matteo

    2008-06-01

    Full Text Available Abstract Introduction Independent lung ventilation is a form of protective ventilation strategy used in adult asymmetric acute lung injury, where the application of conventional mechanical ventilation can produce ventilator-induced lung injury and ventilation-perfusion mismatch. Only a few experiences have been published on the use of independent lung ventilation in newborn patients. Case presentation We present a case of independent lung ventilation in a 16-day-old infant of 3.5 kg body weight who had an asymmetric lung injury due to respiratory syncytial virus bronchiolitis. We used independent lung ventilation applying conventional protective pressure controlled ventilation to the less-compromised lung, with a respiratory frequency proportional to the age of the patient, and a pressure controlled high-frequency ventilation to the atelectatic lung. This was done because a single tube conventional ventilation protective strategy would have exposed the less-compromised lung to a high mean airways pressure. The target of independent lung ventilation is to provide adequate gas exchange at a safe mean airways pressure level and to expand the atelectatic lung. Independent lung ventilation was accomplished for 24 hours. Daily chest radiograph and gas exchange were used to evaluate the efficacy of independent lung ventilation. Extubation was performed after 48 hours of conventional single-tube mechanical ventilation following independent lung ventilation. Conclusion This case report demonstrates the feasibility of independent lung ventilation with two separate tubes in neonates as a treatment of an asymmetric acute lung injury.

  14. Acute fibrinous and organising pneumonia following lung transplantation is associated with severe allograft dysfunction and poor outcome: a case series

    Directory of Open Access Journals (Sweden)

    Keith Meyer

    2015-01-01

    Full Text Available   Acute fibrinous and organising pneumonia (AFOP is a histopathologic variant of acute lung injury that has been associated with infection and inflammatory disorders and has been reported as a complication of lung transplantation. A retrospective chart review was performed for all patients transplanted at the University of Wisconsin Hospital and Clinics from January 1995 to December 2013 (n = 561. We identified 6 recipients whose clinical course was complicated by AFOP. All recipients were found to have AFOP on lung biopsy or at post-mortem examination, and 5 of the 6 patients suffered progressive allograft dysfunction that led to fatal outcome. Only 1 of the 6 patients stabilised with augmented immunosuppression and had subsequent improvement and stabilisation of allograft function. We could not clearly identify any specific cause of AFOP, such as drug toxicity or infection. Lung transplantation can be complicated by lung injury with an AFOP pattern on histopathologic examination of lung biopsy specimens. The presence of an AFOP pattern was associated with irreversible decline in lung function that was refractory to therapeutic interventions in 5 of our 6 cases and was associated with severe allograft dysfunction and death in these 5 individuals. AFOP should be considered as a potential diagnosis when lung transplant recipients develop progressive decline in lung function that is consistent with a clinical diagnosis of chronic lung allograft dysfunction.  

  15. Pathophysiology of transfusion-related acute lung injury.

    Science.gov (United States)

    Looney, Mark R; Gilliss, Brian M; Matthay, Michael A

    2010-09-01

    The purpose of this review is to summarize the recent experimental and clinical literature on the pathogenesis of transfusion-related acute lung injury (TRALI). In both experimental and clinical TRALI, an immune priming step is generally necessary to produce lung injury. Experimental studies have used mainly lipopolysaccharide (LPS) as the priming step, whereas in clinical TRALI the specific priming events are currently being defined and include recent surgery and active infections. Experimental studies have modeled TRALI by using anti-major histocompatibility complex antibodies, antineutrophil antibodies, and also bioactive lipids isolated from stored human blood. A common theme among the experimental TRALI models is the central importance of neutrophils in mediating the early immune response and lung vascular injury. New work has focused on the interplay between neutrophils and platelets in the lung microcirculation. Finally, plasma mitigation strategies implemented in several countries are showing early promise in decreasing the incidence of TRALI from high plasma volume blood products. TRALI requires an immune priming step followed by transfusion of a blood product with either leukocyte allo-antibodies or biological response modifiers. TRALI invokes an acute immune response dominated by neutrophils interacting with platelets and the lung endothelium.

  16. Punica granatum L. Leaf Extract Attenuates Lung Inflammation in Mice with Acute Lung Injury.

    Science.gov (United States)

    Pinheiro, Aruanã Joaquim Matheus Costa Rodrigues; Gonçalves, Jaciara Sá; Dourado, Ádylla Wilenna Alves; de Sousa, Eduardo Martins; Brito, Natilene Mesquita; Silva, Lanna Karinny; Batista, Marisa Cristina Aranha; de Sá, Joicy Cortez; Monteiro, Cinara Regina Aragão Vieira; Fernandes, Elizabeth Soares; Monteiro-Neto, Valério; Campbell, Lee Ann; Zago, Patrícia Maria Wiziack; Lima-Neto, Lidio Gonçalves

    2018-01-01

    The hydroalcoholic extract of Punica granatum (pomegranate) leaves was previously demonstrated to be anti-inflammatory in a rat model of lipopolysaccharide- (LPS-) induced acute peritonitis. Here, we investigated the anti-inflammatory effects of the ethyl acetate fraction obtained from the pomegranate leaf hydroalcoholic extract (EAFPg) on the LPS-induced acute lung injury (ALI) mouse model. Male Swiss mice received either EAFPg at different doses or dexamethasone (per os) prior to LPS intranasal instillation. Vehicle-treated mice were used as controls. Animals were culled at 4 h after LPS challenge, and the bronchoalveolar lavage fluid (BALF) and lung samples were collected for analysis. EAFPg and kaempferol effects on NO and cytokine production by LPS-stimulated RAW 264.7 macrophages were also investigated. Pretreatment with EAFPg (100-300 mg/kg) markedly reduced cell accumulation (specially neutrophils) and collagen deposition in the lungs of ALI mice. The same animals presented with reduced lung and BALF TNF- α and IL-1 β expression in comparison with vehicle controls ( p < 0.05). Additionally, incubation with either EAFPg or kaempferol (100  μ g/ml) reduced NO production and cytokine gene expression in cultured LPS-treated RAW 264.7 macrophages. Overall, these results demonstrate that the prophylactic treatment with EAFPg attenuates acute lung inflammation. We suggest this fraction may be useful in treating ALI.

  17. Methylprednisolone fails to attenuate lung injury in a mouse model of transfusion related acute lung injury

    NARCIS (Netherlands)

    Müller, Marcella C. A.; Tuinman, Pieter R.; van der Sluijs, Koenraad F.; Boon, Louis; Roelofs, Joris J.; Vroom, Margreeth B.; Juffermans, Nicole P.

    2014-01-01

    Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related morbidity and mortality. Anecdotally, TRALI patients have been treated with corticosteroids. However, evidence for its therapeutic rationale in TRALI is lacking. We determined the effects of corticosteroids on

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

    Science.gov (United States)

    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

    2016-08-01

    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.

  19. Mesenchymal stem cell derived secretome and extracellular vesicles for acute lung injury and other inflammatory lung diseases.

    Science.gov (United States)

    Monsel, Antoine; Zhu, Ying-Gang; Gudapati, Varun; Lim, Hyungsun; Lee, Jae W

    2016-07-01

    Acute respiratory distress syndrome is a major cause of respiratory failure in critically ill patients. Despite extensive research into its pathophysiology, mortality remains high. No effective pharmacotherapy exists. Based largely on numerous preclinical studies, administration of mesenchymal stem or stromal cell (MSC) as a therapeutic for acute lung injury holds great promise, and clinical trials are currently underway. However, concern for the use of stem cells, specifically the risk of iatrogenic tumor formation, remains unresolved. Accumulating evidence now suggest that novel cell-free therapies including MSC-derived conditioned medium and extracellular vesicles released from MSCs might constitute compelling alternatives. The current review summarizes the preclinical studies testing MSC conditioned medium and/or MSC extracellular vesicles as treatment for acute lung injury and other inflammatory lung diseases. While certain logistical obstacles limit the clinical applications of MSC conditioned medium such as the volume required for treatment, the therapeutic application of MSC extracellular vesicles remains promising, primarily due to ability of extracellular vesicles to maintain the functional phenotype of the parent cell. However, utilization of MSC extracellular vesicles will require large-scale production and standardization concerning identification, characterization and quantification.

  20. Lung function after allogeneic hematopoietic stem cell transplantation in children

    DEFF Research Database (Denmark)

    Uhlving, Hilde Hylland; Larsen Bang, Cæcilie; Christensen, Ib Jarle

    2013-01-01

    Reduction in pulmonary function (PF) has been reported in up to 85% of pediatric patients during the first year after hematopoietic stem cell transplantation (HSCT). Our understanding of the etiology for this decrease in lung function is, however, sparse. The aim of this study was to describe PF......-versus-host disease (GvHD). Other factors associated with PF decline were malignant diagnosis, busulfan-based conditioning, patient and donor age, female donor to male recipient, as well as chronic GvHD. Mild to moderate decline in PF is frequent and appears associated with acute GvHD and other parameters...

  1. Experimental models of transfusion-related acute lung injury.

    Science.gov (United States)

    Gilliss, Brian M; Looney, Mark R

    2011-01-01

    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 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. Copyright © 2011 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    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

  3. The metalloproteinase ADAM8 promotes leukocyte recruitment in vitro and in acute lung inflammation.

    Science.gov (United States)

    Dreymueller, Daniela; Pruessmeyer, Jessica; Schumacher, Julian; Fellendorf, Sandra; Hess, Franz Martin; Seifert, Anke; Babendreyer, Aaron; Bartsch, Jörg W; Ludwig, Andreas

    2017-09-01

    Alveolar leukocyte recruitment is a hallmark of acute lung inflammation and involves transmigration of leukocytes through endothelial and epithelial layers. The disintegrin and metalloproteinase (ADAM) 8 is expressed on human isolated leukocytic cells and can be further upregulated on cultured endothelial and epithelial cells by proinflammatory cytokines. By shRNA-mediated knockdown we show that leukocytic ADAM8 is required on monocytic THP-1 cells for chemokine-induced chemotaxis as well as transendothelial and transepithelial migration. Furthermore, ADAM8 promotes α L -integrin upregulation and THP-1 cell adhesion to endothelial cells. On endothelial cells ADAM8 enhances transendothelial migration and increases cytokine-induced permeability. On epithelial cells the protease facilitates migration in a wound closure assay but does not affect transepithelial leukocyte migration. Blood leukocytes and bone marrow-derived macrophages (BMDM) from ADAM8-deficient mice show suppressed chemotactic response. Intranasal application of LPS to mice is accompanied with ADAM8 upregulation in the lung. In this model of acute lung inflammation ADAM8-deficient mice are protected against leukocyte infiltration. Finally, transfer experiments of BMDM in mice indicate that ADAM8 exerts a promigratory function predominantly on leukocytes. Our study provides in vitro and in vivo evidence that ADAM8 on leukocytes holds a proinflammatory function in acute lung inflammation by promoting alveolar leukocyte recruitment. Copyright © 2017 the American Physiological Society.

  4. Acute Abdomen: A Rare Presentation of Lung Cancer Metastasis

    OpenAIRE

    Guérin, E.; Gilbert, O.; Dequanter, D.

    2009-01-01

    Surgical emergencies caused by bowel metastases from carcinoma of the lung are very rare. We describe two cases of symptomatic gastrointestinal metastatic small cell carcinoma: the first one concerns a 69-year-old man with an acute abdomen and the second is a 72-year-old man complaining of a gastric ulcer symptoms. We also discuss the current management and the prognosis of these patients.

  5. Early blood purification therapy of severe acute pancreatitis complicated by acute lung injury.

    Science.gov (United States)

    Guo, H; Suo, D-W; Zhu, H-P; Sun, X-M; Chen, J

    2016-03-01

    Severe acute pancreatitis (SAP) can often be complicated by acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), leading to increased mortality. Early blood purification clears inflammatory cytokines and promotes immune function recovery. Here we evaluated the usefulness of this therapy in SAP complicated by ALI. 32 patients received routine treatment (control group), whereas other 32 patients received routine treatment and early blood purification therapy (study group). We evaluated respiratory indexes (PaO2, PaO2/FiO2, alveolar-arterial oxygen difference, intrapulmonary arteriovenous shunt percentage, and respiratory rate), blood biochemical (creatinine, blood urea nitrogen, alanine aminotransferase, and lactate levels) and inflammatory (CRP, IL-10, TNF-α, and IL-10/TNF-α ratio) markers, and prognostic outcomes (multiple organ dysfunction syndrome [MODS] and APACHE II scores) before and 72 hours after the treatment. We also documented mechanical ventilation use, occurrence of MODS and ARDS, and mortality rates. There were no deaths. Mechanical ventilation was used in a similar percentage of patients in either group. Treatment in study group led to a faster and better recovery of respiratory indexes, and less pronounced changes in the levels of blood urea nitrogen and alanine aminotransferase. Inflammatory markers also normalized better in the study group. Furthermore, MODS and APACHE II scores decreased to a greater extent in the study group, paralleled by a lower occurrence of MPDS and ARDS. Early blood purification therapy improves respiratory function and inflammatory markers in patients with SAP complicated by ALI, and decreases the occurrence of MODS and ARDS.

  6. Risk Factors for Mortality and Outcomes in Pediatric Acute Lung Injury/Acute Respiratory Distress Syndrome.

    Science.gov (United States)

    Panico, Flávia F; Troster, Eduardo J; Oliveira, Cindy S; Faria, Aline; Lucena, Michelle; João, Paulo R D; Saad, Everardo D; Foronda, Flávia A K; Delgado, Artur F; de Carvalho, Werther Brunow

    2015-09-01

    Children admitted to PICUs often present with or develop respiratory failure that requires mechanical ventilation. We prospectively identified children admitted to three general PICUs, with the goal of identifying risk factors for mortality. Prospective multicenter observational study. Three general PICUs, two in São Paulo and one in Curitiba, Brazil. Children aged between 1 month and 15 years, consecutively admitted between August 2008 and July 2010, with acute lung injury or acute respiratory distress syndrome that developed at least 12 hours after invasive or noninvasive mechanical ventilation. None. We used logistic regression models to explore the relationship between death and independent variables. Of 3,046 patients admitted to the three PICUs, 1,658 patients underwent mechanical ventilation, and 84 fulfilled the acute lung injury/acute respiratory distress syndrome inclusion criteria and were analyzed. Nearly 60% were boys, and the median age was 31 months. Pressure control/assist control was the initial mode of mechanical ventilation in 86% of cases, and the median durations of mechanical ventilation and PICU stay were 12 and 15 days, respectively. None of the eight patients with acute lung injury died, whereas 33 of 76 of the remaining patients with acute respiratory distress syndrome died, for an overall mortality rate of 39.3% (95% CI, 28.8-50.6%). In different multivariate logistic regression model, the number of organ dysfunctions at admission, peak inspiratory pressure, airway pressure gradient on day 1, and the mean airway pressure gradient over the first 7 days of mechanical ventilation were significantly associated with mortality. Mortality is high in pediatric acute lung injury/acute respiratory distress syndrome. Mechanical ventilation-associated risk factors for death among such patients are potential targets for intervention.

  7. Lung function and postural changes during pregnancy.

    Science.gov (United States)

    Nørregaard, O; Schultz, P; Ostergaard, A; Dahl, R

    1989-11-01

    The aim of this study was to determine the effects of postural changes on lung function in pregnant women during the first, second, third trimester and post partum. A significant decrease in FRC, PEF and FEV1 was observed as a result of the postural changes. Arterial oxygenation, MVV and DLCO remained largely the same.

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

    Directory of Open Access Journals (Sweden)

    Lin Chia-Chih

    2012-03-01

    Full Text Available Abstract 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 μg/g, PMA 4 μg/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

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

    Science.gov (United States)

    Lin, Chia-Chih; Hsieh, Nan-Kuang; Liou, Huey Ling; Chen, Hsing I

    2012-03-01

    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. 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 μg/g), PMA 4 μg/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. 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. 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

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

    OpenAIRE

    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...

  11. Lung Inflammation Associated With Clinical Acute Necrotizing Pancreatitis in Dogs.

    Science.gov (United States)

    Vrolyk, V; Wobeser, B K; Al-Dissi, A N; Carr, A; Singh, B

    2017-01-01

    Although dogs with acute necrotizing pancreatitis (ANP) can develop respiratory complications, there are no data describing lung injury in clinical cases of ANP in dogs. Therefore, we conducted a study to characterize lung injury and determine if pulmonary intravascular macrophages (PIMs) are induced in dogs with ANP ( n = 21) compared with control dogs ( n = 6). Two pathologists independently graded histologic sections of pancreas from clinical cases to characterize the severity of ANP (total scores of 3-10) compared with controls showing histologically normal pancreas (total scores of 0). Based on histological grading, lungs from dogs with ANP showed inflammation (median score, 1.5; range, 0-3), but the scores did not differ statistically from the control lungs (median score, 0.5; range, 0-2). A grid intersects-counting method showed an increase in the numbers of MAC387-positive alveolar septal mononuclear phagocyte profiles in lungs of dogs with ANP (ratio median, 0.0243; range, 0.0093-0.0734, with 2 outliers at 0.1523 and 0.1978) compared with controls (ratio median, 0.0019; range, 0.0017-0.0031; P dogs with ANP showed labeling for von Willebrand factor in alveolar septal capillary endothelial cells, septal inflammatory cells, and alveolar macrophages. Toll-like receptor 4 and interleukin 6 were variably expressed in alveolar macrophages and septal inflammatory cells in lungs from both ANP and control dogs. Inducible nitric oxide synthase was detected in alveolar macrophages of dogs with ANP only. These data show that dogs with ANP have lung inflammation, including the recruitment of PIMs and expression of inflammatory mediators.

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

    Directory of Open Access Journals (Sweden)

    Yuichi Ozawa

    Full Text Available 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.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.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 = 5.29-155; p < 0.001 and performance status (≥2; odds ratio = 4.22; 95% confidence interval = 1.06-20.8; 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 = 1.0-37.4; p = 0.038.Pretreatment computed tomography evaluations of the presence of and area size occupied by preexisting interstitial lung

  13. Respiratory muscle function in interstitial lung disease.

    Science.gov (United States)

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

    2013-07-01

    Interstitial lung diseases limit daily activities, impair quality of life and result in (exertional) dyspnoea. This has mainly been attributed to a decline in lung function and impaired gas exchange. However, the contribution of respiratory muscle dysfunction to these limitations remains to be conclusively investigated. Interstitial lung disease patients and matched controls performed body plethysmography, a standardised 6-min walk test, volitional tests (respiratory drive (P0.1), global maximal inspiratory mouth occlusion pressure (PImax), sniff nasal pressure (SnPna) and inspiratory muscle load) and nonvolitional tests on respiratory muscle function and strength (twitch mouth and transdiaphragmatic pressure during bilateral magnetic phrenic nerve stimulation (TwPmo and TwPdi)). 25 patients and 24 controls were included in the study. PImax and SnPna remained unaltered (both p>0.05), whereas P0.1 and the load on the inspiratory muscles were higher (both prespiratory muscle strength remains preserved. Central respiratory drive and the load imposed on the inspiratory muscles are increased. Whether impaired respiratory muscle function impacts morbidity and mortality in interstitial lung disease patients needs to be investigated in future studies.

  14. Pre-operative optimisation of lung function

    OpenAIRE

    Azhar, Naheed

    2015-01-01

    The anaesthetic management of patients with pre-existing pulmonary disease is a challenging task. It is associated with increased morbidity in the form of post-operative pulmonary complications. Pre-operative optimisation of lung function helps in reducing these complications. Patients are advised to stop smoking for a period of 4–6 weeks. This reduces airway reactivity, improves mucociliary function and decreases carboxy-haemoglobin. The widely used incentive spirometry may be useful only wh...

  15. Reduced lung function among sisal processors.

    Science.gov (United States)

    Kayumba, Akwilina; Moen, Bente Elisabeth; Bråtveit, Magne; Eduard, Wijnand; Mashalla, Yohana

    2011-09-01

    The objective of this study was to examine lung function and chronic respiratory symptoms among sisal workers in Tanzania and compare the results with a control group. A cross-sectional study on chronic respiratory symptoms and lung function was conducted in 2006 among male Tanzanian sisal processing workers from six sisal estates. Participants included 86 workers in decortication departments, 68 workers in brushing departments and 30 low exposed security guards. The response rate was 97%. Chronic respiratory symptoms and background information were obtained by structured interview. Forced ventilatory capacity (FVC) and forced expiratory volume in 1 s (FEV(1)) were estimated before and after a work shift, and FEV(1)/FVC ratio calculated. Workers were aged 19-85, with the oldest in the brushing and security departments. Chronic cough and chest tightness were experienced by 38% and 68% of workers in brushing departments, 20% and 6% of workers in decortication and 7% and 0% of security workers, respectively. A reduced FEV(1)/FVC ratio related to years of work was found among workers in brushing departments when adjusting for age, smoking, previous respiratory illnesses and body mass index, using regression analyses. Work in decortication departments was not related to reduced lung function parameters. The prevalence of FEV(1)/FVC<70 was above 50 for all three groups. Lung function parameters were similar before and after work shifts, except that peak expiratory flow increased among workers in brushing departments after work shifts. The results indicate a relationship between work in sisal brushing departments and the development of obstructive lung disorders.

  16. Gastrodin protects against LPS-induced acute lung injury by activating Nrf2 signaling pathway.

    Science.gov (United States)

    Zhang, Zhuo; Zhou, Jie; Song, Daqiang; Sun, Yuhong; Liao, Changli; Jiang, Xian

    2017-05-09

    Gastrodin (GAS), a phenolic glucoside derived from Gastrodiaelata Blume, has been reported to have anti-inflammatory effect. The aim of this study was to investigate the effects of GAS on LPS-induced acute lung injury in mice. ALI was induced by the intranasal administration of LPS and GAS was given 1 h or 12 h after LPS treatment. The results indicated that GAS treatment markedly attenuated the damage of lung injury induced by LPS. GAS attenuated the activity of myeloperoxidase (MPO) and down-regulated the levels of pro-inflammatory cytokines TNF-α, IL-6 and IL-1β in BALF. LPS-induced lung edema and lung function were also reversed by GAS. Furthermore, GAS was found to inhibit LPS-induced inflammatory cells infiltration. In addition, treatment of GAS inhibited LPS-induced NF-κB activation and up-regulated the expression of Nrf2 and HO-1. In conclusion, our results indicated that GAS had anti-inflammatory effects on LPS-induced acute lung injury. The anti-inflammatory mechanism of GAS was through the inhibition of NF-κB and activation of Nrf2 signaling pathways.

  17. Prenatal and postnatal genetic influence on lung function development

    DEFF Research Database (Denmark)

    Kreiner-Møller, Eskil; Bisgaard, Hans; Bønnelykke, Klaus

    2014-01-01

    BACKGROUND: It is unknown to what extent adult lung function genes affect lung function development from birth to childhood. OBJECTIVE: Our aim was to study the association of candidate genetic variants with neonatal lung function and lung function development until age 7 years. METHODS: Lung...... repeated at age 7 years. Genetic risk scores were calculated based on reported single nucleotide polymorphisms for adult lung function (FEV1/forced expiratory vital capacity [FVC] ratio and FEV1) as the number of risk alleles weighted on known effect size. These genetic risk scores were analyzed against...... lung function measures as z scores at birth (forced expiratory volume in 0.5 seconds [FEV0.5], forced expiratory flow at 50% of functional vital capacity [FEF50], and provocative dose of methacholine causing a 15% decrease in lung function [PD15]) and at age 7 years (FEV1, FEF50, and provocative dose...

  18. Using bosentan to treat paraquat poisoning-induced acute lung injury in rats.

    Directory of Open Access Journals (Sweden)

    Zhongchen Zhang

    Full Text Available BACKGROUND: Paraquat poisoning is well known for causing multiple organ function failure (MODS and high mortality. Acute lung injury and advanced pulmonary fibrosis are the most serious complications. Bosentan is a dual endothelin receptor antagonist. It plays an important role in treating PF. There is no related literature on the use of bosentan therapy for paraquat poisoning. OBJECTIVE: To study the use of bosentan to treat acute lung injury and pulmonary fibrosis as induced by paraquat. METHOD: A total of 120 adult Wister male rats were randomly assigned to three groups: the paraquat poisoning group (rats were intragastrically administered with paraquat at 50 mg/kg body weight once at the beginning; the bosentan therapy group (rats were administered bosentan at 100 mg/kg body weight by intragastric administration half an hour after paraquat was administered, then the same dose was administered once a day; and a control group (rats were administered intragastric physiological saline. On the 3rd, 7th, 14th, and 21st days following paraquat exposure, rats were sacrificed, and samples of lung tissue and venous blood were collected. The levels of transforming growth factor-β1 (TGF-β1, endothelin-1 (ET-1, and hydroxyproline (HYP in the plasma and lung homogenate were determined. Optical and electronic microscopes were used to examine pathological changes. RESULT: The TGF-β1, ET-1, and HYP of the paraquat poisoning group were significantly higher than in the control group, and they were significantly lower in the 21st day therapy group than in the paraquat poisoning group on the same day. Under the optical and electronic microscopes, lung tissue damage was observed to be more severe but was then reduced after bosentan was administered. CONCLUSION: Bosentan can reduce inflammation factor release. It has a therapeutic effect on acute lung injury as induced by paraquat.

  19. Novel swine model of transfusion-related acute lung injury.

    Science.gov (United States)

    Okazaki, Hitoshi; Ishikawa, Osamu; Iijima, Takehiko; Kohira, Takahiro; Teranishi, Mai; Kawasaki, Shin; Saito, Akira; Mikami, Yu; Sugiura, Asuka; Hashimoto, Shiho; Shimada, Eiko; Uchikawa, Makoto; Matsuhashi, Mika; Tsuno, Nelson H; Tanaka, Minoru; Kiyokawa, Nobutaka; Fujimoto, Junichiro; Nagase, Takahide; Tadokoro, Kenji; Takahashi, Koki

    2014-12-01

    Transfusion-related acute lung injury (TRALI) is a life-threatening complication of blood transfusion. Antibodies against human leukocyte antigens in donors' plasma are the major causes of TRALI. Several animal models of TRALI have been developed, and the mechanism underlying TRALI development has been extensively investigated using rodent models. Although sheep models of nonimmune TRALI have been developed, large-animal models of antibody-mediated TRALI are not yet available. To develop a swine model of TRALI, male Clawn strain miniature pigs were used. A monoclonal antibody (MoAb) against swine leukocyte antigens (SLAs) Class I (4G8, 0.3 or 1.0 mg/kg body weight [BW]) and a control antibody (1.0 mg/kg BW) were injected into the peripheral vein after priming with or without 1 μg/kg BW lipopolysaccharide (LPS; n = 3 each). Lung injury was assessed using PaO2 /FiO2 (P/F) ratio and by chest X-ray imaging. Histopathologic analysis was also conducted. Lung injury could be induced by injecting 4G8 at an amount of 1.0 mg/kg BW, after LPS. The P/F ratio 90 minutes after the administration of 4G8 significantly decreased (p Lung injury was confirmed by histopathologic analysis. Lung injury in pigs was successfully induced by anti-SLA MoAb. Priming with LPS is a prerequisite for inducing lung injury and the amount of the antibody is a critical condition. © 2014 AABB.

  20. Lung function changes in wildland firefighters working at prescribed burns.

    Energy Technology Data Exchange (ETDEWEB)

    Adetona, Olorunfemi; Hall, Daniel, B.; Naeher, L,P.

    2011-10-01

    Although decline in lung function across workshift has been observed in wildland firefighters, measurements have been restricted to days when they worked at fires. Consequently, such results could have been confounded by normal circadian variation associated with lung function. We investigated the across-shift changes in lung function of wildland firefighters, and the effect of cumulative exposure on lung function during the burn season.

  1. Enforced mouth breathing decreases lung function in mild asthmatics.

    Science.gov (United States)

    Hallani, Mervat; Wheatley, John R; Amis, Terence C

    2008-06-01

    Nasal breathing provides a protective influence against exercise-induced asthma. We hypothesized that enforced oral breathing in resting mild asthmatic subjects may lead to a reduction in lung function. Asymptomatic resting mild asthmatic volunteers (n = 8) were instructed to breathe either nasally only (N; tape over lips) or orally only (O; nose clip) for 1 h each, on separate days. Lung function (% predicted FEV(1)) was measured using standard spirometry at baseline and every 10 min for 1 h. 'Difficulty in breathing' was rated using a Borg scale at the conclusion of the N and O periods. Baseline FEV(1) on the N (101.2 +/- 3.8% predicted) and O (102.7 +/- 3.9% predicted) days was not significantly different (P > 0.3). At 60 min, FEV(1) on the O day (96.5 +/- 4.1% predicted) was significantly less than on the N day (101.0 +/- 3.5% predicted; P 0.3), whereas on the O day, FEV(1) fell progressively (slope = -0.06 +/- 0.01% FEV(1)/min, P breathing in' at the end of the O day (1.5 +/- 0.4 arbitrary units) than on the N day (0.4 +/- 0.3 arbitrary unit; P oral breathing causes a decrease in lung function in mild asthmatic subjects at rest, initiating asthma symptoms in some. Oral breathing may play a role in the pathogenesis of acute asthma exacerbations.

  2. Diagnostic value of plasma and bronchoalveolar lavage samples in acute lung allograft rejection: differential cytology.

    Science.gov (United States)

    Speck, Nicole E; Schuurmans, Macé M; Murer, Christian; Benden, Christian; Huber, Lars C

    2016-06-21

    Diagnosis of acute lung allograft rejection is currently based on transbronchial lung biopsies. Additional methods to detect acute allograft dysfunction derived from plasma and bronchoalveolar lavage samples might facilitate diagnosis and ultimately improve allograft survival. This review article gives an overview of the cell profiles of bronchoalveolar lavage and plasma samples during acute lung allograft rejection. The value of these cells and changes within the pattern of differential cytology to support the diagnosis of acute lung allograft rejection is discussed. Current findings on the topic are highlighted and trends for future research are identified.

  3. Pulmonary Surfactants for Acute and Chronic Lung Diseases (Part II

    Directory of Open Access Journals (Sweden)

    O. A. Rozenberg

    2014-01-01

    Full Text Available Part 2 of the review considers the problem of surfactant therapy for acute respiratory distress syndrome (ARDS in adults and young and old children. It gives information on the results of surfactant therapy and prevention of ARDS in patients with severe concurrent trauma, inhalation injuries, complications due to complex expanded chest surgery, or severe pneumonias, including bilateral pneumonia in the presence of A/H1N1 influenza. There are data on the use of a surfactant in obstetric care and prevention of primary graft dysfunction during lung transplantation. The results of longterm use of surfactant therapy in Russia, suggesting that death rates from ARDS may be substantially reduced (to 20% are discussed. Examples of surfactant therapy for other noncritical lung diseases, such as permanent athelectasis, chronic obstructive pulmonary diseases, and asthma, as well tuberculosis, are also considered.

  4. Contributions of high mobility group box protein in experimental and clinical acute lung injury.

    Science.gov (United States)

    Ueno, Hiroshi; Matsuda, Tomoyuki; Hashimoto, Satoru; Amaya, Fumimasa; Kitamura, Yoshihiro; Tanaka, Masaki; Kobayashi, Atsuko; Maruyama, Ikuro; Yamada, Shingo; Hasegawa, Naoki; Soejima, Junko; Koh, Hidefumi; Ishizaka, Akitoshi

    2004-12-15

    This study was performed to examine the putative role of high mobility group box (HMGB) protein in the pathogenesis of acute lung injury (ALI). Observations were made (1) in 21 patients who were septic with ALI and 15 patients with normal lung function and (2) in a mouse model 24 hours after intratracheal instillation of lipopolysaccharide (LPS). The concentrations of HMGB1 were increased in plasma and lung epithelial lining fluid of patients with ALI and mice instilled with LPS. LPS-induced ALI was mitigated by anti-HMGB1 antibody. Although this protein was not detected in the plasma of control humans or mice, the concentrations of HMGB1 in lung epithelial lining fluid or in bronchoalveolar lavage fluid were unexpectedly high. The nuclear expression of HMGB1 was apparent in epithelial cells surrounding terminal bronchioles in normal mice, whereas its nuclear and cytoplasmic expression was observed in alveolar macrophages in LPS-instilled mice. Lung instillation of HMGB2 did not cause as much inflammation as HMGB1. Extracellular HMGB1 may play a key role in the pathogenesis of clinical and experimental ALI. However, its expression in normal airways is noteworthy and suggests that it also plays a physiologic role in the lung.

  5. Cleaved caspase-3 in lung epithelium of children who died with acute respiratory distress syndrome

    NARCIS (Netherlands)

    Bem, Reinout A.; van der Loos, Chris M.; van Woensel, Job B. M.; Bos, Albert P.

    2010-01-01

    OBJECTIVE: To investigate the extent of cleaved caspase-3 immunostaining in lung epithelial cells in children with acute respiratory distress syndrome. DESIGN: Observational study in sixteen children who died with acute respiratory distress syndrome and diffuse alveolar damage. SETTING: Pediatric

  6. A suspected case of transfusion-related acute lung injury

    Directory of Open Access Journals (Sweden)

    Lulu Sherif

    2011-01-01

    Full Text Available Transfusion-related acute lung injury (TRALI is a rare but serious complication of blood transfusion. We present a suspected case of TRALI in a 39-year-old female patient who underwent total abdominal hysterectomy under uneventful general anesthesia. The patient developed acute desaturation due to noncardiogenic pulmonary edema while receiving compatible blood transfusion on the second postoperative day. As her symptoms were refractory to supportive treatment, she was mechanically ventilated for 3 days and successfully extubated on the fourth day. By exclusion, a clinical diagnosis of TRALI was made. The treatment for TRALI requires discontinuing transfusion and giving respiratory and cardiovascular support. Most cases show clinical improvement in first few hours and resolve completely within 96 h.

  7. [Protective effect of curcumin on oleic-induced acute lung injury in rats].

    Science.gov (United States)

    Zhu, Rui-fang; Zhou, Min; He, Jian-lin; Ding, Fu-yun; Yu, Shu-qin; Xu, Guang-lin

    2008-09-01

    To investigate the effect of curcumine on acute lung injury induced by oleic acid in rat and the possible mechanism of action. The rats were divided into 6 groups randomly: normal group, control group, curcumine groups (5, 10, 20 mg x kg(-1)) and dexamethasone group (1 mg x kg(-1)). During the experiment, acute lung injury was induced by oleic acid in rat. The changes of dynamic lung compliance were recorded by anrise 2005 pulmonary function test apparatus, light microscope was used to examine histological changes and lung index as well as wet to dry weight ratio was calculated by weighting method. Lung vascular permeability and protein level in BALF were detected by ultraviolet spectrophotometry, and the concentrations of TNF-alpha, IL-6 and IL-10 in BALF were measured by enzyme linked immunosorbent assay (ELISA). The result showed that the changes of pulmonary compliance were inhibited and pulmonary function was improved by curcumine. The OA-induced elevation of lung index was restrained, as well as wet to dry weight ratio, lung vascular permeability, protein level, TNF-alpha (250.4 +/- 21.6 vs. 172.53 +/- 14.88, 122.2 +/- 10.98, 108.69 +/- 3.39) ng x L(-1), IL-6 (763.6 +/- 88.33 vs. 207.41 +/- 15.55, 172.13 +/- 21.91, 142.92 +/- 4.32) ng x L(-1) in BALF in curcumine groups, IL-10 (98.90 +/- 2.99 vs. 208.44 +/- 16.30, 218.43 +/- 6.23, 252.70 +/- 20.58) ng x L(-1) in BALF was increased, respectively significantly. Light microscope findings shown that the impairment in curcumine groups was far less severe than that in model groups. Pretreatment of curcumine showed beneficial effect on acute lung injury induced by oleic acid in rats. The mediation of both proinflammatory factor and anti-inflammatory factor by curcumine may be involved in mechanism of action of curcumine effects.

  8. Mesenchymal Stem Cells From Bone Marrow, Adipose Tissue, and Lung Tissue Differentially Mitigate Lung and Distal Organ Damage in Experimental Acute Respiratory Distress Syndrome.

    Science.gov (United States)

    Silva, Johnatas D; Lopes-Pacheco, Miquéias; Paz, Ana H R; Cruz, Fernanda F; Melo, Elga B; de Oliveira, Milena V; Xisto, Débora G; Capelozzi, Vera L; Morales, Marcelo M; Pelosi, Paolo; Cirne-Lima, Elizabeth; Rocco, Patricia R M

    2018-02-01

    Mesenchymal stem cells-based therapies have shown promising effects in experimental acute respiratory distress syndrome. Different mesenchymal stem cells sources may result in diverse effects in respiratory diseases; however, there is no information regarding the best source of mesenchymal stem cells to treat pulmonary acute respiratory distress syndrome. We tested the hypothesis that mesenchymal stem cells derived from bone marrow, adipose tissue, and lung tissue would lead to different beneficial effects on lung and distal organ damage in experimental pulmonary acute respiratory distress syndrome. Animal study and primary cell culture. Laboratory investigation. Seventy-five Wistar rats. Wistar rats received saline (control) or Escherichia coli lipopolysaccharide (acute respiratory distress syndrome) intratracheally. On day 2, acute respiratory distress syndrome animals were further randomized to receive saline or bone marrow, adipose tissue, or lung tissue mesenchymal stem cells (1 × 10 cells) IV. Lung mechanics, histology, and protein levels of inflammatory mediators and growth factors were analyzed 5 days after mesenchymal stem cells administration. RAW 264.7 cells (a macrophage cell line) were incubated with lipopolysaccharide followed by coculture or not with bone marrow, adipose tissue, and lung tissue mesenchymal stem cells (10 cells/mL medium). Regardless of mesenchymal stem cells source, cells administration improved lung function and reduced alveolar collapse, tissue cellularity, collagen, and elastic fiber content in lung tissue, as well as decreased apoptotic cell counts in liver. Bone marrow and adipose tissue mesenchymal stem cells administration also reduced levels of tumor necrosis factor-α, interleukin-1β, keratinocyte-derived chemokine, transforming growth factor-β, and vascular endothelial growth factor, as well as apoptotic cell counts in lung and kidney, while increasing expression of keratinocyte growth factor in lung tissue

  9. Effects of smoking in pregnancy on neonatal lung function

    OpenAIRE

    Milner, A.; Marsh, M.; Ingram, D.; Fox, G.; Susiva, C.

    1999-01-01

    AIMS—To assess the effects of smoking during pregnancy on lung mechanics and lung volumes in the immediate neonatal period, before infants are exposed to passive smoking.
METHODS—Lung function tests were carried out within 72 hours of delivery in infants born to 100 non-smoking and 189 smoking mothers. Lung growth was assessed by plethysmography and lung mechanics using the single breath occlusion technique and oesophageal balloon/ pneumotachography. Antenatal maternal serum cotin...

  10. Acute Lung Injury: Making the Injured Lung Perform Better and Rebuilding Healthy Lungs

    Science.gov (United States)

    2014-04-01

    Hence, those398 Cell Stem Cell 10, 398–411, April 6, 2012 ª2012 Elsevier Inc.interested in purifying thyroid, lung, liver, or pancreatic stem or... pancreatic lineage (Micallef et al., 2005), no tools have been engineered that can allow the isolation of the most primor- dial murine lung and thyroid...timed pregnancy , identification of the vaginal plug was considered as embryonic day (E) 0.5. To activate CreERT2, 1 mg tamoxifen (TAM) (5 mg/ml, Sigma

  11. Inhaled nitric oxide for acute respiratory distress syndrome (ARDS) and acute lung injury in children and adults

    DEFF Research Database (Denmark)

    Afshari, Arash; Brok, Jesper; Møller, Ann

    2010-01-01

    Acute hypoxaemic respiratory failure (AHRF), defined as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), are critical conditions. AHRF results from a number of systemic conditions and is associated with high mortality and morbidity in all ages. Inhaled nitric oxide (INO) has...

  12. VEGF Promotes Malaria-Associated Acute Lung Injury in Mice

    Science.gov (United States)

    Carapau, Daniel; Pena, Ana C.; Ataíde, Ricardo; Monteiro, Carla A. A.; Félix, Nuno; Costa-Silva, Artur; Marinho, Claudio R. F.; Dias, Sérgio; Mota, Maria M.

    2010-01-01

    The spectrum of the clinical presentation and severity of malaria infections is broad, ranging from uncomplicated febrile illness to severe forms of disease such as cerebral malaria (CM), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), pregnancy-associated malaria (PAM) or severe anemia (SA). Rodent models that mimic human CM, PAM and SA syndromes have been established. Here, we show that DBA/2 mice infected with P. berghei ANKA constitute a new model for malaria-associated ALI. Up to 60% of the mice showed dyspnea, airway obstruction and hypoxemia and died between days 7 and 12 post-infection. The most common pathological findings were pleural effusion, pulmonary hemorrhage and edema, consistent with increased lung vessel permeability, while the blood-brain barrier was intact. Malaria-associated ALI correlated with high levels of circulating VEGF, produced de novo in the spleen, and its blockage led to protection of mice from this syndrome. In addition, either splenectomization or administration of the anti-inflammatory molecule carbon monoxide led to a significant reduction in the levels of sera VEGF and to protection from ALI. The similarities between the physiopathological lesions described here and the ones occurring in humans, as well as the demonstration that VEGF is a critical host factor in the onset of malaria-associated ALI in mice, not only offers important mechanistic insights into the processes underlying the pathology related with malaria but may also pave the way for interventional studies. PMID:20502682

  13. Overexpression of IL-38 protein in anticancer drug-induced lung injury and acute exacerbation of idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Tominaga, Masaki; Okamoto, Masaki; Kawayama, Tomotaka; Matsuoka, Masanobu; Kaieda, Shinjiro; Sakazaki, Yuki; Kinoshita, Takashi; Mori, Daisuke; Inoue, Akira; Hoshino, Tomoaki

    2017-09-01

    Interleukin (IL)-38, a member of the IL-1 family, shows high homology to IL-1 receptor antagonist (IL-1Ra) and IL-36 receptor antagonist (IL-36Ra). Its function in interstitial lung disease (ILD) is still unknown. To determine the expression pattern of IL-38 mRNA, a panel of cDNAs derived from various tissues was analyzed by quantitative real-time PCR. Immunohistochemical reactivity with anti-human IL-38 monoclonal antibody (clone H127C) was evaluated semi-quantitatively in lung tissue samples from 12 patients with idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP), 5 with acute exacerbation of IPF, and 10 with anticancer drug-induced ILD (bleomycin in 5 and epidermal growth factor receptor-tyrosine kinase inhibitor in 5). Control lung tissues were obtained from areas of normal lung in 22 lung cancer patients who underwent extirpation surgery. IL-38 transcripts were strongly expressed in the lung, spleen, synoviocytes, and peripheral blood mononuclear cells, and at a lower level in pancreas and muscle. IL-38 protein was not strongly expressed in normal pulmonary alveolar tissues in all 22 control lungs. In contrast, IL-38 was overexpressed in the lungs of 4 of 5 (80%) patients with acute IPF exacerbation and 100% (10/10) of the patients with drug-induced ILD. IL-38 overexpression was limited to hyperplastic type II pneumocytes, which are considered to reflect regenerative change following diffuse alveolar damage in ILD. IL-38 may play an important role in acute and/or chronic inflammation in anticancer drug-induced lung injury and acute exacerbation of IPF. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    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-α (TNF-α), interleukin 1β (IL-1β) 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-α, and IL-1β, 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. Copyright © 2010 Elsevier B.V. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jinshan; Xue, Jinling; Xu, Bi; Xie, Jiani [Environmental Simulation and Pollution Control State Key Joint Laboratory, School of Environment, Tsinghua University, Beijing 100084 (China); Qiao, Juan, E-mail: qjuan@tsinghua.edu.cn [Department of Chemistry, Tsinghua University, Beijing 100084 (China); Lu, Yun, E-mail: luyun@tsinghua.edu.cn [Environmental Simulation and Pollution Control State Key Joint Laboratory, School of Environment, Tsinghua University, Beijing 100084 (China)

    2016-02-13

    Highlights: • Chlorination is effective to reduce the inflammation inducing capacity of LPS in lung. • LAL-detected endotoxin activity is not correlated to the potency of inflammation induction. • Alkyl chain of LPS was chlorinated in chlorination process. • LPS aggregate size decreases after chlorination. - Abstract: 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.

  16. Nutritional immunomodulation in critically ill children with acute lung injury: feasibility and impact on circulating biomarkers.

    Science.gov (United States)

    Jacobs, Brian R; Nadkarni, Vinay; Goldstein, Brahm; Checchia, Paul; Ayad, Onsy; Bean, Judy; DeMichele, Stephen

    2013-01-01

    Respiratory failure caused by acute lung injury or acute respiratory distress syndrome is associated with significant morbidity in children. Enteral nutrition enriched with eicosapentaenoic acid, γ-linolenic acid and antioxidants (eicosapentaenoic acid + γ-linolenic acid) can safely modulate plasma phospholipid fatty acid profiles, reduce inflammation, and improve clinical outcomes in adults. There is little information regarding the use of enteral eicosapentaenoic acid + γ-linolenic acid to modulate plasma phospholipid fatty acid profiles in children. We sought to determine if continuous feeding of enteral nutrition containing eicosapentaenoic acid, γ-linolenic acid, and antioxidants was feasible in critically ill children with acute lung injury or acute respiratory distress syndrome. We further evaluated the impact of such an approach on the alteration of plasma phospholipid fatty acid concentrations. Prospective, blinded, randomized, controlled, multicenter trial. PICU. Twenty-six critically ill children (age 6.2 ± 0.9 yr, PaO2/FIO2 185 ± 15) with the diagnosis of acute lung injury or acute respiratory distress syndrome. Mechanically ventilated children received either eicosapentaenoic acid + γ-linolenic acid or a standard pediatric enteral formula. Clinical, biochemical, plasma fatty acid, and safety data were assessed at baseline, study days 4 and 7. At baseline, there were no significant differences in the two study groups. Both groups met enteral feeding goals within 30 hrs and had similar caloric delivery. There were no differences in formula tolerance as measured by serum chemistries, liver and renal function, and hematology studies after 7 days of feeding either eicosapentaenoic acid + γ-linolenic acid or pediatric enteral formula. On study day 4 and 7, plasma phospholipid fatty acid profiles in the eicosapentaenoic acid + γ-linolenic acid group showed a significant increase in anti-inflammatory circulating markers. Providing enteral nutrition

  17. Paraquat poisoning: an experimental model of dose-dependent acute lung injury due to surfactant dysfunction

    Directory of Open Access Journals (Sweden)

    M.F.R. Silva

    1998-03-01

    Full Text Available Since the most characteristic feature of paraquat poisoning is lung damage, a prospective controlled study was performed on excised rat lungs in order to estimate the intensity of lesion after different doses. Twenty-five male, 2-3-month-old non-SPF Wistar rats, divided into 5 groups, received paraquat dichloride in a single intraperitoneal injection (0, 1, 5, 25, or 50 mg/kg body weight 24 h before the experiment. Static pressure-volume (PV curves were performed in air- and saline-filled lungs; an estimator of surface tension and tissue works was computed by integrating the area of both curves and reported as work/ml of volume displacement. Paraquat induced a dose-dependent increase of inspiratory surface tension work that reached a significant two-fold order of magnitude for 25 and 50 mg/kg body weight (P<0.05, ANOVA, sparing lung tissue. This kind of lesion was probably due to functional abnormalities of the surfactant system, as was shown by the increase in the hysteresis of the paraquat groups at the highest doses. Hence, paraquat poisoning provides a suitable model of acute lung injury with alveolar instability that can be easily used in experimental protocols of mechanical ventilation

  18. [Expression of various matrix metalloproteinases in mice with hyperoxia-induced acute lung injury].

    Science.gov (United States)

    Zhang, Xiang-feng; Ding, Shao-fang; Gao, Yuan-ming; Liang, Ying; Foda, Hussein D

    2006-08-01

    To investigate the role of matrix metalloproteinases (MMPs) and extracellular matrix metalloproteinase inducer (EMMPRIN) in the pathogenesis of acute lung injury induced by hyperoxia. Fifty four mice were exposed in sealed cages to >98% oxygen (for 24-72 hours), and another 18 mice to room air. The severity of lung injury was assessed, and the expression of mRNA and protein of MMP-2, MMP-9 and EMMPRIN in lung tissue, after exposure for 24, 48 and 72 hours of hyperoxia were studied by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Hyperoxia caused acute lung injury; this was accompanied by increased expression of an upregulation of MMP-2, MMP-9 and EMMPRIN mRNA and protein in lung tissues. Hyperoxia causes acute lung injury in mice; increases in MMP-2, MMP-9 and EMMPRIN may play an important role in the development of hyperoxia induced lung injury in mice.

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

    DEFF Research Database (Denmark)

    Gaunsbaek, Maria Quisgaard; Rasmussen, Karina Juhl; Beers, Michael F.

    2013-01-01

    in three murine models of lung injury, using a validated ELISA technology for estimation of SP-D levels. METHODS: Mice were exposed to lipopolysaccharide, bleomycin, or Pneumocystis carinii (Pc) and sacrificed at different time points. RESULTS: In lipopolysaccharide-challenged mice, the level of SP...... injury, with a sustained increment during chronic inflammation compared with acute inflammation. A quick upregulation of SP-D in serum in response to acute airway inflammation supports the notion that SP-D translocates from the airways into the vascular system, in favor of being synthesized systemically....... The study also confirms the concept of using increased SP-D serum levels as a biomarker of especially chronic airway inflammation....

  20. Pre-operative optimisation of lung function

    Directory of Open Access Journals (Sweden)

    Naheed Azhar

    2015-01-01

    Full Text Available The anaesthetic management of patients with pre-existing pulmonary disease is a challenging task. It is associated with increased morbidity in the form of post-operative pulmonary complications. Pre-operative optimisation of lung function helps in reducing these complications. Patients are advised to stop smoking for a period of 4–6 weeks. This reduces airway reactivity, improves mucociliary function and decreases carboxy-haemoglobin. The widely used incentive spirometry may be useful only when combined with other respiratory muscle exercises. Volume-based inspiratory devices have the best results. Pharmacotherapy of asthma and chronic obstructive pulmonary disease must be optimised before considering the patient for elective surgery. Beta 2 agonists, inhaled corticosteroids and systemic corticosteroids, are the main drugs used for this and several drugs play an adjunctive role in medical therapy. A graded approach has been suggested to manage these patients for elective surgery with an aim to achieve optimal pulmonary function.

  1. Carbonic anhydrase inhibitor attenuates ischemia-reperfusion induced acute lung injury.

    Directory of Open Access Journals (Sweden)

    Chou-Chin Lan

    Full Text Available Ischemia-reperfusion (IR-induced acute lung injury (ALI is implicated in several clinical conditions including lung transplantation, cardiopulmonary bypass surgery, re-expansion of collapsed lung from pneumothorax or pleural effusion and etc. IR-induced ALI remains a challenge in the current treatment. Carbonic anhydrase has important physiological function and influences on transport of CO2. Some investigators suggest that CO2 influences lung injury. Therefore, carbonic anhydrase should have the role in ALI. This study was undertaken to define the effect of a carbonic anhydrase inhibitor, acetazolamide (AZA, in IR-induced ALI, that was conducted in a rat model of isolated-perfused lung with 30 minutes of ischemia and 90 minutes of reperfusion. The animals were divided into six groups (n = 6 per group: sham, sham + AZA 200 mg/kg body weight (BW, IR, IR + AZA 100 mg/kg BW, IR + AZA 200 mg/kg BW and IR+ AZA 400 mg/kg BW. IR caused significant pulmonary micro-vascular hyper-permeability, pulmonary edema, pulmonary hypertension, neutrophilic sequestration, and an increase in the expression of pro-inflammatory cytokines. Increases in carbonic anhydrase expression and perfusate pCO2 levels were noted, while decreased Na-K-ATPase expression was noted after IR. Administration of 200mg/kg BW and 400mg/kg BW AZA significantly suppressed the expression of pro-inflammatory cytokines (TNF-α, IL-1, IL-6 and IL-17 and attenuated IR-induced lung injury, represented by decreases in pulmonary hyper-permeability, pulmonary edema, pulmonary hypertension and neutrophilic sequestration. AZA attenuated IR-induced lung injury, associated with decreases in carbonic anhydrase expression and pCO2 levels, as well as restoration of Na-K-ATPase expression.

  2. Amelioration of meconium-induced acute lung injury by parecoxib in a rabbit model

    Science.gov (United States)

    Li, Ai-Min; Zhang, Li-Na; Li, Wen-Zhi

    2015-01-01

    Cyclooxygenase-2 (COX-2) plays important roles in various inflammatory conditions and is significantly increased in meconium-induced lung injury. We investigated the effects of parecoxib on meconium-induced acute lung injury (ALI) in rabbits. Twenty-four rabbits were randomized into sham, control, and parecoxib groups. Rabbits in the control and parecoxib groups underwent tracheal instillation of meconium, followed by intravenous injection of saline or parecoxib and 4 h of ventilation. The airway pressure, dynamic compliance, and ratio of partial pressure of oxygen in arterial blood to fraction of inspired oxygen (PaO2/FiO2 ratio) were recorded at baseline (T0) and 4 h after instillation (T1-T4). The lung tissue wet-to-dry weight ratio; neutrophil percentage; and total protein, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-8, prostaglandin E2, and malondialdehyde levels in bronchoalveolar lavage fluid (BALF) were evaluated. The myeloperoxidase activity, COX-2 expression, and degree of histopathologic injury in lung tissue were also analyzed. The airway pressure, compliance, and PaO2/FiO2 ratio were significantly improved by parecoxib after meconium instillation. The lung wet-to-dry weight ratio, total protein level, and neutrophil percentage in BALF were lowest in the parecoxib group. The TNF-α, IL-1β, IL-8, prostaglandin E2, and malondialdehyde levels in the BALF were lowest in the parecoxib group. The COX-2 expression and myeloperoxidase activity in lung tissue were significantly reduced by parecoxib. The degree of lung injury was also reduced. In conclusions: Parecoxib effectively ameliorates respiratory function and attenuates meconium-induced ALI. These effects are correlated with prostaglandin E2 and COX-2 inhibition. PMID:26221218

  3. Genetic Variation in GSTP1, Lung Function, Risk of Lung Cancer, and Mortality

    DEFF Research Database (Denmark)

    Nørskov, Marianne S.; Dahl, Morten; Tybjærg-Hansen, Anne

    2017-01-01

    66,069 individuals from the white general population for two common functional variants in the glutathione S-transferase pi 1 gene (GSTP1)—amino acid isoleucine 105 changed to a valine (Ile105Val) and amino acid alanine 114 changed to a valine (Ala114Val)—and recorded lung function, lung cancer......, tobacco-related cancer, and death as outcomes. Results Lung function was increased stepwise with the Ile105Val genotype overall (p smokers separately (p

  4. Pulmonary function change in patients with Sauropus androgynus-related obstructive lung disease 15 years later

    Directory of Open Access Journals (Sweden)

    Chih-Ying Ou

    2013-10-01

    Conclusion: After an acute deterioration, patients with S androgynus-related obstructive lung disease had a stationary pulmonary function over a period of 15 years, and their clinical manifestations were less severe than age- and FEV1-matched COPD patients. A further study with a larger sample size may be needed to confirm these findings.

  5. Biomarkers of acute lung injury: worth their salt?

    Directory of Open Access Journals (Sweden)

    Proudfoot Alastair G

    2011-12-01

    Full Text Available Abstract The validation of biomarkers has become a key goal of translational biomedical research. The purpose of this article is to discuss the role of biomarkers in the management of acute lung injury (ALI and related research. Biomarkers should be sensitive and specific indicators of clinically important processes and should change in a relevant timeframe to affect recruitment to trials or clinical management. We do not believe that they necessarily need to reflect pathogenic processes. We critically examined current strategies used to identify biomarkers and which, owing to expedience, have been dominated by reanalysis of blood derived markers from large multicenter Phase 3 studies. Combining new and existing validated biomarkers with physiological and other data may add predictive power and facilitate the development of important aids to research and therapy.

  6. Artificial Ventilation-Induced Acute Lung Lesion: Experimental, Morphological Study

    Directory of Open Access Journals (Sweden)

    A. M. Golubev

    2006-01-01

    Full Text Available Objective: to elucidate the pattern of morphological changes in the lung during artificial ventilation.Materials and methods. Experiments were carried out on 30 non-inbred albino male rats weighing 250—320 g. The anesthetized animals were ventilated for 1—4 hours by a TSE Animal Respirator at a flow of 0.6—4 l/min, a respiration rate of 60 min, a tidal volume of 10—12 ml, and a peak inspiratory pressure of 100—400 mm H2O. Artificial ventilation was not made in control animals. Following 1, 2, and 3 hours and 1, 1.5, 2, and 3 days, the anesthetized animals were withdrawn from the experiment through cardiac vascular fascicle ligation. Lung pieces were fixed in neural 4% formalin and embedded in paraffin. Histological sections were stained with hematoxylin-eosin and the periodic acid Schiff reaction was performed. Morphometric studies were conducted and the data were then statistically processed (Student’s t-test.Results. An hour after artificial ventilation, the interalveolar septa were thickened due to edema and cellular infiltration. There were microatelectases. The bronchioles were deformed; their lumens contained desquamated epithelium and mucus. The alveolar lumens contained red blood cells and macrophages. Perivascular connective tissue was edematous and exhibited epithelial desquamation. Later on, the observed changes increased. There were individual differences in the rate of morphological changes during artificial ventilation (AV.Conclusion. AV is followed by the development of structural changes that are typical of acute lung lesion. 

  7. Assisted ventilation modes reduce the expression of lung inflammatory and fibrogenic mediators in a model of mild acute lung injury.

    Science.gov (United States)

    Saddy, Felipe; Oliveira, Gisele P; Garcia, Cristiane S N B; Nardelli, Liliane M; Rzezinski, Andreia F; Ornellas, Debora S; Morales, Marcelo M; Capelozzi, Vera L; Pelosi, Paolo; Rocco, Patricia R M

    2010-08-01

    The goal of the study was to compare the effects of different assisted ventilation modes with pressure controlled ventilation (PCV) on lung histology, arterial blood gases, inflammatory and fibrogenic mediators in experimental acute lung injury (ALI). Paraquat-induced ALI rats were studied. At 24 h, animals were anaesthetised and further randomized as follows (n = 6/group): (1) pressure controlled ventilation mode (PCV) with tidal volume (V (T)) = 6 ml/kg and inspiratory to expiratory ratio (I:E) = 1:2; (2) three assisted ventilation modes: (a) assist-pressure controlled ventilation (APCV1:2) with I:E = 1:2, (b) APCV1:1 with I:E = 1:1; and (c) biphasic positive airway pressure and pressure support ventilation (BiVent + PSV), and (3) spontaneous breathing without PEEP in air. PCV, APCV1:1, and APCV1:2 were set with P (insp) = 10 cmH(2)O and PEEP = 5 cmH(2)O. BiVent + PSV was set with two levels of CPAP [inspiratory pressure (P (High) = 10 cmH(2)O) and positive end-expiratory pressure (P (Low) = 5 cmH(2)O)] and inspiratory/expiratory times: T (High) = 0.3 s and T (Low) = 0.3 s. PSV was set as follows: 2 cmH(2)O above P (High) and 7 cmH(2)O above P (Low). All rats were mechanically ventilated in air and PEEP = 5 cmH(2)O for 1 h. Assisted ventilation modes led to better functional improvement and less lung injury compared to PCV. APCV1:1 and BiVent + PSV presented similar oxygenation levels, which were higher than in APCV1:2. Bivent + PSV led to less alveolar epithelium injury and lower expression of tumour necrosis factor-alpha, interleukin-6, and type III procollagen. In this experimental ALI model, assisted ventilation modes presented greater beneficial effects on respiratory function and a reduction in lung injury compared to PCV. Among assisted ventilation modes, Bi-Vent + PSV demonstrated better functional results with less lung damage and expression of inflammatory mediators.

  8. Systemic inflammation and lung function: A longitudinal analysis.

    Science.gov (United States)

    Hancox, Robert J; Gray, Andrew R; Sears, Malcolm R; Poulton, Richie

    2016-02-01

    Systemic inflammation is associated with impaired lung function in healthy adults as well as in patients with lung disease. The mechanism for this association is unknown and it is unclear if systemic inflammation leads to impaired lung function or if poor lung function leads to inflammation. We explored the temporal associations between blood C-reactive protein (CRP), fibrinogen, and white blood cells, and lung function in young adults. Spirometry, plethysmography, and diffusion capacity were measured in a population-based cohort at ages 32 and 38 years. High-sensitivity CRP, fibrinogen, and white blood cells were measured at the same ages. Higher levels of CRP and, to a lesser extent, fibrinogen were associated with lower lung volumes in cross-sectional analyses at both ages 32 and 38 years. Higher CRP and fibrinogen at age 32 were associated with higher FEV1 and FEV1/FVC at age 38, but not other measures of lung function. Lower lung volumes (total lung capacity, functional residual capacity, and residual volume) but not airflow obstruction (FEV1/FVC) at age 32 were associated with higher CRP at age 38. Associations between age 32 lung function and fibrinogen at follow-up were weaker, but consistent. There were no longitudinal associations between white blood cells and lung function. We found no evidence that systemic inflammation causes a decline in lung function. However, lower lung volumes were associated with higher CRP and fibrinogen at follow-up indicating that pulmonary restriction may be a risk factor for systemic inflammation. The mechanism for this association remains unclear. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Optical and Functional Imaging in Lung Cancer

    NARCIS (Netherlands)

    K.H. van der Leest (Cor)

    2010-01-01

    textabstractLung cancer is the second most common cancer in men and women, and is the leading cause of cancer related death. In industrialized countries the mortality rate of lung cancer is higher than the mortality rate of breast, colorectal and prostate cancer combined 1. When lung cancer is

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Silvie Kremserova

    2016-01-01

    Full Text Available 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.

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

    Directory of Open Access Journals (Sweden)

    Minlong Zhang

    2014-10-01

    Full Text Available Inflammation is involved in the pathogenesis of seawater aspiration-induced acute lung injury (ALI. Although several studies have shown that Semaphorin 7A (SEMA7A promotes inflammation, there are limited reports regarding immunological function of SEMA7A in seawater aspiration-induced ALI. Therefore, we investigated the role of SEMA7A during seawater aspiration-induced ALI. Male Sprague–Dawley rats were underwent seawater instillation. Then, lung samples were collected at an indicated time for analysis. In addition, rat pulmonary microvascular endothelial cells (RPMVECs were cultured and then stimulated with 25% seawater for indicated time point. After these treatments, cells samples were collected for analysis. In vivo, seawater instillation induced lung histopathologic changes, pro-inflammation cytokines release and increased expression of SEMA7A. In vitro, seawater stimulation led to pro-inflammation cytokine release, cytoskeleton remodeling and increased monolayer permeability in pulmonary microvascular endothelial cells. In addition, knockdown of hypoxia-inducible factor (HIF-1α 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.

  13. Endothelial Semaphorin 7A promotes inflammation in seawater aspiration-induced acute lung injury.

    Science.gov (United States)

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

    2014-10-28

    Inflammation is involved in the pathogenesis of seawater aspiration-induced acute lung injury (ALI). Although several studies have shown that Semaphorin 7A (SEMA7A) promotes inflammation, there are limited reports regarding immunological function of SEMA7A in seawater aspiration-induced ALI. Therefore, we investigated the role of SEMA7A during seawater aspiration-induced ALI. Male Sprague-Dawley rats were underwent seawater instillation. Then, lung samples were collected at an indicated time for analysis. In addition, rat pulmonary microvascular endothelial cells (RPMVECs) were cultured and then stimulated with 25% seawater for indicated time point. After these treatments, cells samples were collected for analysis. In vivo, seawater instillation induced lung histopathologic changes, pro-inflammation cytokines release and increased expression of SEMA7A. In vitro, seawater stimulation led to pro-inflammation cytokine release, cytoskeleton remodeling and increased monolayer permeability in pulmonary microvascular endothelial cells. In addition, knockdown of hypoxia-inducible factor (HIF)-1α 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.

  14. Spontaneous breathing with biphasic positive airway pressure attenuates lung injury in hydrochloric acid-induced acute respiratory distress syndrome.

    Science.gov (United States)

    Xia, Jingen; Zhang, Heng; Sun, Bing; Yang, Rui; He, Hangyong; Zhan, Qingyuan

    2014-06-01

    It has been proved that spontaneous breathing (SB) with biphasic positive airway pressure (BIPAP) can improve lung aeration in acute respiratory distress syndrome compared with controlled mechanical ventilation. The authors hypothesized that SB with BIPAP would attenuate lung injury in acute respiratory distress syndrome compared with pressure-controlled ventilation. Twenty male New Zealand white rabbits with hydrochloric acid aspiration-induced acute respiratory distress syndrome were randomly ventilated using the BIPAP either with SB (BIPAP plus SB group) or without SB (BIPAP minus SB group) for 5 h. Inspiration pressure was adjusted to maintain the tidal volume at 6 ml/kg. Both groups received the same positive end-expiratory pressure level at 5 cm H2O for hemodynamic goals. Eight healthy animals without ventilatory support served as the control group. The BIPAP plus SB group presented a lower ratio of dead space ventilation to tidal volume, a lower respiratory rate, and lower minute ventilation. No significant difference in the protein levels of interleukin-6 and interleukin-8 in plasma, bronchoalveolar lavage fluid, and lung tissue were measured between the two experimental groups. However, SB resulted in lower messenger ribonucleic acid levels of interleukin-6 (mean ± SD; 1.8 ± 0.7 vs. 2.6 ± 0.5; P = 0.008) and interleukin-8 (2.2 ± 0.5 vs. 2.9 ± 0.6; P = 0.014) in lung tissues. In addition, lung histopathology revealed less injury in the BIPAP plus SB group (lung injury score, 13.8 ± 4.6 vs. 21.8 ± 5.7; P hydrochloric acid-induced acute respiratory distress syndrome, SB with BIPAP attenuated lung injury and improved respiratory function compared with controlled ventilation with low tidal volume.

  15. Early COPD patients with lung hyperinflation associated with poorer lung function but better bronchodilator responsiveness

    Science.gov (United States)

    Chen, Chunlan; Jian, Wenhua; Gao, Yi; Xie, Yanqing; Song, Yan; Zheng, Jinping

    2016-01-01

    Background It is unknown whether aggressive medication strategies should be used for early COPD with or without lung hyperinflation. We aimed to explore the characteristics and bronchodilator responsiveness of early COPD patients (stages I and II) with/without lung hyperinflation. Methods Four hundred and six patients with COPD who performed both lung volume and bronchodilation tests were retrospectively analyzed. Residual volume to total lung capacity >120% of predicted values indicated lung hyperinflation. The characteristics and bronchodilator responsiveness were compared between the patients with and without lung hyperinflation across all stages of COPD. Results The percentages of patients with lung hyperinflation were 72.7% in the entire cohort, 19.4% in stage I, 68.5% in stage II, 95.3% in stage III, and 100.0% in stage IV. The patients with lung hyperinflation exhibited poorer lung function but better bronchodilator responsiveness of both forced expiratory volume in 1 second and forced vital capacity than those without lung hyperinflation during early COPD (t=2.21–5.70, P=0.000–0.029), especially in stage I, while age, body mass index, smoking status, smoking history, and disease duration were similar between the two subgroups in the same stages. From stages I to IV of subgroups with lung hyperinflation, stage I patients had the best bronchodilator responsiveness. Use of bronchodilator responsiveness of forced vital capacity to detect the presence of lung hyperinflation in COPD patients showed relatively high sensitivities (69.5%–75.3%) and specificities (70.3%–75.7%). Conclusion We demonstrated the novel finding that early COPD patients with lung hyperinflation are associated with poorer lung function but better bronchodilator responsiveness and established a simple method for detecting lung hyperinflation. PMID:27785008

  16. [Assessment of differential lung function by electrical impedance tomography].

    Science.gov (United States)

    de Lema, J Bruno; Serrano, Ernesto; Feixas, Teresa; Calaf, Núria; Camacho, María Valle; Riu, Pere J; Casan, Pere

    2008-08-01

    To compare unilateral lung function estimated by 2 methods: electrical impedance tomography (EIT) and ventilation-perfusion lung scintigraphy. This prospective clinical study was carried out in the pulmonary function laboratory of a general hospital. Twenty patients diagnosed with lung cancer (17 men and 3 women, ranging in age from 25 to 77 years) who were candidates for lung resection underwent ventilation-perfusion lung scanning breathing a radioactive gas. Differential lung function was estimated based on images taken at 2 intercostal spaces in which ventilation and perfusion were represented by changes in bioelectrical impedance. Each lung's contribution to overall respiratory function was also calculated based on scintigraphy. The right lung contributed a mean (SD) of 54% (9%) of ventilation (range, 32%-71%) according to EIT. Scintigraphy similarly estimated the right lung's contribution to be 52% (10%) of total ventilation (range, 31%-80%) and 50% (9%) of perfusion (range, 37%-71%). The difference between the 2 estimates was not significant (t test), and the correlation coefficients between them were r=0.90 for ventilation and r=0.72 for perfusion (P< .05 in both cases). The analysis of agreement showed that the mean difference between the methods was 1.9% (95% confidence interval [CI], 10.5% to -6.8%) for ventilation and 3.4% (95% CI, 17.1% to -10.3%) for perfusion. EIT is able to estimate differential lung function as accurately as ventilation-perfusion scintigraphy.

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

    Directory of Open Access Journals (Sweden)

    Duan Yingli

    2012-01-01

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

  18. Lung structure and function relation in systemic sclerosis: Application of lung densitometry

    Energy Technology Data Exchange (ETDEWEB)

    Ninaber, Maarten K., E-mail: m.k.ninaber@lumc.nl [Department of Pulmonology, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden (Netherlands); Stolk, Jan; Smit, Jasper; Le Roy, Ernest J. [Department of Pulmonology, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden (Netherlands); Kroft, Lucia J.M. [Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden (Netherlands); Els Bakker, M. [Division of Image Processing, Radiology, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden (Netherlands); Vries Bouwstra, Jeska K. de; Schouffoer, Anne A. [Department of Rheumatology, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden (Netherlands); Staring, Marius; Stoel, Berend C. [Division of Image Processing, Radiology, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden (Netherlands)

    2015-05-15

    Highlights: • A quantitative CT parameter of lung parenchyma in systemic sclerosis is presented. • We examine the optimal percentage threshold for the percentile density. • The 85th percentile density threshold correlated significantly with lung function. • A lung structure–function relation is confirmed. • We report applicability of Perc85 in progression mapping of interstitial lung disease. - Abstract: Introduction: Interstitial lung disease occurs frequently in patients with systemic sclerosis (SSc). Quantitative computed tomography (CT) densitometry using the percentile density method may provide a sensitive assessment of lung structure for monitoring parenchymal damage. Therefore, we aimed to evaluate the optimal percentile density score in SSc by quantitative CT densitometry, against pulmonary function. Material and methods: We investigated 41 SSc patients by chest CT scan, spirometry and gas transfer tests. Lung volumes and the nth percentile density (between 1 and 99%) of the entire lungs were calculated from CT histograms. The nth percentile density is defined as the threshold value of densities expressed in Hounsfield units. A prerequisite for an optimal percentage was its correlation with baseline DLCO %predicted. Two patients showed distinct changes in lung function 2 years after baseline. We obtained CT scans from these patients and performed progression analysis. Results: Regression analysis for the relation between DLCO %predicted and the nth percentile density was optimal at 85% (Perc85). There was significant agreement between Perc85 and DLCO %predicted (R = −0.49, P = 0.001) and FVC %predicted (R = −0.64, P < 0.001). Two patients showed a marked change in Perc85 over a 2 year period, but the localization of change differed clearly. Conclusions: We identified Perc85 as optimal lung density parameter, which correlated significantly with DLCO and FVC, confirming a lung parenchymal structure–function relation in SSc. This provides

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

    Directory of Open Access Journals (Sweden)

    Hodder R

    2012-08-01

    Full Text Available Rick Hodder*Divisions of Pulmonary and Critical Care, University of Ottawa and The Ottawa Hospital, Ottawa, Canada, *Dr Rick Hodder passed away on Tuesday April 17,2012. Please see the Dedication for more information on Dr Hodder.Abstract: Emergency department clinicians are frequently called upon to assess, diagnose, and stabilize patients who present with acute respiratory failure. This review describes a rapid initial approach to acute respiratory failure in adults, illustrated by two common examples: (1 an airway disease – acute potentially fatal asthma, and (2 a pulmonary parenchymal disease – acute lung injury/acute respiratory distress syndrome. As such patients are usually admitted to hospital, discussion will be focused on those initial management aspects most relevant to the emergency department clinician.Keywords: acute asthma, acute lung injury, ARDS, acute respiratory failure

  20. Monoacylglycerol lipase (MAGL inhibition attenuates acute lung injury in mice.

    Directory of Open Access Journals (Sweden)

    Carolina Costola-de-Souza

    Full Text Available 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-morpholinylethyl]-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.

  1. Measurement of lung volume by lung perfusion scanning using SPECT and prediction of postoperative respiratory function

    International Nuclear Information System (INIS)

    Andou, Akio; Shimizu, Nobuyosi; Maruyama, Shuichiro

    1992-01-01

    Measurement of lung volume by lung perfusion scanning using single photon emission computed tomography (SPECT) and its usefulness for the prediction of respiratory function after lung resection were investigated. The lung volumes calculated in 5 patients by SPECT (threshold level 20%) using 99m Tc-macroaggregated albumin (MAA), related very closely to the actually measured lung volumes. This results prompted us to calculate the total lung volume and the volume of the lobe to be resected in 18 patients with lung cancer by SPECT. Based on the data obtained, postoperative respiratory function was predicted. The predicted values of forced vital capacity (FVC), forced expiratory volume (FEV 1.0 ), and maximum vital volume (MVV) showed closer correlations with the actually measured postoperative values (FVC, FEV 1.0 , MVV : r=0.944, r=0.917, r=0.795 respectively), than the values predicted by the ordinary lung perfusion scanning. This method facilitates more detailed evaluation of local lung function on a lobe-by-lobe basis, and can be applied clinically to predict postoperative respiratory function. (author)

  2. Lung function in South African children with cystic fibrosis | Zar ...

    African Journals Online (AJOL)

    Objective: To determine the pattern of lung function in stable cystic fibrosis (CF) patients and to investigate the relationship of abnormal lung function to demographic variables, CF genotype and pulmonary colonisation with Pseudomonas aeruginosa (PA). Design: A descriptive study done at the CF clinic at Red Cross War ...

  3. Effect of low- intensity continuous training on lung function and ...

    African Journals Online (AJOL)

    Background: The decline in cardiorespiratory fitness and lung function was higher in smokers. Training method could mitigate some of the negative consequences of smoking among smokers unable or unwilling to quit. Objective: To examine the effects of continuous training on lungs functional capability and ...

  4. Interaction between asthma and lung function growth in early life

    DEFF Research Database (Denmark)

    Bisgaard, Hans; Jensen, Signe Marie; Bønnelykke, Klaus

    2012-01-01

    The causal direction between asthma and lung function deficit is unknown, but important for the focus of preventive measures and research into the origins of asthma.......The causal direction between asthma and lung function deficit is unknown, but important for the focus of preventive measures and research into the origins of asthma....

  5. Acute exhibition to high concentrations of chlorine and their effect at lung level

    International Nuclear Information System (INIS)

    Diaz J, Maria Claudia; Sanchez M, Jully Mariana; Jaramillo, Luis Fernando; Russi C, Hernando

    2004-01-01

    The bronchiolitis of occupational origin has been described as consequences of injuries by acute inhalation due to the exhibition to diverse substances; an interesting case was revised where after exhibition to chlorine and hypochlorite of calcium; lung manifestations were developed

  6. A genetic approach to understanding asthma and lung function development

    DEFF Research Database (Denmark)

    Kreiner-Møller, Eskil

    2014-01-01

    Asthma is a common heritable disease of the airways with recurrent episodes of symptoms and reversible airflow obstruction that has increased dramatically in prevalence. The disease is highly heterogeneous with varying age at onset and clinical presentation and most likely represents several...... their effect. In paper I, we investigated the known effect of adult lung function loci on the development of lung function and bronchial responsiveness in children from birth until 7 years of age in the COPSAC2000 birth cohort of 411 children. We measured lung function and bronchial responsiveness at one month...... of age using the raised volume rapid thoracoabdominal compression technique in sedated neonates and repeated the measurements at age 7 utilizing traditional spirometry assessments. Lung function genetic variants identified in adults were not associated with neonatal lung function or bronchial...

  7. Lung function in fragrance industry employees.

    Science.gov (United States)

    Dix, G R

    2013-07-01

    Production employees in the UK fragrance industry are exposed to large numbers of chemical substances and mixtures. There is a lack of published literature describing the effects of occupational respiratory exposure in this industry. To investigate whether occupational respiratory exposure to chemicals in the UK fragrance industry is linked to a statistically significant change in lung function as measured using spirometry. A multi-site cross-sectional study in which five UK companies took part, comprising an exposed group (fragrance production and associated functions) and a control group (non-exposed industry employees, e.g. office staff). Spirometric measurements (forced expiratory volume in 1 second, forced vital capacity and peak expiratory flow) were taken pre- and post-shift. Participants provided information on potential confounding factors (smoking, history of respiratory problems and body mass index). Post-shift measurements were compared between groups, using analysis of covariance to adjust for the baseline pre-shift measurements. A total of 112 subjects participated: 60 in the exposed group and 52 in control group (response rate 33 and 24%, respectively). Adjusted mean differences in post-shift spirometric measurements between exposed and control groups were not statistically significant. No significant effects were observed on the spirometric performance of the study population. This work is the first step in a novel area of research, and the industry would benefit from further such research.

  8. Cell Origin Dictates Programming of Resident versus Recruited Macrophages during Acute Lung Injury.

    Science.gov (United States)

    Mould, Kara J; Barthel, Lea; Mohning, Michael P; Thomas, Stacey M; McCubbrey, Alexandra L; Danhorn, Thomas; Leach, Sonia M; Fingerlin, Tasha E; O'Connor, Brian P; Reisz, Julie A; D'Alessandro, Angelo; Bratton, Donna L; Jakubzick, Claudia V; Janssen, William J

    2017-09-01

    Two populations of alveolar macrophages (AMs) coexist in the inflamed lung: resident AMs that arise during embryogenesis, and recruited AMs that originate postnatally from circulating monocytes. The objective of this study was to determine whether origin or environment dictates the transcriptional, metabolic, and functional programming of these two ontologically distinct populations over the time course of acute inflammation. RNA sequencing demonstrated marked transcriptional differences between resident and recruited AMs affecting three main areas: proliferation, inflammatory signaling, and metabolism. Functional assays and metabolomic studies confirmed these differences and demonstrated that resident AMs proliferate locally and are governed by increased tricarboxylic acid cycle and amino acid metabolism. Conversely, recruited AMs produce inflammatory cytokines in association with increased glycolytic and arginine metabolism. Collectively, the data show that even though they coexist in the same environment, inflammatory macrophage subsets have distinct immunometabolic programs and perform specialized functions during inflammation that are associated with their cellular origin.

  9. [Effect of lung strain on pulmonary edema in dogs with acute respiratory distress syndrome].

    Science.gov (United States)

    Liu, Qi; Zheng, Hui; Li, Wen; Zeng, Qingsi; Cheng, Zhe; Chen, Rongchang

    2015-09-22

    To explore the effect of lung strain on pulmonary edema in dogs with acute respiratory distress syndrome (ARDS) preliminarily. Twenty dogs were recruited to induct ARDS models by venous injection of oleic acid and grouped into Group S1.0, S1.5, S2.0, S2.5 randomly, the lung strain was previously designated as 1.0, 1.5, 2.0 or 2.5 for each group. The ventilation was used to support the dogs for 24 hours with tidal volume calculated from lung strain, functional residual capacity and the volume recruitment by positive end expiratory pressure. Extra vascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI) were tested by thermodilution technique and wet to dry ratio of lung tissue was evaluated by weighing method. The tidal volume of Group S1.0, S1.5, S2.0, S2.5 was (7.5 ± 1.7), (13.9 ± 5.8), (17.9 ± 4.7) and (20.3 ± 7.9) ml/kg, respectively. After ventilation for 4 h, EVLWI in Group S2.0 and Group S2.5 were higher than them in Group S1.0 and Group S1.5 ((38.9 ± 6.5), (40.1 ± 7.7) vs (26.6 ± 5.2), (28.8 ± 5.4) ml/kg; F = 5.627, P = 0.009). At the end of study, PVPI of Group S2.5 increased significantly versus Group S1.0, S1.5 and S2.0 (16.7 ± 5.4 vs 7.0 ± 2.3, 9.2 ± 2.2, 11.5 ± 6.0; F = 4.329, P = 0.022). Wet to dry ratios of lung tissue in Group S2.0 and Group S2.5 were significantly higher than Group S1.0 and Group S1.5 (10.4 ± 1.2, 10.8 ± 1.5 vs 8.3 ± 1.2, 8.0 ± 2.2; F = 5.627, P = 0.009) after ventilation. Lung strain above 2.0 aggravates pulmonary edema dramatically and the effect might be slight if lung strain was smaller than 1.5.

  10. Vestibular function after acute vestibular neuritis

    OpenAIRE

    Halmagyi, G M; Weber, K P; Curthoys, I S

    2010-01-01

    PURPOSE: To review the extent and mechanism of the recovery of vestibular function after sudden, isolated, spontaneous, unilateral loss of most or all peripheral vestibular function - usually called acute vestibular neuritis. METHODS: Critical review of published literature and personal experience. RESULTS: The symptoms and signs of acute vestibular neuritis are vertigo, vomiting, nystagmus with ipsiversive slow-phases, ipsiversive lateropulsion and ocular tilt reaction (the static symptoms) ...

  11. KGFR promotes Na+ channel expression in a rat acute lung injury ...

    African Journals Online (AJOL)

    recovery of alveolar epithelial cells from acute lung injury (ALI). Objectives: To evaluate the ... alveolar type II (ATII) epithelial cells was determined by PCR, immunohistochemistry and immunoelectron microscopy of rat lung tissues. Results: ..... regeneration, differentiation and wound-healing abilities of alveolar epithelial ...

  12. Blood transfusion : Transfusion-related acute lung injury: back to basics

    NARCIS (Netherlands)

    Peters, A.L.

    2017-01-01

    Transfusion-related acute lung injury (TRALI) is a life-threatening disease affecting the lungs. TRALI can develop within 6 hours after transfusion and almost all patients with TRALI require mechanical ventilation at the intensive care department. Nevertheless up to 40% of patients do not recover

  13. [Pulmonary apoptosis and necrosis in hyperoxia-induced acute mouse lung injury].

    Science.gov (United States)

    Zhang, Xiang-feng; Foda, Hussein D

    2004-07-01

    To investigate the pathways to cell death in hyperoxia-induced lung injury and the functional significance of apoptosis in vivo in response to hyperoxia. Seventy-two mice were exposed in sealed cages > 98% oxygen (for 24 - 72 h) or room air, and the severity of lung injury and epithelium sloughing was evaluated. The extent and location of apoptosis in injured lung tissues were studied by terminal transferase dUTP end labeling assay (TUNEL), reverse transcript-polymerase chain reaction (RT-PCR) and immunohistochemistry. Hyperoxia caused acute lung injury; the hyperoxic stress resulted in marked epithelium sloughing. TUNEL assay exhibited increased apoptosis index both in alveolar epithelial cells and bronchial epithelial cells in sections from mice after 48 h hyperoxia compared with their control group (0.51 +/- 0.10, 0.46 +/- 0.08 verse 0.04 +/- 0.02, 0.02 +/- 0.01). This was accompanied by increased expression of caspase-3 mRNA in lung tissues after 48 h hyperoxia compared with their control group (0.53 +/- 0.09 verse 0.34 +/- 0.07), the expression was higher at 72 h of hyperoxia (0.60 +/- 0.08). Immunohistochemistry study showed caspase-3 protein was located in cytoplasm and nuclei of airway epithelial cells, alveolar epithelial cells and macrophage in hyperoxia mice. The expression of caspase-3 protein in airway epithelium significantly increased at 24 h of hyperoxia compared with their control group (41.62 +/- 3.46 verse 15.86 +/- 1.84), the expression level was highest at 72 h of hyperoxia (55.24 +/- 6.80). Both apoptosis and necrosis contribute to cell death during hyperoxia. Apoptosis plays an important role in alveolar damage and cell death from hyperoxia.

  14. Acute Gene Expression Profile of Lung Tissue Following Sulfur Mustard Inhalation Exposure in Large Anesthetized Swine.

    Science.gov (United States)

    Jugg, Bronwen J A; Hoard-Fruchey, Heidi; Rothwell, Cristin; Dillman, James F; David, Jonathan; Jenner, John; Sciuto, Alfred M

    2016-10-17

    Sulfur mustard (HD) is a vesicating and alkylating agent widely used on the battlefield during World War I and more recently in the Iran-Iraq War. It targets the eyes, skin, and lungs, producing skin burns, conjunctivitis, and compromised respiratory function; early acute effects lead to long-term consequences. However, it is the effects on the lungs that drive morbidity and eventual mortality. The temporal postexposure response to HD within lung tissue raises the question of whether toxicity is driven by the alkylating properties of HD on critical homeostatic pathways. We have established an anesthetized swine model of inhaled HD vapor exposure to investigate the toxic effects of HD 12 h postexposure. Large white female swine were anesthetized and instrumented prior to exposure to air, 60 (sublethal) or 100 μg·kg -1 (∼LD 40 ) doses of HD (10 min). Physiological parameters were continuously assessed. Data indicate that exposure to 100 μg·kg -1 HD lowered arterial blood oxygenation and increased shunt fraction and lavage protein compared with those of air-exposed controls and the 60 μg·kg -1 dose of HD. Histopathology showed an increased total pathology score between the 100 μg·kg -1 HD group and air-exposed controls. Principal component analysis of differentially expressed genes demonstrated a distinct and separable response of inhaled HD between air-exposed controls and the 60 and 100 μg·kg -1 doses of HD. Canonical pathway analysis demonstrated changes in acute phase response signaling, aryl hydrocarbon receptor signaling, NRF-2 mediated oxidative stress, and zymosterol biosynthesis in the 60 and 100 μg·kg -1 HD dose group. Transcriptional changes also indicated alterations in immune response, cancer, and cell signaling and metabolism canonical pathways. The 100 μg·kg -1 dose group also showed significant changes in cholesterol biosynthesis. Taken together, exposure to inhaled HD had a significant effect on physiological responses coinciding with

  15. Lung tissue remodeling in the acute respiratory distress syndrome

    Directory of Open Access Journals (Sweden)

    Souza Alba Barros de

    2003-01-01

    Full Text Available Acute respiratory distress syndrome (ARDS is characterized by diffuse alveolar damage, and evolves progressively with three phases: exsudative, fibroproliferative, and fibrotic. In the exudative phase, there are interstitial and alveolar edemas with hyaline membrane. The fibropro­liferative phase is characterized by exudate organization and fibroelastogenesis. There is proliferation of type II pneumocytes to cover the damaged epithelial surface, followed by differentiation into type I pneumocytes. The fibroproliferative phase starts early, and its severity is related to the patient?s prognosis. The alterations observed in the phenotype of the pulmonary parenchyma cells steer the tissue remodeling towards either progressive fibrosis or the restoration of normal alveolar architecture. The fibrotic phase is characterized by abnormal and excessive deposition of extracellular matrix proteins, mainly collagen. The dynamic control of collagen deposition and degradation is regulated by metalloproteinases and their tissular regulators. The deposition of proteoglycans in the extracellular matrix of ARDS patients needs better study. The regulation of extracellular matrix remodeling, in normal conditions or in several pulmonary diseases, such as ARDS, results from a complex mechanism that integrate the transcription of elements that destroy the matrix protein and produce activation/inhibition of several cellular types of lung tissue. This review article will analyze the ECM organization in ARDS, the different pulmonary parenchyma remodeling mechanisms, and the role of cytokines in the regulation of the different matrix components during the remodeling process.

  16. Arginase 1: an unexpected mediator of pulmonary capillary barrier dysfunction in models of acute lung injury.

    Science.gov (United States)

    Lucas, Rudolf; Czikora, Istvàn; Sridhar, Supriya; Zemskov, Evgeny A; Oseghale, Aluya; Circo, Sebastian; Cederbaum, Stephen D; Chakraborty, Trinad; Fulton, David J; Caldwell, Robert W; Romero, Maritza J

    2013-01-01

    The integrity of epithelial and endothelial barriers in the lower airspaces of the lungs has to be tightly regulated, in order to prevent leakage and to assure efficient gas exchange between the alveoli and capillaries. Both G(-) and G(+) bacterial toxins, such as lipopolysaccharide and pneumolysin, respectively, can be released in high concentrations within the pulmonary compartments upon antibiotic treatment of patients suffering from acute respiratory distress syndrome (ARDS) or severe pneumonia. These toxins are able to impair endothelial barrier function, either directly, or indirectly, by induction of pro-inflammatory mediators and neutrophil sequestration. Toxin-induced endothelial hyperpermeability can involve myosin light chain phosphorylation and/or microtubule rearrangement. Endothelial nitric oxide synthase (eNOS) was proposed to be a guardian of basal barrier function, since eNOS knock-out mice display an impaired expression of inter-endothelial junction proteins and as such an increased vascular permeability, as compared to wild type mice. The enzyme arginase, the activity of which can be regulated by the redox status of the cell, exists in two isoforms - arginase 1 (cytosolic) and arginase 2 (mitochondrial) - both of which can be expressed in lung microvascular endothelial cells. Upon activation, arginase competes with eNOS for the substrate l-arginine, as such impairing eNOS-dependent NO generation and promoting reactive oxygen species generation by the enzyme. This mini-review will discuss recent findings regarding the interaction between bacterial toxins and arginase during acute lung injury and will as such address the role of arginase in bacterial toxin-induced pulmonary endothelial barrier dysfunction.

  17. Arginase 1: an unexpected mediator of pulmonary capillary barrier dysfunction in models of acute lung injury

    Directory of Open Access Journals (Sweden)

    Rudolf eLucas

    2013-08-01

    Full Text Available The integrity of epithelial and endothelial barriers in the lower airspaces of the lungs has to be tightly regulated, in order to prevent leakage and to assure efficient gas exchange between the alveoli and capillaries. Both G- and G+ bacterial toxins, such as LPS and pneumolysin, respectively, can be released in high concentrations within the pulmonary compartments upon antibiotic treatment of patients suffering from acute respiratory distress syndrome (ARDS or severe pneumonia. These toxins are able to impair endothelial barrier function, either directly, or indirectly, by induction of pro-inflammatory mediators and neutrophil sequestration. Toxin-induced endothelial hyperpermeability can involve myosin light chain phosphorylation and/or microtubule rearrangement. Endothelial nitric oxide synthase (eNOS was proposed to be a guardian of basal barrier function, since eNOS knock-out mice display an impaired expression of inter-endothelial junction proteins and as such an increased vascular permeability, as compared to wild type mice. The enzyme arginase, the activity of which can be regulated by the redox status of the cell, exists in two isoforms - arginase 1 (cytosolic and arginase 2 (mitochondrial - both of which can be expressed in lung microvascular endothelial cells. Upon activation, arginase competes with eNOS for the substrate L-arginine, as such impairing eNOS-dependent NO generation and promoting ROS generation by the enzyme. This mini-review will discuss recent findings regarding the interaction between bacterial toxins and arginase during acute lung injury and will as such address the role of arginase in bacterial toxin-induced pulmonary endothelial barrier dysfunction.

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

    Science.gov (United States)

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

    2014-08-01

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

  19. The effect of irradiation on lung function and perfusion in patients with lung cancer

    International Nuclear Information System (INIS)

    Abratt, Raymond P.; Willcox, Paul A.

    1995-01-01

    Purpose: To prospectively study the changes in lung function in patients with lung carcinoma treated with relatively high doses of irradiation. Methods and Materials: Lung function was assessed prior to and at 6 and 12 months following radiation therapy by a clinical dyspnea score, formal pulmonary function tests (lung volume spirometry and diffusion capacity) as well as an ipsilateral hemithorax lung perfusion scan. Changes in dyspnea score were evaluated by the chi-square and the Fishers exact test. Changes in formal lung function tests were compared with the t-test for dependent data and correlations with the t-test for independent data. Fifty-one patients were entered into the study. There were 42 evaluable patients at 6 months after irradiation and 22 evaluable patients at 12 months after irradiation. Results: A worsening of dyspnea score from 1 to 2, which is clinically acceptable, occurred in 50% or more of patients. However, a dyspnea score of 3, which is a serious complication, developed in only 5% of patients. The diffusion capacity (DLCO) decreased by 14% at 6 months and 12% at 12 months) (p < 0.0001). The forced vital capacity and total lung capacity decreased between 6% and 8% at 6 month and 12 months, which was statistically significant. The forced expiratory volume in 1 s decreased between 2 and 3% at 6 month and 12 months, which was not statistically significant. The ipsilateral hemithorax perfusion decreased by 17 and 20% at 6 and 12 months (p < 0.0001). There was no correlation between the initial hemithorax perfusion, or its decrease at follow up and the decrease in DLCO. Conclusion: Lung irradiation results in some loss of lung function in patients with lung cancer with a projected survival of 6 months or more. The pretreatment DLCO assessment should be useful in predicting clinical tolerance to irradiation

  20. Relationship between radiation dose and lung function in patients with lung cancer receiving radiotherapy

    International Nuclear Information System (INIS)

    Harsaker, V.; Dale, E.; Bruland, O.S.; Olsen, D.R.

    2003-01-01

    In patients with inoperable non-small cell lung cancer (NSCLC), radical radiotherapy is the treatment of choice. The dose is limited by consequential pneumonitis and lung fibrosis. Hence, a better understanding of the relationship between the dose-volume distributions and normal tissue side effects is needed. CT is a non-invasive method to monitor the development of fibrosis and pneumonitis, and spirometry is an established tool to measure lung function. NSCLC patients were included in a multicenter trial and treated with megavoltage conformal radiotherapy. In a subgroup comprising 16 patients, a total dose of 59-63 Gy with 1.8-1.9 Gy per fraction was given. Dose-volume histograms were calculated and corrected according to the linear-quadratic formula using alpha/beta=3 Gy. The patients underwent repetitive CT examinations (mean follow-up, 133 days) following radiotherapy, and pre and post treatment spirometry (mean follow-up, 240 days). A significant correlation was demonstrated between local lung dose and changes in CT numbers >30 days after treatment (p 40 Gy Gy there was a sudden increase in CT numbers at 70-90 days. Somewhat unexpectedly, the highest mean lung doses were found in patients with the least reductions in lung function (peak expiratory flow; p<0.001). The correlation between CT numbers, radiation dose and time after treatment show that CT may be used to monitor development of lung fibrosis/pneumonitis after radiotherapy for lung cancer. Paradoxically, the patients with the highest mean lung doses experienced the minimum deterioration of lung function. This may be explained by reduction in the volume of existing tumour masses obstructing the airways, leading to relief of symptoms. This finding stresses the role of radiotherapy for lung cancer, especially where the treatment aim is palliative

  1. Leptin receptor polymorphisms and lung function decline in COPD

    OpenAIRE

    Hansel, N.N.; Gao, L.; Rafaels, N.M.; Mathias, R.A.; Neptune, E.R.; Tankersley, C.; Grant, A.V.; Connett, J.; Beaty, T.H.; Wise, R.A.; Barnes, K.C.

    2009-01-01

    Only a fraction of all smokers develop chronic obstructive pulmonary disease (COPD), suggesting a large role for genetic susceptibility. The leptin receptor (LEPR) is present in human lung tissue and may play a role in COPD pathogenesis. The present study examined the association between genetic variants in the LEPR gene and lung function decline in COPD.

  2. [Lung ultrasound in acute and critical care medicine].

    Science.gov (United States)

    Zechner, P M; Seibel, A; Aichinger, G; Steigerwald, M; Dorr, K; Scheiermann, P; Schellhaas, S; Cuca, C; Breitkreutz, R

    2012-07-01

    The development of modern critical care lung ultrasound is based on the classical representation of anatomical structures and the need for the assessment of specific sonography artefacts and phenomena. The air and fluid content of the lungs is interpreted using few typical artefacts and phenomena, with which the most important differential diagnoses can be made. According to a recent international consensus conference these include lung sliding, lung pulse, B-lines, lung point, reverberation artefacts, subpleural consolidations and intrapleural fluid collections. An increased number of B-lines is an unspecific sign for an increased quantity of fluid in the lungs resembling interstitial syndromes, for example in the case of cardiogenic pulmonary edema or lung contusion. In the diagnosis of interstitial syndromes lung ultrasound provides higher diagnostic accuracy (95%) than auscultation (55%) and chest radiography (72%). Diagnosis of pneumonia and pulmonary embolism can be achieved at the bedside by evaluating subpleural lung consolidations. Detection of lung sliding can help to detect asymmetrical ventilation and allows the exclusion of a pneumothorax. Ultrasound-based diagnosis of pneumothorax is superior to supine anterior chest radiography: for ultrasound the sensitivity is 92-100% and the specificity 91-100%. For the diagnosis of pneumothorax a simple algorithm was therefore designed: in the presence of lung sliding, lung pulse or B-lines, pneumothorax can be ruled out, in contrast a positive lung point is a highly specific sign of the presence of pneumothorax. Furthermore, lung ultrasound allows not only diagnosis of pleural effusion with significantly higher sensitivity than chest x-ray but also visual control in ultrasound-guided thoracocentesis.

  3. Transfusion-related acute lung injury: Current understanding and preventive strategies

    NARCIS (Netherlands)

    Vlaar, A. P. J.

    2012-01-01

    Transfusion-related acute lung injury (TRALI) is the most serious complication of transfusion medicine. TRALI is defined as the onset of acute hypoxia within 6 hours of a blood transfusion in the absence of hydrostatic pulmonary oedema. The past decades have resulted in a better understanding of the

  4. Acute lung injury in children : from viral infection and mechanical ventilation to inflammation and apoptosis

    NARCIS (Netherlands)

    Bern, R.A.

    2010-01-01

    Acute lung injury (ALI), ook bekend als acute respiratory distress syndrome (ARDS), is een uitgebreide ontstekingsreactie in beide longen door een longziekte of een aandoening elders in het lichaam. Kinderen lijken minder gevoelig voor de ziekte dan volwassenen, wellicht door de manier waarop de

  5. Nonpulmonary treatments for pediatric acute respiratory distress syndrome: proceedings from the Pediatric Acute Lung Injury Consensus Conference.

    Science.gov (United States)

    Valentine, Stacey L; Nadkarni, Vinay M; Curley, Martha A Q

    2015-06-01

    To describe the recommendations from the Pediatric Acute Lung Injury Consensus Conference on nonpulmonary treatments in pediatric acute respiratory distress syndrome. Consensus conference of experts in pediatric acute lung injury. A panel of 27 experts met over the course of 2 years to develop a taxonomy to define pediatric acute respiratory distress syndrome and to make recommendations regarding treatment and research priorities. The nonpulmonary subgroup comprised three experts. When published data were lacking, a modified Delphi approach emphasizing strong professional agreement was utilized. The Pediatric Acute Lung Injury Consensus Conference experts developed and voted on a total of 151 recommendations addressing the topics related to pediatric acute respiratory distress syndrome, 30 of which related to nonpulmonary treatment. All 30 recommendations had strong agreement. Patients with pediatric acute respiratory distress syndrome should receive 1) minimal yet effective targeted sedation to facilitate mechanical ventilation; 2) neuromuscular blockade, if sedation alone is inadequate to achieve effective mechanical ventilation; 3) a nutrition plan to facilitate their recovery, maintain their growth, and meet their metabolic needs; 4) goal-directed fluid management to maintain adequate intravascular volume, end-organ perfusion, and optimal delivery of oxygen; and 5) goal-directed RBC transfusion to maintain adequate oxygen delivery. Future clinical trials in pediatric acute respiratory distress syndrome should report sedation, neuromuscular blockade, nutrition, fluid management, and transfusion exposures to allow comparison across studies. The Consensus Conference developed pediatric-specific definitions for pediatric acute respiratory distress syndrome and recommendations regarding treatment and future research priorities. These recommendations for nonpulmonary treatment in pediatric acute respiratory distress syndrome are intended to promote optimization and

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

    Directory of Open Access Journals (Sweden)

    Ronaldo Lopes Torres

    2014-06-01

    Full Text Available 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.

  7. Lung Function Profiles among Individuals with Nonmalignant Asbestos-related Disorders

    Directory of Open Access Journals (Sweden)

    Eun-Kee Park

    2014-12-01

    Conclusion: Lung function measurement differs in individuals with different ARDs. Monitoring of lung function among asbestos-exposed populations is a simple means of facilitating earlier interventions.

  8. Prediction of postoperative lung function after pulmonary resection

    International Nuclear Information System (INIS)

    Yoshikawa, Koichi

    1988-01-01

    Lung scintigraphy and ordinary lung function test as well as split lung function test by using bronchospirometry was performed in 78 patients with primary lung cancer and clinical significance of ventilation and perfusion scintigraphy was evaluated. Results obtained from this study are as follows. 1) The ratio of right VC to total VC obtained by preoperative bronchospirometry was well correlated to the ratio of right lung count to the total lung count obtained by ventiration and/or perfusion scintigraphy (r = 0.84, r = 0.69). 2) Evaluation of the data obtained from the patients undergoing pneumonectomy indicated that the right and left VC obtained preoperatively by bronchospirometry have their clinical significance only in the form of left to right ratio not in the form their absolure value. 3) As to the reliability of predicting the residual vital capacity after pneumonectomy on the basis of left-to-right of lung scintigraphy, ventilation scintigraphy is more reliable than perfusion scintigraphy. 4) Irrespective of using ventilation scintigraphy or perfusion scintigraphy, Ali's formular showed high reliability in predicting the residual vital capacity as well as FEV 1.0 after lobectomy. 5) Reduction of the perfusion rate in the operated side of the lung is more marked than of the ventilation rate, resulting in a significant elevation of ventilation/perfusion ratio of the operated side of the lung. From the results descrived above, it can be said that lung ventilation and perfusion scintigraphy are very useful method to predict the residual lung function as well as the change of ventilation/perfusion ratio after pulmonary resection. (author)

  9. Kaempferol attenuates acute lung injury in caecal ligation and puncture model of sepsis in mice.

    Science.gov (United States)

    Rabha, Dipankar Jyoti; Singh, Thakur Uttam; Rungsung, Soya; Kumar, Tarun; Parida, Subhashree; Lingaraju, Madhu Cholenahalli; Paul, Avishek; Sahoo, Monalisa; Kumar, Dinesh

    2018-03-01

    Kaempferol is a flavonoid and important part of the diet. Kaempferol has shown antioxidant, antiinflammatory and antidiabetic activities in various studies. However, protective potential of kaempferol in acute lung injury induced by sepsis and its mechanism remains unclear. The present study was undertaken to evaluate the effect of kaempferol in sepsis-induced acute lung injury in mice and its possible mechanism of action. Acute lung injury was induced by CLP surgery in mice. Kaempferol (100 mg/kg bw) was administered orally one hour before caecal ligation and puncture surgery in mice. Mice were divided into four groups sham, KEM+sham, sepsis (CLP), and KEM+sepsis. Assessment of lung injury was done by estimation of protein content in lung tissue, lung edema, proinflammatory cytokines in plasma and lung tissue, oxidative stress, antioxidant enzymes, nitrite production, and histopathology. Kaempferol pretreated mice showed significant (P Kaempferol pretreatment showed reduction in cytokines IL-6, IL-1β, and TNF-α in plasma as well as in lung tissue in comparison with septic mice without pretreatment. Pretreatment with kaempferol did not show any reduction in MDA level in comparison with septic mice. Antioxidant enzymes SOD and catalase and nonenzymatic antioxidant GSH activities were also increased with kaempferol pretreatment in septic mice. Further, kaempferol pretreatment reduced the lung tissue nitrite level (P Kaempferol pretreatment did not decrease bacterial load in septic mice. Mice pretreated with kaempferol followed by sepsis showed lesser infiltration of cells and more arranged alveolar structure in histopathological analysis. The study suggests that kaempferol showed attenuation in sepsis-induced acute lung injury in mice through suppression of oxidative stress, iNOS, and ICAM-1 pathways.

  10. RGD peptides protects against acute lung injury in septic mice through Wisp1-integrin β6 pathway inhibition.

    Science.gov (United States)

    Ding, Xibing; Wang, Xin; Zhao, Xiang; Jin, Shuqing; Tong, Yao; Ren, Hao; Chen, Zhixia; Li, Quan

    2015-04-01

    Acute lung injury is a common consequence of sepsis, a life-threatening inflammatory response caused by severe infection. In this study, we elucidate the attenuating effects of synthetic Arg-Gly-Asp-Ser peptides (RGDs) on acute lung injury in a sepsis mouse model. We further reveal that the beneficial effects of RGDs stem from their negative regulation of the Wisp1 (WNT1-inducible signaling pathway)-integrin β6 pathway. After inducing sepsis using cecal ligation and puncture (CLP), mice were randomized into experimental and control groups, and survival rates were recorded over 7 days, whereas only 20% of mice subjected to CLP survived when compared with untreated controls; the addition of RGDs to this treatment regimen dramatically increased the survival rate to 80%. Histological analysis revealed acute lung injury in CLP-treated mice, whereas those subjected to the combined treatment of CLP and RGDs showed a considerable decrease in lung injury severity. The addition of RGDs also dramatically attenuated other common sepsis-associated effects, such as increased white blood cell number in bronchoalveolar lavage fluid and decreased pulmonary capillary barrier function. Furthermore, treatment with RGDs decreased the serum and bronchoalveolar lavage fluid levels of inflammatory cytokines such as tumor necrosis factor α and interleukin 6, contrary to the CLP treatment alone that increased the levels of these proteins. Interestingly, however, RGDs had no detectable effect on bacterial invasion following sepsis induction. In addition, mice treated with RGDs showed decreased levels of wisp1 and integrin β6 when compared with CLP-treated mice. In the present study, a linkage between Wisp1 and integrin β6 was evaluated in vivo. Most strikingly, RGDs resulted in a decreased association of Wisp1 with integrin β6 based on coimmunoprecipitation analyses. These data suggest that RGDs ameliorate acute lung injury in a sepsis mouse model by inhibiting the Wisp1-integrin β6

  11. Early COPD patients with lung hyperinflation associated with poorer lung function but better bronchodilator responsiveness

    Directory of Open Access Journals (Sweden)

    Chen C

    2016-10-01

    Full Text Available Chunlan Chen,* Wenhua Jian,* Yi Gao, Yanqing Xie, Yan Song, Jinping Zheng State Key Laboratory of Respiratory Disease, China National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Diseases, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: It is unknown whether aggressive medication strategies should be used for early COPD with or without lung hyperinflation. We aimed to explore the characteristics and bronchodilator responsiveness of early COPD patients (stages I and II with/without lung hyperinflation.Methods: Four hundred and six patients with COPD who performed both lung volume and bronchodilation tests were retrospectively analyzed. Residual volume to total lung capacity >120% of predicted values indicated lung hyperinflation. The characteristics and bronchodilator responsiveness were compared between the patients with and without lung hyperinflation across all stages of COPD.Results: The percentages of patients with lung hyperinflation were 72.7% in the entire cohort, 19.4% in stage I, 68.5% in stage II, 95.3% in stage III, and 100.0% in stage IV. The patients with lung hyperinflation exhibited poorer lung function but better bronchodilator responsiveness of both forced expiratory volume in 1 second and forced vital capacity than those without lung hyperinflation during early COPD (t=2.21–5.70, P=0.000–0.029, especially in stage I, while age, body mass index, smoking status, smoking history, and disease duration were similar between the two subgroups in the same stages. From stages I to IV of subgroups with lung hyperinflation, stage I patients had the best bronchodilator responsiveness. Use of bronchodilator responsiveness of forced vital capacity to detect the presence of lung hyperinflation in COPD patients showed relatively high sensitivities (69.5%–75.3% and specificities (70.3%

  12. Regional Lung Function Profiles of Stage I and III Lung Cancer Patients: An Evaluation for Functional Avoidance Radiation Therapy

    International Nuclear Information System (INIS)

    Vinogradskiy, Yevgeniy; Schubert, Leah; Diot, Quentin; Waxweiller, Timothy; Koo, Phillip; Castillo, Richard; Castillo, Edward; Guerrero, Thomas; Rusthoven, Chad; Gaspar, Laurie; Kavanagh, Brian; Miften, Moyed

    2016-01-01

    Purpose: The development of clinical trials is underway to use 4-dimensional computed tomography (4DCT) ventilation imaging to preferentially spare functional lung in patients undergoing radiation therapy. The purpose of this work was to generate data to aide with clinical trial design by retrospectively characterizing dosimetric and functional profiles for patients with different stages of lung cancer. Methods and Materials: A total of 118 lung cancer patients (36% stage I and 64% stage III) from 2 institutions were used for the study. A 4DCT-ventilation map was calculated using the patient's 4DCT imaging, deformable image registration, and a density-change–based algorithm. To assess each patient's spatial ventilation profile both quantitative and qualitative metrics were developed, including an observer-based defect observation and metrics based on the ventilation in each lung third. For each patient we used the clinical doses to calculate functionally weighted mean lung doses and metrics that assessed the interplay between the spatial location of the dose and high-functioning lung. Results: Both qualitative and quantitative metrics revealed a significant difference in functional profiles between the 2 stage groups (P<.01). We determined that 65% of stage III and 28% of stage I patients had ventilation defects. Average functionally weighted mean lung dose was 19.6 Gy and 5.4 Gy for stage III and I patients, respectively, with both groups containing patients with large spatial overlap between dose and high-function regions. Conclusion: Our 118-patient retrospective study found that 65% of stage III patients have regionally variant ventilation profiles that are suitable for functional avoidance. Our results suggest that regardless of disease stage, it is possible to have unique spatial interplay between dose and high-functional lung, highlighting the importance of evaluating the function of each patient and developing a personalized functional

  13. Vestibular function after acute vestibular neuritis.

    Science.gov (United States)

    Halmagyi, G M; Weber, K P; Curthoys, I S

    2010-01-01

    To review the extent and mechanism of the recovery of vestibular function after sudden, isolated, spontaneous, unilateral loss of most or all peripheral vestibular function - usually called acute vestibular neuritis. Critical review of published literature and personal experience. The symptoms and signs of acute vestibular neuritis are vertigo, vomiting, nystagmus with ipsiversive slow-phases, ipsiversive lateropulsion and ocular tilt reaction (the static symptoms) and impairment of vestibulo-ocular reflexes from the ipsilesional semicircular canals on impulsive testing (the dynamic symptoms). Peripheral vestibular function might not improve and while static symptoms invariably resolve, albeit often not totally, dynamic symptoms only improve slightly if at all. The persistent loss of balance that some patients experience after acute vestibular neuritis can be due to inadequate central compensation or to incomplete peripheral recovery and vestibular rehabilitation has a role in the treatment of both.

  14. Magnetic resonance imaging of respiratory movement and lung function

    International Nuclear Information System (INIS)

    Tetzlaff, R.; Eichinger, M.

    2009-01-01

    Lung function measurements are the domain of spirometry or plethysmography. These methods have proven their value in clinical practice, nevertheless, being global measurements the functional indices only describe the sum of all functional units of the lung. Impairment of only a single component of the respiratory pump or of a small part of lung parenchyma can be compensated by unaffected lung tissue. Dynamic imaging can help to detect such local changes and lead to earlier adapted therapy. Magnetic resonance imaging (MRI) seems to be perfect for this application as it is not hampered by image distortion as is projection radiography and it does not expose the patient to potentially harmful radiation like computed tomography. Unfortunately, lung parenchyma is not easy to image using MRI due to its low signal intensity. For this reason first applications of MRI in lung function measurements concentrated on the movement of the thoracic wall and the diaphragm. Recent technical advances in MRI however might allow measurements of regional dynamics of the lungs. (orig.) [de

  15. Role and importance of ultrasound lung comets in acute cardiac care.

    Science.gov (United States)

    Ricci, Fabrizio; Aquilani, Roberta; Radico, Francesco; Bianco, Francesco; Dipace, Gioacchino Giuseppe; Miniero, Ester; De Caterina, Raffaele; Gallina, Sabina

    2015-04-01

    Lung ultrasonography is an emerging, user-friendly and easy-to-use technique that can be performed quickly at the patient's bedside to evaluate several pathologic conditions affecting the lung. Ultrasound lung comets (ULCs) are an echographic sign of uncertain biophysical characterisation mostly attributed to water-thickened subpleural interlobular septa, but invariably associated with increased extravascular lung water. ULCs have thus been proposed as a complementary tool for the assessment and monitoring of acute heart failure and are now entering into statements in international recommendation documents. Adding lung ultrasonography to conventional echocardiography allows for performing an integrated cardiopulmonary ultrasound examination, and this is an important opportunity for the cardiologist. The technique allows the simultaneous gathering of considerable information about the heart and the lungs to investigate acute and chronic cardio-pulmonary conditions within a non-invasive, radiation-free, single-probe, all-in-one examination. We have here reviewed the pertinent literature on the physical origin of ULCs and on their role and importance in intensive and acute cardiac care settings. We also here propose a new algorithm aimed at implementing evaluation in the diagnostic work-up of patients with suspected acute heart failure. © The European Society of Cardiology 2014.

  16. Ventilator induced lung injury (VILI) in acute respiratory distress ...

    African Journals Online (AJOL)

    The lung protective ventilation strategy- Low tidal volume ventilation has shown some reduction in mortality in patients with ARDS but mortality is still high in patient with severe ARDS secondary to Pneumocystis jiroveci pneumonia (PJP) despite of lung protective ventilation strategy. In patients with Severe ARDS due to PJP ...

  17. Diagnostic and Therapeutic Aspects of Acute Lung Injury: empirical studies

    NARCIS (Netherlands)

    R.A. Lachmann

    2006-01-01

    textabstractThe thesis emphases research on prognostic markers as well as on different approaches for treating lung injury. Thereby, the prevention and treatment of pneumonia and possible ventilation induced bacterial translocation from the lung into the blood represents the main focus of

  18. Abnormal lung function at preschool age - asthma in adolescence?

    Science.gov (United States)

    Lajunen, Katariina; Kalliola, Satu; Kotaniemi-Syrjänen, Anne; Sarna, Seppo; Malmberg, L Pekka; Pelkonen, Anna S; Mäkelä, Mika J

    2018-03-06

    Asthma often begins early in childhood. However, the risk for persistence is challenging to evaluate. This longitudinal study relates lung function assessed with impulse oscillometry (IOS) in preschool children to asthma in adolescence. Lung function was measured with IOS in 255 children with asthma-like symptoms aged 4-7 years. Baseline measurements were followed by exercise challenge and bronchodilation tests. At age 12-16 years, 121 children participated in the follow-up visit, when lung function was assessed with spirometry, followed by a bronchodilation test. Asthma symptoms and medication were recorded by a questionnaire and atopy defined by skin prick tests. Abnormal baseline values in preschool IOS were significantly associated with low lung function, the need for asthma medication, and asthma symptoms in adolescence. Preschool abnormal R5 at baseline (z-score ≥1.645 SD) showed 9.2 odds ratio (95%CI 2.7;31.7) for abnormal FEV1/FVC, use of asthma medication in adolescence, and 9.9 odds ratio (95%CI 2.9;34.4) for asthma symptoms. Positive exercise challenge and modified asthma-predictive index at preschool age predicted asthma symptoms and the need for asthma medication, but not abnormal lung function at teenage. Abnormal preschool IOS is associated with asthma and poor lung function in adolescence and might be utilised for identification of asthma persistence. Copyright © 2018. Published by Elsevier Inc.

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

    Directory of Open Access Journals (Sweden)

    Qiu-ping Liu

    2014-01-01

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

  20. Pre- and post-bronchodilator lung function as predictors of mortality in the Lung Health Study

    Directory of Open Access Journals (Sweden)

    Diaz-Guzman Enrique

    2011-10-01

    Full Text Available Abstract Background Chronic obstructive pulmonary disease (COPD is supposed to be classified on the basis of post-bronchodilator lung function. Most longitudinal studies of COPD, though, do not have post-bronchodilator lung function available. We used pre-and post bronchodilator lung function data from the Lung Health Study to determine whether these measures differ in their ability to predict mortality. Methods We limited our analysis to subjects who were of black or white race, on whom we had complete data, and who participated at either the 1 year or the 5 year follow-up visit. We classified subjects based on their baseline lung function, according to COPD Classification criteria using both pre- and post-bronchodilator lung function. We conducted a survival analysis and logistic regression predicting death and controlling for age, sex, race, treatment group, smoking status, and measures of lung function (either pre- or post-bronchodilator. We calculated hazard ratios (HR with 95% confidence intervals (CI and also calculated area under the curve for the logistic regression models. Results By year 15 of the study, 721 of the original 5,887 study subjects had died. In the year 1 sample survival models, a higher FEV1 % predicted lower mortality in both the pre-bronchodilator (HR 0.87, 95% CI 0.81, 0.94 per 10% increase and post-bronchodilator (HR 0.84, 95% CI 0.77, 0.90 models. The area under the curve for the respective models was 69.2% and 69.4%. Similarly, using categories, when compared to people with "normal" lung function, subjects with Stage 3 or 4 disease had similar mortality in both the pre- (HR 1.51, 95% CI 0.75, 3.03 and post-bronchodilator (HR 1.45, 95% CI 0.41, 5.15 models. In the year 5 sample, when a larger proportion of subjects had Stage 3 or 4 disease (6.4% in the pre-bronchodilator group, mortality was significantly increased in both the pre- (HR 2.68, 95% CI 1.51, 4.75 and post-bronchodilator (HR 2.46, 95% CI 1.63, 3

  1. Acute Respiratory Distress Syndrome Caused by Leukemic Infiltration of the Lung

    Directory of Open Access Journals (Sweden)

    Yao-Kuang Wu

    2008-05-01

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

  2. Genetic variants affecting cross-sectional lung function in adults show little or no effect on longitudinal lung function decline

    DEFF Research Database (Denmark)

    John, Catherine; Soler Artigas, María; Hui, Jennie

    2017-01-01

    across eight time points). A mixed model was fitted and weighted risk scores were calculated for the joint effect of 26 known regions on baseline and longitudinal changes in FEV1 and FEV1/FVC. Potential additional regions of interest were identified and followed up in two independent cohorts. RESULTS......: The 26 regions previously associated with cross-sectional lung function jointly showed a strong effect on baseline lung function (p=4.44×10-16 for FEV1/FVC) but no effect on longitudinal decline (p=0.160 for FEV1/FVC). This was replicated in an independent cohort. 39 additional regions of interest (48...... variants) were identified; these associations were not replicated in two further cohorts. CONCLUSIONS: Previously identified genetic variants jointly have a strong effect on cross-sectional lung function in adults but little or no effect on the rate of decline of lung function. It is possible...

  3. Lung volume recruitment acutely increases respiratory system compliance in individuals with severe respiratory muscle weakness

    Directory of Open Access Journals (Sweden)

    Yannick Molgat-Seon

    2017-03-01

    Full Text Available The aim of the present study was to determine whether lung volume recruitment (LVR acutely increases respiratory system compliance (Crs in individuals with severe respiratory muscle weakness (RMW. Individuals with RMW resulting from neuromuscular disease or quadriplegia (n=12 and healthy controls (n=12 underwent pulmonary function testing and the measurement of Crs at baseline, immediately after, 1 h after and 2 h after a single standardised session of LVR. The LVR session involved 10 consecutive supramaximal lung inflations with a manual resuscitation bag to the highest tolerable mouth pressure or a maximum of 50 cmH2O. Each LVR inflation was followed by brief breath-hold and a maximal expiration to residual volume. At baseline, individuals with RMW had lower Crs than controls (37±5 cmH2O versus 109±10 mL·cmH2O−1, p0.05. LVR had no significant effect on measures of pulmonary function at any time point in either group (all p>0.05. During inflations, mean arterial pressure decreased significantly relative to baseline by 10.4±2.8 mmHg and 17.3±3.0 mmHg in individuals with RMW and controls, respectively (both p<0.05. LVR acutely increases Crs in individuals with RMW. However, the high airway pressures during inflations cause reductions in mean arterial pressure that should be considered when applying this technique.

  4. Functional outcomes after lung transplant in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Cerón Navarro, José; de Aguiar Quevedo, Karol; Ansótegui Barrera, Emilio; Jordá Aragón, Carlos; Peñalver Cuesta, Juan Carlos; Mancheño Franch, Nuria; Vera Sempere, Francisco José; Padilla Alarcón, Jose

    2015-03-01

    Lung transplantation (LT) is a therapeutic option with controversial results in chronic obstructive pulmonary disease (COPD). We aimed to analyze the outcomes of transplantation in terms of lung function and to identify prognostic factors. A retrospective analysis of 107 patients with COPD receiving lung transplants in the La Fe Hospital between 1991 and 2008 was performed. Preoperative variables, pulmonary function tests before and after LT, surgical procedure variables and long-term monitoring, expressed as mean or percentage, as applicable, were analyzed. Spirometric results before and after LT were analyzed. Linear or logistic regression were used for multivariate analysis depending on the variable. Ninety-four men (87.9%) and 13 women (12.1%) were transplanted, with a mean age±standard deviation of 52.58±8.05 years; 71% of LTs were double-lung transplantations. Spirometric values improved after LT: FVC: +1.22L (+34.9%), FEV1: +1.66L (+56.7%) and FEF25-75: +1.85L (+50.8%); P=.001. This functional improvement was maintained after 5 years only in the group with BODE score >7 (P=.001). Recipient height, type of LT, use of extracorporeal circulation during the surgical procedure, presence of bronchiolitis obliterans syndrome and the age and cause of death of the donor significantly influenced lung function over time. LT improves lung function in COPD patients. This improvement was maintained at 5years only in patients with BODE>7. Double lung transplantation provides better functional results than single-lung transplantation. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

  5. ACUTE STROKE: FUNCTIONAL OUTCOME PREDICTORS

    OpenAIRE

    Sujatha; Ramalingam; Vinodkumar; Vasumathi; Valarmathi; Anu

    2016-01-01

    BACKGROUND Ischemic strokes account for >80% of total stroke events. Biochemical modalities like serum uric acid, ESR, CRP, Serum Fibrinogen will be a low cost and useful way to predict functional outcome after ischemic stroke. The Barthel ADL index it is an ordinal scale helping us to measure performances in ADL-activities in daily living. The present study aims to study the Biochemical parameters Uric Acid, CRP, ESR and Fibrinogen in Ischemic Stroke patients and to assess fu...

  6. Titanium Dioxide Exposure Induces Acute Eosinophilic Lung Inflammation in Rabbits

    Science.gov (United States)

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

    2014-01-01

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

  7. The acute effects of body position strategies and respiratory therapy in paralyzed patients with acute lung injury.

    Science.gov (United States)

    Davis, K; Johannigman, J A; Campbell, R S; Marraccini, A; Luchette, F A; Frame, S B; Branson, R D

    2001-01-01

    Routine turning of critically ill patients is a standard of care. In recent years, specialized beds that provide automated turning have been introduced. These beds have been reported to improve lung function, reduce hospital-acquired pneumonia, and facilitate secretion removal. This trial was designed to measure the physiological effects of routine turning and respiratory therapy in comparison with continuous lateral rotation (CLR). The study was a prospective, quasi-experimental, random assignment, trial with patients serving as their own controls. Paralyzed, sedated patients with acute respiratory distress syndrome were eligible for study. Patients were randomized to receive four turning and secretion management regimens in random sequence for 6 h each over a period of 24 h: (1) routine turning every 2 h from the left to right lateral position; (2) routine turning every 2 h from the left to right lateral position including a 15-min period of manual percussion and postural drainage (P&PD); (3) CLR with a specialized bed that turned patients from left to right lateral position, pausing at each position for 2 min; and (4) CLR with a specialized bed that turned patients from left to right lateral position pausing at each position for 2 min, and a 15-min period of percussion provided by the pneumatic cushions of the bed every 2 h. Nineteen patients were entered into the study. There were no statistically significant differences in the measured cardiorespiratory variables. There was a tendency for the ratio of partial pressure of arterial oxygen to fractional inspired oxygen concentration (PaO2/FIO2) to increase (174 +/- 31 versus 188 +/- 36; P = 0.068) and for the ratio of deadspace to tidal volume (Vd/Vt) to decrease (0.62 +/- 0.18 versus 0.59 +/- 0.18; P = 0.19) during periods of CLR, but these differences did not achieve statistical significance. There were statistically significant increases in sputum volume during the periods of CLR. The addition of P&PD did not

  8. Role of macrophage migration inhibitory factor in acute lung injury in mice with acute pancreatitis complicated by endotoxemia.

    Science.gov (United States)

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

    2006-08-01

    Acute pancreatitis accompanied by a subsequent infectious attack can often lead to multisystem organ dysfunction, including acute lung injury (ALI), but the molecular mechanisms are poorly defined. In this study, we explored the role of the priming insult by induction of cerulein pancreatitis, which was followed by the second attack due to endotoxemia, in the development of ALI in mice. Experiments revealed that LPS injection in mice with acute pancreatitis caused the development of ALI, as indicated by blood-gas derangements, pulmonary vascular hyperpermeability, increased inflammatory cell counts in bronchoalveolar lavage, and histologic lung damage. This was associated with the pancreatitis-induced increase in expression of macrophage migration inhibitory factor (MIF) in the lungs, together with elevated expression of Toll-like receptor (TLR)-4, both of which were inhibited by administration of anti-protease-activated receptor (PAR)-2 antibody. Furthermore, anti-MIF antibody treatment suppressed the pancreatitis-induced elevation of TLR-4 pulmonary expression. Genetic removal of MIF from mice resulted in less development of ALI in the setting of acute pancreatitis complicated by endotoxemia. These findings demonstrate that activation of protease-activated receptor-2 with trypsin, which can be released after pancreatitis induction, positively regulates the transcript level of MIF, and increased MIF results in exaggerated pulmonary expression of TLR-4, leading to the development of ALI with a subsequent infectious attack. We thus suggest that interventions designed to modulate MIF may have therapeutic advantages in treating ALI in patients with acute pancreatitis complicated by bacterial infection.

  9. Functional lung imaging during HFV in preterm rabbits.

    Directory of Open Access Journals (Sweden)

    Jordan Thurgood

    Full Text Available Although high frequency ventilation (HFV is an effective mode of ventilation, there is limited information available in regard to lung dynamics during HFV. To improve the knowledge of lung function during HFV we have developed a novel lung imaging and analysis technique. The technique can determine complex lung motion information in vivo with a temporal resolution capable of observing HFV dynamics. Using high-speed synchrotron based phase contrast X-ray imaging and cross-correlation analysis, this method is capable of recording data in more than 60 independent regions across a preterm rabbit lung in excess of 300 frames per second (fps. This technique is utilised to determine regional intra-breath lung mechanics of preterm rabbit pups during HFV. Whilst ventilated at fixed pressures, each animal was ventilated at frequencies of 1, 3, 5 and 10 Hz. A 50% decrease in delivered tidal volume was measured at 10 Hz compared to 1 Hz, yet at the higher frequency a 500% increase in minute activity was measured. Additionally, HFV induced greater homogeneity of lung expansion activity suggesting this ventilation strategy potentially minimizes tissue damage and improves gas mixing. The development of this technique permits greater insight and further research into lung mechanics and may have implications for the improvement of ventilation strategies used to support severe pulmonary trauma and disease.

  10. Histopathological investigation of differences between female and male rats on radiation-induced acute lung toxicity

    Directory of Open Access Journals (Sweden)

    Bilal BU

    2014-06-01

    Full Text Available Radiation-induced acute and chronic lung toxicity is one of the important adverse events that has a negative influence on quality of life. It is widely accepted today that there are important factors such as personal sensibility and genetic differences between patients which effect both treatment response and treatment toxicity. In this study, the influence of gender differences on acute lung toxicity due to radiotherapy is investigated. Accordingly, it is examined if there is a relation between gender and histopathologically proven vasculitis and pneumonia in the lung tissues of male and female rats that are sacrificed 6 weeks after radiotherapy. It is concluded that the gender differences in rats have no effect on lung toxicity.

  11. Acute subdural hematoma, Head injury, Functional reco

    African Journals Online (AJOL)

    kim

    Division of Neurosurgery, Department of Surgery, Kenyatta National Hospital, University of Nairobi,. Nairobi, Kenya. 2. Department of Human Anatomy, School of Medicine, University of Nairobi, Kenya. E-Mail Contact - KIBOI Julius Githinji : Mots-clés: Keywords: Acute subdural hematoma, Head injury, Functional recovery, ...

  12. RGD-tagged helical rosette nanotubes aggravate acute lipopolysaccharide-induced lung inflammation

    Directory of Open Access Journals (Sweden)

    Suri SS

    2011-12-01

    Full Text Available Sarabjeet Singh Suri1, Steven Mills1, Gurpreet Kaur Aulakh1, Felaniaina Rakotondradany2, Hicham Fenniri2, Baljit Singh11Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon; 2National Institute for Nanotechnology and Department of Chemistry, Edmonton, CanadaAbstract: Rosette nanotubes (RNT are a novel class of self-assembled biocompatible nanotubes that offer a built-in strategy for engineering structure and function through covalent tagging of synthetic self-assembling modules (G∧C motif. In this report, the G∧C motif was tagged with peptide Arg-Gly-Asp-Ser-Lys (RGDSK-G∧C and amino acid Lys (K-G∧C which, upon co-assembly, generate RNTs featuring RGDSK and K on their surface in predefined molar ratios. These hybrid RNTs, referred to as Kx/RGDSKy-RNT, where x and y refer to the molar ratios of K-G∧C and RGDSK–G∧C, were designed to target neutrophil integrins. A mouse model was used to investigate the effects of intravenous Kx/RGDSKy-RNT on acute lipopolysaccharide (LPS-induced lung inflammation. Healthy male C57BL/6 mice were treated intranasally with Escherichia coli LPS 80 µg and/or intravenously with K90/RGDSK10-RNT. Here we provide the first evidence that intravenous administration of K90/RGDSK10-RNT aggravates the proinflammatory effect of LPS in the mouse. LPS and K90/RGDSK10-RNT treatment groups showed significantly increased infiltration of polymorphonuclear cells in bronchoalveolar lavage fluid at all time points compared with the saline control. The combined effect of LPS and K90/RGDSK10-RNT was more pronounced than LPS alone, as shown by a significant increase in the expression of interleukin-1ß, MCP-1, MIP-1, and KC-1 in the bronchoalveolar lavage fluid and myeloperoxidase activity in the lung tissues. We conclude that K90/RGDSK10-RNT promotes acute lung inflammation, and when used along with LPS, leads to exaggerated immune response in the lung.Keywords: RGD peptide, helical rosette

  13. Effect of cannabis smoking on lung function and respiratory symptoms: a structured literature review

    Science.gov (United States)

    Ribeiro, Luis IG; Ind, Philip W

    2016-01-01

    As cannabis use increases, physicians need to be familiar with the effects of both cannabis and tobacco on the lungs. However, there have been very few long-term studies of cannabis smoking, mostly due to legality issues and the confounding effects of tobacco. It was previously thought that cannabis and tobacco had similar long-term effects as both cause chronic bronchitis. However, recent large studies have shown that, instead of reducing forced expiratory volume in 1 s and forced vital capacity (FVC), marijuana smoking is associated with increased FVC. The cause of this is unclear, but acute bronchodilator and anti-inflammatory effects of cannabis may be relevant. Bullous lung disease, barotrauma and cannabis smoking have been recognised in case reports and small series. More work is needed to address the effects of cannabis on lung function, imaging and histological changes. PMID:27763599

  14. Changes in regional and overall lung function after bronchography

    International Nuclear Information System (INIS)

    Richez, M.; Ravez, P.; Godart, G.; Halloy, J.L.; Robience, Y.

    1980-01-01

    This investigation compares the effects of unilateral bronchography on classical pulmonary function paramerts (spirometry, CO transfer, flowvolume curve, and arterial blood gases)and radioisotopic measurements by means of 99 sup(m)Tc-labeled microspheres and 81 sup(m)Kr. The regional changes of ventilation and perfusion were quantified by a radioisotopic index, which was established for each zone of interest: explored lung and unexplored lung. The quantitative study of regional perfusion and ventilation reveals significant reduction of ventilation for lung bases, but not for lung apices. The radioisotopic measurements show a reduction of perfusion parallel to the reduction of ventilation. There is no significant correlation between traditional pulmonary function parameters and isotopic indices. Radioisotopy proved a sensitive tool for investigation of unilateral alterations. (orig.) [de

  15. Regional differences in prediction models of lung function in Germany

    Directory of Open Access Journals (Sweden)

    Schäper Christoph

    2010-04-01

    Full Text Available Abstract Background Little is known about the influencing potential of specific characteristics on lung function in different populations. The aim of this analysis was to determine whether lung function determinants differ between subpopulations within Germany and whether prediction equations developed for one subpopulation are also adequate for another subpopulation. Methods Within three studies (KORA C, SHIP-I, ECRHS-I in different areas of Germany 4059 adults performed lung function tests. The available data consisted of forced expiratory volume in one second, forced vital capacity and peak expiratory flow rate. For each study multivariate regression models were developed to predict lung function and Bland-Altman plots were established to evaluate the agreement between predicted and measured values. Results The final regression equations for FEV1 and FVC showed adjusted r-square values between 0.65 and 0.75, and for PEF they were between 0.46 and 0.61. In all studies gender, age, height and pack-years were significant determinants, each with a similar effect size. Regarding other predictors there were some, although not statistically significant, differences between the studies. Bland-Altman plots indicated that the regression models for each individual study adequately predict medium (i.e. normal but not extremely high or low lung function values in the whole study population. Conclusions Simple models with gender, age and height explain a substantial part of lung function variance whereas further determinants add less than 5% to the total explained r-squared, at least for FEV1 and FVC. Thus, for different adult subpopulations of Germany one simple model for each lung function measures is still sufficient.

  16. Dihydro-Resveratrol Ameliorates Lung Injury in Rats with Cerulein-Induced Acute Pancreatitis.

    Science.gov (United States)

    Lin, Ze-Si; Ku, Chuen Fai; Guan, Yi-Fu; Xiao, Hai-Tao; Shi, Xiao-Ke; Wang, Hong-Qi; Bian, Zhao-Xiang; Tsang, Siu Wai; Zhang, Hong-Jie

    2016-04-01

    Acute pancreatitis is an inflammatory process originated in the pancreas; however, it often leads to systemic complications that affect distant organs. Acute respiratory distress syndrome is indeed the predominant cause of death in patients with severe acute pancreatitis. In this study, we aimed to delineate the ameliorative effect of dihydro-resveratrol, a prominent analog of trans-resveratrol, against acute pancreatitis-associated lung injury and the underlying molecular actions. Acute pancreatitis was induced in rats with repetitive injections of cerulein (50 µg/kg/h) and a shot of lipopolysaccharide (7.5 mg/kg). By means of histological examination and biochemical assays, the severity of lung injury was assessed in the aspects of tissue damages, myeloperoxidase activity, and levels of pro-inflammatory cytokines. When treated with dihydro-resveratrol, pulmonary architectural distortion, hemorrhage, interstitial edema, and alveolar thickening were significantly reduced in rats with acute pancreatitis. In addition, the production of pro-inflammatory cytokines and the activity of myeloperoxidase in pulmonary tissues were notably repressed. Importantly, nuclear factor-kappaB (NF-κB) activation was attenuated. This study is the first to report the oral administration of dihydro-resveratrol ameliorated acute pancreatitis-associated lung injury via an inhibitory modulation of pro-inflammatory response, which was associated with a suppression of the NF-κB signaling pathway. Copyright © 2016 John Wiley & Sons, Ltd.

  17. Partial ventilatory support modalities in acute lung injury and acute respiratory distress syndrome-a systematic review.

    Directory of Open Access Journals (Sweden)

    Sarah M McMullen

    Full Text Available The efficacy of partial ventilatory support modes that allow spontaneous breathing in patients with acute lung injury (ALI and acute respiratory distress syndrome (ARDS is unclear. The objective of this scoping review was to assess the effects of partial ventilatory support on mortality, duration of mechanical ventilation, and both hospital and intensive care unit (ICU lengths of stay (LOS for patients with ALI and ARDS; the secondary objective was to describe physiologic effects on hemodynamics, respiratory system and other organ function.MEDLINE (1966-2009, Cochrane, and EmBase (1980-2009 databases were searched using common ventilator modes as keywords and reference lists from retrieved manuscripts hand searched for additional studies. Two researchers independently reviewed and graded the studies using a modified Oxford Centre for Evidence-Based Medicine grading system. Studies in adult ALI/ARDS patients were included for primary objectives and pre-clinical studies for supporting evidence.Two randomized controlled trials (RCTs were identified, in addition to six prospective cohort studies, one retrospective cohort study, one case control study, 41 clinical physiologic studies and 28 pre-clinical studies. No study was powered to assess mortality, one RCT showed shorter ICU length of stay, and the other demonstrated more ventilator free days. Beneficial effects of preserved spontaneous breathing were mainly physiological effects demonstrated as improvement of gas exchange, hemodynamics and non-pulmonary organ perfusion and function.The use of partial ventilatory support modalities is often feasible in patients with ALI/ARDS, and may be associated with short-term physiological benefits without appreciable impact on clinically important outcomes.

  18. Consumption of Hydrogen Water Reduces Paraquat-Induced Acute Lung Injury in Rats

    Directory of Open Access Journals (Sweden)

    Shulin Liu

    2011-01-01

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

  19. Lung function is associated with arterial stiffness in children.

    Directory of Open Access Journals (Sweden)

    Julian G Ayer

    Full Text Available BACKGROUND: In older adults, an independent association exists between impaired lung function and cardiovascular disease. This interaction might be related to the effects of aging and/or smoking. In order to explore possible childhood antecedents to this association, we hypothesized that decreased lung function and vascular stiffness might be related, in early life. OBJECTIVE: To determine the relationship between lung function and carotid augmentation index (AIx, a measure of vascular stiffness, in 8-year old children. METHODS: Data on brachial blood pressure, lung function (FEV(1, FVC, FEV(1/FVC, obtained by spirometry and carotid AIx75 (AIx standardised to an arbitrary heart rate of 75 beats per minute, obtained by applanation tonometry was available in 249 community-based 8-year old children. These healthy children had been subjects in a randomised controlled trial of two interventions (omega-3 fatty acid supplementation and house-dust mite avoidance to prevent asthma. Smoking in pregnancy and childhood environmental tobacco smoke (ETS exposure was prospectively collected by questionnaire. The association between lung function and carotid AIx75 was assessed in multivariate models that included sex, height, smoking status during pregnancy, ETS exposure and randomisation groups (house dust mite avoidance and dietary intervention as covariates. RESULTS: In the fully adjusted models, Carotid AIx75 was independently associated with FEV1 (standardised β = -0.17,b = -6.72, partial R(2 = .02, p = 0.03, FVC (standardised β = -0.29, b = -9.31, partial R(2 = 0.04, p<0.001 and FEV1/FVC (standardised β = .13, b = 18.4, partial R(2 = 0.02, p = 0.04. CONCLUSION: Lower lung volumes are associated with increased vascular stiffness at an early age. The interaction between lung function and vascular stiffness may thus represent more than just age-related alterations in both the pulmonary and vascular systems.

  20. Effects of frequency and inspiratory plateau pressure during recruitment manoeuvres on lung and distal organs in acute lung injury.

    Science.gov (United States)

    Steimback, Paula W; Oliveira, Gisele P; Rzezinski, Andréia F; Silva, Pedro L; Garcia, Cristiane S N B; Rangel, Graziela; Morales, Marcelo M; Lapa E Silva, José R; Capelozzi, Vera L; Pelosi, Paolo; Rocco, Patricia R M

    2009-06-01

    To evaluate the effects of frequency and inspiratory plateau pressure (Pplat) during recruitment manoeuvres (RMs) on lung and distal organs in acute lung injury (ALI). We studied paraquat-induced ALI rats. At 24 h, rats were anesthetized and RMs were applied using continuous positive airway pressure (CPAP, 40 cmH(2)O/40 s) or three-different sigh strategies: (a) 180 sighs/h and Pplat = 40 cmH(2)O (S180/40), (b) 10 sighs/h and Pplat = 40 cmH(2)O (S10/40), and (c) 10 sighs/h and Pplat = 20 cmH(2)O (S10/20). S180/40 yielded alveolar hyperinflation and increased lung and kidney epithelial cell apoptosis as well as type III procollagen (PCIII) mRNA expression. S10/40 resulted in a reduction in epithelial cell apoptosis and PCIII expression. Static elastance and alveolar collapse were higher in S10/20 than S10/40. The reduction in sigh frequency led to a protective effect on lung and distal organs, while the combination with reduced Pplat worsened lung mechanics and histology.

  1. Alda-1 Protects Against Acrolein-Induced Acute Lung Injury and Endothelial Barrier Dysfunction.

    Science.gov (United States)

    Lu, Qing; Mundy, Miles; Chambers, Eboni; Lange, Thilo; Newton, Julie; Borgas, Diana; Yao, Hongwei; Choudhary, Gaurav; Basak, Rajshekhar; Oldham, Mahogany; Rounds, Sharon

    2017-12-01

    Inhalation of acrolein, a highly reactive aldehyde, causes lung edema. The underlying mechanism is poorly understood and there is no effective treatment. In this study, we demonstrated that acrolein not only dose-dependently induced lung edema but also promoted LPS-induced acute lung injury. Importantly, acrolein-induced lung injury was prevented and rescued by Alda-1, an activator of mitochondrial aldehyde dehydrogenase 2. Acrolein also dose-dependently increased monolayer permeability, disrupted adherens junctions and focal adhesion complexes, and caused intercellular gap formation in primary cultured lung microvascular endothelial cells (LMVECs). These effects were attenuated by Alda-1 and the antioxidant N-acetylcysteine, but not by the NADPH inhibitor apocynin. Furthermore, acrolein inhibited AMP-activated protein kinase (AMPK) and increased mitochondrial reactive oxygen species levels in LMVECs-effects that were associated with impaired mitochondrial respiration. AMPK total protein levels were also reduced in lung tissue of mice and LMVECs exposed to acrolein. Activation of AMPK with 5-aminoimidazole-4-carboxamide-1-β-4-ribofuranoside blunted an acrolein-induced increase in endothelial monolayer permeability, but not mitochondrial oxidative stress or inhibition of mitochondrial respiration. Our results suggest that acrolein-induced mitochondrial dysfunction may not contribute to endothelial barrier dysfunction. We speculate that detoxification of acrolein by Alda-1 and activation of AMPK may be novel approaches to prevent and treat acrolein-associated acute lung injury, which may occur after smoke inhalation.

  2. Computed Tomography Measure of Lung at Risk and Lung Function Decline in Chronic Obstructive Pulmonary Disease.

    Science.gov (United States)

    Bhatt, Surya P; Bodduluri, Sandeep; Hoffman, Eric A; Newell, John D; Sieren, Jessica C; Dransfield, Mark T; Reinhardt, Joseph M

    2017-09-01

    The rate of decline of lung function is greater than age-related change in a substantial proportion of patients with chronic obstructive pulmonary disease, even after smoking cessation. Regions of the lung adjacent to emphysematous areas are subject to abnormal stretch during respiration, and this biomechanical stress likely influences emphysema initiation and progression. To assess whether quantifying this penumbra of lung at risk would predict FEV 1 decline. We analyzed paired inspiratory-expiratory computed tomography images at baseline of 680 subjects participating in a large multicenter study (COPDGene) over approximately 5 years. By matching inspiratory and expiratory images voxel by voxel using image registration, we calculated the Jacobian determinant, a measure of local lung expansion and contraction with respiration. We measured the distance between each normal voxel to the nearest emphysematous voxel, and quantified the percentage of normal voxels within each millimeter distance from emphysematous voxels as mechanically affected lung (MAL). Multivariable regression analyses were performed to assess the relationship between the Jacobian determinant, MAL, and FEV 1 decline. The mean (SD) rate of decline in FEV 1 was 39.0 (58.6) ml/yr. There was a progressive decrease in the mean Jacobian determinant of both emphysematous and normal voxels with increasing disease stage (P < 0.001). On multivariable analyses, the mean Jacobian determinant of normal voxels within 2 mm of emphysematous voxels (MAL 2 ) was significantly associated with FEV 1 decline. In mild-moderate disease, for participants at or above the median MAL 2 (threshold, 36.9%), the mean decline in FEV 1 was 56.4 (68.0) ml/yr versus 43.2 (59.9) ml/yr for those below the median (P = 0.044). Areas of normal-appearing lung are mechanically influenced by emphysematous areas and this lung at risk is associated with lung function decline. Clinical trial registered with www.clinicaltrials.gov (NCT

  3. Src tyrosine kinase inhibition prevents pulmonary ischemia-reperfusion-induced acute lung injury.

    Science.gov (United States)

    Oyaizu, Takeshi; Fung, Shan-Yu; Shiozaki, Atsushi; Guan, Zehong; Zhang, Qiao; dos Santos, Claudia C; Han, Bing; Mura, Marco; Keshavjee, Shaf; Liu, Mingyao

    2012-05-01

    Pulmonary ischemia-reperfusion is a pathological process seen in several clinical conditions, including lung transplantation, cardiopulmonary bypass, resuscitation for circulatory arrest, atherosclerosis, and pulmonary embolism. A better understanding of its molecular mechanisms is very important. Rat left lung underwent in situ ischemia for 60 min, followed by 2 h of reperfusion. The gene expression profiles and Src protein tyrosine kinase (PTK) phosphorylation were studied over time, and PP2, an Src PTK inhibitor, was intravenously administered 10 min before lung ischemia to determine the role of Src PTK in lung injury. Reperfusion following ischemia significantly changed the expression of 169 genes, with Mmp8, Mmp9, S100a9, and S100a8 being the most upregulated genes. Ischemia alone only affected expression of 9 genes in the lung. However, Src PTK phosphorylation (activation) was increased in the ischemic lung, mainly on the alveolar wall. Src PTK inhibitor pretreatment decreased phosphorylation of Src PTKs, total protein tyrosine phosphorylation, and STAT3 phosphorylation. It increased phosphorylation of the p85α subunit of PI3 kinase, a signal pathway that can inhibit coagulation and inflammation. PP2 reduced leukocyte infiltration in the lung, apoptotic cell death, fibrin deposition, and severity of acute lung injury after reperfusion. Src inhibition also significantly reduced CXCL1 (GRO/KI) and CCL2 (MCP-1) chemokine levels in the serum. During pulmonary ischemia, Src PTK activation, rather than alteration in gene expression, may play a critical role in reperfusion-induced lung injury. Src PTK inhibition presents a new prophylactic treatment for pulmonary ischemia-reperfusion-induced acute lung injury.

  4. Hypertonic saline reduces inflammation and enhances the resolution of oleic acid induced acute lung injury

    Directory of Open Access Journals (Sweden)

    Costello Joseph F

    2008-07-01

    Full Text Available Abstract Background Hypertonic saline (HTS reduces the severity of lung injury in ischemia-reperfusion, endotoxin-induced and ventilation-induced lung injury. However, the potential for HTS to modulate the resolution of lung injury is not known. We investigated the potential for hypertonic saline to modulate the evolution and resolution of oleic acid induced lung injury. Methods Adult male Sprague Dawley rats were used in all experiments. Series 1 examined the potential for HTS to reduce the severity of evolving oleic acid (OA induced acute lung injury. Following intravenous OA administration, animals were randomized to receive isotonic (Control, n = 12 or hypertonic saline (HTS, n = 12, and the extent of lung injury assessed after 6 hours. Series 2 examined the potential for HTS to enhance the resolution of oleic acid (OA induced acute lung injury. Following intravenous OA administration, animals were randomized to receive isotonic (Control, n = 6 or hypertonic saline (HTS, n = 6, and the extent of lung injury assessed after 6 hours. Results In Series I, HTS significantly reduced bronchoalveolar lavage (BAL neutrophil count compared to Control [61.5 ± 9.08 versus 102.6 ± 11.89 × 103 cells.ml-1]. However, there were no between group differences with regard to: A-a O2 gradient [11.9 ± 0.5 vs. 12.0 ± 0.5 KPa]; arterial PO2; static lung compliance, or histologic injury. In contrast, in Series 2, hypertonic saline significantly reduced histologic injury and reduced BAL neutrophil count [24.5 ± 5.9 versus 46.8 ± 4.4 × 103 cells.ml-1], and interleukin-6 levels [681.9 ± 190.4 versus 1365.7 ± 246.8 pg.ml-1]. Conclusion These findings demonstrate, for the first time, the potential for HTS to reduce pulmonary inflammation and enhance the resolution of oleic acid induced lung injury.

  5. Lung function imaging methods in Cystic Fibrosis pulmonary disease.

    Science.gov (United States)

    Kołodziej, Magdalena; de Veer, Michael J; Cholewa, Marian; Egan, Gary F; Thompson, Bruce R

    2017-05-17

    Monitoring of pulmonary physiology is fundamental to the clinical management of patients with Cystic Fibrosis. The current standard clinical practise uses spirometry to assess lung function which delivers a clinically relevant functional readout of total lung function, however does not supply any visible or localised information. High Resolution Computed Tomography (HRCT) is a well-established current 'gold standard' method for monitoring lung anatomical changes in Cystic Fibrosis patients. HRCT provides excellent morphological information, however, the X-ray radiation dose can become significant if multiple scans are required to monitor chronic diseases such as cystic fibrosis. X-ray phase-contrast imaging is another emerging X-ray based methodology for Cystic Fibrosis lung assessment which provides dynamic morphological and functional information, albeit with even higher X-ray doses than HRCT. Magnetic Resonance Imaging (MRI) is a non-ionising radiation imaging method that is garnering growing interest among researchers and clinicians working with Cystic Fibrosis patients. Recent advances in MRI have opened up the possibilities to observe lung function in real time to potentially allow sensitive and accurate assessment of disease progression. The use of hyperpolarized gas or non-contrast enhanced MRI can be tailored to clinical needs. While MRI offers significant promise it still suffers from poor spatial resolution and the development of an objective scoring system especially for ventilation assessment.

  6. Hydrogen alleviates hyperoxic acute lung injury related endoplasmic reticulum stress in rats through upregulation of SIRT1.

    Science.gov (United States)

    Sun, Qiang; Han, Wenjie; Hu, Huijun; Fan, Danfeng; Li, Yanbo; Zhang, Yu; Lv, Yan; Li, Mingxin; Pan, Shuyi

    2017-06-01

    Hyperoxic acute lung injury (HALI) is a major clinical problem for patients undergoing supplemental oxygen therapy. Currently in clinical settings there exist no effective means of prevention or treatment methods. Our previous study found that: hydrogen could reduce HALI, as well as oxidative stress. This research will further explore the mechanism underlying the protective effect of hydrogen on oxygen toxicity. Rats were randomly assigned into three experimental groups and were exposed in a oxygen chamber for 60 continuous hours: 100% balanced air (control); 100% oxygen (HALI); 100% oxygen with hydrogen treatment (HALI + HRS). We examined lung function by wet to dry ratio of lung, lung pleural effusion and cell apoptosis. We also detected endoplasmic reticulum stress (ERS) by examining the expression of CHOP, GRP78 and XBP1. We further investigated the role of Sirtuin 1 (SIRT1) in HALI, which contributes to cellular regulation including ERS, by examining its expression after hydrogen treatment with SIRT1 inhibitor. Hydrogen could significantly reduce HALI by reducing lung edema and apoptosis, inhibiting the elevating of ERS and increased SIRT1 expression. By inhibition of SIRT1 expression, the effect of hydrogen on prevention of HALI is significantly weakened, the inhibition of the ERS was also reversed. Our findings indicate that hydrogen could reduce HALI related ERS and the mechanism of hydrogen may be associated with upregulation of SIRT1, this study reveals the molecular mechanisms underlying the protective effect of hydrogen, which provides a new theoretical basis for clinical application of hydrogen.

  7. Role of lung perfusion scintigraphy in predicting post-operative lung function in lung cancer patients undergoing pneumonectomy

    International Nuclear Information System (INIS)

    Rai, Sujith; Shah, S.; Purandare, N.C.; Pramesh, C.S.; George, K.; Rangarajan, V.

    2010-01-01

    Full text: Surgery has been the mainstay of treatment for patients with early stage non-small cell lung cancer. There is an increased risk of postoperative complications, especially in patients with poor respiratory reserve, with pneumonectomy resulting in an unacceptable quality of life. The high risk of morbidity and mortality makes it mandatory to triage patients with anatomically resectable disease as suitable candidates for surgery. Aim: 1. The purpose of the study is to evaluate the role of lung perfusion scan in predicting postoperative lung function in lung cancer patients undergoing pneumonectomy based on the pre-operative Forced Expiratory Volume in 1 sec (FEV1). 2. The predicted post-operative FEV1 will be compared with the patient's lung function clinically based on a) number of days patient was on ventilation post-operatively, b) post-op respiratory complications/lung collapse. Materials and Methods: Imaging was done on Infinia Hawkeye (GE) dual headed gamma camera on 30 patients of lung cancer undergoing Pneumonectomy. Patients were injected 5 mCi of 99m Tc-MAA and planar and tomographic images were obtained. A predicted postoperative value of FEV1 was calculated by the formula: postop predicted FEV1 = preop FEV1 - (FEV1 % contribution by affected lung/100). Patient's post-operative FEV1 was calculated for pneumonectomy. Patient was observed post-operatively and the following parameters were noted 1) Number of days patient was on ventilation post-operatively 2) Post-operative respiratory complications/lung collapse Pre-operative PFT's and 99m Tc-MAA lung perfusion scan was done on 30 patients (mean age 45 yrs, range 18-64 yrs) and lung function in 1st week post-pneumonectomy based on their number of days on ventilation post-operatively and respiratory complications/lung collapse was noted. Result: 1) 20 patients underwent left pneumonectomy, 10 patients underwent right Pneumonectomy. 2) Predicted FEV1 for pneumonectomy patients was (mean ± SD 1.49

  8. Regional lung function (133Xe-radiospirometry) in bronchial cancer

    International Nuclear Information System (INIS)

    Arborelius, M.; Kristersson, S.; Lindell, S.E.

    1976-01-01

    In a prospective study of all patients with bronchial cancer in the city of Malmoe, all patients considered for surgery were examined with regard to overall function (conventional spirometry) and regional lung function (133-Xe-radiospirometry). Out of 116 consecutive cases examined with 133-Xe-radiospirometry before surgery,

  9. Leptin receptor polymorphisms and lung function decline in COPD.

    Science.gov (United States)

    Hansel, N N; Gao, L; Rafaels, N M; Mathias, R A; Neptune, E R; Tankersley, C; Grant, A V; Connett, J; Beaty, T H; Wise, R A; Barnes, K C

    2009-07-01

    Only a fraction of all smokers develop chronic obstructive pulmonary disease (COPD), suggesting a large role for genetic susceptibility. The leptin receptor (LEPR) is present in human lung tissue and may play a role in COPD pathogenesis. The present study examined the association between genetic variants in the LEPR gene and lung function decline in COPD. In total, 429 European Americans were randomly selected from the National Heart Lung and Blood Institute Lung Health Study. 36 single nucleotide polymorphisms (SNPs) in LEPR were genotyped using the Illumina GoldenGate platform (Broad Institute, Cambridge, MA, USA). Mean annual decline in forced expiratory volume in 1 s % predicted over the 5-yr period was calculated using linear regression. Linear regression models were also used to adjust for potential confounders. In addition, in vivo expression of the receptor gene was assessed with immunohistochemistry on lungs from smoke-exposed inbred mice. We identified significant associations (pCOPD pathogenesis. We identified genetic variants in the LEPR gene significantly associated with lung function decline in a population of smokers with COPD. Our results support a role for LEPR as a novel candidate gene for COPD.

  10. Plasma 25-hydroxyvitamin D, lung function and risk of chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Afzal, Shoaib; Lange, Peter; Bojesen, Stig Egil

    2014-01-01

    25-hydroxyvitamin D (25(OH)D) may be associated with lung function through modulation of pulmonary protease-antiprotease imbalance, airway inflammation, lung remodelling and oxidative stress. We examined the association of plasma 25(OH)D levels with lung function, lung function decline and risk o...

  11. The association between systemic inflammatory cellular levels and lung function: a population-based study.

    Directory of Open Access Journals (Sweden)

    Tricia McKeever

    Full Text Available BACKGROUND: Lower lung function is associated with an elevated systemic white cell count in men. However, these observations have not been demonstrated in a representative population that includes females and may be susceptible to confounding by recent airway infections or recent cigarette smoking. We tested the hypothesis that lung function is inversely associated with systemic white cell count in a population-based study. METHODS: The study population consisted adults aged 17-90+ years who participated in the Third National Health and Nutrition Examination Survey who did not report a recent cough, cold or acute illness in a non-smoking and smoking population. RESULTS: In non-smoking adults with the highest quintile of the total white cell count had a FEV(1 125.3 ml lower than those in the lowest quintile (95% confidence interval CI: -163.1 to -87.5. Adults with the highest quintile of the total white cell count had a FVC 151.1 ml lower than those in the lowest quintile (95% confidence interval CI: -195.0 to -107.2. Similar associations were observed for granulocytes, mononuclear cells and lymphocytes. In current smokers, similar smaller associations observed for total white cell count, granulocytes and mononuclear cells. CONCLUSIONS: Systemic cellular inflammation levels are inversely associated with lung function in a population of both non-smokers and smokers without acute illnesses. This may contribute to the increased mortality observed in individuals with a higher baseline white cell count.

  12. Ischemic acute kidney injury induces a distant organ functional and genomic response distinguishable from bilateral nephrectomy.

    Science.gov (United States)

    Hassoun, Heitham T; Grigoryev, Dmitry N; Lie, Mihaela L; Liu, Manchang; Cheadle, Chris; Tuder, Rubin M; Rabb, Hamid

    2007-07-01

    Acute kidney injury (AKI) is associated with significant mortality, which increases further when combined with acute lung injury. Experiments in rodents have shown that kidney ischemia-reperfusion injury (IRI) facilitates lung injury and inflammation. To identify potential ischemia-specific lung molecular pathways involved, we conducted global gene expression profiling of lung 6 or 36 h following 1) bilateral kidney IRI, 2) bilateral nephrectomy (BNx), and 3) sham laparotomy in C57BL/6J mice. Bronchoalveolar lavage fluid analysis revealed increased total protein, and lung histology revealed increased cellular inflammation following IRI, but not BNx, compared with sham controls. Total RNA from whole lung was isolated and hybridized to 430MOEA (22,626 genes) GeneChips (n = 3/group), which were analyzed by robust multichip average and significance analysis of microarrays and linked to gene ontology (GO) terms using MAPPFinder. The microarray power analysis predicted that the false discovery rate (q or =50%-fold change compared with sham would represent significant changes in gene expression. Analysis identified 266 and 455 ischemia-specific, AKI-associated lung genes with increased expression and 615 and 204 with decreased expression at 6 and 36 h, respectively, compared with sham controls. Real-time PCR analysis validated select array changes in lung serum amyloid A3 and endothelin-1. GO analysis revealed significant activation (Z > 1.95) of several proinflammatory and proapoptotic biological processes. Ischemic AKI induces functional and transcriptional changes in the lung distinct from those induced by uremia alone. Further investigation using this lung molecular signature induced by kidney IRI will provide mechanistic insights and new therapies for critically ill patients with AKI.

  13. Lung-protective mechanical ventilation does not protect against acute kidney injury in patients without lung injury at onset of mechanical ventilation

    NARCIS (Netherlands)

    Cortjens, Bart; Royakkers, Annick A. N. M.; Determann, Rogier M.; van Suijlen, Jeroen D. E.; Kamphuis, Stephan S.; Foppen, Jannetje; de Boer, Anita; Wieland, Cathrien W.; Spronk, Peter E.; Schultz, Marcus J.; Bouman, Catherine S. C.

    2012-01-01

    Introduction: Preclinical and clinical studies suggest that mechanical ventilation contributes to the development of acute kidney injury (AKI), particularly in the setting of lung-injurious ventilator strategies. Objective: To determine whether ventilator settings in critically ill patients without

  14. Menopause Is Associated with Accelerated Lung Function Decline.

    Science.gov (United States)

    Triebner, Kai; Matulonga, Bobette; Johannessen, Ane; Suske, Sandra; Benediktsdóttir, Bryndís; Demoly, Pascal; Dharmage, Shyamali C; Franklin, Karl A; Garcia-Aymerich, Judith; Gullón Blanco, José Antonio; Heinrich, Joachim; Holm, Mathias; Jarvis, Debbie; Jõgi, Rain; Lindberg, Eva; Moratalla Rovira, Jesús Martínez; Muniozguren Agirre, Nerea; Pin, Isabelle; Probst-Hensch, Nicole; Puggini, Luca; Raherison, Chantal; Sánchez-Ramos, José Luis; Schlünssen, Vivi; Sunyer, Jordi; Svanes, Cecilie; Hustad, Steinar; Leynaert, Bénédicte; Gómez Real, Francisco

    2017-04-15

    Menopause is associated with changes in sex hormones, which affect immunity, inflammation, and osteoporosis and may impair lung function. Lung function decline has not previously been investigated in relation to menopause. To study whether lung function decline, assessed by FVC and FEV 1 , is accelerated in women who undergo menopause. The population-based longitudinal European Community Respiratory Health Survey provided serum samples, spirometry, and questionnaire data about respiratory and reproductive health from three study waves (n = 1,438). We measured follicle-stimulating hormone and luteinizing hormone and added information on menstrual patterns to determine menopausal status using latent class analysis. Associations with lung function decline were investigated using linear mixed effects models, adjusting for age, height, weight, pack-years, current smoking, age at completed full-time education, spirometer, and including study center as random effect. Menopausal status was associated with accelerated lung function decline. The adjusted mean FVC decline was increased by -10.2 ml/yr (95% confidence interval [CI], -13.1 to -7.2) in transitional women and -12.5 ml/yr (95% CI, -16.2 to -8.9) in post-menopausal women, compared with women menstruating regularly. The adjusted mean FEV 1 decline increased by -3.8 ml/yr (95% CI, -6.3 to -2.9) in transitional women and -5.2 ml/yr (95% CI, -8.3 to -2.0) in post-menopausal women. Lung function declined more rapidly among transitional and post-menopausal women, in particular for FVC, beyond the expected age change. Clinicians should be aware that respiratory health often deteriorates during reproductive aging.

  15. Tetramethylpyrazine attenuates oleic acid-induced acute lung injury ...

    African Journals Online (AJOL)

    The protein expression of NF-kB in the lung was measured by immunohistochemistry and Western blotting. The results showed an increase in tumor necrosis factor α and interleukin 1β in the ALI/ARDS rat models. The activation of NF-kB was suppressed by TMP in the ALI/ARDS rats. The suppression of those molecules is ...

  16. Updates on functional characterisation of bronchopulmonary dysplasia – the contribution of lung function testing

    Directory of Open Access Journals (Sweden)

    Anne eGreenough

    2015-05-01

    Full Text Available Bronchopulmonary dysplasia (BPD is a chronic lung disease that predominantly affects prematurely born infants. Initially BPD was described in infants who had suffered severe respiratory failure and required high pressure, mechanical ventilation with high concentrations of supplementary oxygen. It now also occurs in very prematurely born infants who initially had minimal or even no signs of lung disease. These differences impact on the nature of the lung function abnormalities suffered by BPD infants, which is also influenced by the criteria used to diagnose BPD and the oxygen saturation level used to determine the supplementary oxygen requirement. Key also to interpreting lung function data in this population is whether appropriate lung function tests have been used and in an adequately sized population to make meaningful conclusions. It should also be emphasised that BPD is a poor predictor of long term respiratory morbidity. Bearing in mind those caveats, studies have consistently demonstrated that infants who develop BPD have low compliance and functional residual capacities and raised resistances in the neonatal period. There is, however, no agreement with regard to which early lung function measurement predicts the development of BPD, likely reflecting different techniques were used in different populations in often underpowered studies. During infancy, lung function generally improves, but importantly airflow limitation persists and small airway function appears to decline. Assessment of lung function has demonstrated that improvements in lung function following diuretics or bronchodilators have not translated into long term improvements in respiratory outcomes. In contrast, early differences in lung function related to different ventilation modes have led to investigation and demonstration that prophylactic, neonatal high frequency oscillation appears to protect small airway function.

  17. Praeruptorin D and E attenuate lipopolysaccharide/hydrochloric acid induced acute lung injury in mice.

    Science.gov (United States)

    Yu, Peng-Jiu; Li, Jing-Rong; Zhu, Zheng-Guang; Kong, Huan-Yu; Jin, Hong; Zhang, Jun-Yan; Tian, Yuan-Xin; Li, Zhong-Huang; Wu, Xiao-Yun; Zhang, Jia-Jie; Wu, Shu-Guang

    2013-06-15

    Acute lung injury is a life-threatening syndrome characterized by overwhelming lung inflammation and increased microvascular permeability, which causes a high mortality rate worldwide. The dry root of Peucedanum praeruptorum Dunn has been long used to treat respiratory diseases in China. In the present study, Praeruptorin A, C, D and E (PA, PC, PD and PE), four pyranocoumarins extracted from this herb, have been investigated for the pharmacological effects in experimental lung injury mouse models. In lipopolysaccharide (LPS) challenged mice, PA and PC did not show protective effect against lung injury at the dose of 80 mg/kg. However, PD and PE significantly inhibited the infiltration of activated polymorphonuclear leukocytes (PMNs) and decreased the levels of TNF-α and IL-6 in bronchoalveolar lavage fluid at the same dose. There was no statistically significant difference between PD and PE group. Further study demonstrated that PD and PE suppressed protein extravasations in bronchoalveolar lavage fluid, attenuated myeloperoxidase (MPO) activity and the pathological changes in the lung. Both PD and PE suppressed LPS induced Nuclear Factor-kappa B (NF-κB) pathway activation in the lung by decreasing the cytoplasmic loss of Inhibitor κB-α (IκB-α) protein and inhibiting the translocation of p65 from cytoplasm to nucleus. We also extended our study to acid-induced acute lung injury and found that these two compounds protected mice from hydrochloric acid (HCl)-induced lung injury by inhibiting PMNs influx, IL-6 release and protein exudation. Taken together, these results suggested that PD and PE might be useful in the therapy of lung injury. Copyright © 2013 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    REYHANEH SEPEHR

    2013-07-01

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

  19. Bench to bedside: targeting coagulation and fibrinolysis in acute lung injury

    NARCIS (Netherlands)

    Ware, Lorraine B.; Camerer, Eric; Welty-Wolf, Karen; Schultz, Marcus J.; Matthay, Michael A.

    2006-01-01

    Substantial progress has been made in understanding the contribution of alterations in coagulation and fibrinolysis to the pathogenesis of acute lung injury (ALI). Findings from mouse, rat, baboon, and human studies indicate that alterations in coagulation and fibrinolysis may be of major

  20. Lack of evidence of CD40 ligand involvement in transfusion-related acute lung injury

    NARCIS (Netherlands)

    Tuinman, P. R.; Gerards, M. C.; Jongsma, G.; Vlaar, A. P.; Boon, L.; Juffermans, N. P.

    2011-01-01

    Activated platelets have been implicated in playing a major role in transfusion-related acute lung injury (TRALI), as platelets can trigger neutrophils, resulting in vascular damage. We hypothesized that binding of platelet CD40 ligand (CD40L) to endothelial CD40 is essential in the onset of TRALI.

  1. Acute esophagus toxicity in lung cancer patients after intensity modulated radiation therapy and concurrent chemotherapy

    NARCIS (Netherlands)

    Kwint, Margriet; Uyterlinde, Wilma; Nijkamp, Jasper; Chen, Chun; de Bois, Josien; Sonke, Jan-Jakob; van den Heuvel, Michel; Knegjens, Joost; van Herk, Marcel; Belderbos, José

    2012-01-01

    The purpose of this study was to investigate the dose-effect relation between acute esophageal toxicity (AET) and the dose-volume parameters of the esophagus after intensity modulated radiation therapy (IMRT) and concurrent chemotherapy for patients with non-small cell lung cancer (NSCLC). One

  2. The divergent clinical presentations of transfusion-related acute lung injury illustrated by two case reports

    NARCIS (Netherlands)

    Vlaar, Alexander P. J.; Porcelijn, Leendert; van Rooijen-Schreurs, Ingeborgh H. M.; Lardy, Neubury Maxton; Kersten, Marie Jose; Juffermans, Nicole P.

    2010-01-01

    Background: Although the 2-event pathogenesis of transfusion-related (TR) acute lung injury (ALI) has been accepted as an explanatory model, case reports classically describe patients without other risk factors for ALI. Patients who exhibit another risk factor for the onset of ALI may be neglected

  3. The inflammation-coagulation axis as an important intermediate pathway in acute lung injury

    NARCIS (Netherlands)

    Levi, Marcel; Schultz, Marcus

    2008-01-01

    Markers of inflammation, coagulation, and fibrinolysis predict an adverse outcome in patients with sepsis. These markers also seem predictive of an adverse outcome in patients with localized infection and inflammation, such as in acute lung injury. Whether this is entirely related to the disease or

  4. The Epidemiology of Transfusion-related Acute Lung Injury Varies According to the Applied Definition of Lung Injury Onset Time.

    Science.gov (United States)

    Vande Vusse, Lisa K; Caldwell, Ellen; Tran, Edward; Hogl, Laurie; Dinwiddie, Steven; López, José A; Maier, Ronald V; Watkins, Timothy R

    2015-09-01

    Research that applies an unreliable definition for transfusion-related acute lung injury (TRALI) may draw false conclusions about its risk factors and biology. The effectiveness of preventive strategies may decrease as a consequence. However, the reliability of the consensus TRALI definition is unknown. To prospectively study the effect of applying two plausible definitions of acute respiratory distress syndrome onset time on TRALI epidemiology. We studied 316 adults admitted to the intensive care unit and transfused red blood cells within 24 hours of blunt trauma. We identified patients with acute respiratory distress syndrome, and defined acute respiratory distress syndrome onset time two ways: (1) the time at which the first radiographic or oxygenation criterion was met, and (2) the time both criteria were met. We categorized two corresponding groups of TRALI cases transfused in the 6 hours before acute respiratory distress syndrome onset. We used Cohen's kappa to measure agreement between the TRALI cases and implicated blood components identified by the two acute respiratory distress syndrome onset time definitions. In a nested case-control study, we examined potential risk factors for each group of TRALI cases, including demographics, injury severity, and characteristics of blood components transfused in the 6 hours before acute respiratory distress syndrome onset. Forty-two of 113 patients with acute respiratory distress syndrome were TRALI cases per the first acute respiratory distress syndrome onset time definition and 63 per the second definition. There was slight agreement between the two groups of TRALI cases (κ = 0.16; 95% confidence interval, -0.01 to 0.33) and between the implicated blood components (κ = 0.15, 95% confidence interval, 0.11-0.20). Age, Injury Severity Score, high plasma-volume components, and transfused plasma volume were risk factors for TRALI when applying the second acute respiratory distress syndrome onset time definition

  5. Cooperation between Monocyte-Derived Cells and Lymphoid Cells in the Acute Response to a Bacterial Lung Pathogen.

    Directory of Open Access Journals (Sweden)

    Andrew S Brown

    2016-06-01

    Full Text Available Legionella pneumophila is the causative agent of Legionnaires' disease, a potentially fatal lung infection. Alveolar macrophages support intracellular replication of L. pneumophila, however the contributions of other immune cell types to bacterial killing during infection are unclear. Here, we used recently described methods to characterise the major inflammatory cells in lung after acute respiratory infection of mice with L. pneumophila. We observed that the numbers of alveolar macrophages rapidly decreased after infection coincident with a rapid infiltration of the lung by monocyte-derived cells (MC, which, together with neutrophils, became the dominant inflammatory cells associated with the bacteria. Using mice in which the ability of MC to infiltrate tissues is impaired it was found that MC were required for bacterial clearance and were the major source of IL12. IL12 was needed to induce IFNγ production by lymphoid cells including NK cells, memory T cells, NKT cells and γδ T cells. Memory T cells that produced IFNγ appeared to be circulating effector/memory T cells that infiltrated the lung after infection. IFNγ production by memory T cells was stimulated in an antigen-independent fashion and could effectively clear bacteria from the lung indicating that memory T cells are an important contributor to innate bacterial defence. We also determined that a major function of IFNγ was to stimulate bactericidal activity of MC. On the other hand, neutrophils did not require IFNγ to kill bacteria and alveolar macrophages remained poorly bactericidal even in the presence of IFNγ. This work has revealed a cooperative innate immune circuit between lymphoid cells and MC that combats acute L. pneumophila infection and defines a specific role for IFNγ in anti-bacterial immunity.

  6. Acute kidney injury and residual renal function

    OpenAIRE

    Ronco, Claudio; Rosner, Mitchell H

    2012-01-01

    Acute kidney injury (AKI) occurring in patients admitted to the ICU may result in impaired renal function on long-term follow-up after ICU discharge. The damage induced by subclinical or manifest episodes of AKI may, in fact, produce an irreversible loss of a variable amount of renal mass with deleterious effects on overall renal function. This may be the case even though baseline glomerular filtration rate appears to return to normal but renal reserve is impaired. This may have an important ...

  7. Flecainide Improve Sepsis Induced Acute Lung Injury by Controlling Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Jia Song

    2016-08-01

    Full Text Available Background: Flecainide is an antiarrhythmic agent that is used primarily in the treatment of cardiac arrhythmias. Some evidences also suggest that flecainide can participate in alveolar fluid clearance and inflammatory responses. This experiment was aimed to evaluate the effects of flecainide on sepsis induced acute lung injury in a rat model. Methods: Rats were treated with subcutaneous infusion of saline or flecainide (0.1 or 0.2 mg/kg/hr by a mini-osmotic pump. Subcutaneous infusion was started 3 hours before and continued until 8 hours after intraperitoneal injection of saline or endotoxin. Animals were sacrificed for analyses of severity of acute lung injury with wet to dry (W/D ratio and lung injury score (LIS in lung and inflammatory responses with level of leukocyte, polymorphonuclear neutrophils (PMNs and inteleukin-8 (IL-8 in bronchoalveolar lavages fluid (BALF. Results: Flecainide markedly improved dose dependently sepsis induced acute lung injury as analysed by W/D ratio (from 2.24 ± 0.11 to 1.76 ± 0.09, p < 0.05 and LIS (from 3 to 1, p < 0.05, and inflammatory response as determined by leukocyte (from 443 ± 127 to 229 ± 95, p < 0.05, PMNs (from 41.43 ± 17.63 to 2.43 ± 2.61, p < 0.05 and IL-8 (from 95.00 ± 15.28 to 40.00 ± 10.21, p < 0.05 in BALF. Conclusions: Flecanide improve sepsis induced acute lung injury in rats by controlling inflammatory responses.

  8. Residential ozone and lung function in the elderly

    DEFF Research Database (Denmark)

    Braeuner, Elvira V.; Karottki, Dorina Gabriela; Frederiksen, Marie

    2016-01-01

    Ground level ozone arises primarily from traffic, it is a powerful oxidant and its primary target organ is the lung. Most epidemiological studies reporting the health effects of ozone have estimated individual exposure from measurements obtained from outdoor monitors but surrogates of personal...... exposure may not adequately reflect personal exposures. Also, the main focus has been on infants and children. Our purpose was to assess associations between urban background ozone and indoor residential ozone levels as well as to investigate the effects of indoor residential ozone on lung function in 51...... elderly non-smokers. Indoor ozone was measured passively in homes, while urban background outdoor ozone was monitored continuously at a fixed monitoring station located on the roof of the 20-m high university H.C. Ørsteds campus building in a park area. Lung function was measured at baseline as well...

  9. Peroxisome Proliferator-Activated Receptors and Acute Lung Injury

    Directory of Open Access Journals (Sweden)

    Rosanna Di Paola

    2007-01-01

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

  10. Ambient air pollution and children's lung function in China.

    Science.gov (United States)

    Liu, Ling; Zhang, Jinliang

    2009-01-01

    To describe the correlations between ambient air pollutants (TSP, SO(2), NO(x)) and the level of children's lung function (FVC, FEV(1), MMEF) in China. We collected the research articles on ambient air pollution and children's lung function published from 1985 to 2006 and selected 11 articles finally according to the following criteria: (1) Children between the age of 7 and 15 as objects; (2) Local air quality monitoring results were reported; (3) Strict quality control was taken when testing children's lung function; (4) The results were expressed by the average of measured value. Then we analyzed the correlation relationship between the level of ambient air pollutants and children's lung function and compared the effects of ambient air pollutants on children's lung function of boy and girl. The selected articles included the results of 7 cities in China. Among them, the results of 6 cities' studies revealed that the levels of children's lung function were significantly lower in the areas with heavy ambient air pollution than those in the areas with light ambient air pollution. According to the articles, the average levels of TSP were at the range of 0.084 mg/m(3)-0.835 mg/m(3), SO(2) were 0.013 mg/m(3)-0.929 mg/m(3), NO(x) were 0.044 mg/m(3)-0.229 mg/m(3). Correlation analysis showed significant negative correlation between the levels of TSP and SO(2) and children's FVC and FEV(1), as well as the levels of NO(x) and children's MMEF. The correlation coefficient was -0.797 (t=-4.384, P=0.001) between TSP and FVC, -0.693 (t=-4.190, Pair pollution were significantly greater for boy. The levels of ambient air TSP and SO(2) correlated with the damage of the big airway function of children, while NO(x)NO(x) affected the small airway function chiefly. Furthermore, lung function of girl was more susceptible to ambient air pollutants than boy.

  11. Pulmonary Surfactants for Acute and Chronic Lung Diseases (Part I

    Directory of Open Access Journals (Sweden)

    O. A. Rozenberg

    2014-01-01

    Full Text Available Part 1 of the review gives information on the composition and properties of a pulmonary surfactant and quantitative and qual itative impairments in the pulmonary surfactant system in different neonatal and adult abnormalities and describes the composition of commercial synthetic and natural surfactants. The results of surfactant therapy for respiratory distress syndrome and other lung diseases with secondary surfactant deficiency in the newborns are analyzed.

  12. [LUNG ULTRASOUND IN PATIENTS WITH HEMATOLOGICAL MALIGNANCIES AND ACUTE RESPIRATORY FAILURE DUE TO PNEUMONIA.

    Science.gov (United States)

    Novikov, V A; Galstyan, G M; Gemdzh, I An E G; Kostina, I E; Gitis, M K

    2017-09-01

    To compare the accuracy of bedside lung ultrasound (LUS) and chest computed tomography (CT) for the de- tection of lung lesions in patients with hematological malignancies and acute respiratory failure (ARF). 39 patients with hematological malignancies and ARF were enrolled in prospective study. The investigation of the patients included LUS, chest C, extravascular lung water index (EVLW) by transpulmonary ther- modilution, and bronchoalveolar lavage (BAL). There was correlation between the total number of B-lines and E VLW index (r = 0,40; p pneu- mocystis pneumonia. B-lines were detected often in patients with Pneumocystis pneumonia. Sensitivity ofLUS pleural effusion assessment was 95%, specificity was 90%. LUS is high sensitivity and specificity method to detect lung lesions in patients with ARF.

  13. Surfactant treatment before reperfusion improves the immediate function of lung transplants in rats

    NARCIS (Netherlands)

    Erasmus, ME; Petersen, AH; Hofstede, G; Haagsman, HP; Oetomo, SB; Prop, J

    An impaired function of alveolar surfactant can cause lung transplant dysfunction early after reperfusion. In this study it was investigated whether treatment with surfactant before reperfusion improves the immediate function of lung transplants and whether an improved transplant function was

  14. Acute aortic occlusion due to tumor embolism in a patient with lung malignancy

    Directory of Open Access Journals (Sweden)

    Stella Lioudaki

    2017-07-01

    Full Text Available Objectives: Acute lower limb ischemia caused by tumor embolization is rare, despite the fact that cancer is a common cause of hypercoagulability predisposing to venous thrombosis. Arterial embolization is mostly associated with intracardiac tumors while lung malignancies are the second most common cause of tumor embolism. Methods: In this report, we present a male patient who developed acute bilateral lower limb ischemia in the immediate postoperative period after a thoracotomy for attempted left upper lobe resection for lung cancer. Results: The patient was treated with a subclavian-bifemoral bypass, since an initial attempted embolectomy was unsuccessful. Histopathological characteristics of thrombus obtained during embolectomy were consistent with the histopathology of the primary tumor. Conclusion: Acute ischemia is an emergency that should be diagnosed and treated immediately. Interestingly, in this case, the presence of epidural anesthesia masked the initial symptoms and delayed diagnosis. Preoperative assessment with transesophageal echocardiography may reveal patients at high risk for tumor embolism.

  15. Splenectomy exacerbates lung injury after ischemic acute kidney injury in mice

    Science.gov (United States)

    Andrés-Hernando, Ana; Altmann, Christopher; Ahuja, Nilesh; Lanaspa, Miguel A.; Nemenoff, Raphael; He, Zhibin; Ishimoto, Takuji; Simpson, Pete A.; Weiser-Evans, Mary C.; Bacalja, Jasna

    2011-01-01

    Patients with acute kidney injury (AKI) have increased serum proinflammatory cytokines and an increased occurrence of respiratory complications. The aim of the present study was to examine the effect of renal and extrarenal cytokine production on AKI-mediated lung injury in mice. C57Bl/6 mice underwent sham surgery, splenectomy, ischemic AKI, or ischemic AKI with splenectomy and kidney, spleen, and liver cytokine mRNA, serum cytokines, and lung injury were examined. The proinflammatory cytokines IL-6, CXCL1, IL-1β, and TNF-α were increased in the kidney, spleen, and liver within 6 h of ischemic AKI. Since splenic proinflammatory cytokines were increased, we hypothesized that splenectomy would protect against AKI-mediated lung injury. On the contrary, splenectomy with AKI resulted in increased serum IL-6 and worse lung injury as judged by increased lung capillary leak, higher lung myeloperoxidase activity, and higher lung CXCL1 vs. AKI alone. Splenectomy itself was not associated with increased serum IL-6 or lung injury vs. sham. To investigate the mechanism of the increased proinflammatory response, splenic production of the anti-inflammatory cytokine IL-10 was determined and was markedly upregulated. To confirm that splenic IL-10 downregulates the proinflammatory response of AKI, IL-10 was administered to splenectomized mice with AKI, which reduced serum IL-6 and improved lung injury. Our data demonstrate that AKI in the absence of a counter anti-inflammatory response by splenic IL-10 production results in an exuberant proinflammatory response and lung injury. PMID:21677145

  16. Lung function, oxygen saturation and symptoms among street ...

    African Journals Online (AJOL)

    Chronic inhalation of dust impairs lung function and may cause respiratory symptoms. However, knowledge about the type of dust that can cause these problems is uncertain. Very little attention has been paid to the health of workers chronically exposed to dust raised by street sweeping without precautionary measures.

  17. Assessment of respiratory symptoms and lung function among textile ...

    African Journals Online (AJOL)

    The smokers among the exposed and unexposed workers had significantly lower lung function values than nonsmokers. Conclusion: Respiratory symptoms were more prevalent among workers in most dusty sections of the factory. Use of protective mask should be enforced. Workers in the spinning and weaving sections of ...

  18. Lung function profiles and aerobic capacity of adult cigarette and ...

    African Journals Online (AJOL)

    Lung function profiles and aerobic capacity of adult cigarette and hookah smokers after 12 weeks intermittent training. ... All subjects performed 30 min of interval exercise (2 min of work followed by 1 min of rest) three times a week for 12 weeks at an intensity estimated at 70% of the subject's maximum aerobic capacity ...

  19. Enhanced Lung Function and Prevention of Peroxidative Damage ...

    African Journals Online (AJOL)

    This study was designed to assess the effects of vitamin E supplementation on the lung function and lipid peroxidation status of asthmatic children. Fifteen asthmatics (ten male and five female) aged between 6 and 13years, all in a stable state, were recruited from the paediatric out-patient respiratory clinic of the Lagos ...

  20. Lung Function Test in Asthmatics Patients in UBTH: Medical ...

    African Journals Online (AJOL)

    2004-06-30

    This report describes the result of a study on lung function tests on 75 asthmatics seen within a 6-month period (January 1 to June 30, 2004) at the University of Benin Teaching Hospital (UBTH), Benin City, Nigeria. There was a preponderance of females (60%) to males (40%); The result also showed that a large proportion ...

  1. A Correlation of Symptomatology with Lung Function in Patients with ...

    African Journals Online (AJOL)

    2017-06-28

    Jun 28, 2017 ... How to cite this article: Ajiya A, Salisu AD, Nwaorgu O. A correlation of symptomatology with lung function in patients with allergic rhinosinusitis. Niger J Clin Pract 2017;20:647-51. Access this article online. Quick Response Code: Website: www.njcponline.com. DOI: 10.4103/1119-3077.187321. PMID: XXX.

  2. 79 lung function, oxygen saturation and symptoms among street ...

    African Journals Online (AJOL)

    admin

    Summary: Chronic inhalation of dust impairs lung function and may cause respiratory symptoms. However, knowledge about the type of dust that can cause these problems is uncertain. Very little attention has been paid to the health of workers chronically exposed to dust raised by street sweeping without precautionary ...

  3. Predicting functional recovery after acute ankle sprain.

    Directory of Open Access Journals (Sweden)

    Sean R O'Connor

    Full Text Available Ankle sprains are among the most common acute musculoskeletal conditions presenting to primary care. Their clinical course is variable but there are limited recommendations on prognostic factors. Our primary aim was to identify clinical predictors of short and medium term functional recovery after ankle sprain.A secondary analysis of data from adult participants (N = 85 with an acute ankle sprain, enrolled in a randomized controlled trial was undertaken. The predictive value of variables (age, BMI, gender, injury mechanism, previous injury, weight-bearing status, medial joint line pain, pain during weight-bearing dorsiflexion and lateral hop test recorded at baseline and at 4 weeks post injury were investigated for their prognostic ability. Recovery was determined from measures of subjective ankle function at short (4 weeks and medium term (4 months follow ups. Multivariate stepwise linear regression analyses were undertaken to evaluate the association between the aforementioned variables and functional recovery.Greater age, greater injury grade and weight-bearing status at baseline were associated with lower function at 4 weeks post injury (p<0.01; adjusted R square=0.34. Greater age, weight-bearing status at baseline and non-inversion injury mechanisms were associated with lower function at 4 months (p<0.01; adjusted R square=0.20. Pain on medial palpation and pain on dorsiflexion at 4 weeks were the most valuable prognostic indicators of function at 4 months (p< 0.01; adjusted R square=0.49.The results of the present study provide further evidence that ankle sprains have a variable clinical course. Age, injury grade, mechanism and weight-bearing status at baseline provide some prognostic information for short and medium term recovery. Clinical assessment variables at 4 weeks were the strongest predictors of recovery, explaining 50% of the variance in ankle function at 4 months. Further prospective research is required to highlight the factors

  4. Study of regional lung function with xenon 133

    International Nuclear Information System (INIS)

    Devaux, D.; Wagner, R.; Germain, M.; Chardon, G.

    1975-01-01

    Exploration of regional lung function includes study of the closed circuit perfusion and ventilation respectively by injection and inhalation of xenon 133. The radiation is measured across the chest using 4 fixed scintillation counters, placed opposite the subject's back, 2 per lung field. Theoretical regional values using 15 normal young subjects are determined. Three cases justified the practical interest of this method. The percentage of variation for the parameters studied was about 10%. The method proved very useful for the clinician to whom it provides a numerical assessment of regional ventilation and perfusion [fr

  5. Activation of PPARα by Wy-14643 ameliorates systemic lipopolysaccharide-induced acute lung injury

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-07-05

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

  6. Activation of PPARα by Wy-14643 ameliorates systemic lipopolysaccharide-induced acute lung injury

    International Nuclear Information System (INIS)

    Yoo, Seong Ho; Abdelmegeed, Mohamed A.; Song, Byoung-Joon

    2013-01-01

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

  7. Lung perfusion SPECT in predicting postoperative pulmonary function in lung cancer

    International Nuclear Information System (INIS)

    Hirose, Yoshiaki; Imaeda, Takeyoshi; Doi, Hidetaka; Kokubo, Mitsuharu; Sakai, Satoshi; Hirose, Hajime

    1993-01-01

    The aim of this prospective study is to evaluate the availability of preoperative perfusion SPECT in predicting postoperative pulmonary function following resection. Twenty-three patients with lung cancer who were candidates for lobectomy were investigated preoperatively with spirometry, x-ray computed tomography and 99m Tc-macroaggregated albumin SPECT. Their postoperative pulmonary functions were predicted with these examinations. The forced vital capacity and the forced expiratory volume in one second were selected as parameters for overall pulmonary function. The postoperative pulmonary function was predicted by the following formula: Predicted postoperative value=observed preoperative value x precent perfusion of the lung not to be resected. The patients were reinvestigated with spirometry at 3 months and 6 months after lobectomy, and the values obtained were statistically compared with the predicted values. Close relationships were found between predicted and observed forced vital capacity (r=0.87, p<0.001), and predicted and observed forced expiratory volume in one second (r=0.90, p<0.001). The accurate prediction of pulmonary function after lobectomy could be achieved by means of lung perfusion SPECT. (author)

  8. Treatment for Sulfur Mustard Lung Injuries; New Therapeutic Approaches from Acute to Chronic Phase

    Directory of Open Access Journals (Sweden)

    Zohreh Poursaleh

    2012-09-01

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

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

    Directory of Open Access Journals (Sweden)

    Poursaleh Zohreh

    2012-09-01

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

  10. A multivariate analysis of serum nutrient levels and lung function

    Directory of Open Access Journals (Sweden)

    Smit Henriette A

    2008-09-01

    Full Text Available Abstract Background There is mounting evidence that estimates of intakes of a range of dietary nutrients are related to both lung function level and rate of decline, but far less evidence on the relation between lung function and objective measures of serum levels of individual nutrients. The aim of this study was to conduct a comprehensive examination of the independent associations of a wide range of serum markers of nutritional status with lung function, measured as the one-second forced expiratory volume (FEV1. Methods Using data from the Third National Health and Nutrition Examination Survey, a US population-based cross-sectional study, we investigated the relation between 21 serum markers of potentially relevant nutrients and FEV1, with adjustment for potential confounding factors. Systematic approaches were used to guide the analysis. Results In a mutually adjusted model, higher serum levels of antioxidant vitamins (vitamin A, beta-cryptoxanthin, vitamin C, vitamin E, selenium, normalized calcium, chloride, and iron were independently associated with higher levels of FEV1. Higher concentrations of potassium and sodium were associated with lower FEV1. Conclusion Maintaining higher serum concentrations of dietary antioxidant vitamins and selenium is potentially beneficial to lung health. In addition other novel associations found in this study merit further investigation.

  11. Deterioration in lung function following hemithorax irradiation for pleural mesothelioma

    International Nuclear Information System (INIS)

    Maasilta, P.

    1991-01-01

    Thirty-four patients receiving high-dose hemithorax irradiation as part of the treatment for pleural mesothelioma were studied with regard to changes in lung function following irradiation, and these changes were correlated with the radiologically-assessed lung injury. The latter was scored from 0 to 500 and found to be severe by 6 months (mean score 360), very severe by 9 months (mean score 430), and nearly total by 12 months (mean score 480) after treatment. Forced vital capacity and diffusing capacity both showed a significant decline at 1.5-2 months following the end of radiotherapy and thereafter up to the end of the 1 year follow-up period. Neither of these variables could be correlated consistently with the radiologically-assessed changes. Hypoxemia and pathological physiological shunting increased transiently 1-2 months after irradiation in 2 of the 6 patients monitored. The observed radiologically-assessed final effects of high-dose hemithorax irradiation are compatible with a total loss of lung function on the irradiated side. Before this form of treatment is used, lung function should be evaluated as for pneumonectomy

  12. Functional residual capacity measurement by heptafluoropropane in ventilated newborn lungs

    OpenAIRE

    Kusztrich, Ariane

    2012-01-01

    Objective: Heptafluoropropane is an inert gas commercially used as propellant for inhalers. Since heptafluoropropane can be detected in low concentrations, it could also be used as a tracer gas to measure functional residual capacity. The aim of the present study was to validate functional residual capacity measurements by heptafluoropropane wash-in/wash-out (0.8%) during mechanical ventilation in small, surfactant-depleted lungs using a newborn piglet model. Design: Prospective laborato...

  13. Sodium butyrate protects against severe burn-induced remote acute lung injury in rats.

    Directory of Open Access Journals (Sweden)

    Xun Liang

    Full Text Available High-mobility group box 1 protein (HMGB1, a ubiquitous nuclear protein, drives proinflammatory responses when released extracellularly. It plays a key role as a distal mediator in the development of acute lung injury (ALI. Sodium butyrate, an inhibitor of histone deacetylase, has been demonstrated to inhibit HMGB1 expression. This study investigates the effect of sodium butyrate on burn-induced lung injury. Sprague-Dawley rats were divided into three groups: 1 sham group, sham burn treatment; 2 burn group, third-degree burns over 30% total body surface area (TBSA with lactated Ringer's solution for resuscitation; 3 burn plus sodium butyrate group, third-degree burns over 30% TBSA with lactated Ringer's solution containing sodium butyrate for resuscitation. The burned animals were sacrificed at 12, 24, and 48 h after burn injury. Lung injury was assessed in terms of histologic changes and wet weight to dry weight (W/D ratio. Tumor necrosis factor (TNF-α and interleukin (IL-8 protein concentrations in bronchoalveolar lavage fluid (BALF and serum were measured by enzyme-linked immunosorbent assay, and HMGB1 expression in the lung was determined by Western blot analysis. Pulmonary myeloperoxidase (MPO activity and malondialdehyde (MDA concentration were measured to reflect neutrophil infiltration and oxidative stress in the lung, respectively. As a result, sodium butyrate significantly inhibited the HMGB1 expressions in the lungs, reduced the lung W/D ratio, and improved the pulmonary histologic changes induced by burn trauma. Furthermore, sodium butyrate administration decreased the TNF-α and IL-8 concentrations in BALF and serum, suppressed MPO activity, and reduced the MDA content in the lungs after severe burn. These results suggest that sodium butyrate attenuates inflammatory responses, neutrophil infiltration, and oxidative stress in the lungs, and protects against remote ALI induced by severe burn, which is associated with inhibiting HMGB1

  14. Sodium Butyrate Protects against Severe Burn-Induced Remote Acute Lung Injury in Rats

    Science.gov (United States)

    Liu, Sheng; Guo, Feng; Sun, Li; Wang, Yong-Jie; Sun, Ye-Xiang; Chen, Xu-Lin

    2013-01-01

    High-mobility group box 1 protein (HMGB1), a ubiquitous nuclear protein, drives proinflammatory responses when released extracellularly. It plays a key role as a distal mediator in the development of acute lung injury (ALI). Sodium butyrate, an inhibitor of histone deacetylase, has been demonstrated to inhibit HMGB1 expression. This study investigates the effect of sodium butyrate on burn-induced lung injury. Sprague–Dawley rats were divided into three groups: 1) sham group, sham burn treatment; 2) burn group, third-degree burns over 30% total body surface area (TBSA) with lactated Ringer’s solution for resuscitation; 3) burn plus sodium butyrate group, third-degree burns over 30% TBSA with lactated Ringer’s solution containing sodium butyrate for resuscitation. The burned animals were sacrificed at 12, 24, and 48 h after burn injury. Lung injury was assessed in terms of histologic changes and wet weight to dry weight (W/D) ratio. Tumor necrosis factor (TNF)-α and interleukin (IL)-8 protein concentrations in bronchoalveolar lavage fluid (BALF) and serum were measured by enzyme-linked immunosorbent assay, and HMGB1 expression in the lung was determined by Western blot analysis. Pulmonary myeloperoxidase (MPO) activity and malondialdehyde (MDA) concentration were measured to reflect neutrophil infiltration and oxidative stress in the lung, respectively. As a result, sodium butyrate significantly inhibited the HMGB1 expressions in the lungs, reduced the lung W/D ratio, and improved the pulmonary histologic changes induced by burn trauma. Furthermore, sodium butyrate administration decreased the TNF-α and IL-8 concentrations in BALF and serum, suppressed MPO activity, and reduced the MDA content in the lungs after severe burn. These results suggest that sodium butyrate attenuates inflammatory responses, neutrophil infiltration, and oxidative stress in the lungs, and protects against remote ALI induced by severe burn, which is associated with inhibiting HMGB1

  15. [Penehyclidine hydrochloride attenuates LPS-induced acute lung injury in rats].

    Science.gov (United States)

    Guo, Yan; Wei, Min; Yan, Zhiqiang; Wang, Guoxia

    2017-11-01

    Objective To study the protective effect of penehyclidine hydrochloride (PHCD) against acute lung injury induced by lipopolysaccharide (LPS) in rats. Methods 36 Sprague Dawley (SD) rats were randomly divided into control group, LPS-induced shock group (LPS group), and PHCD treated group (PHCD group). Rat shock model was prepared by intraperitoneal injection of LPS (5 mg/kg). The rats of PHCD group were treated with PHCD (1.0 mg/kg) by caudal vein injection. Rat blood gas analysis was performed 6 hours after the injection. Lung wet/dry mass ratio (W/D) was detected after the rats were sacrificed. The levels of tumor necrosis factor α (TNF-α), interleukin 8 (IL-8), and IL-6 in bronchoalveolar lavage fluid (BALF) were tested by ELISA. The lung tissue inflammation was observed by HE staining. The expression of inducible nitric oxide synthase (iNOS) was detected by real-time quantitative PCR and Western blot analysis. Results Compared with the control group, lung W/D and blood lactate acid (LAC) increased significantly in the LPS group, while the blood pH and the arterial oxygen partial pressure (PaO 2 ) decreased markedly. The levels of TNF-α, IL-8 and IL-6 significantly increased in lung BALF of the LPS-induced rats, and the expression of iNOS increased significantly. HE staining showed that LPS treatment caused pulmonary edema, congestion and inflammatory cell infiltration. After PHCD treatment, lung W/D and LAC were reduced; the pH and PaO 2 were elevated compared with LPS-induced rats; the levels of TNF-α, IL-8 and IL-6 in BALF were evidently down-regulated; the expression of iNOS decreased obviously. HE staining showed that the lung inflammation was attenuated by PHCD treatment. Conclusion PHCD attenuates lung injury by inhibiting LPS-induced lung inflammation.

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

    International Nuclear Information System (INIS)

    Lee, Ye-Ji; Lee, Seung-Hae; Youn, Young-So; Choi, Ji-Yeon; Song, Keung-Sub; Cho, Min-Sun; Kang, Jihee Lee

    2012-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Priscila Cilene León Bueno de Camargo

    2014-08-01

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

  18. LUNG FUNCTION AND RESPIRATORY MUSCLE STRENGTH IN OBESE IN CHILDREN

    Directory of Open Access Journals (Sweden)

    E. G. Furman

    2015-01-01

    Full Text Available Background. It is known that obesity may influence the state of respiratory function and it is associated with a number of diseases of the respiratory system. Obesity in itself, even in the absence of other known causes, can cause a feeling of shortness of breath at rest. At the same time, the cardinal symptom of respiratory muscle weakness is shortness of breath, which promotes the reduction of exercise tolerance. At the moment the problem state of respiratory function and respiratory muscles in children with different degrees of obesity is relevant and understudied. Aim. Investigation of lung function and respiratory muscle strength in obese in children. Methods. 46 children with obesity were examined, with a prevalence of obesity of mixed origin with progressive, aged 7 to 16 years. We evaluated the lung function and strength of respiratory muscles in the form of maximum inspiratory pressure at the mouth (MIP, maximal expiratory pressure at the mouth (MEP and nasal inspiratory pressure in the sniff-test (SNIP. Results. The children with obesity complained of dyspnea. The respiratory muscle dysfunction observed in the form of reduction of its forces. Reduced respiratory muscle strength ( 80% of the norm was in 44% of patients on the MIP and 38% on the MEP and was increased with increasing body mass index. Conclusion. Children with obesity need to monitor the lung function and evaluate the strength of the respiratory muscles for early detection of functional disorders of the respiratory system. 

  19. Lung inflammation biomarkers and lung function in children chronically exposed to arsenic

    Energy Technology Data Exchange (ETDEWEB)

    Olivas-Calderón, Edgar, E-mail: edgar_olivascalderon@hotmail.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); School of Medicine, University Juarez of Durango, Gomez Palacio, Durango (Mexico); Recio-Vega, Rogelio, E-mail: rrecio@yahoo.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); Gandolfi, A. Jay, E-mail: gandolfi@pharmacy.arizona.edu [Southwest Environmental Health Science Center, University of Arizona, Tucson, AZ (United States); Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ (United States); Lantz, R. Clark, E-mail: lantz@email.arizona.edu [Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ (United States); Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ (United States); González-Cortes, Tania, E-mail: taniagc2201@hotmail.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); Gonzalez-De Alba, Cesar, E-mail: cesargonzalezalba@hotmail.com [Department of Environmental Health, Biomedical Research Center, School of Medicine, University of Coahuila, Torreon, Coahuila (Mexico); Froines, John R., E-mail: jfroines@ucla.edu [Center for Environmental and Occupational Health, School of Public Health, University of California at Los Angeles, Los Angeles, CA (United States); Espinosa-Fematt, Jorge A., E-mail: dr.jorge.espinosa@gmail.com [School of Medicine, University Juarez of Durango, Gomez Palacio, Durango (Mexico)

    2015-09-01

    Evidence suggests that exposure to arsenic in drinking water during early childhood or in utero has been associated with an increase in respiratory symptoms or diseases in the adulthood, however only a few studies have been carried out during those sensitive windows of exposure. Recently our group demonstrated that the exposure to arsenic during early childhood or in utero in children was associated with impairment in the lung function and suggested that this adverse effect could be due to a chronic inflammation response to the metalloid. Therefore, we designed this cross-sectional study in a cohort of children associating lung inflammatory biomarkers and lung function with urinary As levels. A total of 275 healthy children were partitioned into four study groups according with their arsenic urinary levels. Inflammation biomarkers were measured in sputum by ELISA and the lung function was evaluated by spirometry. Fifty eight percent of the studied children were found to have a restrictive spirometric pattern. In the two highest exposed groups, the soluble receptor for advanced glycation end products' (sRAGE) sputum level was significantly lower and matrix metalloproteinase-9 (MMP-9) concentration was higher. When the biomarkers were correlated to the urinary arsenic species, negative associations were found between dimethylarsinic (DMA), monomethylarsonic percentage (%MMA) and dimethylarsinic percentage (%DMA) with sRAGE and positive associations between %DMA with MMP-9 and with the MMP-9/tissue inhibitor of metalloproteinase (TIMP-1) ratio. In conclusion, chronic arsenic exposure of children negatively correlates with sRAGE, and positively correlated with MMP-9 and MMP-9/TIMP-1 levels, and increases the frequency of an abnormal spirometric pattern. Arsenic-induced alterations in inflammatory biomarkers may contribute to the development of restrictive lung diseases. - Highlights: • First study in children evaluating lung inflammatory biomarkers and As levels

  20. Taraxacum officinale protects against lipopolysaccharide-induced acute lung injury in mice.

    Science.gov (United States)

    Liu, Liben; Xiong, Huanzhang; Ping, Jiaqi; Ju, Yulin; Zhang, Xuemei

    2010-07-20

    Taraxacum officinale has been frequently used as a remedy for inflammatory diseases. In the present study, we investigated the in vivo protective effect of Taraxacum officinale on acute lung injury (ALI) induced by lipopolysaccharide (LPS) in mice. Taraxacum officinale at 2.5, 5 and 10 mg/kg was orally administered once per day for 5 days consecutively, followed by 500 microg/kg LPS was instilled intranasally. The lung wet/dry weight (W/D) ratio, protein concentration and the number of inflammatory cells in bronchoalveolar lavage fluid (BALF) were determined. Superoxidase dismutase (SOD) and myeloperoxidase (MPO) activities, and histological change in the lungs were examined. The levels of inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in the BALF were measured using ELISA. We found that Taraxacum officinale decreased the lung W/D ratio, protein concentration and the number of neutrophils in the BALF at 24 h after LPS challenge. Taraxacum officinale decreased LPS-induced MPO activity and increased SOD activity in the lungs. In addition, histopathological examination indicated that Taraxacum officinale attenuated tissue injury of the lungs in LPS-induced ALI. Furthermore, Taraxacum officinale also inhibited the production of inflammatory cytokines TNF-alpha and IL-6 in the BALF at 6h after LPS challenge in a dose-dependent manner. These results suggest that Taraxacum officinale protects against LPS-induced ALI in mice. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  1. Carnosine markedly ameliorates H9N2 swine influenza virus-induced acute lung injury.

    Science.gov (United States)

    Xu, Tong; Wang, Cunlian; Zhang, Ruihua; Xu, Mingju; Liu, Baojian; Wei, Dong; Wang, Guohua; Tian, Shufei

    2015-10-01

    Oxidative stress injury is an important pathogenesis of influenza virus in critically ill patients. The present study investigated the efficacy of carnosine, an antioxidant and free radical scavenger, on a model of acute lung injury (ALI) induced by H9N2 swine influenza virus. Female specific-pathogen-free BALB/c mice were randomized into four groups and treated as follows: (1) H9N2 group, (2) mock control group, (3) H9N2+carnosine group and (4) carnosine control group. The H9N2 group mice were inoculated intranasally with A/Swine/Hebei/012/2008/ (H9N2) virus (100 μl) in allantoic fluid (AF), whilst mock-infected animals were intranasally inoculated with non-infectious AF. Carnosine [10 mg (kg body mass)- 1] was administered orally (100 μl) for 7 days consecutively. The survival rate, lung water content, TNF-α and IL-1β levels, lung histopathology, myeloperoxidase (MPO) activity, and Toll-like receptor (TLR)-4 levels were determined at 2, 4, 6, 8 and 14 days after inoculation. Carnosine treatment effectively decreased the mortality (43 versus 75 %, P lungs and decreased the lung wet/dry mass ratio (P lungs of infected mice (P < 0.05), which supported the use of carnosine for managing severe influenza cases.

  2. Niacinamide abrogates the organ dysfunction and acute lung injury caused by endotoxin.

    Science.gov (United States)

    Kao, Shang-Jyh; Liu, Demeral David; Su, Chain-Fa; Chen, Hsing I

    2007-09-01

    Poly (ADP-ribose) synthabse (PARS) or polymerase (PARP) is a cytotoxic enzyme causing cellular damage. Niacinamide inhibits PARS or PARP. The present experiment tests the effects of niacinamide (NCA) on organ dysfunction and acute lung injury (ALI) following lipopolysaccharide (LPS). LPS was administered to anesthetized rats and to isolated rat lungs. In anesthetized rats, LPS caused systemic hypotension and increased biochemical factors, nitrate/nitrite (NOx), methyl guanidine (MG), tumor necrosis factoralpha (TNFalpha), and interleukin-1beta (IL-1beta). In isolated lungs, LPS increased lung weight (LW) to body weight ratio, LW gain, protein and dye tracer leakage, and capillary permeability. The insult also increased NOx, MG, TNFalpha, and IL-1beta in lung perfusate, while decreased adenosine triphosphate (ATP) content with an increase in PARP activity in lung tissue. Pathological examination revealed pulmonary edema with inflammatory cell infiltration. These changes were abrogated by posttreatment (30 min after LPS) with NCA. Following LPS, the inducible NO synthase (iNOS) mRNA expression was increased. NCA reduced the iNOS expression. Niacinamide exerts protective effects on the organ dysfunction and ALI caused by endotoxin. The mechanisms may be mediated through the inhibition on the PARP activity, iNOS expression and the subsequent suppression of NO, free radicals, and proinflammatory cytokines with restoration of ATP.

  3. Dexmedetomidine mitigates CLP-stimulated acute lung injury via restraining the RAGE pathway.

    Science.gov (United States)

    Hu, Hongyi; Shi, Dongsheng; Hu, Chenlu; Yuan, Xiao; Zhang, Juan; Sun, Huaqin

    2017-01-01

    RAGE pathway plays crucial effects in causing acute lung injury (ALI). Dexmedetomidine (DEX) is showed to mitigate sepsis-stimulated ALI. However, its mechanisms have not been verified. The study was to evaluate whether the RAGE pathway participated in the actions of DEX on sepsis-stimulated ALI in rats. Male rats were administrated with intravenously DEX 30 min after sepsis. At 24 h of sepsis, lung myeloperoxidase (MPO) and macrophages in the bronchoalveolarlavage fluid (BALF) were observed. The actions of DEX on pro-inflammatory molecules and related mechanisms were determined by immunological methods. It was indicated that DEX markedly attenuated CLP-stimulated augment of lung inflammatory cells infiltration, along with significantly mitigated MPO activity. Besides, DEX obviously reduced lung wet/dry weight ratio and the levels of HMGB1 and RAGE in BALF and lung tissue. Moreover, DEX post-treatment apparently attenuated the histopathological lung injury compared with CLP model group. Furthermore, western blot analysis revealed that DEX efficiently restrained the activation of IκB-α, NF-κB p65, and MAPK. Our studies demonstrated that DEX attenuates the aggravation of sepsis-stimulated ALI via down regulation of RAGE pathway, which has a potential value in the clinical therapy.

  4. Impact of patient positioning on lung ultrasound findings in acute heart failure.

    Science.gov (United States)

    Frasure, Sarah E; Matilsky, Danielle K; Siadecki, Sebastian D; Platz, Elke; Saul, Turandot; Lewiss, Resa E

    2015-08-01

    The purpose of this study was to compare lung ultrasound findings in both the supine and upright positions in heart failure patients presenting with dyspnea or chest pain. We performed lung ultrasonography on 50 heart failure patients in the emergency department. Each subject underwent eight-zone lung sonography in the seated upright position, followed by a repeat ultrasound in the supine position. Each ultrasound video clip was later assigned a score (0-2 B-lines=0 points, 3-7 B-lines=1 point, >7 B-lines=2 points) by a physician who was blinded to patient position, chest zone, and clinical information. The median B-line score on eight-zone lung ultrasound was significantly higher in the supine (6, interquartile range (IQR) 2-10) vs the sitting position (5, IQR 1-8; pposition (6, IQR 4-10) compared to the sitting position (5, IQR 2-8; p=0.002). Subjects without any acute pulmonary findings on CXR (n=19) had similar median eight-zone B-line scores in sitting (4, IQR 1-7) and supine positions (4, IQR 1-9, p=0.093). Our findings suggest that patient positioning may impact the number of B-lines on lung ultrasound in a heart failure population. A consistent approach to patient positioning during lung ultrasonography may be necessary in order to monitor dynamic changes in heart failure. © The European Society of Cardiology 2014.

  5. Evaluation of N-acetylcysteine treatment in acute pancreatitis-induced lung injury.

    Science.gov (United States)

    Yubero, Sara; Ramudo, Laura; Manso, Manuel A; Collía, Francisco; De Dios, Isabel

    2012-07-01

    Pulmonary complications are frequent during acute pancreatitis (AP). We investigate the effects of N-acetylcysteine (NAC) on lung injury in mild and severe AP. ANIMALS AND TREATMENT: Mild and severe AP was induced in rats by bile-pancreatic duct obstruction (BPDO) and infusion of 3.5 % sodium taurocholate (NaTc) into the bile-pancreatic duct, respectively. NAC (50 mg/kg) was given 1 h before and 1 h after AP. Amylase activity was measured in plasma. Lungs were harvested for mRNA expression analysis of monocyte chemoattractant protein-1 (MCP-1), cytokine-induced neutrophil chemoattractant (CINC), P-selectin and intercellular adhesion molecule-1 (ICAM-1), myeloperoxidase (MPO) activity and histological examination. Hyperamylasemia was reduced by NAC in both AP models. NAC down-regulated MCP-1, CINC and P-selectin in BPDO- but not in NaTc-induced AP. Pulmonary insults did not vary in mild AP and were exacerbated in severe AP by NAC treatment. NAC reduced lung MPO activity in mild but not in severe AP. Although NAC treatment down-regulated inflammatory mediators in lungs during AP it did not prevent leukocyte infiltration, which could be responsible for maintaining the lung injury. As a result, NAC aggravated the lung damage in severe AP and failed to exert beneficial effects in the mild disease model.

  6. Natural antioxidant betanin protects rats from paraquat-induced acute lung injury interstitial pneumonia.

    Science.gov (United States)

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

    2015-01-01

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

  7. An Inhaled Inhibitor of Myristoylated Alanine-Rich C Kinase Substrate Reverses LPS-Induced Acute Lung Injury in Mice.

    Science.gov (United States)

    Yin, Qi; Fang, Shijing; Park, Joungjoa; Crews, Anne L; Parikh, Indu; Adler, Kenneth B

    2016-11-01

    Intratracheal instillation of bacterial LPS is a well-established model of acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS). Because the myristoylated alanine-rich C kinase substrate (MARCKS) protein is involved in neutrophil migration and proinflammatory cytokine production, we examined whether an aerosolized peptide that inhibits MARCKS function could attenuate LPS-induced lung injury in mice. The peptide, BIO-11006, was delivered at 50 μM via inhalation either just before intratracheal instillation of 5 μg of LPS into Balb/C mice, or 4, 12, 24, or 36 hours after LPS instillation. Effects of BIO-11006 were evaluated via analysis of mouse disease-related behavior, lung histology, bronchoalveolar lavage fluid total protein, neutrophil counts and percentages, cytokine (KC [CXCl1, mouse IL-8 equivalent] and TNF-α) expression, and activation of NF-κB in lung tissue. Treatment with aerosolized BIO-11006 at 0, 4, 12, 24, and even 36 hours after LPS instillation reversed the disease process: mouse behavior returned to normal after two treatments 12 hours apart with the inhaled peptide after LPS injury, whereas control LPS-instilled animals treated with PBS only remained moribund. Histological appearance of inflammation, bronchoalveolar lavage fluid protein levels, leukocyte and neutrophil numbers, KC and TNF-α gene and protein expression, and NF-κB activation were all significantly attenuated by inhaled BIO-11006 at all time points. These results implicate MARCKS protein in the pathogenesis of ALI/ARDS and suggest that MARCKS-inhibitory peptide(s), delivered by inhalation, could represent a new and potent therapeutic treatment for ALI/ARDS, even if administered well after the disease process has begun.

  8. Serum carotenoids, alpha-tocopherol, and lung function among Dutch elderly

    NARCIS (Netherlands)

    Grievink, L.; Waart, de F.G.; Schouten, E.G.; Kok, F.J.

    2000-01-01

    Antioxidant vitamins (provitamins) may protect against loss of lung function over time. We studied the association between serum carotenoids (-carotene, -carotene, lycopene, -cryptoxanthin, zeaxanthin, and lutein), -tocopherol, and lung function among noninstitutionalized Dutch elderly age 65 to 85

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-11-01

    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

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

    International Nuclear Information System (INIS)

    Wang, Chaoyun; Huang, Qingxian; Wang, Chunhua; Zhu, Xiaoxi; Duan, Yunfeng; Yuan, Shuai; Bai, Xianyong

    2013-01-01

    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 2 ), carbon dioxide tension, pH, and the PaO 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 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

  11. Usefulness of Bronchial Thermoplasty for Patients with a Deteriorating Lung Function.

    Science.gov (United States)

    Minami, Daisuke; Ando, Chihiro; Nakasuka, Takamasa; Iwamoto, Yoshitaka; Sato, Ken; Fujiwara, Keiichi; Shibayama, Takuo; Yonei, Toshiro; Sato, Toshio

    2018-01-01

    Bronchial thermoplasty is a novel procedure for patients with severe asthma showing a stable lung function. We herein report two cases with a deteriorating lung function. The lung function tended to improve in one case, while the other case discontinued mepolizumab medication after the procedure. Treatment was performed safely under general anesthesia in both cases. The use of bronchial thermoplasty may therefore be useful for the treatment of patients with a deteriorating lung function.

  12. Low cognitive ability in early adulthood is associated with reduced lung function in middle age

    DEFF Research Database (Denmark)

    Carroll, Douglas; Batty, G David; Mortensen, Laust Hvas

    2011-01-01

    Reduced lung function has been linked to poorer cognitive ability later in life. In the present study, the authors examined the converse: whether there was a prospective association between cognitive ability in early adulthood and lung function in middle age.......Reduced lung function has been linked to poorer cognitive ability later in life. In the present study, the authors examined the converse: whether there was a prospective association between cognitive ability in early adulthood and lung function in middle age....

  13. Parenchymal and Functional Lung Changes after Stereotactic Body Radiotherapy for Early-Stage Non-Small Cell Lung Cancer—Experiences from a Single Institution

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    Juliane Hörner-Rieber

    2017-09-01

    Full Text Available IntroductionThis study aimed to evaluate parenchymal and functional lung changes following stereotactic body radiotherapy (SBRT for early-stage non-small cell lung cancer (NSCLC patients and to correlate radiological and functional findings with patient and treatment characteristics as well as survival.Materials and methodsSeventy patients with early-stage NSCLC treated with SBRT from 2004 to 2015 with more than 1 year of CT follow-up scans were analyzed. Incidence, morphology, severity of acute and late lung abnormalities as well as pulmonary function changes were evaluated and correlated with outcome.ResultsMedian follow-up time was 32.2 months with 2-year overall survival (OS of 83% and local progression-free survival of 88%, respectively. Regarding parenchymal changes, most patients only developed mild to moderate CT abnormalities. Mean ipsilateral lung dose (MLD in biological effective dose and planning target volume size were significantly associated with maximum severity score of parenchymal changes (p = 0.014, p < 0.001. Furthermore, both maximum severity score and MLD were significantly connected with OS in univariate analysis (p = 0.043, p = 0.025. For functional lung changes, we detected significantly reduced total lung capacity, forced expiratory volume in 1 s, and forced vital capacity (FVC parameters after SBRT (p ≤ 0.001. Multivariate analyses revealed SBRT with an MLD ≥ 9.72 Gy and FVC reduction ≥0.54 L as independent prognostic factors for inferior OS (p = 0.029, p = 0.004.ConclusionSBRT was generally tolerated well with only mild toxicity. For evaluating the possible prognostic impact of MLD and FVC reduction on survival detected in this analysis, larger prospective studies are truly needed.

  14. Maximal hysteresis: a new method to set positive end-expiratory pressure in acute lung injury?

    Science.gov (United States)

    Koefoed-Nielsen, J; Andersen, G; Barklin, A; Bach, A; Lunde, S; Tønnesen, E; Larsson, A

    2008-05-01

    No methods are superior when setting positive end-expiratory pressure (PEEP) in acute lung injury (ALI). In ALI, the vertical distance (hysteresis) between the inspiratory and expiratory limbs of a static pressure-volume (PV) loop mainly indicates lung recruitment. We hypothesized that PEEP set at the pressure where hysteresis is 90% of its maximum (90%MH) would give similar oxygenation, but less cardiovascular depression than PEEP set at the pressure at lower inflection point (LIP) on the inspiratory limb or at the point of maximal curvature (PMC) on the expiratory limb in ALI. In 12 mechanically ventilated pigs, ALI was induced in a randomized fashion by lung lavage, lung lavage plus injurious ventilation, or by oleic acid. From a static PV loop obtained by an interrupted low-flow method, the pressures at LIP [25 (25, 25) cmH(2)O, mean and 25, 75 percentiles], at PMC [24 (20, 24) cmH(2)O], and at 90% MH [19 (18, 19) cmH(2)O] were determined and used for the PEEP-settings. We measured lung inflation (by computed tomography), end-expiratory lung volume (EELV), airway pressures, compliance of the respiratory system (Crs), blood gases, cardiac output and arterial blood pressure. There were no differences between the PEEP settings in EELV or oxygenation, but the 90%MH setting gave lower end-inspiratory pause pressure (P<0.025), higher Crs (P<0.025), less hyper-aeration (P<0.025) and better maintained hemodynamics. In this porcine lung injury model, PEEP set at 90% MH gave better lung mechanics and hemodynamics, than PEEP set at PMC or LIP.

  15. The relationship of lung function with ambient temperature.

    Science.gov (United States)

    Collaco, Joseph M; Appel, Lawrence J; McGready, John; Cutting, Garry R

    2018-01-01

    Lung function is complex trait with both genetic and environmental factors contributing to variation. It is unknown how geographic factors such as climate affect population respiratory health. To determine whether ambient air temperature is associated with lung function (FEV1) in the general population. Associations between spirometry data from two National Health and Nutrition Examination Survey (NHANES) periods representative of the U.S. non-institutionalized population and mean annual ambient temperature were assessed using survey-weighted multivariate regression. The NHANES III (1988-94) cohort included 14,088 individuals (55.6% female) and the NHANES 2007-12 cohort included 14,036 individuals (52.3% female), with mean ages of 37.4±23.4 and 34.4±21.8 years old and FEV1 percent predicted values of 99.8±15.8% and 99.2±14.5%, respectively. After adjustment for confounders, warmer ambient temperatures were associated with lower lung function in both cohorts (NHANES III p = 0.020; NHANES 2007-2012 p = 0.014). The effect was similar in both cohorts with a 0.71% and 0.59% predicted FEV1 decrease for every 10°F increase in mean temperature in the NHANES III and NHANES 2007-2012 cohorts, respectively. This corresponds to ~2 percent predicted difference in FEV1 between the warmest and coldest regions in the continental United States. In the general U.S. population, residing in regions with warmer ambient air temperatures was associated with lower lung function with an effect size similar to that of traffic pollution. Rising temperatures associated with climate change could have effects on pulmonary function in the general population.

  16. The relationship of lung function with ambient temperature.

    Directory of Open Access Journals (Sweden)

    Joseph M Collaco

    Full Text Available Lung function is complex trait with both genetic and environmental factors contributing to variation. It is unknown how geographic factors such as climate affect population respiratory health.To determine whether ambient air temperature is associated with lung function (FEV1 in the general population.Associations between spirometry data from two National Health and Nutrition Examination Survey (NHANES periods representative of the U.S. non-institutionalized population and mean annual ambient temperature were assessed using survey-weighted multivariate regression.The NHANES III (1988-94 cohort included 14,088 individuals (55.6% female and the NHANES 2007-12 cohort included 14,036 individuals (52.3% female, with mean ages of 37.4±23.4 and 34.4±21.8 years old and FEV1 percent predicted values of 99.8±15.8% and 99.2±14.5%, respectively.After adjustment for confounders, warmer ambient temperatures were associated with lower lung function in both cohorts (NHANES III p = 0.020; NHANES 2007-2012 p = 0.014. The effect was similar in both cohorts with a 0.71% and 0.59% predicted FEV1 decrease for every 10°F increase in mean temperature in the NHANES III and NHANES 2007-2012 cohorts, respectively. This corresponds to ~2 percent predicted difference in FEV1 between the warmest and coldest regions in the continental United States.In the general U.S. population, residing in regions with warmer ambient air temperatures was associated with lower lung function with an effect size similar to that of traffic pollution. Rising temperatures associated with climate change could have effects on pulmonary function in the general population.

  17. The timing and extent of acute physiotherapy involvement following lung transplantation: An observational study.

    Science.gov (United States)

    Tarrant, Benjamin James; Holland, Anne; Le Maitre, Caitlin; Robinson, Rebecca; Corbett, Monique; Bondarenko, Janet; Button, Brenda; Thompson, Bruce; Snell, Greg

    2018-03-12

    Physiotherapy "standard care" for the acute post lung transplant recipient has not yet been documented. We aimed to analyse how soon patients commence exercise and how much time is dedicated to this during physiotherapy sessions acutely post lung transplantation. Prospective observational study of bilateral sequential and single lung transplant recipients for any indication, ≥18 years. Participants were observed during 6 physiotherapy sessions: 3 initial and 3 prior to acute inpatient discharge. Duration and content of each session was recorded, consisting of physical exercise and non-exercise tasks. Thirty participants, 20 male, median age 58.5 (interquartile range 54.5-65.0) were observed over 173 sessions. Chronic obstructive pulmonary disease was the most common transplant indication (n = 12, 40%). Bilateral lung transplant was performed in 90% (n = 27) of participants. First time to mobilise was 2 (2-3) days. Participants received 14 (12.8-23.8) sessions over 18 (17-31) days. The mean duration of physiotherapy in the initial phase was 107.8 (standard deviation 21.8) min, with 22.9 (7.5) min spent exercising. In the final phase, exercise time increased to 28.1 (11.4) min out of 84.1 (24.6) min. Assessment was the most common non-exercise component, at 26.6 (7.9) and 22.1 (12.5) min across the three initial and final sessions. Lung transplant recipients spent 21-34% of observed sessions performing physical exercise beginning 48 hr following surgery. Remaining physiotherapist time was spent on assessment, respiratory interventions, education, and patient-specific duties. The use of physiotherapy assistants, structured, progressive exercise programs, and continued workplace innovation may enable a higher percentage of physiotherapist supervised physical exercise in the future. Copyright © 2018 John Wiley & Sons, Ltd.

  18. N-acetylcysteine alleviates the meconium-induced acute lung injury.

    Science.gov (United States)

    Mokra, D; Drgova, A; Petras, M; Mokry, J; Antosova, M; Calkovska, A

    2015-01-01

    Meconium aspiration in newborns causes lung inflammation and injury, which may lead to meconium aspiration syndrome (MAS). In this study, the effect of the antioxidant N-acetylcysteine on respiratory and inflammatory parameters were studied in a model of MAS. Oxygen-ventilated rabbits were intratracheally given 4 mL/kg of meconium (25 mg/mL) or saline. Thirty minutes later, meconium-instilled animals were administered N-acetylcysteine (10 mg/kg; i.v.), or were left without treatment. The animals were oxygen-ventilated for additional 5 h. Ventilatory pressures, oxygenation, right-to-left pulmonary shunts, and leukocyte count were measured. At the end of experiment, trachea and lung were excised. The left lung was saline-lavaged and a total and differential count of cells in bronchoalveolar lavage fluid (BAL) was determined. Right lung tissue strips were used for detection of lung edema (expressed as wet/dry weight ratio) and peroxidation (expressed by thiobarbituric acid-reactive substances, TBARS). In lung and tracheal strips, airway reactivity to acetylcholine was measured. In addition, TBARS and total antioxidant status were determined in the plasma. Meconium instillation induced polymorphonuclear-derived inflammation and oxidative stress. N-acetylcysteine improved oxygenation, reduced lung edema, decreased polymorphonuclears in BAL fluid, and diminished peroxidation and meconium-induced airway hyperreactivity compared with untreated animals. In conclusion, N-acetylcysteine effectively improved lung functions in an animal model of MAS.

  19. Chorioamnionitis and subsequent lung function in preterm infants.

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    Marcus H Jones

    Full Text Available OBJECTIVE: To explore the relationship between prematurity, gender and chorioamnionitis as determinants of early life lung function in premature infants. METHODS: Placenta and membranes were collected from preterm deliveries (<37 weeks gestational age and evaluated for histological chorioamnionitis (HCA. Patients were followed and lung function was performed in the first year of life by Raised Volume-Rapid Thoracic Compression Technique. RESULTS: Ninety-five infants (43 males born prematurely (median gestational age 34.2 weeks were recruited. HCA was detected in 66 (69% of the placentas, and of these 55(58% were scored HCA Grade 1, and 11(12% HCA Grade 2. Infants exposed to HCA Grade 1 and Grade 2, when compared to those not exposed, presented significantly lower gestational ages, higher prevalence of RDS, clinical early-onset sepsis, and the use of supplemental oxygen more than 28 days. Infants exposed to HCA also had significantly lower maximal flows. There was a significant negative trend for z-scores of lung function in relation to levels of HCA; infants had lower maximal expiratory flows with increasing level of HCA. (p = 0.012 for FEF50, p = 0.014 for FEF25-75 and p = 0.32 for FEV0.5. Two-way ANOVA adjusted for length and gestational age indicated a significant interaction between sex and HCA in determining expiratory flows (p<0.01 for FEF50, FEF25-75 and p<0.05 for FEV0.5. Post-hoc comparisons revealed that female preterm infants exposed to HCA Grade 1 and Grade 2 had significant lower lung function than those not exposed, and this effect was not observed among males. CONCLUSIONS: Our findings show a sex-specific negative effect of prenatal inflammation on lung function of female preterm infants. This study confirms and expands knowledge upon the known association between chorioamnionitis and early life chronic lung disease.

  20. Prospective longitudinal evaluation of lung function during the first year of life after extracorporeal membrane oxygenation

    NARCIS (Netherlands)

    Hofhuis, W.; Hanekamp, M.N.; Ijsselstijn, H.; Nieuwhof, E.M.; Hop, W.C.J.; Tibboel, D.; Jongste, J.C. de; Merkus, P.J.F.M.

    2011-01-01

    OBJECTIVE: To collect longitudinal data on lung function in the first year of life after extracorporeal membrane oxygenation and to evaluate relationships between lung function and perinatal factors. Longitudinal data on lung function in the first year of life after extracorporeal membrane

  1. Lung Function Status of Workers Exposed to Welding Fume: A Preliminary Study

    Directory of Open Access Journals (Sweden)

    Mulyana Mulyana

    2016-04-01

    CONCLUSION: Lung function parameters status were significantly lower in welder than non-welder, and working period was the most important indicator for lung function status evaluation among welder. KEYWORDS: vital capacity, VC, forced vital capacity, FCV, forced expiratory volume in one second, FEV1, lung function, ratio of FEV1/FVC, working period

  2. Respiratory and lower limb muscle function in interstitial lung disease.

    Science.gov (United States)

    Panagiotou, Marios; Polychronopoulos, Vlasis; Strange, Charlie

    2016-05-01

    Growing evidence suggests that respiratory and limb muscle function may be impaired in patients with interstitial lung disease (ILD). Importantly, muscle dysfunction could promote dyspnoea, fatigue and functional limitation all of which are cardinal features of ILD. This article examines the risk factors for skeletal muscle dysfunction in ILD, reviews the current evidence on overall respiratory and limb muscle function and focuses on the occurrence and implications of skeletal muscle dysfunction in ILD. Research limitations and pathways to address the current knowledge gaps are highlighted. © The Author(s) 2016.

  3. Midterm renal functions following acute renal infarction

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    Sakir Ongun

    2015-10-01

    Full Text Available The aim of this study was to explore clinical features of renal infarction (RI that may have a role in diagnosis and treatment in our patient cohort and provide data on midterm renal functions. Medical records of patients with diagnosis of acute RI, established by contrast enhanced computed tomography (CT and at least 1 year follow-up data, who were hospitalized in our clinic between 1998 and 2012 were retrospectively reviewed; including descriptive data, clinical signs and symptoms, etiologic factors, laboratory findings, and prescribed treatments. Patients with solitary infarct were treated with acetylsalicylic acid (ASA only, whereas patients with atrial fibrillation (AF or multiple or global infarct were treated with anticoagulants. Estimated Glomerular Filtration Rate (eGFR referring to renal functions was determined by the Modification of Diet in Renal Disease (MDRD formula. Twenty-seven renal units of 23 patients with acute RI were identified. The mean age was 59.7 ± 15.7 years. Fourteen patients (60.8% with RI had atrial fibrillation (AF as an etiologic factor of which four had concomitant mesenteric ischemia at diagnosis. At presentation, 20 patients (86.9% had elevated serum lactate dehydrogenase (LDH, 18 patients (78.2% had leukocytosis, and 16 patients (69.5% had microscopic hematuria. Two patients with concomitant mesenteric ischemia and AF passed away during follow up. Mean eGFR was 70.8 ± 23.2 mL/min/1.73 m2 at admission and increased to 82.3 ± 23.4 mL/min/1.73 m2 at 1 year follow up. RI should be considered in patients with persistent flank or abdominal pain, particularly if they are at high risk of thromboembolism. Antiplatelet and/or anticoagulant drugs are both effective treatment options according to the amplitude of the infarct for preserving kidney functions.

  4. A study of experimental acute lung injury in pigs on zero end-expiratory pressure.

    Science.gov (United States)

    Guérin, Claude; Levrat, Albrice; Pontier, Sandrine; Annat, Guy

    2008-03-01

    Tidal expiratory flow limitation (EFL) has been reported in humans with acute lung injury (ALI) and assumed to be associated with small airway closure. Detection of EFL is important because by selecting positive end-expiratory pressure at such a level that EFL is no longer present in the tidal breath, the repeated opening and closure of small airways can be prevented. The objective of this study was to investigate the occurrence of EFL in two experimental models of ALI. Ten female piglets. Animals were anaesthetized, tracheotomized and mechanically ventilated on zero end-expiratory pressure. Acute lung injury was induced by oleic acid (OA) (n = 5) or saline lavage (SL) (n = 5). Tidal EFL was assessed by the negative expiratory pressure test. Lung and chest wall mechanics were partitioned using an oesophageal balloon. Resistance and static elastance were assessed by a rapid airway occlusion technique at baseline ventilatory settings. There was no EFL at any time before and after ALI in both models. This may be due to an increased elastance which promoted higher expiratory flow after ALI and to a decreased chest wall to lung static elastance ratio which could favour small airways patency. The similar increase in total lung resistance, in the two models, after ALI was mostly due to an increased airway resistance in the OA model and to the lung tissue resistance in the SL model. Tidal EFL was not detected in experimental ALI. This finding casts some doubt about the usefulness of some experimental models of ALI to mimic some reported findings in human ALI.

  5. Deletion of ASK1 Protects against Hyperoxia-Induced Acute Lung Injury.

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    Jutaro Fukumoto

    Full Text Available 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-1β and TNF-α, 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.

  6. Does granulocyte colony-stimulating factor exacerbate radiation-induced acute lung injury in rats?

    International Nuclear Information System (INIS)

    Miura, Gouji; Awaya, Hitomi; Matsumoto, Tsuneo; Tanaka, Nobuyuki; Matsunaga, Naofumi

    2000-01-01

    Radiation pneumonitis (RP) frequently occurs as a complication of thoracic irradiation. However, the mechanism of RP is not well known. Activated neutrophils are a possible pathogenesis of RP. Neutrophil activation induced by granulocyte colony-stimulating factor (G-CSF) may exacerbate RP. We studied the effects of recombinant human G-CSF on acute lung injury induced by thoracic irradiation using rats. Animals were divided into three groups: sham irradiation with saline control, irradiation alone, and irradiation with G-CSF. Actual irradiation was given as a single fraction of 16 Gy delivered to the right hemithorax. G-CSF at a dose of 12 μg/body was administered subcutaneously once a day from 14 to 18 days after actual irradiation. Lung injury was evaluated 21 days after irradiation by bronchoalveolar lavage (BAL) fluid findings and the lung wet/dry weight (W/D) ratio. Neutrophil and lymphocyte counts in BAL fluid and the W/D ratio were significantly increased in the irradiation alone and the irradiation with G-CSF groups compared with those of the sham irradiation+saline control group. However, there was no significant difference observed between the irradiation alone and irradiation with G-CSF groups. In conclusion, this study suggests that postradiation administration of G-CSF does not exacerbate acute lung injury induced by thoracic irradiation in rats. (author)

  7. Does granulocyte colony-stimulating factor exacerbate radiation-induced acute lung injury in rats?

    Energy Technology Data Exchange (ETDEWEB)

    Miura, Gouji; Awaya, Hitomi; Matsumoto, Tsuneo; Tanaka, Nobuyuki; Matsunaga, Naofumi [Yamaguchi Univ., Ube (Japan). School of Medicine

    2000-08-01

    Radiation pneumonitis (RP) frequently occurs as a complication of thoracic irradiation. However, the mechanism of RP is not well known. Activated neutrophils are a possible pathogenesis of RP. Neutrophil activation induced by granulocyte colony-stimulating factor (G-CSF) may exacerbate RP. We studied the effects of recombinant human G-CSF on acute lung injury induced by thoracic irradiation using rats. Animals were divided into three groups: sham irradiation with saline control, irradiation alone, and irradiation with G-CSF. Actual irradiation was given as a single fraction of 16 Gy delivered to the right hemithorax. G-CSF at a dose of 12 {mu}g/body was administered subcutaneously once a day from 14 to 18 days after actual irradiation. Lung injury was evaluated 21 days after irradiation by bronchoalveolar lavage (BAL) fluid findings and the lung wet/dry weight (W/D) ratio. Neutrophil and lymphocyte counts in BAL fluid and the W/D ratio were significantly increased in the irradiation alone and the irradiation with G-CSF groups compared with those of the sham irradiation+saline control group. However, there was no significant difference observed between the irradiation alone and irradiation with G-CSF groups. In conclusion, this study suggests that postradiation administration of G-CSF does not exacerbate acute lung injury induced by thoracic irradiation in rats. (author)

  8. Morphological Signs of Acute Lung Injury of Varying Etiology (Experimental Study

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    V. V. Moroz

    2010-01-01

    Full Text Available Objective: to reveal pulmonary morphological changes in acute lung injury (ALI of varying etiology. Material and methods. An experiment was carried out on 4 groups of albino non-inbred male rats weighing 300—400 g. The following ALI models were 1 acidin-pepsin solution (PH-1.2 aspiration; 2 blood aspiration; 3 blood loss (50% circulating blood volume concurrent with vascular thrombosis in the microcirculatory bed; 4 artificial ventilation-induced ALI. The duration of the study was 1 hour to 3 days. Histological lung slices were stained with hematoxylin and eosin; a Schiff reaction was conducted. Results. All the animals developed interstitial edema, exhibited desquamation of the bronchial epithelium; damage to the capillary endothelium and basement membranes; segmental leukocyte, macrophage, and lymphocyte infiltration of intraalveolar septa, atelectases, hemorrhages, and sludges. Conclusion. Morphological signs in ALI are nonspecific and they do not depend on an etiological factor. Morphological changes in ALI result in damage to the endothelium of lung capillaries and their basement membranes, higher capillary permeability, extravascular fluid accumulation, and protein exudation with the development of noncardiogenic pulmonary edema. Key words: acute lung injury, blood loss, artificial ventilation, aspiration.

  9. Paraquat poisoning: Acute lung injury - a missed diagnosis.

    Science.gov (United States)

    Ntshalintshali, Sipho D; Manzini, Thandekile C

    2017-04-25

    Paraquat is a herbicide of great toxicological importance because it is associated with high mortality rates, mainly due to respiratory failure. We report the case of a 28-year-old man admitted to the casualty department at Ngwelezana Hospital, Empangeni, KwaZulu-Natal, South Africa, with a history of vomiting and abdominal pain after ingestion of ~100 mL of an unknown substance, later identified as paraquat, together with an unknown amount of alcohol, in a suicide attempt. He developed respiratory distress associated with lung parenchymal infiltrates that required ventilatory support and later a spontaneous pneumothorax, and died in the intensive care unit. We discuss the importance of a high index of suspicion of paraquat poisoning in rural areas, where paraquat is readily available as a herbicide on farms, in patients with a similar presentation. We further stress the importance of identifying the classic radiological progression after paraquat poisoning, to help avoid a delay in diagnosis if the culprit substance is not known (as happened in our case). Lastly, we look at the importance of avoiding oxygen supplementation, and early administration of immunosuppressive therapy, to improve outcome.

  10. Lung function and long-term exposure to cement dust

    DEFF Research Database (Denmark)

    Rasmussen, F V; Borchsenius, L; Holstein, B

    1977-01-01

    and one men were grouped as cement factory workers, 649 were grouped as blue collar workers, 218 as white collar workers and 102 men had predominantly been occupied in farming, forestry and fishing. On the average the investigated men had spent more than 75% of their total occupational life in their main......In a cross-sectional epidemiological survey a selected group of former and present cement factory workers and a random sample of the corresponding urban population underwent dynamic spirometry. Based upon life experience the subjects were grouped into four occupational categories. Three hundred...... throughout life had better ventilatory lung function than any of the other three occupational categories. No significant differences in lung function between cement factory workers and other blue collar workers with comparable smoking habits could be demonstrated by use of the maximal midexpiratory flow...

  11. Aspiration-Induced Acute Lung Injury in Victims with Isolated Severe Brain Injury

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    Yu. A. Gorodovikova

    2009-01-01

    Full Text Available Objective: to determine the time and development rate of acute lung injury (ALI in severe brain injury (SBI complicated by aspiration of gastric contents or blood. Subjects and methods. Twenty-nine patients aged 19 to 70 years, who had isolated SBI, of whom there were 24 males and 5 females, were examined. The patients were divided into 2 groups: those with aspiration of gastric contents (n=9 or blood (n=10. A control group included 10 patients with SBI without aspiration. A PiCCO plus device was used to determine pulmonary extravascular fluid. ALI was diagnosed in accordance with the recommendations of the Research Institute of General Reanimatology, Russian Academy of Medical Sciences. Results. SBI patients with aspiration of gastric contents or blood were found to have significantly increased pulmonary extravascular water (p<0.01 and a lower oxygenation index (<300, which correlated with each other. ALI was recorded in the first hours after injury in about 50% of cases in both patients with gastric contents aspiration and those with blood aspiration. Conclusion. In patients with SBI complicated by aspiration of gastric contents or blood, pulmonary extravascular fluid accumulation concurrent with other signs of injury may be regarded as a criterion for acute lung injury. Key words: severe brain injury, aspiration, acute lung lesion.

  12. A critical role for muscle ring finger-1 in acute lung injury-associated skeletal muscle wasting.

    Science.gov (United States)

    Files, D Clark; D'Alessio, Franco R; Johnston, Laura F; Kesari, Priya; Aggarwal, Neil R; Garibaldi, Brian T; Mock, Jason R; Simmers, Jessica L; DeGorordo, Antonio; Murdoch, Jared; Willis, Monte S; Patterson, Cam; Tankersley, Clarke G; Messi, Maria L; Liu, Chun; Delbono, Osvaldo; Furlow, J David; Bodine, Sue C; Cohn, Ronald D; King, Landon S; Crow, Michael T

    2012-04-15

    Acute lung injury (ALI) is a debilitating condition associated with severe skeletal muscle weakness that persists in humans long after lung injury has resolved. The molecular mechanisms underlying this condition are unknown. To identify the muscle-specific molecular mechanisms responsible for muscle wasting in a mouse model of ALI. Changes in skeletal muscle weight, fiber size, in vivo contractile performance, and expression of mRNAs and proteins encoding muscle atrophy-associated genes for muscle ring finger-1 (MuRF1) and atrogin1 were measured. Genetic inactivation of MuRF1 or electroporation-mediated transduction of miRNA-based short hairpin RNAs targeting either MuRF1 or atrogin1 were used to identify their role in ALI-associated skeletal muscle wasting. Mice with ALI developed profound muscle atrophy and preferential loss of muscle contractile proteins associated with reduced muscle function in vivo. Although mRNA expression of the muscle-specific ubiquitin ligases, MuRF1 and atrogin1, was increased in ALI mice, only MuRF1 protein levels were up-regulated. Consistent with these changes, suppression of MuRF1 by genetic or biochemical approaches prevented muscle fiber atrophy, whereas suppression of atrogin1 expression was without effect. Despite resolution of lung injury and down-regulation of MuRF1 and atrogin1, force generation in ALI mice remained suppressed. These data show that MuRF1 is responsible for mediating muscle atrophy that occurs during the period of active lung injury in ALI mice and that, as in humans, skeletal muscle dysfunction persists despite resolution of lung injury.

  13. Dietary phosphorus acutely impairs endothelial function.

    Science.gov (United States)

    Shuto, Emi; Taketani, Yutaka; Tanaka, Rieko; Harada, Nagakatsu; Isshiki, Masashi; Sato, Minako; Nashiki, Kunitaka; Amo, Kikuko; Yamamoto, Hironori; Higashi, Yukihito; Nakaya, Yutaka; Takeda, Eiji

    2009-07-01

    Excessive dietary phosphorus may increase cardiovascular risk in healthy individuals as well as in patients with chronic kidney disease, but the mechanisms underlying this risk are not completely understood. To determine whether postprandial hyperphosphatemia may promote endothelial dysfunction, we investigated the acute effect of phosphorus loading on endothelial function in vitro and in vivo. Exposing bovine aortic endothelial cells to a phosphorus load increased production of reactive oxygen species, which depended on phosphorus influx via sodium-dependent phosphate transporters, and decreased nitric oxide production via inhibitory phosphorylation of endothelial nitric oxide synthase. Phosphorus loading inhibited endothelium-dependent vasodilation of rat aortic rings. In 11 healthy men, we alternately served meals containing 400 mg or 1200 mg of phosphorus in a double-blind crossover study and measured flow-mediated dilation of the brachial artery before and 2 h after the meals. The high dietary phosphorus load increased serum phosphorus at 2 h and significantly decreased flow-mediated dilation. Flow-mediated dilation correlated inversely with serum phosphorus. Taken together, these findings suggest that endothelial dysfunction mediated by acute postprandial hyperphosphatemia may contribute to the relationship between serum phosphorus level and the risk for cardiovascular morbidity and mortality.

  14. Scavenger receptor AI/II truncation, lung function and COPD

    DEFF Research Database (Denmark)

    Thomsen, M; Nordestgaard, B G; Tybjaerg-Hansen, A

    2011-01-01

    The scavenger receptor A-I/II (SRA-I/II) on alveolar macrophages is involved in recognition and clearance of modified lipids and inhaled particulates. A rare variant of the SRA-I/II gene, Arg293X, truncates the distal collagen-like domain, which is essential for ligand recognition. We tested...... whether the Arg293X variant is associated with reduced lung function and risk of chronic obstructive pulmonary disease (COPD) in the general population....

  15. High free testosterone index increases lung function in adult males

    Directory of Open Access Journals (Sweden)

    Martiem Mawi

    2012-08-01

    Full Text Available Background Increasing age and decreased testosterone concentrations in males influence muscle strength and muscle mass, particularly in skeletal muscle. There have been few studies on decreased lung function resulting from reduced mass and strength of respiratory muscles. The aim of the present study was to investigate the existence of an association between free testosterone index (FTI and lung function in males aged between 40 and 80 years. Methods This cross-sectional study involved 167 males aged between 40 and 80 years in Cilandak subdistrict, South Jakarta. Total serum testosterone and sex hormone-binding globulin (SHBG concentrations were determined by electrochemiluminescence immunoassay (ECLIA using Roche Elecsys Reagent Kit Cat 11776061 and Elecsys 2010 reagent (Cobas e601, respectively FTI was calculated using the formula free testosterone/SHBG x 100%. Forced expiratory volume in 1 second (VEP1 was assessed by means of an AS 500 spirometer. Results Mean age of the subjects was 53.32 ± 8.26 years, mean total serum testosterone concentration was 532.59 ± 206.92 ng/dL, mean SHBG concentration 41.26 ± 21.14 nmol/L, mean FTI 48.22 ± 14.34 %, and mean VEP1 was 1.63 ± 0.54 L. There was a significant association between both SHBG and FTI on the one hand and VEP1 on the other, with Pearson correlation coefficients of -0.199 (p=0.010 and 0.271 (p=0.000, respectively. Linear multiple regression analysis indicated that FTI was the most influential variable on lung function (VEP1, higher FTI values indicating higher VEP1 (â=0.008: p=0.004. Conclusion In males aged 40-80 years, higher FTI values indicate better lung function as determined by means of VEP1.

  16. Ambient particulate matter and lung function growth in Chinese children.

    Science.gov (United States)

    Roy, Ananya; Hu, Wei; Wei, Fusheng; Korn, Leo; Chapman, Robert S; Zhang, Junfeng Jim

    2012-05-01

    Exposure to particulate matter (PM) has been associated with deficits in lung function growth among children in Western countries. However, few studies have explored this association in developing countries, where PM levels are often substantially higher. Children (n = 3273) 6-12 years of age were recruited from 8 schools in 4 Chinese cities. The lung function parameters of forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) were measured using computerized spirometers twice a year for up to 3 years (1993-1996). Dichotomous samplers placed in each schoolyard were used to measure PM2.5 and PM10 (PM with diameter ≤ 2.5 μm and ≤ 10 μm, respectively). Multivariable generalized estimating equations were used to examine the association between the quarterly average PM levels and lung function growth during the period of follow-up. Annual average PM2.5 and PM10 levels in the 4 cities ranged from 57 to 158 μg/m and 95 to 268 μg/m, respectively. In multivariable models, an increase of 10 μg/m of PM2.5 was associated with decreases of 2.7 mL FEV1 (95% confidence interval = -3.5 to -2.0), 3.5 mL FVC (-4.3 to -2.7), 1.4 mL/year FEV1 growth (-1.8 to -0.9), and 1.5 mL/year FVC growth (-2.0 to -1.0). Similar results were seen with PM10 exposure. Exposure to ambient particulate matter was associated with decreased growth in lung function among Chinese children.

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

    Directory of Open Access Journals (Sweden)

    Guo Li

    2015-01-01

    Full Text Available 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-β1 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 TNFα, IL-1β, 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.

  18. Cyclist route choice, traffic-related air pollution, and lung function: a scripted exposure study.

    Science.gov (United States)

    Jarjour, Sarah; Jerrett, Michael; Westerdahl, Dane; de Nazelle, Audrey; Hanning, Cooper; Daly, Laura; Lipsitt, Jonah; Balmes, John

    2013-02-07

    A travel mode shift to active transportation such as bicycling would help reduce traffic volume and related air pollution emissions as well as promote increased physical activity level. Cyclists, however, are at risk for exposure to vehicle-related air pollutants due to their proximity to vehicle traffic and elevated respiratory rates. To promote safe bicycle commuting, the City of Berkeley, California, has designated a network of residential streets as "Bicycle Boulevards." We hypothesized that cyclist exposure to air pollution would be lower on these Bicycle Boulevards when compared to busier roads and this elevated exposure may result in reduced lung function. We recruited 15 healthy adults to cycle on two routes - a low-traffic Bicycle Boulevard route and a high-traffic route. Each participant cycled on the low-traffic route once and the high-traffic route once. We mounted pollutant monitors and a global positioning system (GPS) on the bicycles. The monitors were all synced to GPS time so pollutant measurements could be spatially plotted. We measured lung function using spirometry before and after each bike ride. We found that fine and ultrafine particulate matter, carbon monoxide, and black carbon were all elevated on the high-traffic route compared to the low-traffic route. There were no corresponding changes in the lung function of healthy non-asthmatic study subjects. We also found that wind-speed affected pollution concentrations. These results suggest that by selecting low-traffic Bicycle Boulevards instead of heavily trafficked roads, cyclists can reduce their exposure to vehicle-related air pollution. The lung function results indicate that elevated pollutant exposure may not have acute negative effects on healthy cyclists, but further research is necessary to determine long-term effects on a more diverse population. This study and broader field of research have the potential to encourage policy-makers and city planners to expand infrastructure to

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

    Science.gov (United States)

    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 thereby increases the lung K. pneumoniae burden. As hypothesized, we found that allergic airway inflammation decreased the number of K. pneumoniae-induced airway neutrophils and lung IL-17A, IL-17F, and IL-22 expression. Despite the marked reduction in postinfection airway neutrophilia and lung expression of Th17 cytokines, allergic airway inflammation significantly decreased the lung K. pneumoniae burden and postinfection mortality. We showed that the decreased lung K. pneumoniae burden was independent of IL-4, IL-5, and IL-17A and partially dependent on IL-13 and STAT6. Additionally, we demonstrated that the decreased lung K. pneumoniae burden associated with allergic airway inflammation was both neutrophil and CCL8 dependent. These findings suggest a novel role for CCL8 in lung antibacterial immunity against K. pneumoniae and suggest new mechanisms of orchestrating lung antibacterial immunity. PMID:24958709

  20. RAGE deficiency attenuates the protective effect of Lidocaine against sepsis-induced acute lung injury.

    Science.gov (United States)

    Zhang, Zhuo; Zhou, Jie; Liao, Changli; Li, Xiaobing; Liu, Minghua; Song, Daqiang; Jiang, Xian

    2017-04-01

    Lidocaine (Lido) is reported to suppress inflammatory responses and exhibit a therapeutic effect in models of cecal ligation and puncture (CLP)-induced acute lung injury (ALI). The receptor for advanced glycation end product (RAGE) exerts pro-inflammatory effects by enhancing pro-inflammatory cytokine production. However, the precise mechanism by which Lido confers protection against ALI is not clear. ALI was induced in RAGE WT and RAGE knockout (KO) rats using cecal ligation and puncture (CLP) operations for 24 h. The results showed that Lido significantly inhibited CLP-induced lung inflammation and histopathological lung injury. Furthermore, Lido significantly reduced CLP-induced upregulation of HMGB1 and RAGE expression and activation of the NF-κB and MAPK signaling pathways. With the use of RAGE KO rats, we demonstrate here that RAGE deficiency attenuates the protective effect of Lido against CLP-induced lung inflammatory cell infiltration and histopathological lung injury. These results suggest that RAGE deficiency attenuates the protective effect of Lido against CLP-induced ALI by attenuating the pro-inflammatory cytokines production.

  1. Characterization of inflammation in a rat model of acute lung injury after repeated pulmonary lavage.

    Science.gov (United States)

    Menk, Mario; Graw, Jan Adriaan; Steinkraus, Henrik; Haefen, Clarissa von; Sifringer, Marco; Spies, Claudia D; Lachmann, Burkhard; Schwaiberger, David

    2015-01-01

    Repeated pulmonary lavage allows to reliably reproduce failure of gas exchange and major histological findings of acute lung injury (ALI). However, because the capacity of pulmonary lavage to induce pulmonary inflammation is not well established in rodents, this study aims to characterize the induction of pulmonary inflammation in a rat model of ALI. Male adult rats were divided into a treatment group (n = 9) that received pulmonary lavage with consecutive mechanical ventilation, and a control group that received mechanical ventilation only (n = 9). Arterial blood gas analyses were performed every 30 min throughout the study. Pressure-volume curves, and lung tissue and plasma samples, were obtained at 240 min after the start of mechanical ventilation. Protein content and surface activity of bronchoalveolar lavage fluid was assessed. Transcriptional and translational regulation of pro- and anti-inflammatory cytokines IL-1β, TNF-α, IL-6, and IL-10 was determined in lungs and plasma. Markers of cellular stress were measured in lung tissue. Pulmonary lavage significantly decreased lung compliance, induced hypoxia and hypercapnia, and mediated respiratory acidosis. Protein content of lavage fluid was significantly increased and contained washed out surfactant. Expression of IL-1β, TNF-α, and IL-6 mRNA and protein expression of IL-1β and TNF-α was significantly induced in lavaged lungs, without spillover into the systemic circulation. Markers of cellular stress were significantly upregulated in lavaged lungs. This model of ALI applied in rats can induce pulmonary inflammation. The model might be used to develop therapeutic strategies that target pulmonary inflammation in ALI.

  2. Chest wall mechanics and abdominal pressure during general anaesthesia in normal and obese individuals and in acute lung injury.

    Science.gov (United States)

    Pelosi, Paolo; Luecke, Thomas; Rocco, Patricia R M

    2011-02-01

    This article discusses the methods available to evaluate chest wall mechanics and the relationship between intraabdominal pressure (IAP) and chest wall mechanics during general anaesthesia in normal and obese individuals, as well as in acute lung injury/acute respiratory distress syndrome. The interactions between the abdominal and thoracic compartments pose a specific challenge for intensive care physicians. IAP affects respiratory system, lung and chest wall elastance in an unpredictable way. Thus, transpulmonary pressure should be measured if IAP is more than 12 mmHg or if chest wall elastance is compromised for other reasons, even though the absolute values of pleural and transpulmonary pressures are not easily obtained at bedside. We suggest defining intraabdominal hypertension (IAH) as IAP at least 20 mmHg and abdominal compartment syndrome (ACS) as IAP at least 20 mmHg associated with failure of one or more organs, although further studies are required to confirm this hypothesis. Additionally, in the presence of IAH, controlled mechanical ventilation should be applied and positive end-expiratory pressure individually titrated. Prophylactic open abdomen should be considered in the presence of ACS. Increased IAP markedly affects respiratory function and complicates patient management. Frequent assessment of IAP is recommended.

  3. Decrease in pulmonary function and oxygenation after lung resection

    Directory of Open Access Journals (Sweden)

    Barbara Cristina Brocki

    2018-01-01

    Full Text Available Respiratory deficits are common following curative intent lung cancer surgery and may reduce the patient's ability to be physically active. We evaluated the influence of surgery on pulmonary function, respiratory muscle strength and physical performance after lung resection. Pulmonary function, respiratory muscle strength (maximal inspiratory/expiratory pressure and 6-min walk test (6MWT were assessed pre-operatively, 2 weeks post-operatively and 6 months post-operatively in 80 patients (age 68±9 years. Video-assisted thoracoscopic surgery was performed in 58% of cases. Two weeks post-operatively, we found a significant decline in pulmonary function (forced vital capacity −0.6±0.6 L and forced expiratory volume in 1 s −0.43±0.4 L; both p<0.0001, 6MWT (−37.6±74.8 m; p<0.0001 and oxygenation (−2.9±4.7 units; p<0.001, while maximal inspiratory and maximal expiratory pressure were unaffected. At 6 months post-operatively, pulmonary function and oxygenation remained significantly decreased (p<0.001, whereas 6MWT was recovered. We conclude that lung resection has a significant short- and long-term impact on pulmonary function and oxygenation, but not on respiratory muscle strength. Future research should focus on mechanisms negatively influencing post-operative pulmonary function other than impaired respiratory muscle strength.

  4. Positional effects on lung mechanics of ventilated preterm infants with acute and chronic lung disease.

    Science.gov (United States)

    Vendettuoli, V; Veneroni, C; Zannin, E; Mercadante, D; Matassa, P; Pedotti, A; Colnaghi, M; Dellacà, R L; Mosca, F

    2015-08-01

    The role of prone position in preterm infants has not been completely clarified. We investigated prone versus supine posture-related changes in respiratory system resistance (Rrs) and reactance (Xrs) measured by the Forced Oscillation Technique (FOT) in mechanically ventilated preterm newborns. Patients were studied in the supine versus prone positions in random order. Oxygen saturation, transcutaneous partial pressure of oxygen (ptcO2 ), carbon dioxide (ptcCO2 ), Rrs and Xrs were measured in each position. Nine patients with respiratory distress syndrome (RDS) and nine with evolving broncho-pulmonary dysplasia (BPD) were studied. Rrs was, on average, 9.8 (1.3, 18.3 as 95%CI) cmH2 O*s/l lower in the prone compared to the supine position (P = 0.02), while no differences in Xrs, ptcO2 , ptcCO2 , and breathing pattern were observed between postures. Only patients with evolving BPD showed a significant reduction of Rrs from 69.0 ± 27.4 to 53.0 ± 16.7 cmH2 O*s/l, P = 0.01. No significant correlations were found between changes in lung mechanics and ptcO2 , ptcCO2 , or breathing pattern. On short-term basis, prone positioning does not offer significant advantages in lung mechanics in mechanically ventilated infants with RDS, while it is associated with lower Rrs values in patients with evolving BPD. © 2014 Wiley Periodicals, Inc.

  5. Monitoring of cardiac output and lung ventilation by Electrical Impedance Tomography in a porcine model of acute lung injury.

    Science.gov (United States)

    Hochhausen, Nadine; Dohmeier, Henriette; Rossaint, Rolf; Czaplik, Michael

    2017-07-01

    Adequate medical treatment of the Acute Respiratory Distress Syndrome is still challenging since patient-individual aspects have to be taken into account. Lung protective ventilation and hemodynamic stability have always been two of the most crucial aims of intensive care therapy. For both aspects, a continuous - preferably non-invasive - monitoring is desirable that is available at the bedside. Unfortunately, there is no technique clinically established yet, that provides both measurement of cardiac stroke volume and ventilation dynamics in real-time. Electrical Impedance Tomography (EIT) is a promising technique to close this gap. The aim of the study was to investigate if stroke volume can be estimated by a self-developed software using EIT-based image analysis. In addition, two EIT-derived parameters, namely Global Inhomogeneity Index (GII) and Impedance Ratio (IR), were calculated to evaluate homogeneity of air distribution. Experimental acute lung injury (ALI) was provoked in seven female pigs (German Landrace) by lipopolysaccharide (LPS). All animals suffered from experimental ALI 3 to 4 hours after LPS infusion. At defined time points, respiratory and hemodynamic parameters, blood gas analyses and EIT-recordings were performed. Eight hours after ALI, animals were euthanized. Stroke volume, derived from pulmonary artery catheter (PAC), decreased continuously up to four hours after ALI. Then, stroke volume increased slightly. Stroke volume, derived from the self-developed tool, showed the same characteristics (p=0.047, r = 0.365). In addition to the GII and IR individually, both classified scores showed a high correlation with the Horowitz Index, defined as p a O 2 /FiO 2 . To conclude, EIT-derived measures enabled a reliable estimation of cardiac stroke volume and regional distribution of ventilation.

  6. The kinetics of autophagy in the lung following acute spinal cord injury in rats.

    Science.gov (United States)

    Chu, Ruiliang; Wang, Jiuling; Bi, Yang; Nan, Guoxin

    2018-01-31

    Lung injury is a major cause of respiratory complications following an acute spinal cord injury (ASCI), which are associated with a high mortality rate. Autophagy has been shown to be involved in a variety of lung diseases; however, whether autophagy is activated in the lung following ASCI remains unknown. The objective of this study was to investigate the induction of autophagy in the lung after ASCI. This is an experimental animal study of ASCI investigating kinetics of autophagy in the lung following ASCI. One hundred and forty-four rats (N=144) were divided into two groups: (1) a sham (n=72) and (2) an injury group (n=72). Allen's method was used to induce an injury at the level of the 10th thoracic vertebra. Rats were sacrificed at 6, 12, 24, 48, and 72 hours, 1 week, and 2 weeks after surgery. Lung pathology and apoptosis were assessed to determine the level of damage in the lung. LC3, RAB7, P62, and Beclin 1 were used to detect the induction of autophagy. The study was funded by the Natural Science Foundation of China (NSFC,81272172); National Key Specialty Construction of Clinical Projects of China (#2013-544). The funder of the present study had no capacity to influence the scholarly conduct of the research, interpretation of results, or dissemination of study outcomes. In the injury group, pathologic changes (i.e., pulmonary congestion, hemorrhage, inflammatory exudation, and alveolar collapse) occurred within the lung tissue within 72 hours after ASCI. Apoptosis of the lung cells gradually increased and peaked 72 hours after ASCI. Within 24 hours of ASCI, LC3 expression decreased, recovered, and gradually increased from 24 hours to 72 hours. As RAB7 decreased, P62 increased, and the ratio of RAB7/LC3 significantly decreased. After ASCI, autophagy in the injured lung underwent dynamic changes, as early autophagosome formation decreased and late autophagosomes accumulated; thus, autophagy is in a state of inhibition. Copyright © 2018 Elsevier Inc. All

  7. Lung clearance of /sup 99m/Tc-DTPA in patients with acute lung injury and pulmonary edema

    International Nuclear Information System (INIS)

    Coates, G.; O'Brodovich, H.; Dolovich, M.

    1988-01-01

    Several acute and chronic conditions that alter the integrity of the pulmonary epithelium increased the rate of absorption or clearance into the circulation of small solutes deposited in the alveoli. Technetium 99m diethylenetriamine pentaacetic acid can be deposited in the lungs as a submicronic aerosol and its rate of clearance measured with a gamma camera or simple probe. This clearance technique is currently being used to evaluate patients who have developed pulmonary edema and also to detect those patients from a high risk group who are likely to develop adult respiratory distress syndrome (ARDS). Its role in the evaluation of patients with pulmonary edema is still under active investigation. It is clear that a single measurement in patients who smoke is not useful, but repeated measurements may provide important information. The lung clearance measurement is very sensitive to changes in epithelial integrity but is not specific for ARDS. It may be most useful in combination with other predictive tests or when the clearance rate is normal. 54 references

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

    Science.gov (United States)

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

  9. Scintigraphy at 3 months after single lung transplantation and observations of primary graft dysfunction and lung function

    DEFF Research Database (Denmark)

    Belmaati, Esther Okeke; Iversen, Martin; Kofoed, Klaus F

    2012-01-01

    Scintigraphy has been used as a tool to detect dysfunction of the lung before and after transplantation. The aims of this study were to evaluate the development of the ventilation-perfusion relationships in single lung transplant recipients in the first year, at 3 months after transplantation......, and to investigate whether scintigraphic findings at 3 months were predictive for the outcome at 12 months in relation to primary graft dysfunction (PGD) and lung function. A retrospective study was carried out on all patients who prospectively and consecutively were referred for a routine lung scintigraphy...... abnormal. There was a significant difference in the normal versus abnormal perfusion and ventilation scintigraphic images evaluated from the same patients. Ventilation was distributed more homogenously in the transplanted lung than perfusion in the same lung. The relative distribution of perfusion...

  10. Regional intratidal gas distribution in acute lung injury and acute respiratory distress syndrome assessed by electric impedance tomography.

    Science.gov (United States)

    Lowhagen, K; Lundin, S; Stenqvist, O

    2010-12-01

    Regional tidal volume distribution and end-expiratory lung volume (EELV) distribution in patients with acute lung injury and acute respiratory distress syndrome (ALI, ARDS) have previously been investigated using computed tomograpy and electric impedance tomography (EIT). In the present study, we utilized the high temporal resolution of EIT to assess intratidal gas distribution. Sixteen ventilator patients with ALI/ARDS were studied. EIT was used for analysis of intertidal, intratidal and EELV regional distribution. Intratidal regional gas distribution (ITV) was analyzed by dividing the regional tidal impedance signal into eight iso-volume parts. Alveolar pressure/volume curves during ongoing ventilation and volume-dependent compliance during the initial inspiration (Cini) were calculated. A low-pressure (~32 cm H2O) recruitment maneuver and a decremental PEEPtrial were implemented. The increase in EELV was preferentially distributed to non-dependent lung regions. The intratidal gas distribution pattern was similar to the tidal volume distribution following increased PEEP; non-dependent distribution decreased and dependent distribution increased during inspiration. Cini increased, indicating successful recruitment. The distribution varied widely among individual patients. In one patient with a low EELV, the ITV pattern showed that non-dependent distribution increased and dependent distribution decreased. This coincided with minimal improvement in volume-dependent compliance. This patient probably needed higher recruitment pressure. In one patient with a high baseline EELV, there was very little change in regional ITV, and non-dependent Cini decreased. This was probably a patient with low potential recruitability, who required only moderate PEEP. On-line intratidal gas distribution monitoring offers additional information on recruitability and optimal PEEP.

  11. Airway hyperresponsiveness and development of lung function in adolescence and adulthood

    DEFF Research Database (Denmark)

    Harmsen, Lotte; Ulrik, Charlotte S; Porsbjerg, Celeste

    2014-01-01

    BACKGROUND: Long-term longitudinal studies of lung function from childhood to adulthood are important in linking our understanding of childhood risk factors to adult disease. Airway hyperresponsiveness has been shown to independently affect lung function growth in studies of adolescence. The obje......BACKGROUND: Long-term longitudinal studies of lung function from childhood to adulthood are important in linking our understanding of childhood risk factors to adult disease. Airway hyperresponsiveness has been shown to independently affect lung function growth in studies of adolescence...... attained level of lung function at age 18, which persisted throughout the follow-up until the last examination at age 27-37 years. CONCLUSION: Airway hyperresponsiveness has an independent deleterious effect on lung function development from 7 to 37 years resulting in a lower maximal attained lung function...

  12. Lansoprazole-induced acute lung and liver injury: a case report.

    Science.gov (United States)

    Atkins, Christopher; Maheswaran, Tina; Rushbrook, Simon; Kamath, Ajay

    2014-12-01

    A 61-year old woman was admitted with increasing dyspnea and deranged liver function tests. A chest X-ray revealed small volume lungs with reticulo-nodular shadowing. High resolution computed tomography of the chest revealed interlobular septal thickening. The patient subsequently underwent an open lung biopsy and ultrasound-guided liver biopsy, which were consistent with a hypersensitivity pneumonitis and drug-induced liver injury respectively. The patient had previously been commenced on lansoprazole 10 days before the onset of symptoms; this had been stopped at diagnosis. High dose prednisolone was commenced, and the patient went on to make a full recovery. Hypersensitivity pneumonitis is a form of interstitial lung disease that is rarely associated with lansoprazole; this is the first report of it causing an idiosyncratic reaction affecting the lung and liver simultaneously. This case demonstrates the importance of obtaining a full drug history, as early identification of the offending agent will improve outcomes.

  13. Functional exercise capacity, lung function and chest wall deformity in patients with adolescent idiopathic scoliosis

    Directory of Open Access Journals (Sweden)

    Evandro Fornias Sperandio

    Full Text Available AbstractIntroduction The adolescent idiopathic scoliosis (AIS causes changes on the compliance of the chest. These changes may be associated with impaired lung function and reduced functional exercise capacity of these adolescents. We aimed to evaluate the correlation between functional exercise capacity, lung function and geometry of the chest at different stages of AIS.Materials and methods The study was carried out in a cross-sectional design which were evaluated 27 AIS patients at different stages of the disease. For chest wall evaluation, were created geometry angles/distances (A/D, which were quantified by Software Postural Assessment. The functional exercise capacity was assessed by a portable gas analyzer during the incremental shuttle walk test (ISWT. Besides that, manovacuometry and spirometry were also performed.Results Linear regressions showed that oxygen uptake (peak VO2 was correlated with distance travelled in the ISWT (R2 = 0.52, maximal respiratory pressures, cough peak flow (R2 = 0.59 and some thoracic deformity markers (D1, D2 and A6.Discussion We observed that the chest wall alterations, lung function and respiratory muscle strength are related to the functional exercise capacity and may impair the physical activity performance in AIS patients.Final considerations There is correlation between functional exercise capacity, lung function and geometry of the chest in AIS patients. Our results point to the possible impact of the AIS in the physical activities of these adolescents. Therefore, efforts to prevent the disease progression are extremely important.

  14. Practice of excessive F(IO(2)) and effect on pulmonary outcomes in mechanically ventilated patients with acute lung injury.

    Science.gov (United States)

    Rachmale, Sonal; Li, Guangxi; Wilson, Gregory; Malinchoc, Michael; Gajic, Ognjen

    2012-11-01

    Optimal titration of inspired oxygen is important to prevent hyperoxia in mechanically ventilated patients in ICUs. There is mounting evidence of the deleterious effects of hyperoxia; however, there is a paucity of data about F(IO(2)) practice and oxygen exposure among patients in ICUs. We therefore sought to assess excessive F(IO(2)) exposure in mechanically ventilated patients with acute lung injury and to evaluate the effect on pulmonary outcomes. From a database of ICU patients with acute lung injury identified by prospective electronic medical record screening, we identified those who underwent invasive mechanical ventilation for > 48 hours from January 1 to December 31, 2008. Ventilator settings, including F(IO(2)) and corresponding S(pO(2)), were collected from the electronic medical record at 15-min intervals for the first 48 hours. Excessive F(IO(2)) was defined as F(IO(2)) > 0.5 despite S(pO(2)) > 92%. The association between the duration of excessive exposure and pulmonary outcomes was assessed by change in oxygenation index from baseline to 48 hours and was analyzed by univariate and multivariate linear regression analysis. Of 210 patients who met the inclusion criteria, 155 (74%) were exposed to excessive F(IO(2)) for a median duration of 17 hours (interquartile range 7.5-33 h). Prolonged exposure to excessive F(IO(2)) correlated with worse oxygenation index at 48 hours in a dose-response manner (P IO(2)) and longer duration of exposure were associated with worsening oxygenation index at 48 hours (P < .001), more days on mechanical ventilation, longer ICU stay, and longer hospital stay (P = .004). No mortality difference was noted. Excessive oxygen supplementation is common in mechanically ventilated patients with ALI and may be associated with worsening lung function.

  15. C/EBP homologous protein deficiency aggravates acute pancreatitis and associated lung injury

    Science.gov (United States)

    Weng, Te-I; Wu, Hsiao-Yi; Chen, Bo-Lin; Jhuang, Jie-Yang; Huang, Kuo-How; Chiang, Chih-Kang; Liu, Shing-Hwa

    2013-01-01

    AIM: To investigate the pathophysiological role of C/EBP homologous protein (CHOP) in severe acute pancreatitis and associated lung injury. METHODS: A severe acute pancreatitis model was induced with 6 injections of cerulein (Cn, 50 μg/kg) at 1-h intervals, then intraperitoneal injection of lipopolysaccharide (LPS, 7.5 mg/kg) in CHOP-deficient (Chop-/-) mice and wild-type (WT) mice. Animals were sacrificed under anesthesia, 3 h or 18 h after LPS injection. Serum amylase, lipase, and cytokines [interleukin (IL)-6 and tumor necrosis factor (TNF)-α], pathological changes, acute lung injury, and apoptosis in the pancreas were evaluated. Serum amylase and lipase activities were detected using a medical automatic chemical analyzer. Enzyme-linked immunosorbent assay kits were used to evaluate TNF-α and IL-6 levels in mouse serum and lung tissue homogenates. Apoptotic cells in sections of pancreatic tissues were determined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) analysis. The mouse carotid arteries were cannulated and arterial blood samples were collected for PaO2 analysis. The oxygenation index was expressed as PaO2/FiO2. RESULTS: Administration of Cn and LPS for 9 and 24 h induced severe acute pancreatitis in Chop-/- and WT mice. When comparing Chop-/- mice and WT mice, we observed that CHOP-deficient mice had greater increases in serum TNF-α (214.40 ± 19.52 pg/mL vs 150.40 ± 16.70 pg/mL; P = 0.037), amylase (4236.40 ± 646.32 U/L vs 2535.30 ± 81.83 U/L; P = 0.041), lipase (1678.20 ± 170.57 U/L vs 1046.21 ± 35.37 U/L; P = 0.008), and IL-6 (2054.44 ± 293.81 pg/mL vs 1316.10 ± 108.74 pg/mL; P = 0.046) than WT mice. The histopathological changes in the pancreases and lungs, decreased PaO2/FiO2 ratio, and increased TNF-α and IL-6 levels in the lungs were greater in Chop-/- mice than in WT mice (pancreas: Chop-/- vs WT mice, hemorrhage, P = 0.005; edema, P = 0.005; inflammatory cells infiltration, P = 0.005; total

  16. High resolution CT of the lungs in acute disseminated tuberculosis and a pediatric radiology perspectice of the term 'miliary'

    International Nuclear Information System (INIS)

    Jamieson, D.H.; Cremin, B.J.

    1993-01-01

    High resolution CT (HRCT) of the lungs in six children with acute disseminated tuberculosis was evaluated. There was a wide variation in the HRCT appearances. This covered differences in size, distribution and concentration of nodular opacities. Coalescence of nodules and the presence of intestitial thickening was variable. The recognition of acute disseminated tuberculosis is important for diagnosis and has prognostic implications. The use of the term 'acute disseminated tuberculosis' rather than 'miliary tuberculosis' is advocated. (orig.)

  17. Lung and respiratory muscle function in facioscapulohumeral muscular dystrophy.

    Science.gov (United States)

    Stübgen, Joerg-Patrick; Schultz, Cedric

    2009-06-01

    Pulmonary dysfunction is not a well-recognized feature of facioscapulohumeral muscular dystrophy (FSHD). The aim of this study was to establish the prevalence and type of pulmonary and respiratory muscle dysfunction in FSHD. Sixteen patients with moderately advanced FSHD and 16 healthy controls were evaluated. Standard lung and respiratory muscle function tests were performed. Diaphragm muscle inspiratory action was evaluated with transdiaphragmatic pressure measurements. Lung function tests showed an increased residual volume in five patients. There was a significant difference in global respiratory muscle function in patients versus controls; weakness was mild, and it affected expiratory more than inspiratory muscles. There was no significant difference in the diaphragm inspiratory action of patients versus controls. The dystrophic process that underlies FSHD did not significantly involve the muscles of the diaphragm, but it caused mild global respiratory muscle weakness that affected expiratory more than inspiratory muscles. It is probably not necessary to routinely monitor respiratory muscle function in ambulant FSHD patients who lack symptoms or signs of respiratory impairment.

  18. Lung T lymphocyte trafficking and activation during ischemic acute kidney injury.

    Science.gov (United States)

    Lie, Mihaela L; White, Laura E; Santora, Rachel J; Park, Jong M; Rabb, Hamid; Hassoun, Heitham T

    2012-09-15

    Despite advances in renal replacement therapy, the mortality rate for acute kidney injury (AKI) remains unacceptably high, likely owing to extrarenal organ dysfunction. Kidney ischemia-reperfusion injury (IRI) activates cellular and soluble mediators that facilitate organ crosstalk and induce caspase-dependent lung apoptosis and injury through a TNFR1-dependent pathway. Given that T lymphocytes mediate local IRI in the kidney and are known to drive TNFR1-mediated apoptosis, we hypothesized that T lymphocytes activated during kidney IRI would traffic to the lung and mediate pulmonary apoptosis during AKI. In an established murine model of kidney IRI, we identified trafficking of CD3+ T lymphocytes to the lung during kidney IRI by flow cytometry and immunohistochemistry. T lymphocytes were primarily of the CD3+CD8+ phenotype; however, both CD3+CD4+ and CD3+CD8+ T lymphocytes expressed CD69 and CD25 activation markers during ischemic AKI. The activated lung T lymphocytes did not demonstrate an increased expression of intracellular TNF-α or surface TNFR1. Kidney IRI induced pulmonary apoptosis measured by caspase-3 activation in wild-type controls, but not in T cell-deficient (T(nu/nu)) mice. Adoptive transfer of murine wild-type T lymphocytes into T(nu/nu) mice restored the injury phenotype with increased cellular apoptosis and lung microvascular barrier dysfunction, suggesting that ischemic AKI-induced pulmonary apoptosis is T cell dependent. Kidney-lung crosstalk during AKI represents a complex biological process, and although T lymphocytes appear to serve a prominent role in the interorgan effects of AKI, further experiments are necessary to elucidate the specific role of activated T cells in modulating pulmonary apoptosis.

  19. Inflammation in lung after acute myocardial infarction is induced by dendritic cell-mediated immune response.

    Science.gov (United States)

    Hu, L J; Ren, W Y; Shen, Q J; Ji, H Y; Zhu, L

    2017-01-01

    The present study was performed to describe the changes of lung tissues in mice with acute myocardial infarction (AMI) and also explain the cell mechanism involved in inflammation in lung. AMI was established by left coronary ligation in mice. Then mice were divided into three groups: control group, MW1 group (sampling after surgery for one week) and MW2 group (sampling after surgery for two weeks). Afterwards, measurement of lung weight and lung histology, cell sorting in bronchoalveolar lavage (BAL) fluid and detection of several adhesive molecules, inflammatory molecules as well as enzyme associated with inflammation were performed. Moreover, dendritic cells (DCs) were isolated from bone marrow of C57B/L6 mice. After incubating with necrotic myocardium, the expression of antigen presenting molecules, co-stimulatory molecules and inflammatory molecules were detected by flow cytometry or immunohistochemistry in DCs. We also detected T-cell proliferation after incubating with necrotic myocardium-treated DCs. AMI induced pathological changes of lung tissue and increased inflammatory cell amount in BAL fluid. AMI also increased the expression of several inflammatory factors, adhesive molecules and enzymes associated with inflammation. CD11c and TLR9, which are DC surface markers, showed a significantly increased expression in mice with AMI. Additionally, necrotic myocardium significantly increased the expression of co-stimulatory factors including CD83 and CD80, inflammatory cytokines including TNF-α, IFN-γ and NF-κB in DCs. Furthermore, DCs treated with necrotic myocardium also significantly promoted T-cell proliferation. AMI induced inflammation in lung and these pathological changes were mediated by DC-associated immune response.

  20. Prediction of residual lung function after lung surgery, and examination of blood perfusion in the pre- and postoperative lung using three-dimensional SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Shimatani, Shinji [Toho Univ., Tokyo (Japan). School of Medicine

    2001-01-01

    In order to predict postoperative pulmonary function after lung surgery, preoperative {sup 99m}Tc-macroaggregated albumin (MAA) lung perfusion scans with single-photon emission computed tomography (SPECT) were performed. Spirometry was also performed before and 4-6 months after surgery in 40 patients. In addition, changes in blood perfusion in the pre- and postoperative lung were examined by postoperative lung perfusion scans in 18 of the 40 patients. We measured the three-dimensional (3-D) imaging volume of the operative and contralateral lungs using the volumes rendering method at blood perfusion thresholds of 20, 50 and 75%, utilizing {sup 99m}Tc-MAA lung perfusion, and predicted pulmonary function by means of the measured volumes. We examined the correlation between predicted and the measured values of postoperative pulmonary function, forced vital capacity (FVC) and forced expiratory volume in one second (FEV{sub 1.0}). The correlation between FEV{sub 1.0} predicted by SPECT (threshold 50%) and measured postoperative lung function resembled that between lung function predicted by the standard planar method and measured FEV{sub 1.0} in the lobectomy group. We then examined the ratios of both pre- and postoperative blood perfusion volumes obtained using 3-D imaging at lung perfusion threshold ranges of 10% each (PV20-29, PV30-39) to pre- and postoperative total perfusion (PV20-100). In the lobectomy group, the postoperative PV20-29/PV20-100 value was significantly higher for the operative side lung than the preoperative PV20-29/PV20-100 value, and the postoperative PV50-59, 60-69, 70-79, 80-89 and 90-100/PV20-100 values were significantly lower than the respective preoperative values. However, in the contralateral lung, the respective pre- and postoperative PV/PV20-100 values were almost identical. These findings suggest that the rate of low blood perfusion increased while the rate of middle to high perfusion decreased in the lobectomy group in the operative

  1. Protective effect of florfenicol on acute lung injury induced by lipopolysaccharide in mice.

    Science.gov (United States)

    Zhang, Xuemei; Song, Keji; Xiong, Huanzhang; Li, Hongyu; Chu, Xiao; Deng, Xuming

    2009-12-01

    Florfenicol, an antibiotic used to treat infection, has previously been shown to modulate early cytokine responses and increase mouse survival in endotoxemia. In the present study, we investigated in vivo the effect of florfenicol on acute lung injury (ALI) induced by lipopolysaccharide (LPS). In the mouse model of LPS-induced inflammatory lung injury, we found that pretreatment with a single 100mg/kg dose of florfenicol significantly decreases the W/D ratio of lungs and protein concentration in the bronchoalveolar lavage fluid (BALF) and significantly reduces the number of total cells, neutrophils and macrophages in the BALF at 24h after LPS challenge. In addition, histopathological examination indicates that florfenicol significantly attenuates tissue injury of the lungs in LPS-induced ALI. Furthermore, florfenicol also inhibits the production of several inflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha) at 6 and 12h, interleukin-6 (IL-6) at 12 and 24h, and interleukin-1ss (IL-1ss) at 12h, in the BALF after LPS challenge. These results suggest that florfenicol protects against LPS-induced ALI in mice.

  2. Saikosaponin a Ameliorates LPS-Induced Acute Lung Injury in Mice.

    Science.gov (United States)

    Du, Zhi-An; Sun, Mei-Na; Hu, Zhan-Sheng

    2018-02-01

    The purpose of this study was to investigate the protective effects of Saikosaponin a (SSa), a triterpene saponin derived from Radix bupleuri, on lipopolysaccharide (LPS)-induced acute lung injury (ALI) using a murine model. The mice were given SSa 1 h after intranasal instillation of LPS. Then, lung histopathological examination, the wet/dry (W/D) ratio, myeloperoxidase (MPO), and inflammatory cytokines in bronchoalveolar lavage fluid (BALF) were detected in this study. The results showed that SSa reduced lung pathological injury induced by LPS. Furthermore, LPS-induced lung W/D ratio, MPO activity, and inflammatory cytokines TNF-α and IL-1β in BALF were significantly inhibited by SSa. In addition, SSa suppressed LPS-induced NF-κB activation and NLRP3 inflammasome expression. In conclusion, we found that SSa played a critical anti-inflammatory effect through inhibition of NF-κB and NLRP3 signaling pathways and protected against LPS-induced ALI.

  3. Characterization of a murine model of monocrotaline pyrrole-induced acute lung injury

    Directory of Open Access Journals (Sweden)

    Pullamsetti Soni S

    2008-12-01

    Full Text Available Abstract Background New animal models of chronic pulmonary hypertension in mice are needed. The injection of monocrotaline is an established model of pulmonary hypertension in rats. The aim of this study was to establish a murine model of pulmonary hypertension by injection of the active metabolite, monocrotaline pyrrole. Methods Survival studies, computed tomographic scanning, histology, bronchoalveolar lavage were performed, and arterial blood gases and hemodynamics were measured in animals which received an intravenous injection of different doses of monocrotaline pyrrole. Results Monocrotaline pyrrole induced pulmonary hypertension in Sprague Dawley rats. When injected into mice, monocrotaline pyrrole induced dose-dependant mortality in C57Bl6/N and BALB/c mice (dose range 6–15 mg/kg bodyweight. At a dose of 10 mg/kg bodyweight, mice developed a typical early-phase acute lung injury, characterized by lung edema, neutrophil influx, hypoxemia and reduced lung compliance. In the late phase, monocrotaline pyrrole injection resulted in limited lung fibrosis and no obvious pulmonary hypertension. Conclusion Monocrotaline and monocrotaline pyrrole pneumotoxicity substantially differs between the animal species.

  4. Acute hemodynamic changes during lung recruitment in lavage and endotoxin-induced ALI.

    Science.gov (United States)

    Odenstedt, Helena; Aneman, Anders; Kárason, Sigurbergur; Stenqvist, Ola; Lundin, Stefan

    2005-01-01

    To assess acute cardiorespiratory effects of recruitment manoeuvres in experimental acute lung injury. Experimental study in animal models of acute lung injury. Experimental laboratory at a University Medical Centre. Ten pigs with bronchoalveolar lavage and eight pigs with endotoxin-induced ALI. Two kinds of recruitment manoeuvres during 1 min; a) vital capacity manoeuvres (ViCM) consisting in a sustained inflation at 30 cmH(2)O and 40 cmH(2)O; b) manoeuvres obtained during ongoing pressure-controlled ventilation (PCRM) with peak airway pressure 30 cmH(2)O, positive end-expiratory pressure (PEEP) 15 and peak airway pressure 40, PEEP 20. Recruitment manoeuvres were repeated after volume expansion (dextran 8 ml/kg). Oxygenation, mean arterial, and pulmonary artery pressures, aortic, mesenteric, and renal blood flow were monitored. Lower pressure recruitment manoeuvres (ViCM30 and PCRM30/15) did not significantly improve oxygenation. With ViCM and PCRM at peak airway pressure 40 cmH(2)O, PaO(2) increased to similar levels in both lavage and endotoxin groups. Aortic blood flow was reduced from baseline during PCRM40/20 and ViCM40 by 57+/-3% and 61+/-6% in the lavage group and by 57+/-8% and 82+/-7% (Pdepression may be attenuated using recruitment manoeuvres during ongoing pressure-controlled ventilation and by prior volume expansion.

  5. Pulmonary Function Testing After Stereotactic Body Radiotherapy to the Lung

    Energy Technology Data Exchange (ETDEWEB)

    Bishawi, Muath [Division of Cardiothoracic Surgery, Stony Brook University Medical Center, Stony Brook, NY (United States); Kim, Bong [Division of Radiology, Stony Brook University Medical Center, Stony Brook, NY (United States); Moore, William H. [Division of Radiation Oncology, Stony Brook University, Stony Brook, NY (United States); Bilfinger, Thomas V., E-mail: Thomas.bilfinger@stonybrook.edu [Division of Cardiothoracic Surgery, Stony Brook University Medical Center, Stony Brook, NY (United States)

    2012-01-01

    Purpose: Surgical resection remains the standard of care for operable early-stage non-small-cell lung cancer (NSCLC). However, some patients are not fit for surgery because of comorbidites such as chronic obstructive pulmonary disease (COPD) and other medical conditions. We aimed to evaluate pulmonary function and tumor volume before and after stereotactic body radiotherapy (SBRT) for patients with and without COPD in early-stage lung cancer. Methods and Materials: A review of prospectively collected data of Stage I and II lung cancers, all treated with SBRT, was performed. The total SBRT treatment was 60 Gy administered in three 20 Gy fractions. The patients were analyzed based on their COPD status, using their pretreatment pulmonary function test cutoffs as established by the American Thoracic Society guidelines (forced expiratory volume [FEV]% {<=}50% predicted, FEV%/forced vital capacity [FVC]% {<=}70%). Changes in tumor volume were also assessed by computed tomography. Results: Of a total of 30 patients with Stage I and II lung cancer, there were 7 patients in the COPD group (4 men, 3 women), and 23 in t he No-COPD group (9 men, 14 women). At a mean follow-up time of 4 months, for the COPD and No-COPD patients, pretreatment and posttreatment FEV% was similar: 39 {+-} 5 vs. 40 {+-} 9 (p = 0.4) and 77 {+-} 0.5 vs. 73 {+-} 24 (p = 0.9), respectively. The diffusing capacity of the lungs for carbon monoxide (DL{sub CO}) did significantly increase for the No-COPD group after SBRT treatment: 60 {+-} 24 vs. 69 {+-} 22 (p = 0.022); however, DL{sub CO} was unchanged for the COPD group: 49 {+-} 13 vs. 50 {+-} 14 (p = 0.8). Although pretreatment tumor volume was comparable for both groups, tumor volume significantly shrank in the No-COPD group from 19 {+-} 24 to 9 {+-} 16 (p < 0.001), and there was a trend in the COPD patients from 12 {+-} 9 to 6 {+-} 5 (p = 0.06). Conclusion: SBRT did not seem to have an effect on FEV{sub 1} and FVC, but it shrank tumor volume and

  6. Automatic lung segmentation in functional SPECT images using active shape models trained on reference lung shapes from CT.

    Science.gov (United States)

    Cheimariotis, Grigorios-Aris; Al-Mashat, Mariam; Haris, Kostas; Aletras, Anthony H; Jögi, Jonas; Bajc, Marika; Maglaveras, Nicolaos; Heiberg, Einar

    2018-02-01

    Image segmentation is an essential step in quantifying the extent of reduced or absent lung function. The aim of this study is to develop and validate a new tool for automatic segmentation of lungs in ventilation and perfusion SPECT images and compare automatic and manual SPECT lung segmentations with reference computed tomography (CT) volumes. A total of 77 subjects (69 patients with obstructive lung disease, and 8 subjects without apparent perfusion of ventilation loss) performed low-dose CT followed by ventilation/perfusion (V/P) SPECT examination in a hybrid gamma camera system. In the training phase, lung shapes from the 57 anatomical low-dose CT images were used to construct two active shape models (right lung and left lung) which were then used for image segmentation. The algorithm was validated in 20 patients, comparing its results to reference delineation of corresponding CT images, and by comparing automatic segmentation to manual delineations in SPECT images. The Dice coefficient between automatic SPECT delineations and manual SPECT delineations were 0.83 ± 0.04% for the right and 0.82 ± 0.05% for the left lung. There was statistically significant difference between reference volumes from CT and automatic delineations for the right (R = 0.53, p = 0.02) and left lung (R = 0.69, p automatic quantification of wide range of measurements.

  7. Protective effect of carvacrol on acute lung injury induced by lipopolysaccharide in mice.

    Science.gov (United States)

    Feng, Xiaosheng; Jia, Aiqing

    2014-08-01

    Carvacrol, the major component of Plectranthus amboinicus, has been known to exhibit anti-inflammatory activities. The aim of this study was to investigate the effects of carvacrol on lipopolysaccharide (LPS)-induced endotoxemia and acute lung injury (ALI) in mice. Mice were injected intraperitoneally (i.p.) with LPS and the mortality of mice for 7 days were observed twice a day. Meanwhile, the protective effect of carvacrol (20, 40 or 80 mg/kg) on LPS-induced endotoxemia were detected. Using an experimental model of LPS-induced ALI, we examined the effect of carvacrol in resolving lung injury. The results showed that carvacrol could improve survival during lethal endotoxemia and attenuate LPS-induced ALI in mice. The anti-inflammatory mechanisms of carvacrol may be due to its ability to inhibit NF-κB and MAPKs signaling pathways, thereby inhibiting inflammatory cytokines TNF-α, IL-6 and IL-1β production.

  8. The acute effects of body position strategies and respiratory therapy in paralyzed patients with acute lung injury

    OpenAIRE

    Davis, Kenneth; Johannigman, Jay A; Campbell, Robert S; Marraccini, Ann; Luchette, Fred A; Frame, Scott B; Branson, Richard D

    2001-01-01

    Background: Routine turning of critically ill patients is a standard of care. In recent years, specialized beds that provide automated turning have been introduced. These beds have been reported to improve lung function, reduce hospital-acquired pneumonia, and facilitate secretion removal. This trial was designed to measure the physiological effects of routine turning and respiratory therapy in comparison with continuous lateral rotation (CLR). Methods: The study was a prospective, quasi-expe...

  9. Low-Flow Extracorporeal Carbon Dioxide Removal Using the Hemolung Respiratory Dialysis System® to Facilitate Lung-Protective Mechanical Ventilation in Acute Respiratory Distress Syndrome.

    Science.gov (United States)

    Akkanti, Bindu; Rajagopal, Keshava; Patel, Kirti P; Aravind, Sangeeta; Nunez-Centanu, Emmanuel; Hussain, Rahat; Shabari, Farshad Raissi; Hofstetter, Wayne L; Vaporciyan, Ara A; Banjac, Igor S; Kar, Biswajit; Gregoric, Igor D; Loyalka, Pranav

    2017-06-01

    Extracorporeal carbon dioxide removal (ECCO 2 R) permits reductions in alveolar ventilation requirements that the lungs would otherwise have to provide. This concept was applied to a case of hypercapnia refractory to high-level invasive mechanical ventilator support. We present a case of an 18-year-old man who developed post-pneumonectomy acute respiratory distress syndrome (ARDS) after resection of a mediastinal germ cell tumor involving the left lung hilum. Hypercapnia and hypoxemia persisted despite ventilator support even at traumatic levels. ECCO 2 R using a miniaturized system was instituted and provided effective carbon dioxide elimination. This facilitated establishment of lung-protective ventilator settings and lung function recovery. Extracorporeal lung support increasingly is being applied to treat ARDS. However, conventional extracorporeal membrane oxygenation (ECMO) generally involves using large cannulae capable of carrying high flow rates. A subset of patients with ARDS has mixed hypercapnia and hypoxemia despite high-level ventilator support. In the absence of profound hypoxemia, ECCO 2 R may be used to reduce ventilator support requirements to lung-protective levels, while avoiding risks associated with conventional ECMO.

  10. Chemokine (C-C Motif) Receptor-Like 2 is not essential for lung injury, lung inflammation, or airway hyperresponsiveness induced by acute exposure to ozone.

    Science.gov (United States)

    Malik, Farhan; Cromar, Kevin R; Atkins, Constance L; Price, Roger E; Jackson, William T; Siddiqui, Saad R; Spencer, Chantal Y; Mitchell, Nicholas C; Haque, Ikram U; Johnston, Richard A

    2017-12-01

    Inhalation of ozone (O 3 ), a gaseous air pollutant, causes lung injury, lung inflammation, and airway hyperresponsiveness. Macrophages, mast cells, and neutrophils contribute to one or more of these sequelae induced by O 3 Furthermore, each of these aforementioned cells express chemokine (C-C motif) receptor-like 2 (Ccrl2), an atypical chemokine receptor that facilitates leukocyte chemotaxis. Given that Ccrl2 is expressed by cells essential to the development of O 3 -induced lung pathology and that chemerin, a Ccrl2 ligand, is increased in bronchoalveolar lavage fluid (BALF) by O 3 , we hypothesized that Ccrl2 contributes to the development of lung injury, lung inflammation, and airway hyperresponsiveness induced by O 3 To that end, we measured indices of lung injury (BALF protein, BALF epithelial cells, and bronchiolar epithelial injury), lung inflammation (BALF cytokines and BALF leukocytes), and airway responsiveness to acetyl- β -methylcholine chloride (respiratory system resistance) in wild-type and mice genetically deficient in Ccrl2 (Ccrl2-deficient mice) 4 and/or 24 hours following cessation of acute exposure to either filtered room air (air) or O 3 In air-exposed mice, BALF chemerin was greater in Ccrl2-deficient as compared to wild-type mice. O 3 increased BALF chemerin in mice of both genotypes, yet following O 3 exposure, BALF chemerin was greater in Ccrl2-deficient as compared to wild-type mice. O 3 increased indices of lung injury, lung inflammation, and airway responsiveness. Nevertheless, no indices were different between genotypes following O 3 exposure. In conclusion, we demonstrate that Ccrl2 modulates chemerin levels in the epithelial lining fluid of the lungs but does not contribute to the development of O 3 -induced lung pathology. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  11. Lung morphology in acute respiratory distress syndrome (ARDS): comparison of chest X-ray and CT findings

    International Nuclear Information System (INIS)

    Keske, U.; Pappert, D.; Lewandowski, K.; Gerlach, H.; Hierholzer, J.; Hosten, N.; Schneider, M.; Paust, E.; Falke, K.J.; Felix, R.

    1994-01-01

    Lung morphology of the acute respiratory distress syndrome (ARDS) was analyzed in chest X-ray and computed tomography (CT). 81 patients with ARDS were examined (409 chest X-rays, 95 of those were compared with CTs). CT showed increased lung densities mostly in the dependent posterior, paravertebral lungs. In chest X-rays, these areas superimpose to the perihilar lung and thus cause the chest X-ray finding of a 'central', perihilar oedema. Bronchopneumograms, which are a frequent finding in ARDS, are mostly caused by the increased lung density in the dependent parts of the lungs. Systematic comparison of chest X-ray and CT-findings enables a better understanding of the chest X-ray morphology of ARDS. (orig.) [de

  12. Neurally adjusted ventilatory assist decreases ventilator-induced lung injury and non-pulmonary organ dysfunction in rabbits with acute lung injury

    NARCIS (Netherlands)

    Brander, Lukas; Sinderby, Christer; Lecomte, François; Leong-Poi, Howard; Bell, David; Beck, Jennifer; Tsoporis, James N.; Vaschetto, Rosanna; Schultz, Marcus J.; Parker, Thomas G.; Villar, Jesús; Zhang, Haibo; Slutsky, Arthur S.

    2009-01-01

    OBJECTIVE: To determine if neurally adjusted ventilatory assist (NAVA) that delivers pressure in proportion to diaphragm electrical activity is as protective to acutely injured lungs (ALI) and non-pulmonary organs as volume controlled (VC), low tidal volume (Vt), high positive end-expiratory

  13. The role of the acute phase protein PTX3 in the ventilator-induced lung injury

    Directory of Open Access Journals (Sweden)

    JM Real

    2008-06-01

    Full Text Available The pentraxin 3 (PTX3 is an acute phase proinflammatory protein produced by fibroblasts and alveolar epithelial cells. We have previously demonstrated that PTX3 is a key modulator of inflammation. Mechanical ventilation (MV is a life saving therapeutic approach for patients with acute lung injury that, nevertheless could lead to an inflammatory response and tissue injury (ventilator-induced lung injury: VILI, representing a major cause of iatrogenic lung damage in intensive units. Our objective was to investigate the role of PTX3 in VILI. PTX3 transgenic, knockout and Wt control mice (n = 12/group were ventilated (45ml·kg–1 until respiratory system Elastance increased 50% (Ers150%, an indicator of VILI. Histological analysis demonstrated that using a Ers150% was appropriate for our analysis since identical degrees of inflammation were observed in Tg, KO and Wt mice as assessed by leukocyte infiltration, oedema, alveolar collapse and number of breaks in alveolar septa. However, Tg mice reached Ers150% faster than Wt controls (p = 0.0225. We also showed that the lack of PTX3 does not abolish the occurrence of VILI in KOs. Gene expression profile of PTX3, IL-1beta, IL-6, KC, IFNgamma, TGFbeta and PCIII were investigated by QPCR. MV drastically up modulated PTX3 as well as IL-1beta, IL-6, IFNgamma and KC. Alternatively, mice were ventilated for 20, 40 and 60 min. The faster kinetics of Tg mice to reach Ers150% was accompanied by an earlier augmentation of IL-1b and PTX3 expression. The kinetics of local PTX3 expression in the lungs of ventilated mice strongly suggests the involvement of this pentraxin in the pathogenesis of VILI.

  14. Abdominal Muscle Activity during Mechanical Ventilation Increases Lung Injury in Severe Acute Respiratory Distress Syndrome.

    Directory of Open Access Journals (Sweden)

    Xianming Zhang

    Full Text Available It has proved that muscle paralysis was more protective for injured lung in severe acute respiratory distress syndrome (ARDS, but the precise mechanism is not clear. The purpose of this study was to test the hypothesis that abdominal muscle activity during mechanically ventilation increases lung injury in severe ARDS.Eighteen male Beagles were studied under mechanical ventilation with anesthesia. Severe ARDS was induced by repetitive oleic acid infusion. After lung injury, Beagles were randomly assigned into spontaneous breathing group (BIPAPSB and abdominal muscle paralysis group (BIPAPAP. All groups were ventilated with BIPAP model for 8h, and the high pressure titrated to reached a tidal volume of 6ml/kg, the low pressure was set at 10 cmH2O, with I:E ratio 1:1, and respiratory rate adjusted to a PaCO2 of 35-60 mmHg. Six Beagles without ventilator support comprised the control group. Respiratory variables, end-expiratory volume (EELV and gas exchange were assessed during mechanical ventilation. The levels of Interleukin (IL-6, IL-8 in lung tissue and plasma were measured by qRT-PCR and ELISA respectively. Lung injury scores were determined at end of the experiment.For the comparable ventilator setting, as compared with BIPAPSB group, the BIPAPAP group presented higher EELV (427±47 vs. 366±38 ml and oxygenation index (293±36 vs. 226±31 mmHg, lower levels of IL-6(216.6±48.0 vs. 297.5±71.2 pg/ml and IL-8(246.8±78.2 vs. 357.5±69.3 pg/ml in plasma, and lower express levels of IL-6 mRNA (15.0±3.8 vs. 21.2±3.7 and IL-8 mRNA (18.9±6.8 vs. 29.5±7.9 in lung tissues. In addition, less lung histopathology injury were revealed in the BIPAPAP group (22.5±2.0 vs. 25.2±2.1.Abdominal muscle activity during mechanically ventilation is one of the injurious factors in severe ARDS, so abdominal muscle paralysis might be an effective strategy to minimize ventilator-induce lung injury.

  15. Hydrogen Gas Inhalation Attenuates Seawater Instillation-Induced Acute Lung Injury via the Nrf2 Pathway in Rabbits.

    Science.gov (United States)

    Diao, Mengyuan; Zhang, Sheng; Wu, Lifeng; Huan, Le; Huang, Fenglou; Cui, Yunliang; Lin, Zhaofen

    2016-12-01

    Seawater instillation-induced acute lung injury involves oxidative stress and apoptosis. Although hydrogen gas inhalation is reportedly protective in multiple types of lung injury, the effect of hydrogen gas inhalation on seawater instillation-induced acute lung injury remains unknown. This study investigated the effect of hydrogen gas on seawater instillation-induced acute lung injury and explored the mechanisms involved. Rabbits were randomly assigned to control, hydrogen (2 % hydrogen gas inhalation), seawater (3 mL/kg seawater instillation), and seawater + hydrogen (3 mL/kg seawater instillation + 2 % hydrogen gas inhalation) groups. Arterial partial oxygen pressure and lung wet/dry weight ratio were detected. Protein content in bronchoalveolar lavage fluid (BALF) and serum as well as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 levels were determined. Hematoxylin-eosin staining was used to monitor changes in lung specimens, and malondialdehyde (MDA) content and myeloperoxidase (MPO) activity were assayed. In addition, NF-E2-related factor (Nrf) 2 and heme oxygenase (HO)-1 mRNA and protein expression were measured, and apoptosis was assessed by measuring caspase-3 expression and using terminal deoxy-nucleotidyl transferase dUTP nick end-labeling (TUNEL) staining. Hydrogen gas inhalation markedly improved lung endothelial permeability and decreased both MDA content and MPO activity in lung tissue; these changes were associated with decreases in TNF-α, IL-1β, and IL-6 in BALF. Hydrogen gas also alleviated histopathological changes and cell apoptosis. Moreover, Nrf2 and HO-1 expressions were significantly activated and caspase-3 expression was inhibited. These results demonstrate that hydrogen gas inhalation attenuates seawater instillation-induced acute lung injury in rabbits and that the protective effects observed may be related to the activation of the Nrf2 pathway.

  16. Exposure, lung function, and symptoms in car painters exposed to hexamethylendiisocyanate and biuret modified hexamethylendiisocyanate

    Energy Technology Data Exchange (ETDEWEB)

    Alexandersson, R.; Hedenstierna, G.; Plato, N.; Kolmodin-Hedman, B.

    1987-11-01

    Individuals who paint cars often complain to doctors about respiratory problems. Car painters are exposed to isocyanates, especially hexamethylendiisocyanate (HDI), and biuret modified HDI (HDI-BT). The mean exposure to HDI-BT was 115 micrograms/m3 in the air (range 10-385 micrograms/m3), which exceeds the time-weighted Swedish threshold level of 90 micrograms/m3. Exposure to HDI was about 1.0 microgram/m3 with brief peaks. This study investigated the effect of HDI and HDI-BT on lung function and included two control groups: (1) car platers, exposed to the same solvents and grinding dust as car painters, but not to isocyanates, and (2) car mechanics (controls), not exposed to the mentioned agents. Car painters and car platers were compared to car mechanics on Monday before work. Acute effects of car painting were tested by comparing the lung function values on Monday morning with those on Friday afternoon. Pulmonary function was evaluated by means of spirometry and a single breath nitrogen washout. Spirometry in painters and platers did not differ from that in controls, i.e., car mechanics. Closing volume in relation to vital capacity (CV%) was increased in car painters, suggestive of a small airways disease on Monday before work and tended to increase during a work week. Car platers did not differ from controls.

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

    Directory of Open Access Journals (Sweden)

    Zappa Maria

    2011-08-01

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

  18. Mechanism underlying acute lung injury due to sulfur mustard exposure in rats.

    Science.gov (United States)

    Xiaoji, Zhu; Xiao, Meng; Rui, Xu; Haibo, Chu; Chao, Zhao; Chengjin, Lian; Tao, Wang; Wenjun, Guo; Shengming, Zhang

    2016-08-01

    Sulfur mustard (SM), a bifunctional alkylating agent that causes severe lung damage, is a significant threat to both military and civilian populations. The mechanisms mediating the cytotoxic effects of SM are unknown and were investigated in this study. The purpose of this study was to establish a rat model of SM-induced lung injury to observe the resulting changes in the lungs. Male rats (Sprague Dawley) were anesthetized, intratracheally intubated, and exposed to 2 mg/kg of SM by intratracheal instillation. Animals were euthanized 6, 24, 48, and 72 h post-exposure, and bronchoalveolar lavage fluid (BALF) and lung tissues were collected. Exposure of rats to SM resulted in rapid pulmonary toxicity, including partial bronchiolar epithelium cell shedding, focal ulceration, and an increased amount of inflammatory exudate and number of cells in the alveoli. There was also evidence that the protein content and cell count of BALF peaked at 48 h, and the alveolar septum was widened and filled with lymphocytes. SM exposure also resulted in partial loss of type I alveolar epithelial cell membranes, fuzzy mitochondrial cristae, detachment and dissociation of ribosomes attached to the surface of rough endoplasmic reticulum, cracked, missing, and disorganized microvilli of type II alveolar epithelial cells, and increased apoptotic cells in the alveolar septum. The propylene glycol control group, however, was the same as the normal group. These data demonstrate that the mechanism of a high concentration of SM (2 mg/kg) induced acute lung injury include histologic changes, inflammatory reactions, apoptosis, oxidative stress, and nuclear DNA damage; the degree of injury is time dependent. © The Author(s) 2014.

  19. Respiratory symptoms and lung function in bauxite miners.

    Science.gov (United States)

    Beach, J R; de Klerk, N H; Fritschi, L; Sim, M R; Musk, A W; Benke, G; Abramson, M J; McNeil, J J

    2001-09-01

    To determine whether cumulative bauxite exposure is associated with respiratory symptoms or changes in lung function in a group of bauxite miners. Current employees at three bauxite mines in Australia were invited to participate in a survey comprising: questionnaire on demographic details, respiratory symptoms, and work history; skin prick tests for four common aeroallergens; and spirometry. A task exposure matrix was constructed for bauxite exposure in all tasks in all jobs based on monitoring data. Data were examined for associations between cumulative bauxite exposure, and respiratory symptoms and lung function, by regression analyses. The participation rate was 86%. Self-reported work-related respiratory symptoms were reported by relatively few subjects (1.5%-11.8%). After adjustment for age and smoking no significant differences in the prevalence of respiratory symptoms were identified between subjects, in the quartiles of cumulative bauxite exposure distribution. The forced expiratory volume in I s (FEV1) of the exposed group was found to be significantly lower than that for the unexposed group. After adjustment for age, height, and smoking there were no statistically significant differences between quartiles in FEVI, forced vital capacity (FVC) and FEVl/FVC ratio. These data provide little evidence of a serious adverse effect on respiratory health associated with exposure to bauxite in an open-cut bauxite mine in present day conditions.

  20. Serum-surfactant SP-D correlates inversely to lung function in cystic fibrosis

    DEFF Research Database (Denmark)

    Olesen, Hanne Vebert; Holmskov, Uffe; Schiøtz, Peter Oluf

    2010-01-01

    BACKGROUND: Cystic fibrosis (CF) affects the lungs causing infections and inflammation. Surfactant protein D (SP-D) is an innate defense lectin primarily secreted in the lungs. We investigated the influence of the SP-D Met11Thr polymorphism on CF lung function; and serum SP-D as a marker for CF...

  1. Lung function studied by servo-controlled ventilator and respiratory mass spectrometer

    International Nuclear Information System (INIS)

    Piiper, J.

    1987-01-01

    The gas exchange function of lungs is studied. The gas concentration, measured by mass spectrometry and the lung volume and rate of change of lung volume are discussed. A servo-controlled ventilator is presented. Several experimental projects performed on anesthetized paralyzed dogs are reported. (M.A.C.) [pt

  2. Agmatine Protects against Zymosan-Induced Acute Lung Injury in Mice by Inhibiting NF-κB-Mediated Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Xuanfei Li

    2014-01-01

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

  3. Lung function studies in diagnostics and follow-up of pulmonary sarcoidosis

    International Nuclear Information System (INIS)

    Braadvik, I.

    1994-06-01

    In 66 patients the relationship between lung volumes and lung mechanics in pulmonary sarcoidosis was investigated. Lung volumes, static lung mechanics, lung resistance, dynamic lung mechanics and arterial blood gases at rest and during exercise were obtained. Fifteen functionally compromised patients received steroids during one year. They were re-investigated during the treatment and at a follow-up after an average of 7 years. In another 41 patients with newly diagnosed sarcoidosis, the kinetics of the lung clearance of 99m Tc-DTPA measured over 180 minutes was explored, and compared to kinetics in healthy smokers. The relationship between lung clearance and lung volumes, lung mechanics, arterial blood gases and disease activity assessed with serum angiotensin-converting enzyme and 67 Ga scintigraphy was studied. Reducing lung volumes and compliance, increased resistance and arterial oxygen tension were common. Vital capacity (VC), and changes of VC at follow-up, corresponded to the slope of the static elastic pressure/volume curve, and to the variation of it. Other static lung volumes reflected rather the position of the curve along the volume axis. Reduced VC also reflected obstruction. Forced expiratory volume in one second revealed to equal extent lung stiffness and obstruction. Lung mechanics showed abnormalities not always evident from spirometry.In 50% of the patients lung clearance of 99m Tc-DTPA disclosed an abnormally fast mono-exponential clearance or a bi-exponential clearance, which however differed from that in smokers. Lung clearance more readily detected abnormal function than did spirometry. Clearance did nor correlate with other investigations. 67 Ga lung activity was higher in patients with a pathologic lung clearance

  4. Comparison of different degrees of variability in tidal volume to prevent deterioration of respiratory system elastance in experimental acute lung inflammation.

    Science.gov (United States)

    Kiss, T; Silva, P L; Huhle, R; Moraes, L; Santos, R S; Felix, N S; Santos, C L; Morales, M M; Capelozzi, V L; Kasper, M; Pelosi, P; Gama de Abreu, M; Rocco, P R M

    2016-05-01

    Variable ventilation improves respiratory function, but it is not known whether the amount of variability in tidal volume (VT) can be reduced in recruited lungs without a deterioration of respiratory system elastance. Acute lung inflammation was induced by intratracheal instillation of lipopolysaccharide in 35 Wistar rats. Twenty-eight animals were anaesthetized and ventilated in volume-controlled mode. Lungs were recruited by random variation of VT (mean 6 ml kg(-1), coefficient of variation 30%, normal distribution) for 30 min. Animals were randomly assigned to different amounts of VT variability (n=7 for 90 min per group): 30, 15, 7.5, or 0%. Lung function, diffuse alveolar damage, and gene expression of biological markers associated with cell mechanical stress, inflammation, and fibrogenesis were assessed. Seven animals were not ventilated and served as controls for post-mortem analyses. A VT variability of 30%, but not 15, 7.5, or 0%, prevented deterioration of respiratory system elastance [Mean (SD) -7.5 (8.7%), Prespiratory system elastance and was not associated with lung histological damage. © The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Long-term pulmonary function after surgery for lung cancer.

    Science.gov (United States)

    Kobayashi, Naohiro; Kobayashi, Keisuke; Kikuchi, Shinji; Goto, Yukinobu; Ichimura, Hideo; Endo, Katsuyuki; Sato, Yukio

    2017-05-01

    Many patients with lung cancer have been cured by surgical intervention. However, the long-term effects of lung resection on pulmonary function are unclear. Therefore, we investigated long-term pulmonary function after surgery. We retrospectively reviewed the medical records of patients who underwent surgery for lung cancer between 2001 and 2009. A total of 445 patients who had survived more than 5 years since the surgery were included. The patients were divided into lobectomy, segmentectomy and partial resection groups. The time-dependent changes in pulmonary function were investigated. The percentages of the vital capacity and forced expiratory volume in 1 second (FEV 1 ) at postoperative year (POY) 1 vs preoperative values were 92.9 ± 11.1% and 91.3 ± 13.0% in the lobectomy group, 95.9 ± 9.0% and 93.8 ± 10.5% in the segmentectomy group and 97.8 ± 7.3% and 98.1 ± 8.3% in the partial resection group, respectively. The values in the lobectomy group were significantly lower than those in the segmentectomy and partial resection groups. The percentages of vital capacity and FEV 1 at POY 5 vs preoperative values were 90.0 ± 11.5% and 86.2 ± 11.9% in the lobectomy group, 93.4 ± 9.8% and 91.1 ± 9.8% in the segmentectomy group and 94.3 ± 8.8% and 94.0 ± 8.0% in the partial resection group, respectively. The decrease in the rates from POY 1 to POY 5 were not significantly different among the procedures. Pulmonary function declined with pulmonary resection. After the patient recovered from the operation, pulmonary function decreased with time regardless of the surgical procedure. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  6. Relationship of the Functional Movement Screen In-Line Lunge to Power, Speed, and Balance Measures

    OpenAIRE

    Hartigan, Erin H.; Lawrence, Michael; Bisson, Brian M.; Torgerson, Erik; Knight, Ryan C.

    2014-01-01

    Background: The in-line lunge of the Functional Movement Screen (FMS) evaluates lateral stability, balance, and movement asymmetries. Athletes who score poorly on the in-line lunge should avoid activities requiring power or speed until scores are improved, yet relationships between the in-line lunge scores and other measures of balance, power, and speed are unknown. Hypothesis: (1) Lunge scores will correlate with center of pressure (COP), maximum jump height (MJH), and 36.6-meter sprint time...

  7. Structural and functional changes in the minipig lung following irradiation of different lung volumes at a constant mean lung dose; Strukturelle und funktionelle Veraenderungen an der Lunge von Minischweinen nach Bestrahlung unterschiedlich grosser Lungenvolumina mit gleicher mittlerer Lungendosis

    Energy Technology Data Exchange (ETDEWEB)

    Kusche, S.; Herrmann, T.; Appold, S.; Hoelscher, T.; Bruechner, K.; Geyer, P.; Baumann, M.; Kumpf, R.

    2004-07-01

    Minipigs were subjected to irradiation of different lung volumes at approximately the same mean lung dose (D{sub m}ean) and examined for structural and morphological changes of the lung. The outcome confirmed earlier findings on the pig lung. While no significant differences between irradiation groups was found in terms of functional lung changes, there was a clear correlation between functional changes observed and the mean lung dose. This is in good agreement with data from clinical studies. It follows that the mean lung dose is of predictive value in considering functional lung damage in the assessment of different irradiation regimes. By contrast structural damage was found to correlate with applied dose. [German] Es wurden an Minischweinen unterschiedliche grosse Lungenvolumina mit vergleichbaren mittleren Lungendosen (mean lung dose, D{sub mean}) bestrahlt und die funktionellen und morphologischen Veraenderungen bestimmt. Die Untersuchungen zu funktionellen und morphologischen Veaenderungen bestaetigen fruehere Untersuchungen an der Schweinelunge. Hinsichtlich funktioneller Lungenveraenderungen fand sich kein signifikanter Unterschied zwischen den Bestrahlungsarmen, aber es konnte eine eindeutige Korrelation dieser Veraenderungen mit der mittleren Lungendosis D{sub mean} nachgewiesen werden. Dies steht in gutem Einklang mit Daten aus klinischen Untersuchungen. Somit bestaetigt sich, dass die mean lung dose eine praediktive Bedeutung zur Abschaetzung funktionaler Schaeden der Lunge bei der Beurteilung unterschiedlicher Bestrahlungsplaene hat. Die strukturellen Schaeden korrelieren hingegen mit der applizierten Dosis. (orig.)

  8. SU-E-J-86: Lobar Lung Function Quantification by PET Galligas and CT Ventilation Imaging in Lung Cancer Patients

    International Nuclear Information System (INIS)

    Eslick, E; Kipritidis, J; Keall, P; Bailey, D; Bailey, E

    2014-01-01

    Purpose: The purpose of this study was to quantify the lobar lung function using the novel PET Galligas ([68Ga]-carbon nanoparticle) ventilation imaging and the investigational CT ventilation imaging in lung cancer patients pre-treatment. Methods: We present results on our first three lung cancer patients (2 male, mean age 78 years) as part of an ongoing ethics approved study. For each patient a PET Galligas ventilation (PET-V) image and a pair of breath hold CT images (end-exhale and end-inhale tidal volumes) were acquired using a Siemens Biograph PET CT. CT-ventilation (CT-V) images were created from the pair of CT images using deformable image registration (DIR) algorithms and the Hounsfield Unit (HU) ventilation metric. A comparison of ventilation quantification from each modality was done on the lobar level and the voxel level. A Bland-Altman plot was used to assess the difference in mean percentage contribution of each lobe to the total lung function between the two modalities. For each patient, a voxel-wise Spearmans correlation was calculated for the whole lungs between the two modalities. Results: The Bland-Altman plot demonstrated strong agreement between PET-V and CT-V for assessment of lobar function (r=0.99, p<0.001; range mean difference: −5.5 to 3.0). The correlation between PET-V and CT-V at the voxel level was moderate(r=0.60, p<0.001). Conclusion: This preliminary study on the three patients data sets demonstrated strong agreement between PET and CT ventilation imaging for the assessment of pre-treatment lung function at the lobar level. Agreement was only moderate at the level of voxel correlations. These results indicate that CT ventilation imaging has potential for assessing pre-treatment lobar lung function in lung cancer patients

  9. Ketamine attenuates sepsis-induced acute lung injury via regulation of HMGB1-RAGE pathways.

    Science.gov (United States)

    Li, Kehan; Yang, Jianxue; Han, Xuechang

    2016-05-01

    High mobility group box protein 1 (HMGB1) and receptor for the advanced glycation end product (RAGE) play important roles in the development of sepsis-induced acute lung injury (ALI). Ketamine is considered to confer protective effects on ALI during sepsis. In this study, we investigated the effects of ketamine on HMGB1-RAGE activation in a rat model of sepsis-induced ALI. ALI was induced in wild type (WT) and RAGE deficient (RAGE(-/-)) rats by cecal ligation and puncture (CLP) or HMGB1 to mimic sepsis-induced ALI. Rats were randomly divided to six groups: sham-operation+normal saline (NS, 10 mL/kg), sham-operation+ketamine (10 mg/kg), CLP/HMGB1+NS (10 mL/kg), CLP/HMGB1+ketamine (5 mg/kg), CLP/HMGB1+ketamine (7.5 mg/kg), and CLP/HMGB1+ketamine (10 mg/kg) groups. NS and ketamine were administered at 3 and 12 h after CLP/HMGB1 via intraperitoneal injection. Pathological changes of lung, inflammatory cell counts, expression of HMGB1 and RAGE, and concentrations of various inflammatory mediators in bronchoalveolar lavage fluids (BALF) and lung tissue were then assessed. Nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPK) signaling pathways in the lung were also evaluated. CLP/HMGB1 increased the wet to dry weight ratio and myeloperoxidase activity in lung, the number of total cells, neutrophils, and macrophages in the BALF, and inflammatory mediators in the BALF and lung tissues. Moreover, expression of HMGB1 and RAGE in lung tissues was increased after CLP. Ketamine inhibited all the above effects. It also inhibited the activation of IκB-α, NF-κB p65, and MAPK. Ketamine protects rats against HMGB1-RAGE activation in a rat model of sepsis-induced ALI. These effects may partially result from reductions in NF-κB and MAPK. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

  10. Acute cigarette smoke exposure causes lung injury in rabbits treated with ibuprofen

    International Nuclear Information System (INIS)

    Witten, M.L.; Lemen, R.J.; Quan, S.F.; Sobonya, R.E.; Magarelli, J.L.; Bruck, D.C.

    1987-01-01

    We studied lung clearance of aerosolized technetium-labeled diethylenetriamine pentaacetic acid (/sup 99m/TcDTPA), plasma concentrations of 6-keto-PGF1 alpha and thromboxane B2, and pulmonary edema as indices of lung injury in rabbits exposed to cigarette smoke (CSE). Forty-six rabbits were randomly assigned to 4 groups: control sham smoke exposure (SS, N = 9), sham smoke exposure ibuprofen-pretreated (SS-I, N = 10), CSE (N = 9), sham smoke exposure ibuprofen-pretreated (SS-I, N = 10), CSE (N = 9), and CSE ibuprofen-pretreated (CSE-I, N = 19). Ibuprofen (cyclooxygenase eicosanoid inhibitor) was administered as a single daily intramuscular injection (25 mg/kg) for 7 days before the experiment. Cigarette or sham smoke was delivered by syringe in a series of 5, 10, 20, and 30 tidal volume breaths with a 15-min counting period between each subset of breaths to determine /sup 99m/TcDTPA biological half-life (T1/2). In the ibuprofen pretreated group, CSE caused significant decreases in /sup 99m/TcDTPA T1/2 and dynamic lung compliance. Furthermore, these changes in lung function were accompanied by severe injury to type I alveolar cell epithelium, pulmonary edema, and frequently death of the rabbits. These findings suggest that inhibition of the cyclooxygenase pathway before CSE exacerbates lung injury in rabbits

  11. Ventilator „Chirana Aura V“ In Two Models Of Neonatal Acute Lung Injury - A Pilot Study

    Directory of Open Access Journals (Sweden)

    Tomclkova L.

    2014-05-01

    Full Text Available In severe respiratory insufficiency, neonatal and pediatric patients should be ventilated artificially by a ventilator. Aim of this experimental study was to evaluate whether the newly developed ventilator Chirana Aura V may effectively ventilate the lungs of animals with two different models of acute lung injury: acute respiratory distress syndrome (ARDS induced by repetitive saline lavage and meconium aspiration syndrome (MAS induced by intratracheal instillation of neonatal meconium. The experiments were performed on 10 adult rabbits (New Zealand white. In ARDS group (n=5, the lungs were repetitively lavaged with saline (30 ml/kg until partial pressure of oxygen (PaO2 in arterial blood was under 26.7 kPa at inspiratory fraction of oxygen FiO2=1.0. In MAS group (n=5, animals were instilled 4 ml/kg of suspension of human meconium (25 mg/ml. When the model of acute lung injury was developed, animals were ventilated for additional 2 hours with pressure control ventilation (PCV regime by ventilator Chirana Aura V. Ventilatory parameters, blood gases, acid-base balance, end-tidal CO2, O2 saturation of hemoglobin, oxygenation indexes, ventilation efficiency index, dynamic lung compliance, and right-to-left pulmonary shunts were measured and calculated in regular time intervals. In both experimental groups, used ventilatory settings provided acceptable gas exchange within the period of observation. Thus, the results indicate that ventilator Chirana Aura V might be suitable for ventilation of animal models of acute lung injury. However, further pre-clinical investigation is needed before its use may be recommended in neonatal and/or pediatric patients with acute lung injury.

  12. Sinus surgery can improve quality of life, lung infections, and lung function in patients with primary ciliary dyskinesia

    DEFF Research Database (Denmark)

    Alanin, Mikkel Christian; Aanaes, Kasper; Hoiby, Niels

    2017-01-01

    Background Chronic rhinosinusitis (CRS) and bacterial sinusitis are ubiquitous in patients with primary ciliary dyskinesia (PCD). From the sinuses, Pseudomonas aeruginosa can infect the lungs. Methods We studied the effect of endoscopic sinus surgery (ESS) on symptoms of CRS and lower airway...... patients (62%). Four patients with preoperative P. aeruginosa lung colonization (25%) had no regrowth during follow-up; 2 of these had P. aeruginosa sinusitis. Sinonasal symptoms were improved 12 months after ESS and we observed a trend toward better lung function after ESS. Conclusion We demonstrated...

  13. Seawater-drowning-induced acute lung injury: From molecular mechanisms to potential treatments.

    Science.gov (United States)

    Jin, Faguang; Li, Congcong

    2017-06-01

    Drowning is a crucial public safety problem and is the third leading cause of accidental fatality, claiming ~372,000 lives annually, worldwide. In near-drowning patients, acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is one of the most common complications. Approximately 1/3 of near-drowning patients fulfill the criteria for ALI or ARDS. In the present article, the current literature of near-drowning, pathophysiologic changes and the molecular mechanisms of seawater-drowning-induced ALI and ARDS was reviewed. Seawater is three times more hyperosmolar than plasma, and following inhalation of seawater the hyperosmotic seawater may cause serious injury in the lung and alveoli. The perturbing effects of seawater may be primarily categorized into insufficiency of pulmonary surfactant, blood-air barrier disruption, formation of pulmonary edema, inflammation, oxidative stress, autophagy, apoptosis and various other hypertonic stimulation. Potential treatments for seawater-induced ALI/ARDS were also presented, in addition to suggestions for further studies. A total of nine therapeutic strategies had been tested and all had focused on modulating the over-activated immunoreactions. In conclusion, seawater drowning is a complex injury process and the exact mechanisms and potential treatments require further exploration.

  14. Bioactive Components from Qingwen Baidu Decoction against LPS-Induced Acute Lung Injury in Rats

    Directory of Open Access Journals (Sweden)

    Qi Zhang

    2017-04-01

    Full Text Available Qingwen Baidu Decoction (QBD is an extraordinarily “cold” formula. It was traditionally used to cure epidemic hemorrhagic fever, intestinal typhoid fever, influenza, sepsis and so on. The purpose of this study was to discover relationships between the change of the constituents in different extracts of QBD and the pharmacological effect in a rat model of acute lung injury (ALI induced by lipopolysaccharide (LPS. The study aimed to discover the changes in constituents of different QBD extracts and the pharmacological effects on acute lung injury (ALI induced by LPS. The results demonstrated that high dose and middle dose of QBD had significantly potent anti-inflammatory effects and reduced pulmonary edema caused by ALI in rats (p < 0.05. To explore the underlying constituents of QBD, we assessed its influence of six different QBD extracts on ALI and analyzed the different constituents in the corresponding HPLC chromatograms by a Principal Component Analysis (PCA method. The results showed that the pharmacological effect of QBD was related to the polarity of its extracts, and the medium polarity extracts E2 and E5 in particular displayed much better protective effects against ALI than other groups. Moreover, HPLC-DAD-ESI-MSn and PCA analysis showed that verbascoside and angoroside C played a key role in reducing pulmonary edema. In addition, the current study revealed that ethyl gallate, pentagalloylglucose, galloyl paeoniflorin, mudanpioside C and harpagoside can treat ALI mainly by reducing the total cells and infiltration of activated polymorphonuclear leukocytes (PMNs.

  15. Seawater-drowning-induced acute lung injury: From molecular mechanisms to potential treatments

    Science.gov (United States)

    Jin, Faguang; Li, Congcong

    2017-01-01

    Drowning is a crucial public safety problem and is the third leading cause of accidental fatality, claiming ~372,000 lives annually, worldwide. In near-drowning patients, acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is one of the most common complications. Approximately 1/3 of near-drowning patients fulfill the criteria for ALI or ARDS. In the present article, the current literature of near-drowning, pathophysiologic changes and the molecular mechanisms of seawater-drowning-induced ALI and ARDS was reviewed. Seawater is three times more hyperosmolar than plasma, and following inhalation of seawater the hyperosmotic seawater may cause serious injury in the lung and alveoli. The perturbing effects of seawater may be primarily categorized into insufficiency of pulmonary surfactant, blood-air barrier disruption, formation of pulmonary edema, inflammation, oxidative stress, autophagy, apoptosis and various other hypertonic stimulation. Potential treatments for seawater-induced ALI/ARDS were also presented, in addition to suggestions for further studies. A total of nine therapeutic strategies had been tested and all had focused on modulating the over-activated immunoreactions. In conclusion, seawater drowning is a complex injury process and the exact mechanisms and potential treatments require further exploration. PMID:28587319

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

    Science.gov (United States)

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

    2013-06-01

    Scleroderma (SD) is a systemic disease that predominantly affects the skin. Diffuse infiltrative lung disease (DILD) is rare and occurs most often in the course of the disease. We analyzed seven cases of DILO of SD recorded between 2003 and 2010 among 196 PID (3.6%). Functional signs were limited to respiratory dyspnea, it was associated to dysphagia in six cases, dry syndrome in five cases and Raynaud's phenomenon in four cases. Clinical examination found crackles in the bases of the thorax in all cases and specific cutaneous signs in six cases. The chest radiograph showed that interstitial disease predominates at the lung bases in all cases with a large aspect of the pulmonary arteries in two cases. The chest CT scan confirmed the predominance of basal and peripheral damage with signs of fibrosis in six cases. The pulmonary function objectified a severe restrictive ventilatory defect in all cases. Bronchoscopy showed a normal macroscopic appearance in all cases, the broncho-alveolar lavage was predominated by neutrophilic formula in four cases. SCL 70 antibodies were positive in four cases. All patients were treated by steroids with improvement of dyspnea and stabilization of radiographs. A patient had died in an array of acute respiratory failure and one patient was lost to follow-up. DILD in scleroderma is rare and seldom reveals the disease, it affects the patient's prognosis especially when associated with arterial pulmonary hypertension. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  17. Glucagon-like peptide-1 (GLP-1) reduces mortality and improves lung function in a model of experimental obstructive lung disease in female mice.

    Science.gov (United States)

    Viby, Niels-Erik; Isidor, Marie S; Buggeskov, Katrine B; Poulsen, Steen S; Hansen, Jacob B; Kissow, Hannelouise

    2013-12-01

    The incretin hormone glucagon-like peptide-1 (GLP-1) is an important insulin secretagogue and GLP-1 analogs are used for the treatment of type 2 diabetes. GLP-1 displays antiinflammatory and surfactant-releasing effects. Thus, we hypothesize that treatment with GLP-1 analogs will improve pulmonary function in a mouse model of obstructive lung disease. Female mice were sensitized with injected ovalbumin and treated with GLP-1 receptor (GLP-1R) agonists. Exacerbation was induced with inhalations of ovalbumin and lipopolysaccharide. Lung function was evaluated with a measurement of enhanced pause in a whole-body plethysmograph. mRNA levels of GLP-1R, surfactants (SFTPs), and a number of inflammatory markers were measured. GLP-1R was highly expressed in lung tissue. Mice treated with GLP-1R agonists had a noticeably better clinical appearance than the control group. Enhanced pause increased dramatically at day 17 in all control mice, but the increase was significantly less in the groups of GLP-1R agonist-treated mice (P agonist-treated mice (P agonist treatment. These results show that GLP-1R agonists have potential therapeutic potential in the treatment of obstructive pulmonary diseases, such as chronic obstructive pulmonary disease, by decreasing the severity of acute exacerbations. The mechanism of action does not seem to be the modulation of inflammation and SFTP expression.

  18. Effects of SDF-1/CXCR4 on Acute Lung Injury Induced by Cardiopulmonary Bypass.

    Science.gov (United States)

    Shi, Hai; Lu, Rujian; Wang, Shuo; Chen, Honglin; Wang, Fei; Liu, Kun

    2017-06-01

    Acute lung injury (ALI) is one of the most important complications after cardiopulmonary bypass (CPB) and the complex pathophysiology remains to be resolved incomplete. SDF-1/CXCR4 chemokine axis can chemotactically accumulate inflammatory cell to local tissue and regulate the release of inflammatory factors, and SDF-1 has a strong chemotaxis effect on neutrophils with CXCR4. Since CPB animal model was difficult to establish, there was still no report about the effect of SDF-1/CXCR4 on neutrophil chemotaxis in ALI after CPB. Here, a stable CPB rat model was constructed to clarify the role of SDF-1/CXCR4 axis in the CPB-induced ALI. Real-time quantitative PCR (RT-qPCR), Western blot analysis, and enzyme-linked immunosorbent assay (ELISA) were used to detect the changes of SDF-1 and CXCR4 in lung tissues, blood, bronchoalveolar lavage (BALF), and/or isolated neutrophils. SDF-1/CXCR4 was increased after CPB, both of that were increased in blood; CXCR4 was increased in neutrophils; SDF-1/CXCR4 was also increased in BALF of CPB model. Results indicated that SDF-1/CXCR4 axis played a key role in the process of early ALI after CPB, also showed that lung injury was significantly reduce after blocking SDF-1/CXCR4 axis, suggest that CXCR4 might be a new target for ALI treatment.

  19. Cordycepin inhibits LPS-induced acute lung injury by inhibiting inflammation and oxidative stress.

    Science.gov (United States)

    Lei, Jiaji; Wei, Youlei; Song, Pengcheng; Li, Yongchao; Zhang, Tianze; Feng, Qingjiang; Xu, Guangquan

    2018-01-05

    Acute lung injury (ALI) is a common severe clinical syndrome in intensive care unit. Inflammation has been reported to play a critical role in the development of ALI. Cordycepin, an active component isolated from Cordyceps militaris, has been reported to have anti-inflammatory effects. However, the anti-inflammatory effects of cordycepin on LPS-induced ALI remain unclear. Therefore, in the present study, we assessed whether cordycepin could attenuate ALI induced by LPS. The mice were conditioned with cordycepin 1h before intranasal instillation of LPS. Lung wet/dry (W/D) ratio, MPO activity, MDA content, and inflammatory cytokines production were detected. The expression of NF-κB p65, I-κB, Nrf2, and HO-1 were detected by western blot analysis. We found that LPS significantly increased lung wet/dry (W/D) ratio, MPO activity, MDA content, and inflammatory cytokines production. However, the increases were significantly inhibited by treatment of cordycepin. LPS-induced NF-κB activation was also suppressed by cordycepin. In addition, cordycepin was found to up-regulate the expression of Nrf2 and HO-1 in a dose-dependent manner. In conclusion, our results demonstrated that cordycepin could attenuate LPS-induced ALI effectively, probably due to inhibition of inflammation and oxidative stress. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Effects of alliin on LPS-induced acute lung injury by activating PPARγ.

    Science.gov (United States)

    Wang, Yi-Luan; Guo, Xian-Yang; He, Wei; Chen, Ru-Jie; Zhuang, Rong

    2017-09-01

    Alliin is a garlic organosulfur compound that possesses various pharmacological properties. In the present study, the protective effects and molecular mechanism of alliin on Lipopolysaccharides (LPS)-induced acute lung injury (ALI) were analyzed. LPS-induced ALI was induced in BALB/c mice by intranasal instillation of LPS. Alliin was administered intraperitoneally to mice 1 h after LPS treatment. The results showed that alliin markedly inhibited lung myeloperoxidase (MPO) activity and wet/dry (W/D) ratio induced by LPS. Alliin also inhibited TNF-α and IL-1β in the bronchoalveolar lavage fluid (BALF) induced by LPS. Furthermore, LPS-induced lung pathological injury was attenuated by treatment of alliin. LPS-induced NF-κB activation was significantly inhibited by alliin. In addition, the expression of peroxisome proliferator-activated receptor γ (PPARγ) was up-regulated by treatment of alliin. Taken together, these results suggested that alliin protected against LPS-induced ALI by activating PPARγ, which subsequently inhibited LPS-induced NF-κB activation and inflammatory response. Alliin might be used as an anti-inflammatory agent in the treatment of ALI. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Mesenchymal stromal cell treatment prevents H9N2 avian influenza virus-induced acute lung injury in mice.

    Science.gov (United States)

    Li, Yan; Xu, Jun; Shi, Weiqing; Chen, Cheng; Shao, Yan; Zhu, Limei; Lu, Wei; Han, XiaoDong

    2016-10-28

    The avian influenza virus (AIV) can cross species barriers and expand its host range from birds to mammals, even humans. Avian influenza is characterized by pronounced activation of the proinflammatory cytokine cascade, which perpetuates the inflammatory response, leading to persistent systemic inflammatory response syndrome and pulmonary infection in animals and humans. There are currently no specific treatment strategies for avian influenza. We hypothesized that mesenchymal stromal cells (MSCs) would have beneficial effects in the treatment of H9N2 AIV-induced acute lung injury in mice. Six- to 8-week-old C57BL/6 mice were infected intranasally with 1 × 10 4 MID 50 of A/HONG KONG/2108/2003 [H9N2 (HK)] H9N2 virus to induce acute lung injury. After 30 min, syngeneic MSCs were delivered through the caudal vein. Three days after infection, we measured the survival rate, lung weight, arterial blood gas, and cytokines in both bronchoalveolar lavage fluid (BALF) and serum, and assessed pathological changes to the lungs. MSC administration significantly palliated H9N2 AIV-induced pulmonary inflammation by reducing chemokines and proinflammatory cytokines levels, as well as reducing inflammatory cell recruit into the lungs. Thus, H9N2 AIV-induced lung injury was markedly alleviated in mice treated with MSCs. Lung histopathology and arterial blood gas analysis were improved in mice with H9N2 AIV-induced lung injury following MSC treatment. MSC treatment significantly reduces H9N2 AIV-induced acute lung injury in mice and is associated with reduced pulmonary inflammation. These results indicate a potential role for MSC therapy in the treatment of clinical avian influenza.

  2. Lung function in retired coke oven plant workers.

    Science.gov (United States)

    Chau, N; Bertrand, J P; Guenzi, M; Mayer, L; Téculescu, D; Mur, J M; Patris, A; Moulin, J J; Pham, Q T

    1992-01-01

    Lung function was studied in 354 coke oven plant workers in the Lorraine collieries (Houillères du Bassin de Lorraine, France) who retired between 1963 and 1982 and were still alive on 1 January 1988. A spirometric examination was performed on 68.4% of them in the occupational health service. Occupational exposure to respiratory hazards throughout their career was retraced for each subject. No adverse effect of occupational exposure on ventilatory function was found. Ventilatory function was, however negatively linked with smoking and with the presence of a respiratory symptom or discrete abnormalities visible on pulmonary x ray films. The functional values were mostly slightly lower than predicted values and the most reduced index was the mean expiratory flow, FEF25-75%. The decrease in forced expiratory volume in one second (FEV1) was often parallel to that in forced vital capacity (FVC), but it was more pronounced for subjects who had worked underground, for smokers of more than 30 pack-years, and for subjects having a respiratory symptom. Pulmonary function indices were probably overestimated because of the exclusion of deceased subjects and the bias of the participants. PMID:1599869

  3. Activation of TRPV1-dependent calcium oscillation exacerbates seawater inhalation-induced acute lung injury.

    Science.gov (United States)

    Li, Congcong; Bo, Liyan; Liu, Qingqing; Liu, Wei; Chen, Xiangjun; Xu, Dunquan; Jin, Faguang

    2016-03-01

    Calcium is an important second messenger and it is widely recognized that acute lung injury (ALI) is often caused by oscillations of cytosolic free Ca2+. Previous studies have indicated that the activation of transient receptor potential‑vanilloid (TRPV) channels and subsequent Ca2+ entry initiates an acute calcium‑dependent permeability increase during ALI. However, whether seawater exposure induces such an effect through the activation of TRPV channels remains unknown. In the current study, the effect of calcium, a component of seawater, on the inflammatory reactions that occur during seawater drowning‑induced ALI, was examined. The results demonstrated that a high concentration of calcium ions in seawater increased lung tissue myeloperoxidase activity and the secretion of inflammatory mediators, such as tumor necrosis factor‑α (TNF‑α) and interleukin (IL)‑1β and IL‑6. Further study demonstrated that the seawater challenge elevated cytosolic Ca2+ concentration, indicated by [Ca2+]c, by inducing calcium influx from the extracellular medium via TRPV1 channels. The elevated [Ca2+c] may have resulted in the increased release of TNF‑α and IL‑1β via increased phosphorylation of nuclear factor‑κB (NF‑κB). It was concluded that a high concentration of calcium in seawater exacerbated lung injury, and TRPV1 channels were notable mediators of the calcium increase initiated by the seawater challenge. Calcium influx through TRPV1 may have led to greater phosphorylation of NF‑κB and increased release of TNF‑α and IL‑1β.

  4. A cross sectional study on lung functions in athletes, singers, and ...

    African Journals Online (AJOL)

    Physical activity when performed regularly has beneficial effects on the various systems of the body, pulmonary functions inclusive. This study was aimed at determining the effect singing and athletics have on the lung functions as compared to sedentary lifestyle, and whether athletes differ in lung functions from singers in ...

  5. Pulmonary microvascular hyperpermeability and expression of vascular endothelial growth factor in smoke inhalation- and pneumonia-induced acute lung injury.

    Science.gov (United States)

    Lange, Matthias; Hamahata, Atsumori; Traber, Daniel L; Connelly, Rhykka; Nakano, Yoshimitsu; Traber, Lillian D; Schmalstieg, Frank C; Herndon, David N; Enkhbaatar, Perenlei

    2012-11-01

    Acute lung injury (ALI) and sepsis are major contributors to the morbidity and mortality of critically ill patients. The current study was designed further evaluate the mechanism of pulmonary vascular hyperpermeability in sheep with these injuries. Sheep were randomized to a sham-injured control group (n=6) or ALI/sepsis group (n=7). The sheep in the ALI/sepsis group received inhalation injury followed by instillation of Pseudomonas aeruginosa into the lungs. These groups were monitored for 24 h. Additional sheep (n=16) received the injury and lung tissue was harvested at different time points to measure lung wet/dry weight ratio, vascular endothelial growth factor (VEGF) mRNA and protein expression as well as 3-nitrotyrosine protein expression in lung homogenates. The injury induced severe deterioration in pulmonary gas exchange, increases in lung lymph flow and protein content, and lung water content (P<0.01 each). These alterations were associated with elevated lung and plasma nitrite/nitrate concentrations, increased tracheal blood flow, and enhanced VEGF mRNA and protein expression in lung tissue as well as enhanced 3-nitrotyrosine protein expression (P<0.05 each). This study describes the time course of pulmonary microvascular hyperpermeability in a clinical relevant large animal model and may improve the experimental design of future studies. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.

  6. The Nitrated Fatty Acid 10-Nitro-oleate Diminishes Severity of LPS-Induced Acute Lung Injury in Mice

    Directory of Open Access Journals (Sweden)

    Aravind T. Reddy

    2012-01-01

    Full Text Available Acute lung injury (ALI is an inflammatory condition culminating in respiratory failure. There is currently no effective pharmacological treatment. Nitrated fatty acids (NFAs have been shown to exert anti-inflammatory effects. We therefore hypothesized that delivery of NFAs directly to the site of inflammation would reduce the severity of ALI. Pulmonary delivery of 10-nitro-oleate following endotoxin-induced ALI in mice reduced markers of lung inflammation and injury, including capillary leakage, lung edema, infiltration of neutrophils into the lung, and oxidant stress, as well as plasma levels of proinflammatory cytokines. Nitro-oleate delivery likewise downregulated expression of proinflammatory genes by alveolar macrophages, key cells in regulation of lung inflammation. These effects may be accounted for by the observed increases in the activity of PPAR-γ and the PPAR-γ-induced antioxidant transcription factor Nrf2, together with the decreased activity of NF-κB. Our results demonstrate that pulmonary delivery of NFAs reduces severity of acute lung injury and suggest potential utility of these molecules in other inflammatory lung diseases.

  7. Pilates Method for Lung Function and Functional Capacity in Obese Adults.

    Science.gov (United States)

    Niehues, Janaina Rocha; Gonzáles, Inês; Lemos, Robson Rodrigues; Haas, Patrícia

    2015-01-01

    Obesity is defined as the condition in which the body mass index (BMI) is ≥ 30 kg/m2 and is responsible for decreased quality of life and functional limitations. The harmful effects on ventilatory function include reduced lung capacity and volume; diaphragmatic muscle weakness; decreased lung compliance and stiffness; and weakness of the abdominal muscles, among others. Pilates is a method of resistance training that works with low-impact muscle exercises and is based on isometric exercises. The current article is a review of the literature that aims to investigate the hypothesis that the Pilates method, as a complementary method of training, might be beneficial to pulmonary function and functional capacity in obese adults. The intent of the review was to evaluate the use of Pilates as an innovative intervention in the respiratory dysfunctions of obese adults. In studies with other populations, it has been observed that Pilates can be effective in improving chest capacity and expansion and lung volume. That finding is due to the fact that Pilates works through the center of force, made ​​up of the abdominal muscles and gluteus muscles lumbar, which are responsible for the stabilization of the static and dynamic body that is associated with breath control. It has been observed that different Pilates exercises increase the activation and recruitment of the abdominal muscles. Those muscles are important in respiration, both in expiration and inspiration, through the facilitation of diaphragmatic action. In that way, strengthening the abdominal muscles can help improve respiratory function, leading to improvements in lung volume and capacity. The results found in the current literature review support the authors' observations that Pilates promotes the strengthening of the abdominal muscles and that improvements in diaphragmatic function may result in positive outcomes in respiratory function, thereby improving functional capacity. However, the authors did not

  8. Mate tea reduced acute lung inflammation in mice exposed to cigarette smoke.

    Science.gov (United States)

    Lanzetti, Manuella; Bezerra, Frank Silva; Romana-Souza, Bruna; Brando-Lima, Aline Cristina; Koatz, Vera Lúcia Gonçalves; Porto, Luís Cristóvão; Valenca, Samuel Santos

    2008-04-01

    Short-term cigarette smoke exposure has been associated with acute lung inflammation (ALI) and oxidative damage. We studied mate tea (Ilex paraguariensis infusion) as a possible nutritional resource for ALI. C57BL/6 mice (n = 30) were administered with mate tea orally (150 mg/kg, CSMO), mate tea intraperitonially (150 mg/kg, CSMIP), or the vehicle (CS) and then exposed to cigarette smoke for 5 d (six cigarettes per day). The control group was sham-smoked (n = 30). One day after the final exposure, mice were sacrificed. Bronchoalveolar lavages were performed and lungs removed for biochemical (lung homogenates) and histologic analyses. Mate tea reduced the increase of alveolar macrophages and neutrophils in bronchoalveolar lavages (cells x 10(3)/mL) of the CSMO (214.3 +/- 21.4 and 12.2 +/- 4.9) and CSMIP (248.3 +/- 11.1 and 12.1 +/- 2.3) groups compared with the CS group (425.9 +/- 28.1 and 140.5 +/- 20.1). Mate tea reduced lipid peroxidation (the control group was considered 100%) and tumor necrosis factor-alpha (picograms per milliliter) in the CSMO group (61.3 +/- 11.3 and 185.3 +/- 21.8) compared with the CS group (150.0 +/- 18.1 and 242.3 +/- 13.2). Matrix metalloprotease-9 activity was higher in the CS group and lower in the CSMO group. Oxidative and inflammatory markers in the CSMO group were not different from those in the control group. These data imply a potential antioxidant role for mate tea on ALI. Further studies are needed to determine such mechanisms and to explore its potential as an anti-inflammatory and nutritional resource in lung damaged by cigarette smoke exposure.

  9. LPS Induced Acute Lung Injury Involves the NF-κB-mediated Downregulation of SOX18.

    Science.gov (United States)

    Gross, Christine M; Kellner, Manuela; Wang, Ting; Lu, Qing; Sun, Xutong; Zemskov, Evgeny A; Noonepalle, Satish; Kangath, Archana; Kumar, Sanjiv; Gonzalez-Garay, Manuel; Desai, Ankit A; Aggarwal, Saurabh; Gorshkov, Boris; Klinger, Christina; Verin, Alexander D; Catravas, John D; Jacobson, Jeffrey R; Yuan, Jason X-J; Rafikov, Ruslan; Garcia, Joe G N; Black, Stephen M

    2017-11-08

    One of the early events in the progression of lipopolysaccharide (LPS)-mediated acute lung injury (ALI) in mice is the disruption of the pulmonary endothelial barrier resulting in lung edema. However, the molecular mechanisms by which the endothelial barrier becomes compromised remain unresolved. The SRY-related High Mobility Group box (Sox) group-F family member, Sox18, is a barrier- protective protein through its ability to increase the expression of the tight junction protein, Claudin-5. Thus, the purpose of this study was to determine if down-regulation of the Sox18-Claudin-5 axis plays a role in the pulmonary endothelial barrier disruption associated with LPS exposure. Our data indicate that both Sox18 and Claudin-5 expression is decreased in two models of in vivo LPS exposure (intraperitoneal, intratracheal). A similar down-regulation was observed in cultured human lung microvascular endothelial cells (HLMVECs) exposed to LPS. Sox18 over-expression in HLMVECs or in the mouse lung attenuated the LPS-mediated vascular barrier disruption. Conversely, reduced Claudin-5 expression (siRNA) reduced the HLMVEC barrier protective effects of Sox18 over-expression. The mechanism by which LPS decreases Sox18 expression was identified as transcriptional repression through binding of p65 NF-kB to a Sox18 promoter sequence located between -1082 and -1073 bp with peroxynitrite contributing to LPS-mediated NF-kB activation. We conclude that NFkB-dependent decreases in the Sox18-Claudin 5 axis is essentially involved in the disruption of human EC barrier integrity associated with LPS-mediated ALI.

  10. Heme Attenuation Ameliorates Irritant Gas Inhalation-Induced Acute Lung Injury

    Science.gov (United States)

    Aggarwal, Saurabh; Lam, Adam; Bolisetty, Subhashini; Carlisle, Matthew A.; Traylor, Amie; Agarwal, Anupam

    2016-01-01

    Abstract Aims: Exposure to irritant gases, such as bromine (Br2), poses an environmental and occupational hazard that results in severe lung and systemic injury. However, the mechanism(s) of Br2 toxicity and the therapeutic responses required to mitigate lung damage are not known. Previously, it was demonstrated that Br2 upregulates the heme degrading enzyme, heme oxygenase-1 (HO-1). Since heme is a major inducer of HO-1, we determined whether an increase in heme and heme-dependent oxidative injury underlies the pathogenesis of Br2 toxicity. Results: C57BL/6 mice were exposed to Br2 gas (600 ppm, 30 min) and returned to room air. Thirty minutes postexposure, mice were injected intraperitoneally with a single dose of the heme scavenging protein, hemopexin (Hx) (3 μg/gm body weight), or saline. Twenty-four hours postexposure, saline-treated mice had elevated total heme in bronchoalveolar lavage fluid (BALF) and plasma and acute lung injury (ALI) culminating in 80% mortality after 10 days. Hx treatment significantly lowered heme, decreased evidence of ALI (lower protein and inflammatory cells in BALF, lower lung wet-to-dry weight ratios, and decreased airway hyperreactivity to methacholine), and reduced mortality. In addition, Br2 caused more severe ALI and mortality in mice with HO-1 gene deletion (HO-1−/−) compared to wild-type controls, while transgenic mice overexpressing the human HO-1 gene (hHO-1) showed significant protection. Innovation: This is the first study delineating the role of heme in ALI caused by Br2. Conclusion: The data suggest that attenuating heme may prove to be a useful adjuvant therapy to treat patients with ALI. Antioxid. Redox Signal. 24, 99–112. PMID:26376667

  11. Ghrelin ameliorates acute lung injury induced by oleic acid via inhibition of endoplasmic reticulum stress.

    Science.gov (United States)

    Tian, Xiuli; Liu, Zhijun; Yu, Ting; Yang, Haitao; Feng, Linlin

    2018-03-01

    Acute lung injury (ALI) is associated with excessive mortality and lacks appropriate therapy. Ghrelin is a novel peptide that protects the lung against ALI. This study aimed to investigate whether endoplasmic reticulum stress (ERS) mediates the protective effect of ghrelin on ALI. We used a rat oleic acid (OA)-induced ALI model. Pulmonary impairment was detected by hematoxylin and eosin (HE) staining, lung mechanics, wet/dry weight ratio, and arterial blood gas analysis. Plasma and lung content of ghrelin was examined by ELISA, and mRNA expression was measured by quantitative real-time PCR. Protein levels were detected by western blot. Rats with OA treatment showed significant pulmonary injury, edema, inflammatory cellular infiltration, cytokine release, hypoxia and CO 2 retention as compared with controls. Plasma and pulmonary content of ghrelin was reduced in rats with ALI, and mRNA expression was downregulated. Ghrelin (10nmol/kg) treatment ameliorated the above symptoms, but treatment with the ghrelin antagonists D-Lys 3 GHRP-6 (1μmol/kg) and JMV 2959 (6mg/kg) exacerbated the symptoms. ERS induced by OA was prevented by ghrelin and augmented by ghrelin antagonist treatment. The ERS inducer, tunicamycin (Tm) prevented the ameliorative effect of ghrelin on ALI. The decreased ratio of p-Akt and Akt induced by OA was improved by ghrelin treatment, and was further exacerbated by ghrelin antagonists. Ghrelin protects against ALI by inhibiting ERS. These results provide a new target for prevention and therapy of ALI. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Identification of distinct genes associated with seawater aspiration-induced acute lung injury by gene expression profile analysis

    Science.gov (United States)

    Liu, Wei; Pan, Lei; Zhang, Minlong; Bo, Liyan; Li, Congcong; Liu, Qingqing; Wang, Li; Jin, Faguang

    2016-01-01

    Seawater aspiration-induced acute lung injury (ALI) is a syndrome associated with a high mortality rate, which is characterized by severe hypoxemia, pulmonary edema and inflammation. The present study is the first, to the best of our knowledge, to analyze gene expression profiles from a rat model of seawater aspiration-induced ALI. Adult male Sprague-Dawley rats were instilled with seawater (4 ml/kg) in the seawater aspiration-induced ALI group (S group) or with distilled water (4 ml/kg) in the distilled water negative control group (D group). In the blank control group (C group) the rats' tracheae were exposed without instillation. Subsequently, lung samples were examined by histopathology; total protein concentration was detected in bronchoalveolar lavage fluid (BALF); lung wet/dry weight ratios were determined; and transcript expression was detected by gene sequencing analysis. The results demonstrated that histopathological alterations, pulmonary edema and total protein concentrations in BALF were increased in the S group compared with in the D group. Analysis of differential gene expression identified up and downregulated genes in the S group compared with in the D and C groups. A gene ontology analysis of the differential gene expression revealed enrichment of genes in the functional pathways associated with neutrophil chemotaxis, immune and defense responses, and cytokine activity. Kyoto Encyclopedia of Genes and Genomes analysis revealed that the cytokine-cytokine receptor interaction pathway was one of the most important pathways involved in seawater aspiration-induced ALI. In conclusion, activation of the cytokine-cytokine receptor interaction pathway may have an essential role in the progression of seawater aspiration-induced ALI, and the downregulation of tumor necrosis factor superfamily member 10 may enhance inflammation. Furthermore, IL-6 may be considered a biomarker in seawater aspiration-induced ALI. PMID:27509884

  13. A risk score to predict acute renal failure in adult patients after lung transplantation.

    Science.gov (United States)

    Grimm, Joshua C; Lui, Cecillia; Kilic, Arman; Valero, Vicente; Sciortino, Christopher M; Whitman, Glenn J R; Shah, Ashish S

    2015-01-01

    Despite the significant morbidity associated with renal failure after lung transplantation (LTx), no predictive models currently exist. Accordingly, the purpose of this study was to develop a preoperative risk score based on recipient-, donor-, and transplant-specific characteristics to predict postoperative acute renal failure in candidates for transplantation. The United Network of Organ Sharing (UNOS) database was queried for adult patients (≥ 18 years of age) undergoing LTx between 2005 and 2012. The population was randomly divided into derivation (80%) and validation (20%) cohorts. The primary outcome of interest was new-onset renal failure. Variables predictive of acute renal failure (exploratory p value renal failure to construct the risk stratification score (RSS). During the study period, 10,963 patients underwent lung transplantation, and the incidence of renal failure was 5.5% (598 patients). Baseline recipient-, donor-, and transplant-related factors were similar between the cohorts. Eighteen covariates were included in the multivariable model, and 10 were assigned values based on their relative odds ratios (ORs). Scores were stratified into 3 groups, with an observed rate of acute renal failure of 3.1%, 5.3%, and 15.6% in the low-, moderate-, and high-risk groups, respectively. The incidence of renal failure was found to be significantly increased in the highest risk group (p renal failure highly correlated with actual rates observed in the population (r = 0.86). We introduce a novel and simple RSS that is highly predictive of renal failure after LTx. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  14. Acute effect of a physical exercise session on cognitive functioning ...

    African Journals Online (AJOL)

    Acute effect of a physical exercise session on cognitive functioning: Moderately active sportspersons versus sedentary individuals. Karel J. Van Deventer, Carynne Cozens, Kyle D. Du Plessis, Reghard P. La Grange ...

  15. A longitudinal study of lung function in jute processing workers.

    Science.gov (United States)

    Liu, Z; Zhou, C; Lou, J

    1992-01-01

    A 5-y follow-up study of pulmonary function was conducted in 1982 and in 1987 for 50 current and retired jute-processing workers who had been employed for more than 10 y in a jute mill in China. Control subjects, who had no history of dust or gas exposure, were selected from a paper-packing plant in the same city. Forced expiratory maneuvers were conducted in the same manner in both 1982 and 1987. The jute workers' pulmonary functions, i.e., forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1.0), and forced expiratory flow (FEF25-75%), were more compromised than were pulmonary functions in the controls for the same 5-y period; however, only the increased incidence of abnormal FEV1.0s in jute workers was statistically significant. Male jute workers had significantly higher annual decrements of FVC, FEV1.0, and FEF25-75% than did control workers. Regression analysis indicated that in 1987, predicted values of FEV1.0 and FEF25-75% for the jute workers were related to years of employment. Our results suggest that long-term exposure to jute dust could produce chronic loss of lung function.

  16. Socioeconomic status, lung function and admission to hospital for COPD

    DEFF Research Database (Denmark)

    Prescott, E; Lange, P; Vestbo, J

    1999-01-01

    . Association between socioeconomic factors and forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) at study entry was analysed by linear regression. The relation between socioeconomic factors and risk of admission to hospital for COPD from study entry until 1993 was assessed...... and duration of smoking and inhalation, the difference was 220+/-31 mL and 363+/-39 mL in females and males, respectively. Results for FVC were of the same magnitude. Using a socioeconomic index which combined information on education and household income the association with lung function did not differ...... by age. A total of 219 females and 265 males were admitted to hospital for COPD during follow-up. Education and income were significantly associated with admission to hospital. After detailed adjustment for smoking the relative risks (95% confidence intervals) for medium and high versus low socioeconomic...

  17. Socioeconomic status, lung function and admission to hospital for COPD

    DEFF Research Database (Denmark)

    Prescott, E; Lange, P; Vestbo, J

    1999-01-01

    This study analysed the effect of education and income on development of chronic obstructive pulmonary disease (COPD) assessing lung function and hospital admission. The study population consisted of 14,223 subjects, aged 20-90 yrs, randomly sampled from the population of Copenhagen in 1976...... index in females were 0.74 (0.55-1.02) and 0.27 (0.10-0.73), respectively. Corresponding relative risks in males were 0.47 (0.36-0.63) and 0.35 (0.17-0.70). The results indicate that socioeconomic factors operating from early in life affect the adult risk of developing chronic obstructive pulmonary....... Association between socioeconomic factors and forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) at study entry was analysed by linear regression. The relation between socioeconomic factors and risk of admission to hospital for COPD from study entry until 1993 was assessed...

  18. Persistent Chlamydia Pneumoniae serology is related to decline in lung function in women but not in men. Effect of persistent Chlamydia pneumoniae infection on lung function

    Directory of Open Access Journals (Sweden)

    Gislason Thorarinn

    2010-08-01

    Full Text Available Abstract Background Chlamydia pneumoniae (C pn infection causes an acute inflammation in the respiratory system that may become persistent, but little is known about the long-term respiratory effects of C pn infections. Aim: To estimate the long term respiratory effects of C pn with change in forced expiratory volume in one second (FEV1 and forced vital capacity (FVC as a main outcome variable. Methods The study comprised of 1109 subjects (500 men and 609 women, mean age 28 ± 6 years that participated in the Reykjavik Heart Study of the Young. Spirometry and blood samples for measurements of IgG antibodies for C pn were done at inclusion and at the end of the follow-up period (mean follow-up time 27 ± 4 years. Results Having IgG against C pn at both examinations was significantly associated to a larger decrease in FEV1 (6 mL/year and FVC (7 mL/year in women but not in men. In women the association between C pn and larger FEV1 decline was only found in women that smoked at baseline where having C pn IgG was associated with 10 mL/year decline compared to smokers without C pn IgG. These results were still significant after adjustment for age, smoking and change in body weight. Conclusion Our results indicate that persistent C pn serology is related to increased decline in lung function in women but not in men. This effect was, however, primarily found in smoking women. This study is a further indication that the pathophysiological process leading to lung impairment may differ between men and women.

  19. Synthetic surfactant containing SP-B and SP-C mimics is superior to single-peptide formulations in rabbits with chemical acute lung injury

    Directory of Open Access Journals (Sweden)

    Frans J. Walther

    2014-05-01

    Full Text Available Background. Chemical spills are on the rise and inhalation of toxic chemicals may induce chemical acute lung injury (ALI/acute respiratory distress syndrome (ARDS. Although the pathophysiology of ALI/ARDS is well understood, the absence of specific antidotes has limited the effectiveness of therapeutic interventions.Objectives. Surfactant inactivation and formation of free radicals are important pathways in (chemical ALI. We tested the potential of lipid mixtures with advanced surfactant protein B and C (SP-B and C mimics to improve oxygenation and lung compliance in rabbits with lavage- and chemical-induced ALI/ARDS.Methods. Ventilated young adult rabbits underwent repeated saline lung lavages or underwent intratracheal instillation of hydrochloric acid to induce ALI/ARDS. After establishment of respiratory failure rabbits were treated with a single intratracheal dose of 100 mg/kg of synthetic surfactant composed of 3% Super Mini-B (S-MB, a SP-B mimic, and/or SP-C33 UCLA, a SP-C mimic, in a lipid mixture (DPPC:POPC:POPG 5:3:2 by weight, the clinical surfactant Infasurf®, a bovine lung lavage extract with SP-B and C, or synthetic lipids alone. End-points consisted of arterial oxygenation, dynamic lung compliance, and protein and lipid content in bronchoalveolar lavage fluid. Potential mechanism of surfactant action for S-MB and SP-C33 UCLA were investigated with captive bubble surfactometry (CBS assays.Results. All three surfactant peptide/lipid mixtures and Infasurf equally lowered the minimum surface tension on CBS, and also improved oxygenation and lung compliance. In both animal models, the two-peptide synthetic surfactant with S-MB and SP-C33 UCLA led to better arterial oxygenation and lung compliance than single peptide synthetic surfactants and Infasurf. Synthetic surfactants and Infasurf improved lung function further in lavage- than in chemical-induced respiratory failure, with the difference probably due to greater capillary

  20. Functional genomics highlights differential induction of antiviral pathways in the lungs of SARS-CoV-infected macaques.

    Directory of Open Access Journals (Sweden)

    Anna de Lang

    2007-08-01

    Full Text Available The pathogenesis of severe acute respiratory syndrome coronavirus (SARS-CoV is likely mediated by disproportional immune responses and the ability of the virus to circumvent innate immunity. Using functional genomics, we analyzed early host responses to SARS-CoV infection in the lungs of adolescent cynomolgus macaques (Macaca fascicularis that show lung pathology similar to that observed in human adults with SARS. Analysis of gene signatures revealed induction of a strong innate immune response characterized by the stimulation of various cytokine and chemokine genes, including interleukin (IL-6, IL-8, and IP-10, which corresponds to the host response seen in acute respiratory distress syndrome. As opposed to many in vitro experiments, SARS-CoV induced a wide range of type I interferons (IFNs and nuclear translocation of phosphorylated signal transducer and activator of transcription 1 in the lungs of macaques. Using immunohistochemistry, we revealed that these antiviral signaling pathways were differentially regulated in distinctive subsets of cells. Our studies emphasize that the induction of early IFN signaling may be critical to confer protection against SARS-CoV infection and highlight the strength of combining functional genomics with immunohistochemistry to further unravel the pathogenesis of SARS.

  1. Ultrasound lung comets for the differential diagnosis of acute cardiogenic dyspnoea: a comparison with natriuretic peptides.

    Science.gov (United States)

    Gargani, L; Frassi, F; Soldati, G; Tesorio, P; Gheorghiade, M; Picano, E

    2008-01-01

    Acute dyspnoea as a presenting symptom is a frequent diagnostic challenge for physicians. The main differential diagnosis is between dyspnoea of cardiac and non-cardiac origin. Natriuretic peptides have been shown to be useful in this setting. Ultrasound lung comets (ULCs) are a simple, echographic method which can be used to assess pulmonary congestion. To evaluate the accuracy of ULCs for predicting dyspnoea of cardiac origin compared to natriuretic peptides. We evaluated 149 patients admitted with acute dyspnoea. Chest sonography and NT-proBNP assessments were performed a maximum of 4 h apart and independently analyzed. ULCs were evaluated via cardiac probes placed on the anterior and lateral chest. Two independent physicians, blinded to ULCs and NT-proBNP findings, reviewed all the medical records to establish the aetiologic diagnosis of dyspnoea. Cardiogenic dyspnoea was confirmed in 122 patients and ruled-out in 27 patients. The number of ULCs was significantly correlated to NT-proBNP values (r=.69, p<.0001). Receiver operating characteristic analysis, showed an area under the curve of .893 for ULCs and .978 (p=.001) for NT-proBNP, in predicting the cardiac origin of dyspnoea. In patients admitted with acute dyspnoea, pulmonary congestion, sonographically imaged as ULCs, is significantly correlated to NT-proBNP values. The accuracy of ULCs in predicting the cardiac origin of dyspnoea is high.

  2. Angiotensin II type 2 receptor agonist Compound 21 attenuates pulmonary inflammation in a model of acute lung injury

    Directory of Open Access Journals (Sweden)

    Menk M

    2018-05-01

    Full Text Available Mario Menk, Jan Adriaan Graw, Clarissa von Haefen, Hendrik Steinkraus, Burkhard Lachmann, Claudia D Spies, David Schwaiberger Department of Anesthesiology and Operative Intensive Care Medicine, Charité – University Medicine Berlin, FreieUniversität Berlin, Humboldt-Universitätzu Berlin, and Berlin Institute of Health, Germany Purpose: Although the role of the angiotensin II type 2 (AT2 receptor in acute lung injury is not yet completely understood, a protective role of this receptor subtype has been suggested. We hypothesized that, in a rodent model of acute lung injury, stimulation of the AT2 receptor with the direct agonist Compound 21 (C21 might have a beneficial effect on pulmonary inflammation and might improve pulmonary gas exchange. Materials and methods: Male adult rats were divided into a treatment group that received pulmonary lavage followed by mechanical ventilation (LAV, n=9, a group receiving pulmonary lavage, mechanical ventilation, and direct stimulation of the AT2 receptor with C21 (LAV+C21, n=9, and a control group that received mechanical ventilation only (control, n=9. Arterial blood gas analysis was performed every 30 min throughout the 240-min observation period. Lung tissue and plasma samples were obtained at 240 min after the start of mechanical ventilation. Protein content and surface activity of bronchoalveolar lavage fluid were assessed and the wet/dry-weight ratio of lungs was determined. Transcriptional and translational regulation of pro- and antiinflammatory cytokines IL-1β, tumor necrosis factor-alpha, IL-6, IL-10, and IL-4 was determined in lungs and in plasma. Results: Pulmonary lavage led to a significant impairment of gas exchange, the formation of lung edema, and the induction of pulmonary inflammation. Protein content of lavage fluid was increased and contained washed-out surfactant. Direct AT2 receptor stimulation with C21 led to a significant inhibition of tumor necrosis factor-alpha and IL-6

  3. Attenuation of acute nitrogen mustard-induced lung injury, inflammation and fibrogenesis by a nitric oxide synthase inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    Malaviya, Rama; Venosa, Alessandro [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Hall, LeRoy [Drug Safety Sciences, Johnson and Johnson, Raritan, NJ 08869 (United States); Gow, Andrew J. [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Sinko, Patrick J. [Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Laskin, Jeffrey D. [Department of Environmental and Occupational Medicine, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 08854 (United States); Laskin, Debra L., E-mail: laskin@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States)

    2012-12-15

    Nitrogen mustard (NM) is a toxic vesicant known to cause damage to the respiratory tract. Injury is associated with increased expression of inducible nitric oxide synthase (iNOS). In these studies we analyzed the effects of transient inhibition of iNOS using aminoguanidine (AG) on NM-induced pulmonary toxicity. Rats were treated intratracheally with 0.125 mg/kg NM or control. Bronchoalveolar lavage fluid (BAL) and lung tissue were collected 1 d–28 d later and lung injury, oxidative stress and fibrosis assessed. NM exposure resulted in progressive histopathological changes in the lung including multifocal lesions, perivascular and peribronchial edema, inflammatory cell accumulation, alveolar fibrin deposition, bronchiolization of alveolar septal walls, and fibrosis. This was correlated with trichrome staining and expression of proliferating cell nuclear antigen (PCNA). Expression of heme oxygenase (HO)-1 and manganese superoxide dismutase (Mn-SOD) was also increased in the lung following NM exposure, along with levels of protein and inflammatory cells in BAL, consistent with oxidative stress and alveolar-epithelial injury. Both classically activated proinflammatory (iNOS{sup +} and cyclooxygenase-2{sup +}) and alternatively activated profibrotic (YM-1{sup +} and galectin-3{sup +}) macrophages appeared in the lung following NM administration; this was evident within 1 d, and persisted for 28 d. AG administration (50 mg/kg, 2 ×/day, 1 d–3 d) abrogated NM-induced injury, oxidative stress and inflammation at 1 d and 3 d post exposure, with no effects at 7 d or 28 d. These findings indicate that nitric oxide generated via iNOS contributes to acute NM-induced lung toxicity, however, transient inhibition of iNOS is not sufficient to protect against pulmonary fibrosis. -- Highlights: ► Nitrogen mustard (NM) induces acute lung injury and fibrosis. ► Pulmonary toxicity is associated with increased expression of iNOS. ► Transient inhibition of iNOS attenuates acute

  4. Acute and repeated inhalation lung injury by 3-methoxybutyl chloroformate in rats: CT-pathologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Yeon Soo [Department of Radiology, Holy Family Hospital, College of Medicine, Catholic University of Korea, 2, Sosa-dong, Wonmi-gu, Pucheon, Kyung gi-do 420-717 (Korea, Republic of); Chung, Myung Hee [Department of Radiology, Holy Family Hospital, College of Medicine, Catholic University of Korea, 2, Sosa-dong, Wonmi-gu, Pucheon, Kyung gi-do 420-717 (Korea, Republic of)]. E-mail: mhchung@catholic.ac.kr; Park, Seog Hee [Department of Radiology, Kangnam St. Mary Hospital, Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-040 (Korea, Republic of); Kim, Hyeon-Yeong [Industrial Chemicals Research Center, Industrial Safety and Health Research Institute KISCO, 104-8, Moonji-dong, Yusong-gu, Taejon-si 305-380 (Korea, Republic of); Choi, Byung Gil [Department of Radiology, Kangnam St. Mary Hospital, Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-040 (Korea, Republic of); Lim, Hyun Wook [Department of Radiology, Holy Family Hospital, College of Medicine, Catholic University of Korea, 2, Sosa-dong, Wonmi-gu, Pucheon, Kyung gi-do 420-717 (Korea, Republic of); Kim, Jin Ah [Department of Pathology, Holy Family Hospital, Catholic University of Korea, 2, Sosa-dong, Wonmi-gu, Pucheon-si, Kyung gi-do 420-717 (Korea, Republic of); Yoo, Won Jong [Department of Radiology, Holy Family Hospital, College of Medicine, Catholic University of Korea, 2, Sosa-dong, Wonmi-gu, Pucheon, Kyung gi-do 420-717 (Korea, Republic of)

    2007-05-15

    Objectives: To investigate the acute and repeated pulmonary damage in Sprague-Dawley rats caused by the inhalation of 3-methoxybutyl chloroformate (3-MBCF) using computed tomography (CT), and to correlate these results with those obtained from a pathological study. Methods: Sixty, 7-week-old rats were exposed to 3-MBCF vapor via inhalation (6 h/day) for 1 day (N = 20), 3 days (N = 20), and 28 days (5 days/week) (N = 20) using whole body exposure chambers at a concentration of 0 (control), 3, 6 and 12 ppm. CT examinations including densitometry and histopathologic studies were carried out. For the follow-up study, the rats exposed for 3 days were scanned using CT and their pathology was examined at 7, 14, and 28 days. Results: There was a significant decrease in the parenchymal density in the groups exposed to the 3-MBCF vapors for 1 day at 3 ppm (p = 0.022) or 6 ppm (p = 0.010), compared with the control. The parenchymal density of the rats exposed to12 ppm was significantly higher. The pathological findings in this period, the grades of vascular congestion, tracheobronchial exfoliation, and alveolar rupture were significant. In the groups exposed for 3 days, there was a large decrease in the parenchymal density with increasing dose (control: -675.48 {+-} 32.82 HU, 3 ppm: -720.65 {+-} 34.21 HU, 6 ppm: -756.41 {+-} 41.68 HU, 12 ppm: -812.56 {+-} 53.48 HU) (p = 0.000). There were significant density differences between each dose in the groups exposed for 28 days (p = 0.000). The CT findings include an irregular lung surface, areas of multifocal, wedge-shaped increased density, a heterogeneous lung density, bronchial dilatation, and axial peribronchovascular bundle thickening. The histopathology examination revealed the development of alveolar interstitial thickening and vasculitis, and an aggravation of the mainstem bronchial exudates and bronchial inflammation. The alveolar wall ruptures and bronchial dilatation became severe during this period. On the follow

  5. Acute subdural hematoma, Head injury, Functional reco

    African Journals Online (AJOL)

    kim

    Results. A total of 259 patients were diagnosed with acute subdural hematomas during the study period. The mean age was 41.1 years + 19.659 and 223 (86.1%) were men while 36 (13.9%) were women. The most common cause of injury was assault (44.8%) with road traffic and falls accounting for 24.7% and 30.5%.

  6. Proteasome function is not impaired in healthy aging of the lung.

    Science.gov (United States)

    Caniard, Anne; Ballweg, Korbinian; Lukas, Christina; Yildirim, Ali Ö; Eickelberg, Oliver; Meiners, Silke

    2015-10-01

    Aging is the progressive loss of cellular function which inevitably leads to death. Failure of proteostasis including the decrease in proteasome function is one hallmark of aging. In the lung, proteasome activity was shown to be impaired in age-related diseases such as chronic obstructive pulmonary disease. However, little is known on proteasome function during healthy aging. Here, we comprehensively analyzed healthy lung aging and proteasome function in wildtype, proteasome reporter and immunoproteasome knockout mice. Wildtype mice spontaneously developed senile lung emphysema while expression and activity of proteasome complexes and turnover of ubiquitinated substrates was not grossly altered in lungs of aged mice. Immunoproteasome subunits were specifically upregulated in the aged lung and the caspase-like proteasome activity concomitantly decreased. Aged knockout mice for the LMP2 or LMP7 immunoproteasome subunits showed no alteration in proteasome activities but exhibited typical lung aging phenotypes suggesting that immunoproteasome function is dispensable for physiological lung aging in mice. Our results indicate that healthy aging of the lung does not involve impairment of proteasome function. Apparently, the reserve capacity of the proteostasis systems in the lung is sufficient to avoid severe proteostasis imbalance during healthy aging.

  7. Lung function and bronchial responsiveness after Mycoplasma pneumoniae infection in early childhood

    DEFF Research Database (Denmark)

    Boysen, Birgitte Kjær; Jensen, Jørgen S; Nielsen, Kim G

    2008-01-01

    by whole-body plethysmography and bronchial hyperresponsiveness was assessed by cold, dry air hyperventilation. Neither baseline lung function nor bronchial response to cold dry air hyperventilation differed between M. pneumoniae-positive and -negative children: mean baseline lung function were 1.17 versus...

  8. CT-quantified emphysema distribution is associated with lung function decline

    NARCIS (Netherlands)

    Hoesein, F.A.A.M.; Rikxoort, E.M. van; Ginneken, B. van; de Jong, P. A.; Prokop, M.; Lammers, J.W.; Zanen, P.

    2012-01-01

    Emphysema distribution is associated with COPD. It is however unknown whether CT-quantified emphysema distribution (upper/lower lobe) is associated with lung function decline in heavy (former) smokers.587 male participants underwent lung CT-scanning and pulmonary function testing at baseline and

  9. Lung split function test and pneumonectomy. A lower limit for operability

    DEFF Research Database (Denmark)

    Tønnesen, K H; Dige-Petersen, H; Lund, J O

    1978-01-01

    Regional 133Xe ventilation/perfusion studies were used to predict residual lung function after pulmonary resections. The accuracy of the method was good as checked by postoperative spirometry in 11 patients. In 25 patients with impaired lung function and pulmonary cancer, who were consecutively...

  10. Air Pollution Exposure and Lung Function in Children : The ESCAPE Project

    NARCIS (Netherlands)

    Gehring, Ulrike; Gruzieva, Olena; Agius, Raymond M.; Beelen, Rob; Custovic, Adnan; Cyrys, Josef; Eeftens, Marloes; Flexeder, Claudia; Fuertes, Elaine; Heinrich, Joachim; Hoffmann, Barbara; de Jongste, Johan C.; Kerkhof, Marjan; Kluemper, Claudia; Korek, Michal; Moelter, Anna; Schultz, Erica S.; Simpson, Angela; Sugiri, Dorothea; Svartengren, Magnus; von Berg, Andrea; Wijga, Alet H.; Pershagen, Goeran; Brunekreef, Bert

    2013-01-01

    BACKGROUND: There is evidence for adverse effects of outdoor air pollution on lung function of children. Quantitative summaries of the effects of air pollution on lung function, however, are lacking due to large differences among studies. OBJECTIVES: We aimed to study the association between

  11. The practice of reporting transfusion-related acute lung injury: a national survey among clinical and preclinical disciplines

    NARCIS (Netherlands)

    Vlaar, Alexander P.; Wortel, Kim; Binnekade, Jan M.; van Oers, Marinus H. J.; Beckers, Erik; Gajic, Ognjen; Schultz, Marcus J.; Juffermans, Nicole P.

    2010-01-01

    BACKGROUND: Transfusion-related acute lung injury (TRALI) is hypothesized to be a "two-hit" entity, in which an inflammatory condition (e. g., sepsis) predisposes to TRALI. TRALI is a clinical diagnosis. Disciplines involved in managing TRALI may differ in decision-making on the reporting of TRALI.

  12. Role of CC chemokines (macrophage inflammatory protein-1 beta, monocyte chemoattractant protein-1, RANTES) in acute lung injury in rats

    DEFF Research Database (Denmark)

    Bless, N M; Huber-Lang, M; Guo, R F

    2000-01-01

    The role of the CC chemokines, macrophage inflammatory protein-1 beta (MIP-1 beta), monocyte chemotactic peptide-1 (MCP-1), and RANTES, in acute lung inflammatory injury induced by intrapulmonary deposition of IgG immune complexes injury in rats was determined. Rat MIP-1 beta, MCP-1, and RANTES w...

  13. Prevention of Non-immune Mediated Transfusion-related Acute Lung Injury; from Blood Bank to Patient

    NARCIS (Netherlands)

    van Bruggen, Robin; de Korte, Dirk

    2012-01-01

    Transfusion-related acute lung injury (TRALI) is a severe form of pulmonary insufficiency induced by transfusion. TRALI is the leading cause of transfusion-related death, and is caused by the infusion of either anti-leukocyte antibodies in plasma containing blood products or neutrophil priming

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

    Directory of Open Access Journals (Sweden)

    Dongdong Liu

    2014-01-01

    Full Text Available 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.

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

    International Nuclear Information System (INIS)

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

    2013-01-01

    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 2 > 0.95). After exposure to hyperoxia, lung injury, levels of 8-iso-prostaglandin F 2 alpha (8-iso-PGF 2α) (LC–MS/MS), apoptosis (TUNEL) and inflammatory markers (suspension bead array) were determined. Cytochrome P450 (CYP)1A expression in the lung was assessed using immunohistochemistry and western blotting. After exposure to hyperoxia, males showed greater lung injury, neutrophil infiltration and apoptosis, compared to air-breathing controls than females. Pulmonary 8-iso-PGF 2α levels were higher in males than females after hyperoxia exposure. Sexually dimorphic increases in levels of IL-6 (F > M) and VEGF (M > F) in the lungs were also observed. CYP1A1 expression in the lung was higher in female mice compared to males under hyperoxic conditions. Overall, our results support the hypothesis that male mice are more susceptible than females to hyperoxic lung injury and that differences in inflammatory and oxidative stress markers contribute to these sex-specific dimorphic effects. In conclusion, this paper describes the establishment of an animal model that shows sex differences in hyperoxic lung injury in a temporal manner and thus has important implications for lung diseases mediated by hyperoxia in humans. - Highlights: • Male mice were more susceptible to hyperoxic lung injury than females. • Sex differences in inflammatory markers were observed. • CYP1A expression was higher in females after hyperoxia exposure

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-10-15

    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.

  17. Interaction of dependent and non-dependent regions of the acutely injured lung during a stepwise recruitment manoeuvre.

    Science.gov (United States)

    Gómez-Laberge, Camille; Rettig, Jordan S; Smallwood, Craig D; Boyd, Theonia K; Arnold, John H; Wolf, Gerhard K

    2013-02-01

    The benefit of treating acute lung injury with recruitment manoeuvres is controversial. An impediment to settling this debate is the difficulty in visualizing how distinct lung regions respond to the manoeuvre. Here, regional lung mechanics were studied by electrical impedance tomography (EIT) during a stepwise recruitment manoeuvre in a porcine model with acute lung injury. The following interaction between dependent and non-dependent regions consistently occurred: atelectasis in the most dependent region was reversed only after the non-dependent region became overdistended. EIT estimates of overdistension and atelectasis were validated by histological examination of lung tissue, confirming that the dependent region was primarily atelectatic and the non-dependent region was primarily overdistended. The pulmonary pressure-volume equation, originally designed for modelling measurements at the airway opening, was adapted for EIT-based regional estimates of overdistension and atelectasis. The adaptation accurately modelled the regional EIT data from dependent and non-dependent regions (R(2) > 0.93, P < 0.0001) and predicted their interaction during recruitment. In conclusion, EIT imaging of regional lung mechanics reveals that overdistension in the non-dependent region precedes atelectasis reversal in the dependent region during a stepwise recruitment manoeuvre.

  18. A plethysmographic method for measuring function in locally irradiated mouse lung

    International Nuclear Information System (INIS)

    Travis, E.L.; Vojnovic, B.; Hirst, D.G.; Davies, E.E.

    1979-01-01

    A plethysmograph has been developed to measure pulmonary function in mice after single doses of X rays to both lungs. The apparatus consists of a whole-body airtight chamber fitted with a Lavalier microphone. The microphone acts as a sensitive electrical capacitance manometer converting pressure changes in the chamber into an electrical signal which is electronically processed and recorded on a pen recorder. Two parameters of lung function were simultaneously monitored, breathing rate and amplitude. Lung function has been tested in male CBA mice aged two to six months and in animals which have received graded X-ray doses to both lungs. No diurnal rhythm or age-related increase has been observed up to six months in control mice. The two lung-function parameters exhibited a dose-dependent response in irradiated lungs tested 16 weeks after irradiation; the response was reproducible in successive experiments. Respiration rate was increased above a threshold dose of 11 Gy (1100 rad), while amplitude decreased, also with a threshold at 11 Gy. These changes were observed before hisotological evidence of fibrosis became apparent and before pulmonary insufficiency led to deaths in the higher dose groups. The measurement of lung function by plethysmography is an alternative to lethality for assessing radiation damage in the lungs of small animals. The technique is non-destructive, responding to lower doses than LD 50 , and allows quantitative assessment of sequential changes in the lungs in each mouse over long post-irradiation times. (author)

  19. Transfusion-related acute lung injury: a dangerous and underdiagnosed noncardiogenic pulmonary edema.

    Science.gov (United States)

    Jaworski, Krzysztof; Maślanka, Krystyna; Kosior, Dariusz A

    2013-01-01

    Transfusion-related acute lung injury (TRALI) is one of the leading causes of death associated with transfusion of blood and blood components. The understanding of the etiology and pathophysiology of this syndrome has much improved during the last decades, nevertheless numerous issues are still unresolved and symptomatic treatment remains the cornerstone of medical management. Consequently more attention is directed at primary as well as secondary prevention. The awareness of the problem within the medical society is still unsatisfactory which results in a high number of unrecognized cases or of inaccurate diagnoses one of which is cardiogenic pulmonary edema. The aim of this review is to make the TRALI syndrome more familiar to clinicians and to emphasize how significant proper medical management is both for the patients presenting TRALI symptoms as well as for future recipients of blood components.

  20. The acute in vitro and in vivo radiosensitivity of human lung tumour lines

    International Nuclear Information System (INIS)

    Duchesne, G.M.; Peacock, J.H.; Steel, G.G.

    1986-01-01

    Eleven human lung tumour lines have been established in xenograft or tissue culture, and the responses to acute irradiation of the 10 lines which cloned in soft agar were assayed. In vitro radiosensitivity was evaluated using the multitarget and linear quadratic models of cell survival and the surviving fraction at 2 Gy. Significant differences in the response of the different cell types were found, the large-cell phenotype exhibiting radioresistance, and small-cell carcinomas and adenocarcinomas being radiosensitive. No differences in the capacity of the different tumour types to repair radiation damage were demonstrated. In vivo and spheroid response was modified by the effects of hypoxia and cell-contact phenomena. The results suggested that hyperfractionation would be useful in the clinical management of adenocarcinoma and small-cell carcinoma. (Auth.)

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

    Directory of Open Access Journals (Sweden)

    Olivia Meira Dias

    2014-01-01

    Full Text Available 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.

  2. Longitudinal study of lung function in a cohort of primary ciliary dyskinesia

    DEFF Research Database (Denmark)

    Ellerman, A; Bisgaard, H

    1997-01-01

    Patients with primary ciliary dyskinesia (PCD) have pronounced stasis of their respiratory secretions and therefore recurrent lower airway infections, which raises concerns for the development of lung function. Twenty four patients with PCD have been studied prospectively with a standardized regime...... in our clinic for 2-16 yrs with clinic visits, including spirometry 2-4 times per year, daily physiotherapy and monthly sputum cultures with subsequent specific antibiotic treatment. Lung function was significantly lower in the 12 PCD patients entering the cohort as adults when compared to the PCD......, respectively, the lung function remained stable in most patients. It is concluded that primary ciliary dyskinesia is accompanied by a progressive deterioration in lung function if undertreated, but lung function can be maintained with appropriate antibiotic treatment and regular physiotherapy. This emphasizes...

  3. Lung function not affected by asbestos exposure in workers with normal Computed Tomography scan.

    Science.gov (United States)

    Schikowsky, Christian; Felten, Michael K; Eisenhawer, Christian; Das, Marco; Kraus, Thomas

    2017-05-01

    It has been suggested that asbestos exposure affects lung function, even in the absence of asbestos-related pulmonary interstitial or pleural changes or emphysema. We analyzed associations between well-known asbestos-related risk factors, such as individual cumulative asbestos exposure, and key lung function parameters in formerly asbestos-exposed power industry workers (N = 207) with normal CT scans. For this, we excluded participants with emphysema, fibrosis, pleural changes, or any combination of these. The lung function parameters of FVC, FEV1, DLCO/VA, and airway resistance were significantly associated with the burden of smoking, BMI and years since end of exposure (only DLCO/VA). However, they were not affected by factors directly related to amount (eg, cumulative exposure) or duration of asbestos exposure. Our results confirm the well-known correlation between lung function, smoking habits, and BMI. However, we found no significant association between lung function and asbestos exposure. © 2017 Wiley Periodicals, Inc.

  4. [System analytical approach of lung function and hemodynamics].

    Science.gov (United States)

    Naszlady, Attila; Kiss, Lajos

    2009-02-15

    The authors critically analyse the traditional views in physiology and complete them with new statements based on computer model simulations of lung function and of hemodynamics. Conclusions are derived for the clinical practice as follows: the four-dimensional function curves are similar in both systems; there is a "waterfall" zone in the pulmonary blood perfusion; the various time constants of pulmonary regions can modify the blood gas values; pulmonary capillary pressure is equal to pulmonary arterial diastole pressure; heart is not a pressure pump, but a flow source; ventricles are loaded by the input impedance of the arterial systems and not by the total vascular (ohmlike) resistance; optimum heart rate in rest depends on the length of the aorta; this law of heart rate, based on the principle of resonance is valid along the mammalian allometric line; tachycardia decreases the input impedance; using positive end expiratory pressure respirators the blood gas of pulmonary artery should be followed; coronary circulation should be assessed in beat per milliliter, the milliliter per minute may be false. These statements are compared to related references.

  5. Cardiovascular responses to high-frequency oscillatory ventilation during acute lung injury in sheep.

    Science.gov (United States)

    Nakagawa, Rikimaru; Koizumi, Tomonobu; Ono, Koichi; Tsushima, Kenji; Yoshikawa, Sumiko; Kubo, Keishi; Otagiri, Tetutarou

    2007-01-01

    The present study was designed to evaluate pulmonary and systemic hemodynamics and blood gas changes on switching from conventional mechanical ventilation (CMV) to high-frequency oscillatory ventilation (HFOV) in a large animal model of acute lung injury. Eleven anesthetised sheep chronically instrumented with vascular monitoring were prepared. Animals received oleic acid (0.08 ml x kg(-1)) intravenously and were ventilated for 4 h h after the administration of oleic acid. The animals were then randomized into the two following different ventilation modes: CMV (tidal volume [V(T)], 6 ml x kg(-1); respiratory rate [RR], 25 x min(-1)) with positive end-expiratory pressure (PEEP) of 12 cmH(2)O; or CMV under the same settings without PEEP. HFOV was then switched. The setting of mean airway pressure with a fixed stroke volume was changed between 25, 18, and 12 cmH(2)O every 20 min. Mean pulmonary artery pressure, pulmonary artery occlusive pressure (Paop), left atrium pressure, systemic arterial pressure, cardiac output (CO), and blood gas composition under each setting were measured before and after HFOV. Switching to HFOV, from without PEEP, resulted in significant increases in Paop and PaO2 and a decrease in CO at higher (25, 18 cmH(2)O) mean airway pressure. However, when changed from low V(T) and PEEP, HFOV produced further improvements in oxygenation without any deterioration of cardiovascular depression. Thus, switching to HFOV from CMV with low V(T) and high PEEP may have little influence on pulmonary or systemic hemodynamics in acute lung injury. We conclude that hemodynamic responses are dependent on the predefined setting of PEEP during CMV, and on applied mean airway pressure during HFOV.

  6. Effects of positive end-expiratory pressure on the sigmoid equation in experimental acute lung injury.

    Science.gov (United States)

    Bayle, Frederique; Guerin, Claude; Viale, Jean-Paul; Richard, Jean-Christophe; Annat, Guy

    2004-11-01

    To describe inflation and deflation volume-pressure (V-P) curves of the respiratory system by the sigmoidal equation at different levels of positive end-expiratory pressure (PEEP) in acute lung injury. Experimental study. Physiological laboratory in a university setting. Six pigs of 25 kg each. Acute lung injury was induced by oleic acid. PEEP was applied from 0 to 15 cm H(2)O and from 15 to 0 cm H(2)O for 10 min in steps of 5 cmH(2)O. Inflation and deflation V-P curves were constructed from an automated super-syringe that delivers a constant flow of 7 l/min in both inspiratory and expiratory directions. V-P curves were obtained at each level of PEEP without disconnecting the animal from the ventilator. The experimental data were fitted to the sigmoid equation which provided the true inflection point (c), the point of maximal compliance increase (Pmci) reflecting opening/closure and the point of maximal compliance decrease (Pmcd) reflecting end of recruitment/onset of de-recruitment. The sigmoid equation provided an excellent fit. The values of the coefficients of determination were greater than 0.970 (median 0.996, IQR 0.994-0.997 for the 84 determinations). Negative values of Pmci in the deflation limb of the V-P curve were recorded in five pigs, suggesting closure below the volume range studied. Inflation and deflation V-P curves at different PEEPs can be fitted by the sigmoid equation. However, further work is needed to investigate the meaning of negative values for Pmci.

  7. Mast cells modulate acute ozone-induced inflammation of the murine lung

    Energy Technology Data Exchange (ETDEWEB)

    Kleeberger, S.R.; Seiden, J.E.; Levitt, R.C.; Zhang, L.Y. (Johns Hopkins School of Public Health, Baltimore, MD (United States))

    1993-11-01

    We hypothesized that mast cells modulate lung inflammation that develops after acute ozone (O3) exposure. Two tests were done: (1) genetically mast-cell-deficient (WBB6F1-W/Wv, WCB6F1-SI/SId) and bone-marrow-transplanted W/Wv mice were exposed to O3 or filtered air, and the inflammatory responses were compared with those of mast-cell-sufficient congenic mice (WBB6F1-(+)/+, WCB6F1-(+)/+); (2) genetically O3-susceptible C57BL/6J mice were treated pharmacologically with putative mast-cell modulators or vehicle, and the O3-induced inflammatory responses were compared. Mice were exposed to 1.75 ppm O3 or air for 3 h, and lung inflammation was assessed by bronchoalveolar lavage (BAL) 6 and 24 h after exposure. Relative to O3-exposed W/Wv and SI/SId mice, the mean numbers of lavageable polymorphonuclear leukocytes (PMNs) and total BAL protein concentration (a marker of permeability) were significantly greater in the respective O3-exposed normal congenic +/+ mice (p < 0.05). Mast cells were reconstituted in W/Wv mice by transplantation of bone marrow cells from congenic +/+ mice, and O3-induced lung inflammation was assessed in the mast-cell-replete W/Wv mice. After O3 exposure, the changes in lavageable PMNs and total protein of mast-cell-replete W/Wv mice were not different from age-matched normal +/+ control mice, and they were significantly greater than those of sham-transplanted W/Wv mice (p < 0.05). Genetically susceptible C57BL/6J mice were pretreated with a mast-cell stabilizer (nedocromil sodium), secretagogue (compound 48/80), or vehicle, and the mice were exposed to O3.

  8. Erythropoietin Pretreatment Attenuates Seawater Aspiration-Induced Acute Lung Injury in Rats.

    Science.gov (United States)

    Ji, Mu-Huo; Tong, Jian-Hua; Tan, Yuan-Hui; Cao, Zhen-Yu; Ou, Cong-Yang; Li, Wei-Yan; Yang, Jian-Jun; Peng, Y G; Zhu, Si-Hai

    2016-02-01

    Seawater drowning-induced acute lung injury (ALI) is a serious clinical condition characterized by increased alveolar-capillary permeability, excessive inflammatory responses, and refractory hypoxemia. However, current therapeutic options are largely supportive; thus, it is of great interest to search for alternative agents to treat seawater aspiration-induced ALI. Erythropoietin (EPO) is a multifunctional agent with antiinflammatory, antioxidative, and antiapoptotic properties. However, the effects of EPO on seawater aspiration-induced ALI remain unclear. In the present study, male rats were randomly assigned to the naive group, normal saline group, seawater group, or seawater + EPO group. EPO was administered intraperitoneally at 48 and 24 h before seawater aspiration. Arterial blood gas analysis was performed with a gas analyzer at baseline, 30 min, 1 h, 4 h, and 24 h after seawater aspiration, respectively. Histological scores, computed tomography scan, nuclear factor kappa B p65, inducible nitric oxide synthase, caspase-3, tumor necrosis factor-alpha, interleukin (IL)-1β, IL-6, IL-10, wet-to-dry weight ratio, myeloperoxidase activity, malondialdehyde, and superoxide dismutase in the lung were determined 30 min after seawater aspiration. Our results showed that EPO pretreatment alleviated seawater aspiration-induced ALI, as indicated by increased arterial partial oxygen tension and decreased lung histological scores. Furthermore, EPO pretreatment attenuated seawater aspiration-induced increase in the expressions of pulmonary nuclear factor kappa B p65, inducible nitric oxide synthase, caspase-3, tumor necrosis factor-alpha, IL-1β, myeloperoxidase activity, and malondialdehyde when compared with the seawater group. Collectively, our study suggested that EPO pretreatment attenuates seawater aspiration-induced ALI by down-regulation of pulmonary pro-inflammatory cytokines, oxidative stress, and apoptosis.

  9. Systemic not just mesenteric lymph causes acute lung injury following hemorrhagic shock.

    Science.gov (United States)

    Diebel, Lawrence N; Liberati, David M; Ledgerwood, Anna M; Lucas, Charles E

    2008-10-01

    Recent studies have demonstrated a significant role for factor(s) present in mesenteric lymph following hemorrhagic shock in the etiology of post-hemorrhagic shock acute lung injury (ALI). Earlier studies have shown that ischemia-reperfusion insults to systemic tissue beds can also result in ALI. We therefore hypothesized that factors in systemic lymph may cause lung injury after hemorrhagic shock; this was studied in vitro. Confluent human pulmonary microvascular endothelial cells (HMVEC) maintained in a 2-chamber cell culture system were exposed to systemic lymph obtained from dogs exposed to sham operation or hemorrhagic shock and resuscitation. HMVEC injury was indexed by apoptosis (% Apo, Hoechst staining) and permeability to albumin (microL/min). HMVEC activation was indexed by surface expression of intracellular adhesion molecule-1 (ICAM-1) expressed as mean fluorescence intensity using flow cytometry. There was a 2-fold increase in HMVEC permeability and apoptotic rate after incubation with postshock systemic lymph. A similar effect was noted with ICAM expression, which was 2.5 fold higher after incubation with postshock lymph. These biologic effects were first noted with the 120-minute postresuscitation lymph. Lymph obtained during shock or from sham animals had no effect. Pulmonary microvascular endothelial dysfunction is evident after exposure to lymph obtained from systemic sites after hemorrhagic shock. The "unique" properties ascribed to post-hemorrhagic shock mesenteric lymph in causing ALI seem to be shared by lymph from systemic sites as well.

  10. A case of lung cancer associated with acute respiratory distress syndrome after thoracic radiotherapy

    International Nuclear Information System (INIS)

    Enoki, Masafumi; Tojima, Hirokazu

    1996-01-01

    A 73-year-old man presented with dyspnea, cough, fever, appetite loss and stridor due to bronchial stenosis. Fiber-optic bronchoscopy revealed an endobronchial lesion in the right main bronchus and biopsy specimens showed poorly differentiated squamous cell carcinoma. The clinical stage of lung cancer was IIIB (T4N2M0). The patient received 60 Gy in 30 fractions over 43 days to a field including the right hilum and mediastinum. The tumor decreased in size and stenosis of the bronchus disappeared. A week after completion of radiation the patient began to have high grade fever and dyspnea, and progressive hypoxia developed. A chest radiograph showed diffuse bilateral interstitial infiltrates. Despite mechanical ventilation with PEEP and the administration of steroids, he died of respiratory failure three weeks after completion of radiation. Necropsy specimens obtained from the left lung revealed massive deposition of fibrin in the alveolar airspaces associated with hyaline membranes and hyperplasia of type II cells indicating diffuse alveolar damage. The patient had mild pulmonary fibrosis on a CT scan taken before the start of radiotherapy. We conclude that care should be taken if the case has pulmonary fibrosis because radiation therapy can precipitate severe radiation pneumonitis and acute respiratory distress syndrome in such cases. (author)

  11. Rabdosia japonica var. glaucocalyx Flavonoids Fraction Attenuates Lipopolysaccharide-Induced Acute Lung Injury in Mice

    Directory of Open Access Journals (Sweden)

    Chun-jun Chu

    2014-01-01

    Full Text Available Rabdosia japonica var. glaucocalyx (Maxim. Hara, belonging to the Labiatae family, is widely used as an anti-inflammatory and antitumor drug for the treatment of different inflammations and cancers. Aim of the Study. To investigate therapeutic effects and possible mechanism of the flavonoids fraction of Rabdosia japonica var. glaucocalyx (Maxim. Hara (RJFs in acute lung injury (ALI mice induced by lipopolysaccharide (LPS. Materials and Methods. Mice were orally administrated with RJFs (6.4, 12.8, and 25.6 mg/kg per day for 7 days, consecutively, before LPS challenge. Lung specimens and the bronchoalveolar lavage fluid (BALF were isolated for histopathological examinations and biochemical analysis. The level of complement 3 (C3 in serum was quantified by a sandwich ELISA kit. Results. RJFs significantly attenuated LPS-induced ALI via reducing productions of the level of inflammatory mediators (TNF-α, IL-6, and IL-1β, and significantly reduced complement deposition with decreasing the level of C3 in serum, which was exhibited together with the lowered myeloperoxidase (MPO activity and nitric oxide (NO and protein concentration in BALF. Conclusions. RJFs significantly attenuate LPS-induced ALI via reducing productions of proinflammatory mediators, decreasing the level of complement, and reducing radicals.

  12. Tumor necrosis factor-α induced protein 6 attenuates acute lung injury following paraquat exposure.

    Science.gov (United States)

    Xu, Jiajun; Zhen, Jiantao; Zhu, Jingfa; Lin, Qingming

    2016-01-01

    Paraquat exposure commonly occurs in the developing countries and the mortality rate is high. However, there is currently no consensus on the efficacy of treatment for paraquat exposure. The study was aimed to explore the effects of tumor necrosis factor-α (TNF-α) induced protein 6 (TSG-6) on acute lung injury (ALI) following paraquat exposure in rats. Male Sprague-Dawley (SD) rats were randomly divided into the sham group (n = 8), the paraquat group (n = 8), and the paraquat TSG-6-treated group (n = 8). Rats were administered with 50 mg/kg of paraquat intraperitoneally. At 1 h after exposure, rats were treated with 30 μg of recombinant human TSG-6 (rhTSG-6) intraperitoneally. After 6 h of exposure, ALI scores were evaluated by histology and the expression of pro-inflammatory cytokines in lung was assayed using real-time RT-PCR. ALI scores were significantly lower in the paraquat TSG-6-treated group, compared with the paraquat group (p paraquat TSG-6-treated group, compared with the paraquat group (p paraquat exposure by suppressing inflammatory response.

  13. Acute stress affects prospective memory functions via associative memory processes.

    Science.gov (United States)

    Szőllősi, Ágnes; Pajkossy, Péter; Demeter, Gyula; Kéri, Szabolcs; Racsmány, Mihály

    2018-01-01

    Recent findings suggest that acute stress can improve the execution of delayed intentions (prospective memory, PM). However, it is unclear whether this improvement can be explained by altered executive control processes or by altered associative memory functioning. To investigate this issue, we used physical-psychosocial stressors to induce acute stress in laboratory settings. Then participants completed event- and time-based PM tasks requiring the different contribution of control processes and a control task (letter fluency) frequently used to measure executive functions. According to our results, acute stress had no impact on ongoing task performance, time-based PM, and verbal fluency, whereas it enhanced event-based PM as measured by response speed for the prospective cues. Our findings indicate that, here, acute stress did not affect executive control processes. We suggest that stress affected event-based PM via associative memory processes. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. LINKING LUNG AIRWAY STRUCTURE TO PULMONARY FUNCTION VIA COMPOSITE BRIDGE REGRESSION.

    Science.gov (United States)

    Chen, Kun; Hoffman, Eric A; Seetharaman, Indu; Jiao, Feiran; Lin, Ching-Long; Chan, Kung-Sik

    2016-12-01

    The human lung airway is a complex inverted tree-like structure. Detailed airway measurements can be extracted from MDCT-scanned lung images, such as segmental wall thickness, airway diameter, parent-child branch angles, etc. The wealth of lung airway data provides a unique opportunity for advancing our understanding of the fundamental structure-function relationships within the lung. An important problem is to construct and identify important lung airway features in normal subjects and connect these to standardized pulmonary function test results such as FEV1%. Among other things, the problem is complicated by the fact that a particular airway feature may be an important (relevant) predictor only when it pertains to segments of certain generations. Thus, the key is an efficient, consistent method for simultaneously conducting group selection (lung airway feature types) and within-group variable selection (airway generations), i.e., bi-level selection. Here we streamline a comprehensive procedure to process the lung airway data via imputation, normalization, transformation and groupwise principal component analysis, and then adopt a new composite penalized regression approach for conducting bi-level feature selection. As a prototype of composite penalization, the proposed composite bridge regression method is shown to admit an efficient algorithm, enjoy bi-level oracle properties, and outperform several existing methods. We analyze the MDCT lung image data from a cohort of 132 subjects with normal lung function. Our results show that, lung function in terms of FEV1% is promoted by having a less dense and more homogeneous lung comprising an airway whose segments enjoy more heterogeneity in wall thicknesses, larger mean diameters, lumen areas and branch angles. These data hold the potential of defining more accurately the "normal" subject population with borderline atypical lung functions that are clearly influenced by many genetic and environmental factors.

  15. The association of systemic microvascular changes with lung function and lung density: a cross-sectional study.

    Directory of Open Access Journals (Sweden)

    Bianca Harris

    Full Text Available Smoking causes endothelial dysfunction and systemic microvascular disease with resultant end-organ damage in the kidneys, eyes and heart. Little is known about microvascular changes in smoking-related lung disease. We tested if microvascular changes in the retina, kidneys and heart were associated with obstructive spirometry and low lung density on computed tomography. The Multi-Ethnic Study of Atherosclerosis recruited participants age 45-84 years without clinical cardiovascular disease. Measures of microvascular function included retinal arteriolar and venular caliber, urine albumin-to-creatinine ratio and, in a subset, myocardial blood flow on magnetic resonance imaging. Spirometry was measured following ATS/ERS guidelines. Low attenuation areas (LAA were measured on lung fields of cardiac computed tomograms. Regression models adjusted for pulmonary and cardiac risk factors, medications and body size. Among 3,397 participants, retinal venular caliber was inversely associated with forced expiratory volume in one second (FEV(1 (P<0.001 and FEV(1/forced vital capacity (FVC ratio (P = 0.04. Albumin-to-creatinine ratio was inversely associated with FEV(1 (P = 0.002 but not FEV(1/FVC. Myocardial blood flow (n = 126 was associated with lower FEV(1 (P = 0.02, lower FEV(1/FVC (P = 0.001 and greater percentage LAA (P = 0.04. Associations were of greater magnitude among smokers. Low lung function was associated with microvascular changes in the retina, kidneys and heart, and low lung density was associated with impaired myocardial microvascular perfusion. These cross-sectional results suggest that microvascular damage with end-organ dysfunction in all circulations may pertain to the lung, that lung dysfunction may contribute to systemic microvascular disease, or that there may be a shared predisposition.

  16. Acute functional deterioration in a child with cerebral palsy.

    LENUS (Irish Health Repository)

    Smyth, Elizabeth

    2012-01-01

    We describe a case of acute functional deterioration in a 13-year-old girl with severe spastic diplegia (GMFCS III) and a new diagnosis of diffuse intrinsic pontine glioma (DIPG). She presented with acute deterioration in mobility and motor function over 1 month, which was associated with dysarthria, dysphagia and behavioural change. Her mother had noticed subtle functional deterioration over the 2 months prior to this. Her physiotherapist who was concerned about her acute functional deterioration referred her for emergency review. Neurological imaging revealed a diffuse pontine lesion consistent with DIPG. She was subsequently referred to oncology. She deteriorated further, clinically, over the next few days and following discussion with the team; her family opted for palliative treatment, given the poor prognosis associated with DIPG.

  17. Lung ultrasound and chest x-ray for detecting pneumonia in an acute geriatric ward.

    Science.gov (United States)

    Ticinesi, Andrea; Lauretani, Fulvio; Nouvenne, Antonio; Mori, Giulia; Chiussi, Giulia; Maggio, Marcello; Meschi, Tiziana

    2016-07-01

    Our aim was to compare the accuracy of lung ultrasound (LUS) and standard chest x-ray (CXR) for diagnosing pneumonia in older patients with acute respiratory symptoms (dyspnea, cough, hemoptysis, and atypical chest pain) admitted to an acute-care geriatric ward. We enrolled 169 (80 M, 89 F) multimorbid patients aged 83.0 ± 9.2 years from January 1 to October 31, 2015. Each participant underwent CXR and bedside LUS within 6 hours from ward admission. LUS was performed by skilled clinicians, blinded to CXR results and clinical history. The final diagnosis (pneumonia vs no-pneumonia) was established by another clinician reviewing clinical and laboratory data independent of LUS results and possibly prescribing chest contrast-enhanced CT. Diagnostic parameters of CXR and LUS were compared with McNemar test on the whole cohort and after stratification for Rockwood Clinical Frailty Scale. Diagnostic accuracy for pneumonia (96 patients) was significantly higher in LUS (0.90, 95% confidence interval [CI] 0.83-0.96) compared with CXR (0.67, 95%CI 0.60-0.74, P pneumonia, particularly in those with frailty. A wider use of LUS should be implemented in this setting.

  18. Acute respiratory failure in critically ill patients with interstitial lung disease.

    Directory of Open Access Journals (Sweden)

    Lara Zafrani

    Full Text Available 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.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.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 (1.20-17.33; OR, 7.68; (1.78-33.22 and OR 10.60; (2.25-49.97 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; (0.005-0.21. In mechanically ventilated patients, overdistension induced by high PEEP settings was associated with CT fibrosis and hospital mortality.Mortality is high in ILD-associated ARF. CT and echocardiography are valuable prognostic tools. Prompt corticosteroid therapy may improve survival.

  19. The Pseudomonas aeruginosa Type III Secretion System Has an Exotoxin S/T/Y Independent Pathogenic Role during Acute Lung Infection

    Science.gov (United States)

    Galle, Marlies; Jin, Shouguang; Bogaert, Pieter; Haegman, Mira; Vandenabeele, Peter; Beyaert, Rudi

    2012-01-01

    The type III secretion system (T3SS) is a complex nanomachine of many pathogenic Gram-negative bacteria. It forms a proteinaceous channel that is inserted into the host eukaryotic cell membrane for injection of bacterial proteins that manipulate host cell signaling. However, few studies have focused on the effector-independent functions of the T3SS. Using a murine model of acute lung infection with Pseudomonas aeruginosa, an important human opportunistic pathogen, we compared the pathogenicity of mutant bacteria that lack all of the known effector toxins ( ΔSTY), with mutant bacteria that also lack the major translocator protein PopB (ΔSTY/ΔPopB) and so cannot form a functional T3SS channel in the host cell membrane. Mortality was higher among mice challenged with ΔSTY compared to mice challenged with ΔSTY/ΔPopB mutant bacteria. In addition, mice infected with ΔSTY showed decreased bacterial clearance from the lungs compared to those infected with ΔSTY/ΔPopB. Infection was in both cases associated with substantial killing of lung infiltrating macrophages. However, macrophages from ΔSTY-infected mice died by pro-inflammatory necrosis characterized by membrane permeabilization and caspase-1 mediated IL-1β production, whereas macrophages from ΔSTY/ΔPopB infected mice died by apoptosis, which is characterized by annexin V positive staining of the cell membrane and caspase-3 activation. This was confirmed in macrophages infected in vitro. These results demonstrate a T3SS effector toxin independent role for the T3SS, in particular the T3SS translocator protein PopB, in the pathogenicity of P. aeruginosa during acute lung infection. PMID:22844497

  20. Lung Function Abnormalities in Smokers with Ischemic Heart Disease.

    Science.gov (United States)

    Franssen, Frits M E; Soriano, Joan B; Roche, Nicolas; Bloomfield, Paul H; Brusselle, Guy; Fabbri, Leonardo M; García-Rio, Francisco; Kearney, Mark T; Kwon, Namhee; Lundbäck, Bo; Rabe, Klaus F; Raillard, Alice; Muellerova, Hana; Cockcroft, John R

    2016-09-01

    The aim of the ALICE (Airflow Limitation in Cardiac Diseases in Europe) study was to investigate the prevalence of airflow limitation in patients with ischemic heart disease and the effects on quality of life, healthcare use, and future health risk. To examine prebronchodilator and post-bronchodilator spirometry in outpatients aged greater than or equal to 40 years with clinically documented ischemic heart disease who were current or former smokers. This multicenter, cross-sectional study was conducted in 15 cardiovascular outpatient clinics in nine European countries. Airflow limitation was defined as post-bronchodilator FEV1/FVC less than 0.70. Among the 3,103 patients with ischemic heart disease who were recruited, lung function was defined for 2,730 patients. Airflow limitation was observed in 30.5% of patients with ischemic heart disease: 11.3% had mild airflow limitation, 15.8% moderate airflow limitation, 3.3% severe airflow limitation, and 0.1% very severe airflow limitation. Most patients with airflow limitation (70.6%) had no previous spirometry testing or diagnosed pulmonary disease. Airflow limitation was associated with greater respiratory symptomatology, impaired health status, and more frequent emergency room visits (P < 0.05). Airflow limitation compatible with chronic obstructive pulmonary disease affects almost one-third of patients with ischemic heart disease. Although airflow limitation is associated with additional morbidity and societal burden, it is largely undiagnosed and untreated. Clinical trial registered with www.clinicaltrials.gov (NCT 01485159).

  1. Association of lung function genes with chronic obstructive pulmonary disease.

    Science.gov (United States)

    Kim, Woo Jin; Lim, Myoung Nam; Hong, Yoonki; Silverman, Edwin K; Lee, Ji-Hyun; Jung, Bock Hyun; Ra, Seung Won; Choi, Hye Sook; Jung, Young Ju; Park, Yong Bum; Park, Myung Jae; Lee, Sei Won; Lee, Jae Seung; Oh, Yeon-Mok; Lee, Sang Do

    2014-08-01

    Spirometric measurements of pulmonary function are important in diagnosing and determining the severity of chronic obstructive pulmonary disease (COPD). We performed this study to determine whether candidate genes identified in genome-wide association studies of spirometric measurements were associated with COPD and if they interacted with smoking intensity. The current analysis included 1,000 COPD subjects and 1,000 controls recruited from 24 hospital-based pulmonary clinics. Thirteen SNPs, chosen based on genome-wide association studies of spirometric measurements in the Korean population cohorts, were genotyped. Genetic association tests were performed, adjusting for age, sex, and smoking intensity, using models including a SNP-by-smoking interaction term. PID1 and FAM13A were significantly associated with COPD susceptibility. There were also significant interactions between SNPs in ACN9 and FAM13A and smoking pack-years, and an association of ACN9 with COPD in the lowest smoking tertile. The risk allele of FAM13A was associated with increased expression of FAM13A in the lung. We have validated associations of FAM13A and PID1 with COPD. ACN9 showed significant interaction with smoking and is a potential candidate gene for COPD. Significant associations of genetic variants of FAM13A with gene expression levels suggest that the associated loci may act as genetic regulatory elements for FAM13A gene expression.

  2. Ex vivo administration of trimetazidine improves post-transplant lung function in pig model.

    Science.gov (United States)

    Cosgun, Tugba; Iskender, Ilker; Yamada, Yoshito; Arni, Stephan; Lipiski, Miriam; van Tilburg, Koen; Weder, Walter; Inci, Ilhan

    2017-07-01

    Ex vivo lung perfusion (EVLP) is not only used to assess marginal donor lungs but is also used as a platform to deliver therapeutic agents outside the body. We previously showed the beneficial effects of trimetazidine (TMZ) on ischaemia reperfusion (IR) injury in a rat model. This study evaluated the effects of TMZ in a pig EVLP transplant model. Pig lungs were retrieved and stored for 24 h at 4°C, followed by 4 h of EVLP. Allografts were randomly allocated to 2 groups ( n  = 5 each). TMZ (5 mg/kg) was added to the prime solution prior to EVLP. After EVLP, left lungs were transplanted and recipients were observed for 4 h. Allograft gas exchange function and lung mechanics were recorded hourly throughout reperfusion. Microscopic lung injury and inflammatory and biochemical parameters were assessed. There was a trend towards better oxygenation during EVLP in the TMZ group ( P  = 0.06). After transplantation, pulmonary gas exchange was significantly better during the 4-h reperfusion period and after isolation of the allografts for 10 min ( P  Ex vivo treatment of donor lungs with TMZ significantly improved immediate post-transplant lung function. Further studies are warranted to understand the effect of this strategy on long-term lung function. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  3. Acute respiratory distress after transfusion

    Directory of Open Access Journals (Sweden)

    Michael Jožef Gradišek

    2012-12-01

    Conclusions: Transfusion-related acute lung injury (TRALI and transfusion-associated circulatory overload (TACO are clinical syndromes with predominant pulmonary injury and respiratory distress. Anaphylactic reaction, hemolytic transfusion reaction and transfusion of contaminated blood products also impair lung function but are less frequent. Transfusion in critically ill and injured patient is an independent risk factor for acute lung injury. It remains to be determined whether transfusion is the cause of increased mortality or only an indicator of disease severity

  4. Using SPECT-guidance to protect functional lung with optimizing intensity modulated radiotherapy in stage III non-small cell lung cancer patients

    International Nuclear Information System (INIS)

    Wang Zhongtang; Li Baosheng; Sun Hongfu; Fang Yongcun; Chen Jinhu; Yan Jing

    2008-01-01

    Objective: To explore the possibility of using lung perfusion single photon emission computed tomography (SPECT) scans to protect functional lung with optimizing intensity modulated radiotherapy (IMRT) plan in patients with stage m non-small cell lung cancer (NSCLC). Methods: Twenty-four patients with stage III NSCLC who were candidated for radiotherapy were enrolled. All patients had PET-CT scans and SPECT scans. The two sets of images were accurately co-registered in the planning system. SPECT images were used to define a volume of functional lung (FL) and non-functional lung (NFL). The region of ≥30% maximum radioactive counts was FL and the other region was NFL. Then SPECT images were classified by comparing lung perfusion deficit with area of radiological abnormality. Grade O: no lung perfusion deficit. Grade 1: the size of radiological abnormality was similar to the area of lung perfusion deficit. Grade 2: the area of lung perfusion was bigger than that of radiological abnormality, and extended to 1 pulmonary lobe. Grade 3: the area of lung perfusion deficit exceed 1 pulmonary lobe. The optimized IMRT objective was to minimize the dose to FL. the difference between the two sets of IMRT plans was studied. Results: All patients had lung perfusion deficits, 8 patients with grade 1 damage, 6 patients with grade 2 damage, and 10 patient with grade 3 damage. After IMRT plan optimized, both the percentage of whole lung volume received dose (WLV) and the percentage of functional lung volume received dose (FLV) were decreased. However, the FLVs was decreased more significantly. There was significant difference in WLV 10 , WLV 15 , WLV 20 , WLV 25 , WLV 30 and FLV 10 , FLV 15 , FLV 20 , FLV 25 , FLV 30 between the two sets of IMRT plans (P<0.05). Conclusions: It is convenient to SPECT-guidance to protect functional lung with optimizing IMRT in stage III NSCLC patients, potentially reducing lung toxicity. (authors)

  5. A coin-like peripheral small cell lung carcinoma associated with acute paraneoplastic axonal Guillain-Barre-like syndrome.

    Science.gov (United States)

    Jung, Ioan; Gurzu, Simona; Balasa, Rodica; Motataianu, Anca; Contac, Anca Otilia; Halmaciu, Ioana; Popescu, Septimiu; Simu, Iunius

    2015-06-01

    A 65-year-old previously healthy male heavy smoker was hospitalized with a 2-week history of progressive muscle weakness in the lower and upper extremities. After 10 days of hospitalization, urinary sphincter incompetence and fecal incontinence were added and tetraparesis was established. The computer-tomography scan examination revealed a massive right hydrothorax and multifocal solid acinar structures with peripheral localization in the left lung, which suggested pulmonary cancer. Bone marrow metastases were also suspected. Based on the examination results, the final diagnosis was acute paraneoplastic axonal Guillain-Barre-like syndrome. The patient died 3 weeks after hospitalization. At autopsy, bronchopneumonia and a right hydrothorax were confirmed. Several 4 to 5-mm-sized round peripherally located white nodules were identified in the left lung, without any central tumor mass. Under microscope, a coin-shaped peripheral/subpleural small cell carcinoma was diagnosed, with generalized bone metastases. A huge thrombus in the abdominal aorta and acute pancreatitis was also seen at autopsy. This case highlights the difficulty of diagnosis of lung carcinomas and the necessity of a complex differential diagnosis of severe progressive ascending neuropathies. This is the 6th reported case of small cell lung cancer-associated acute Guillain-Barre-like syndrome and the first report about an association with a coin-like peripheral pattern.

  6. NFAT5 participates in seawater inhalation-induced acute lung injury via modulation of NF-κB activity

    Science.gov (United States)

    Li, Congcong; Liu, Manling; Bo, Liyan; Liu, Wei; Liu, Qingqing; Chen, Xiangjun; Xu, Dunquan; Li, Zhichao; Jin, Faguang

    2016-01-01

    Nuclear factor of activated T cells 5 (NFAT5) is a transcription factor that can be activated by extracellular tonicity. It has been reported that NFAT5 may increase the transcription of certain osmoprotective genes in the renal system, and the aim of the current study was to explore the role of NFAT5 in seawater inhalation-induced acute lung injury. Though establishing the model of seawater inhalation-induced acute lung injury, it was demonstrated that seawater inhalation enhanced the transcription and protein expression of NFAT5 (evaluated by reverse transcription-polymerase chain reaction, immunohistochemistry stain and western blotting) and activation of nuclear factor (NF)-κB (evaluated by western blotting and mRNA expression levels of three NF-κB-dependent genes) both in lung tissue and rat alveolar macrophage cells (NR8383 cells). When expression of NFAT5 was reduced in NR8383 cells using an siRNA targeted to NFAT5, the phosphorylation of NF-κB and transcription of NF-κB-dependent genes were significantly reduced. In addition, the elevated content of certain inflammatory cytokines [tumor necrosis factor α, interleukin (IL)-1 and IL-8] were markedly reduced. In conclusion, NFAT5 serves an important pathophysiological role in seawater inhalation-induced acute lung injury by modulating NF-κB activity, and these data suggest that NFAT5 may be a promising therapeutic target. PMID:27779669

  7. Effects of ultraprotective ventilation, extracorporeal carbon dioxide removal, and spontaneous breathing on lung morphofunction and inflammation in experimental severe acute respiratory distress syndrome.

    Science.gov (United States)

    Güldner, Andreas; Kiss, Thomas; Bluth, Thomas; Uhlig, Christopher; Braune, Anja; Carvalho, Nadja; Quast, Theresa; Rentzsch, Ines; Huhle, Robert; Spieth, Peter; Richter, Torsten; Saddy, Felipe; Rocco, Patricia R M; Kasper, Michael; Koch, Thea; Pelosi, Paolo; de Abreu, Marcelo Gama

    2015-03-01

    To investigate the role of ultraprotective mechanical ventilation (UP-MV) and extracorporeal carbon dioxide removal with and without spontaneous breathing (SB) to improve respiratory function and lung protection in experimental severe acute respiratory distress syndrome. Severe acute respiratory distress syndrome was induced by saline lung lavage and mechanical ventilation (MV) with higher tidal volume (VT) in 28 anesthetized pigs (32.8 to 52.5 kg). Animals (n = 7 per group) were randomly assigned to 6 h of MV (airway pressure release ventilation) with: (1) conventional P-MV with VT ≈6 ml/kg (P-MVcontr); (2) UP-MV with VT ≈3 ml/kg (UP-MVcontr); (3) UP-MV with VT ≈3 ml/kg and SB (UP-MVspont); and (4) UP-MV with VT ≈3 ml/kg and pressure supported SB (UP-MVPS). In UP-MV groups, extracorporeal carbon dioxide removal was used. The authors found that: (1) UP-MVcontr reduced diffuse alveolar damage score in dorsal lung zones (median[interquartile]) (12.0 [7.0 to 16.8] vs. 22.5 [13.8 to 40.8]), but worsened oxygenation and intrapulmonary shunt, compared to P-MVcontr; (2) UP-MVspont and UP-MVPS improved oxygenation and intrapulmonary shunt, and redistributed ventilation towards dorsal areas, as compared to UP-MVcontr; (3) compared to P-MVcontr, UP-MVcontr and UP-MVspont, UP-MVPS yielded higher levels of tumor necrosis factor-α (6.9 [6.5 to 10.1] vs. 2.8 [2.2 to 3.0], 3.6 [3.0 to 4.7] and 4.0 [2.8 to 4.4] pg/mg, respectively) and interleukin-8 (216.8 [113.5 to 343.5] vs. 59.8 [45.3 to 66.7], 37.6 [18.8 to 52.0], and 59.5 [36.1 to 79.7] pg/mg, respectively) in dorsal lung zones. In this model of severe acute respiratory distress syndrome, MV with VT ≈3 ml/kg and extracorporeal carbon dioxide removal without SB slightly reduced lung histologic damage, but not inflammation, as compared to MV with VT = 4 to 6 ml/kg. During UP-MV, pressure supported SB increased lung inflammation.

  8. Cytochrome b5 and cytokeratin 17 are biomarkers in bronchoalveolar fluid signifying onset of acute lung injury.

    Science.gov (United States)

    Ménoret, Antoine; Kumar, Sanjeev; Vella, Anthony T

    2012-01-01

    Acute lung injury (ALI) is characterized by pulmonary edema and acute inflammation leading to pulmonary dysfunction and potentially death. Early medical intervention may ameliorate the severity of ALI, but unfortunately, there are no reliable biomarkers for early diagnosis. We screened for biomarkers in a mouse model of ALI. In this model, inhalation of S. aureus enterotoxin A causes increased capillary permeability, cell damage, and increase protein and cytokine concentration in the lungs. We set out to find predictive biomarkers of ALI in bronchoalveolar lavage (BAL) fluid before the onset of clinical manifestations. A cutting edge proteomic approach was used to compare BAL fluid harvested 16 h post S. aureus enterotoxin A inhalation versus BAL fluid from vehicle alone treated mice. The proteomic PF 2D platform permitted comparative analysis of proteomic maps and mass spectrometry identified cytochrome b5 and cytokeratin 17 in BAL fluid of mice challenged with S. aureus enterotoxin A. Validation of cytochrome b5 showed tropic expression in epithelial cells of the bronchioles. Importantly, S. aureus enterotoxin A inhalation significantly decreased cytochrome b5 during the onset of lung injury. Validation of cytokeratin 17 showed ubiquitous expression in lung tissue and increased presence in BAL fluid after S. aureus enterotoxin A inhalation. Therefore, these new biomarkers may be predictive of ALI onset in patients and could provide insight regarding the basis of lung injury and inflammation.

  9. Acute brain trauma, lung injury, and pneumonia: more than just altered mental status and decreased airway protection.

    Science.gov (United States)

    Hu, Parker J; Pittet, Jean-Francois; Kerby, Jeffrey D; Bosarge, Patrick L; Wagener, Brant M

    2017-07-01

    Traumatic brain injury (TBI) is a major cause of mortality and morbidity worldwide. Even when patients survive the initial insult, there is significant morbidity and mortality secondary to subsequent pulmonary edema, acute lung injury (ALI), and nosocomial pneumonia. Whereas the relationship between TBI and secondary pulmonary complications is recognized, little is known about the mechanistic interplay of the two phenomena. Changes in mental status secondary to acute brain injury certainly impair airway- and lung-protective mechanisms. However, clinical and translational evidence suggests that more specific neuronal and cellular mechanisms contribute to impaired systemic and lung immunity that increases the risk of TBI-mediated lung injury and infection. To better understand the cellular mechanisms of that immune impairment, we review here the current clinical data that support TBI-induced impairment of systemic and lung immunity. Furthermore, we also review the animal models that attempt to reproduce human TBI. Additionally, we examine the possible role of damage-associated molecular patterns, the chlolinergic anti-inflammatory pathway, and sex dimorphism in post-TBI ALI. In the last part of the review, we discuss current treatments and future pharmacological therapies, including fever control, tracheostomy, and corticosteroids, aimed to prevent and treat pulmonary edema, ALI, and nosocomial pneumonia after TBI. Copyright © 2017 the American Physiological Society.

  10. Relationship between ultrasound bone parameters, lung function, and body mass index in healthy student population.

    Science.gov (United States)

    Cvijetić, Selma; Pipinić, Ivana Sabolić; Varnai, Veda Maria; Macan, Jelena

    2017-03-01

    Low bone mineral density has been reported in paediatric and adult patients with different lung diseases, but limited data are available on the association between lung function and bone density in a healthy young population. We explored the predictors of association between bone mass and pulmonary function in healthy first-year university students, focusing on body mass index (BMI). In this cross-sectional study we measured bone density with ultrasound and lung function with spirometry in 370 university students (271 girls and 99 boys). Information on lifestyle habits, such as physical activity, smoking, and alcohol consumption were obtained with a questionnaire. All lung function and bone parameters were significantly higher in boys than in girls (Pstudents had a significantly lower forced vital capacity (FVC%) (P=0.001 girls; P=0.012 boys), while overweight students had a significantly higher FVC% than normal weight students (P=0.024 girls; P=0.001 boys). BMI significantly correlated with FVC% (P=0.001) and forced expiratory volume in 1 second (FEV1 %) in both genders (P=0.001 girls; P=0.018 boys) and with broadband ultrasound attenuation (BUA) in boys. There were no significant associations between any of the bone and lung function parameters either in boys or girls. The most important determinant of lung function and ultrasound bone parameters in our study population was body mass index, with no direct association between bone density and lung function.

  11. Effects of Sigh on Regional Lung Strain and Ventilation Heterogeneity in Acute Respiratory Failure Patients Undergoing Assisted Mechanical Ventilation.

    Science.gov (United States)

    Mauri, Tommaso; Eronia, Nilde; Abbruzzese, Chiara; Marcolin, Roberto; Coppadoro, Andrea; Spadaro, Savino; Patroniti, Nicolo'; Bellani, Giacomo; Pesenti, Antonio

    2015-09-01

    In acute respiratory failure patients undergoing pressure support ventilation, a short cyclic recruitment maneuver (Sigh) might induce reaeration of collapsed lung regions, possibly decreasing regional lung strain and improving the homogeneity of ventilation distribution. We aimed to describe the regional effects of different Sigh rates on reaeration, strain, and ventilation heterogeneity, as measured by thoracic electrical impedance tomography. Prospective, randomized, cross-over study. General ICU of a single university-affiliated hospital. We enrolled 20 critically ill patients intubated and mechanically ventilated with PaO2/FIO2 up to 300 mm Hg and positive end-expiratory pressure at least 5 cm H2O (15 with acute respiratory distress syndrome), undergoing pressure support ventilation as per clinical decision. Sigh was added to pressure support ventilation as a 35 cm H2O continuous positive airway pressure period lasting 3-4 seconds at different rates (no-Sigh vs 0.5, 1, and 2 Sigh(s)/min). All study phases were randomly performed and lasted 20 minutes. In the last minutes of each phase, we measured arterial blood gases, changes in end-expiratory lung volume of nondependent and dependent regions, tidal volume reaching nondependent and dependent lung (Vtnondep and Vtdep), dynamic intratidal ventilation heterogeneity, defined as the average ratio of Vt reaching nondependent/Vt reaching dependent lung regions along inspiration (VtHit). With Sigh, oxygenation improved (p ventilation heterogeneity. Our study generates the hypothesis that in ventilated acute respiratory failure patients, Sigh may enhance regional lung protection.

  12. Lung segmentectomy: does it offer a real functional benefit over lobectomy?

    Directory of Open Access Journals (Sweden)

    Anne Charloux

    2017-10-01

    Full Text Available Anatomical segmentectomy has been developed to offer better pulmonary function preservation than lobectomy, in stage IA lung cancer. Despite the retrospective nature of most of the studies and the lack of randomised studies, a substantial body of literature today allows us to evaluate to what extent lung function decreases after segmentectomy and whether segmentectomy offers a real functional benefit over lobectomy. From the available series, it emerges that the mean decrease in forced expiratory volume in 1 s (FEV1 is low, ranging from −9% to −24% of the initial value within 2 months and −3 to −13% 12 months after segmentectomy. This reduction in lung function is significantly lower than that induced by lobectomy, but saves only a few per cent of pre-operative FEV1. Moreover, the published results do not firmly establish the functional benefit of segmentectomy over lobectomy in patients with poor lung function. Some issues remain to be addressed, including whether video-assisted thoracic surgery (VATS segmentectomy may preserve lung function better than VATS lobectomy in patients with poor lung function, especially within the early days after surgery, and whether this may translate to lowering the functional limit for surgery. Eventually, trials comparing stereotactic ablative body radiotherapy, radiofrequency ablation and segmentectomy functional consequences are warranted.

  13. Lung segmentectomy: does it offer a real functional benefit over lobectomy?

    Science.gov (United States)

    Charloux, Anne; Quoix, Elisabeth

    2017-12-31

    Anatomical segmentectomy has been developed to offer better pulmonary function preservation than lobectomy, in stage IA lung cancer. Despite the retrospective nature of most of the studies and the lack of randomised studies, a substantial body of literature today allows us to evaluate to what extent lung function decreases after segmentectomy and whether segmentectomy offers a real functional benefit over lobectomy. From the available series, it emerges that the mean decrease in forced expiratory volume in 1 s (FEV 1 ) is low, ranging from -9% to -24% of the initial value within 2 months and -3 to -13% 12 months after segmentectomy. This reduction in lung function is significantly lower than that induced by lobectomy, but saves only a few per cent of pre-operative FEV 1 Moreover, the published results do not firmly establish the functional benefit of segmentectomy over lobectomy in patients with poor lung function. Some issues remain to be addressed, including whether video-assisted thoracic surgery (VATS) segmentectomy may preserve lung function better than VATS lobectomy in patients with poor lung function, especially within the early days after surgery, and whether this may translate to lowering the functional limit for surgery. Eventually, trials comparing stereotactic ablative body radiotherapy, radiofrequency ablation and segmentectomy functional consequences are warranted. Copyright ©ERS 2017.

  14. High blood pressure, antihypertensive medication and lung function in a general adult population

    Science.gov (United States)

    2011-01-01

    Background Several studies showed that blood pressure and lung function are associated. Additionally, a potential effect of antihypertensive medication, especially beta-blockers, on lung function has been discussed. However, side effects of beta-blockers have been investigated mainly in patients with already reduced lung function. Thus, aim of this analysis is to determine whether hypertension and antihypertensive medication have an adverse effect on lung function in a general adult population. Methods Within the population-based KORA F4 study 1319 adults aged 40-65 years performed lung function tests and blood pressure measurements. Additionally, information on anthropometric measurements, medical history and use of antihypertensive medication was available. Multivariable regression models were applied to study the association between blood pressure, antihypertensive medication and lung function. Results High blood pressure as well as antihypertensive medication were associated with lower forced expiratory volume in one second (p = 0.02 respectively p = 0.05; R2: 0.65) and forced vital capacity values (p = 0.01 respectively p = 0.05, R2: 0.73). Furthermore, a detailed analysis of antihypertensive medication pointed out that only the use of beta-blockers was associated with reduced lung function, whereas other antihypertensive medication had no effect on lung function. The adverse effect of beta-blockers was significant for forced vital capacity (p = 0.04; R2: 0.65), while the association with forced expiratory volume in one second showed a trend toward significance (p = 0.07; R2: 0.73). In the same model high blood pressure was associated with reduced forced vital capacity (p = 0.01) and forced expiratory volume in one second (p = 0.03) values, too. Conclusion Our analysis indicates that both high blood pressure and the use of beta-blockers, but not the use of other antihypertensive medication, are associated with reduced lung function in a general adult

  15. Neuromuscular function during a forward lunge in meniscectomized patients

    DEFF Research Database (Denmark)

    Thorlund, Jonas Bloch; Damgaard, Jacob; Roos, Ewa M.

    2012-01-01

    This study aimed to investigate differences in knee joint kinematics, ground reaction force kinetics and neuromuscular activity including muscle coactivation, and medial versus lateral muscle activity during a forward lunge between the operated and contralateral legs of meniscectomized patients...

  16. Gene expression of the concentration-sensitive sodium channel is suppressed in lipopolysaccharide-induced acute lung injury in mice.

    Science.gov (United States)

    Hagiwara, Teruki; Yoshida, Shigeru; Hidaka, Yuji

    2017-04-01

    The concentration-sensitive sodium channel (Na C ) is expressed in alveolar type II epithelial cells and pulmonary microvascular endothelial cells in mouse lungs. We recently reported that Na C contributes to amiloride-insensitive sodium transport in mouse lungs (Respiratory Physiology & Neurobiology, 2016). However, details regarding its physiological role in the lung remain unknown. To examine whether Na C is involved in alveolar fluid clearance during an acute lung injury (ALI), we analyzed the relationship between Na C gene expression in the lung and the development of pulmonary edema in lipopolysaccharide (LPS)-induced ALI mice. LPS-induced ALI mice were prepared by the intratracheal administration of LPS. Bronchoalveolar lavage (BAL) neutrophils and lung water content (LWCs) were used as a marker of ALI and pulmonary edema, respectively. Na C protein production in the lung was detected by immunoblotting and immunofluorescence. The gene expressions of Na C and the epithelial sodium channel (ENaC) of LPS-induced ALI mice were examined by quantitative RT-PCR over a time course of 14 days. The BAL neutrophil count increased until day 2 after LPS administration and had nearly recovered by day 6. LWCs in LPS-induced mice gradually increased until day 8 and had recovered by day 14. The expression of the Na C protein in the lungs of LPS-induced mice dramatically decreased from day 2 to day 6, but recovered by day 8. The mRNA expression of Na C decreased in the lung, as well as those for α-, β-, and γ-ENaC during ALI. Thus, Na C expression is suppressed during the development stage of pulmonary edema and then recovers in the convalescent phase. Our results suggest that suppression of the gene expression of Na C is involved in the development of pulmonary edema in ALI.

  17. Lung function loss, smoking, vitamin C intake, and polymorphisms of the glutamate-cysteine ligase genes

    NARCIS (Netherlands)

    Siedlinski, Mateusz; Postma, Dirkje S.; van Diemen, Cleo C.; Blokstra, Anneke; Smit, Henriette A.; Boezen, H. Marike

    2008-01-01

    Rationale: Smoking-induced oxidative stress contributes to chronic obstructive pulmonary disease, a lung disease characterized by low lung function and increasing mortality worldwide. The counterbalance for this effect may be provided by, for example, increased intake of the antioxidant vitamin C or

  18. The Effect of Wood Dust on Lung Function of Woodworkers in Na ...

    African Journals Online (AJOL)

    Background The wood industry is one of the occupations where exposure to wood dust has been shown to lead to chronic lung diseases long after such exposure has ceased. This study assessed the effect of wood dust and other irritants on lung function of wood workers in Na'ibawa market, Kano. Method Using a ...

  19. Dietary factors and lung function in the general population : wine and resveratrol intake

    NARCIS (Netherlands)

    Siedlinski, M; Boer, J M A; Smit, H A; Postma, D S; Boezen, H M

    Wine intake is associated with a better lung function in the general population, yet the source of this effect is unknown. Resveratrol, a polyphenol in wine, has anti-inflammatory properties in the lung, its effects being partially mediated via induction of Sirtuin (SIRT) 1 activity. We assessed the

  20. No relationship between lung function and high-sensitive C-reactive protein in adolescence

    DEFF Research Database (Denmark)

    Nybo, Mads; Hansen, Henrik Steen; Siersted, Hans Christian

    2010-01-01

      Several studies on adults have indicated that lower spirometric lung function may be associated with increased systemic inflammation, but no studies have investigated if this association is already present in adolescence. Objective:  We explored the temporal relationship between changes in lung...

  1. Assessing the Effects of Fibrosis on Lung Function by Light Microscopy-Coupled Stereology

    DEFF Research Database (Denmark)

    Pilecki, Bartosz; Sørensen, Grith Lykke

    2017-01-01

    Pulmonary diseases such as fibrosis are characterized by structural abnormalities that lead to impairment of proper lung function. Stereological analysis of serial tissue sections allows detection and quantitation of subtle changes in lung architecture. Here, we describe a stereology-based method...

  2. Forward lunge as a functional performance test in ACL deficient subjects: test-retest reliability

    DEFF Research Database (Denmark)

    Alkjaer, Tine; Henriksen, Marius; Dyhre-Poulsen, Poul

    2009-01-01

    The forward lunge movement may be used as a functional performance test of anterior cruciate ligament (ACL) deficient and reconstructed subjects. The purposes were 1) to determine the test-retest reliability of a forward lunge in healthy subjects and 2) to determine the required numbers...

  3. No association between vitamin D and atopy, asthma, lung function or atopic dermatitis

    DEFF Research Database (Denmark)

    Thuesen, B H; Heede, N G; Tang, L

    2015-01-01

    allergens were measured by standard procedures. Wheezing, asthma and AD were assessed from questionnaires and lung function was measured by spirometry. We found no statistically significant associations between s25(OH)D and prevalence or incidence of atopy, AD, asthma or wheezing. Associations with lung...

  4. Incidence Proportion of Acute Cor Pulmonale in Patients with Acute Respiratory Distress Syndrome Subjected to Lung Protective Ventilation: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Das, Saurabh Kumar; Choupoo, Nang Sujali; Saikia, Priyam; Lahkar, Amitabh

    2017-06-01

    Reported incidence of acute cor pulmonale (ACP) in patients with acute respiratory distress syndrome (ARDS) varies from 10% to 84%, despite being subjected to lung protective ventilation according to the current guidelines. The objective of this review is to find pooled cumulative incidence of ACP in patients with ARDS undergoing lung protective ventilation. We searched MEDLINE, EMBASE, Cochrane Library, KoreaMed, LILACS, and WHO Clinical Trial Registry. Cross-sectional or cohort studies were included if they reported or provided data that could be used to calculate the incidence proportion of ACP. Inverse variance heterogeneity (IVhet) and random effect model were used for the main outcome and measures. We included 16 studies encompassing 1661 patients. The cumulative incidence of ACP using IVhet analysis was 23% (95% confidence interval [CI] = 18%-28%) over 3 days of lung protective ventilation. Random effect analysis of 7 studies (1250 patients) revealed pooled odd ratio of mortality of 1.16 (95% CI = 0.80-1.67, P = 0.44) due to ACP. Patients with ARDS have a 23% risk of developing ACP with lung protective ventilation. Findings of this review indicate the need of updating existing guidelines for ventilating ARDS patients to incorporate right ventricle protective strategy.

  5. [Effect of thalidomide in a mouse model of paraquat-induced acute lung injury and the underlying mechanisms].

    Science.gov (United States)

    Zhao, Guangju; Cai, Xiaoxia; She, Xingrong; Li, Dong; Hong, Guangliang; Wu, Bin; Li, Mengfang; Lu, Zhongqiu

    2014-11-01

    To investigate the effects of thalidomide in a mouse model of paraquat-induced acute lung injury and the mechanisms underlying the properties of thalidomide. Male ICR mice were randomly allocated into four groups: nomal control group (n = 30), thalidomide control group (n = 30), paraquat poisioning group (n = 30) and thalidomide treatment group (n = 90). Mice were sacrificed at 1d, 3d and 7d after paraquat poisioning. The level of (MDA) malondialdehyde, Superoxidedi-smutase (SOD) and glutathione (GSH) in the lung tissue were measuerd by chemical colorimetry. The expression of Nrf2 mRNA was determined by RT-PCR; Nuclear protein Nrf2 was abserved by Western blotting; Pathological changes of lung tissue were observed under light microscope by HE stain; the lung apoptosis cells were detected by TUNEL. The levels of MDA, SOD and the expressions Nrf2 mRNA and protein Nrf2 in lung tissue were all markedly increased in mice of paraquat poisioning group than those in nomal group at 1 d, 3 d, 7 d. In contrast, the levels of GSH were decreaseel (Pparaquat poisioning group, the pulmonary SOD, Nrf2 mRNA and protein were increased and the lung wet dry ratio were all significantly decreased in mice of THD treatment group at 1 d, 3 d, 7 d (Pparaquat poisioning. The apoptosis index was markedly decreased in THD treatment groups comparing to paraquat piosioning group (Pparaquat poisioning, thalidomide could attenuate paraquat-induced acute lung injury and its mechanism may be activating the Nrf2-ARE signaling pathway to protect mouse from Lipid peroxide damage.

  6. Acute pancreatitis

    Science.gov (United States)

    ... its blood vessels. This problem is called acute pancreatitis. Acute pancreatitis affects men more often than women. Certain ... well it can be treated. Complications of acute pancreatitis may include: Acute kidney failure Long-term lung damage (ARDS) Buildup ...

  7. Relationship between body balance, lung function, nutritional status and functional capacity in adults with cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Jennifer T. S. Penafortes

    2013-10-01

    Full Text Available BACKGROUND: Cystic fibrosis (CF is a hereditary condition in which lung disease affects all patients. In addition to pulmonary involvement, the multisystemic components of CF cause significant physical limitations. However, the impact of lung function on balance control in CF has not been studied. OBJECTIVE: To assess body balance in adults with CF and to test its possible associations with lung function, nutritional status, and functional capacity. METHOD: This was a cross-sectional study in which 14 adults with CF underwent pulmonary function testing (spirometry, body plethysmography, and carbon monoxide diffusing capacity (DLco, respiratory muscle strength, 6-min walking distance (6MWD, Berg balance scale (BBS, nutritional analysis (body mass index and bioelectrical impedance, and stabilometry. Body balance was quantified using stabilometry; all participants performed the following two trials: opened base, eyes open (OBEO; closed base, eyes closed (CBEC. RESULTS: In stabilometry, the median for the lateral range and anterior-posterior range in the CBEC trial was 0.10 (0.08-0.11 and 0.13 (0.11-0.22, respectively (p<0.05. The maximal inspiratory pressure (MIP correlated inversely with the lateral standard deviation (ρ=–0.61; p<0.05 as the DLco correlated positively with the anterior-posterior range (ρ=0.54; p<0.05. There were significant relationships between body composition indexes and almost all stabilometric variables measured. There were no relationships of the BBS and 6MWD with the stabilometric variables. CONCLUSIONS: In adults with CF, imbalance occurs mainly in the anterior-posterior direction and is especially associated with body composition.

  8. H-1 Nuclear Magnetic Resonance Metabolomics Analysis Identifies Novel Urinary Biomarkers for Lung Function

    Energy Technology Data Exchange (ETDEWEB)

    MCClay, Joseph L.; Adkins, Daniel E.; Isern, Nancy G.; O' Connell, Thomas M.; Wooten, Jan B.; Zedler, Barbara K.; Dasika, Madhukar S.; Webb, B. T.; Webb-Robertson, Bobbie-Jo M.; Pounds, Joel G.; Murrelle, Edward L.; Leppert, Mark F.; van den Oord, Edwin J.

    2010-06-04

    Chronic obstructive pulmonary disease (COPD), characterized by chronic airflow limitation, is a serious and growing public health concern. The major environmental risk factor for COPD is tobacco smoking, but the biological mechanisms underlying COPD are not well understood. In this study, we used proton nuclear magnetic resonance (1H-NMR) spectroscopy to identify and quantify metabolites associated with lung function in COPD. Plasma and urine were collected from 197 adults with COPD and from 195 adults without COPD. Samples were assayed using a 600 MHz NMR spectrometer, and the resulting spectra were analyzed against quantitative spirometric measures of lung function. After correcting for false discoveries and adjusting for covariates (sex, age, smoking) several spectral regions in urine were found to be significantly associated with baseline lung function. These regions correspond to the metabolites trigonelline, hippurate and formate. Concentrations of each metabolite, standardized to urinary creatinine, were associated with baseline lung function (minimum p-value = 0.0002 for trigonelline). No significant associations were found with plasma metabolites. Two of the three urinary metabolites positively associated with baseline lung function, i.e. hippurate and formate, are often related to gut microflora. This suggests that the microbiome composition is variable between individuals with different lung function. Alternatively, the nature and origins of all three associated metabolites may reflect lifestyle differences affecting overall health. Our results will require replication and validation, but demonstrate the utility of NMR metabolomics as a screening tool for identifying novel biomarkers of lung disease or disease risk.

  9. 18F-fluoro-2-deoxyglucose PET informs neutrophil accumulation and activation in lipopolysaccharide-induced acute lung injury.

    Science.gov (United States)

    Rodrigues, Rosana S; Bozza, Fernando A; Hanrahan, Christopher J; Wang, Li-Ming; Wu, Qi; Hoffman, John M; Zimmerman, Guy A; Morton, Kathryn A

    2017-05-01

    Molecular imaging of the earliest events related to the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) could facilitate therapeutic development and patient management. We previously reported that 18 F-fluoro-2-deoxyglucose ( 18 F-FDG) PET identifies ALI/ARDS prior to radiographic abnormalities. The purpose of this study was to establish the time courses of 18 F-FDG uptake, edema and neutrophil recruitment in an endotoxin-induced acute lung injury model and to examine molecular events required for 14 C-2DG uptake in activated neutrophils. Lung uptake of 18 F-FDG was measured by PET in control male Sprague Dawley rats and at 2, 6 and 24h following the intraperitoneal injection of 10mg/kg LPS. Lung edema (attenuation) was measured by microCT. Neutrophil influx into the lungs was measured by myeloperoxidase assay. Control and activated human donor neutrophils were compared for uptake of 14 C-2DG, transcription and content of hexokinase and GLUT isoforms and for hexokinase (HK) activity. Significant uptake of 18 F-FDG occurred by 2h following LPS, and progressively increased to 24h. Lung uptake of 18 F-FDG preceded increased CT attenuation (lung edema). Myeloperoxidase activity in the lungs, supporting neutrophil influx, paralleled 18 F-FDG uptake. Activation of isolated human neutrophils resulted in increased uptake of 14 C-2DG, expression of GLUT 3 and GLUT 4 and expression and increased HK1 activity. Systemic endotoxin-induced ALI results in very early and progressive uptake of 18 F-FDG, parallels neutrophil accumulation and occurs earlier than lung injury edema. Activated neutrophils show increased uptake of 14 C-2DG, expression of specific GLUT3, GLUT4 and HK1 protein and HK activity. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: 18 F-FDG pulmonary uptake is an early biomarker of neutrophil recruitment in ALI and is associated with specific molecular events that mediate 14 C-2DG uptake in activated neutrophils. 18 F

  10. Relationship of the functional movement screen in-line lunge to power, speed, and balance measures.

    Science.gov (United States)

    Hartigan, Erin H; Lawrence, Michael; Bisson, Brian M; Torgerson, Erik; Knight, Ryan C

    2014-05-01

    The in-line lunge of the Functional Movement Screen (FMS) evaluates lateral stability, balance, and movement asymmetries. Athletes who score poorly on the in-line lunge should avoid activities requiring power or speed until scores are improved, yet relationships between the in-line lunge scores and other measures of balance, power, and speed are unknown. (1) Lunge scores will correlate with center of pressure (COP), maximum jump height (MJH), and 36.6-meter sprint time and (2) there will be no differences between limbs on lunge scores, MJH, or COP. Descriptive laboratory study. Level 3. Thirty-seven healthy, active participants completed the first 3 tasks of the FMS (eg, deep squat, hurdle step, in-line lunge), unilateral drop jumps, and 36.6-meter sprints. A 3-dimensional motion analysis system captured MJH. Force platforms measured COP excursion. A laser timing system measured 36.6-m sprint time. Statistical analyses were used to determine whether a relationship existed between lunge scores and COP, MJH, and 36.6-m speed (Spearman rho tests) and whether differences existed between limbs in lunge scores (Wilcoxon signed-rank test), MJH, and COP (paired t tests). Lunge scores were not significantly correlated with COP, MJH, or 36.6-m sprint time. Lunge scores, COP excursion, and MJH were not statistically different between limbs. Performance on the FMS in-line lunge was not related to balance, power, or speed. Healthy participants were symmetrical in lunging measures and MJH. Scores on the FMS in-line lunge should not be attributed to power, speed, or balance performance without further examination. However, assessing limb symmetry appears to be clinically relevant.

  11. Relationship of the Functional Movement Screen In-Line Lunge to Power, Speed, and Balance Measures

    Science.gov (United States)

    Hartigan, Erin H.; Lawrence, Michael; Bisson, Brian M.; Torgerson, Erik; Knight, Ryan C.

    2014-01-01

    Background: The in-line lunge of the Functional Movement Screen (FMS) evaluates lateral stability, balance, and movement asymmetries. Athletes who score poorly on the in-line lunge should avoid activities requiring power or speed until scores are improved, yet relationships between the in-line lunge scores and other measures of balance, power, and speed are unknown. Hypothesis: (1) Lunge scores will correlate with center of pressure (COP), maximum jump height (MJH), and 36.6-meter sprint time and (2) there will be no differences between limbs on lunge scores, MJH, or COP. Study Design: Descriptive laboratory study. Level of Evidence: Level 3. Methods: Thirty-seven healthy, active participants completed the first 3 tasks of the FMS (eg, deep squat, hurdle step, in-line lunge), unilateral drop jumps, and 36.6-meter sprints. A 3-dimensional motion analysis system captured MJH. Force platforms measured COP excursion. A laser timing system measured 36.6-m sprint time. Statistical analyses were used to determine whether a relationship existed between lunge scores and COP, MJH, and 36.6-m speed (Spearman rho tests) and whether differences existed between limbs in lunge scores (Wilcoxon signed-rank test), MJH, and COP (paired t tests). Results: Lunge scores were not significantly correlated with COP, MJH, or 36.6-m sprint time. Lunge scores, COP excursion, and MJH were not statistically different between limbs. Conclusion: Performance on the FMS in-line lunge was not related to balance, power, or speed. Healthy participants were symmetrical in lunging measures and MJH. Clinical Relevance: Scores on the FMS in-line lunge should not be attributed to power, speed, or balance performance without further examination. However, assessing limb symmetry appears to be clinically relevant. PMID:24790688

  12. Cooccurrence of and remission from general anxiety, depression, and posttraumatic stress disorder symptoms after acute lung injury: a 2-year longitudinal study.

    Science.gov (United States)

    Bienvenu, O Joseph; Colantuoni, Elizabeth; Mendez-Tellez, Pedro A; Shanholtz, Carl; Dennison-Himmelfarb, Cheryl R; Pronovost, Peter J; Needham, Dale M

    2015-03-01

    To evaluate the cooccurrence, and predictors of remission, of general anxiety, depression, and posttraumatic stress disorder symptoms during 2-year follow-up in survivors of acute lung injury treated in an ICU. Prospective cohort study, with follow-up at 3, 6, 12, and 24 months post-acute lung injury. Thirteen medical and surgical ICUs in four hospitals. Survivors among 520 patients with acute lung injury. The outcomes of interest were measured using the Hospital Anxiety and Depression Scale anxiety and depression subscales (scores ≥ 8 indicating substantial symptoms) and the Impact of Event Scale-Revised (scores ≥ 1.6 indicating substantial posttraumatic stress disorder symptoms). Of the 520 enrolled patients, 274 died before 3-month follow-up; 186 of 196 consenting survivors (95%) completed at least one Hospital Anxiety and Depression Scale and Impact of Event Scale-Revised assessment during 2-year follow-up, and most completed multiple assessments. Across follow-up time points, the prevalence of suprathreshold general anxiety, depression, and posttraumatic stress disorder symptoms ranged from 38% to 44%, 26% to 33%, and 22% to 24%, respectively; more than half of the patients had suprathreshold symptoms in at least one domain during 2-year follow-up. The majority of survivors (59%) with any suprathreshold symptoms were above threshold for two or more types of symptoms (i.e., general anxiety, depression, and/or posttraumatic stress disorder). In fact, the most common pattern involved simultaneous general anxiety, depression, and posttraumatic stress disorder symptoms. Most patients with general anxiety, depression, or posttraumatic stress disorder symptoms during 2-year follow-up had suprathreshold symptoms at 24-month (last) follow-up. Higher Short-Form-36 physical functioning domain scores at the prior visit were associated with a greater likelihood of remission from general anxiety and posttraumatic stress disorder symptoms during follow-up. The majority

  13. Propofol pretreatment attenuates lipopolysaccharide-induced acute lung injury in rats by activating the phosphoinositide-3-kinase/Akt pathway

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    Zhao, L.L. [Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu Province (China); Hu, G.C. [Department of Pharmacology, College of Medicine, University of Illinois at Chicago, Chicago, IL (United States); Zhu, S.S. [Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu Province (China); Li, J.F. [Department of Anesthesiology, Tengzhou Central People' s Hospital, Liaocheng, Shandong Province (China); Liu, G.J. [Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu Province (China)

    2014-10-14

    The aim of this study was to investigate the effect of propofol pretreatment on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and the role of the phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) pathway in this procedure. Survival was determined 48 h after LPS injection. At 1 h after LPS challenge, the lung wet- to dry-weight ratio was examined, and concentrations of protein, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in bronchoalveolar lavage fluid (BALF) were determined using the bicinchoninic acid method or ELISA. Lung injury was assayed via lung histological examination. PI3K and p-Akt expression levels in the lung tissue were determined by Western blotting. Propofol pretreatment prolonged survival, decreased the concentrations of protein, TNF-α, and IL-6 in BALF, attenuated ALI, and increased PI3K and p-Akt expression in the lung tissue of LPS-challenged rats, whereas treatment with wortmannin, a PI3K/Akt pathway specific inhibitor, blunted this effect. Our study indicates that propofol pretreatment attenuated LPS-induced ALI, partly by activation of the PI3K/Akt pathway.

  14. Activation of Epac alleviates inflammation and vascular leakage in LPS-induced acute murine lung injury.

    Science.gov (United States)

    Wang, Xuefeng; Song, Shunde; Hu, Zhengqiang; Zhang, Zhewen; Li, Yajun; Yan, Chunguang; Li, Zigang; Tang, Huifang

    2017-12-01

    Exchange protein directly activated by cAMP (Epac) is an important molecule in cAMP signal transduction, but the effect of Epac on lipopolysaccharide (LPS)-induced acute lung injury (ALI) is unclear. In this study, we treated in vitro and in vivo models with the Epac activator 8CPT to determine the effect and related mechanisms of Epac. The in vitro results indicate that 8CPT inhibits lipopolysaccharide (LPS)-induced tumor necrosis factor-α (TNF-α) release from mouse macrophages (MH-S), whereas the protein kinase A (PKA) activator 6BnZ has no effect. Furthermore, Epac over-expression can significantly suppress TNF-α release from LPS induced MH-S cell, while Epac siRNA can slightly increase TNF-α release. Moreover, 8CPT reduces LPS-induced microvascular permeability in human pulmonary microvascular endothelial cells (HPMVECs), whereas the PKA activator 6BnZ has no effect. In mice with LPS-induced ALI, 8CPT significantly reduces LPS-induced inflammatory cytokine release, neutrophil recruitment, and albumin leakage. LPS simultaneously decreases the Epac but not the PKA levels. However, 8CPT reverses the decreased Epac levels. Furthermore, the mechanism involves the small GTPase Rac1/2 but not the mitogen-activated protein kinase (MAPK) pathway. Thus, Epac activation reduces inflammation and microvascular permeability in LPS-induced lung injury and an Epac activator represents a novel choice for the early therapy of ALI. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  15. Geraniol alleviates LPS-induced acute lung injury in mice via inhibiting inflammation and apoptosis

    Science.gov (United States)

    Jiang, Kangfeng; Zhang, Tao; Yin, Nannan; Ma, Xiaofei; Zhao, Gan; Wu, Haichong; Qiu, Changwei; Deng, Ganzhen

    2017-01-01

    Geraniol (GOH), a special type of acyclic monoterpene alcohol, has been widely used to treat many diseases associated with inflammation and apoptosis. Acute lung injury (ALI) is a common clinical disease in humans characterized by pulmonary inflammation and apoptosis. In the present study, we investigated the protective effects of GOH in a mouse model of ALI induced by the intranasal administration of lipopolysaccharide (LPS) and elucidated the underlying molecular mechanisms in RAW 264.7 cells. In vivo, GOH treatment markedly ameliorated pathological injury and pulmonary cell apoptosis and reduced the wet/dry (W/D) weight ratio of lungs, myeloperoxidase (MPO) activity and the production of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α). In vitro, the levels of pro-inflammatory cytokines, iNOS and COX-2 were significantly increased in LPS-stimulated RAW 264.7 cells, an effect that was decreased by GOH treatment. Moreover, GOH treatment dramatically reduced the expression of Toll-like receptor 4 (TLR4) and then prevented the nuclear factor-κB (NF-κB) activation. GOH treatment also promoted anti-apoptotic Bcl-2 expression and inhibited pro-apoptotic Bax and Caspase-3 expression. Furthermore, knockdown of TLR4 expression exerted a similar effect and inhibited the phosphorylation of p65, as well as the Bax and Caspase-3 expression. Taken together, these results suggest that GOH treatment alleviates LPS-induced ALI via inhibiting pulmonary inflammation and apoptosis, a finding that might be associated with the inhibition of TLR4-mediated NF-κB and Bcl-2/Bax signalling pathways. PMID:29050341

  16. Brominated indoles from a marine mollusc inhibit inflammation in a murine model of acute lung injury.

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    Tarek B Ahmad

    Full Text Available New drug leads for the treatment of inflammation are urgently needed. Marine molluscs are widely used as traditional medicines for the treatment of inflammation. Here we report the positive effects of a hypobranchial gland (HBG extract and the dominant bioactive compound 6-bromoisatin from the Muricidae mollusc Dicathais orbita, for reducing lipopolysaccharide (LPS induced acute lung inflammation in a mouse model. Both 6-bromoisatin and the HBG extract suppressed the inflammatory response in mice that were pre-treated by oral gavage at 48, 24 and 1 h prior to LPS infusion. The inflammatory antagonists were tested at concentrations of 0.5 mg/g and 0.1 mg/g HBG extract and 0.1 mg/g and 0.05 mg/g 6-bromoisatin in carrier oil and all treatments reduced inflammation as indicated by a significant suppression of inflammatory markers present in bronchoalveolar lavage fluid (BALF, in comparison to LPS induced positive control mice administered the carrier oil alone (p < 0.0001. Tumour necrosis factor-alpha (TNFα and interleukin-1 beta (IL-1β levels, in addition to total protein concentration were all significantly reduced in BALF from mice treated with the extract or 6-bromoisatin. Furthermore, all treatment groups showed significant reductions in neutrophil sequestration and preservation of the lung tissue architecture compared to the positive control (p < 0.0001. The combined results from this study and our previous in vitro studies indicate that 6-bromoisatin in the HGB extracts inhibit the activation of inflammatory signalling pathway. The results from this study further confirm that the HBG extract from Muricidae molluscs and 6-bromoisatin are bioavailable and effective in vivo, thus have potential for development as natural therapeutic agents for inflammation.

  17. TIP peptide inhalation in experimental acute lung injury: effect of repetitive dosage and different synthetic variants.

    Science.gov (United States)

    Hartmann, Erik K; Thomas, Rainer; Liu, Tanghua; Stefaniak, Joanna; Ziebart, Alexander; Duenges, Bastian; Eckle, Daniel; Markstaller, Klaus; David, Matthias

    2014-01-01

    Inhalation of TIP peptides that mimic the lectin-like domain of TNF-α is a novel approach to attenuate pulmonary oedema on the threshold to clinical application. A placebo-controlled porcine model of acute respiratory distress syndrome (ARDS) demonstrated a reduced thermodilution-derived extravascular lung water index (EVLWI) and improved gas exchange through TIP peptide inhalation within three hours. Based on these findings, the present study compares a single versus a repetitive inhalation of a TIP peptide (TIP-A) and two alternate peptide versions (TIP-A, TIP-B). Following animal care committee approval ARDS was induced by bronchoalveolar lavage followed by injurious ventilation in 21 anaesthetized pigs. A randomised-blinded three-group setting compared the single-dosed peptide variants TIP-A and TIP-B as well as single versus repetitive inhalation of TIP-A (n = 7 per group). Over two three-hour intervals parameters of gas exchange, transpulmonary thermodilution, calculated alveolar fluid clearance, and ventilation/perfusion-distribution were assessed. Post-mortem measurements included pulmonary wet/dry ratio and haemorrhage/congestion scoring. The repetitive TIP-A inhalation led to a significantly lower wet/dry ratio than a single dose and a small but significantly lower EVLWI. However, EVLWI changes over time and the derived alveolar fluid clearance did not differ significantly. The comparison of TIP-A and B showed no relevant differences. Gas exchange and ventilation/perfusion-distribution significantly improved in all groups without intergroup differences. No differences were found in haemorrhage/congestion scoring. In comparison to a single application the repetitive inhalation of a TIP peptide in three-hour intervals may lead to a small additional reduction the lung water content. Two alternate TIP peptide versions showed interchangeable characteristics.

  18. Nitric oxide contamination of hospital compressed air improves gas exchange in patients with acute lung injury.

    Science.gov (United States)

    Tan, P Seow Koon; Genc, F; Delgado, E; Kellum, J A; Pinsky, M R

    2002-08-01

    We tested the hypothesis that NO contamination of hospital compressed air also improves PaO(2) in patients with acute lung injury (ALI) and following lung transplant (LTx). Prospective clinical study. Cardiothoracic intensive care unit. Subjects following cardiac surgery (CABG, n=7); with ALI (n=7), and following LTx (n=5). Four sequential 15-min steps at a constant FiO(2) were used: hospital compressed air-O(2) (H1), N(2)-O(2) (A1), repeat compressed air-O(2) (H2), and repeat N(2)-O(2) (A2). NO levels were measured from the endotracheal tube. Cardiorespiratory values included PaO(2) were measured at the end of each step. FiO(2) was 0.46+/-0.05, 0.53+/-0.15, and 0.47+/-0.06 (mean+/-SD) for three groups, respectively. Inhaled NO levels during H1 varied among subjects (30-550 ppb, 27-300 ppb, and 5-220 ppb, respectively). Exhaled NO levels were not detected in 4/7 of CABG (0-300 ppb), 3/6 of ALI (0-140 ppb), and 3/5 of LTx (0-59 ppb) patients during H1, whereas during A1 all but one patient in ALI and three CABG patients had measurable exhaled NO levels (P<0.05). Small but significant decreases in PaO(2) occurred for all groups from H1 to A1 and H2 to A2 (132-99 Torr and 128-120 Torr, P <0.01, respectively). There was no correlation between inhaled NO during H1 and exhaled NO during A1 or the change in PaO(2) from H1 to A1. Low-level NO contamination improves PaO(2) in patients with ALI and following LTx.

  19. Extracorporeal lung perfusion and ventilation to improve donor lung function and increase the number of organs available for transplantation.

    Science.gov (United States)

    Valenza, F; Rosso, L; Gatti, S; Coppola, S; Froio, S; Colombo, J; Dossi, R; Pizzocri, M; Salice, V; Nosotti, M; Reggiani, P; Tosi, D; Palleschi, A; Pappalettera, M; Ferrero, S; Perazzoli, A; Costantini, D; Scalamogna, M; Rossi, G; Colombo, C; Santambrogio, L; Gattinoni, L

    2012-09-01

    Ex vivo lung perfusion (EVLP) has been validated as a valuable technique to increase the pool of organs available for lung transplantation. After a preclinical experience, we obtained permission from the Ethics Committee of our institution to transplant lungs after EVLP reconditioning. ABO compatibility, size match, and donor arterial oxygen pressure (PaO(2))/fraction of inspired oxygen (FiO(2)) ≤ 300 mm Hg were considered to be inclusion criteria, whereas the presence of chest trauma and lung contusion, evidence of gastric content aspiration, pneumonia, sepsis, or systemic disease were exclusion criteria. We only considered subjects on an extra corporeal